BuzzSugar

Fat March: Episode One Recap

FitSugar — Tue, 07 Aug 2007 12:30:00 -0700

Raise your hand if you watched Fat March on ABC last night....

My hand is raised but not proudly. As one of the biggest fans of The Biggest Loser, Fat March could have also been one of my favorites, however it didn't even come close. The show starts off with twelve contestants who are obese, who apparently knew they were going on the show to lose weight, but they weren't sure as to how. The premise was revealed as this: The contestants will be granted $100,000 each if they all walk 500 miles. Oddly, it kind of reminds me of a hodgepodge of all the reality shows currently on TV. There are challenges along the way and contestants get voted off. Each person that leaves the march, either by quitting or getting voted off, means $10,000 less in the jackpot for those that make it to the end. So far, the group is down to $80,000 -- This is because one person quit and another was voted off. I will be shocked if they end up with any money at the finish line.

I see how ABC could have thought this was a good idea for a show, but it does fall short. The reason I like The Biggest Loser is because it offers many tips for the viewers to lose weight. It is motivational and inspirational. The contestants work their asses off and it shows. The Fat March did not offer any tips and came off as just a bunch of folks whining about having to walk. Also, walking 13 miles per day is not something an average person can integrate into their daily life and it's just not realistic for those of us watching.

One thing I do think was interesting was to see how hard walking was on the contestants' bodies. 2.5 miles was all they had to walk on day one and it was incredibly hard for them. This is because the extra weight an obese person puts is the pressure of seven times their body weight on their knee joints each time they take a step. As a result most of the contestants had hardly walked around the block in the past few years, let alone a mile or two. One thing to be learned from this is the enormous toll fat can take on your body. Test yourself and try to walk 2.5 miles on your own in one day (either outside or on the treadmill). If that proves too difficult, you more than likely seriously need to get in shape.

I'm going to keep watching the show because I want to see how much weight they end up losing. Did any of you guys watch it? What did you think? I'd love to hear your thoughts in the comments section below.

Healthy Dose Link Time!!!!!!

FitSugar — Mon, 06 Aug 2007 13:30:00 -0700

That's Fit wants to help you recover quickly from your workout, so you are excited to get out there and do it again.

iFit&Healthy has the skinny on Bravo's Workout Rebecca Cardon's workout. Let me tell you this girl can bench press!

Complete Running Network shares my love of running skirts. It is great to run like a girl, is all I can say.

About: Yoga wants to help you do the splits! The Monkey Pose - Hanumanasana is an extreme hip opener, but not worth pulling a hamstring.

Back in Skinny Jeans knows how to order at Starbucks to cut the calories. If you love your coffee, she has 7 tips for ya!

fitPod has a new music mix for you. Steady State will help you deepen your stretching.

Leslie of The Weighting Game has a sneak peek of of ABC's new reality weight loss show "Fat March." Marching is definitely involved.

YumSugar has a quick dinner recipe for you: Tuna and Cannellini Bean Salad.

Looks like we are not the only folks checking out Heidi from the Hills - The Skinny Website is too.

diet-blog wants to help you beat back pain and gives you 5 ways to conquer the problem.

LIFT shows you the marriage of road kill and bike design. It is truly beautiful in a really odd way.

Mark's Daily Apple has a modest proposal for deconstructing health care in America.

Networks Ready New Crop of Insulting Reality Shows

BuzzSugar — Thu, 14 Jun 2007 09:30:00 -0700

Donald Trump and Fox are planning a show called "Lady or a Tramp," in which rowdy, bawdy party girls will be sent to charm school and taught proper manners. Great, because 1) when I think manners, I think Trump, and 2) I really needed another reality show to showcase the worst of womankind. They'd never do a show like this with partyboys, would they?
ABC is filming a reality series in which overweight people will walk from Boston to Washington, D.C. (the show passed through Baltimore this week). Which might not be so bad, really, except for the cringe-worthy name: "Fat March."
Fox and ABC are reportedly fighting for the rights to a series that would attempt to find the worst driver in America. Because reckless driving is hilarious - right, Lindsay Lohan?

NBC has announced a special called "Science of Love," which will attempt to figure out whether instinct or science has a better chance of picking someone's ideal mate. The guy testing the methods will be NFL player Adam Johnson, which leads me to wonder: Between this, "Age of Love," and Jesse Palmer's season of "The Bachelor," what's with all these professional athletes who can't get dates?

Source

Weight control and diet

FitSugar — Wed, 08 Oct 2008 17:34:58 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Cancer and Weight Control:

Cancer prevention guidelines from the American Cancer Society stress the importance of maintaining a healthy weight throughout life. A healthy weight is even more important than eating specific healthy foods, when it comes to cancer prevention.

Drug Warning:

The US Food and Drug Administration (FDA) is warning consumers not to buy a product known as the "Brazilian diet pill." This product is labeled as a dietary supplement, but contains several chemicals found in powerful prescription drugs. The products are also known as Emagrece Sim and Herbathin dietary supplements.

New Over-the-Counter Medication:

In February 2007, the FDA approved the first over-the-counter (OTC) weight-loss drug. Orlistat, previously available only by prescription as Xenical, will be available OTC at half its prescription strength. It will be sold under the name alli. Those eager to use the new pill should consider its cost and modest benefits compared with its side effects, most commonly oily diarrhea. This pill, which prevents fat absorption from food, also increases the risk of not absorbing important nutrients from food while using it. The FDA recommends taking a daily multivitamin supplement when using alli.

Research News:

A small study in Norway found that a diet low in fat and high in carbohydrates ("carbs") increases symptoms of psychological distress, such as depression and anger. The study compared three different diets with varying amounts of fat and carbohydrates.
A study released in March 2007 found that obesity in young girls results in early puberty -- as early as age 9.

Effects of Obesity on the Body:

Obesity is associated with certain problems related to infertility, such as uterine fibroids or menstrual irregularities. In men, obesity can contribute to reduced testosterone levels.
People who are obese are at higher risk for carpal tunnel syndrome and other problems involving nerves in their wrists and hands.
The Pickwickian syndrome, named for an overweight character in a Dickens novel, occurs in severe obesity when lack of oxygen produces intense and chronic sleepiness and, eventually, heart failure.

Introduction

A stable weight depends on a good balance between the energy you get from food and the energy you use. You use energy during the day in three ways:

As energy expended during rest (basal metabolism)
As energy used to break down food (thermogenesis)
As energy used during physical activity

Basal metabolism accounts for about two-thirds of spent energy. Your body generally uses this energy to keep your body temperature steady and keep the muscles of your heart and intestine working. Thermogenesis accounts for about 10% of spent energy.

When a person consumes more calories than the energy they use, the body stores the extra calories in fat cells. Fat cells function as energy reservoirs. They enlarge or shrink depending on how people use energy. If people do not balance energy input and output by eating right and exercising, fat can build up. This can lead to weight gain.

When energy input is equal to energy output, there is no expansion of fat cells (lipocytes) to accommodate excess. It is only when more calories are taken in than used that the extra fat is stored in the lipocytes and the person begins to accumulate fat.

Obesity is determined by measuring body fat, not just body weight. People might be over the weight limit for normal standards, but if they are very muscular with low body fat, they are not obese. Others might be normal or underweight, but still have excessive body fat. The following measurements and factors are used to determine whether or not a person is overweight to a degree that threatens their health:

Body mass index (BMI) (a measure of body fat)
Waist circumference (size around the waist)
Waist-hip ratio
Skin fold measurement (anthropometry)
The presence or absence of other disease risk factors (e.g., smoking, high blood pressure, unhealthy cholesterol levels, diabetes, relatives with heart disease)

A person's disease risk factors plus BMI may be the most important components in determining health risks with weight.

The Body Mass Index (BMI). The current standard measurement for obesity is the body mass index (BMI). In general, a BMI of 25 - 29.9 means you are overweight. Obesity is a BMI of 30 and above. Obesity is then classified into three categories:

Class 1: BMI of 30 - 34.9
Class II: BMI 35 - 39.9
Class III: BMI of 40 and greater

These guidelines are very important for people at risk for diabetes, heart disease, or certain cancers. It is also used to determine treatment approaches such as when surgery may be appropriate. The higher the BMI, the greater the risk for significant health problems.

Calculating Body Mass Index (BMI). One's body mass index (BMI) is calculated by multiplying a person's weight in pounds by 703, dividing by the height in inches, and then dividing that number by the height in inches. The steps are as follows:

Multiply one's weight in pounds by 703
Divide that answer by height in inches
Divide that answer again by height in inches

For example, a woman who weighs 150 pounds and is five feet eight inches (or 68 inches) tall has a BMI of 22.8.

Waist Circumference and Waist-Hip Ratio. The extent of abdominal fat can also be used in assessing risk of disease. Some studies suggest that:

Women whose waistlines are over 31.5 inches and men whose waists measure over 37 inches should watch their weight.
A waist size greater than 35 inches in women and 40 inches in men is associated with a higher risk for heart disease, diabetes, and impaired functioning.

Evidence strongly suggests that more body fat around the abdomen and hips (the apple-shape) is a more consistent predictor of heart problems and health risks than BMI.

The distribution of fat can be evaluated by dividing waist size by hip size. For example, a woman with a 30-inch waist and 40-inch hip circumference would have a ratio of 0.75; one with a 41-inch waist and 39-inch hips would have a ratio of 1.05. The lower the ratio the better. The risk of heart disease rises sharply for women with ratios above 0.8 and for men with ratios above 1.0.

Click the icon to see a depiction of the waist-to-hip ratio.

Anthropometry. Anthropometry is the measurement of skin fold thickness in different areas, particularly around the triceps, shoulder blades, and hips. This measurement is useful in determining how much weight is due to muscle or fat.

Biological and Medical Causes

Obesity results when a person consumes more calories than they need for the energy they use. Several different factors may influence weight gain.

About 90% of people who lose weight through dieting gain every pound back regardless of their weight-loss method.

Some evidence suggests that every person has an inherited weight. This range varies by only about 10% either up or down from some set point. For instance, a man whose "genetically-determined" weight is 200 pounds would tend to swing from 180 - 220 pounds. He would be unlikely to lose or gain more than this.

Genetic factors may play some part in 70 - 80% of obesity cases.

Appetite is determined by processes that occur both in the brain and gastrointestinal tract. Eating patterns are controlled by areas in the hypothalamus and pituitary glands (in the brain). The body produces a number of molecules that increases or decreases appetite. In some cases, the following factors may produce imbalances in this process:

Insulin. Insulin is a hormone that helps change blood sugar (glucose) into energy. During digestion, carbohydrates from our diet break down into different types of sugar molecules (including glucose). Proteins from our diet break down into smaller molecules called amino acids. Immediately after eating, blood glucose levels rise. This triggers the release of insulin, which pours into the bloodstream. Insulin pushes the glucose and amino acids into cells and muscles. Insulin and other hormones determine which nutrients will be burned for energy or stored for future use. The inability to use insulin efficiently (insulin resistance) has been associated with both obesity and diabetes.
Leptin. Leptin is a hormone that is released by fat cells. A number of scientists think this hormone may also be released by cells in the stomach. Leptin appears to play an important role in insulin resistance and fat storage in the body, but its role in obesity is unclear. The most likely scenario is that leptin levels rise as the cells store more fat. This increase in leptin levels decreases appetite. Falling levels of leptin make you feel hungry. In people who have genetically lower levels of leptin, however, the brain may be tricked into thinking that it is always starving because there is no leptin to decrease appetite. This can lead to weight gain.
Resistin. Resistin is a hormone produced by fat cells. It makes the body resistant to insulin activity. Some experts believe it may help explain the role of obesity in diabetes type 2.
Intestinal Chemicals. Ghrelin is a chemical produced in the stomach. It appears to be important in triggering the desire to eat. Peptide YY3–36 (PYY) is a substance secreted in the intestines after a meal. The level of PYY is proportionate to the number of calories a person eats. PYY tells the brain that you feel full. Deficiencies in ghrelin and PYY may contribute to some cases of obesity. Researchers are hoping that blocking ghrelin or infusing PYY may be possible treatments for obesity.
Other Chemicals. Many brain chemicals are being studied for their role in appetite stimulation and weight gain. Among them are neuropeptide Y, melanocortins, agouti-related protein, and melanocyte stimulating hormone. Pain-relieving chemicals called endorphins may be critical in reducing appetite and regulating energy use. Cholecystokinin, a hormone released in the upper intestine that stimulates digestive juices, may work to control meal size.

Insulin is a hormone produced by the pancreas that is necessary for cells to be able to use blood sugar.

Genetics may directly contribute to severe obesity in people with family histories of the problem. Genetic factors such as slow metabolisms may also make people more likely to be overweight. At least seven genetic mutations have been associated with specific and uncommon cases of severe obesity. Some are outlined below.

HOB1 (human obesity 1) is a gene that is linked to a high BMI in women.
Leptin gene variants have been linked to leptin deficiencies and obesity.
Melanocortin-4 receptor is a gene that helps turn off the urge to eat. It may not work properly in those with a family history of obesity.
Researchers have also identified a mutation in a gene for a protein called proopiomelanocortin, which results in a syndrome of obesity, red hair, and deficiencies in stress hormones.
A protein called agouti-related protein increases hunger. About 5% of severely obese people have mutations that over-respond to agouti-related protein.

Genetics also determine the number of fat cells a person has. Some people are simply born with more. It should be noted that even when genetic factors are present, a person can still control their diet.

The Thrifty Gene. Some experts think the existence of a so-called "thrifty" gene regulates changes in hormone levels, to accommodate seasonal changes. Theoretically, it works in the following manner:

In certain populations, hormones are released during seasons when food supplies have traditionally been low. This leads to insulin resistance and increased fat storage.
The process is reversed in seasons when food is readily available.
Because modern industrialization has made high carbohydrate and fatty foods available all year long, the gene no longer serves a useful function. Fat, originally stored for famine situations, is not used.

This theory could explain why the previously nomadic Native American tribes who now have Western dietary habits have such high rates of Type 2 diabetes and obesity. In the past, the traditional low-fat, high-fiber foods tribe members ate may have protected them from obesity and type 2 diabetes. Today, these tribes' diet consists of more Western foods, which are higher in fat. Furthermore, these foods are readily available year-round, and many members of the tribe are sedentary. The result is a very high incidence of Type 2 diabetes and obesity. Although genetic abnormalities may make it harder or easier to lose weight, the occurrence of obesity has dramatically increased over the past two decades, and genes cannot have changed within that short amount of time. Our ability to use the food that we eat evolved so that our body could conserve energy and store fat during times of famine. Most cases of obesity now occur in people with normal body function who live in industrialized nations, where there is more than enough food.

A number of medical conditions may contribute to being overweight, but rarely are they a primary cause of obesity.

Hypothyroidism is sometimes associated with weight gain. But, patients with an underactive thyroid generally show only a moderate weight increase of five to 10 pounds.
Very rare genetic disorders, including Froehlich's syndrome in boys, Laurence-Moon-Biedl, and the Prader-Willi syndromes, cause obesity.
Abnormalities or injury to the hypothalamus gland can cause hypothalamic obesity.
Cushing's disease is a rare condition caused by high levels of steroid hormones. It results in obesity, a moon-shaped face, and muscle wasting.
Obesity is also linked to polycystic ovarian syndrome, a hormonal disorder in women.

Click the icon to see an image of polycystic ovaries.

Some prescription medications contribute to weight gain, usually by increasing appetite. Such drugs include the following:

Corticosteroids
Female hormone treatments, including some oral birth control pills (effect is usually temporary), and certain progestins (such as Megestrol) used to treat cancer
Antidepressants and anti-psychotic drugs, including lithium and valproate
Insulin and insulin-stimulating drugs used to treat diabetes often lead to weight gain, a particularly unfortunate conflict of interest for obese individuals with type 2 diabetes

You should not stop taking any medications without your doctor's knowledge.

Cultural and Emotional Causes

Enough food is produced in the US to supply 3,800 calories every day to each man, woman, and child in the country, far more than the average person needs to sustain life. In a 2002 study, participants carefully recorded everything they ate and drank, and all activities and psychological factors surrounding the eating events. The people who gained weight ate more and their portions were larger than those who did not. This may be an obvious conclusion, but the public press often plays up biologic factors involved with obesity and overlooks the simple notion that Americans eat too much and exercise too little.

Obesity is dramatically increasing not only in American children and adults, but also in every country that has adopted similar cultural habits. The World Health Organization now considers obesity to be a global epidemic and a public health problem as more nations become "Westernized." In spite of the proven health risks of obesity, the government, insurance companies, and the medical profession do not spend nearly enough money to balance the commercial and cultural pressures that are producing millions of overweight people.

In 2007, the Robert Wood Johnson Foundation sounded a positive note with the announcement of a $500 million initiative, aimed at “reversing the childhood obesity epidemic by 2015.” The money will be used for research, education, and activities that promote healthy eating among America’s children.

Perhaps the primary reason for the dramatic rise in obesity is the sedentary (inactive) lives led by most Americans, including children and young people. In a 2003 study comparing modern life to the past, researchers found that labor saving devices had reduced a person's energy use by 111 calories a day -- adding up to an extra 11 pounds a year. Half the difference in energy use was due to less walking. At the same time, according to the U.S. Centers for Disease Control and Prevention, between 1970 and 2000 the typical American man increased his caloric intake by 168 calories a day (good for 17 pounds a year) while the average woman added 335 calories a day.

Regular television watching has been singled as the most hazardous pastime. According to a major 2003 study, for every 2 hours a person spends in front of the TV each day, the risk for obesity increases by 23% and for type 2 diabetes by 14%. In the study, TV watching produced the lowest metabolic rates compared to sewing, playing board games, reading, writing, and driving a car. Just the act of watching TV encourages unhealthy snacks and eating patterns. In addition, the advertising on the television complicates the problem by promoting fast foods, cereal, and snack products that are high in salt, fats, and carbohydrates. Even worse, much of these advertisements are directed at children -- the most vulnerable group.

People are not only eating more food than they did 20 years ago, they are also replacing home cooking with packaged foods, fast food, and dining out. This behavior, according to studies, places people at higher risk for obesity. Fast foods may be more harmful than restaurant cooking. These foods tend to be served in larger portions. They generally contain more calories and unhealthy fats, and less nutritious ingredients, than homemade or restaurant meals. Snack foods and sweet beverages, including juice and soft drinks, are specific problems that add to the increasing rates of obesity. Frequent small, healthy meals (instead of two or three large daily meals) have been associated with lower weights.

People react differently to stress. Some overeat and gain weight and others stop eating and lose weight. People who gain weight in response to stress often overeat foods high in sugar, fats, and salt. A 2003 study on rats suggested that stress hormones increase the pleasure of eating such so-called "comfort foods." Furthermore, the study supported previous research showing that stress-related eating was connected to the unhealthy accumulation of abdominal fat.

Risk Factors

Where you live plays a role in your risk for obesity. Simply living in the United States makes a person more susceptible to obesity. The prevalence of obesity in America has risen dramatically over the past few years and continues to increase.

According to the latest figures available, 32.2% of American adults (aged 20 and older) are obese (BMI over 30) -- up from about 23% in the early 1990s.
The number of Americans aged 20 - 74 who were overweight also increased -- from about 44.8% in 1960 to 65.2% in 2002.
The rate of extreme obesity (BMI > 40) increased from 0.8% in 1960 to 4.9% in 2002.
Obesity has increased in every state, in both men and women, across all age groups, and in every ethnic group, although some groups may face slightly higher risks than others.

Fat tends to settle in certain regions, depending on gender. Women gain fat predominantly in the stomach, hips and thighs, while men tend to gain fat in the belly and waist.

Risk by Age. People of any age are at risk for obesity. More children and adolescents are overweight in America than ever before. Gaining some weight is inevitable with age and adding about 10 pounds to a normal base weight over time is not harmful. The current weight gain in American adults over 50, however, is significant. By age 55, the average American has added nearly 40 pounds of fat during the course of adulthood. This condition is made worse by the fact that muscle and bone mass decrease with age.

Risk by Gender. In men, BMI tends to increase until age 50 and then it levels off. In women, weight tends to increase until age 70 before it plateaus. A 2000 study found that there are three high-risk periods for weight gain in women.

The first is at the onset of menstruation, particularly if it is early. In fact, a study released in March 2007 found that obesity in young girls results in early puberty -- as early as age 9. This, in turn, increases the risk for more weight gain as girls enter puberty.
The second is after pregnancy, with higher risk for women who are already overweight.
Finally, many women gain weight after menopause.

These findings are significant because they may allow women to target high-risk times, and consequently prevent unnecessary weight gain.

Risk by Economic Group. Obesity is more prevalent in lower economic groups. One 2002 study reported that women who reported that they did not have enough food were more likely to be overweight than those who said they had sufficient food. Researchers discovered that the low-income women tended to have fewer fruits and vegetables but were actually taking in more calories a day than higher-income women. However, obesity is increasing in young adults with college education as well as in other groups.

Ethnic Groups. Among ethnic groups in general, African-American women are more overweight than Caucasian women but African-American men are less obese than Caucasian men. (Currently, 80% of African-American women are overweight.) Hispanic men and women tend to weigh more than Caucasians.

US Regions. Regionally, the prevalence of obesity is lowest in the Western states and highest in the South.

A number of dietary habits put people at risk for becoming overweight:

Night-Eating Syndrome. Night-eating syndrome is defined as having no appetite in the morning, insomnia, and consuming more than half of daily food intake after 6:00 PM. It is associated with obesity and is difficult to treat. Stress reduction and relaxation techniques may be helpful.
Binge Eating and Eating Disorders. About 30% of people who are obese are binge eaters who typically consume 5,000 - 15,000 calories in one sitting. To be diagnosed as a binge eater, a person has to binge at least twice a week for 6 months. Many experts believe that binge-eating carbohydrates causes an increase in a natural opiate leading to dependence on carbohydrates. Therefore, this condition should be treated as an addiction. Other eating disorders are bulimia and anorexia. Bulimia is binge eating followed by purging in order to lose weight. Anorexia nervosa is a mental illness in which the person refuses to maintain weight at the normal level. The patient with anorexia has a terrible fear of getting fat, and an abnormal perception of what his or her body looks like. Both conditions pose risks for serious medical problems, and anorexia nervosa can be life-threatening. A combined approach using behavioral therapy and antidepressants may help these individuals. [See In-Depth Report #49: Eating disorders.]
Restrained Eating. Some people, mostly middle-aged women who have normal weight, have a pattern referred to as restrained eating. This pattern requires a high level of conscious control and usually maintains a lower weight. However, such restraint places these individuals at higher risk for loss of control and subsequent overeating.
Infrequent Eating. There is some evidence to suggest that eating small frequent meals uses more calories than infrequent large meals. It should be strongly noted, however, that packaged snack foods add calories and some do not produce a feeling of being full, so that people simply eat more than they should.

Anyone with Sedentary Lifestyles. Office workers, drivers, and anyone whose lifestyle involves sitting for long periods are at higher risk for obesity.

Ex-Smokers. The trend toward weight increase has followed the trend for quitting smoking. Nicotine increases the metabolic rate, and quitting, even without eating more, can cause weight gain, which may be considerable. It is important to note that weight control is not a valid reason to smoke. People in previous centuries did not smoke cigarettes, nor were they usually obese.

Shift-Workers. A recent study found that individuals who work late shifts (between 4 p.m. and 8 a.m.) tend to eat more and take longer naps than day workers and are more likely to gain excess weight.

People with Disabilities. Obesity rates are higher than average in people with physical or mental disabilities. Those with disabilities in the lower part of the body, such as the legs, are at highest risk.

Overweight in children and adolescents is rising at an alarming rate. In 2004, 19% of young children aged 6 - 11 were overweight, an increase of 8% from 1994. Among children aged 25, 13.9% were overweight in 2004, up from 7.2% 10 years earlier.

Definition of Overweight in Children

Children and adolescents are considered to be overweight if their BMI is above 95% of the children in their age and sex categories. Ethnic variations, timing of growth spurts, and higher normal fat levels around puberty can affect these measurements.

Causes and Risk Factors for Overweight in Children

Lifestyle Factors. Without educational or parental guidance, children are extremely vulnerable to the intense cultural pressures that are largely responsible for the obesity epidemic. The following are some specific problems created by the culture:

Excessive television watching plays a critical role in obesity in children. Not only is it a sedentary activity, but television also offers innumerable temptations with its advertisements for fast foods, sugar cereals, and unhealthy snacks. In one study obesity rates were lowest in children who watched television 1 hour or less a day and highest in those who watched 4 or more hours.
Sugar, particularly from soda, other sweetened beverages, and fruit juice, may be the major contributor to childhood obesity. One study reported that drinking soda regularly increases a child's risk for obesity by 60%. The average American adolescent consumes 15 - 20 extra teaspoons of sugar a day just from soda and sugary drinks. (Juice, while better than soda, is still filled with sugar.)
Less physical exercise and greater sedentary activities play another significant role in obesity in children. A high level of physical activity -- not just using up energy -- is important for weight control in young people. Unfortunately, according to one study, the annual distance walked by children has fallen by nearly 30% since 1972, partially because more parents are driving their children to school out of fear of abduction, molestation, and traffic accidents. Schools are also offering fewer opportunities for daily physical activities than in the past.

Neither the media nor the educational system has strong well-financed programs that encourage healthy alternatives, including exercise and healthy foods.

Family History. Parental obesity more than doubles the risk that a young child, whether thin or overweight, will become obese as an adult. In older children and teenagers, obesity in parents starts to count less as a predictor for body weight than their own weight. The risk for obesity may be due to environmental or genetic factors, or both.

Ethnic and Socioeconomic Factors. As in adult populations, children from lower socioeconomic groups and minority populations are at higher risk for obesity. For example, among young Mexican Americans and African-Americans, there has been an increase in overweight prevalence of about 13% to over 23%.

Factors Surrounding Birth. The following factors surrounding birth are associated with a child's weight:

Low birth weight is a risk factor for later obesity and diabetes. One theory is that humans have a "thrifty gene" that produces metabolic changes in infants with low birth weight. Such changes affect insulin and fat accumulation, in order to produce a "catch-up" weight in these young children as quickly as possible. This rapid weight gain in infancy increases the risk for obesity in children and young adults.
In a study of African-American children, having an overweight pregnant mother increased the risk for later weight gain, but low birth weight did not.

Although some small studies have reported protection against obesity from breastfeeding, evidence is weak. In a 2003 study, for example, children who were breast fed for 3 - 5 months had a lower risk for obesity, but prolonged breastfeeding had no effect. Nevertheless, given the healthful effects of breast feeding and the possibility that it may have even a slight impact on childhood obesity, it is highly recommended.

Biological Effect of Childhood Overweight on Adult Weight

Achieving a healthy weight becomes more difficult as children get older. The odds of obesity persisting into adulthood ranges from 20% in 4 year olds to 80% in teenagers. One reason for the persistence is biological. The fat cells change in number or mass depending on a person's age:

Fat cells themselves multiply during two growth periods: early childhood and adolescence. Overeating during those times increases the number of fat cells. Some people are also just born with more fat cells.
After adolescence, fat cells tend to increase in mass rather than quantity, so that adults who overeat and gain weight tend to have larger fat cells, not more of them. This growth in mass may be responsible for the greater risk of persistent obesity among teenagers compared to small children who are overweight. Losing weight after adolescence reduces the size of the fat cells but not their number, so weight loss becomes much more difficult.

Health Consequences of Childhood Overweight

Children and adolescents who are overweight have poorer health than other children. Studies are reporting unhealthy cholesterol levels and high blood pressure in overweight children and adolescents. Of great concern is the dramatic increase in type 2 diabetes in young people, which is largely due to the increase in overweight children. Overweight in children is also linked to asthma, gallbladder problems, sleep apnea, and liver abnormalities. Overweight girls are more likely to enter puberty early, according to a new study, and subsequently be at higher risk for breast cancer.

It is not clear yet how many of these childhood problems persist in people who achieve normal weight as adults. Staying overweight into adulthood certainly carries health risks.

Managing Overweight Children

Childhood obesity is best treated by a non-drug, multidisciplinary approach including diet, behavior modification, and exercise. Evidence suggests that reducing calories by only 200 - 260 per day would prevent weight gain in most overweight children. Here some tips for children who are overweight:

Limit (or avoid, if possible) take out, fast foods, high-sugar snacks, commercial packaged snacks, soda, and sugar-sweetened beverages (including too much juice).
Let children snack but make sure the snacks are healthy. Eating small frequent healthy meals (instead of two or three large ones) has been associated with being thinner and having a better cholesterol profile.
Let children choose their own food portions. One study indicated that children naturally ate 25% less when they chose their own portion size. When they were given larger portions their bite sizes were larger and they ate more.
Do not criticize a child for being overweight. It does not help and such attitudes could put children at risk for eating disorders, which are equal or even greater dangers to their health.
Limit television, video games, and computer use to a few hours a week. This can contribute significantly to weight control, regardless of diet and physical activity.
For young children, try the traffic-light diet. Food is designated with stoplight colors depending on their high caloric content: Green for go (low calories); yellow for "eat with caution" (medium calories); red for "stop" (high calories).
Try a low glycemic index diet. This may be as beneficial, and possibly more, than a standard reduced-fat diet in overweight children. Such a diet focuses on certain carbohydrates (for example, dried beans and soy), which raise blood sugar more slowly than other types of carbohydrates. This diet is sometimes used in diabetes, and as a dietary approach in overweight adults. [See In-Depth Report #42: Diabetes diet.]

Click the icon to see an image about TV watching.

Click the icon to see an image of childhood overweight.

Complications

General Adverse Effects of Obesity. Obesity, defined as a BMI of 30 or over, accounts for nearly 300,000 deaths in the U.S. each year. It is associated with more chronic health problems than smoking, heavy drinking, or poverty. Furthermore, given the current increase in obesity, it will surpass smoking as the most important preventable cause of death in America.

Some studies indicate the following health risks by body mass:

The lowest risks for heart disease, diabetes, and some cancers are in people with BMI values of 21 - 25.
The risks increase slightly when BMI values are between 25 - 27.
The risks are significant in BMIs between 27 - 30.
The same risks are dramatic at BMIs over 30.

Anyone with chronic health problems such as heart or lung disease, stroke, or arthritis, should be concerned about extra weight. This same concern also applies to people with known risk factors for such conditions.

Metabolic Changes. As fat stores increase, the fat cells themselves enlarge and produce chemicals that increase the risk for several diseases. Such diseases may include diabetes, high blood pressure, gallbladder disease, and some cancers.
Increased Mass. The increased body weight itself causes problems that result in injury and diseases, including osteoarthritis and sleep apnea.
Harmful Fat Cell Types. Weight concentrated around the abdomen and in the upper part of the body (the apple shape) poses a higher health risk than fat that settles around the hips and flank (the pear shape). Fat cells in the upper part of the body appear to have different qualities from those found in the lower parts. In fact, studies suggest a higher risk for diabetes in people with the "apple shape" and lower risk in those who are "pear shaped."

Weight gain in the area of and above the waist (apple type) is more dangerous than weight gained around the hips and flank area (pear type). Fat cells in the upper body have different qualities than those found in hips and thighs.

General Adverse Effects of Being Overweight (Not Obese). It is still not clear if being overweight (a BMI of 25 - 29.9) hurts healthy people with no risk factors for serious illnesses.

According to one 2001 study, just being overweight increased the risk for developing diabetes, gallstones, hypertension, heart disease, stroke, and colon cancer. The risk rose according to how much the individuals were overweight. In any case, adults who are overweight in middle age face a poor quality of life as they age, with the quality declining the greater the weight. One study suggested, however, that being over 65 and overweight (but not obese) is not associated with higher mortality rates.

Some experts argue, in fact, that in anyone who is not severely obese, it is the unhealthy diet and sedentary lifestyle that causes harm -- not weight per se. In support of this argument, a British study found that overweight fit individuals had half the death rate of unfit trim individuals.

Being somewhat overweight may also have some benefits under specific circumstances:

In older women, some excess fat may produce extra estrogen that helps slow down bone loss, and insulates bones from fall-related injuries. It should be strongly noted, however, that when older overweight women lose weight they report less pain, improved vitality, and improved physical function. The same positive effect of overweight does not appear to hold in older men.
Conditioned athletes may have high BMIs because of very dense muscle tissue. Being fit in general may protect many overweight people.
Some evidence suggests that Caucasians have the lowest mortality with BMIs of 24.3 - 24.7 while African-Americans are better off in the range of 26.8 - 27.1.
Children may have higher normal fat levels during growth spurts and around puberty.

Individuals with a BMI of at least 30 have a 10 - 50% increased rate of death from all causes, compared with individuals with a BMI of 20 - 25. Mortality rates from many causes are higher in obese people, but heart disease is the primary cause of death. People who are obese have almost three times the risk for heart disease as people with normal weights. Being physically unfit adds to the risk.

Weight concentrated around the abdomen and in the upper part of the body (apple shape) is particularly associated with insulin resistance and diabetes, heart disease, high blood pressure, stroke, and unhealthy cholesterol levels. Fat that settles in a pear shape around the hips and lower body appears to have a lower association with these conditions.

Obesity poses many dangers to the heart and circulatory system.

Damage in the Blood Vessels. As people age, changes in body fat (particularly increasing abdominal fat) seem to cause stiffness in the aorta, the major blood vessel leading from the heart. Studies are finding higher levels of a factor called C-reactive protein (CRP) in people with obesity and abdominal fat. CRP is now considered to be a marker for inflammation and damage in the arteries. (Losing weight reduces CRP levels.)

High Blood Pressure. High blood pressure is the health problem most commonly associated with obesity, and the greater the weight, the greater the risk. High blood pressure carries serious risks of stroke, heart attack, and heart failure. The link between obesity and high blood pressure is complex, and may be a combination of genetic, population, and biological factors. Many studies have reported that modest weight loss is beneficial for reducing existing high blood pressure. [See In-Depth Report #14: High blood pressure.]

Heart Failure. An important 2002 study reported that obesity might account for 11% of heart failure cases in men and 14% in women. This link existed independently of other risk factors, such as high blood pressure, sleep apnea, and diabetes, which are also associated with obesity. The biologic mechanisms involved in obesity that lead specifically to heart failure are not clear. [See In-Depth Report #13: Heart failure.]

Unhealthy Cholesterol Levels and Lipid Levels. The effect of obesity on cholesterol levels is complex. Although obesity does not appear to be strongly associated with overall cholesterol levels, among obese individuals triglyceride levels (the major form of fat storage in the body) are usually high, while HDL levels (the "good" cholesterol) tend to be low. Both conditions are risk factors for heart disease. [See In-Depth Report #23: Cholesterol.]

Click the icon to see an image of coronary artery disease.

Stroke. Obesity is also associated with a higher risk for stroke. [See In-Depth Report #45: Stroke.]

Type 2 Diabetes and Insulin Resistance. Most people with type 2 diabetes are obese and, in fact, studies strongly suggest that weight loss may be the key in controlling the current epidemic of type 2 diabetes. The common factor appears to be insulin resistance. Insulin is a critical hormone in the use of sugar. In type 2 diabetes, different factors cause the body to become insulin resistant -- that is, the body can no longer respond properly to insulin. This has the effect of increasing sugar levels in the blood, the hallmark of diabetes. Both obesity and insulin resistance, at different phases, are marked by high levels of certain chemicals. It is not known yet if the higher levels are simply a product of obesity, or play some role in causing diabetes.

Insulin resistance is also associated with high blood pressure and abnormalities in blood clotting. Some research indicates that obesity, in fact, is the one common element linking insulin resistance, diabetes type 2, and high blood pressure. [See In-Depth Report #60: Diabetes - type 2.]

Metabolic Syndrome. Metabolic syndrome (also called syndrome X) is a pre-diabetic condition that is significantly associated with heart disease and higher mortality rates from all causes. The syndrome consists of obesity marked by abdominal fat, unhealthy cholesterol levels, high blood pressure, and insulin resistance. A 2002 study estimated that nearly a quarter of the U.S. population now has this condition. Even worse, according to a 2003 study, nearly a million American teenagers have this syndrome. A combination of weight loss and exercise is an effective treatment for this syndrome.

The American Cancer Society released new cancer prevention guidelines in September 2006. The guidelines stress the importance of keeping a healthy weight throughout life. The Society indicates that healthy weight is even more important than eating specific healthy foods, when it comes to cancer prevention.

Obesity has been associated with a higher risk for cancer in general and specific cancers in particular. Studies have also suggested that restricting calories reduces the risk for cancer. Some experts believe that effective weight control for children and adults could reduce cancer rates by 30 - 40%. One way obesity may increase the risk for cancer is its association with high levels of hormones called growth factors, which can trigger rapid cell production leading to cancer.

Uterine Cancers. The risk of uterine cancer in obese women appears to be two or three times higher than in thinner women.

Prostate Cancer. New studies from 2005 and 2006 report that obesity is associated with an increase in prostate cancer mortality, although not with the risk for less aggressive forms of prostate cancer.

Click the icon to see an image of prostate cancer.

Breast Cancer. Studies are mixed on the association between obesity and breast cancer. A number of studies have linked obesity to breast cancer in postmenopausal women, particularly in women who begin to gain weight after age 18.

Click the icon to see an illustrated series detailing a breast cancer surgery (mastectomy).

Gallbladder Cancer. Obese women are at higher risk for gallbladder cancer.

Gastrointestinal Cancers. A number of cancers in the gastrointestinal tract have been associated with obesity:

Cancer of the esophagus may be due to a higher incidence of gastroesophageal reflux disorder (heartburn) in people who are overweight.
Colon cancer has been linked to increased body mass in both men and women.
Pancreatic cancer and obesity have been weakly linked, with one study reporting a lower risk in overweight people who are physically active.

Click the icon to see an illustrated series detailing a colon cancer surgery.

Muscles and Bones

Obesity places stress on bones and muscles. Studies report that the incidence of osteoarthritis is significantly increased in people who are overweight. People who are obese are also at higher risk for carpal tunnel syndrome and other problems involving nerves in their wrists and hands. It should be noted that some weight may be protective against osteoporosis (loss of bone thickness).

Obesity increases the risk for the following mouth and eye disorders:

Gum disease
Cataracts
Maculopathy, an eye disease related to aging

Infertility. Abnormal amounts of body fat, either 10 - 15% too high or too low, can contribute to infertility in women. Obesity is specially related to certain infertility problems, such as uterine fibroids or menstrual irregularities. In men, obesity can contribute to reduced testosterone levels.

Effect on Pregnancy. Obesity has many dangerous effects on pregnancy. These include high blood pressure, gestational diabetes (diabetes, usually temporary, that occurs during pregnancy), urinary tract infections, blood clots, prolonged labor, and higher fetal death rate in late stages of pregnancy. Obesity is also associated with increased rates of cesarean delivery. Infants of women who are obese are also at higher risk for neural tube birth defects, which affect the brain or spine. Folic acid supplements, ordinarily effective in preventing these conditions, may not be as protective in overweight women.

Obesity is thought to be a risk factor for symptoms of adult-onset asthma. Though there is evidence that obesity causes wheezing and shortness of breath, it does not appear to be strongly associated with the disease mechanisms in the lungs that cause true asthma.

Obesity also puts people at risk for hypoxia, a condition in which there is not enough oxygen to meet the body's needs. Obese people need to work harder to breathe. They tend to have breathing muscles and lungs that do not work as well as those in thinner people.

The Pickwickian syndrome, named for an overweight character in a Dickens novel, occurs in severe obesity when lack of oxygen produces intense and chronic sleepiness and, eventually, heart failure.

Nonalcoholic Fatty Liver Disease. People with obesity, particularly if they also have type 2 diabetes, are at higher risk for a condition called nonalcoholic fatty liver disease, also called nonalcoholic steatohepatitis (NASH). This condition causes liver damage that is similar to liver injury seen in alcoholism. In some cases, it can be very serious and require liver transplantation. It occurs in about half of people with diabetes, and 20 - 50% of obese people, depending on how severe their obesity is. NASH can also occur in overweight children.

Gallstones. The incidence of gallstones is significantly higher in obese women and men. The risk for stone formation is also high if a person loses weight too quickly. In people on ultra-low calorie diets, gallstones may be prevented by taking ursodeoxycholic acid (Actigall).

Click the icon to see an image of gallstones.

People who are obese and nap tend to fall asleep faster and sleep longer during the day. At night, however, it takes them longer to fall asleep, and they sleep less than people with normal weights. In an apparent vicious circle, studies have suggested that obesity not only interferes with sleep but that sleep problems may actually contribute to obesity.

Sleep Apnea. Obesity, particularly the apple shape, is strongly associated with sleep apnea, which occurs when the upper throat relaxes and collapses from time to time during sleep. This collapse temporarily blocks the passage of air. Sleep apnea is increasingly being viewed as a potentially serious health problem, which may lead to complications such as heart disease and stroke. Some studies suggest that among overweight people, those who have sleep apnea have a greater risk of heart disease than those without it. In one study, the more obese a person with sleep apnea was, the higher the pressure on the airway, and therefore the greater the obstruction of the airway. Obstructive sleep apnea may also add to obesity, however, as sleepy people tend to be sedentary. Some studies indicate that treating sleep apnea may help people lose abdominal fat.

Narcolepsy. A small European study found a link between narcolepsy (a sleep disorder characterized by excessive daytime sleepiness with frequent daily sleep attacks) and high BMI.

Depression. A number of studies have reported an association between depression and obesity, particularly in obese women. There may be a number of factors to explain the link. In some cases of atypical depression, people overeat and may gain weight. Overweight people may also become depressed because of social problems and a poor self-image. In these cases, depression usually disappears when people lose weight.

There is evidence, however, that obesity itself may impair levels of tryptophan -- a chemical needed to make serotonin, a brain chemical associated with mental well-being. In one study, even after people lost weight, tryptophan levels were lower than normal.

There does not appear to be any association between depression and obesity in men.

Social Problems. One long-term study reported that overweight young women completed fewer years of school, were 20% less likely to be married, and had 10% higher rates of household poverty than their thinner peer. Obese young men were also less likely to be married, and their incomes were lower than their thinner peers. Nevertheless, studies consistently show that overweight males (both boys and men) are not as severely emotionally affected as females of any age. Women and girls tend to blame themselves for being heavy, while males tend to blame being overweight on outside factors.

Weight Loss and Maintenance

Even modest weight loss can reduce the risk factors for heart disease and diabetes. The simplest (but still difficult) approach to weight loss is reducing calories and exercising at least 150 minutes a week. Behavioral and mental changes in eating habits, physical activity, and attitudes about food and weight are also essential to weight management. For people who are very overweight and cannot lose weight through lifestyle changes, a number of effective weight-loss medications are available. For those with severe obesity, surgical procedures are proving to be very beneficial.

Some Tips for Losing Weight. The following are some general suggestions for dieters:

Start with realistic goals. Diet failure is extremely common, and the odds of significant weight loss are low, particularly in people with the highest weights. People who are able to restrict calories, engage in an exercise program, and get help in making behavioral changes can expect to lose between 5 - 10% of their current body weight. That is generally all that is needed to achieve meaningful health changes. Certainly, the distorted image of a super-thin female shape should not be anyone's goal.
Maintain a regular exercise program, assuming you have no health problems that will stop you. Choose a program that you enjoy. Check with your doctor about any health considerations. [See In-Depth Report #29: Exercise.]
Do not use hunger pangs as cues to eat. A stomach that has been stretched by large meals will continue to signal hunger for large amounts of food until its size reduces over time with smaller meals.
Be honest about how much you eat and start by recording all calories in writing. Studies suggest that when many people report their own calories intake they significantly underestimate their consumption of high-calorie and over-estimate the low-calorie foods. People who do not carefully note everything they eat tend to take in too many calories when they believe they are dieting.
Observe weekend eating. People tend to eat more on the weekends. If it is difficult to monitor all meals during the week, it be may be useful to at least track eating habits during the weekends.
Once the pounds are lost, do your best to keep the healthier weight. Make daily, even hourly, conscious decisions about eating and exercising activities. Such thinking, in many cases, can become automatic and not painful.
Don't give up, even after repeated weight loss failures. Most studies indicate that yo-yo dieting or weight cycling have no bad psychological or physical effects. Repeated dieting also does not harm the body's ability to burn calories efficiently.
Weight loss, in any case, should not be the only or even the primary goal for people concerned about their health. The success of weight loss efforts should be evaluated according to improvements in disease risk factors or symptoms, and by the adoption of healthy lifestyle habits, not just by the number of pounds lost.


Lifestyle	Reduce rate of eating. Keep food records. Eliminate environmental triggers to eating. Identify high-risk situations for overeating. Separate eating from other activities.
Exercise	Face up to emotional barriers to exercise. Understand the link between exercise and weight control. Establish reasonable exercise goals. Develop a plan for regular activity. Add increased activity into daily lifestyle.
Attitudes	Develop reasonable weight-loss goals. Avoid "all or none" thinking. Focus attention away from the scale and toward behavior. Uncouple weight from self-esteem. If you "fall off the wagon," take steps to ensure the situation does not repeat (recover from lapses with constructive action).
Relationships	Understand the key role of social support to health. Identify supportive others. Match personal style to support-seeking activities. Be specific in making support requests. Be assertive but reinforcing in drawing help from others.
Nutrition	Resist the temptation of popular fad diets. Eat with your health in mind; do not concentrate on what should be "off-limits." Eat with moderation in mind. Maximize fiber. Develop a tailored plan.
From Brownell KD. The LEARN Program for Weight Control. 7th ed. Dallas, Tex: American Health Publishing Company; 1998.

Weight Management

There are many approaches to dieting and many claims for great success with various fad diets. To date, although many diets achieve effective immediate weight loss, none has emerged as an effective tool for maintaining healthy weight. The only definite recommendation that can be made about any diet plan is to be sure it includes an exercise program, assuming there are no health problems to forbid it.

The original food pyramid, with four food groups, has been replaced with an updated food guide called "My Pyramid." This illustrates the relative proportions of different foods that make up a nutritious, well-balanced diet and includes exercise.

Calorie restriction has been the cornerstone of obesity treatment. The standard dietary recommendations for losing weight are the following:

As a rough rule of thumb, one pound of fat equals about 3,500 calories. A person could lose a pound a week by reducing daily caloric intake by about 500 calories a day. Naturally, the more severe the daily calorie restriction, the faster the weight loss. Very-low calorie diets have also been associated with better success, but extreme diets can have some serious health consequences.
To determine your daily calories requirements, multiply the number of pounds of ideal weight by 12 - 15 calories. The number of calories per pound depends on gender, age, and activity levels. For instance, a 50-year old woman who wants to maintain a weight of 135 pounds and is mildly active might require only 12 calories per pound (1,620 calories a day). A 25-year old female athlete who wants to maintain the same weight might require 25 calories per pound 2,025 (calories a day).
Fat intake should be no more than 30% of total calories. Most fats should be in the form of monounsaturated fats (such as olive oil). Saturated fats (found in animal products) should be avoided.

Extreme diets of less than 1,100 calories carry health risks. They are also often followed by bingeing or overeating, and a return to the obese state. Such diets often do not have enough vitamins and minerals, which must then be taken as supplements. Most of the initial weight loss is in fluids. Later, fat is lost, but so is muscle, which can account for more than 30% of the weight loss. No one should be on severe diets for longer than 16 weeks, or fast for more than 2 or 3 days. Severe dieting has unpleasant side effects including fatigue, intolerance to cold, hair loss, gallstone formation, and menstrual irregularities. There have been rare reports of death from heart arrhythmias when liquid formulas did not have sufficient nutrients. Pregnant women who excessively diet during the first trimester put their unborn children at risk for birth defects. Of note, those whose diets include a high intake of fluids and much reduced protein and sodium are at risk for hyponatremia, which can cause fatigue, confusion, dizziness, and in extreme cases, coma and death.

This dietary approach requires counting only grams of fat with the goal of achieving 30% or fewer calories from fat. One gram of fat contains nine calories, while one gram of carbohydrates or protein has only four calories. Fat in your diet converts more readily to fat in the body, compared with carbohydrates or proteins. Simply switching to low-fat or skimmed dairy products may be enough for some people.

There are possible drawbacks to this approach:

Some people who reduce their fat intake may not get enough basic nutrients, including vitamins A and E, folic acid, calcium, iron, and zinc. People on low-fat diets should eat a wide variety of foods and take a multivitamin supplement, if appropriate. Calcium deficiencies may be particularly harmful in women at risk for osteoporosis.
Many people start eating foods with too many carbohydrates, believing that they are not adding calories. No one should use a low-fat diet as an excuse for eating too many carbohydrates, particularly starchy foods and sugar. A high-calorie diet from any source will add pounds.
A small study in Norway found that a diet low in fat and high in carbohydrates ("carbs") increases symptoms of psychological distress, such as depression and anger. The study compared three different diets that had varying amounts of fat and carbohydrates in each. The diets contained the same amount of calories, but differed in the percentage and type of fat. People on the low-fat, high-carbohydrate diet reported more anger and depression compared with the other two diets.
Replacing fatty foods, such as cakes, cookies, and chips, with their commercial "low-fat" counterparts does not constitute a low-fat diet. These foods generally contain more sugar and hence calories, not to mention other ingredients, which have virtually no nutritional value. In fact, a 2002 study suggested that increasing sugar may, over time, reduce levels of HDL ("good") cholesterol.
Very low-fat diets may increase the risk for stroke from hemorrhage in the brain.

Some fat in a diet is essential. It should come from plant oils and fish, however, and not from animal products or hardened oils, such as margarine. Trans-fatty acids, found in hardened oils, are actually more of a risk factor for obesity than saturated fats from animal products, although both should be avoided.

Fiber and Complex Carbohydrates. In all cases, complex carbohydrates found in whole grains and vegetables are preferred over those found in starch-heavy foods, such as pastas, white-flour products, and potatoes. Fiber is an important component of many complex carbohydrates. Fiber is almost always found only in plants, particularly vegetables, fruits, whole grains, nuts, and legumes (beans and peas). One exception is chitosan, a dietary fiber made from shellfish skeletons. Fiber cannot be digested but passes through the intestines, drawing water with it, and is eliminated as part of feces content. The following are specific advantages from high-fiber diets (up to 55 grams a day):

Insoluble fiber (found in wheat bran, whole grains, seeds, nuts, and fruit and vegetable peels) has been associated with weight loss. Studies also suggest that diets rich in fiber from whole grains reduce the risk for type 2 diabetes.
Soluble fiber (found in dried beans, oat bran, barley, apples, citrus fruits, and potatoes) has important benefits for the heart, particularly for achieving healthy cholesterol levels and possibly benefiting blood pressure as well. Simply adding breakfast cereal to a diet appears to reduce cholesterol levels. People who increase their levels of soluble fiber should also increase water and fluid intake.

High-protein, low carbohydrate diets, such as the Atkins and South Beach diets, have been touted as effective ways to produce short-term weight loss. Because of their emphasis on fats and proteins, many experts are concerned about long-term health problems. A report in the March 2006 Lancet linked the Atkins diet to life-threatening complications that caused the death of one woman. The 40-year-old woman had a deadly buildup of acids called ketones in her blood, a condition called ketoacidosis. Ketoacidosis can cause coma and death. Ketones are a known by-product of high protein, low carbohydrate diets. At low levels they can cause nausea, lightheadedness, and bad breath.

The long-term effects of these diets are still unknown. For example, the Atkins diet restricts some vegetables and most fruits, which are known to protect against serious diseases such as heart problems and cancer. The diet may also cause too much calcium to build up in the urine. This can increase the risk for kidney stones and osteoporosis. In addition, high-protein intake, particularly from meat, can be harmful in people with kidney problems. Individuals at risk for kidney stones, or those who have other kidney problems, should not go on high-protein diets without talking to their doctor first. Unfortunately, many people with diabetes are at risk of kidney problems, which could reverse any possible benefits a high-protein diet may bring them. Eating a lot of meat has also been associated with certain common cancers, notably prostate and colon cancers. A 2002 study suggested that such diets during pregnancy may increase the risk for high blood pressure in the child.

Still, significant studies say that such diets improve cholesterol and blood sugar levels. Studies in 2002 and 2003 have indicated that these diets lower blood glucose levels, which can be important in people who are diabetic. The diets also reduce triglyceride levels (unhealthy fat molecules) and increases HDL (" good") cholesterol levels. High triglyceride and low HDL levels are important risk factors for heart disease, and are common in people with type 2 diabetes. Studies are mixed on whether this type of diet reduces overall cholesterol or LDL ("bad") cholesterol levels.

Experts that promote the low carbohydrate approach argue that heart problems from obesity are due to insulin disturbances from sugar imbalances. Therefore, they believe that restricting carbohydrates is the best approach for obesity -- especially for overweight people with diabetes. More research is needed, however, to determine the long-term impact of such diets on health.

High-protein, low-carbohydrate diets include Atkins, Protein Power, Sugar Busters, and Dr. Stillman. The Atkins diet is one of the most popular and has a four-phase program:

Induction. For the first 2 weeks, individuals consume no more than 20 grams of carbohydrates a day. The diet consists of pure protein and fats. There is no fruit, bread, grains, starchy vegetables, or dairy products other than cheese, cream, or butter. This phase is not suitable for children, pregnant women, or anyone with kidney disease.
On-going Weight Loss. After the first phase, individuals continue to lose weight while they increase carbohydrate levels by five grams each day.
Premaintenance. When individuals get close to their weight goal, they add another 10 grams of carbohydrates per day as long as they do not begin to gain weight. Weight loss is very slow at this time, but the individual is now getting used to maintenance.
Maintenance. Lifetime maintenance is usually between 40 and 100 grams of carbohydrates a day, depending on steady weight level.

Anyone who chooses this diet should prefer fish or soy products to meat as protein sources. Fish may reduce leptin, a hormone associated with fat storage and heart diseases, and would be the best protein source. People on this diet should also choose monounsaturated fats (as in olive oil) over saturated fats or trans-fatty acids fat. Patients often need supplements, at least a multivitamin and possibly calcium, chromium, omega-3 fatty acids (found in fish oil), and other supplements.

The South Beach and Zone diets encourage healthy fats. They also allow certain carbohydrates. For example the Zone uses healthy carbohydrates (vegetables and dried beans) and unsaturated fats. The South Beach diet uses carbohydrates that have a lower impact on blood sugar levels. This is called a low-glycemic index. Low-glycemic foods include barley, dried bean and peas, milk, strawberries, and apples. High-glycemic foods include refined grains, white bread, white potatoes, and bananas and other tropical fruits. The glycemic index was developed for use in diabetes -- not for weight loss. Nevertheless, there is some evidence that foods with low glycemic indexes may produce a feeling of fullness and so discourage further eating. As with any high-protein diets, people at risk for kidney stones, or those who have other kidney problems, should avoid these plans.

Replacing fats and sugars with substitutes may help many people who have trouble maintaining weight. In fact, in one 2003 study, people with type 2 diabetes used the artificial sweetener sucralose and a beta-glucan fat substitute (derived from oats) as part of a low-calorie diet. At the end of the 4 weeks, they achieved better weight, glucose control, and HDL levels than those on a standard diabetic diet.

Fat Substitutes. Fat substitutes added to commercial foods or used in baking deliver some of the desirable qualities of fat, but do not add as many calories. It should be stressed that eliminating all fats from a diet can be harmful to general health.

Fat substitutes include the following:

Stanols. Stanols are plant compounds used in margarines (Benecol, Take Control). Benecol is derived from pine bark and Take Control from soybeans. Two servings a day of either brand, as part of a low-fat, diet can lower LDL and total cholesterol by impairing its absorption in the intestinal tract. Some studies have reported that the use of stanols can allow lower doses of statins (cholesterol lowering medications). Stanols do not appear to block absorption of fat-soluble nutrients or vitamins, as olestra does.
Olestra (Olean) passes through the body without leaving behind any calories from fat. Studies suggest that it improves cholesterol levels and helps people lose weight when it is used to replace a third of normal dietary fats. (Note that simply adding snacks containing olestra does not appear to have any effect on cholesterol or weight loss.) Early reports of cramps and diarrhea after eating food containing olestra have not proven to be significant. Of greater concern is the fact that even small amounts of olestra deplete the body of certain vitamins and nutrients that may help protect against serious diseases, including cancer. The FDA requires that the missing vitamins be added back to olestra products, but not other nutrients. The side health effects, if any, are unknown.
Beta-glucan is a soluble fiber found in oats and barley. Products using this substance (e.g., Nu-Trim) may reduce cholesterol and have additional health benefits.

A number of other fat-substitutes are also available. Although studies to date are not showing any significant side effects, these products' effect on weight control is uncertain, since many of the products containing them may be high in sugar.

Artificial Sweeteners. Many artificial or low-calories sweeteners are available. A 2002 study confirmed that people who consumed artificial sweeteners and reduced their sugar intake weighed less over time than those who took in similar types and amounts of drinks and food containing sugar. It should be noted that using these artificial sweeteners should not give dieters a license to increase their fat intake. Studies indicate that consuming some sugar is not a significant contributor to weight gain, as long as the total amount of calories in the diet is under control. There is some public concern about chemicals used to produce many of these sweeteners, and the side effects seen in studies using rats. Natural low-calories sweeteners are available that may be more acceptable to many people.

Saccharin (Sugar Twin, Sweet n' Low, Sucaryl, and Featherweight). Saccharin has been used for years. Some studies found that large amounts of saccharin cause bladder cancer in rats. However, the rats were fed huge amounts that do not apply to human diets. Currently there is no evidence that saccharin causes cancer in humans.
Aspartame (Nutra-Sweet, Equal, NutraTase). Aspartame has come under scrutiny because of rare reports of nervous system disorders, including headaches or dizziness, associated with its use. People with phenylketonuria (PKU), a genetic condition, should not use it. Studies have not reported any serious health dangers, but some people may be sensitive to it.
Sucralose (Splenda). Sucralose has no bitter aftertaste and works well in baking, unlike other artificial sweeteners. It is made from real sugar by replacing part of the sugar with chlorine. Some people are concerned because chlorinated molecules used in major industrial chemicals have been associated with cancer and birth defects. Over 100 studies have been conducted on sucralose over a 20-year period, with no reports of such risks.
Acesulfame-potassium (Sweet One, SwissSweet, Sunette). It has been used in the U.S. since 1988 with no reported side effects.
Neotame (Neotame). Neotame is a synthetic variation of aspartame, but was developed to avoid its side effects. The association with aspartame has raised some concerns. Studies to date have reported no effects that would cause alarm, and it appears to be safe for general consumption.
D-tagatose (Tagatose). This reduced-calorie sweetener is made from lactose, which is the sugar found in dairy products and other foods. It may be especially beneficial for people with type 2 diabetes. It may also have additional benefits that help the intestinal tract.
Alitame (Aclame) is formed from amino acids, the building blocks of proteins. It has the potential to be used in all products that contain sugar, including baked goods.
Stevioside (Stevia). This is a natural sweetener derived from a South American plant. It is available in health food stores. People with diabetes should avoid alcohol-based forms. It has not been carefully tested.

Other sugar substitutes being investigated include glycyrrhizin (derived from licorice) and dihycrochalcone (derived from citrus fruits).

Some studies have reported good success with meal replacement beverages (Slim-Fast, Sweet Success). They contain major nutrients needed for daily requirements. Each serving typically contains between 200 - 250 calories and replaces one meal. (Note: Using them for all meals reduces calories to a severe extent and can be harmful.)

One study reported that most subjects who had undergone a 12-week weight loss program and then used Ultra Slim Fast supplements as directed for maintenance kept off more than half their weight loss after more than 3 years. A quarter of the subjects were still losing weight.

Medical evidence suggests that a diet rich in magnesium could reduce a person's risk of metabolic syndrome, a cluster of problems including obesity, high blood pressure, and high cholesterol. Metabolic syndrome can lead to diabetes and heart disease. A long-term study of thousands of Americans found that the risk for metabolic syndrome decreased in those who consumed the most magnesium from meals. The findings were published in the journal Circulation.

Commercial and Non-Profit Support Programs for Weight Loss. There are many different types of weight-loss program. (This report cannot address all of the many commercial and nonprofit weight-loss programs currently available, nor can it assess their claims.)

Taking off Pounds Sensibly (TOPS), a nonprofit support organization with many local chapters, is one of the least expensive programs, costing $20 a year.

Most of the commercial programs such as Weight Watchers, Jenny Craig, and NutriSystem offer individual or group support, lifestyle changes and packaged meals. These programs tend to be expensive. There are few well-conducted studies on these programs. One 2003 study reported modest weight loss over 2 years with Weight Watchers compared to a self-help program. There were no differences in heart risk factors.

Cognitive Behavioral Approaches. Most support programs use some form of cognitive-behavioral methods to change the daily patterns associated with eating. They are very useful for preventing relapse after initial weight loss. The following is a typical approach:

The patient first records in a diary all activity related to eating patterns, including the times of day, length of meal, emotional states, companions, and, of course, the kind and amounts of food eaten. Most people -- even professional dieticians, according to one study -- tend to underreport their daily calorie intake. However, writing it down is still a good method for increasing a person's awareness of eating patterns. (One patient said that recording circumstances surrounding relapses was a particularly valuable guide for understanding the stresses leading to her own eating behaviors.)
The patient reviews the diary with a therapist or group to set realistic goals and identify patterns that the patient can change. For instance, if food is normally eaten while watching television, then the patient may be advised to eat in another room instead.
Good eating habits are reinforced by rewards. These rewards are other pleasures that substitute the high calorie consumption and sedentary activities.

Behavioral modification has been shown to be helpful particularly for people who have an overly strong response to the taste, smell, and appearance of food. It also may be useful for binge eaters.

Stress-Reduction Techniques. Stress reduction and relaxation techniques may be helpful for some people with obesity, such as those whose weight is related to night-eating syndrome. [See In-Depth Report #31: Stress.]

Changing Sedentary Habits. Making even small changes in physical activity can expend energy. For example, simply getting up to turn the TV on and off instead of using the remote, and standing (instead of sitting) while talking on the phone may help a person lose up to five pounds a year. Other suggestions include cooking one's own food (instead of eating take-out or fast food), walking to as many places as possible, using stairs instead of escalators or elevators, and gardening. Even fidgeting may be helpful in keeping pounds off, and, in one study, chewing gum increased energy expenditure.

No one should rely on such mild activities, however, for serious weight loss. Only high levels of physical activity -- not just using up energy -- help prevent obesity.

Approach to Exercise. Exercise, which replaces fat with muscle, is the critical companion for any weight control program. In a one-year study, women who regularly averaged 3.5 days (176 minutes) of exercise each week lost significantly more weight than women who did not exercise regularly. Women who exercised more than 195 minutes a week lost nearly 7% of their abdominal fat.

People who exercise are more apt to stay on a diet plan. Exercise improves psychological well-being and replaces sedentary habits that usually lead to snacking. Exercise may even act as a mild appetite suppressant. Moreover, exercise improves overall health even with modest weight loss. In support of this, a British study found that overweight fit individuals had half the death rate of unfit trim individuals.

Be aware, however, that the pounds won't melt off magically. Losing significant weight requires both intensive exercise and calorie restriction. In addition, if a person exercises but doesn't diet, any actual pounds lost may be minimal, because denser and heavier muscle mass replaces fat. Nonetheless, regardless of weight loss, a fit body will look more toned and be healthier. In addition, exercise benefits the heart even with modest weight loss.

The following are some suggestions and observations on exercise and weight loss:

The more strenuous the exercise, the better the chances for short-term and long-term success. With intense exercise, the metabolism continues to burn calories before returning to its resting level. This state of elevated metabolism can last for as little as a few minutes after light exercise to as long as several hours after prolonged or heavy exercise.
Of the standard aerobic machines, the treadmill burns the most calories. It may be particularly effective when used in short multiple bouts during the day. In fact, frequent exercise sessions as short as 10 minutes in duration (about four times a day) may be the most successful exercise program for obese people.
Resistance, or strength, training is excellent for replacing fat with muscles. It should be performed two or three times a week.
As people slim down, their initial level of physical activity becomes easier and they burn fewer calories per mile of walking or jogging. The rate of weight loss slows down, sometimes discouragingly so, after an initial dramatic head start using diet and exercise combinations. People should be aware of this phenomenon and keep adding to their daily exercise program.
As people age, they also need to exercise more to keep off the same amount of weight.
Changes in fat and muscle distribution may differ between men and women as they exercise. Men tend to lose abdominal fat (which lowers their risk for heart disease faster than reducing general body fat). Exercise, however, does not appear to have the same effect on weight distribution in women. In one interesting study, women in aerobic and strength training programs lost fat in their arms and trunk, but did not gain muscle tissue in these regions.

Warning Note. Because obesity is one of the risk factors for heart disease and diabetes, anyone who is overweight must discuss their exercise program with a doctor before starting. Sudden demanding exercise, in such cases, can be very dangerous. [See In-Depth Report #29: Exercise.]

Medications

There are several different drugs used for weight loss. Unless specifically instructed by a doctor, people should use non-drug methods for losing weight. Except under rare circumstances, pregnant or nursing women should never take diet medications of any sort, including herbal and over-the-counter remedies.

A 2001 study reported that 7% of American adults use nonprescription weight-loss products. People must be cautious when using any weight-loss medications, including over-the counter diet pills and herbal or so-called natural remedies. Buying unverified products over the Internet can be particularly dangerous.

Green tea. Perhaps the best alternative advice for people who are overweight is to drink tea. Studies have indicated that regular tea drinking is associated with lower weight, particularly in people who drink it for years. Green tea specifically has been associated with increased energy expenditure. One study reported that people who took a green tea extract (Exolise) lost weight and reduced their waist size. Better evidence is needed to confirm the results on this supplement.

Thermogenic Approach to Weight Loss. An approach to weight loss called thermogenic (also hepatothermic) therapy is based on the idea that certain natural compounds have properties that enable the liver to increase energy in the cells and stimulate the metabolism. Theoretically, the result would be fat loss. Among the natural substances used in such products are EPA-rich fish oil, sesamin, hydroxycitrate, pantethine, L-carnitine, pyruvate, aloe vera, aspartate, chromium, coenzyme Q10, green tea polyphenols, aloe vera, DHEA derivatives, cilostazol, diazoxide, and fibrate drugs.

Nearly all the current over-the-counter dietary aids contain some combination of these ingredients. There is no evidence that any of these ingredients can produce weight loss, and some may even have harmful effects.

Chromium is a common ingredient in many diet supplements (e.g., Xenadrine, Dexatrim, Acutrim Natural, Twinlab Diet Fuel). It is claimed to specifically promote fat loss, rather than lean muscle loss. Some evidence suggests that niacin-bound chromium may improve insulin sensitivity. On the negative side, animal studies have suggested that chromium may have damaging effects on genetic materials in cells. This could cause sterility.

Ephedra, Ephedrine, and Ma Huang. The FDA does not allow the sale of drugs that contain ephedrine. In May 2004, the FDA banned the sale of dietary supplements that contain ephedra (also called Ma Huang). Ephedra has been linked to serious side effects, including strokes and heart attacks.

Brazilian Diet Pill. The US Food and Drug Administration (FDA) is warning consumers not to buy a product known as the "Brazilian diet pill." This product is labeled as a dietary supplement, but contains several chemicals found in powerful prescription drugs. The products are also known as Emagrece Sim and Herbathin dietary supplements.

Conjugated Linoleic Acid (CLA). Conjugated linoleic acid is found in many dietary products (e.g., Biosculpt Liquid, Body Success, GNC Optibolic Body Answers Dietary Formula). There is no evidence that it produces weight loss. Furthermore, there is some concern that CLA might increase insulin resistance and a dangerous inflammatory response in people with obesity.

Tiratricol. Over-the-counter products containing tiratricol, a thyroid hormone, have been sold for weight loss. Such products may increase the risk for thyroid disorders, heart attack, and stroke.

Laxative Actions in Natural Substances. Many dietary herbal teas contain laxatives, which can cause gastrointestinal distress, and, if overused, may lead to chronic pain, constipation, and dependency. In rare cases, dehydration and death have occurred. Some laxative substances found in teas include senna, aloe, buckthorn, rhubarb root, cascara, and castor oil.

Guar Gum. Some fiber supplements containing guar gum have also caused obstruction of the gastrointestinal tract.

Chitosan. Chitosan, a dietary fiber from shellfish, prevents a small amount of fat from being absorbed in the intestine. Well-conducted studies, however, have not found it to be effective. Products containing it include Cheat & Lean Fat Blocker, Natrol, Chroma Slim, and Enforma. People who are allergic to shellfish should not take these supplements.

Plantain. Dietary remedies that list the ingredient plantain may contain digitalis, a powerful chemical that affects the heart. NOTE: This substance should not be confused with the harmless banana-like plant also called plantain.

Orlistat (Xenical) can help about one-third of obese patients with modest weight loss, and can assist in long-term maintenance of weight loss. It works by slowing the absorption of fat (by about 30%) in the intestine. Studies indicate that between 50 - 80% of patients can achieve weight loss of 5% or greater, depending on other lifestyle changes. However, many people regain a significant portion of this weight back within 2 years. It does not work for all patients, however. In one survey of patients who took it, 10% gained weight or did not lose any, and 43% lost less than 5%. Nevertheless, orlistat may delay or even prevent the onset or progression of diabetes and improve cholesterol levels, regardless of weight loss.

The drug can cause gastrointestinal problems and may interfere with absorption of the fat-soluble vitamins A, D, and E and other important nutrients. The most unpleasant side effect is oily leakage of feces from the anus. Restricting fats can reduce this effect. People with bowel disease should probably avoid it. In spite of these side effects, most patients are able to tolerate this agent.

In February 2007, the FDA approved an over-the-counter (OTC) version of orlistat. It will be sold under the name alli, and will be available at half the prescription strength of Xenical. Those eager to use the new pill should consider its cost and modest benefits compared with its side effects, most commonly oily diarrhea. This pill, which prevents fat absorption from food, also increases the risk of not absorbing important nutrients from food while using it. The FDA recommends taking a daily multivitamin supplement when using alli.

Sibutramine (Meridia) helps balance the brain chemicals serotonin and norepinephrine. This helps increase metabolism, causes a feeling of fullness, and increases energy levels. It may be particularly useful for binge-eaters. Studies indicate that sibutramine is effective in achieving weight loss, although the weight loss slows considerably after the first 3 months. The drug also appears to improve cholesterol and lipid (fat) levels, and may have other effects that benefit the heart.

Side effects of sibutramine are common. They include dry mouth, constipation, and insomnia. In one study, almost half the patients dropped out as a result of these side effects. There have been reports of increases in heart rate and blood pressure while taking this medication, although a 2001 study indicates that blood pressure stabilizes over time.

At this time, people who have a history of high blood pressure, stroke, heart disease, or arrhythmias should not take this drug. People taking decongestants, bronchodilators (such as for asthma), monoamine oxidase inhibitors, or serotonin reuptake inhibitors should also avoid sibutramine.

Phentermine and Other Sympathomimetics. Sympathomimetics are drugs that act like the stress hormone (and chemical messenger) norepinephrine. These medications act as stimulants in the brain. Some are approved for treating obesity, but only for short-term use. They include:

Phentermine (Ionamin, Adipex-P, Fastin)
Benzphetamine (Didrex)
Phendimetrazine (Adipost, Bontril, Melfiat, Plegine, Prelu-2, Statobex)

Phentermine is the most commonly prescribed appetite suppressant, and is less expensive than orlistat or sibutramine. Its effects are not long lasting, however. It can also raise blood pressure. In addition, phentermine is associated with depression, which is already a problem in many cases of obesity. A combination (Phen-Pro) containing phentermine and the antidepressant fluoxetine (Prozac) is being investigated to help reduce this problem. Note: Neither phentermine nor such combinations are associated with the heart problems linked to the previous phentermine combination known as Fen-Phen (phentermine and fenfluramine).

Amphetamines. The amphetamines dextroamphetamine (Dexedrine), methamphetamine (Desoxyn), and phenmetrazine (Pleudin) are powerful stimulants. They were used most often in the past but are no longer prescribed for weight loss. These drugs improve mood and produce some modest weight loss over the short term, but carry serious risks of addiction, agitation, and insomnia.

Rimonabant. Rimonabant (Accompli) belongs to a new class of drugs called selective CB1 blockers. The drug is designed to block receptors in the brain associated with the regulation of eating. Rimonabant also targets receptors in fat tissue. The Rimonabant in Obesity-Lipids (RIO-Lipids) study looked at how rimonabant affected metabolic risk factors in high-risk overweight or obese patients with blood fat disorders. The study involved more than 1,000 participants. The findings, published in the November 2005 New England Journal of Medicine, said that people who took the drug significantly reduced their body weight and size of their waist.

Earlier studies involving the drug reported that obese patients treated with 20 mg of rimonabant lost significantly more weight and inches from their waist than patients who received placebo. The drug also appeared to have beneficial effects on raising HDL ("good") cholesterol levels.

Note: Fake rimonabant has been found for sale on several web sites. Patients should be aware that this drug is still experimental, and rimonabant is not available for sale. Buying and taking counterfeit drugs can have serious health consequences. In addition, an FDA advisory panel in April 2007 rejected the drug, citing fears it may cause psychiatric problems and seizures in some patients.

Axokine. Axokine is a type of drug called a ciliary neurotrophic factor. It signals the brain to suppress one's appetite. It is proving to be effective in achieving weight loss, and also improves cholesterol, lipid, and glucose levels regardless of food intake. It could be particularly helpful for people with type 2 diabetes. Early study results found that severely obese patient who took the drug lost more weight than those who took a dummy pill (placebo). Nearly half (46%) of patients who took the drug lost at least 10 pounds, compared to 5% of those who received the placebo. Study participants tolerated the drug well. There were no reports of serious side effects.

Zonisamide. Zonisamide (Zonegran) is an anti-seizure medication that is also being investigated for weight loss. In one study, patients who took it lost more weight than those on placebo. Zonisamide increases the risk for kidney stones, which can be reduced with increased fluid intake and citrate. It has also been associated with reduced sweating and a sudden rise in body temperature, especially in hot weather. Other side effects include dizziness, forgetfulness, headache, and nausea.

Topiramate. Topiramate (Topamax) is another anti-seizure medication being investigated for weight reduction. Three clinical trials have reported that patients given topiramate lost more weight than those receiving placebo. Weight loss was sustained for up to 1 year. The drug is also being studied for binge-eating disorders associated with obesity.

Other Treatments

Surgical procedures for obesity may be appropriate for some dangerously obese people, and may reduce heart problems and many of the risks associated with obesity. These risks include high blood pressure, sleep apnea, and diabetes. In fact, some evidence suggests that surgery may provide much greater control of weight and diabetes than nonsurgical weight-loss methods. Studies are reporting significant reductions in diabetes, and the need for diabetic medications, after surgery. Other medical conditions that often improve after surgery include heartburn, arthritis, and other joint and circulation problems.

Bariatric surgeries produce weight loss through one of two approaches:

Restrictive Banding Procedures. These procedures restrict the amount of food by closing off parts of the stomach with bands.
Malabsorptive Bypass Procedures. This approach restricts the amount of food and also reduces absorption by using a bypass of parts of the intestine.

The malabsorptive procedures are more successful in achieving weight loss than the banding approach, but they carry a greater risk for nutritional deficiencies.

Most people who have bariatric surgery lose about two-thirds of excess weight within 2 years. In addition, diseases associated with obesity (such as diabetes, high blood pressure, sleep apnea, joint pain, and incontinence) often improve.

Researchers at the Mayo Clinic looked at records from patients who had the surgery between 1990 and 2003. They found that those who had bariatric surgery reduced their risk of cardiovascular events such as a heart attack much more than those who lost weight without surgery. The findings were published in the September 2005 Mayo Clinic Proceedings.

Other studies have shown that even though most patients maintain significant weight loss, the majority regain about to 10% of their weight. Patients must still develop a healthy life style and be calorie conscious after the operation. Follow-up must be life-long.

Any surgical candidate must have failed consistently in losing weight through less invasive methods. Experts recommend bariatric surgery only for the following:

Those whose BMI is above 40 (about 100 pounds overweight)
Those with BMIs of over 35 who have type 2 diabetes or serious obesity-related medical problems
Those with severe obesity that interfered with employment, normal physical activity (e.g., walking), and important relationship

About a third of people who undergo these procedures achieve normal weight, and 80% experience some weigh loss. They are less successful than the bypass procedures, but carry a lower risk of nutritional deficiencies.

Vertical Banded Gastroplasty. Vertical banded gastroplasty (VBG) was the most common restrictive procedure. It involves creating a hole through both stomach walls and sealing the edges with a staple. This narrows the stomach, similar to a funnel, and allows only small amounts of food to pass through.

Laparoscopic Gastric Banding. Laparoscopic gastric banding (the Lap-Band) usually does not require a major incision and avoids some of the major complications of gastric bypass:

It employs an adjustable silicone band that is placed around the upper part of the stomach.
A small balloon-like reservoir attached to the band under the abdominal skin contains saline, which can be added or removed to tighten or loosen the band.
The procedure restricts the amount of food a person can eat and gives the feeling of fullness.

The band is removable, if necessary. Studies to date indicate that the intestinal tract returns to normal afterward. Studies, including those done in the elderly, have reported significant weight loss and improved quality of life with the procedure.

Malabsorptive procedures produce greater weight loss than restrictive procedures. Patients generally achieve about two-thirds of their weight loss within 2 years. Furthermore, in a 2003 study, after standard bypass surgery, 83% of patients with type 2 diabetes experienced normal blood glucose levels and the rest had significant reductions.

Roux-en-Y Gastric Bypass Procedure. This is the most common and successful malabsorptive surgery in the United States. It involves creating a small stomach pouch that serves as a reservoir and restricts food intake. The pouch eventually holds up to 3 ounces of food and has a small outlet that delays emptying and causes a feeling of fullness. Then the surgeon creates a Y-shaped section in the small intestine that attaches to the pouch. This section allows food to bypass the lower stomach and upper part of the intestine. One 2003 study reported that this procedure was associated with significant weight loss, and 80% of patients with type 2 diabetes were able to reduce their medications. A more recent study, published in the March 14, 2006, issue of Archives of Surgery, found that gastric bypass surgery also helps lower the blood pressure of very obese patients.

The procedure produces greater and more sustained weight loss than banding procedures, but it is also more complicated, and carries a higher risk of nutritional deficiencies. Laparoscopy techniques, which are less invasive, are now preferred over open surgery. They achieve equally good results with fewer complications.

Biliopancreatic Diversion. This procedure is more complicated and removes portions of the stomach. The pouch that is created attaches directly to the lower part of the small intestine. It poses a higher risk for nutritional deficiencies than other procedures and is not used as often.

Click the icon to see an image of gastric bypass surgery.

General Side Effects and Complications. Side effects and complications of bariatric procedures are common, and up to 25% of patients require corrective or repeat procedures. After any of these procedures people must chew all their food carefully, and they cannot eat large amounts of food at one time. If patients do not follow these guidelines, they will experience nausea, abdominal distress, or both.

Complications from any bariatric procedure includes the following:

Vomiting: This is the most common complication, and it is most common with banding procedures.
Nutritional deficiencies: There is a strong risk of nutritional deficiencies, particularly with malabsorptive operations. This complication can lead to anemia and increase the risk of bone loss and osteoporosis. Taking enough mineral and vitamin supplements is important after bariatric surgery.
Deep-vein thrombosis: There is a significant risk for deep-vein thrombosis (blood clots in the veins).
Abdominal hernia: This is another common complication. Newer, laparoscopic techniques do not carry this risk, but not all individuals are candidates for this less-invasive approach.
Rapid weight loss after surgery: This complication puts people at high risk for gallstones.
Women who wish to be pregnant should wait until their weight has stabilized. Rapid weight loss and nutritional deficiencies can harm the fetus.

People at highest risk for complications are those with heart or lung problems, severe obesity, and a history of abdominal surgeries. The mortality rate from bariatric surgeries is 0.2%, which is lower than the morality rates from severe obesity itself. Other surgical variations and less invasive techniques using laparoscopy have been developed.

Specific Complications of Restrictive Banding Procedures. Nausea, vomiting, or both occurs in half the patients, and severe heartburn occurs in a third. Device-related complications include band slippage, pouch dilation (widening), or both in nearly a quarter of patients, and obstruction in 12% of patients. Very serious complications are rare, but include blood clots, bleeding, infection, pneumonia, and perforation (tearing) of the stomach.

Specific Complications of Malabsorptive Bypass Procedures. Vomiting often occurs. Nutritional deficiencies occur more often in these procedures. The so-called dumping syndrome is a common unpleasant side effect, which occurs when food waste moves too quickly through the intestine. Symptoms include nausea, weakness, sweating, and faintness (particularly after eating sweets).

Spot Exercising. Anyone seeking to lose weight must expect that the results may not be as cosmetically satisfying as one would wish. Spot exercising (training particular areas of the body) is ineffective in reducing fat in specific locations because exercise draws on fat stores throughout the body. Gimmicky devices such as bust developers, vacuum pants, and exercise belts do absolutely nothing to reduce fat or add bulk in specific locations. Electrical pads wrapped around the waist, arms, or thighs were reported to cause burns and fires.

Cellulite-Removal Creams. Many women try to reduce fat in their thighs (cellulite) with creams that contain aminophylline (Skinny Dip, Thermojetics Body Toning Cream, Smooth Contours). Studies provide no evidence that these creams are effective. Their apparent effect on fat may simply be from narrowing blood vessels and forcing water from the skin, which could be dangerous for people with blood flow problems.

Endermologie. Endermologie uses motorized rollers and regulated suction to smooth out cellulite. In one study, about 28.6% of patients reported improved appearance after using it.

Liposuction. Liposuction eliminates fat in specific areas, such as the abdomen, thighs, buttocks, or knees. Special instruments are inserted through the skin into the pockets and suction is used to move the fat, break it up, and remove it. Small tubes may be used to drain blood and fluid during the first few days. The pain after the operation can be severe and often the skin does not contract, resulting in a flabby look. Complications can include burns from the vibrators, bruising, blood clots, and bleeding. Weight gain generally tends to develop in other locations after the operation. Some doctors are using this procedure in overweight people with diabetes to remove abdominal fat. Although there is no proof that it has an effect on diabetes, some experts believe the procedure deserves attention.

Liposuction is not recommended for major weight loss.

Resources

www.healthierus.gov/dietaryguidelines -- Dietary Guidelines for Americans 2005
www.naaso.org -- North American Association for the Study of Obesity
www.eatright.org -- American Dietetic Association
www.nutrition.gov. -- Nutrition.gov
www.asbs.org -- American Society for Bariatric Surgery
www.cnpp.usda.gov -- Center for Nutrition Policy and Promotion
http://fnic.nal.usda.gov -- Food and Nutrition Information Center
www.americanheart.org -- American Heart Association
www.nationaleatingdisorders.org -- National Eating Disorders Organization
www.aabt.org -- Association for Advancement of Behavior Therapy
www.fda.gov -- Food and Drug Administration
http://win.niddk.nih.gov -- Weight-Control Information Network

References

US Food and Drug Administration FDA Approves Orlistat for Over-the-Counter Use. Rockville, MD: National Press Office; February 7, 2007.

Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, 1999-2004. Journal of the American Medical Association. 2006; 295:1549-1555.

National Center for Health Statistics. Chartbook on Trends in the Health of Americans. Health, United States, 2005. Hyattsville, MD: Public Health Service. 2005

National Institute of Diabetes and Digestive and Kidney Diseases - Weight-control Information Network. Statistics Related to Overweight and Obesity. Available online.

National Center for Health Statistics. Prevalence of Overweight Among Children and Adolescents: United States, 2003-2004.

Morino M, Toppino M, Bonnet G, Rosa R, et al. Laparoscopic vertical banded gastroplasty for morbid obesity. Assessment of efficacy. Surg Endosc. 2002 Nov;16(11):1566-72.

Brethauer SA, Schauer PR, Chand B. Risks and benefits of bariatric surgery: Current evidence. Cleveland Clinic Journal Of Medicine. 2006 Nov; 73(11): 993-1007.

Rosenthal RJ, Szomstein S, Kennedy CI, et al. Laparoscopic surgery for morbid obesity: 1,001 consecutive bariatric operations performed at The Bariatric Institute, Cleveland Clinic Florida. Obes Surg. 2006 Feb;16(2):119-24.

He K, Liu K, Daviglus ML, et al. Magnesium Intake and Incidence of Metabolic Syndrome Among Young Adults. Circulation. 2006: Published online before print. March 27, 2006.

Chen TY, Smith W, Rosenstock JL, Lessnau KD. A life-threatening complication of Atkins diet. Lancet. 2006 Mar 18;367(9514):958.

Lopez-Jimenez F, Bhatia S, Collazo-Clavell ML, Sarr MG, Somers VK. Safety and efficacy of bariatric surgery in patients with coronary artery disease. Mayo Clin Proc. 2005 Sep;80(9):1157-62.

Sidhaye A, Cheskin LJ. Pharmacologic treatment of obesity. Adv Psychosom Med. 2006;27:42-52.

Fernstrom JD, Courcoulas AP, Houck PR, Fernstrom MH. Long-term changes in blood pressure in extremely obese patients who have undergone bariatric surgery. Arch Surg. 2006 Mar;141(3):276-83.

Despres JP, Golay A, Sjostrom L; Rimonabant in Obesity-Lipids Study Group. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med. 2005 Nov 17;353(20):2121-34.

Lanningham-Foster L, Nysse LJ, Levine JA. Labor saved, calories lost: the energetic impact of domestic labor-saving devices. Obes Res. 2003 Oct;11(10):1178-81.

Review Date:
6/14/2007
Reviewed By:
A.D.A.M. Editorial Team: Greg Juhn, M.T.P.W., David R. Eltz, Kelli A. Stacy. Previously reviewed by Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital (4/30/2007).

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

A.D.A.M. Copyright

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2009 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

adam.com

Hypercholesterolemia

FitSugar — Wed, 08 Oct 2008 17:34:56 -0700

Overview

Signs and Symptoms
Causes
Risk Factors
Diagnosis
Preventive Care
Treatment Approach
Other Considerations
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Hypercholesterolemia, or high cholesterol, occurs when there is too much cholesterol in the body. Cholesterol is a soft, waxy, fat-like substance that is a natural component of all the cells of the body. Your body makes all the cholesterol it needs. Any added cholesterol, which comes through the foods you eat, can cause harm.

High cholesterol raises your risk for heart disease, heart attack, and stroke. When there is too much cholesterol circulating in the blood, it can create sticky deposits (called plaque) along the artery walls. Plaque can eventually narrow or block the flow of blood to the brain, heart, and other organs.

The normal range for total blood cholesterol is between 140 and 200 mg per decilitre (mg/dL) of blood (usually just expressed as a number). However, the total number doesn't tell the whole story: There are two types of cholesterol -- HDL (high-density lipoproteins, or "good" cholesterol) and LDL (low-density lipoproteins, or "bad" cholesterol). The amount of HDL relative to LDL is considered a more important indicator of your risk for heart disease. There is a third kind of fatty material, triglycerides, found in the blood, that also plays a role (generally as triglyceride levels rise, HDL or "good" cholesterol falls). High cholesterol is characterized by high levels of LDL cholesterol, normal or low levels of HDL cholesterol, and normal or high levels of triglycerides.

More and more Americans have high cholesterol. While heredity may be a factor for some people, lack of exercise plus diets high in saturated fats appear to be the main culprits. High cholesterol can be prevented, often with lifestyle changes (diet and exercise) alone. If these do not work, your doctor may recommend medications to bring down your cholesterol levels.

Signs and Symptoms

High cholesterol generally occurs without any symptoms, especially in early stages. The only way to tell if your cholesterol is high is through a blood test.

Causes

In some cases, high levels cholesterol may be inherited -- your liver may make too much cholesterol, or your body may not remove LDL from your blood as efficiently as normal. High cholesterol or triglycerides can also be associated with other diseases, such as diabetes. In most cases, however, high cholesterol is the result of a diet high in saturated fat and a lack of regular exercise. High cholesterol is more common in people who are overweight or obese, a condition that is true of as much as half of the adult U.S. population.

Risk Factors

There are certain factors that put a person at increased risk of having high cholesterol. While some factors cannot be altered by changes in lifestyle, many can be changed. The most important risk factors for high cholesterol are:

Obesity
Eating a diet high in saturated fat and trans fatty acids (found frequently in processed and fried foods)
Not getting enough exercise
Family history of heart disease
High blood pressure
Smoking cigarettes
Diabetes

Diagnosis

Since most people have few if any symptoms of high cholesterol, a blood test is the only way to check levels of cholesterol in your blood. If your levels are above 200 mg/dL or your HDL below 40, your doctor may do a fasting lipid profile (a test performed after you abstain from food for 12 hours).

Although cholesterol levels above 200 are generally considered high, the optimal level for LDL cholesterol depends on whether you are at risk for or have heart disease.

Total cholesterol levels:

Desirable: Below 200 mg/dL
Borderline high: 200 - 239
High: Above 240

LDL cholesterol levels:

Optimal for people with heart disease or at high risk: Below 70 mg/dL
Optimal for people at risk of heart disease: Below 100
Optimal: 100 - 129
Borderline high: 130 - 159
High: 160 - 189

HDL cholesterol levels:

Poor: Below 40 mg/dL
Acceptable: 40 - 59
Optimal: 60 or above

Triglyceride levels:

Optimal: Below 150 mg/dL
Borderline high: 150 - 199
High: Above 200

Adults with normal total and HDL cholesterol levels should have their cholesterol checked every 5 years. If you have high cholesterol, you should be checked every 2 - 6 months and have liver function tests as well if you are on cholesterol-lowering medication.

Preventive Care

Most people can lower cholesterol levels by eating a well-balanced diet, getting regular exercise, and losing any excess weight.

Diet

A healthy diet can help you lose any excess pounds. Even losing just 5 or 10 pounds may help you lower your cholesterol. To eat a healthy diet:

Cut down on saturated fats and trans fats. No more than 10 percent of your daily calories should come from saturated fat, and you should avoid trans fats completely. Choose unsaturated fats, such as olive oil and canola oil, instead.
Eat whole grains -- whole wheat bread and pasta, oatmeal, oat bran, and brown rice.
Eat more fruits and vegetables, which are high in fiber and can help lower cholesterol levels.
Limit cholesterol in your diet. The highest amounts are found in egg yolks, whole milk products, and organ meats.
Eat fatty fish. The American Heart Association recommends that people eat at least 2 servings of fatty fish (such as salmon or herring) each week.

The American Heart Association (AHA) has developed dietary guidelines that help lower fat and cholesterol intake and reduce the risk of heart disease. The AHA does not recommend very low-fat diets, because new research shows that people benefit from unsaturated ("good") fats, such as those found in olive oil, in their diet.

Many fad diets are popular, but they may not help you lose weight and keep it off -- and in some cases, they may not even be healthy. Any healthy diet will include a variety of foods. If a diet bans an entire food group (such as carbohydrates), it's probably not healthy.

The AHA recommends the following for healthy eating:

Grains: 6 - 8 servings per day (half should be whole grains)
Vegetables: 3 - 5 servings per day
Fruits: 4 - 5 servings per day
Fat-free or low-fat dairy: 2 - 3 servings per day
Lean meat, poultry, seafood: 3 - 6 oz. per day (about the size of a deck of cards)
Fats and oils: 2 - 3 tbsp. per day (use unsaturated fats such as olive oil or canola oil)
Nuts, seeds, legumes: 3 - 5 servings per week
Sweets, sugars: 5 or fewer servings per week (the fewer, the better)

In addition, the AHA also recommends eating 2 servings of fatty fish (such as salmon, herring, or lake trout) per week; holding sodium (salt, including salt already added to food) to less than 2,400 mg per day; and limiting alcohol intake to one drink a day for women and two for men.

The Mediterranean style diet concentrates on whole grains, fresh fruits and vegetables, fish, olive oil, and moderate, daily wine consumption. This diet is not low-fat. Instead, it is low in saturated fat but high in monounsaturated fat. This diet is naturally rich in fiber, antioxidants, and omega-3 fatty acids. It appears to be heart-healthy: In a long-term study of 423 patients who had a heart attack, those who followed a Mediterranean style diet had a 50 - 70% lower risk of recurrent heart disease compared with people who received no special dietary counseling.

Losing Weight

Being overweight increases risk of high cholesterol and heart disease. Even a 5- to 10-pound weight loss can lower LDL twice as much as diet alone. Weight loss often results in lower triglyceride levels and increased HDL, too. To maintain a healthy diet, you should aim for a gradual, weekly weight loss of 1/2 to 1 pound.

Getting Exercise

Regular exercise both reduces the risk of death from heart disease and helps lower LDL cholesterol levels, especially when combined with a healthy diet. Thirty minutes of moderate exercise three to five times per week can help you lose weight or maintain a proper weight, reduce LDL and triglyceride levels, and increase levels of HDL. Exercise may also lower blood pressure. Talk with your doctor before starting a new exercise plan.

Treatment Approach

Lowering your cholesterol level reduces your risk of heart disease and stroke. Studies have shown that for every 1% reduction in cholesterol levels there is a 2% reduction in the rate of heart disease. People who already have heart disease or are at higher risk benefit most from lowering their cholesterol.

Changes in lifestyle -- better diet, more exercise -- are the most effective means of both preventing and, in less severe cases, treating high LDL cholesterol levels. In addition to lifestyle changes, specific cholesterol-lowering medications are often prescribed.

Medications

If, after making adjustments to your diet and exercise habits, your LDL cholesterol remains high, your doctor may prescribe medications to lower it. If your cholesterol is extremely elevated (more than 200 mg/dL), you may start drug therapy at the same time you make lifestyle changes. Drugs commonly used to treat high cholesterol include:

Statins (such as lovastatin, pravastatin, simvastatin, atorvastatin, and fluvastatin) -- These are usually the drugs of choice as they are easy to take and have few interactions with other drugs. Side effects can include myositis (inflammation of the muscles), joint pain, stomach upset, and liver damage. People who are pregnant or have liver disease should not take statins.

Niacin (nicotinic acid) -- In prescription form, niacin is sometimes used to lower LDL cholesterol and can be more effective in raising HDL cholesterol than other medications. Side effects may include redness or flushing of the skin (which can be reduced by taking aspirin 30 minutes before the niacin), stomach upset (which usually subsides in a few weeks), headache, dizziness, blurred vision, and liver damage. Dietary supplements of niacin should not be used instead of prescription niacin, as it can cause side effects. Only take niacin for high cholesterol with your doctor's supervision.

Bile acid sequestrants (such as cholestyramine, colestipol, and colesevelam) -- These are used to treat high levels of LDL. Common side effects include bloating, constipation, heartburn, and elevated triglycerides. People who have high levels of triglycerides (fats in the blood) should not take bile acid sequestrants.

Fibric acid derivatives (such as gemfibrozil and clofibrate) -- These medicines are effective at lowering triglyceride levels, and moderately effective at lowering LDL. They are used to treat high triglycerides and low HDL in people who cannot tolerate niacin. Side effects include myositis, stomach upset, sun sensitivity, gallstones, irregular heartbeat, and liver damage.

Probuchol -- This medicine lowers both LDL and HDL. Its use is generally limited to certain types of hereditary high cholesterol or when other cholesterol-lowering medications have been ineffective. Side effects include diarrhea, bloating, nausea, and dizziness

If you do not respond to one class of drugs, you doctor may use a combination of drugs from two classes.

Nutrition and Dietary Supplements

In addition to eating a healthy diet -- low in saturated fat, with plenty of whole grains, fruits, and vegetables -- some specific foods and supplements may help lower cholesterol.

Fiber -- Several studies have shown that soluble fiber (found in beans, oat bran, barley, apples, psyllium, flaxseed, and glucomannan) lowers LDL cholesterol and triglycerides. Fiber can also help you lose weight because it makes you feel full faster. Your doctor will encourage you to get more fiber in your diet. You may also take a fiber supplement. Men should get 30 - 38 g of fiber per day. Women should get 21 - 25 g.

Soy -- Many studies have shown that eating soy protein (tofu, tempeh, miso) rather than animal meat helps lower blood cholesterol levels, especially when you eat a diet low in saturated fat. One study has shown that as little as 20 g of soy protein per day is effective in reducing total cholesterol, and that 40 - 50 g shows faster effects (in 3 weeks instead of 6). One study has shown that soy can help reduce triglyceride levels. The AHA recommends that people with elevated total and LDL cholesterol add soy to their daily diet, and that soy is safe when consumed as part of your regular diet. Before you take soy supplements, however, talk to your doctor. Soy isoflavones may have estrogen-like effects on the body, which might lead to an increased risk of breast and other cancers.

Omega-3 fatty acids, found in fish oil -- There is good evidence that omega-3 fatty acids (namely EPA and DHA) found in fish oil can help prevent heart disease, lower blood pressure, and reduce the level of triglycerides (fats) in the blood. However, fish oil can also raise levels of both HDL and LDL slightly. When taken as a supplement, it can also act as a blood-thinner, so people who already take blood-thinning medication should only take a fish oil supplement under their doctor's supervision. The AHA recommends that people eat at least two servings of fatty fish (such as salmon) per week, and that fish is safe when consumed as part of your regular diet. If you have high cholesterol, talk to your doctor before taking a fish oil supplement.

Alpha-linolenic acid (ALA) -- ALA is another omega-3 fatty acid that may protect the heart against heart disease. However, studies have shown conflicting results about its ability lower LDL, and it does not appear to lower triglyceride levels.

Vitamin C (100 - 200 mg per day) -- Several studies suggest that eating a diet high in vitamin C can help lower cholesterol levels, but there is no evidence that taking extra vitamin C through a supplement will help.

Beta-sitosterol (800 mg to 6 g per day in divided doses about 30 minutes before meals) -- Beta-sitosterol is a plant sterol, a compound that can stop cholesterol from being absorbed by the intestines. Several well-designed scientific studies have shown that beta-sitosterol does lower LDL ("bad") cholesterol levels in the body. Beta-sitosterol may lower the amount of vitamin E and beta-carotene absorbed by the body, so you may want to ask your doctor if you need to take extra vitamin E or carotene.

Policosanol (5 - 10 mg two times per day) -- Policosanol is a mix of waxy alcohols usually derived from sugar cane and yams. Several studies have indicated it may lower LDL ('bad") cholesterol and possibly even raise HDL ("good") cholesterol. One study found that policosanol was equivalent to fluvastatin (Lescol) and simvastatin (Zocor) in lowering cholesterol levels. It may also inhibit blood clots from forming. However, almost all the studies have been conducted in Cuba or Latin America using a proprietary form of policosanol, so it is hard to evaluate the evidence. Policosanol may increase the risk of bleeding, and should not be taken by people who also take blood-thinning medication.

Coenzyme Q10 (CoQ10) -- Researchers believe that CoQ10 may inhibit blood clot formation and boost levels of antioxidants. One study found that people who received daily CoQ10 supplements within 3 days of a heart attack were much less likely to experience subsequent heart attacks and chest pain and were also less likely to die of the condition than those who did not receive the supplements. Still, more research is needed to say whether CoQ10 has any role in preventing or treating atherosclerosis. People who take statins may have low levels of CoQ10. If you take statins you may want to ask your doctor about taking a CoQ10 supplement.

Polyphenols -- Polyphenols are chemical substances found in plants that have antioxidant properties. Test tube, animal, and some population-based studies suggest that the flavonoids quercetin, resveratrol, and catechins (all found in high concentration in red wine, and in grape juice) may help reduce the risk of atherosclerosis by protecting against the damage caused by LDL cholesterol. However, more studies in humans are needed to confirm these findings.

Resveratrol -- A recent study of resveratrol in mice found that it protected against age-related damage to vital organs, including the heart and liver, even when the mice ate a high-fat diet. Although this study is promising, researchers need to confirm its findings and to determine whether resveratrol would have the same effect in humans. To equal the rate at which the mice were given resveratrol, humans would have to consume enormous quantities. In addition, resveratrol may have estrogen-like effects, and researchers don't yet know whether it would pose the same risks as estrogen supplements.

Herbs

The use of herbs is a time-honored approach to strengthening the body and treating disease. Herbs, however, can trigger side effects and can interact with other herbs, supplements, or medications. For these reasons, herbs should be taken with care, under the supervision of a healthcare practitioner.

Hawthorn ( Crataegus monogyna, 900 - 1,800 mg per day in two or three divided doses) -- Hawthorn contains the polyphenols rutin and quercetin, and was used traditionally to treat cardiovascular diseases. Animal and laboratory studies show that hawthorn has antioxidant properties that may help lower high cholesterol and high blood pressure. Talk to your doctor before taking hawthorn, as it can interact with other drugs taken for heart disease and high blood pressure.

Garlic ( Allium sativum, 900 mg per day of garlic powder, standardized to 0.6% allicin) -- Previous clinical trials have shown that fresh garlic and garlic supplements may lower cholesterol levels, prevent blood clots, and destroy plaque. However, more recent studies show no effect on cholesterol. Garlic can increase the risk of bleeding and should not be taken if you are also taking blood-thinning medication.

Red yeast ( Monascus purpureus , 1,200 mg two times per day with meals) -- Several studies indicate that a proprietary form of red yeast (Cholestin) can lower cholesterol levels, and that the herb acts like prescription statin drugs (See "Medications" section). For that reason, you should not take red yeast without a doctor's supervision, especially if you already take statins to lower cholesterol.

Psyllium ( Plantago psyllium, 10 - 30 g per day in divided doses taken 30 - 60 minutes after meals) -- Taking psyllium, a type of fiber, helps lower cholesterol levels as well as blood sugar levels. If you take medicine for diabetes, talk to your doctor before taking psyllium.

Guggul (Commiphora mukul, 3 - 6 g per day) -- Guggul is used in Ayurvedic medicine to treat high cholesterol levels. Scientific studies have found mixed results -- guggul appears to work in Indian populations, but not in people who eat Western-style, high-fat diets.

Other Considerations

Pregnancy

Cholesterol-lowering medications should be avoided during pregnancy.

Prognosis and Complications

Several complications may occur if high cholesterol is left untreated. These include:

Heart disease -- elevated cholesterol levels more than double the risk of heart attack. Lowering cholesterol by 1% reduces the risk of coronary artery disease by 2%.
Stroke -- low levels of HDL cholesterol have been associated with an increased risk of stroke.
Insulin resistance -- 88% of people with low HDL and 84% with high triglycerides also have insulin resistance (which leads to high blood sugar levels). Many people with insulin resistance go on to develop diabetes.

Maintaining the proper weight, eating a diet low in saturated fat, and exercising can lower cholesterol levels and improve long-term prognosis.

Supporting Research

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Review Date:
3/23/2007
Reviewed By:
Steven D. Ehrlich, N.M.D., private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

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Colon and rectal cancers

FitSugar — Wed, 08 Oct 2008 17:35:05 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Risk Factors
Dietary Factors
Prevention
Diagnosis
Staging
Prognosis
Surgery
Medications
Radiation Treatment
Follow-up Testing
Treatment for Metastasized ...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In September 2006, the Food and Drug Administration approved panitumumab (Vectibix) for the treatment of patients with colorectal cancer that has spread to other parts of the body following chemotherapy. Like cetuximab (Ertibux), panitumumab targets the epidermal growth factor receptor (EGFR) on cancer cells. Panitumumab is the first new colorectal cancer drug approved since 2004. The FDA granted accelerated approval to panitumumab based on a clinical trial of patients with metastatic cancer. The average time to disease progression or death was 96 days in patients treated with panitumumab compared to 60 days in patients who received standard care.

Diet and Colorectal Cancer Recurrence

Evidence indicates that diet plays a role in colorectal cancer prevention. Now, a 2007 study in the Journal of the American Medical Association (JAMA) suggests that dietary factors also affect the risk of cancer recurrence. Patients with stage III colorectal cancer who ate lots of red meat, refined grains, and sweets had a higher risk of cancer recurrence and death than patients whose diets were high in fruits and vegetables, poultry, and fish.

Folic Acid No Good for Prevention?

Many experts have long believed that folic acid supplements may help protect against colorectal cancer. But according to a 2007 JAMA study, high-dose folic acid supplements may not prevent colorectal cancer and may actually increase the risk for adenomatous polyp formation. Adenomatous polyps are benign colorectal tumors that can potentially become cancerous. In the study, patients who took folic acid supplements had a greater risk of developing new, more numerous, and larger adenomatous polyps than patients who did not take the supplements.

NSAIDS Not Recommended for Colorectal Cancer Prevention

In March 2007, the U.S. Preventive Services Task Force (USPSTF) recommended against the routine use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) to prevent colorectal cancer in people who are at average risk for this disease. Several recent studies have indicated that aspirin, and NSAIDs such as celecoxib (Celebrex), can help prevent colorectal cancer. But the USPSTF notes that the risks of these drugs outweigh the benefits. Long-term daily use of NSAIDs increases the risk for gastrointestinal bleeding, kidney function problems, and heart attack and stroke.

Introduction

Cancers of the colon and rectum, often referred to collectively as colorectal cancer, are life-threatening tumors that develop in the large intestine.

More than 80% of colorectal tumors evolve from adenomatous polyps. These gland-like growths develop on the mucous membrane that lines the large intestine. They are usually either:

Tubular polyps, which protrude mushroom-like
Villous adenomas, which are flat and spreading and are more apt to become malignant (cancerous)

Polyps are very common and almost always benign. Their numbers increase with age. Polyps are found in about 25% of people by age 50, and 50% of people by age 75. Fewer than 1% of polyps under 1 centimeter (slightly less than half an inch) become cancerous. About 10% of larger polyps become cancerous within 10 years, and about 25% of these larger polyps become cancerous after 20 years. Certain inherited polyps can become cancerous more rapidly.

Digestion takes place in the gastrointestinal (GI) tract, essentially a long tube that extends from the mouth to the anus. It is a complex organ system that first carries food from the mouth down the esophagus to the stomach. Food then travels through the small and large intestines before being excreted through the rectum and out the anus.

The esophagus, stomach, large and small intestine -- aided by the liver, gallbladder, and pancreas -- convert the nutritive components of food into energy and break down the non-nutritive components into waste to be excreted.

The esophagus is a narrow muscular tube, about 9 1/2 inches long that begins below the tongue and ends at the stomach.

In the stomach, acids and stomach motion break food down into particles small enough so that the small intestine can absorb nutrients.

Click the icon to see an image of stomach anatomy.

The small intestine, despite its name, is the longest part of the gastrointestinal tract, extending for about 20 feet. Food passes from the stomach through its three parts: first the duodenum, then the jejunum, and finally the ileum. Most of the digestive process occurs in the small intestine.

Click the icon to see an image of small intestine anatomy.

Undigested material, such as plant fiber, is passed next to the large intestine, mostly in liquid form. The large intestine is wider than the small intestine but only about 6 feet long. It is the final portion of the digestive tract and includes the cecum, the appendix, the colon, and the rectum, which extends to the anus.

Cecum and Appendix. The cecum and the appendix are located in the lower-right quadrant of the abdomen.

Colon. The colon absorbs excess water and salts into the blood. The remaining waste matter is converted to feces through bacterial action. The colon is divided into four major sections.

Click the icon to see an image of large intestine anatomy.

The first section, the ascending colon, extends upward from the cecum on the right side of the abdomen.
The second section, the transverse colon, crosses the upper abdomen to the left side.
The third section extends downward on the left side of the abdomen toward the pelvis and is called the descending colon.
The final section is the sigmoid colon.

Rectum and Anus. Feces are stored in the descending and sigmoid colon until they are passed through the rectum and anus. The rectum extends through the pelvis from the end of the sigmoid colon to the anus.

Causes

In most cases of colon or rectal cancers, the cause or causes are unknown. Defects in genes that normally protect against cancer play the major role in causing polyp cells to continuously spread and become cancerous. Some of these cases are caused by inherited genetic defects, and such patients usually have family histories of colorectal cancer. Most of the genetic mutations involved in colon cancers, however, appear to arise spontaneously (no strong family history) rather than being inherited. In such cases, environmental or other factors trigger genetic changes in the intestine that lead to cancer.

About 6% of cases of colon cancer are due to inherited factors.

APC Gene and Familial Adenomatous Polyposis (FAP). When the adenomatous polyposis coli (APC) gene is normal, it helps suppress tumor growth. In its defective form, it permits high levels of the protein beta-catenin to accumulate, which accelerates cell growth leading to polyps. Various genetic mutations that affect the APC gene directly or indirectly have been identified:

Familial adenomatous polyposis (FAP) is a rare and serious disorder in which the patient inherits an adenomatous polyposis coli (APC) mutation from either parent. It occurs in about 1 in 8,000 people. During early adulthood, hundreds to thousands of polyps grow in the colon. FAP causes less than 1% of all cases of colorectal cancer, but if untreated, virtually everyone who inherits this condition develops cancer before the age of 40. Many of the deaths attributed to FAP can be prevented with early and aggressive surgical treatment.
Non-inherited mutations of the APC gene have been detected in nearly all patients with spontaneous colon cancers.

Hereditary Nonpolyposis Colorectal Cancer (HNPCC). Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, accounts for at least half of colorectal cancers that run in families. (However, only 3% or less of all colorectal cancers are due to this problem). About 50 - 80% of people who inherit the abnormal gene will develop colon cancer. HNPCC tends to develop in the right side of the colon, often in young individuals. (Left-sided cancers can still occur as well.)

People who inherit HNPCC and other defects are prone to other cancers, including uterine and ovarian cancers, as well as cancers of the small intestine and kidney system (very rare). HNPCC is highly associated with genes containing an abnormality called microsatellite instability (MSI), which is a sign of defective DNA repair. Testing tumors for MSI in people with newly diagnosed colon cancer who also have a family history of the disease may prove to be an effective method for identifying patients with hereditary nonpolyposis colorectal cancer. Tests are being developed that can detect the actual HNPCC genetic abnormality (mutation) that was inherited from a father or mother. The two most commonly affected genes are MSH2 and MLH1.

Cyclooxygenases and Prostaglandins. Cyclooxygenase 1 and 2 (COX-1 and COX-2) are enzymes involved in the production of prostaglandins, substances produced by the body that cause inflammation, widen and narrow blood vessels, control muscle contractions, and inhibit hormones that regulate fat metabolism. COX-2, but not COX-1, appears to play a role in the development and spread of colorectal tumors. COX-2 increases the levels of prostaglandin E2 (PGE2), which, in turn, stimulates factors that inhibit apoptosis, the natural process whereby all cells, including cancerous ones, self-destruct. It also activates interleukin-6 (IL-6), a factor in the immune system that is associated with cancer cell invasion.

C-Reactive Protein (CRP). CRP is another indicator of inflammation. In a 2004 study published in the Journal of the American Medical Association, elevated CRP levels predicted the development of colon -- but not rectal -- cancer.

Bile Acid Salts. Deoxycholic acid, which is found in the fat-digesting bile salts released by the gallbladder, appears to have carcinogenic properties. Its effects are now believed to play a role in some cases of colon cancer. Levels of the acid can rise as a result of high-fat diets or certain diseases.

Growth Factors. Chronically higher circulating levels of growth factors, including insulin-like growth factor, have been associated with colorectal cancer.

Inflammatory bowel diseases include Crohn's disease and ulcerative colitis. These chronic disorders cause persistent injuries in the intestinal tract that can, in some cases, produce cancerous changes.

Symptoms

It is possible to have colon or rectal cancer without symptoms. Many patients are free of symptoms until their tumors are quite advanced.

Weight loss and changes in bowel movements are general symptoms for colon cancer, but these symptoms also occur in many other diseases.

Blood in the stools is a common sign of many intestinal cancers. It may appear red if it is fresh or black if it is old. It should be reported to a doctor immediately, even though it is often caused by conditions other than cancer, including:

Hemorrhoids
Minor tears around the rectal or anal areas
Diverticulosis

In addition, stool can change color by:

Eating certain red foods, such as beets or red licorice (red)
Taking iron supplements and medications that have bismuth subsalicylate, most commonly Pepto-Bismol (black)

Nevertheless, blood in the stools is an abnormal finding that should never be ignored. Always report it to your doctor for further advice.

Symptoms of colorectal cancer vary widely depending on the location of the cancer within the large intestine.

Tumors in the Cecum and Ascending Colon (Right Colon). The waste matter in the first portion of the colon is in liquid or semi-liquid form. Tumors that develop here do not change bowel habits or stool formation, but they may cause intermittent or chronic bleeding. Although the stools look normal, patients may develop symptoms of anemia from iron deficiency. Such symptoms include weakness, fatigue, heart palpitations, shortness of breath, and exercise intolerance.

Tumors in the Transverse Colon. As waste material passes across the upper quadrants of the abdomen (the transverse colon), the intestine absorbs water, and the waste matter becomes more solid. In addition to bleeding, tumors here may cause cramps, gas, partial or complete obstruction, and even perforation of the bowel. Anemia can also occur.

Tumors in the Descending Colon and Rectum (Left Colon). When tumors partially block the lower intestine, thin, pencil-shaped stools may form. Bowel habits can change. Tumors in the rectum and lowest part of the intestine can cause pain and a feeling of fullness. Defecation may be painful, or patients may feel the urge to defecate but nothing happens. Bleeding from these locations may be brisk and bright red or maroon, but cancer is often detected before symptoms of chronic anemia develop.

Risk Factors

Colorectal cancer is the third most common cancer in the U.S., with Americans facing a lifetime chance of 5.5 - 6% for this cancer. In 2007, colorectal cancer was expected to cause 153,760 new cases and 52,180 deaths in the United States. About 73% of cancers occur in the colon and 27% in the rectum.

The lifetime risk of cancer of the colon or rectum is 5.9% for men and 5.5% for women.

Colorectal cancer risk increases with age. More than 90% of these cancers occur in people over age 50. The rate of colorectal cancer in patients under 20 years is less than 1 in 100,000 per year. At age 50 about 1 in 2,000 people per year will develop colorectal cancer. After age 65, this rate increases to almost 3 in 1,000.

African-Americans have the highest risk of being diagnosed with, and dying from, colorectal cancer. Among Caucasians, Jews of Eastern European (Ashkenazi) descent have an elevated rate of colorectal cancer. Asian Americans/Pacific Islanders, Hispanics/Latinos, and American Indians/Alaska Natives have a lower risk than Caucasians.

About 20 - 25% of colorectal cancers occur among people with a family history of the disease. (Seventy-five percent of cases are due to other causes.) People who have more than one first-degree relative (sibling or parent) with the disease are especially at high risk. The risk is even higher if the relative was diagnosed with colorectal cancer before the age of 60.

About 5 - 10% of patients with colorectal cancer have an inherited genetic abnormality that causes the disease. Genetic mutations associated with colorectal cancer include familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer.

The risks for colon cancer are far higher in industrialized nations than less developed countries. A Western lifestyle, being sedentary, smoking, and having excess weight have all been associated with increased risk for colorectal cancer. (However, about 75% of cases occur without a known predisposing factor.)

Dietary Factors. Eating a lot of red meat increases the risk for colorectal cancer. Other types of animal protein (low-fat dairy products, fish, poultry) may decrease the risk of developing polyps and colorectal cancer. Studies on fruits, vegetables, and fiber are mixed. Some evidence suggests that diets very low in fruits and vegetables may increase the risk. In any case, eating a variety of fruits and vegetables should be part of a healthy diet.

A 2007 study in the Journal of the American Medical Association suggested that diet may play a role in colorectal cancer recurrence, as well as prevention. The study evaluated patients with stage III colon cancer who had been treated with surgery and chemotherapy. Patients who ate diets high in red and processed meats, refined grains, and sweets had a higher risk of cancer recurrence and poorer survival than patients whose diets were high in fruits and vegetables, poultry, and fish.

Alcohol and Smoking. Alcohol use and smoking increase the risk for colorectal cancer. Patients who smoke and drink may also be diagnosed with colorectal cancer at a younger age than non-drinkers and non-smokers. Several studies suggest that women who smoke are at especially high risk of developing colorectal cancer.

Obesity. There is a demonstrated link between body mass and colon cancer risk for both men and women. The Centers for Disease Control and Prevention has reported that the risk of colon cancer rises as body mass index increases. Obesity has been associated biologically with higher circulating levels of insulin and a hormone called insulin-like growth factor. Chronically high levels of these substances may increase colorectal cancer risk.

Physical Inactivity. More than 50 studies from around the world suggest that physical activity helps prevent colon cancer. In contrast, exercise does not protect against rectal cancer.

Crohn's disease and ulcerative colitis are chronic afflictions of the large intestine known as inflammatory bowel diseases (IBD). Both have been linked to increased risk for colorectal cancer. (Patients with ulcerative colitis have a higher risk than those with Crohn's disease.) Family histories are helpful in determining risk associated with inflammatory bowel disease. Some studies suggest the following:

Patients with IBD who have a family history of colorectal cancer face up to a five-fold risk of colon cancer themselves.
Individuals without IBD who have relatives who suffered from both IBD and colorectal cancer may face a higher risk for developing colorectal cancer themselves.
Individuals without IBD but with a family history of IBD and no colon cancer most likely face no higher risk for cancer themselves.

Crohn's disease, also called regional enteritis, is a chronic inflammation of the intestines that is usually confined to the terminal portion of the small intestine, the ileum. Ulcerative colitis is a similar inflammation of the colon, or large intestine. These and other inflammatory bowel diseases have been linked with an increased risk of colorectal cancer.

Polyps. Polyps are tissue growths, usually benign, that develop in the color or rectum, most often in patients over 50 years of age. When pathologists examine polyps removed from the colon, they classify them as either hyperplastic or adenomatous. Both types are benign, but some adenomas will become malignant. As a preventive measure, polyps should be removed (polypectomy).

Ureterosigmoidostomy. People who have had ureterosigmoidostomy, a surgical procedure to correct a birth defect in the bladder or to treat some bladder cancers, may develop tumors near the site of the defect, which is chronically exposed to urine and feces. Such patients have a 5 - 10% chance of developing colon cancer 15 - 30 years after the operation.

Diabetes. Many studies have identified an association between type 2 diabetes and colon cancer. Both diseases share common risk factors of obesity and physical inactivity, but diabetes itself is a risk factor for colorectal cancer. Both men and women who have diabetes are at risk.

Heart Disease. Coronary artery disease (CAD) increases the risk for colorectal cancer. Both CAD and colorectal cancer share important risk factors, including smoking, high fat diet, sedentary lifestyle, and obesity.

Dietary Factors

Some, but not all, studies have suggested that a high intake of fruits and vegetables can lower the risk for colorectal cancer. One study, for example, reported that these foods do not prevent polyps from forming but may help prevent them from becoming cancerous.

Phytochemicals. Many studies have demonstrated the cancer-fighting effects of plant chemicals called phytochemicals. Fruits and vegetables that contain phytochemicals can often be identified by colors:

Dark green (broccoli, spinach, kale, collard greens, mustard greens). These vegetables contain chemicals called isothiocyanates, which have been associated with a lower risk for cancer in general.
Red (red pepper, tomatoes, watermelon, raspberries, pink grapefruit). Lycopene is a chemical found in these foods that may have strong cancer-protective properties. Cooking tomatoes appears to increase their benefits.
Yellow-orange (carrots, pumpkin, sweet potatoes, oranges, tangerines). The colors in these foods are due to carotenoids. Carotenoids have been associated with health protection, although they may not have much effect on colon cancer itself.
Blue-black (many berries). Dark berries appear to have potent antioxidant chemicals that may be protective against cancer.

Organosulfurs are important food chemicals that are part of the allium family. Studies have reported health benefits from foods containing them. These compounds are found in garlic, leeks, onions, chives, scallions, and shallots. A review of 300 studies concluded that people who eat raw or cooked garlic regularly experience about two-thirds the risk of colorectal cancer as people who eat little or none. Another analysis, however, found the available evidence about garlic to be inconclusive. Garlic supplements, in any case, do not appear to be protective.

Fiber. Studies have been mixed on whether fiber (found in fruits, vegetables, and whole grains) protects the colon from cancer. For example, three major studies in 2002 and 2003 reported no difference in the development of colorectal polyps or cancer recurrence with high intake of fiber. On the other hand, results of the 2003 European Prospective Investigation into Cancer and Nutrition (EPIC) -- the largest study ever conducted on the role of diet in the development of cancer -- suggested that fiber is protective regardless of its source. However, in the study, the greatest benefits were observed for the left side of the colon and the least for the rectum. In any case, fiber, which is only found in plant products, may be beneficial for the heart and have other health advantages.

The role of fats in inflammatory bowel disease is complex and not fully known. A 2006 study from the Women’s Health Initiative found that a low-fat diet did not help reduce the risk for colorectal cancer. However, the study did not distinguish between types of fat.

Monounsaturated fats (olive, peanut, canola oils; avocados, nuts) and omega-3 polyunsaturated fats (fish, flaxseed oil, walnuts) are the healthiest types of fats.
Saturated fats (red meat, butter, high-fat dairy products) and trans-fats (hydrogenated fat found in snack foods, fried foods, commercial baked goods) are unhealthy types of fats.

Dietary guidelines recommend that adults limit the total fat in their diet to 25 - 35% of total daily calories. Saturated fat intake should be less than 7%, and trans fats less than 1%, of total daily calories. (Patients with heart disease or diabetes may need to limit unhealthy fat in their diet even further.) Most fats should come from polyunsaturated and monounsaturated fat sources.

[See In-Depth Report #43: Heart healthy diet; and #42: Diabetes diet.]

Evidence strongly suggests that red meat raises the risk for colon cancer development, and perhaps also recurrence. Red meat contains dietary iron, which has been associated with a higher risk for colon cancer.

High-temperature cooking (grilling, broiling, or pan-frying) has been specifically associated with increased risk for colon polyps and colon cancer. Overcooking meat increases the amount of carcinogens called heterocyclic amines, which has been associated with cancerous changes.

Milk, Lactose, and Probiotics. In one study, adults who drank the most milk had the lowest risk for colon cancer. A 2004 study published in the Journal of the National Cancer Institute supported this conclusion. In this review of 10 epidemiologic studies that included more than 500,000 people, those who consumed more milk and calcium had a lower risk of developing colorectal cancer. Milk contains not only calcium but also other compounds, such as lactose, that may help protect against colon cancer.

Yogurt specifically has been associated with a lower risk for colon cancer if it contains live active bacterial cultures, such as Lactobacillus acidophilus, that are called probiotics. These "friendly bacteria" appear to protect the colon from cancerous changes. (Acidophilus and other probiotic capsules are also available in health food stores.)

Calcium. Calcium, which is found in dairy products, is associated with colon cancer protection. Many studies have shown a possible protective effect from either high-calcium diets or calcium supplements. However, a 2006 study from the Women’s Health Initiative found that calcium and vitamin D supplements do not reduce women’s colorectal cancer risk. Many doctors still recommend that postmenopausal women take these supplements for bone health.

Obesity has been associated with colon cancer. In some studies of people under 67 years old, the amounts of fat and protein were less important than the total number of calories consumed: the higher the energy intake, the greater the risk for developing colon cancer. In older adults, high calorie intake did not make any significant difference. Other studies have indicated that eating too much sugar may increase the risk for colon cancer.

Studies conducted in several countries have found that drinking four or more cups of coffee a day is associated with a lower risk for colorectal cancer. Green tea may have also beneficial properties, but more research is needed in both of these areas.

Folate and B Vitamins. For years, many doctors have believed that the B vitamin folate (called folic acid) may help protect against colorectal cancer, particularly for people who are genetically predisposed to this disease. Folate is found in beans, citrus fruits, and green vegetables, but some studies have indicated that the greatest protective benefits come from taking supplements.

However, an important study published in 2007 in the Journal of the American Medical Association challenged this assumption. The study suggested that high-dose folic acid supplements do not prevent colorectal cancer, and may actually increase the risk for developing certain types of colorectal tumors. The study evaluated over 1,000 men and women who had a recent history of non-cancerous colorectal polyps. (Adenomatous polyps, also called colorectal ademomas, are the most common type of polyp found in colorectal cancer screenings.) The results indicated that patients who took 1 mg/day of folic acid supplements were more likely to develop new adenomatous polyps than patients who did not take supplements. Patients in the folic acid supplement group were also more likely to have advanced adenomas and more numerous adenomas.

Adenomatous polyps are benign tumors, but they can potentially develop into cancerous tumors. Researchers are continuing to investigate the role that folic acid plays in colorectal cancer risk and prevention. It is possible that folic acid may help prevent the initial appearance of adenomatous polyps, but increase the risk for additional polyp formation once they have begun to occur.

Antioxidant Supplements. Antioxidants are chemicals that help eliminate harmful particles called oxygen-free radicals that have been associated with cancerous changes. Some studies have associated supplements of the antioxidants selenium and vitamins A, C, D, and E with lower colon cancer risk, but most studies have found no protective effect.

Prevention

Studies indicate that daily exercise is one of the best ways to reduce the risk of colorectal cancer. The more vigorous the activity, the greater the benefit, but even moderate exercise (walking, stair-climbing) can help reduce colorectal cancer risk. The American Cancer Society (ACS) recommends that people engage in at least moderate exercise for 30 minutes or more at least 5 days a week. The ACS also notes that 45 minutes or more of moderate-to-vigorous activity at least 5 days a week may help further reduce cancer risk.

Some studies also suggest that regular exercise may be beneficial for patients who have been diagnosed with colorectal cancer. Two 2006 studies indicated that exercise may reduce the risk of colorectal cancer recurrence and death for patients with stage I - III cancer.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are very common pain relievers that are available over-the-counter and by prescription. They include aspirin, ibuprofen (Motrin), naproxen (Aleve), and the COX-2 inhibitor celecoxib (Celebrex). Several studies have reported that NSAIDs help reduce the risk of colorectal cancer. However, regular use of NSAIDs, even in low doses, can increase the risk of gastrointestinal bleeding and stomach ulcers. Long-term use of NSAIDs can also increase the risk for heart attack and stroke, especially in people who have a history of heart disease. Several 2006 and 2007 studies in the New England Journal of Medicine reported that celecoxib prevented precancerous polyps, but the drug more than doubled patients’ risk for heart attack and other cardiovascular events.

A 2005 Nurse’s Health Study found that aspirin, but not other NSAIDs, does provide protection against colorectal cancer. However, the risk was only reduced for women who took 2 aspirin a day for more than 10 years. In addition, this dose level greatly increases the risk for gastrointestinal bleeding. Furthermore, a 2007 study in the New England Journal of Medicine suggested that aspirin’s protective effects may only apply to some types of colorectal cancer tumors. Another 2007 study, published in the Lancet, indicated that long-term daily use of aspirin can protect against polyps and colorectal cancer, but experts agree that aspirin’s risks do not outweigh its benefits for most people. (Some people who are at high risk for developing colorectal cancer may benefit from aspirin therapy.)

In March 2007, the U.S. Preventive Services Task Force (USPSTF) recommended against the routine use of aspirin and other NSAIDs to prevent colorectal cancer in people at average risk for this disease. (This recommendation does not apply to people who have a family history of colorectal cancer or who are at high risk for developing colorectal cancer due to other risk factors.) Long-term use of NSAIDs can increase the risk for gastrointestinal bleeding, kidney function problems, and heart problems. Aspirin can also increase the risk for hemorrhagic stroke. Due to these risks, the American Cancer Society and other professional associations also recommend against the use of NSAIDs or other types of medications for colorectal cancer prevention.

Medications containing 5-aminosalicylate (5-ASA) are sometimes given to patients with ulcerative colitis to help control inflammation. These drugs, which include sulfasalazine and mesalamine, are chemically related to aspirin. A 2005 review of clinical trials found that patients with ulcerative colitis who used 5-ASA were 49% less likely to develop colorectal cancer than patients who did not use these drugs

Some studies have suggested that cholesterol-lowering statin drugs may help reduce colorectal cancer risk. A 2006 study in the Journal of the National Cancer Institute did not find any protective benefit for statins.

Estrogen has been associated with a lower risk for colon cancer, perhaps because of specific enzymes that prevent cell proliferation. Drugs containing estrogen, then, may help high-risk women:

There is some evidence that hormone replacement therapy (HRT) reduces the risk of colon cancer in postmenopausal women. It carries other risks, however, including a higher risk for breast and uterine cancer and blood clots. A 2004 New England Journal of Medicine study found that while short-term use of estrogen plus progestin reduced the risk of developing colon cancer, combination HRT users who were diagnosed with the disease had more advanced forms of the cancer. Older women who are at higher risk for colon cancer might discuss risks and benefits of HRT with their doctor.
Oral contraceptives may reduce younger women's risk of colon cancer. Duration of use does not seem to be associated with decreased risk, but protection appears stronger for women who have more recently used oral contraceptives.

Diagnosis

Colon and rectal cancers are diagnosed using the screening tests discussed below. These tests can detect precancerous polyps and colorectal cancers at stages early enough for complete removal and cure.

Unfortunately, only 30 - 40% of adults over 50 years old (mostly in the upper socioeconomic group) have regular screening tests that could detect a cancer early enough for curative treatment. A survey reported that many people are not screened because they are too embarrassed. Those who had already had the tests were willing to have them again if they saved one additional day of their lives.

There is some debate about what is the best screening method. Current screening guidelines offer several different options for patients. Doctors agree that not enough people are screened and that these tests, if adopted with the same regularity as such screening tests as Pap smears, would save many lives. It is especially important for anyone at increased risk or with symptoms, such as rectal bleeding or ulcerative colitis, to have testing at an earlier age.

There is also debate about when people should stop being screened. A 2006 study in the Journal of the American Medical Association indicated that screening provides little benefit for elderly people, especially because colorectal cancers grow very slowly. The researchers suggest that doctors should carefully consider the risks versus benefits of screening patients age 80 and older.

Individuals should discuss with their doctors the risks and benefits of all screening procedures. Some controversy exists over how often people without risk factors for cancer should be screened and which detection method should be used for them.

Guidelines for Adults Age 50 and Over with Average Risk. The following are the five screening options recommended for people age 50 and over who have no symptoms and no family history of colon cancer:

Fecal occult blood test (FOBT) or fecal immunochemical test (FIT) every year
Flexible sigmoidoscopy every 5 years
FOBT or FIT every year plus sigmoidoscopy every 5 years
Double-contrast barium enema every 5 years
Colonoscopy every 10 years

Choosing between Colonoscopy and Sigmoidoscopy. The choice between colonoscopy and sigmoidoscopy for routine screening for older adults with average risk is an area of intense debate. The issues are as follows:

Sigmoidoscopy is less costly, less invasive, quicker, and safer than colonoscopy. Although it allows inspection of only the left side of the colon, any abnormal findings from sigmoidoscopy trigger a full colonoscopy. Therefore, experts estimate that sigmoidoscopy can detect 80% of all significant problems.
Colonoscopy is more sensitive than any other current screening method for detecting colon cancer. It can find 75 - 90% of colorectal cancers. If the goal were to reduce the number of cancer cases, regardless of cost, colonoscopy would be the preferred approach. Colonoscopy, however, is more expensive than sigmoidoscopy and has a slightly higher risk for complications (bowel tears or bleeding when a polyp is removed).

There are 3 basic tests for colon cancer: a stool test (to check for blood), sigmoidoscopy (inspection of the lower colon), and colonoscopy (inspection of the entire colon). All 3 are effective in catching cancers in the early stages, when treatment is most beneficial.

Screening, particularly with colonoscopy, in increased- and high-risk populations can save lives. The most important risk factors are a family history of colorectal cancer and personal history of colorectal cancer, polyps, or chronic inflammatory bowel disease. People with these risk factors should be screened before age 50 and may need more frequent screenings.

Guidelines for Increased-Risk Groups. Anyone with first-degree relatives diagnosed with colon cancer younger than 60, or with two relatives who have been diagnosed with colon cancer at any age, should consider beginning the standard screening regimen with a colonoscopy every 5 years, beginning at age 40 or 10 years before the youngest case in the family (whichever is earlier).

Men of African descent are also considered to be at increased risk for colon cancer and should discuss similar screening guidelines with their doctors.

Guidelines for High-Risk Groups. The following guidelines may be useful for specific high-risk groups.

People who have the mutated hereditary nonpolyposis colorectal cancer gene (MSH2 or MLH-). Frequent colonoscopy (for instance, every 1 - 2 years) beginning in their early 20s. (Regular screening for other cancers, such as uterine cancer, is also reasonable.)
People who have the mutated familial adenomatous polyposis (FAP) gene. Frequent screening with endoscopy (flexible sigmoidoscopy or colonoscopy) beginning in early puberty. Genetic testing is now recommended for family members of people with known FAP.
People with predisposing intestinal problems, such as widespread and active ulcerative colitis or Crohn's disease. Annual screening with colonoscopy with biopsies of suspicious areas.

Guidelines for Follow-Up After Detection of Precancerous Polyps. Patients who have had a previous examination in which polyps were detected (and removed) should have a repeat colonoscopy 1 - 3 years later, depending on the size, number, and type of polyps removed.

The digital rectal examination is used to detect tumors in the rectum, lower intestine, and prostate gland. The doctor inserts a lubricated-gloved finger into the patient's rectum and feels for lumps or other abnormalities. The exam is quick and painless but embarrassing for some. Fewer than 10% of colon cancers develop within the region that can be evaluated by a DRE, so it is not useful as a sole screening test.

Blood in bowel movements is not always visible, in which case it is called occult (hidden) blood. Fecal occult blood tests (FOBTs) are used to detect this hidden blood. The most common FOBT method is called the guaiac-based test. The patient is asked to supply up to six stool specimens in a specially prepared package. A small quantity of feces is smeared on specially treated paper, which reacts to hydrogen peroxide. If blood is present, the paper turns blue.

Accuracy. FOBTs can miss more than 75% of advanced cancers. Nevertheless, large studies have indicated that this simple test, performed annually, saves lives and may reduce the risk of dying from colon cancer by 15 - 33%. The following factors may affect its accuracy:

The levels of iron in the blood can affect results. Patients should not take iron supplements or eat red meats several days before the test.
Certain raw fruits and vegetables that contain the chemical peroxidase (cauliflower, horseradish, radishes, melons, and turnips) can cause a positive test reaction even if no blood is present.
Aspirin and NSAIDs are anticoagulants that can cause minor bleeding. They should not be taken for a week before the test. However, a 2005 study suggested that the prescription anticoagulant warfarin does not affect FOBT results.
Vitamin C and foods rich in this vitamin may cause a false negative reaction and should be avoided a few days before the test.
Bleeding from other causes, such as menstruation, hemorrhoids, gingivitis, or urinary infections, can produce blood in the stools and affect results.

Even if none of these conditions is present, a test that shows hidden blood does not necessarily mean that cancer is present. About 20 - 30% of people with occult blood have noncancerous polyps or other conditions, such as gastritis, and only 5 - 10% actually have cancer. Any abnormal result, however, requires further testing, such as colonoscopy.

Lack of Compliance. Compliance is a major problem. Patients are asked to perform the tests at home and send the test cards to the laboratory. Only 35 - 50% of patients actually follow through. Occult-blood tests that give results at home are available but are extremely inaccurate. In one large study, these tests failed to detect advanced cancer in about 62% of cases, although they may detect some early cancers.

If a digital rectal exam (DRE) or fecal occult blood test (FOBT) shows signs of trouble, several methods to visualize the colon are available. They include colonoscopy, sigmoidoscopy, and double-contrast barium enema. They have the following similarities and differences:

Sigmoidoscopy can only view the rectum and the left side of the colon, while colonoscopy and barium enemas allow a view of the entire large intestine.
Both flexible sigmoidoscopy and colonoscopy involve snaking a fiber optic tube through regions of the rectum and colon to view the walls of the intestine. The tube contains a tiny camera that transmits the image to a video screen. The use of an ultrasound (sound wave) scanner is proving to enhance viewing quality. Barium enemas simply use x-rays.
During either sigmoidoscopy or colonoscopy, the doctor is able to remove polyps or other abnormalities revealed by these procedures with surgical instruments inserted through the tube. It is not possible to remove polyps with a barium enema, which is not invasive.

Sigmoidoscopy. Sigmoidoscopy examines the rectum and the lower two feet of the colon. It cannot, however, detect the roughly half of cancers that occur in the right colon. Right-sided cancers are more common in older people.

The procedure uses a flexible fiber optic tube (it is thus referred to as flexible sigmoidoscopy) that contains a tiny camera and surgical instruments.
It lasts about 10 minutes and may be mildly uncomfortable, but it is not painful and is generally very safe. In one study, 70% of patients reported that the procedure was far less unpleasant than they had expected.

This procedure has been found to reduce the risk of fatal cancers in the rectal and sigmoid area by 60%. If polyps are detected, a colonoscopy is then used.

Colonoscopy. Colonoscopy is the most accurate testing method and can reduce cancer incidence by up to 90%. It is clearly indicated for anyone with an increased risk for colorectal cancer, including those with a personal or family history of the disease. As with sigmoidoscopy, a colonoscopy uses a flexible tube, but it is snaked through the entire large intestine.

For about a day before the procedure the patient eats nothing and drinks a laxative solution that cleans out the colon. The taste of the solution is unpleasant, although it has improved in recent years.
The procedure typically uses a sedative that produces a "twilight" sleep and often makes the procedure more comfortable than sigmoidoscopy.
Air may be introduced into the intestine to widen it and allow the tube to navigate curves. A colonoscopy avoids the risk of radiation associated with a barium enema, but it is important to note that even a colonoscopy does not detect all cancers.

Complications are rare, but include the following:

Hyponatremia. Hyponatremia is a low concentration of sodium in the blood. The complication may be caused by the effects of bowel cleaning before the procedure that can result in water retention and reductions in sodium. When severe, it can cause temporary neurological symptoms, such as confusion, lethargy, unsteadiness, and slurred speech. Researchers suggest that sodium concentrations be measured in patients who develop such symptoms after colonoscopy.
Bowel perforation (very low risk, about 2 in 1,000 procedures). The risk for bowel perforation is greater with colonoscopy than flexible sigmoidoscopy.
Bleeding at the site of biopsy or polyp removal.

Overall, colonoscopy is a safe procedure. However, according to a 2006 study in the Annals of Internal Medicine, serious complications occur in about 5 of every 1,000 colonoscopies. Most of these complications occurred when a biopsy or polyp removal was performed. (The risk for complications without biopsy or polyp removal is about 1 in every 1,000 colonoscopies.) This study looked at colonoscopies in general, including those that are done to diagnose the causes of a patient's symptoms. The risk may be lower for colonoscopies performed solely to screen for colorectal cancer.

Barium Enema. The double-contrast barium enema, which uses an x-ray image, is the less expensive alternative for viewing the entire colon. It is not as accurate as colonoscopy, and if any polyps or abnormalities are revealed on x-ray, a colonoscopy is then required to remove suspicious tissue, so it is now recommended much less often than in the past.

The barium enema is a valuable diagnostic tool that helps detect abnormalities in the large intestine (colon). The barium enema, along with colonoscopy, remains the standard in the diagnosis of colon cancer, ulcerative colitis, and other diseases of the colon.

Screening for familial adenomatous polyposis. Genetic screening for familial adenomatous polyposis (FAP) and hereditary nonpolyposis colon cancer (HNPCC) is now available and may be recommended for high-risk patients. The test for FAP detects a mutation in the adenomatous polyposis coli in up to 90% of people who carry it. Testing for HNPCC mutation is somewhat more complex.

Screening for insulin-like growth factor. A gene that regulates insulin-like growth factor (IGF-2) is functional during fetal development and then becomes inactive. Some evidence now suggests that people who have IGF-2 in adulthood have a higher risk for colon cancer. Blood tests for detecting IGF-2, then, may be helpful in identifying patients who should have more intensive screening. Currently, however, this is only used as a research tool.

Stool DNA Testing. A promising technique for colorectal cancer screening is the detection of altered DNA in cancer cells that have shed from the colon and are excreted in the stool. Such tests may prove to detect both inherited and noninherited genetic mutations. This may become a widely used tool in the future. However, larger clinical studies are needed.

Virtual Colonoscopy. A promising experimental technique called virtual colonoscopy allows three-dimensional imaging of the colon without using invasive instruments. As with standard colonoscopy, the patient takes a laxative first to clear out the intestine. The procedure itself involves pumping air into the colon and scanning the intestine using computed tomography (CT). It is very safe and takes about only 10 minutes. The procedure is similar in accuracy to conventional colonoscopy for detection of larger polyps (6 mm or more in diameter) and is also potentially less expensive. Colonoscopy is required, however, if suspicious areas are found, which may occur frequently with the CT procedure, since it erroneously identifies a high number of nonexistent polyps.

A study published in April 2004 in the Journal of the American Medical Association compared results of standard colonoscopy versus virtual colonoscopy in over 600 patients at nine major medical centers. Virtual colonoscopy had much lower rates of successfully finding polyps than standard colonoscopy. Virtual colonoscopy detected polyps of at least 6 mm in 39% of patients and polyps of at least 10 mm in 55% of patients. By contrast, standard colonoscopy detected 99% of polyps of at least 6 mm, and 100% of polyps of at least 10 mm. In addition, accuracy rates varied widely among the different hospitals. The authors advised that until more improvement in training and technique is achieved, virtual colonoscopy "is not yet ready for widespread clinical application."

Magnetic Resonance Colonography. Magnetic resonance colonography (MRC) is another non-invasive technique for visualizing the colon. The patient receives an enema containing a contrast substance, and then magnetic resonance images are taken. MRC is fast, comfortable, and less invasive than colonoscopy. Currently, however, there is a poor detection rate for flat tumors and for polyp tumors less than 10 mm in diameter.

Staging

A diagnosis of cancer will lead to staging and other tests to help determine the outlook and the appropriate treatments.

The large intestine is a long hollow organ lined with mucous membrane (mucosa). Muscle layers wrap around the entire length and help move food material through to the rectum.

Unlike many other cancers, the size of the tumor is not a major factor in determining the outcome of colorectal cancer. Of greater importance is how far the cancer has spread. To determine this, doctors will assign a stage to the tumor. There are several methods for staging. The older system, known as Dukes', categorizes four basic stages: A, B, C, and D. A more recent system refers to these stages as I, II, III, and IV but divides the categories slightly differently. The term "5-year survival" means that patients have lived at least 5 years since diagnosis. Most patients who live 5 years without a recurrence are considered to be cured of their disease.


Stage	Condition	5-Year Survival
A or I	Tumor superficially involves the inner lining of the intestine.	More than 90%
B or II	Tumor has penetrated through the muscle wall of the intestine but has not reached the lymph nodes.	70 - 85%
C or III	Lymph nodes are involved.	65% or below
D or IV	Tumor has spread to other organs (metastasized), usually the liver first.	5 - 9%

Click the icon to see an image of the stages of cancer.

Researchers are continually seeking to identify tumor markers, substances (usually found in blood samples) that will assist in the diagnosis of cancer and in monitoring effects of treatment.

Carcinoembryonic Antigen. High blood levels of a protein called carcinoembryonic antigen (CEA) sometimes indicate the presence of colon cancer. Unfortunately, it is also elevated in other cancers and in some noncancerous conditions. CEA is not effective as a screening tool for healthy people, but might eventually be helpful for patients with cancer.

An advanced diagnostic technique called polymerase chain reaction (PCR) can detect genetic evidence of CEA. One study indicated that when these microscopic footprints of colon cancer are detected in the lymph nodes of patients with Stage II cancer (whose lymph nodes otherwise appear to be not involved with cancer), the outlook is similar to that of patients with Stage III cancer. Patients without this so-called micrometastasis have a very favorable prognosis. Further research is needed, however, before PCR can be used in widespread practice.
In patients with a history of, or active, colon cancer, follow-up measuring of blood CEA levels may be helpful in detecting recurrence of the cancer and effectiveness of treatments.

Defective P53 Gene. The presence of a defective p53 gene is a marker for very poor prognosis in patients with advanced colon cancer. In its normal state, the gene is important for regulation of cell growth. Testing for this abnormality, however, is not widely done because it is not clear how to use this information.

Other Tumor Markers. Other tumor markers under investigation include a protein called GLUT1, cancer antigen 19-9 (CA 19-9), matrix metalloproteinase-9 (MMP-9) RNA, HER-2/neu oncoprotein, transforming growth factor beta-1 (TGF-beta-1), and CD44.

Click the icon to see an image of drawing blood for culture.

A technique known as a sentinel node biopsy is increasingly performed by experienced surgeons in selected patients. This procedure is used to determine if cancer has spread beyond the nodes, possibly reducing the need for complete axillary lymphadenectomies. It involves the following:

The procedure uses an injection of a tiny amount of a tracer, either a radioactively-labeled substance (radioisotope) or a blue dye, into the tumor site.
The tracer or dye then flows via the lymphatic system into the so-called sentinel node. This is the first lymph node to which any cancer would spread.
The sentinel lymph node and possibly one or two others are then removed.
If they do not show any signs of cancer, it is highly likely that the remainder of the lymph nodes will be cancer free, and further surgery becomes unnecessary.

It is still not known if the sentinel node biopsy has any survival advantages compared to the standard procedures with lymph nodes removal. However, one study indicated that careful and complete removal of potentially cancerous lymph nodes is still very important for improving survival in patients with Stage II and III colorectal cancer.

Whole-body imaging scans that combine positron emission tomography (PET) and computed tomography (CT) may be helpful in accurately staging colorectal cancer, according to preliminary research published in 2006 in the Journal of the American Medical Association.

Prognosis

Survival rates for colorectal cancer have been rising in recent years. The 5-year survival rate is as high as 90% for cancer that has not spread to the lymph nodes (localized cancer). When cancer has spread to lymph nodes and other parts of the body, survival rates drop to 65% and below. Because many cancers are detected at later stages, the overall survival rate is currently about 60%. African-Americans and other minorities tend to have lower survival rates than Caucasians. Studies suggest, however, these higher mortality rates are largely due to less access to optimal health care, including appropriate surgical care and aggressive treatments.

In most cases, age is not a factor in treatment success. Good survival rates are achieved in the elderly as well as in young people. Chances for survival are less in Stage II cancers if the intestine is obstructed or perforated. If cancer has spread to lymph nodes (Stage III), the outlook is better if three or fewer lymph nodes are involved. Treatment can prolong life even when cancer has spread.

Surgery

Surgical removal of the tumor ("resection") along with any affected surrounding tissue is the standard initial treatment for potentially curable colorectal cancers (cancers that have not spread beyond the colon or lymph nodes). Drug and radiation therapy are often used for advanced cancers and are continuously being tested with surgery in different combinations and sequences.

Although choosing a qualified surgeon is critical, choosing a hospital experienced in procedures is also important. The more often colon cancer surgery is performed at a given hospital, the lower the mortality rate at that hospital is likely to be.

Unless cancer is very advanced, most tumors are removed by an operation known as colectomy:

Colectomy involves removing the cancerous part of the colon and nearby lymph nodes.
The surgeon then reconnects the intestine.
If the surgeon cannot reconnect the intestine, usually because of infection or obstruction, the surgeon will perform a colostomy. The need for colostomies is higher after surgery for rectal cancer. In most cases of colon cancer, colostomies are not needed. [See "Colostomy" below.]

Click the icon to see an illustrated series detailing colon cancer treatment.

The Surgical Approach. The standard technique for a colectomy is open, invasive surgery. Laparoscopy, sometimes called “keyhole surgery,” is a less invasive method. Laparoscopy is still considered an investigational technique for treating colon cancer, but it is gaining more acceptance and showing good results in clinical trials.

Open Surgery:

Open surgery uses a wide incision to open the patient's abdomen. The surgeon then performs the procedures with standard surgical instruments. This is the usual method for performing colectomy.

Laparoscopy:

Laparoscopy uses a few small incisions through which the surgeon passes a fiber optic tube (laparoscope) containing a small camera or tiny instruments. It is generally used for early colon cancer (for tumors less than 2 centimeters or for well-defined tumors less than 3 centimeters).
A 2004 New England Journal of Medicine study found that patients who received laparoscopic colectomy had similar rates of surgical complications, cancer recurrence, and survival as those who received traditional open surgery. However, the patients who had laparoscopy recovered faster and did not need as many narcotic painkillers.
Several 2005 studies indicated that laparoscopy works as well as conventional surgery for treatment of colon cancer. However, laparoscopy does not appear to be as effective for rectal cancer.

Click the icon to see an image detailing pelvic laparoscopy.

Click the icon to see an illustrated series detailing a resection of the large intestine.

Other Investigational Measures. Researchers are testing expandable metal tube-like devices called stents to keep the intestine open. Stents may be used before a procedure to allow bowel cleansing or for long-term use to keep open colons that can't be operated on.

A colostomy is performed in order to bypass or remove the lower colon and rectum. The procedure generally involves creating a passage, called a stoma, through the abdominal wall that is connected to the colon. The feces pass through this passage and are eliminated. Patients must learn how to care for the stoma and keep the area sanitary.

A colostomy usually will have one opening (single-barreled), or there may be two loops opening through the skin (double-barreled).

Usually the colostomy is temporary and can be reversed by a second operation after about 3 - 6 months. It the rectum and sphincter muscles in the rectum need to be removed, the colostomy is permanent. Permanent colostomies are more common when the cancerous regions are within 2 - 3 centimeters of the anus. Fortunately, surgical advances and knowledge of the extent of safe margins are reducing the need for permanent colostomies.

Click the icon to see an illustrated series detailing a colostomy procedure.

Managing Permanent Colostomies. In cases where the colostomy is permanent, the patient must wear a colostomy pouch, which sticks to the skin using a special glue. Pouches are available as one- or two-piece systems. The one-piece system is simpler, but the two piece system allows replacement of the pouch without removing the tape.

For best results, the pouch should be emptied when about one-third full. It should be replaced 1 - 2 times a week, depending on signs of leakage (itching or burning of the skin near the stoma). The pouches are odor proof.

Surgical treatments for cancer in the rectum are complex since they involve muscles and tissue that are critical for urinary and sexual function.

Local Excision or Polypectomy for Early Stages. In order to preserve the function of the anal sphincter and prevent the need for colostomy, Stage I and Stage II tumors may be removed by local excision, sometimes followed by chemotherapy and radiation. In this procedure, the tumor is cut out without removal of a major section of rectum. In some cases cancer recurs, but a second operation may be possible. Another treatment for early-stage rectal cancer, called electrocoagulation, destroys tumors using a high frequency electric current. It is being tested in clinical trials.

Radical Resection. In about a third of cases of rectal cancer, the cancer occurs in the lower part of the rectum, where between 70 - 80% of cancers have spread beyond the rectal wall. These patients need a radical resection, in which surrounding structures, including the sphincter muscles that control bowel movements, must often be removed.

The use of chemotherapy and radiation prior to surgery may prevent the need for permanent colostomy in some patients. This is an active area of clinical research, and trials are under way to address this issue. Another technique, called coloanal anastomosis, reconstructs the area to avoid the need for colostomy, and may be appropriate in some patients.

Total Mesorectal Excision. Total mesorectal excision (TME) involves dissection and removal of the entire cancerous area of the rectum along with surrounding fatty regions where the lymph nodes are located (the mesorectum). When successful, TME preserves the sphincter muscle, reducing the need for a permanent colostomy. Increasing use of this procedure is resulting in lower recurrence rates, lower levels of impotence and incontinence, and better overall survival rates compared to other resection techniques. Some experts now recommend it as a first choice for certain patients with locally advanced rectal cancer.

Combining chemotherapy and radiation either before or after TME is yielding promising long-term results and a low risk for local recurrence. There are many questions, however, and it is not clear which approach is better for specific patients.

Side effects of colon surgery include:

Sexual dysfunction. This is of particular concern. In general, colostomy does not usually affect sexual function. However, wide rectal surgery can cause short- or long-term sexual dysfunction. Sildenafil (Viagra) may help men who experience this after surgery.
Irregular bowel movements.
Gas and flatulence. Pouching filters are available to reduce gas. Certain foods produce more gas than others -- usually within 6 - 8 hours after ingestion for colostomy patients. They include beans, oat bran, most fruit, and certain vegetables (cabbage, cauliflower, Brussels sprouts, broccoli, and asparagus). To prevent swallowing air, patients should avoid sipping through straws, chewing gum, and chewing with their mouths open.
Diarrhea.
Bladder complications.
Sense of urinary urgency.
Fecal incontinence. Patients with rectal surgery have a higher risk for bowel dysfunction than those who had a colostomy.
Complications in or around the stoma. These can occur early after surgery to many years after the procedure. They include skin infection or breakdown, hernias, narrowing of the stoma, bleeding, and collapse.

There are no dietary restrictions, although many patients avoid foods that can produce gas. Everyone should drink plenty of fluids and get sufficient fiber.

The potential side effects of sexual and bowel dysfunction for colorectal surgical patients can be devastating, although many patients do very well and live normal productive lives. Positive emotions play a strong role in recovery. Patients who are depressed should discuss with a doctor all aspects of treatment that affect the quality of life, and consider seeking support groups.

Medications

Chemotherapy uses drugs that kill cancer cells throughout the body. There are two situations in which chemotherapy is used:

The adjuvant setting. Adjuvant refers to the use of chemotherapy after surgery in patients with Stage III tumors and selected patients with high-risk Stage II tumors (disease that is potentially curable). The goal of this therapy is to eliminate any cancer cells that surgery may have missed, thereby preventing recurrence and increasing the chance of cure. Patients of all ages, including the elderly, can benefit.
In metastatic disease. In patients with metastatic disease (where the cancer has spread to other parts of the body) the goal of chemotherapy is to shrink tumors, improve symptoms and quality of life, and lengthen life.

In the adjuvant setting, there are some differences in chemotherapy treatments between colon and rectal cancers:

Chemotherapy for Stage II is considered standard care for Stage II rectal cancer but is under debate for colon cancer.
Chemotherapy is standard for patients with Stage III colon cancer. Chemotherapy is also standard for patients with Stage III rectal cancer but is used in combination with radiation.

Chemotherapy for Stage II Colon Cancer. Adjuvant chemotherapy for Stage II colon cancer is controversial. Such patients tend to have a good outcome after surgery, and the positive effects of chemotherapy have been difficult to demonstrate. To date, the survival advantage of adjuvant chemotherapy in this group has been reported to be only in the range of 2%. However, better trials are still needed to confirm or refute the benefits in specific patient groups.

Although not yet known with certainty, some data suggest that certain patients with Stage II cancer may be at higher risk of recurrence and would theoretically benefit from adjuvant therapy. These include patients with cancers that have:

Obstructed the bowel
Perforated the wall of the colon
Adhered to structures outside the intestine

Advanced diagnostic techniques are under investigation for helping to select appropriate candidates for adjuvant therapy. None of these methods, however, are ready to be used routinely to help make treatment decisions. The decision whether to pursue chemotherapy for Stage II disease should be made after careful discussion between the patient and their oncologist, especially after features, such as bowel perforation or obstruction, are taken into account.

Chemotherapy for Stage III Colon Cancer. Since the early 1990s, adjuvant chemotherapy with 5-FU and leucovorin has been the standard of care for Stage III colon cancer. In recent years, the FOLFOX (5-FU, leucovorin, oxaliplatin) regimen has also been used for chemotherapy following surgery. Numerous trials have shown that adjuvant chemotherapy in this setting reduces the absolute risk of death from colon cancer by about one-third and improves survival by 10%. Clinical trials are also investigating combinations of other drugs.

Chemotherapy for Advanced Colorectal Cancer. Chemotherapy is either given directly into the arteries of the liver or intravenously (through a vein) with 5-FU and leucovorin. Oxaliplatin is sometimes added, but recent evidence suggests that the targeted therapy biologic drug bevacizumab may be a better addition. Other alternative chemotherapy choices are capecitabine, or irinotecan combined with cetuximab. Radiation therapy may be used in place of chemotherapy or in combination with it. Studies indicate that chemotherapy offers only a modest improvement in survival, but may help reduce symptoms.

Seven drugs are currently approved for colorectal cancer chemotherapy:

5-fluorouracil (5-FU, Adrucil), which is often given in combination with leucovorin (Wellcovorin). Leucovorin is a vitamin that helps boost the effectiveness of 5-FU.
Capecitabine (Xeloda)
Oxaliplatin (Eloxatin)
Irinotecan (Camptosar)
Bevacizumab (Avastin)
Cetuximab (Erbitux)
Panitumumab (Vectibix)

Capecitabine is a pill form of 5-FU. The other drugs are administered intravenously. Many of these drugs are given in combination with each other. Common chemotherapy combination regimens include:

5-FU / LV (5-FU and leucovorin)
FOLFOX (5-FU with leucovorin and oxaliplatin)
FOLFORI (5-FU with leucovorin and irinotecan)
IFL (Irinotecan, 5-FU, leucovorin)
XELOX (Capecitabine and oxaliplatin)

Side effects occur with all chemotherapeutic drugs. They are more severe with higher doses and increase over the course of treatment. Because cancer cells grow and divide rapidly, anticancer drugs work by killing fast-growing cells. This means that healthy cells that multiply quickly can also be affected. The fast-growing normal cells most likely to be affected are blood cells forming in the bone marrow, and cells in the digestive tract, reproductive system, and hair follicles. Nausea and vomiting is a very common side effect, but drugs such as ondansetron (Zofran) can help provide relief. In general, side effects are nearly always temporary, and medications can help manage them. Most patients are able to continue with normal activities for all but perhaps 1 - 2 days a month.

5-Fluorouracil (5-FU) with Leucovorin. Adjuvant therapy using 5-fluorouracil, either alone or with leucovorin (5-FU/LV), is the standard treatment for patients with high-risk colon cancer (Stage III or select patients with Stage II tumors). Leucovorin, also called folinic acid, is a form of the B vitamin folic acid, which helps increase 5-FU’s effectiveness. Patients are given a series of cycles that usually continue for at least 6 months.

There are many different ways of giving 5-FU, including intravenously over several hours once a week, intravenously daily for 5 consecutive days every month, or as continuous infusion with a portable pump.

The side effects can be quite different, depending on the way 5-FU is given, and women may be more susceptible than men. In one analysis, 53% of women and 40% of men experienced severe side effects, while response rates and survival were similar for both sexes. Many patients, however, tolerate 5-FU with leucovorin well, with manageable side effects. The most common side effects include nausea and vomiting, diarrhea, loss of appetite, hair loss, swelling of hands and feet, rashes, and mouth sores.

Irinotecan. Irinotecan (Camptosar) blocks an enzyme essential for cell division. Irinotecan can be given alone or in combination with 5-FU and leucovorin. This combination therapy (irinotecan plus 5-FU/LV) is also referred to as the "Salz regimen," or IFL. When it was approved in the mid 1990s, irinotecan was the first new drug developed for colon cancer in over 30 years. Studies have shown that irinotecan combined with 5-fluorouracil and leucovorin (5-FU/LV) significantly delays the time at which tumors progress and improves survival in metastatic cancer compared to 5-FU/LV alone. While the survival advantage is small, the combination has become the standard of care for metastatic cancer. Of concern, however, are studies that have reported an increased risk of death from toxic effects with the use of the three-drug combination. These deaths appeared to be related to blood-clotting complications. Doctors should carefully monitor dosages. Diarrhea is a common side effect of irinotecan.

Capecitabine. Capecitabine (Xeloda), an oral form of 5-FU, was approved in 2001 as a treatment for metastatic colorectal cancer. It is the only pill approved for colorectal cancer. A major 2005 study, published in the New England Journal of Medicine, found that capecitabine works as well as the standard 5-FU/LV regimen and causes significantly fewer side effects. The study involved patients with Stage III colon cancer who had undergone surgical removal of the tumor. In 2005, capecitabine was approved for postsurgical treatment of patients with Dukes’ C colon cancer. Capecitabine is also showing promise in combination with radiation therapy for rectal cancers.

Oxaliplatin. Oxaliplatin (Eloxatin) is related to cisplatin, a widely used platinum-based chemotherapy drug. Oxaliplatin is used in combination with 5-FU and leucovorin. (This triple combination therapy is called the FOLFOX regimen.) Oxaliplatin was first approved in 2002 for use in combination with 5-FU and leucovorin as a second-line treatment for cancer that has progressed after initial therapy.

Since 2002, oxaliplatin has received additional approvals as a first-line treatment for advanced colorectal cancer, and as a post-surgical treatment for patients who have undergone tumor resection.

Oxaliplatin can cause pain and tingling sensations in the hands and feet (neuropathy) that is worsened by exposure to cold. Recent research suggests that adding xaliproden (Xaprila) to the FOLFOX regimen may help reduce the frequency of neuropathy without interfering with the benefits of chemotherapy. Xaliproden is a drug used to treat the neurological disease amyotrophic lateral sclerosis (also known as Lou Gehrig's disease).

Bevacizumab. Bevacizumab (Avastin) was approved in February 2004 as a first-line treatment for patients with metastatic colorectal cancer (advanced cancer that has spread in the body). It is used in combination with IFL (irinotecan, 5-FU, leucovorin). Bevacizumab is a genetically engineered monoclonal antibody that targets and inhibits vascular endothelial growth factor (VEGF), a protein that regulates angiogenesis (the development of new blood vessels that feed a tumor's blood supply). It is the first anti-angiogenic therapy approved for the treatment of colorectal cancer.

In a study of 800 patients with metastatic colorectal cancer, bevacizumab administered intravenously along with IFL extended survival by about 5 months longer than IFL alone. Common side effects of bevacizumab include nosebleeds, fatigue, diarrhea, and high blood pressure. Less common side effects include stroke, heart attacks, angina, and formation of holes in the colon and stomach (gastrointestinal perforation).

Cetuximab. Cetuximab (Erbitux) was approved in February 2004 for the treatment of metastatic colorectal cancer. This monoclonal antibody drug targets epidermal growth factor receptor (EGFR), a protein required by cancer cells in order to proliferate. It can be used either in combination with irinotecan or alone for patients who have not responded to irinotecan. Studies of the cetuximab-irinotecan combination suggest it can help in tumor shrinkage. It has a modest effect on survival, prolonging patients’ lives by about an additional month.

Panitumumab. Panitumumab (Vectibix) was approved in September 2006 for treatment of colorectal cancer that has metastasized following standard chemotherapy. Like cetuximab, panitumumab is a monoclonal antibody drug that targets EGFR. In clinical trials, panitumumab helped delay disease progression and prolong survival by about 3 months. About 8% of patients experienced tumor shrinkage. Common side effects of this drug include skin rash, fatigue, abdominal pain, nausea, and diarrhea or constipation. Serious side effects include pulmonary fibrosis, severe skin rash, and skin reactions at the infusion site.

One of the most promising recent developments in cancer treatment research has been the emergence of so-called "targeted therapies." Traditional chemotherapy drugs can be effective, but because they do not distinguish between healthy and cancerous cells their generalized toxicity can cause severe side effects. Targeted therapies work on a molecular level by blocking specific mechanisms associated with cancer cell growth and division. Because they selectively target cancerous cells, they may induce less severe side effects. In addition, these drugs hold the promise of creating options for more individualized cancer treatment based on a patient's genotype. In the future, diagnostic tests may help doctors identify which patients are more likely to respond successfully to specific drugs.

Biologic therapies use the body's immune system to attack the cancer (immunotherapy). These drugs are derived from biological sources and include vaccines, monoclonal antibodies (MAbs), and gene therapies. Many targeted therapies are classified as biologics. Bevacizumab (Avastin), cetixumab (Erbitux), and panitumumab (Vectibix) are currently the three biologic drugs approved for colorectal cancer treatment, but many other drugs are in development.

Targeted therapies involve many different types of drugs and molecular pathways. These include:

Angiogenesis Inhibitors. Anti-angiogenesis drugs inhibit the formation of new blood vessels that supply tumors with the blood, oxygen, and nutrients vital to tumor growth. Angiogenesis inhibitors, such as the monoclonal antibody bevacizumab (Avastin), target vascular endothelial growth factor (VEGF). Cediranib (Recentin), formerly AZD2171, is a new angiogenesis inhibitor that is in Phase III clinical trials for treatment of colorectal cancer.

Tumor Growth Factor Inhibitors. Tumor growth factors, such as epidermal growth factor, stimulate cell growth. Cetixumab (Erbitux) and panitumumab (Vectibix) are the two currently approved colorectal cancer drugs that target the epidermal growth factor receptor (EGFR). Nimotuzumab (TheraCIM) is currently being studied in combination with irinotecan in Phase III trials.

Tyrosine Kinase Inhibitors. Tyrosine kinase is an enzyme associated with EGFR that is involved with the signaling mechanisms that prompt cell growth. The EGFR/tyrosine kinase inhibitor erlotinib (Tarceva), which is approved for the treatment of pancreatic and lung cancers, is being investigated as an adjuvant treatment for metastatic colorectal cancer. Sunitinib (Sutent), which is approved for renal cell carcinoma, is another tyrosine kinase inhibitor in Phase III trials for colorectal cancer.

Radiation Treatment

Radiation therapy uses x-rays to kill cancer cells that might remain after an operation or to shrink large tumors before an operation so that they can be removed surgically. The object of radiation therapy is to damage the tumor as much as possible without harming surrounding tissues. Radiation may be administered in the following ways:

Externally by an x-ray machine (external beam radiation).
By passing radioactive pellets through thin plastic tubes inserted into the intestine.
By implanting tiny radiation seeds directly into the tumor (brachytherapy).
Computer imaging techniques providing 3-dimensional pictures of the cancerous area are allowing precise targeting of radiation to the tumor.

Postoperative radiation treatment combined with chemotherapy is common practice for patients with rectal cancer in Stages II and III. Such patients are at risk of recurrence both at the site of their original tumor and elsewhere in the body. Although there can be significant long-term side effects, the combination of 5-FU and radiation is still considered standard after surgery.

The standard procedure in the U.S. is to apply radiation after surgery (postoperative). Pre-operative chemotherapy and radiation, however, are sometimes used to preserve sphincter-muscle function and reduce the chance that a patient will need a colostomy. Furthermore, some studies suggest that the use of radiation before surgery reduces the likelihood of recurrences and may slightly prolong survival in some patients with rectal cancer. (It has no additional advantages, however, if the subsequent surgery does not completely remove the cancerous regions.) Studies comparing preoperative and postoperative chemotherapy and radiation are currently under way.

Radiation therapy can also be used during surgery (a procedure called intra-operative radiotherapy). It allows the surgeon to move healthy tissue out of the path of the radiation beam.

Short-term side effects of radiation include:

Diarrhea
Skin irritation around the anus
Incontinence
Fatigue
Bowel movement problems

Longer-term complications may include:

Incontinence
Hip and pelvic fractures
Diarrhea
Increased risk for bowel obstruction

Follow-up Testing

The American Society of Clinical Oncology (ASCO) sets guidelines for follow-up testing to detect recurring cancer after the completion of treatment. The following guidelines are based on ASCO’s 2005 updated recommendations.

Most colorectal cancer recurrences happen within 3 years after surgery. American Society of Clinical Oncology recommends that a colorectal cancer patient sees their doctor for a physical examination every 3 - 6 months for the first 3 years, every 6 months for the fourth and fifth years, and at the doctor's and patient's discretion during subsequent years.

Patients should have a colonoscopy 3 years after surgery. If the results are normal, patients should then receive a colonoscopy every 5 years. Some patients with hereditary types of colorectal cancer may need more frequent screenings.

A flexible sigmoidoscopy is recommended every 6 months for 5 years for patients with Stage II or III rectal cancer who did not receive radiation therapy.

Carcinoembryonic antigen (CEA) levels should be measured every 3 months after surgery for 3 years in patients with Stage II or III cancer. High CEA levels in the blood may indicate that the cancer has spread to other parts of the body.

Patients at high risk for cancer recurrence should receive an annual computerized tomography (CT) scan for the first 3 years after treatment. The CT scan can help determine if cancer has spread to the lungs or liver. Patients who have had rectal cancer, and did not have radiation therapy, should receive a pelvic CT scan. The scan is not recommended for most lower-risk patients with Stage I or II colorectal cancer.

American Society of Clinical Oncology does not recommend other follow-up blood tests such as complete blood count, liver function tests, fecal occult blood tests. There appears to be no additional benefit for these tests.

Treatment for Metastasized Colorectal Cancer

The liver is the most frequent site for colorectal cancers to spread (metastasized). Here, treatments may slow the spread of cancer and even prolong survival. Cure is very rare.

When cancer has spread, surgery to remove or bypass obstructions in the intestine may be performed. In these circumstances, surgery is considered palliative in that it may improve symptoms but will not lead to cure. In rare cases, metastatic colon cancer may be cured with surgical removal of tumors in areas to which the cancer has spread, such as the liver, ovaries, and lung. The liver is the most common site of spread. Only selected patients may be eligible for such surgery, but in these patients, 5-year survival has been 25% or higher.

Chemotherapy may help improve symptoms and possibly prolong survival in metastasized colorectal cancers. Several investigational drugs are being tested. Doctors are also testing chemotherapy administered directly into the liver -- a treatment called hepatic arterial infusion (HAI). A 2006 study found that hepatic arterial infusion improves survival and quality of life for patients whose cancer has spread to the liver. The study indicated that HAI works better for these patients than chemotherapy delivered intravenously.

Other investigative techniques used to destroy liver tumors include:

Cryosurgery. This approach freezes the tumor or surrounding tissue.
Embolization. Embolization employs a catheter to deliver substances into the liver that block blood vessels and therefore starve the tumor. Chemotherapy is often administered during this procedure.
Radiation.

For end-stage cancer, hospice care is a compassionate option.

Resources

www.cancer.org -- American Cancer Society
www.cancer.gov -- National Cancer Institute
www.oncolink.org -- OncoLink cancer information
www.asco.org -- American Society of Clinical Oncology
www.plwc.org -- People Living with Cancer
www.nccn.org -- National Comprehensive Cancer Network
www.cancer.gov/clinicaltrials -- Find clinical trials

References

Chan AT, Ogino S, Fuchs CS. Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. N Engl J Med. 2007 May 24;356(21):2131-42.

Cole BF, Baron JA, Sandler RS, Haile RW, Ahnen DJ, Bresalier RS, et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA. 2007 Jun 6;297(21):2351-9.

Flossmann E, Rothwell PM; British Doctors Aspirin Trial and the UK-TIA AspirinTrial. Effect of aspirin on long-term risk of colorectal cancer: consistent evidencefrom randomised and observational studies. Lancet. 2007 May 12;369(9573):1603-13.

Kerr DJ, Dunn JA, Langman MJ, Smith JL, Midgley RS, Stanley A, et al. Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer. N Engl J Med. 2007 Jul 26;357(4):360-9.

Levin TR, Zhao W, Conell C, Seeff LC, Manninen DL, Shapiro JA, Schulman J. Complications of colonoscopy in an integrated health care delivery system. Ann Intern Med. 2006 Dec 19;145(12):880-6.

Meyerhardt JA, Niedzwiecki D, Hollis D, Saltz LB, Hu FB, Mayer RJ, et al. Association of dietary patterns with cancer recurrence and survival in patients with stage III colon cancer. JAMA. 2007 Aug 15;298(7):754-64.

U.S. Preventive Services Task Force. Routine aspirin or nonsteroidal anti-inflammatory drugs for the primary prevention of colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2007 Mar 6;146(5):361-4.

Veit-Haibach P, Kuehle CA, Beyer T, Stergar H, Kuehl H, Schmidt J, et al. Diagnostic accuracy of colorectal cancer staging with whole-body PET/CT colonography. JAMA. 2006 Dec 6;296(21):2590-600.

Review Date:
9/8/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Breast cancer

FitSugar — Wed, 08 Oct 2008 17:34:59 -0700

In This Report

Highlights
Introduction
Risk Factors
Prevention and Lifestyle Fa...
Symptoms
Diagnosis
Prognosis
Treatment
Surgery
Radiation
Medications
Chemotherapy
Hormone Therapy
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approvals

In September 2007, Evista (raloxifene) was approved for prevention of breast cancer in postmenopausal women with osteoporosis, and postmenopausal women at high risk for invasive breast cancer. Raloxifene and tamoxifen are the only two drugs approved for breast cancer prevention in high-risk women.
In March 2007, lapatinib (Tykerb) was approved in combination with capecitabine (Xeloda) for treatment of advanced HER2-positive breast cancer.
In November 2006, trastuzumab (Herceptin) was approved for treatment of early-stage HER2-positive breast cancer. Trastuzumab is also approved for advanced HER2-positive breast cancer.

Screening

The American College of Physicians’ 2007 guidelines recommend that women with a low risk for breast cancer talk to their doctor before starting to have mammogram screening at age 40. Other associations, including the American Cancer Society, continue to recommend annual mammograms for women age 40 and older.
Women at high risk for breast cancer should have an MRI scan along with their annual mammogram, according to 2007 guidelines from the American Cancer Society.
For women who have been diagnosed with cancer in one breast, an MRI can help detect tumors in the other breast, indicates a 2007 study in the New England Journal of Medicine.

Post-Treatment Guidelines

The American Society of Clinical Oncology (ASCO)’s 2006 post-treatment guidelines recommend regular physical exams, breast self-exam, mammograms, and genetic counseling. Know how to recognize the signs of breast cancer recurrence. ASCO does not recommend blood and imaging tests for routine recurrence screening.

Hormone Replacement Therapy (HRT) and Breast Cancer Risk

Fewer women are using HRT, which may explain why new cases of breast cancer among postmenopausal women have declined, suggests a recent New England Journal of Medicine study.

Aromatase Inhibitors

Drug treatment with aromatase inhibitors is improving survival in women with hormone-sensitive advanced breast cancer, suggest recent studies. Switching from tamoxifen to an aromatase inhibitor may help improve the odds for survival.

Introduction

Breast cancers are potentially life-threatening malignancies that develop in one or both breasts. The structure of the female breast is important in understanding this cancer:

The interior of the female breast consists mostly of fatty and fibrous connective tissues.
It is divided into about 20 sections called lobes.
Each lobe is further subdivided into a collection of lobules, structures that contain small milk-producing glands.
These glands secrete milk into a complex system of tiny ducts. The ducts carry the milk through the breast and converge in a collecting chamber located just below the nipple.
Breast cancer is either noninvasive (referred to as in situ, confined to the site of origin) or invasive (spreading).

The female breast is either of two mammary glands (organs of milk secretion) on the chest.

Noninvasive breast cancers include:

Ductal carcinoma in situ (also called intraductal carcinoma or DCIS). DCIS consist of cancer cells in the lining of the duct. DCIS is a non-invasive, early cancer, but if left untreated, it may sometimes progress to an invasive, infiltrating ductal breast cancer.
Lobular carcinoma in situ, or LCIS. Although noninvasive, lobular carcinoma in situ is a marker for an increased risk of invasive cancer in both breasts. (Some experts prefer to call this condition lobular neoplasia rather than refer to it as a cancer.) According to a 2001 report, for patients with LCIS the risk for developing invasive cancer in the same breast is about 18% -- and 14% in the other breast -- after 20 years. These invasive cancers can be either lobular or ductal.

At the time of diagnosis of these early cancers (DCIS and LCIS), there is no evidence of invasion.

Invasive cancer occurs when cancer cells spread beyond the basement membrane, which covers the underlying connective tissue in the breast. This tissue is rich in blood vessels and lymphatic channels that are capable of carrying cancer cells beyond the breast. Invasive breast cancers include the following:

Infiltrating ductal carcinoma. This is invasive breast cancer that penetrates the wall of a duct. It comprises between 70 - 80% of all breast cancer cases.
Infiltrating lobular carcinoma. This invasive cancer has spread through the wall of a lobule. It accounts for 10 - 15% of all breast cancers. It may sometimes appear in both breasts, sometimes in several separate locations.

Click the icon to see an image of the breast.

There are other less common breast cancers that are not discussed in this report.

Risk Factors

About 12 - 13% of women develop breast cancer in their lifetime. Experts estimate that about 178,480 women will be newly diagnosed with invasive breast cancer in the United States in 2007. Another 2,030 men will be diagnosed with breast cancer during the year. Although breast cancer in men is rare, the incidence has been increasing, and men are diagnosed at a later stage than women. An estimated 40,460 women and 450 men will die from breast cancer in 2007. The earlier breast cancer is diagnosed, the earlier the opportunity for treatment. According to the American Cancer Society, over 2 million women who have been treated for breast cancer are alive today.

Age is a major identifiable risk factor. More than 80% of breast cancer cases occur in women over age 50, and especially in women over age 65. The odds by age are as follows:

From ages 30 - 39, a woman’s chance for being diagnosed with breast cancer is 1 in 233
Ages 40 - 49, the odds are 1 in 69
Ages 50 - 59, the odds are 1 in 38
Ages 60 - 69, the odds are 1 in 27
Ages 70 - 79, the odds are 1 in 11
After age 80, the odds are 1 in 8

Breast cancer is more prevalent among Jewish women of Eastern European (Ashkenazi) descent. Meanwhile, African-American women tend to get breast cancer at an earlier age than Caucasians. Although African-American women have lower overall rates of breast cancer, they represent the highest proportion of women who are diagnosed with the disease before age 45. Comparative studies of breast cancer rates among sub-Saharan Africans suggest a genetic component, as African women are diagnosed most frequently between ages 35 - 45.

The mortality rate in African-Americans is twice that of Caucasians, although it is declining. Social and economic factors make it less likely that African-American women will be screened, so they are more likely to be diagnosed at a later stage. They are also less likely to have access to effective treatments. However, there also appears to be a biological basis for African-American women’s poorer prognosis. According to research presented at the 2007 Breast Cancer Symposium, African-American women are more likely to have estrogen receptor-negative tumors, a type of breast cancer that is more difficult to treat.

An estimated 10% of all women with breast cancer have a very strong family history of the disease. Inherited forms of breast cancer often appear in young women under the age of 50. In such families, some members may also be at higher risk for ovarian cancer. These mutations can be inherited from either a mother or father.

Prior to menopause, a mass on the ovary that is smaller than 2 centimeters is probably a follicle cyst that will go away on its own. However, if the growth is larger and doesn't go away over the course of a few menstrual cycles, then it may need to be removed.

BRCA Genes. Inherited mutations in genes known as BRCA1 or BRCA2 are responsible for 30 - 50% of hereditary breast cancers, ovarian cancers, or both in families with a history of these cancers. According to some studies, the risk each gene carries is:

Between 25 - 35% of BRCA1 carriers develop breast cancer by age 70.
Between 35 - 50% of BRCA2 carriers develop the disease. BRCA2 genes also increase the lifetime risk of breast cancer in men.

These mutations are present in only about 0.5% of the overall population. However, certain ethnic groups -- such as Jewish women of Eastern European (Ashkenazi) descent -- have a higher prevalence (2.5%) of BRCA gene mutations. BRCA gene mutations are also seen in some African-American and Hispanic women.

Screening Guidelines for BRCA Genes. In 2005, the U.S. Preventive Services Task Force (USPSTF) released updated guidelines for BRCA testing. While women at high risk should be tested, the USPSTF does not recommend routine genetic counseling or testing for BRCA genes in low-risk women (no family history of BRCA 1 or 2 genetic mutations).

ESR Genes. Genetic variations in estrogen receptor genes (ESRs) may increase the risk for some women but offer protection to others. Mutations in the ESR1 and ESR2 genes may be associated with breast cancer susceptibility for Ashkenazi women over age 50 years.

Other Genetic Factors. Mutations in the tumor suppressor gene p53 are more common in the breast cancer tumors of African-American women than in Caucasian women. Researchers have also identified other defective genes that contribute to breast cancer, such as NOEY2 (which is inherited from the father), CHEK2, and ATM, a mutant gene for the rare disorder ataxia-telangiectasia. (The disease itself is rare, but 1% of the population carries a single copy -- enough to increase the risk for breast cancer.) Cowden's syndrome is an inherited disorder caused by a defective PTEN gene that is associated with a higher risk of breast cancer.

Not all genetic mutations are inherited. In 2007, scientists announced they had located a genetic mutation found in as many as 30 - 40% of breast cancers. The IKBKE mutation appears to occur during the course of a women’s lifetime. It causes overproduction of a kinase protein (IKK-epsilon) that fuels cell growth and tumor development. By identifying this genetic mutation, scientists hope they can develop drugs that will target and block IKK-epsilon production.

Because growth of breast tissue is highly sensitive to estrogens, the more estrogen a woman is exposed to over her lifetime, the higher her risk for breast cancer.

Duration of Estrogen Exposure. Early age at menarche (first menstrual period) or later age at menopause may slightly increase a women’s risk for breast cancer.

Pregnancy. Women who have never had children or who had their first child after age 30 may have a slightly increased breast cancer risk. Having children at an early age, and having multiple pregnancies, reduces breast cancer risk.

Although a few studies have suggested a slightly increased risk for breast cancer in women who have had abortions, the weight of evidence does not support an association between abortion and breast cancer. A large-scale 2007 study found that neither induced abortions nor spontaneous abortions (miscarriages) increases breast cancer risk. However, interrupting a pregnancy does reduce the protective features of a full-term pregnancy.

Studies have been mixed on whether breast-feeding decreases breast cancer risk. Breast-feeding reduces a woman’s total number of menstrual cycles, and thereby estrogen exposure, which may account for its possible protective effects. Some studies suggest that the longer a woman breast-feeds, the lower her risk.

Oral Contraception. Studies have been conflicting about whether estrogen in oral contraception increases the chances for breast cancer. Some studies have found no evidence that oral contraceptive use increases the risk for breast cancer, even in women who have taken birth control pills for 15 years or more or had taken them at young ages. In contrast, other studies have reported a slightly higher risk in women who are current or recent users and in women who take them for more than 4 years before a first full-term pregnancy.

Hormone Replacement Therapy. Many studies have reported a higher risk for breast cancer in postmenopausal women who take hormone replacement therapy (HRT) that contains both estrogen and progestin. A combination of estrogen and testosterone also increases breast cancer risk. A 2005 study suggested that HRT with no or low progestin is safer than standard estrogen-progestin combination therapy.

Several 2006 studies of women who had a hysterectomy indicated that estrogen alone does not increase overall breast cancer risk when the drug is used for 7 years or less. However, women who take estrogen for 10 - 15 years or more do have an increased risk, especially women who are already at higher risk for breast cancer. In addition, HRT increases breast cancer density, making mammograms more difficult to read. This can cause cancer to be diagnosed at a later stage. Women who take estrogen HRT should be aware that they need frequent mammogram screenings.

As further evidence of the association between HRT and breast cancer, a 2007 New England Journal of Medicine study noted that breast cancer rates have fallen as HRT use has declined. The decline in rates occurred among women over the age of 50 and was particularly associated with cancers that were estrogen receptor-positive. This type of cancer requires estrogen for growth. Experts think that postmenopausal women’s discontinuation of estrogen-containing HRT may explain the decrease in rates of new cases of estrogen receptor-positive cancer.

A 2007 position statement from the North American Menopause Society recommends that women who are at risk for breast cancer should avoid hormone therapy and try other options to manage menopausal symptoms such as hot flashes. At this time, most experts recommend that women use HRT only for short-term relief of menopausal symptoms. [See In-Depth Report #40: Menopause.]

Infertility and Infertility Treatments. There has been concern that infertility treatments using the drug clomiphene may increase the risk for breast cancer. A reassuring 2006 study indicated that ovulation induction with clomiphene does not increase breast cancer risk, and may actually decrease it. (Clomphine is related to tamoxifen, a drug that is used for breast cancer prevention in high-risk women.) The study also suggested that women who are infertile because of ovulatory dysfunction have a 25% lower risk for breast cancer than fertile women.

Abnormalities or Breast Conditions Suggesting a Higher Risk. Certain factors and breast conditions may increase the risk for breast cancer:

Dense breast tissue is associated with a higher risk for breast cancer. Studies suggest that women with highly dense tissue have 2 - 6 times the risk of women with the least dense tissue. Genetic factors play a large role in breast density. Hormone replacement therapy also increases breast density. In addition, dense breasts make mammograms more difficult to read, which increases the likelihood of missing early signs of cancer.
Benign proliferative breast disease, or unusual cell growth known as atypical hyperplasia, is a significant risk factor for breast cancer.

Some common benign breast abnormalities that pose few or no risks include the following:

Cysts. These mostly occur in women in their middle-to-late reproductive years and can be eliminated simply by aspirating fluid from them.

Click the icon to see an image of cysts in the breast.

Fibroadenoma. These are solid benign lumps that occur in women ages 15 - 30.
Breast abscesses during breast-feeding.

Click the icon to see an image of a breast abscess.

Nipple discharge. Discharge from the nipple is worrisome to patients, but is unlikely to be a sign of cancer. Unexplained discharge still warrants evaluation, however.

Click the icon to see an image of nipple discharge.

Mastalgia. This is breast pain that occurs in association with, or independently from, the menstrual cycle. About 8 - 10% of women experience moderate-to-severe breast pain associated with their menstrual cycle. In general, breast pain does not need assessment unless it is severe and prolonged.

The following physical characteristics have been associated with increased risk:

Obesity increases the risk for all types of estrogen receptor-positive breast cancers. Women who gain weight after menopause are most at risk. (On a positive note, losing weight after menopause decreases breast cancer risk.) In postmenopausal women, estrogen is produced in fat tissue. High amounts of fatty tissue increase levels of estrogen in the body, leading to faster growth of estrogen-sensitive cancers.
Estrogen is involved in building bone mass. Therefore, women with heavy, dense bones are likely to have higher estrogen levels and to be at greater risk for breast cancer.
Some studies have found a greater risk for breast cancer in taller women, possibly due to the higher estrogen levels associated with greater bone growth. In one study, regardless of their actual height, women who reached their full height at age 13 or younger had a higher risk than those who attained maximum height at age 18, reflecting higher estrogen levels at an earlier age.

Exposure to Estrogen-like Industrial Chemicals. Chemicals with estrogen-like effects, called xenoestrogens, have been under suspicion for years. There has been particular concern with pesticides containing organochlorines (DDT and its metabolites, such as dieldrin) and pyrethroids (permethrin), but at this time evidence of any causal association is very weak.

Exposure to Diethylstilbestrol. Women who took diethylstilbestrol (DES) to prevent miscarriage have a slightly increased risk for breast cancer. Recent studies also suggest a slightly increased risk for their daughters (commonly called "DES daughters"), who were exposed to the drug when their mothers took it during pregnancy.

Radiation Exposure. Heavy exposure to radiation is a significant risk factor for breast cancer. Girls who received high-dose radiation therapy face an increased risk for breast cancer in adulthood. Low-dose radiation exposure before age 20 may increase the risk for women with BRCA genetic mutations.

Researchers theorize that viruses may be involved in some types of breast cancers. A study of breast cancer samples taken from Tunisian women in North Africa found similarities with a virus known to cause breast cancer in mice. The samples were compared with those taken from women living in other global regions. The researchers suggested that a human breast cancer virus may be more prevalent in specific parts of the world.

Prevention and Lifestyle Factors

Evidence indicates that regular exercise, particularly vigorous exercise, may offer some modest protection against breast cancer. Exercise can help reduce body fat, which in turn lowers levels of cancer-promoting hormones such as estrogen. In fact, a 2006 study suggested that physical activity may help women reduce the risk for developing estrogen receptor-positive tumors.

Exercise can also help women who have been diagnosed with breast cancer. Studies indicate that both aerobic and weight training exercises benefit the body and the mind, and improve quality of life for breast cancer survivors. Even moderate exercise can help improve survival. A 2005 study in the Journal of the American Medical Association reported survival benefits for women diagnosed with breast cancer who walked 3 – 5 hours per week at an average pace. The American Cancer Society recommends engaging in 45 - 60 minutes of physical activity at least 5 days a week. A recent study indicated that diet and exercise can reduce the risk of breast cancer recurrence.

Physical activity contributes to health by reducing the heart rate, decreasing the risk for cardiovascular disease, and reducing the amount of bone loss that is associated with age and osteoporosis. Physical activity also helps the body use calories more efficiently, thereby helping in weight loss and maintenance. It can increase basal metabolic rate, reduces appetite, and helps in the reduction of body fat.

Despite much research on the association between diet and breast cancer, there is still little consensus. The best advice is to eat a well-balanced diet and avoid focusing on one "cancer-fighting" food. The American Cancer Society’s dietary guidelines for cancer prevention recommend that people:

Choose foods and amounts that promote a healthy weight.
Eat 5 or more servings of fruits and vegetables each day.
Choose whole grains instead of refined grain products.
Limit consumption of processed and red meat.
Women should limit alcohol consumption to 1 drink per day (women at high risk for breast cancer should consider not drinking alcohol at all).

For breast cancer survivors, the American Cancer Society recommends diets that include lots of fruits and vegetables, low amounts of saturated fat (from meat and high-fat dairy products), moderation in soy foods, and moderate or no alcohol consumption.

Here are results from recent studies evaluating diet and breast cancer, for preventing both the development of cancer and its recurrence:

Fats. Research is still mixed on the role that fats, and which specific types of fats, play in breast cancer risk and prevention. Several studies have indicated that red meat, which is high in saturated fat, may increase breast cancer risk when eaten in large quantities on a daily basis. (Red meat is also high in iron, which in itself may increase breast cancer risk.) According to results from the 2006 Women’s Health Initiative study of dietary fat and breast cancer, experts cannot yet definitely say that a low-fat diet will help prevent breast cancer. However, the study suggested that women who normally eat a very high-fat diet may benefit by reducing their fat intake. In the study, the low-fat diet reduced blood estrogen levels by 15%. The low-fat diet also appeared to reduce the risk for developing progesterone receptor-negative tumors.

Fruits and Vegetables. Fruits and vegetables are important sources of antioxidants, which may help protect against the tissue damage linked to increased cancer risk. Antioxidants include vitamin C, vitamin E, and carotenoids such as beta-carotene and lycopene. Richly colored fruits and vegetables -- not supplements -- are the best sources for these nutrients. These fiber-rich foods are an essential part of a healthy diet. However, it is not clear whether fruits and vegetables can specifically prevent breast cancer development or recurrence. According to a 2007 study of women with early-stage breast cancer, a low-fat diet very high in vegetables, fruit, and fiber does not work any better in preventing breast cancer recurrence than the standard 5 servings a day of fruits and vegetables. (However, a combination of diet and exercise may help.)

Calcium and Vitamin D. Eating lots of foods rich in calcium and vitamin D (such as yogurt and milk) may modestly reduce the risk of breast cancer for premenopausal -- but not postmenopausal -- women, according to a 2007 study. Low-fat or non-fat dairy products are a healthier choice than high-fat ones.

Click the icon to see an image of vitamin D sources.

Soy. Soy is an excellent low-fat protein alternative to meat. Soy contains phytoestrogens, which are estrogen-like plant chemicals. In particular, soy contains a type of phytoestrogen called isoflavones. Because many soy foods (such as tofu) are eaten in Asian countries where women tend to have a lower incidence of breast cancer, research has focused on whether soy may have a protective effect. To date, the evidence does not indicate that soy foods or supplements can reduce breast cancer risk. In addition, some studies suggest that high intakes of soy may actually increase the risk of estrogen-responsive cancers such as breast cancer. Some animal studies have suggested that the isoflavone compound genistein may reduce the protective properties of tamoxifen, a drug used to prevent breast cancer in high-risk women. The American Cancer Society recommends that women with breast cancer eat only moderate amounts of soy foods and avoid taking dietary supplements that contain high amounts of isoflavones.

Click the icon to see an image of phytochemicals.

Lifestyle Factors. Premenopausal women at higher risk, usually because of family history, should take as many preventive measures as possible, starting at an early age. The following lifestyle choices may be beneficial:

Exercising and eating healthily is the first essential rule.
High-risk premenopausal women may choose alternatives to oral contraceptives and, if feasible, consider having children early in their life.
High-risk postmenopausal women may want to forego hormone replacement therapy.
Any woman at high risk for breast cancer should consider avoiding alcohol or drinking it very sparingly.

In spite of some rumors published in the popular press, antiperspirants or use of deodorants after shaving have not been linked with any higher risk for breast cancer.

Tamoxifen and Raloxifene. Drugs known as selective estrogen-receptor modulators (SERMs) act like estrogen in some tissues but behave like estrogen blockers (anti-estrogens) in others. Two SERMs -- tamoxifen (Nolvadex) and raloxifene (Evista) -- are approved for breast cancer prevention for high-risk women. Tamoxifen and raloxifene are not recommended as prevention for women at low risk for breast cancer or its recurrence. Women at high risk for breast cancer should discuss with their doctors the risks and benefits of SERMs.

Tamoxifen (Nolvadex) is the most studied of these drugs. It is currently used to treat breast cancer and was the first drug approved for prevention. Evidence strongly suggests that it halves the risk for estrogen receptor-positive cancers in high-risk women, including those with BRCA2 mutations (although possibly not BRCA1). It also helps prevent recurrence in women who have been treated for breast cancers. However, it has no protective effects against estrogen receptor-negative (hormone-insensitive) cancers.

Tamoxifen can increase the risk for uterine (endometrial) cancers. It can also increase the risk for blood clots, strokes, and endometriosis. Less serious side effects include hot flashes and vaginal discharge.

Raloxifene (Evista) was approved in 2007 for prevention of breast cancer in postmenopausal women with osteoporosis and postmenopausal women at high risk for invasive breast cancer. Raloxifene was previously approved for prevention and treatment of osteoporosis in postmenopausal women. One of raloxifene’s main benefits is that it has a lower risk than tamoxifen of causing uterine cancer. However, raloxifene also has some serious risks.

According to the prescribing information from the Food and Drug Administration (FDA), raloxifene can increase the risk of blood clots. Women with a history of blood clots in the legs, lungs, or eyes should not take this medicine. Although studies indicate raloxifene does not increase the risk of stroke, it can increase the risk of dying from a stroke. Women with a history of stroke or current risk factors for stroke should discuss with their doctors whether raloxifene is an appropriate choice. Less serious side effects of raloxifene include hot flashes, leg cramps, swelling of the legs and feet, flu-like symptoms, joint pain, and sweating. Raloxifene can cause birth defects and is approved only for postmenopausal women. It should not be taken with the cholesterol-lowering drug cholestyramine (Questran) or with estrogens.

The FDA based its approval of raloxifene on results from several major studies. The comparison trial Study of Tamoxifen and Raloxifene (STAR), published in 2006 in the Journal of the American Medical Association, indicated that raloxifene works as well as tamoxifen in reducing the risk of invasive breast cancer, and has a lower risk of causing blood clots. However, the Raloxifene Use for the Heart (RUTH) trial, published in 2006 in the New England Journal of Medicine, suggested that raloxifene carries its own risks for blood clots and fatal strokes and may not be a safe choice for women at high risk of heart disease.

Investigational Drugs for Breast Cancer Prevention.

Aromatase inhibitors. Aromatase inhibitors such as anastrazole (Armidex), letrozole (Femara), and exemestane (Aromasin) are effective treatments for hormone-receptor positive breast cancer. Like tamoxifen, they are also being investigated for protection in high-risk women. However, these drugs may decrease bone mineral density and cognitive function, and increase the risk for falls.
Retinoids. Analogues of vitamin A called retinoids are being studied for protection against breast cancer. One retinoid, fenretinide, appears to offer some protection against a second breast cancer in previously diagnosed, premenopausal women (but not in postmenopausal women). It can cause birth defects and should not be used during pregnancy.

Symptoms

Breast cancers in their early stages are usually painless. Often the first symptom is the discovery of a hard lump. Fifty percent of such masses are found in the upper outer quarter of the breast. The lump may make the affected breast appear elevated or asymmetric. The nipple may be retracted or scaly. Sometimes the skin of the breast is dimpled like the skin of an orange. In some cases there is a bloody or clear discharge from the nipple. Many cancers, however, produce no symptoms and cannot be felt on examination. They can be detected only with a mammogram.

Monthly breast self-exams should always include: visual inspection (with and without a mirror) to note any changes in contour or texture, and manual inspection in standing and reclining positions to note any unusual lumps or thicknesses.

Diagnosis

Breast Examination by a Health Professional. Early detection of breast cancer significantly reduces the risk of death. Women ages 20 - 49 should have a physical examination by a health professional every 1 - 2 years. Those over age 50 should be examined annually. A breast exam by a health professional can find 10 - 25% of breast cancers that are missed by mammograms. Between 6 - 46% of the lumps detected by examination are malignant. (The yield is lowest in younger women and highest in older women.)

Self-Examinations. Woman have been encouraged to perform a self-examination each month, but well-conducted studies in 2002 reported no difference in mortality rates between women who were intensively instructed in self-examination and those who were not. This does not mean women should stop attempting self-examinations, but they should not replace the annual examination done by a health professional, which evidence suggests is beneficial.

1. Pick a time of the month that is easy to remember and perform self-examination at that time each month. The breast has normal patterns of thickness and lumpiness that change within a monthly period, and a consistently scheduled examination will help differentiate between what is normal from abnormal.

2. Stand in front of a mirror. Breasts should be basically the same size (one may be slightly larger than the other). Check for changes or redness in the nipple area. Look for changes in the appearance of the skin. With hands on the hips, push the pelvis forward and pull the shoulders back and observe the breasts for irregularities. Repeat the observation with hands behind the head. Move each arm and shoulder forward.

3. Lie down on the back with a rolled towel under one shoulder. Apply lotion or bath oil over the breast area.

The finger action should be as follows: Using the 2nd, 3rd, and 4th finger pads (not tips) held together, make dime-sized circles. Press lightly first to feel the breast area, then press harder using a circular motion.

Using this motion, start from the collarbone and move downward to underneath the breast. Shift the fingers slightly over, slightly overlapping the previously checked region, and work upward back to the collarbone. Repeat this up-and-down examination until the entire breast area has been examined. Be sure to cover the entire area from the collarbone to the bottom of the breast area and from the middle of the chest to the armpits. Move the towel under the other shoulder and repeat the procedure.

Examine the nipple area, by gently lifting and squeezing it and checking for discharge.

4. Repeat step 3 in an upright position. (The shower is the best place for this, using plenty of soap.)

Note: A lump can be any size or shape and can move around or remain fixed. Of special concern are specific or unusual lumps that appear to be different from the normal varying thicknesses in the breast.

Click the icon to see an image of a breast self-exam.

Current Recommendations for Screening. Mammograms are very effective low-radiation screening methods for breast cancer. At this time, the U.S. Preventive Services Task Force recommends screening mammograms, with or without breast examination, every 1 - 2 years for all women over age 40.

Guidelines from the American College of Physicians (ACP), however, debate whether women with a low risk for breast cancer should begin mammogram screening at age 40. The 2007 guidelines, instead, recommend that women in their 40s ask their doctor when they should begin having the test. In contrast, the American Cancer Society and the U.S. National Cancer Institute continue to endorse annual screening for women age 40 and older.

The ACP's guidelines have created controversy within the medical community. Supporters of the guidelines believe that these new recommendations reflect some of the risks involved in screening younger women. These risks include radiation exposure and unnecessary biopsies. Mammographies in younger women produce a relatively high rate of false-positive results (when the test falsely indicates breast cancer). Scientists are working on new technologies to improve mammography's accuracy, but more work is needed. For example, a 2007 New England Journal of Medicine study reported that computer-aided detection software, which is used to help radiologists interpret mammograms, may instead make readings less accurate.

Opponents of the ACP guidelines argue that mammograms help catch tumors while they are in their earliest and most treatable stages, and that the most deadly types of breast cancer tend to occur in women in their 40s.

In addition, according to a review in the American Cancer Society's journal, mammography rates have declined since 2000. In fact, while many experts believe that the recent decline in new cases of breast cancer is partially due to reduced use of hormone replacement therapy, other experts are concerned that fewer cases of breast cancer are being detected because fewer mammographies are being performed.

After age 50, all guidelines recommend annual screenings. The older a women gets, the greater her risk for developing breast cancer. (Women over age 65 account for most new cases of breast cancer.) Women with risk factors for breast cancer, including a close family member with the disease, should consider having annual mammograms starting 10 years earlier than the age at which the relative was diagnosed.

Click the icon to see an image of a mammogram.

Magnetic Resonance Imaging and Ultrasound. Magnetic resonance imaging (MRI) and ultrasound techniques can detect very small tumors (less than half an inch). However, they are expensive and time-consuming procedures. Nevertheless, some doctors believe they are important in identifying small tumors missed on mammography in women who are receiving lumpectomy or breast-conserving surgeries. Such findings would allow the surgeons to remove the optimal amount of abnormal tissue. Ultrasound may also be particularly important for women with dense breast tissue who show signs of breast cancer.

In a report published in 2007, the American Cancer Society recommended that high-risk women have an MRI of their breast with their annual mammogram, including those who have:

A BRCA1 or BRCA2 mutation
A first-degree relative (parent, sibling, child) with a BRCA1 or BRCA2 mutation, even if they have yet to be tested themselves
A lifetime risk of breast cancer that has been scored at 20 - 25% or greater
Had radiation to the chest between ages 10 - 30
Li-Fraumeni syndrome, Cowden syndrome, or Bannayan-Riley-Ruvalcaba syndrome, or may have one of these genetic syndromes based on a history in a first-degree relative

For women who have had cancer diagnosed in one breast, MRIs can also be very helpful for detecting hidden tumors in the other breast. A landmark 2007 study in the New England Journal of Medicine reported that MRI scans of women who were diagnosed with cancer in one breast detected over 90% of cancers in the other breast that had been previously missed by mammography or clinical breast exam. Currently, few women who are diagnosed with cancer in one breast are offered an MRI of the other breast. Some experts advocate MRIs for all women newly diagnosed with breast cancer; others oppose this view. MRI scans may be most useful for younger women with breast cancer who have dense breast tissue that may obscure tumors from mammography readings. MRIs are less likely to be helpful for older women with early tumors in one breast and clear mammography readings in the other.

It is very important that women have MRIs at qualified centers that perform many of these procedures each year. MRI is a complicated procedure and requires special equipment and experienced radiologists. MRI facilities should also be able to offer biopsies when suspicious findings are detected.

Scintimammography. In scintimammography, a radioactive chemical is injected into the circulatory system, which is then selectively taken up by the tumor and revealed on mammograms. This method is very accurate in detecting the presence or absence of breast cancer, and some doctors hope that it might eventually reduce the number of unnecessary invasive biopsies. It is used for women who have had abnormal mammograms or for women who have dense breast tissue. It is not used for regular screening or as an alternative to mammography.

A definitive diagnosis of breast cancer can be made only by a biopsy (a microscopic examination of a tissue sample of the suspicious area).

When a lump can be felt and is suspicious for cancer on mammography, an excisional biopsy may be recommended. This biopsy is a surgical procedure for removing the suspicious tissue and typically requires general anesthetic.

Click the icon to see an image of breast biopsy.

A core biopsy involves a small incision and the insertion of a spring-loaded hollow needle that removes several samples. The patient only requires local anesthetic.
A wire localization biopsy may be performed if mammography detects abnormalities but there is no lump. With this procedure, using mammography as a guide, the doctor inserts a small wire hook through a hollow needle and into the suspicious tissue. The needle is withdrawn, and the hook is used by the surgeon to locate and remove the lesion. The patient may receive local or general anesthetic.
A new vacuum-assisted device may be useful for some biopsies. This uses a single probe through which a vacuum is used to draw out tissue. It allows several samples to be taken without having to remove and re-insert the probe.

Final analysis of the breast tissue may take several days.

If breast cancer has been determined, the next diagnostic step is to find out how far it has spread. To do this, the doctor performs a procedure called an axillary lymphadenectomy, which partially or completely removes the lymph nodes in the armpit beside the affected breast (called axillary lymph nodes). It may require a hospital stay of 1 - 2 days.

Click the icon to see an image of the axillary lymph nodes.

Once the lymph nodes are removed, they are analyzed to determine whether subsequent treatment needs to be more or less aggressive:

If no cancer is found in the lymph nodes, the condition is referred to as node negative breast cancer. The chances are good that the cancer has not spread and is still local.
If cancer cells are present in the lymph nodes, the cancer is called node positive. Their presence increases the possibility that the cancer has spread microscopically to other areas of the body. In such cases, however, it is still not known if the cancer has metastasized beyond the lymph nodes or, if so, to what extent. The doctor may perform further tests to see if the cancer has spread to the bone (bone scan), lungs (x-ray or CT scan) or brain (MRI or CT scan).

Side effects of the procedure include increased risk for infection and pain, swelling in the arm from fluid build-up, and impaired sensation and restricted movement in the affected arm. Patients might ask their doctor about the availability of physical therapy or upper-body exercises after treatment. In two studies, such programs resulted in quicker recovery and no fluid build-up in the arm.

A technique known as a sentinel node biopsy is a less invasive alternative to axillary lymph node dissection. This procedure can help determine if cancer has spread beyond the nodes. If the doctor finds no evidence of cancer, the patient may not need to have a complete axillary lymphadenectomy.

Click the icon to see an image of a sentinel node biopsy.

Sentinel node biopsy involves:

The procedure uses an injection of a tiny amount of a tracer, either a radioactively-labeled substance (radioisotope) or a blue dye, into the tumor site.
The tracer or dye then flows through the lymphatic system into the sentinel node. This is the first lymph node to which any cancer would spread.
The sentinel lymph node and possibly one or two others are then removed.
If they do not show any signs of cancer, it is highly likely that the remaining lymph nodes will be cancer free, making further surgery unnecessary.

Patients who have a sentinel node biopsy tend to have better arm function and a shorter hospital stay than those who have an axillary node biopsy. The American Society of Clinical Oncology's 2005 guidelines recommend sentinel node biopsy instead of axillary lymph node dissection for women with early stage breast cancer who do not have nodes that can be felt during a physical exam. It is still not known if the sentinel node biopsy has any survival advantages compared to standard lymph node removal procedures.

Women often have to wait several days for results of sentinel node biopsies to learn whether they will require another surgery to remove additional lymph nodes. In 2007, the Food and Drug Administration approved the GeneSearch BLN Assay to help speed sentinel node biopsy testing. This molecular-based lab test can detect within 40 minutes whether cancer has spread to nearby lymph nodes. Because the test delivers rapid results while the patient is still on the operating table, it may help spare women the discomforts of a second surgical procedure and help them get treatment earlier.

Prognosis

In the U.S., about 40,460 women will die from breast cancer this year, making it the second most lethal cancer in women. (Lung cancer is the leading cancer killer in women.) The good news is that early detection and new treatments have improved survival rates. The 5-year survival rate for women diagnosed with cancer is 80%. About 88% of women diagnosed with breast cancer will survive at least 10 years. Unfortunately, women in lower social and economic groups still have significantly lower survival rates than women in higher groups.

Several factors are used to determine successful treatment and the possibility for a cure. They include:

The location of the tumor and how far it has spread
Whether the tumor is hormone receptor-positive or -negative
Genetic factors
Tumor size and shape
Rate of cell division
Biologic markers

The good news is that women are living longer with breast cancer, and at this time more than 2 million American women are survivors. Due to better treatment options, from 1990 - 2003, breast cancer mortality rates declined by 24%. However, survivors must live with the uncertainties of possible recurrent cancer and some risk for complications from the treatment itself.

Recurrences of cancer usually develop within 5 years of treatment. However, 25% of recurrences and half of new cancers in the opposite breast occur after 5 years. One study suggested that the risk factors for a first breast cancer do not necessarily place a woman at any higher risk for recurrence. (Women with a first cancer, however, do have a higher risk for a new cancer in the opposite breast. The outlook for such new cancers is independent from those of the first one.)

The location of the tumor is a major factor in outlook:

If the cancer is ductal carcinoma in situ (DCIS) or has not spread to the lymph nodes (is node-negative), the 5-year survival rates with treatment are up to 98%. However, cancer recurs in 9 - 30% of women with node-negative cancers. Recurrence is a potentially life-threatening problem, even if the disease relapses locally in the same breast. In one study of DCIS patients with locally invasive recurrence, 8-year mortality rates were only 12%.
If the lymph nodes contain cancer cells (are node positive) then survival rates fall. If the tumor is larger than 5 cm or there is widespread involvement in the lymph nodes, the cancer is sometimes referred to as locally advanced. In such cases, the survival rate drops to about 75% and below.
If the cancer has spread (metastasized) to other sites (most often the lung, liver, and bone), the average survival time is about 2 years (with some patients living for many years). New drug therapies, particularly aromatase inhibitors, have helped prolong survival for women with metastatic cancer.

The location of the tumor within the breast is an important predictor. Tumors that develop toward the outside of the breast tend to be less serious than those that occur more toward the middle of the breast.

Breast cancer cells may contain receptors, or binding sites, for the hormones estrogen and progesterone. Cells containing these binding sites are known as hormone receptor-positive cells. If cells lack these connectors, they are called hormone receptor-negative cells. About 75% of breast cancers are estrogen receptor-positive (ER-positive, or ER+). About 65% of ER-positive breast cancers are also progesterone receptor-positive (PR-positive, or PR+). Cells that have receptors for one of these hormones, or both of them, are considered hormone receptor-positive.

Hormone receptor-positive cancer is also called "hormone sensitive" because it responds to hormone therapy such as tamoxifen or aromatose inhibitors. Hormone receptor-negative tumors are referred to as "hormone insensitive" or "hormone resistant."

Women have a better prognosis if their tumors are hormone receptor-positive because these cells grow more slowly than receptor-negative cells. In addition, women with hormone receptor-positive cancer have more treatment options. (Hormone receptor-negative tumors can be treated only with chemotherapy.) A 2007 study in the Journal of Clinical Oncology indicated that recent declines in breast cancer mortality rates have been most significant among women with estrogen receptor-positive tumors, due in part to the widespread use of post-surgical tamoxifen therapy.

Determining a "genetic signature" for a tumor may prove to be a very powerful predictor of the aggressive nature of a breast cancer. Researchers have focused on 70 genes whose activity patterns may help make such predictions. In 2007, the Food and Drug Administration approved MammaPrint, a DNA microarray diagnostic test that profiles these 70 genes. The molecular test may help predict how likely it is that breast cancer will recur within 5 - 10 years. However, the accuracy of the test depends on a woman’s risk. It is more accurate when predicting a low risk for recurrence than a high risk.

The relevance of the inherited BRCA1 or BRCA2 mutations to survival is controversial. Some studies have suggested that these mutations offer a survival advantage. Others suggest that they make no difference or even worsen prognosis. Women with these genetic mutations do have a greater risk for a new cancer to develop. Patients with BRCA1 mutations tend to develop tumors that are hormone receptor negative, which can behave more aggressively.

Researchers are investigating numerous substances in tumor cells that may indicate whether or not a cancer is likely to spread. Such chemical markers may help doctors determine treatments, and some may even prove to be targets for future drugs. The following are only a few of the more well-researched markers.

HER2. The American Cancer Society recommends that all women newly diagnosed with breast cancer get a biopsy test for a growth-promoting protein called HER2/neu. HER2-positive cancer usually occurs in younger women and is more quickly-growing and aggressive than other types of breast cancer. The HER2 marker is present in about 20% of cases of invasive breast cancer. Two types of tests are used to detect HER2:

Immunohistochemistry (IHC)
Fluorescence in-situ hybridization (FISH)

Some doctors think that FISH is a more accurate test than IHC. According to 2006 HER2 testing guidelines from the American Society of Clinical Oncology and the College of American Pathologists, either test may be used as long as it is performed by an accredited laboratory. Tests that are not clearly positive or negative should be repeated. Treatment with trastuzumab (Herceptin) or lapatinib (Tykerb) may help women who test positive for HER2.

Angiogenesis Factors. Angiogenesis is the growth of new blood vessels. High levels of angiogenesis factors indicate that the tumor is developing its own supply of blood vessels, which enable the tumor to send colonies of cancer cells into the bloodstream and spread to other parts of the body. Specific angiogenesis factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), may turn out to be important markers for determining treatment and prognosis. The monoclonal antibody bevacizumab (Avastin) targets VEGF. The drug is showing promise in clinical trials for prolonging progression-free survival in women with metastatic breast cancer.

Others. Many other markers are being investigated, including p53, cathepsin-D, protein c-erbB-2, bcl-2, Ki-67, telomerase, thymidylate synthase, CA 15-3, and carcinogenic embryonic antigen (CEA). The American Society of Clinical Oncology (ASCO) cautions, however, that the value of many of these factors has not yet been confirmed.

Tumor Size and Shape. Large tumors pose a higher risk than small tumors. Undifferentiated tumors, which have indistinct margins, are more dangerous than those with well-defined margins.

Rate of Cell Division. The more rapidly a tumor grows, the more dangerous it is. Several tests measure aspects of cancer cell division and may eventually prove to predict the disease. For example, the mitotic index (MI) is a measurement of the rate at which cells divide. The higher the MI, the more aggressive the cancer. Another test measures cells at a certain phase of their division.

Recent evidence has not supported early reports of survival benefits for women with metastatic breast cancer who engage in support groups. However, some studies have suggested that psychotherapy, group support, or both may relieve pain and reduce stress, particularly in women who are suffering emotionally.

Stress has been ruled out as a risk factor either for breast cancer itself or for its recurrence.

Treatment

The three major treatments of breast cancer are surgery, radiation, and drug therapy. No one treatment fits every patient, and combination therapy is usually required. The choice is determined by many factors, including the age of the patient, menopausal status, the kind of cancer (ductal vs. lobular), its stage, and whether or not the tumor contains hormone-receptors.

Breast cancer treatments are defined as local or systemic:

Local Treatment. Surgery and radiation are considered local therapies because they directly treat the tumor, breast, lymph nodes, or other specific regions. Surgery is usually the standard initial treatment.
Systemic Treatment. Drug treatment is called systemic therapy, because it affects the whole body.

Any or all of these therapies may be used separately or, most often, in different combinations. For example, radiation alone or with chemotherapy or hormone therapy may be beneficial before surgery, if the tumor is large or not easily removed at prevention. Surgery followed by radiation and hormone therapy is usually recommended for women with early-stage, hormone-sensitive cancer. There are numerous clinical trials investigating new treatments and treatment combinations. Patients, especially those with advanced stages of cancer, may wish to consider enrolling in a clinical trial.

Treatment strategies depend in part on the stage of the cancer.

Stage 0 (Carcinoma in Situ). Stage 0 breast cancer is considered non-invasive (‘in situ"), meaning that the cancer is still confined within breast ducts or lobules and has not yet spread to surrounding tissues. Stage 0 cancer is classified as either:

Ductal carcinoma in situ (DCIS). These are cancer cells in the lining of a duct that have not invaded the surrounding breast tissue.
Lobular carcinoma in situ (LCIS). These are cancer cells in the lobules of the breast. LCIS rarely develops into invasive breast cancer, but having it in one breast increases the risk of developing cancer in the other breast.

Treatment options for DCIS include:

Breast-conserving surgery and radiation therapy (followed by hormone therapy for women with hormone-sensitive cancer)
Total mastectomy (followed by hormone therapy for women with hormone-sensitive cancer)
Breast-conserving surgery without radiation therapy

Treatment options for LCIS include:

Regular exams and mammograms to monitor any potential changes (observation treatment)
Hormone therapy to prevent development of breast cancer (for women with hormone-sensitive cancer)
Mastectomy of both breasts was previously used as treatment, but is now rarely recommended

Stage I and II (Early-Stage Invasive). In stage I cancer, cancer cells have not spread beyond the breast, and the tumor is no more than 2 cm (about 3/4 of an inch) across.

Stage II cancer is classified as either stage IIA or stage IIb.

In stage IIA cancer the tumor is either:

No more than 2 centimeters and has spread to the underarm lymph nodes (axillary lymph nodes)
Between 2 - 5 centimeters and has not spread to the underarm lymph nodes

Treatment options for stage I and stage II breast cancer may include:

Breast-conserving surgery (such as lumpectomy) followed by radiation therapy
Modified radical mastectomy with or without breast reconstruction
Post-surgical therapy (adjuvant therapy), including radiation of lymph nodes, chemotherapy, or hormone therapy
Trastuzumab (Herceptin) given along with or following adjuvant chemotherapy for women with HER2-positive cancer

Stage III (Locally Advanced). Stage III breast cancer is classified into several sub-categories: Stage IIIA, stage IIIB, and stage IIIC (operable or inoperable).

In stage IIIA breast cancer, the tumor is usually confined to the underarm lymph nodes. Treatment options for stage IIIA breast cancer are the same as those for stages I and II.

In stage IIIB breast cancer, the tumor has spread to either:

Tissues near the breast (including the skin or chest wall)
Lymph nodes within the breast or under the arm

Stage IIIB treatment options may include:

Chemotherapy, and possibly hormone therapy (sometimes in combination with chemotherapy)
Chemotherapy followed by surgery (breast-conserving surgery or total mastectomy) with lymph node dissection followed by radiation therapy and possibly more chemotherapy or hormone therapy
Clinical trials

Stage IIIC breast cancer is classified as either operable or inoperable.

In operable stage IIIC, the cancer may be found in:

10 or more of the underarm lymph nodes
Lymph nodes beneath the collarbone and near the neck on the same side of the body as the affected breast
Lymph nodes within the breast as well as underarm lymph nodes

Treatment options for operable stage III breast cancer are the same as those for stage I and II breast cancers.

In inoperable stage III breast cancer, the cancer has spread to lymph nodes above the collarbone and near the neck on the same side of the body as the affected breast. Treatment options are the same as those for stage IIIB.

Stage IV (Advanced Cancer). In stage IV, the cancer has spread (metastasized) from the breast to other parts of the body. In about 75% of cases, the cancer has spread to the bone. The cancer at this stage is considered to be chronic and incurable, and the usefulness of treatments is limited. The goals of treatment for stage IV cancer are to stabilize the disease and slow its progression, as well as to reduce pain and discomfort.

Treatment options for stage IV cancer include:

Surgery or radiation for any localized tumors in the breast. A 2006 study indicated that surgical removal of the primary tumor immediately after metastatic cancer diagnosis can dramatically improve survival.
Chemotherapy, hormone therapy, or both. Targeted therapy with trastuzumab (Herceptin) or lapatinib (Tykerb) should be considered for women with HER2-positive cancer.
Cancer that has spread to the brain may require radiation and high-dose steroids.
Cancer that has spread to the bone may be helped by radiation or bisphosphonate drugs. Such treatments can relieve pain and help prevent bone fractures.
Clinical trials of new drugs or drug combinations, or experimental treatments such as high-dose chemotherapy with stem cell transplant.

In 2006, the American Society of Clinical Oncology (ASCO) released updated guidelines on follow-up care for patients who have been treated for breast cancer. ASCO recommends:

Visit your doctor every 3 - 6 months for the first 3 years after your first cancer treatment, every 6 - 12 months during the fourth and fifth year, and once a year thereafter.
Have a mammogram 1 year after the mammogram that diagnosed your cancer (but no earlier than 6 months after radiation therapy), and every 6 - 12 months thereafter.
Perform a breast self-exam every month (however, this is no substitute for a mammogram).
See your gynecologist regularly (women taking tamoxifen should be sure to report any vaginal bleeding).
A year after diagnosis, you can either continue to see your oncologist or transfer your care to your primary care physician.
If you are on hormone therapy, discuss with your oncologist how often to schedule follow-up visits for re-evaluation of your treatment.

ASCO does not recommend the use of laboratory blood tests (complete blood counts, carcinoembryonic antigen) or imaging tests (bone scans, chest x-rays, liver ultrasound, FDG-PET scan, CT scan) for routine breast cancer follow-up.

Genetic counseling may be helpful if you have:

Ashkenazi Jewish heritage
Personal or family history of ovarian cancer
Personal or family history of cancer in both breasts
Any first-degree female relative (mother, sister, daughter) diagnosed with breast cancer before age 50
Two or more first-degree or second-degree (grandparent, aunt, uncle) diagnosed with breast cancer
History of breast cancer in a male relative

Pregnancy after Breast Cancer Treatment. There are no definite recommendations on how long a woman should wait to become pregnant after breast cancer treatment. Because of the connection between estrogen levels and breast cancer cell growth, some experts recommend delaying pregnancy until 2 years after treatment in order to reduce the risk of cancer recurrence and improve odds for survival. However, a 2007 study indicated that conceiving 6 months after treatment does not negatively affect survival. Discuss with your doctor your risk for recurrence, and when it may be safe to attempt pregnancy.

Recurrent breast cancer is considered to be an advanced cancer. In such cases, the disease has come back in spite of the initial treatment. Most recurrences appear within the first 2 - 3 years after treatment, but breast cancer can recur many years later. Treatment options are based on the stage at which the cancer reappears, whether or not the tumor is hormone responsive, and the age of the patient. Between 10 - 20% of recurring cancers are local. Most recurrent cancers are metastatic. All patients with recurring cancer are candidates for clinical trials.

Because most breast cancer recurrences are discovered by patients in between doctor visits, it is important to notify your doctor if you experience any of the following symptoms. These symptoms may be signs of breast cancer recurrence:

New lumps in the breast
Bone pain
Chest pain
Abdominal pain
Shortness of breath or difficulty breathing
Persistent headaches or coughing
Rash on breast
Nipple discharge

Surgery

Surgery forms a part of nearly every patient's treatment for breast cancer. The initial surgical intervention is often a lumpectomy, the removal of the tumor itself. In the past, mastectomy (the removal of the breast) was the standard treatment for nearly all breast cancers. Now, many patients with early-stage cancers can choose breast-conserving treatment, or lumpectomy followed by radiation, with or without chemotherapy.

For invasive breast cancer, studies indicate that lumpectomy or partial mastectomy combined with radiation therapy works as well as a modified radical mastectomy.

Breast-conserving procedures are now appropriate and as successful as mastectomy in most women with early stage breast cancer. All women should discuss these options fully with their doctor. Recurrence rates with conservative surgery are highest in women under age 45. Some women choose mastectomy over breast-conserving treatment even if the latter is appropriate because it gives them a greater sense of security and allows them to avoid radiation therapy.

Lumpectomy. Lumpectomy is the removal of the tumor, often along with lymph nodes in the armpit. It serves as an opportunity for biopsy, a diagnostic tool, and a primary treatment for small local breast tumors. If invasive cancer is found, the doctor will decide to proceed with breast radiation therapy, to remove additional tissue (should the margins of the specimen show signs of cancer), or to perform a mastectomy. Lumpectomy followed by radiation therapy is appropriate and as effective as mastectomy in most women with Stage I or II breast cancers.

Click the icon to see an illustrated series detailing breast lump removal surgery.

Breast-Conserving Surgery (Quadrantectomy). Breast-conserving surgery (sometimes referred to as quadrantectomy) removes the cancer and a large area of breast tissue, occasionally including some of the lining over the chest muscles. It is less invasive than a full mastectomy, but the cosmetic results are less satisfactory than with a lumpectomy. Excellent studies have found that breast-conserving surgeries plus postoperative radiotherapy offer the same survival rates as radical mastectomy in women with early breast cancer. A new technology called partial breast radiation (MammoSite), approved by the Food and Drug Administration in 2002, confines radiation to the tumor site rather than delivering it to the whole breast, and reduces treatment time from 5 weeks to 5 days in women who undergo breast conserving surgery.

Surgery to remove the breast (mastectomy) is important for women with operable breast cancer who are not candidates for breast conserving surgeries. There are different variations on the procedure:

A total mastectomy involves removal of the whole breast and sometimes lymph nodes under the armpit.
A radical mastectomy removes the breast, chest muscles, all of the lymph nodes under the arm, and some additional fat and skin. (A modified radical mastectomy removes the entire breast and armpit lymph nodes, with the underlying chest wall muscle.) A 25-year study supported other research that observed no survival advantages from radical mastectomy compared to the less invasive mastectomies for the great majority of patients. It is rarely used anymore except when cancer is very advanced.

Click the icon to see an illustrated series detailing mastectomy surgery.

Complications and Side Effects of Surgery. Short-term pain and tenderness occur in the area of the procedure, and pain relievers may be necessary.

The most frequent complication of extensive lymph node removal is edema, or swelling, of the arm, which is usually mild and rarely painful but does increase the risk for infection. The likelihood of edema can be lessened by removing only some of the lymph nodes instead of all of them.

Infrequent complications include poor wound healing, bleeding, or a reaction to the anesthesia.

After mastectomy and lymph node removal, women may experience numbness, tingling, and difficulty in extending the arm fully. These effects can last for months or years afterward.

After a mastectomy, some women choose a breast prosthesis or opt for breast reconstruction, which can be performed during the mastectomy itself, if desired. Several studies have indicated that women who take advantage of cosmetic surgery after breast cancer have a better sense of well-being and a higher quality of life than women who do not choose reconstructive surgery. The breast is reshaped using a saline implant or, for a more cosmetic result, a muscle flap is taken from elsewhere in the body. Muscle flap procedures are more complicated, however, and blood transfusions may be required. (It should be noted that implants, including silicone implants, do not appear to put a woman at risk for breast cancer recurrence.) If the nipple is removed, it is rebuilt from other body tissues and color is applied using tattoo techniques. It is nearly impossible to rebuild a breast that is identical to its partner, and additional operations may be necessary to achieve a desirable effect.

Click the icon to see an illustrated series detailing breast reconstruction surgery.

Numerous studies are investigating minimally invasive techniques that use lasers, deep-freezing of cancer cells (cryosurgery), high-intensity ultrasound, and other experimental approaches to kill cancer cells and reduce severe complications of surgery. Radiofrequency ablation, for example, is an approach that uses an electrode inserted into the tumor. It emits radio waves that produce enough heat to destroy cancer cells. Early trials are promising. These procedures, however, are not considered standard at the present time.

Radiation

Radiation therapy uses high-energy x-rays to kill cancer cells or to shrink the size of a tumor in the breast or surrounding tissue. It is used for several weeks following lumpectomy or partial mastectomy, and sometimes after full mastectomy. Radiation therapy can help reduce the chance of breast cancer recurrence in the breast and chest wall. Radiation is also important in advanced stages of cancer for relief of symptoms and to slow progression. Research shows that radiation therapy is helpful for women of all ages, including those over age 65.

Radiation is generally administered in the following ways:

External Beam Radiation. This type of radiation is administered 4 - 6 weeks after surgery and delivered externally by an x-ray machine that targets radiation to the whole breast. It may be delivered to the chest wall in high-risk patients (large tumors, close surgical margins, or lymph node involvement). The treatment is generally given daily (except for weekends) for about 6 weeks. A follow-up boost of radiation therapy in patients with lumpectomies appears to reduce the risk for recurrence.

Brachytherapy. Less commonly, radiation is delivered in implants (called brachytherapy). Implants are most often used as a radiation boost after whole breast radiation. Studies suggest they improve survival in patients at high risk for local recurrence. Some evidence suggests that implants alone can reduce treatment time and may be as effective as external beam radiation in some patients with early stage breast cancer. A new technology for breast brachytherapy (MammoSite) was approved in 2002. The technique provides 5-year local tumor control rates similar to those of whole-breast radiation for selected patients, with much shorter treatment time and good cosmetic results.

Investigators are also testing other approaches to radiation treatment. One uses a combination of neutrons and protons (mixed-beam) or proton beams rather than the standard photon radiation therapy. Intensity-modulated radiation therapy is a promising technique that delivers different doses to multiple target areas using images of specific regions. Such an approach may improve the coverage of breast cancers while reducing the toxic effects to the heart and lungs.

Side effects of radiation include:

Fatigue is very common and increases with subsequent treatments, but most women are able to continue with normal activities. Exercise may be helpful.
Nausea and lack of appetite may develop and worsen as treatment progresses.
Skin changes and burns can occur on the breast skin. Using a cream that contains a corticosteroid, such as mometasone furoate (MMF), may be helpful. After repeated sessions, the skin may become moist and "weepy." Exposing the treated skin to air as much as possible helps healing. (Washing the affected skin with soap and water does not seem to be harmful and in one study was associated with a lower risk for this side effect.)
Uncommonly, the breast may change color, size, or become permanently firm.
Rarely, the nearest arm may swell and develop impaired mobility or even paralysis.

Future complications include:

Radiation to the left breast may increase the long-term risk for developing heart disease and heart attacks.
There is a very small risk (less than 1%) of lung irritation and scarring.
Some studies have reported a higher risk for future cancer in the opposite breast in younger women who have been given radiation to the chest wall.
Radiation therapy can increase the risk of developing other cancers, such as soft tissue malignancies known as sarcomas.

Current advanced imaging techniques use precise radiation that reduces exposure. These newer techniques are likely to reduce the risks for heart disease and other serious complications.

Medications

The most important advances in the cure of breast cancer have come through the use of drug therapy, also called systemic therapy. Surgery and radiation therapy are effective for treating tumors confined to the breast but not for cancer cells that have spread or are at risk of spreading. In such cases, drug therapy is needed.

Drug treatments for breast cancer include:

Chemotherapy. Chemotherapy drugs are "cytotoxic" (cell-killing) drugs. They are given orally or by injection. They work systemically by killing cancer cells throughout the body. (Unfortunately, they also kill normal cells, which accounts for many of their side effects.) Chemotherapy is always used for advanced breast cancer, but may also be used to treat types of early-stage breast cancer.
Hormone Therapy. The goal of hormone therapy is to prevent estrogen from stimulating breast cancer cells. It is recommended for women whose breast cancers are hormone-receptor positive (either estrogen or progesterone), regardless of the size of the tumor and whether or not it has spread to the lymph nodes. Like chemotherapy, hormone therapy works systemically.
Targeted Therapy. Newer biologic drugs target specific proteins involved in cancer. Because they do not work as systemically as chemotherapy or hormone therapy drugs, they tend to cause fewer widespread side effects. Currently, the monoclonal antibody trastuzumab (Herceptin) and the kinase inhibitor lapatinib (Tykerb) are the two targeted therapies approved for breast cancer. These drugs target the HER2/neu protein and are used to treat HER2-positive breast cancers. Bevacizumab (Avastatin) is a monoclonal antibody that targets vascular endothelial growth factor (VEGF), a protein involved in tumor blood vessel formation (angiogenesis). It is being studied in clinical trials for treatment of metastatic breast cancer.

Drug therapy may be used as:

Primary therapy for patients for whom surgery or radiation therapy is not appropriate.
Neoadjuvant therapy (before surgery or radiation) to shrink tumors to a size that can be treated with local therapy.
Adjuvant therapy (following surgery or radiation) to reduce the risk of cancer recurrence.

For metastatic cancer, drugs are used not to cure but to improve quality of life and prolong survival.

Chemotherapy

Chemotherapy needs to be tailored to the type of cancer involved. Women require different treatments depending on whether the tumor is node-negative or -positive, hormone receptor-positive or -negative, or HER2-positive or -negative. Different treatment approaches are also used for early-stage cancer and advanced cancer.

A 2006 study in the Journal of the American Medical Association indicated that women with hormone receptor-negative cancers respond better to chemotherapy than women with hormone receptor-positive cancer. However, some women with hormone receptor-positive cancer do benefit from chemotherapy, as well as from hormone therapy.

Adjuvant chemotherapy is administered following surgery and before radiation therapy. A 2007 study in the Journal of Clinical Oncology suggested that women with early-stage breast cancer can safely wait for up to 12 weeks after surgery before beginning chemotherapy. However, delaying chemotherapy until more than 12 weeks after surgery significantly increases the risk for breast cancer recurrence and can reduce the odds for survival by as much as 60%.

Many different types of chemotherapy drugs are used to treat breast cancer. Common types of chemotherapy drug classes include:

Anthracyclines include doxorubicin (Adriamycin) and epirubicin (Ellence). Anthracycline-based combination regimens are often used to treat early-stage breast cancer, as well as advanced cancer.
Taxanes include paclitaxel (Taxol) and docetaxel (Taxotere). Two 2003 studies suggested that taxane-based therapy is particularly helpful for node-positive breast cancer. A newer formulation of paclitaxel (Abraxane) is used as a secondary treatment for advanced breast cancer.
Platinum-based drugs include oxaliplatin (Eloxatin) and carboplatin (Paraplatin). These drugs may be used in combination regiments for advanced cancer or for cancers associated with BRCA genes.

Some of the abbreviations used for chemotherapy drug combinations (regimens) refer to drug classes rather than drug names. For example, regimens that contain an anthracycline drug (such as doxorubicin) use the letter "A," and regimens that contain a taxane drug (such as docetaxel) use the letter "T." Cyclophosphamide (Cytoxan), fluorouracil (5-FU), and methotrexate (MTX) are standard cancer drugs used in many breast cancer chemotherapy regimens.

Chemotherapy regimens usually consist of 4 - 6 cycles of treatment given over 3 - 6 months. Common chemotherapy regimens for early-stage breast cancer include:

AC (Doxorubicin and cyclophosphamide)
AC followed by T (Doxorubicin and cylophosphamide followed by paclitaxel)
CAF (Cyclophosphamide, doxorubicin, and 5-FU)
CMF (Cyclophosphamide, methotrexate, and 5-FU)
TAC (Docetaxel, doxorubicin, and cyclophosphamide)

Trastuzumab (Herceptin). Trastuzumab is a monoclonal antibody that targets the HER2 protein on cancer cells. HER2-positive cancers account for 15 - 25% of early-stage breast cancer and are associated with more aggressive disease. Younger women tend to be most affected. In November 2006, the Food and Drug Administration approved trastuzumab for treatment of HER2-positive, early-stage breast cancer (cancer confined to the breasts or lymph nodes that has been surgically removed). Trastuzumab is given along with other chemotherapy drugs following lumpectomy or mastectomy. Research indicates that trastuzumab can help prevent cancer recurrence and death among women with early-stage breast cancer, but it increases the risk of heart problems. Trastuzumab can cause heart failure. Women who have heart failure or weak heart muscle (cardiomyopathy) should not use this drug. Women who take trastuzumab need to have regular heart monitoring, especially if they have already have heart problems.

Patients who develop metastatic disease (cancer that spreads throughout the body) are generally not curable. New advances in drug therapies, however, can help shrink tumors, prolong survival, and improve quality of life.

Chemotherapy regimens for advanced cancer may use a single drug or a combination of drugs. Many chemotherapy regimens used for early-stage breast cancer are also used for advanced breast cancer. Some specific combinations for advanced cancer include:

Gemcitabine and paclitaxel. In 2004, the Food and Drug Administration approved the antimetabolite drug gemcitabine (Gemzar) for use in combination with paclitaxel (Taxol) as a first-line treatment option for women with metastatic breast cancer.
Capecitabine (Xeloda) and docetaxel (Taxotere). Capecitabine is an oral drug that is chemically related to 5-FU. It is also being studied in combination with many other drugs.

Numerous chemotherapy drugs and drug combinations are being tested in clinical trials. Patients with advanced breast cancer may also receive other types of drug treatments. Bisphosphonate drugs, such as zoledronic acid (Zometa) and pamidronate (Aredia), are important supportive drugs for preventing fractures and reducing pain in people whose cancer has spread to the bones.

Two targeted therapy drugs are approved for the treatment of HER2-positive advanced breast cancer

Trastuzumab (Herceptin) was approved in 1998 for treatment of metastatic breast cancer. It is used in adjuvant chemotherapy, along with drugs such as paclitaxel.
Lapatinib (Tykerb) was approved in March 2007 for patients who have not been helped by other cancer drugs, including an anthracycline, a taxane, or trastuzumab. Lapatinib is used in combination with capecitabine (Xeloda). Research suggests it may have fewer risks for heart problems than trastuzumab.

Promising new treatments for advanced breast cancer include:

Ixabepilone (BMS-247550). Ixabepilone is the first of a new class of cancer drugs called epothilones. It is showing encouraging results when combined with capecitabine, according to research presented at the 2007 annual meeting of the American Society of Clinical Oncology.
Bevacizumab (Avastin). Bevacizumab is a targeted therapy anti-angiogenesis drug approved for treatment of colorectal and lung cancers. It is being studied in combination with various chemotherapy drugs for treatment of advanced cancer.

Side effects occur with all chemotherapeutic drugs. They are more severe with higher doses and increase over the course of treatment.

Common side effects include:

Nausea and vomiting. Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve these side effects. In one study, a combination of dexamethasone (a corticosteroid) with ondansetron taken within 24 hours of chemotherapy achieved either a major or complete reduction in nausea and vomiting. Aprepitant (Emend), a new drug for preventing chemotherapy-caused nausea and vomiting, was approved in 2006.
Diarrhea
Temporary hair loss
Weight loss
Fatigue
Depression

Serious short- and long-term complications can also occur and may vary depending on the specific drugs used. They include the following:

Anemia. The erythropoietins epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp) stimulate red blood cell production and can help reduce or prevent anemia, resulting in significant improvement in quality of life. Aranesp persists longer in the blood than epoetin alfa and may therefore require fewer injections.
Increased chance for infection from severe reduction in white blood cells (neutropenia). The addition of a drug called granulocyte colony-stimulating factor (filgrastim and lenograstim) is very helpful in reducing the risk for severe infection.
Liver and kidney damage.
Abnormal blood clotting (thrombocytopenia).
Allergic reaction, particularly to platinum-based drugs.
Menstrual abnormalities and infertility. Premature menopause occurs in about 30% of women, particularly in those over 40. A natural hormone medication called a gonadotropin-releasing hormone analogue, which puts women in a temporary pre-pubescent state during chemotherapy, may preserve fertility in some women. Women may also wish to consider embryo cryopreservation -- the harvesting of eggs, followed by in vitro fertilization and freezing of embryos for later use. The American Society of Clinical Oncology recommends that women being treated for cancer see a reproductive specialist to discuss all available fertility preservation options.
Sexual dysfunction.
Rarely, secondary cancers such as leukemia.
A quarter to a third of women report problems in concentration, motor function, and memory, which can be long-term. In one study, women were having these symptoms 2 years after treatment, although by 4 years they had resolved.
Heart problems. Trastuzumab (Herceptin) may increase the risk for heart failure, particularly in women with pre-existing risk factors. Cumulative doses of anthracyclines (doxorubicin, epirubicin) can also damage heart muscles over time and increase the risk for heart failure.
Taxanes can cause a drop in white blood cells and possible problems in the heart and central nervous system. Allergic reactions can occur, more often in taxol than taxotere. Taking a steroid before taxane administration can help prevent such reactions. Taxane therapy may also cause severe joint and muscle pain in some patients, relievable with corticosteroids.

High-dose chemotherapy along with peripheral-blood stem cell rescue or bone marrow transplantation procedures have been used for cancer that has metastasized and, in some cases, for earlier stages of breast cancer in high-risk patients. The objective of this treatment is to be able to give patients very high toxic doses of cell-killing drugs.

Transplantation procedures are based on stem cells, which are produced in the bone marrow. Stem cells are the early forms for all blood cells in the body (including red, white, and immune cells). Cancer treatments can harm these growing cells as well as cancer cells.

Despite the initial enthusiasm over the use of high-dose therapy for treatment of high risk breast cancer, this approach can no longer be generally recommended and should not be used outside of a clinical trial setting. The results of several randomized studies have failed to show a convincing advantage for the use of high-dose therapy. Nevertheless, some experts believe this approach can still be useful in selected patients, and studies continue. In general, however, transplantation has a limited role in breast cancer management, and its use should be restricted to clinical trials.

Hormone Therapy

Hormone therapy works by blocking estrogen that causes cell proliferation. It is used only for patients with hormone receptor-positive tumors. Different types of hormone therapy work in different ways by:

Blocking estrogen receptors in cancer cells (Tamoxifen)
Suppressing estrogen production in the body (Aromatase inhibitors)
Destroying ovaries, which produce estrogen (Ovarian ablation)

Tamoxifen was the first widely used hormonal therapy drug, but it has been replaced by aromatase inhibitors for some women. Aromatase inhibitors are used only to treat postmenopausal women. Tamoxifen is mainly used as adjuvant therapy for premenopausal women with hormone-sensitive breast cancer.

Tamoxifen (Nolvadex) has been the standard hormonal drug used for breast cancer. It belongs to a class of compounds called selective estrogen receptor modulators (SERMs). SERMs chemically resemble estrogen and trick the breast cancer cells into accepting it in place of estrogen. Unlike estrogen, however, they do not stimulate breast cancer cell growth. Because SERMs block estrogen’s effects on cancer cells, they are sometimes referred to as "anti-estrogen" drugs.

Tamoxifen is used for all cancer stages in women of all ages with hormone receptor-positive cancers. In addition, it is used to prevent breast cancer in high-risk women. Another SERM drug, toremifene (Fareston), is an option for women with advanced cancer, but this drug is rarely used in the United States. A third drug, fulvestrant (Faslodex), works in a similar anti-estrogen way to tamoxifen but belongs to a different drug class. Fulvestrant is approved only for postmenopausal women with hormone-sensitive advanced breast cancer in which tamoxifen or aromatase inhibitors no longer work.

To prevent cancer recurrence, women should take tamoxifen for 5 years following surgery and radiation. Tamoxifen is an effective cancer treatment, but it can cause unpleasant side effects and has small (less than 1%) but serious risks for blood clots and uterine (endometrial) cancer. Immediately report any signs of vaginal bleeding to the doctor, as this may be a symptom of uterine cancer.

Less serious, but discomforting, side effects include hot flashes and mood swings. According to a 2007 study, nearly 25% of women stop taking tamoxifen within 1 year because of these symptoms. By 3.5 years, over 33% stop treatment. Taking tamoxifen for fewer than 5 years, however, increases the risk for cancer recurrence and death. Talk with your doctor about antidepressants or other therapies that may help you cope with tamoxifen’s side effects.

Many doctors now recommend that postmenopausal women switch to an aromatase inhibitor after 2 - 3 years of tamoxifen therapy. Several 2007 studies indicated that switching from tamoxifen to an aromatase inhibitor significantly improves survival rates and reduces the risk of death from breast cancer as well as other causes.

Endometrial cancer is a cancerous growth of the endometrium (lining of the uterus). It is the most common uterine cancer.

Aromatase inhibitors block aromatase, an enzyme that is a major source of estrogen in many major body tissues, including the breast, muscle, liver, and fat. Aromatase inhibitors work differently than tamoxifen. Tamoxifen interferes with tumors’ ability to use estrogen by blocking their estrogen receptors. Aromatase inhibitors reduce the overall amount of estrogen in the body.

Because these drugs cannot stop the ovaries of premenopausal women from producing estrogen, they are recommended only for postmenopausal women.

There are currently three aromatase inhibitors approved for treating early-stage, hormone receptor-positive breast cancer in postmenopausal women:

Anastrazole (Armidex) for treatment after surgery
Exemestane (Aromasin) for women who have taken tamoxifen for 2 - 3 years
Letrozole (Femara) for treatment after surgery or for women who have completed 5 years of tamoxifen therapy

All of these drugs are also approved for women with advanced (metastatic) hormone-sensitive breast cancer. Studies indicate that the introduction of aromatase inhibitors has helped greatly in prolonging survival for women with advanced cancer.

Compared to tamoxifen, aromatase inhibitors are less likely to cause blood clots and uterine cancer. However, these drugs are more likely to cause osteoporosis, which can lead to bone loss and fractures. In general, recent studies indicate that aromatase inhibitors are better than tamoxifen in improving survival and reducing the risk of cancer recurrence. Unfortunately, like tamoxifen, they can cause hot flashes, as well as joint pain.

Ovarian ablation literally shuts down estrogen production from the ovaries. Medications can accomplish ovarian ablation. Destroying the ovaries with surgery or radiation can also shut down estrogen production. (Osteoporosis is one serious side effect of this approach, but several therapies are available to help prevent bone loss.)

Chemical Ovarian Ablation. Drug treatment (non-chemotherapy drugs) to block ovarian production of estrogen is called chemical ovarian ablation. It is often reversible. The primary drugs used are luteinizing hormone-releasing hormone (LHRH) agonists, such as goserelin (Zoladex). (They are also sometimes called GnRH agonists). These drugs block the release of the reproductive hormones LH-RH, therefore stopping ovulation and estrogen production.

Studies suggest that women with estrogen-positive early stage cancer who take goserelin have similar survival rates to those who take standard chemotherapy. They also experience fewer serious side effects. A major analysis of four trials using LHRH agonists plus tamoxifen suggested that this combination should be the standard for patients with advanced breast cancers that are hormone-receptor positive, although this is an area of controversy. (Chemotherapy is still more effective in women with estrogen-negative tumors.)

Ovariectomy. Ovariectomy, the removal of the ovaries, has modestly improved breast cancer survival rates in some premenopausal women whose tumors are hormone receptor-positive. In these women, combining this procedure with tamoxifen may improve results beyond those of standard chemotherapies. Ovariectomy does not benefit women after menopause, and its advantages can be blunted in women who have received adjuvant chemotherapy. The procedure causes sterility and can have a major negative emotional impact on younger patients.

Resources

www.cancer.gov -- National Cancer Institute
www.cancer.org -- American Cancer Society
www.asco.org -- American Society of Clinical Oncology
www.oncolink.org -- Oncolink
www.womenshealth.gov -- National Women's Health Information Center
www.nccn.org -- National Comprehensive Cancer Network
www.plwc.org -- People Living With Cancer
www.cancer.gov/clinicaltrials -- Find clinical trials
www.breastcancer.org -- Find clinical trials

References

Bardia A, Hartmann LC, Vachon CM, Vierkant RA, Wang AH, Olson JE, et al. Recreational physical activity and risk of postmenopausal breast cancer based on hormone receptor status. Arch Intern Med. 2006 Dec 11-25;166(22):2478-83.

Barron TI, Connolly R, Bennett K, Feely J, Kennedy MJ. Early discontinuation of tamoxifen: a lesson for oncologists. Cancer. 2007 Mar 1;109(5):832-9.

Boccardo F, Rubagotti A, Aldrighetti D, Buzzi F, Cruciani G, Farris A, et al. Switching to an aromatase inhibitor provides mortality benefit in early breast carcinoma: pooled analysis of 2 consecutive trials. Cancer. 2007 Mar 15;109(6):1060-7.

Boehm JS, Zhao JJ, Yao J, Kim SY, Firestein R, Dunn IF, et al. Integrative genomic approaches identify IKBKE as a breast cancer oncogene. Cell. 2007 Jun 15;129(6):1065-79.

Boyd NF, Guo H, Martin LJ, Sun L, Stone J, Fishell E, et al. Mammographic density and the risk and detection of breast cancer. N Engl J Med. 2007 Jan 18;356(3):227-36.

Breen N, A Cronin K, Meissner HI, Taplin SH, Tangka FK, Tiro JA, et al. Reported drop in mammography : is this cause for concern? Cancer. 2007 Jun 15;109(12):2405-9.

Chia SK, Speers CH, D'Yachkova Y, Kang A, Malfair-Taylor S, Barnett J, et al. The impact of new chemotherapeutic and hormone agents on survival in a population-based cohort of women with metastatic breast cancer. Cancer. 2007 Jul 23;110(5):973-979 [Epub ahead of print]

Cho E, Chen WY, Hunter DJ, Stampfer MJ, Colditz GA, Hankinson SE, et al. Red meat intake and risk of breast cancer among premenopausal women. Arch Intern Med. 2006 Nov 13;166(20):2253-9.

Coombes RC, Kilburn LS, Snowdon CF, Paridaens R, Coleman RE, Jones SE, et al. Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007 Feb 17;369(9561):559-70.

Fenton JJ, Taplin SH, Carney PA, Abraham L, Sickles EA, D'Orsi C, et al. Influence of computer-aided detection on performance of screening mammography. N Engl J Med. 2007 Apr 5;356(14):1399-409.

Geiger AM, Thwin SS, Lash TL, Buist DS, Prout MN, Wei F, et al. Recurrences and second primary breast cancers in older women with initial early-stage disease. Cancer. 2007 Mar 1;109(5):966-74.

Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006 Dec 28;355(26):2733-43.

Ives A, Saunders C, Bulsara M, Semmens J. Pregnancy after breast cancer: population based study. BMJ. 2007 Jan 27;334(7586):194. Epub 2006 Dec 8.

Jatoi I, Chen BE, Anderson WF, Rosenberg PS. Breast cancer mortality trends in the United States according to estrogen receptor status and age at diagnosis. J Clin Oncol. 2007 May 1;25(13):1683-90. Epub 2007 Apr 2.

Kahlenborn C, Modugno F, Potter DM, Severs WB. Oral contraceptive use as a risk factor for premenopausal breast cancer: a meta-analysis. Mayo Clin Proc. 2006 Oct;81(10):1290-302.

Kerlikowske K, Miglioretti DL, Buist DS, Walker R, Carney PA; National Cancer Institute-Sponsored Breast Cancer Surveillance Consortium. Declines in invasive breast cancer and use of postmenopausal hormone therapy in a screening mammography population. J Natl Cancer Inst. 2007 Sep 5;99(17):1335-9. Epub 2007 Aug 14.

Khatcheressian JL, Wolff AC, Smith TJ, Grunfeld E, Muss HB, Vogel VG, et al.American Society of Clinical Oncology 2006 update of the breast cancer follow-up and management guidelines in the adjuvant setting. J Clin Oncol. 2006 Nov 1;24(31):5091-7. Epub 2006 Oct 10.

Lehman CD, Gatsonis C, Kuhl CK, Hendrick RE, Pisano ED, Hanna L, et al. MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. N Engl J Med. 2007 Mar 29;356(13):1295-303. Epub 2007 Mar 28.

Lin J, Manson JE, Lee IM, Cook NR, Buring JE, Zhang SM. Intakes of calcium and vitamin D and breast cancer risk in women. Arch Intern Med. 2007 May 28;167(10):1050-9.

Lohrisch C, Paltiel C, Gelmon K, Speers C, Taylor S, Barnett J, et al. Impact on survival of time from definitive surgery to initiation of adjuvant chemotherapy for early-stage breast cancer. J Clin Oncol. 2006 Oct 20;24(30):4888-94. Epub 2006 Oct 2.

Michels KB, Xue F, Colditz GA, Willett WC. Induced and spontaneous abortion and incidence of breast cancer among young women: a prospective cohort study. Arch Intern Med. 2007 Apr 23;167(:814-20.

Moss SM, Cuckle H, Evans A, Johns L, Waller M, Bobrow L. Effect of mammographic screening from age 40 years on breast cancer mortality at 10 years' follow-up: a randomised controlled trial. Lancet. 2006 Dec 9;368(9552):2053-60.

North American Menopause Society. Estrogen and progestogen use in peri- and postmenopausal women: March 2007 position statement of The North American Menopause Society. Menopause. 2007 Mar-Apr;14(2):168-82.

Perez EA, Lerzo G, Pivot X, Thomas E, Vahdat L, Bosserman L, et al. Efficacy and safety of ixabepilone (BMS-247550) in a phase II study of patients with advanced breast cancer resistant to an anthracycline, a taxane, and capecitabine. J Clin Oncol. 2007 Aug 10;25(23):3407-14. Epub 2007 Jul 2.

Pierce JP, Natarajan L, Caan BJ, Parker BA, Greenberg ER, Flatt SW, et al. Influence of a diet very high in vegetables, fruit, and fiber and low in fat on prognosis following treatment for breast cancer: the Women's Healthy Eating and Living (WHEL) randomized trial. JAMA. 2007 Jul 18;298(3):289-98.

Qaseem A, Snow V, Sherif K, Aronson M, Weiss KB, Owens DK; Clinical Efficacy Assessment Subcommittee of the American College of Physicians. Screening mammography for women 40 to 49 years of age: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2007 Apr 3;146(7):511-5.

Ravdin PM, Cronin KA, Howlader N, Berg CD, Chlebowski RT, Feuer EJ, et al. The decrease in breast-cancer incidence in 2003 in the United States. N Engl J Med. 2007 Apr 19;356(16):1670-4.

Saslow D, Boetes C, Burke W, Harms S, Leach MO, Lehman CD, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007 Mar-Apr;57(2):75-89.

Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M, et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet. 2007 Jan 6;369(9555):29-36.

Terry KL, Willett WC, Rich-Edwards JW, Michels KB. A prospective study of infertility due to ovulatory disorders, ovulation induction, and incidence of breast cancer. Arch Intern Med. 2006 Dec 11-25;166(22):2484-9.

Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007 Jan 1;25(1):118-45. Epub 2006 Dec 11.

Review Date:
1/26/2008
Reviewed By:
A.D.A.M. Editorial Team: David Zieve, MD, MHA, Greg Juhn, MTPW, David R. Eltz, Kelli A. Stacy, ELS. Previously reviewed by Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital (11/01/07).

A.D.A.M. Copyright

adam.com

Menopause

FitSugar — Wed, 08 Oct 2008 17:34:57 -0700

In This Report

Highlights
Introduction
Complications
Symptoms
Lifestyle Changes
Medications
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Black Cohosh Doesn’t Help Hot Flashes

The herbal remedy black cohosh is no better than placebo for treating hot flashes and night sweats, according to a 2006 study in the Annals of Internal Medicine.
Most complementary and alternative medicines are ineffective for relieving menopausal symptoms, according to a 2006 review in the Archives of Internal Medicine.

Hormone Replacement Therapy (HRT)

Short-term use of HRT remains an option for recently menopausal women who have a low risk for stroke, according to a 2007 statement from the North American Menopause Society (NAMS). However, NAMS recommends that women who are at risk for heart disease or breast cancer should consider other approaches for managing hot flashes.
For women who want to discontinue HRT, gradually tapering off the medication or stopping it abruptly appears to make little difference in the recurrence of symptoms, suggests a 2006 study. A gradual approach may delay the reappearance of symptoms, but does not prevent them from returning.

HRT and Heart Disease: Timing Counts

Women who begin HRT within 10 years of menopause have a much lower risk for heart disease and heart attack than women who start HRT later on, indicates a 2007 study in the Journal of the American Medical Association. Experts suggest that HRT is relatively safe for younger women (under age 60) but should not be used by older women. HRT should never be used for prevention of heart disease, and HRT increases the risk for stroke regardless of a woman’s age or when she begins taking it.

HRT and Cancer

A dramatic fall in breast cancer rates has accompanied the decline in HRT use, according to a 2007 study in the New England Journal of Medicine.
Women who use HRT for more than 5 years have a 20% greater risk of developing and dying from ovarian cancer than women who have never used HRT, indicates a 2007 Lancet study of nearly 1 million women.

Introduction

The ovaries contain 200,000 - 400,000 follicles, tiny sacks that contain the materials needed to produce mature eggs, or ova. The ovaries produce two major female hormones: estrogen and progesterone.

The uterus is a hollow muscular organ located in the female pelvis between the bladder and rectum. The ovaries produce the eggs that travel through the fallopian tubes. Once the egg has left the ovary it can be fertilized and implant itself in the lining of the uterus. The main function of the uterus is to nourish the developing fetus prior to birth.

Estrogen. Estrogens have an effect on about 300 different tissues throughout a woman's body:

They are essential for the reproductive process and for the development of the female organs.
Estrogens determine the characteristic female distribution of body fat on the hips and thighs, which develops during adolescence.
They also are involved in tissues in the central nervous system (including the brain), the bones, the liver, and the urinary tract.

Estrogen has different forms:

The most potent form is estradiol.
The other important, but less powerful, estrogens are estrone and estriol.

Most of the estrogens in the body are produced by the ovaries, but they can also be formed by other tissues, such as body fat, skin, and muscle.

Progesterone. Progesterone, the other major female hormone, is necessary for thickening and preparing the uterine lining for the fertilized egg.

As a woman ages, her supply of eggs declines. Menopause occurs naturally after the woman's supply of follicles has been depleted and menstruation ends completely. (Menopause may also be induced if the ovaries are surgically removed.)

Perimenopause. Menopause does not occur suddenly. A period called perimenopause usually begins a few years before the last menstrual cycle. Some experts believe there are three stages in the transition:

Early Stage. The beginning of perimenopause can begin in some women in their 30s, but most often it starts between ages 40 - 44. It is marked by changes in menstrual flow and in the length of the cycle. There may be sudden surges in estrogen.
Middle Stage. In the middle cycle, periods become irregular but they are not skipped.
Late Stage. In the late stages, women begin missing the periods until they finally stop. About 6 months before menopause estrogen levels drop significantly. The fall in estrogen triggers the typical symptoms of vaginal dryness and hot flashes (which can last from half a year to more than 5 years after onset of menopause).

Menopause. At the point at which menopause occurs, the following hormonal changes occur:

Ovarian secretion of estrogen and progesterone ends.
Once the ovaries have stopped producing estrogens, however, they still continue to produce small amounts of the male hormone testosterone, which can be converted to estrogen (estradiol) in body fat.
In addition, the adrenal gland continues to produce androstenedione (a male hormone), which is converted to estrone and estradiol in the body fat.

Click the icon to see an image of the adrenal glands.

The total estrogen produced after menopause, however, is far less than that produced during a woman's reproductive years.

The average age of women at menopause today is 51.4 years although it can occur as early as age 40 to as late as the early 60s. Women now have a life expectancy of more than 80 years. Currently, women can expect to live some 30 or 40 years of their life in the postmenopausal state.

Menopause is not a disease. However, many conditions are associated with estrogen depletion, including heart disease, osteoporosis, and other complications. Fortunately, effective treatments are available for these conditions.

In a number of studies, most women have reported menopause as a positive experience and have welcomed it with relief and as a sign of a new stage in life.

Complications

After a woman reaches menopause, her average life expectancy is 30 - 40 years. During those years, however, she faces certain health risks due to lower levels of estrogen that cause accelerated bone loss and an increase in LDL cholesterol (the so-called bad cholesterol). Her risks for serious disorders are estimated at 46% for heart disease, 20% for stroke, and 15% for hip fracture. In addition, about 8% of people over 75 have dementia, with postmenopausal women having 1.4 - 3 times the risk for Alzheimer's disease compared to men.

Heart disease is the number one killer of women. In 2003, more than 480,000 women died from diseases of the heart and circulation (cardiovascular diseases). Although young women have a much lower risk for cardiovascular disease than young men, after menopause women catch up. After age 51, women’s risk of dying from heart disease is very close to that of men. Estrogen loss is believed to play a major role in this increased risk.

Some studies indicate that women who reach menopause at an early age are at increased risk of heart disease. However, recent research suggests that the reverse may also be true. A 2006 study suggested that women who have heart disease risk factors (smoking, high total cholesterol levels, high blood pressure) during premenopause may enter menopause earlier than women with healthier heart profiles. [See In-Depth Report #3: Coronary artery disease.]

Estrogen has the following effects:

Harmful Effects on Cholesterol and Other Lipids (Fats in the Blood). About 2 years before menopause, as estrogen levels begin to decline, the levels of the harmful low-density lipoprotein (LDL) cholesterol begin to rise, and the advantageous high-density lipoprotein (HDL) levels decrease.
Positive Effect on Blood Flow. Estrogen has significant effects on smoothing, relaxing, and opening blood vessels, thereby increasing blood flow and reducing pressure.
Antioxidant Actions. Estrogen is also an antioxidant. That is, it helps clean up particles called oxygen-free radicals that are released by natural chemical processes in the body, which can cause significant damage, including harm to the arteries.
Mixed Effects on Blood Pressure. The effects of estrogen on blood pressure are not clear. Oral contraceptives, for instance, which contain estrogen, appear to increase pressure slightly.

Blood pressure is the force applied against the walls of the arteries as the heart pumps blood through the body. The pressure is determined by the force and amount of blood pumped and the size and flexibility of the arteries.

Mixed Effects on Blood Clotting. Estrogen affects many blood-clotting factors in the liver: It reduces blood viscosity (stickiness) and may enhance fibrinolysis, the natural process for breaking down blood clots. Unfortunately, estrogen also has other actions that increase the risk for blood clots. Women who take hormone replacement therapy are at risk for thromboembolism -- blood clots that block a vessel.

Click the icon to see an image of thromboembolism.

This action may explain the higher rates of adverse heart events now observed in women with heart disease who take HRT.

Osteoporosis is a disease of the skeleton in which bones become brittle and prone to fracture. In other words, the bone loses density. At age 65, about 30% of women have osteoporosis, and nearly all of them are unaware of their condition. After age 80, up to 70% of women develop osteoporosis. Osteoporosis is a major risk factor for fracture in the spine and hip. The lifetime risk of spinal fracture in women is about 1 in 3 and that for hip fracture is 1 in 6. Furthermore, between 10 - 20% of women who experience a hip fracture die within a year and about 25% require nursing home treatment.

Click the icon to see an image of osteoporosis.

Experts are still puzzled by the extreme speed-up of bone breakdown (resorption) after menopause. Estrogen may have an impact on bone density in various ways:

Estrogen's most important effect on osteoporosis appears to be prevention of bone break down (resorption). Some research suggests that estrogen may control the lifespan of osteoclasts, the cells responsible for bone breakdown.
Part of estrogen's beneficial actions may involve maintaining normal levels of vitamin D, an important nutrient in bone protection.

Risk factors for osteoporosis include:

Being tall and thin
Being Caucasian
Smoking
Taking thyroid hormone
Being sedentary
Early menopause or surgical menopause (removal of ovaries)

Women at risk for osteoporosis should have a bone density test to measure their bone mass and then make a decision about treatment after consulting their doctor. [See In-Depth Report #18:Osteoporosis.]

Depression may occur as a woman transitions into menopause (perimenopause), even among women with no history of clinical depression. Hormonal changes and declines in estrogen levels are probably involved in this process. Research suggests that a depressive disorder is 2.5 times more likely to develop during perimenopause than premenopause. Women who transition to menopause at a younger age are at increased risk of a first episode of depression.

Symptoms of clinical depression include:

Loss of interest or pleasure in activities once enjoyed
Persistent (longer than 2 weeks) sad mood
Decreased energy
Sleep problems (insomnia or oversleeping)
Feelings of guilt, worthlessness, and hopelessness
Difficulty concentrating

Some of these symptoms may overlap with other symptoms that typically accompany perimenopause. Women who experience these symptoms should talk to their doctor. Depression is treatable. [See In-Depth Report #8: Depression.] For many women, depression eases once they reach menopause.

Estrogen, the primary female hormone, appears to have properties that protect against the memory loss and lower mental functioning associated with normal aging. Estrogen's effects on the brain include:

Laboratory studies suggested that estrogen may help block production of beta-amyloid, the source of the sticky plaques found in Alzheimer's brains.
Estrogen may trigger the temporary growth of nerve pathways in the memory portion of the brain.
Estrogen may stimulate production of the neurotransmitters acetylcholine and serotonin, which are depleted in Alzheimer's patients.
Estrogen also appears to smooth, relax, and open blood vessels, which may help blood flow in the brain.
Estrogen is an antioxidant. That is, it helps clean up free-oxygen radicals, the unstable particles thought to play a role in Alzheimer's.
Studies have been mixed on the association between natural estrogen levels and mental functioning in older women.

Estrogen therapy has been associated with reduced gum bleeding and with decreased bone loss around the teeth, and women who take estrogen are less likely to lose their teeth. Thus, the same principle that helps prevent bone loss in osteoporosis is also at work in preventing bone loss in the mouth.

Estrogen, progesterone, or both appear to protect against cataracts.

Click the icon to see an image of a cataract.

Studies also indicate that estrogen helps prevent glaucoma and macular degeneration.

Click the icon to see an image of glaucoma.

Click the icon to see an image of macular degeneration.

The drop in body estrogen levels brought on by menopause may contribute to both urinary stress and urge incontinence.

Women are at increased risk for recurrent urinary tract infections after menopause. Research suggests that estrogen may prevent infection by increasing the number of lactobacilli, a microorganism that fights infection by preventing bacteria from adhering to vaginal cells.

Estrogen may help prevent slackness and dryness in the skin and reduce wrinkles.

Menopause is associated with more sleeping problems, including inability to fall asleep and nighttime wakefulness.

Symptoms

The most prominent symptoms of the transition to menopause include:

Hot flashes and night sweats. Women often experience hot flashes as an intense build-up in body heat, followed by sweating and chills. Some women report accompanying anxiety as the sensation builds. In most cases, hot flashes resolve within 2 years of menopause, although in some women they may persist for years. Women who have a hysterectomy (surgical removal of the uterus) are less likely to experience hot flashes than women who have a natural menopause. However, women who have surgical removal of both ovaries, and who do not receive hormone replacement therapy, may have more severe hot flashes than women who enter menopause naturally.
Heart pounding or racing can occur, with or without hot flashes.
Difficulty sleeping. Insomnia is common during perimenopause. It may be caused by the hot flashes or it may be an independent symptom of hormonal changes. A 2006 study indicated that severe hot flashes are frequently associated with chronic insomnia.
Mood changes. Mood changes are most likely to be a combination of sleeplessness, hormonal swings, and psychological factors as a woman undergoes this intense passage in her life. Once a woman has reached a menopausal state, however, depression is no more common than before, and women with a history of premenstrual depression often experience significant mood improvement.
Sexuality. Sexual responsiveness tends to decline in most women after menopause, although other aspects of sexual function, including interest, frequency, and vaginal dryness vary. It is useful to remember that the symptoms of menopause eventually go away.
Forgetfulness. This appears to be one of the few symptoms that are common across most cultural and ethnic groups.
Urine leakage.
Vaginal dryness.
Joint stiffness.

Women from different ethnic and or cultural groups report different menopausal symptoms. For example, in one study hot flashes occurred in about 30% of Caucasians and 45% of African-Americans. Hispanic women tended to complain of urine leakage, vaginal dryness, and heart pounding. Japanese and Chinese women experienced far fewer menopausal symptoms, except for forgetfulness. All groups complained about this symptom.

Lifestyle Changes

Simple changes in lifestyle and diet can help control menopausal symptoms such as hot flashes. Avoid hot flash triggers like spicy foods, hot beverages, caffeine, and alcohol. Dress in layers so that clothes can be removed when a hot flash occurs. For vaginal dryness, moisturizers, and non-estrogen lubricants, such as KY Jelly, Replens, and Astroglide are available.

When women reach menopause, they are at increased risk for heart disease. A heart-healthy diet is an important way to control cholesterol and blood pressure levels. [See In-Depth Report #42: Heart-healthy diet.]

In 2007, the American Heart Association (AHA) issued revised diet and lifestyle recommendations. The current guidelines recommend:

Balancing calorie intake and physical activity to achieve or maintain a healthy body weight. (Controlling weight, quitting smoking, and exercising regularly are essential companions of any diet program. Try to get at least 30 minutes, and preferably 60 – 90 minutes, of daily exercise.)
Consuming a diet rich in a variety of vegetables and fruits. Vegetables and fruits that are deeply colored (spinach, carrots, peaches, berries) are especially recommended as they have the highest micronutrient content.
Choosing whole-grain, high-fiber foods. These include fruits, vegetables, and legumes (beans). Good whole grain choices include whole wheat, oats/oatmeal, rye, barley, brown rice, buckwheat, bulgur, millet, and quinoa.
Eating fish, especially oily fish, at least twice a week (about 8 ounces/week). Oily fish such as salmon, mackerel, and sardines are rich in the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Consumption of these fatty acids is linked to a reduced risk of sudden death and death from coronary artery disease. Women with existing heart disease may also consider taking a daily dietary supplement of 850 – 1,000 mg of EPA and DHA.
Limiting daily intake of saturated fat (found mostly in animal products) to less than 7% of total calories, trans fat (found in hydrogenated fats, commercially baked products, and many fast foods) to less than 1% of total calories, and cholesterol (found in eggs, dairy products, meat, poultry, fish, shellfish) to less than 300 mg per day. Choose lean meats and vegetable alternatives (such as soy). Select fat-free and low-fat dairy products. Grill, bake, or broil fish, meat, and skinless poultry.
Using little or no salt in your foods. Reducing salt can lower blood pressure and decrease the risk of heart disease and heart failure.
Cutting down on beverages and foods that contain added sugars (corn syrups, sucrose, glucose, fructose, maltrose, dextrose, concentrated fruit juice, honey).
If you consume alcohol, do so in moderation. The AHA recommends limiting alcohol to no more than 1 drink per day for women.
The AHA does not recommend antioxidant supplements (such as vitamin E, C, or beta carotene) or folic acid supplements for prevention of heart disease.

Soy is an excellent food. It is rich in both soluble and insoluble fiber, omega-3 fatty acids, and provides all essential proteins. Soy proteins have more vitamins and minerals than meat or dairy proteins. They also contain polyunsaturated fats, which are better than the saturated fat found in meat. The best sources of soy protein are soy products (tofu, soy milk, soybeans).

For many years, soy was promoted as a food that could help lower cholesterol and improve heart disease risk factors. But an important 2006 review of studies found that soy protein and isoflavone supplement pills do not really have any effects on cholesterol or heart disease prevention. The AHA still recommends soy foods, but not supplements, as a healthy food choice. The benefits of soy on menopausal symptoms are mixed, according to research (see below in Alternative Therapies). A 2006 study reported that increased soy intake does not help reduce the frequency or severity of hot flashes and night sweats.

Soy is high in estrogen-like plant chemicals called isoflavones, which may improve bone health in older women. A 2005 review of 15 clinical trials found that, although the results were mixed, isoflavones appeared to decrease bone loss, especially in younger postmenopausal women. Soy food products, such as tofu, that also contain calcium may be particularly beneficial.

A combination of calcium and vitamin D is important for helping to prevent bone loss. [See In-Depth Report #18: Osteoporosis.]

Calcium. Women should be sure they have sufficient calcium and vitamin D in their diet by consuming low-fat dairy products or calcium-enriched orange juice. Calcium supplements may be another option for some women. For calcium supplements, calcium citrate (Citracal) is better absorbed than calcium carbonate (Tums, Os-Cal) and other types of calcium compounds. Calcium citrate was the first calcium supplement reported to preserve bone density after menopause.

Click the icon to see an image of the benefits of calcium.

The standard recommended calcium dose for adults age 50 years and older is 1,000 – 1,500 mg per day, depending on risk factors. High doses (over 2,500 mg per day) of calcium supplements may increase the risk for kidney stones. (Because many commercial foods are now fortified with calcium, this upper limit may be easier to reach than people think.)

Click the icon to see an image of calcium sources.

For years, doctors have recommended that women take supplements of calcium plus vitamin D to help maintain bone density and reduce the risk for fractures. However, a 2006 New England Journal of Medicine study raised some questions about this approach. In the Women’s Health Initiative study, women were randomly assigned to receive either 1,000 mg of calcium carbonate plus 400 IU of vitamin D a day or placebo. The results indicated that daily calcium and vitamin D supplements:

Improve hip bone density slightly (by 1%)
Prevent hip fracture, but only for women who consistently take the supplements. (Another 2006 study supported this finding.)
Do not prevent spine or other types of fractures
Produce a slight increase in the risk of kidney stones

The medical community has differing views on how to interpret these findings. Some doctors recommend that women over age 60 should still consider taking calcium and vitamin D for bone health. Other doctors feel that due to the risks of kidney stones, supplements are beneficial only for women (especially those over age 70) who do not get enough calcium in their diets. Ask your doctor whether you should take calcium supplements.

Vitamin D. Vitamin D is necessary for the absorption of calcium in the stomach and gastrointestinal tract and is the essential companion to calcium in maintaining strong bones. Some studies suggest that vitamin D protects against osteoporosis only in combination with calcium.

Vitamin D is manufactured in the skin using energy from the ultraviolet rays in sunlight. It can also be obtained from dietary supplements. As a person ages, vitamin D levels decline. Levels also fall during winter months and when people have inadequate sunlight. Pollution may also contribute to less sunlight and declining vitamin D levels.

Click the icon to see an image of vitamin D sources.

Daily dosage guidelines vary. General recommendations include:

400 IU for people age 50 - 60
600 IU for those over age 70 who do not have sufficient exposure to sunlight. (Some evidence suggests that higher doses of vitamin D -- up to 800 IU per day -- may help prevent fractures in people with osteoporosis.)
800 – 1,000 IU for adults over age 50 (the amount recommended by the National Osteoporosis Foundation)

Drinking milk fortified with vitamin D and sunlight exposure supply most people's need for vitamin D. (One cup of whole milk provides about 100 IU of vitamin D.) Oily fish (sardines especially, as well as salmon, fresh tuna, and mackerel) are also important dietary sources of vitamin D. Wild salmon has a much higher vitamin D content than farmed salmon.

Effect on the Heart. One drink a day in women who are not at risk for alcohol abuse may be beneficial for the heart. Red wine in particular contains a substance called resveratrol, which is classified as a phytoestrogen and has estrogen-like effects.

Effect on Bones. Alcohol has different effects on bones depending on how much is consumed. A 2004 study found that moderate wine consumption was linked to improved bone mineral density in postmenopausal women. Alcohol, in moderate amounts, may increase estrogen levels. Excessive drinking, however, has been associated with brittle bones.

Effect on Breast Cancer. Women who drink face an increased risk for breast cancer, but the risk associated with mild-to-moderate drinking is small.

Many women need to increase physical activity and reduce caloric intake before and after menopause. Weight gain is common during these years, and it can be sudden and distressing, particularly when habitual exercise and eating patterns are no longer effective in controlling weight. Gaining weight around the abdomen (the so-called apple shape) is a specific risk factor for heart disease and diabetes and many other health problems. A 2007 study suggested that calcium and vitamin D supplements may help prevent weight gain in postmenopausal women. The benefit was greatest for women who had not been getting enough daily calcium in their diets.

Click the icon to see an image of different types of weight gain.

For protection against all aging diseases, women, whether or not they are taking hormone replacement therapy, should pursue a lifestyle that includes a balanced aerobic and weight resistance exercise program appropriate to their age and medical conditions. Brisk walking, stair climbing, hiking, dancing, and tai chi are all helpful. Several studies report that exercise can help control hot flashes. A healthy diet plus regular, consistent exercise can also help ward off the weight gain associated with menopause. Weight-bearing exercises are specifically helpful for protecting against bone loss. Women should strive for at least 30 minutes of exercise each day (for weight loss, 60 – 90 minutes is preferred). While more exercise is better, any exercise is helpful. A 2007 study showed that postmenopausal sedentary women who exercised only 75 minutes a week experienced improvement in fitness levels.

If a woman smokes, she should quit. Smoking is linked to a decline in estrogen levels. Women who smoke experience menopause about 2 years earlier than nonsmokers. Smoking doubles a woman’s odds of developing coronary heart disease and is a major risk factor for osteoporosis.

Aspirin. The American Heart Association recommends daily low-dose aspirin for all women age 65 years and older who can safely take aspirin. High-risk women may require 75 – 325 mg per day; lower-risk women may benefit from 81 mg a day or 100 mg every other day.

There are many unproven methods for relieving menopausal symptoms, some more effective than others. Acupuncture, meditation, and relaxation techniques are all harmless ways to reduce the stress of menopause, and some people report great benefit from these practices.

Acupuncture, hypnosis, and biofeedback are all alternative ways to control pain. Acupuncture involves the insertion of tiny sterile needles, slightly thicker than a human hair, at specific points on the body.

Women often try herbal or so-called natural remedies to treat menopausal symptoms. There have been numerous studies conducted on various herbal products and other complementary and alterative therapies. These studies have not found that these approaches have any benefit. Some can have adverse side effects.

Many studies have researched plant estrogens (phytoestrogens), which are generally categorized as isoflavones (found in soy and red clover) and lignans (found in whole wheat and flaxseed). No evidence to date indicates that phytoestrogen supplements provide any benefit for hot flashes or other menopausal symptoms. Nevertheless, foods containing them may be healthful.

Supplements containing specific isoflavones found in soy -- typically the estrogen-like compounds genistein and daidzein -- do not appear to provide any benefits compared to the whole soy protein. Taking them separately may, in fact, cause harm, including a possible increase in estrogen-related cancers.

The following herbs are sometimes use for menopausal symptoms and carry certain risks:

Black cohosh (Cimicifuga racemosa), also known as squaw root, is the herbal remedy most studied for menopausal symptoms. Although it contains a plant estrogen, this substance does not act like an estrogen in the human body. Studies have shown mixed results in preventing hot flashes. A rigorous 2006 study found that black cohosh worked no better than placebo for treating hot flashes and night sweats. While it may be ineffective, black cohosh appears to be safe. Headaches and gastrointestinal problems are common side effects.
Dong quai (Angelica sinensis) does not appear helpful for hot flashes or other menopausal symptoms. Do not use dong quai with blood-thinning drugs, such as warfarin, because it may cause bleeding complications.
Ginseng (Panax ginseng) may help menopausal symptoms of depression and sleep problems, but it has no effect on hot flashes.
Kava (Piper methysticum) may relieve anxiety but it does not help hot flashes. This herb is generally considered unsafe, due to several reports of liver failure and death, especially in people with liver disease.
Wild yam (Dioscorea villosa) is an herb sometimes used for menstrual problems as well as menopausal symptoms. It contains a plant progesterone. However, like black cohosh, there is no evidence that the human body can convert this substance into a hormone. Patients should be aware that some commercial herbal wild yam products contain prescription progesterones.
Dehydroepiandrosterone (DHEA) is a weak male hormone secreted by the adrenal gland. It is available as a dietary supplement. DHEA has no benefit for hot flashes and may increase the risk of breast cancer.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like with drugs, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Patients should check with their doctors before using any herbal remedies or dietary supplements.

Medications

Doctors used to believe that HRT could help reduce the risk of heart disease and other health risks in addition to treating menopausal symptoms. The results of an important study, called the Women's Health Initiative (WHI), led doctors to revise their recommendations regarding HRT.

The WHI, started in 1991, enrolled 161,809 women between the ages of 50 - 79 in 40 different medical centers. Part of the study was intended to examine the health benefits and risks of hormone replacement therapy, including the risks of breast cancer, heart attacks, strokes, and blood clots.

In 2002, one component of the WHI, which studied the use of estrogen and progestin in women who had a uterus, was stopped early because the health risks exceeded the health benefits. The main reason for stopping the estrogen-progestin study was a 26% increase in breast cancer. This combination therapy study also showed an increased risk for heart attack, stroke, blood clots, and dementia. There was a reduced risk for colorectal cancer and bone fractures, but these benefits did not outweigh the considerable risks.

In 2004, a second component of the WHI, which studied estrogen-only therapy in women who no longer have a uterus, was stopped early. This was primarily because of an increase in the risk for strokes and blood clots. The study also found the estrogen-only therapy had no effect on heart attack or colorectal cancer risk. An update in 2006 suggested that estrogen-only therapy does not increase breast cancer risk over the short term (average 7 years) but may increase risk when taken for a longer time (15 years or more). Another WHI update, from 2007, indicated that estrogen-only therapy can help reduce calcium deposits in the coronary arteries (a sign of heart disease) for women in their 50s who have had a hysterectomy. However, women who have a uterus cannot take estrogen-only HRT because it increases the risk for uterine cancer. Combination estrogen-progestin HRT does not have the same benefits for cholesterol reduction as estrogen-only HRT.

While the WHI studies indicate that HRT should not be prescribed for prevention of chronic diseases, many doctors still accept its use for short-term treatment of moderate-to-severe hot flashes and other menopausal symptoms, and in women undergoing premature menopause for medical or other reasons. Current guidelines recommend using the lowest possible dose for the shortest duration of time. A 2007 position statement from the North American Menopause Society (NAMS) supports short-term use of HRT for treatment of hot flashes and other vasomotor symptoms in recently menopausal women who have a low risk for stroke. However, NAMS recommends that women who are at risk for heart disease or breast cancer should avoid hormone therapy and try other options to manage symptoms.

When a woman stops taking HRT, perimenopausal symptoms may recur. There is some debate about whether it is better to abruptly stop the medication or to taper it off gradually. A 2006 study suggested that gradual discontinuation of HRT delays -- but does not prevent -- the reappearance of symptoms. However, when a woman reaches full menopause, symptoms will eventually go away.

Hormones Used in HRT. Hormone replacement therapy uses either estrogen alone (known as ET or unopposed estrogen) or in combination with forms of progesterone (known as combined hormone therapy or EPT). Progesterone is referred to by one of several names:

Progesterone is the name for the natural hormone.
Progestin is the term for any hormone, natural or synthetic, that causes progesterone effects.
Progestogen is any hormone that has effects similar to progesterone.

Both ET and EPT are available in many forms, including oral tablets, skin patches, and vaginal and skin applications. A new form approved by the FDA in 2004 is a topical estrogen gel that is applied to the arm.

HRT is mainly recommended for relieving menopausal symptoms, including hot flashes, night sweats, vaginal dryness, sleep problems, and mild depression. HRT does not prevent certain other problems associated with menopausal changes, such as thinning hair.

Oral hormonal medications and skin patches are equally effective in reducing hot flashes, mild depression, and sleep problems. Progestins may sometimes be prescribed alone for hot flashes and other acute menopausal symptoms, though they can cause side effects, such as mood swings, bloating, and breast tenderness. Estrogen creams, rings, or vaginal tablets restore vaginal elasticity and lubrication and improve sexual pleasure.

HRT may be useful for some women at high risk for osteoporosis, although other drugs, such as bisphosphonates, should be considered first. It increases bone density and also appears to improve balance and protects against falling. Studies also report reductions in fractures (especially hip fractures) among women taking HRT, but the benefits may not outweigh the risks of HRT. It appears that the beneficial effects wear off soon after therapy is stopped. Estrogen must be taken life long for maximum protection against osteoporosis, which then increases the risk for adverse health effects.

Heart Disease. HRT does not prevent heart disease and can increase the risk for heart disease and heart attack, especially in older women. An important 2007 Women’s Health Initiative study in the Journal of the American Medical Association indicated that this risk is time and age dependent. The study found that women who began HRT within 10 years of menopause had less risk of heart disease than women who begin HRT later on. This study suggests that HRT may be safest for women younger than age 60, and should be avoided by women older than age 60. Any woman who is considering HRT should be sure to have her blood pressure and cholesterol levels evaluated.

Another 2007 study, published in the New England Journal of Medicine (NEJM), also indicated that timing is important. The NEJM study found that that estrogen-only HRT may help reduce calcium deposits in coronary arteries in younger women (age 50 - 59) who have had a hysterectomy. (Because of the increased risk for uterine cancer, estrogen-only HRT is only appropriate for women who no longer have a uterus. Women who have a uterus need to take estrogen-progestin HRT. And, estrogen can increase the risk for heart attack in women who have advanced heart disease.) Although the NEJM study found some heart benefits for estrogen-only HRT for younger women, experts still advise that HRT should be used for only a few years. Any woman who is considering HRT should be sure to have her blood pressure and cholesterol levels evaluated.

Stroke. HRT increases the risk of stroke, regardless of years since menopause. In addition, HRT appears to worsen the outlook for women who have had a stroke.

Mental Decline. Observational studies had suggested that hormone replacement therapy (HRT) helped prevent mental decline and even Alzheimer's disease after menopause. Other studies have found no differences in mental performance and no protection from Alzheimer's disease in women taking HRT compared to non-users. A 2004 review of the Women’s Health Initiative Memory Study found that combined HRT did not reduce the risk of cognitive impairment, and actually increased the risk of dementia among women ages 65 and over.

Thromboembolism. HRT is associated with a higher risk for thromboembolism, in which blood clots form in deep veins. This places women at risk for pulmonary embolism, in which the blood clot travels to the lungs.

Click the icon to see an image of a pulmonary embolism.

Breast Cancer. Because breast tissue growth is highly sensitive to estrogens, the more a woman is exposed to estrogen over her lifetime, the higher the risk for breast cancer. A number of studies have reported a higher risk for breast cancer in postmenopausal women taking HRT that contains both estrogen and progestin. A combination of estrogen and testosterone also increases breast cancer risk. A 2005 study suggested that HRT with no or low progestin is safer than standard estrogen-progestin combination therapy.

Several 2006 studies of women who had a hysterectomy indicated that estrogen alone does not increase overall breast cancer risk when the drug is used for 7 years or less. However, women who take the drug for 15 years or more do have an increased risk. Women who are at low risk for breast cancer tend to have fewer breast cancers with estrogen alone, while women at higher risk tend to have more breast cancers. In addition, estrogen therapy may cause abnormal mammogram results. Breast tissue density increases with HRT, which makes mammograms more difficult to read and leads to more breast biopsies. Women who take estrogen HRT should be aware that they need frequent mammogram screenings.

As further evidence of the association between HRT and breast cancer, a 2007 New England Journal of Medicine study noted that breast cancer rates have fallen as HRT use has declined.

Endometrial (Uterine) Cancers. Estrogen overstimulates the tissue lining the uterus (the endometrium) and causes uncontrolled cell growth, a condition known as hyperplasia, which is a strong risk factor for cancer. Taking unopposed estrogen replacement therapy (ERT) increases the risk of endometrial cancer at least five-fold. Adding progestin to HRT appears to pose no risk for this cancer. However, a 2007 study indicated that short-term treatment (3 years) with ERT is associated with a relatively low risk of endometrial cancer. Women who take ERT should anticipate uterine bleeding, especially if they are obese, and may need endometrial biopsies and other gynecologic tests.

Ovarian Cancer. HRT appears to increase the risk for ovarian cancer. A 2007 UK study of nearly 1 million women found that women who used HRT for more than 5 years were 20% more likely to develop and die from ovarian cancer than women who had never taken HRT.

Gallstones. HRT is associated with a higher risk for gallstones.

Despite its risks, hormone replacement therapy appears to be the best treatment for hot flashes. Nonhormonal treatments for hot flashes and other menopausal symptoms include:

Antidepressants. The antidepressants known as selective serotonin-reuptake inhibitors (SSRIs) are sometimes used for managing mood changes and hot flashes. They include fluoxetine (Prozac), sertraline (Zoloft), venlafaxine (Effexor), and paroxetine (Paxil, Asimia). A 2006 review of nonhormonal therapies, found that paroxetine in particular may help hot flashes. However, paroxetine, like other antidepressants, can cause headache, anxiety, and sexual problems. A 2007 study suggested that the antidepressant citalopram (Celexa), given alone or with HRT, may help treat hot flashes.

An investigational antidepressant, desvenlafaxine (Pristiq), is also being studied for treatment of hot flashes, night sweats, and perimenopausal sleep problems. Research presented at the 2007 meeting of the American College of Obstetricians and Gynecologists indicated that desvenlaxafine, which is related to venlaxafine, showed promise in improving symptoms.

Gabapentin.Several small studies suggest that gabapentin (Neurontin), a drug used for seizures and nerve pain, may relieve hot flashes. Gabapentin may cause drowsiness, dizziness, fatigue, and swelling of the hands and feet.

Clonidine. Clonidine (Catapres) is a drug used to treat high blood pressure. Studies show it may help manage hot flashes. Side effects include dizziness, drowsiness, dry mouth, and constipation

Testosterone. Some doctors prescribe combinations of estrogen and small amounts of the male hormone testosterone to improve sexual function and increase bone density. Side effects of testosterone include increased body hair, acne, fluid retention, anxiety, and depression. Testosterone also adversely affects cholesterol and lipid levels. A 2006 study indicated that combined estrogen and testosterone can increase the risk of breast cancer.


HRT Form	Brand Name	Active Ingredient	Side Effects
Oral Estrogens	Premarin	Natural conjugated estrogen, which is a mixture of estrogens derived from the urine of pregnant mares	Bleeding after withdrawal. It is a primary reason why many women stop treatment, although usually lighter or shorter compared to before menopause. If it is distressing, patient should consider continuous estrogen and progestin therapy. Irregular bleeding. This should be checked with the doctor for possible problems. Nausea and vomiting. If it occurs, usually does so only during the first 3 months and is minimal. Rarely with low doses. Headaches. Cramps. Risk for blood clots.
	Cenestin	Synthetic conjugated estrogen, which is a mixture of estrogens derived from compounds found in yams and soy
	Estratab, Menest	Plant-derived estrogens, called esterified estrogens. Usually made from modified soy
	Estrace (oral)	Estradiol, the most potent natural estrogen
	Ogen, Ortho-Est	Estropipate, a version of estrone, which is a weaker form of estrogen
	Estrovis	Quinetrol, a synthetic estrogen
	Estinyl	Synthetic form estradiol, the most potent estrogen

Oral Progestins	Provera, Amen, Curretab, Cycrin	Medroxyprogesterone, a synthetic progestin	Breast tenderness. Usually subsides in 3 - 4 months and can be relieved with over-the-counter painkillers and possibly by decreasing caffeine intake and adding vitamin E. Headache. Fluid build-up. Bloating. Fatigue, unusual tiredness, weakness. Depression, irritability, or other mood changes.
	Norlutin, Aygestin, Norlutate	Norethindrone and norethindrone acetate, synthetic progestins
		Norgestrel

Oral Combinations of Estrogen and Progestin	Prempro, Premphase	Conjugated estrogens plus medroxyprogesterone	May have some of the side effects of both estrogen and progestin. Continuous regimens eliminate menstrual bleeding in more than half of women. Investigators are studying the use of higher progestin doses or a lower estrogen doses and comparing combinations for further reduction of bleeding risk.
	Activelle, Femhrt	Estradiol and norethindrone or norethindrone acetate
	Ortho-Prefest	Estradiol and norgestimate
	Angeliq	Estradiol and drospirenone

Skin Patch Administration of HRT	Estraderm, Alora, Climara, Vivelle, FemPatch, Evorel	Estradiol	Skin irritation where the patch is applied most common. Hormonal side effects associated with formulation of patch.
Skin Patch Administration of HRT	CombiPath	Estradiol plus norethindrone (a progestin)

Vaginal Creams for dryness and irritation	Estrace (cream)	Estradiol (potent estrogen)	Hormonal side effects associated with estrogen or progestins, depending on formulation.
	Ogen (cream)	Estropipate (weaker estrogen.)
	Premarin (cream)	Conjugated natural estrogens
	Ortho-dienestrol (cream)	Dienestrol (synthetic estrogen)
	Crinone (cream)	A natural progesterone
Other forms of vaginal administration	Vagifem (vaginal tablet)
	Estring (vagina Ring)	Estradiol
	Other forms: injections, nasal sprays, and as pellets inserted under the skin twice a year.
Topical Gel	EstroGel	Estradiol	Hormonal side effects associated with estrogen.

Resources

www.menopause.org -- North American Menopause Society
www.acog.com -- American College of Obstetricians and Gynecologists
www.nia.nih.gov -- National Institute on Aging
www.nhlbi.nih.gov/whi/recommend.htm -- Women's Health Initiative Study
www.nih.gov/PHTindex.htm -- National Institutes of Health -- Menopausal Hormone Therapy Information
http://nccam.nih.gov/health/menopauseandcam -- National Center for Complementary and Alternative Medicine

References

Beral V; Million Women Study Collaborators; Bull D, Green J, Reeves G. Ovarian cancer and hormone replacement therapy in the Million Women Study. Lancet. 2007 May 19;369(9574):1703-10.

Caan B, Neuhouser M, Aragaki A, Lewis CB, Jackson R, Leboff MS, et al. Calcium plus vitamin d supplementation and the risk of postmenopausal weight gain. Arch Intern Med. 2007 May 14;167(9):893-902.

Church TS, Earnest CP, Skinner JS, Blair SN. Effects of different doses of physical activity on cardiorespiratory fitness among sedentary, overweight or obese postmenopausal women with elevated blood pressure: a randomized controlled trial. JAMA. 2007 May 16;297(19):2081-91.

Haimov-Kochman R, Barak-Glantz E, Arbel R, Leefsma M, Brzezinski A, Milwidsky A, et al. Gradual discontinuation of hormone therapy does not prevent the reappearance of climacteric symptoms: a randomized prospective study. Menopause. 2006 May-Jun;13(3):370-6.

Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, et al. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006 Feb 16;354(7):669-83.

Kalay AE, Demir B, Haberal A, Kalay M, Kandemir O. Efficacy of citalopram on climacteric symptoms. Menopause. 2007 Mar-Apr;14(2):223-9.

Manson JE, Allison MA, Rossouw JE, Carr JJ, Langer RD, Hsia J, et al. Estrogen therapy and coronary-artery calcification. N Engl J Med. 2007 Jun 21;356(25):2591-602.

Mosca L, Banka CL, Benjamin EJ, Berra K, Bushnell C, Dolor RJ, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation. 2007 Mar 20;115(11):1481-501.

Nedrow A, Miller J, Walker M, Nygren P, Huffman LH, Nelson HD. Complementary and alternative therapies for the management of menopause-related symptoms: a systematic evidence review. Arch Intern Med. 2006 Jul 24;166(14):1453-65.

Newton KM, Reed SD, LaCroix AZ, Grothaus LC, Ehrlich K, Guiltinan J. Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial. Ann Intern Med. 2006 Dec 19;145(12):869-79.

North American Menopause Society. The role of local vaginal estrogen for treatment of vaginal atrophy in postmenopausal women: 2007 position statement of The North American Menopause Society. Menopause. 2007 May-Jun;14(3 Pt 1):355-69.

Ohayon MM. Severe hot flashes are associated with chronic insomnia. Arch Intern Med. 2006 Jun 26;166(12):1262-8.

Ravdin PM, Cronin KA, Howlader N, Berg CD, Chlebowski RT, Feuer EJ, et al. The decrease in breast-cancer incidence in 2003 in the United States. N Engl J Med. 2007 Apr 19;356(16):1670-4.

Rossouw JE, Prentice RL, Manson JE, Wu L, Barad D, Barnabei VM, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. 2007 Apr 4;297(13):1465-77.

Steiner AZ, Xiang M, Mack WJ, Shoupe D, Felix JC, Lobo RA, et al. Unopposed estradiol therapy in postmenopausal women: results from two randomized trials. Obstet Gynecol. 2007 Mar;109(3):581-7.

Tamimi RM, Hankinson SE, Chen WY, Rosner B, Colditz GA. Combined estrogen and testosterone use and risk of breast cancer in postmenopausal women. Arch Intern Med. 2006 Jul 24;166(14):1483-9.

Review Date:
6/25/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Next Up at Starbucks: Value Meals

YumSugar — Mon, 09 Feb 2009 15:00:05 -0800

Feeling the sting from other chains such as McDonald's and Dunkin' Donuts, a desperate Starbucks announced last week that it will soon be introducing value meals of its own. The chain plans to launch value pairings in all its company-owned US stores on March 3. Although regular prices for food and drink items vary by store location, Starbucks claims the pairings will provide customers with an average savings of as much as $1.20. This strategy is the latest in a slew of tactics - from creating loyalty programs to ceasing brewing of decaf after noon - that the company has tried over the past year to recover from troubling sales numbers. To see the recession-friendly $3.95 breakfast pairings, which were revealed today, read more.

Tall latte and Starbucks Perfect Oatmeal
Tall latte and slice of reduced-fat cinnamon swirl cake
Tall drip coffee and new bacon sandwich with egg and gouda cheese
Tall drip coffee and new ham sandwich with egg and cheddar
Tall drip coffee and classic sausage, egg, and aged cheddar breakfast sandwich
Tall drip coffee and peppered bacon, egg, and aged cheddar breakfast sandwich
Tall drip coffee and Reduced-fat turkey bacon, cholesterol-free egg, and reduced-fat white cheddar breakfast sandwich

Considering the saga behind Starbucks' breakfast sandwiches, I'm interested in trying out the two new breakfast sandwich options come March.

Do you plan to utilize this new value pricing to your benefit? Do you think it will help the coffee chain turn its sales numbers around?

Source

Parkinson's disease

FitSugar — Wed, 08 Oct 2008 17:35:13 -0700

In This Report

Highlights
Introduction
Symptoms
Risk Factors
Complications
Diagnosis
Treatment
Levadopa (L-dopa)
Other Medications
Surgery
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approvals

In 2007, the FDA approved the first skin patch drug for treatment of Parkinson’s disease. Transdermal rotigotine (Neupro) is a dopamine agonist drug that may help improve symptoms of early-stage Parkinson’s disease. The patch is applied daily.
Rivastigimine (Exelon), an Alzheimer’s disease drug, was approved in 2006 for treatment of mild-to-moderate dementia associated with Parkinson’s disease.

Drug Withdrawal

In 2007, the FDA withdrew the dopamine agonist pergolide (Permax) from the market due to safety concerns. Several articles published in 2007 in the New England Journal of Medicine indicated that pergolide and a similar drug, cabergoline (Dostinex), are associated with heart valve problems. Cabergoline is not approved in the U.S. for treatment of Parkinson’s disease.

Dietary Supplements

In 2007, the U.S. National Institutes of Health launched a large-scale clinical trial to study whether creatine may help slow the progression of Parkinson’s disease. Creatine is a nutritional supplement that is sometimes used to enhance exercise performance.
Coenzyme Q10, an antioxidant dietary supplement, does not help improve Parkinson’s disease symptoms, according to a study published in 2007 in the Archives of Neurology.

Deep-Brain Stimulation

Deep-brain stimulation outperformed drug therapy in a randomized trial comparing these two treatment approaches. In a study published in 2006 in the New England Journal of Medicine, patients who received deep-brain stimulation had better symptom and quality of life improvement than those who were treated with only medications. However, more serious side effects were reported in the deep-brain stimulation group. Deep-brain stimulation is a surgical technique that involves implanting electrodes in a target area of the brain.

Introduction

Parkinson's disease (PD) is a slowly progressive disorder that affects movement, muscle control, and balance. Parkinson's disease is referred to as idiopathic, which means that the cause is unknown. This term distinguishes the primary disease from parkinsonism, which are the symptoms occurring from a known cause. In addition to its effects on motor control, Parkinson's disease is now recognized as a broader condition that can include cognitive and behavioral disturbances, sleep disorders, speech difficulties, and other problems.

Parkinson's disease occurs from the following process in the brain:

PD develops as cells are destroyed in certain parts of the brain stem, particularly the crescent-shaped cell mass known as the substantia nigra.

Parkinson's disease is a slowly progressive disorder that affects movement, muscle control, and balance. Part of the disease process develops as cells are destroyed in certain parts of the brain stem, particularly the crescent-shaped cell mass known as the substantia nigra. Nerve cells in the substantia nigra send out fibers to tissue located in both sides of the brain. There the cells release essential neurotransmitters that help control movement and coordination.

Nerve cells in the substantia nigra send out fibers to the corpus stratia, gray and white bands of tissue located in both sides of the brain.
There the cells release dopamine, an essential neurotransmitter (a chemical messenger in the brain). Loss of dopamine in the corpus stratia is the primary defect in Parkinson's disease.

Dopamine. Dopamine deficiency is the hallmark feature in PD. It is one of three major neurotransmitters known as catecholamines, which help the body respond to stress and prepare it for the fight-or-flight response. Loss of dopamine negatively affects the nerves and muscles controlling movement and coordination, resulting in the major symptoms characteristic of Parkinson's disease. Dopamine also appears to be important for efficient information processing, and deficiencies may also be responsible for problems in memory and concentration that occur in many patients.

Although it is clear that dopamine deficiency is the primary defect in Parkinson's disease, it is not clear what causes dopamine loss. The culprit is less likely to be a single cause than a combination of genetic and biologic factors, which are triggered by some environmental assault.

Other Changes. The PD disease process also appears to impair nerve endings in the heart to cause dysautonomia-- changes in the autonomic (also called sympathetic) nervous system. Such changes may impair the release of norepinephrine, a hormone that regulates blood pressure, pulse rate, perspiration, and other automatic responses to stress. Evidence suggests this may be responsible for the abrupt drops in blood pressure when standing that occur in PD. Further research is underway to determine if the loss of nerve terminals is confined to the heart or if it affects other organs as well.

Click the icon to see an animation about Parkinson's disease.

Apoptosis and Alpha Synuclein. Important research now suggests that three molecules are critical in the development of inherited PD: alpha synuclein, parkin, and ubiquitin, which all interact in the normal brain. Abnormally high levels of alpha synuclein, which is produced in dopamine-rich nerve cells, may play a central role. Normally, two other molecules, parkin and ubiquitin, are involved in the natural self-destruction of synuclein -- a natural process of programmed cell death called apoptosis. If this process goes awry, for instance, with a defective parkin gene, cell death fails to occur. If synuclein is not eliminated in these cells, it builds up and becomes toxic to dopamine. In such cases, synuclein accumulates in Lewy bodies, the deposits of fibrous tissue found in all patients with PD.

Another protein, beta amyloid, also increases the build-up of synuclein. Beta amyloid is a known factor in Alzheimer's disease, and may help explain the co-existence between Alzheimer's and Parkinson's disease in many patients.

Lewy Bodies. The fibrous deposits known as Lewy bodies are the hallmark signs of Parkinson's disease. They are found in the substantia nigra, the place in the brain where dopamine is first released. It is not clear whether Lewy bodies are the major killers of the nerve cells or whether they are simply a byproduct of the degenerative process. They are found not only in the brains of patients with Parkinson's disease but, in rare cases, may show up in cells in other parts of the body (the heart, intestine), causing severe disabling symptoms. These substances are also present in other diseases that cause dementia, such as Alzheimer's, and can occur in people without neurologic symptoms.

The Mitochondria and Oxygen-Free Radicals. Some research has observed that certain patients with PD have significantly low levels of complex I, an enzyme found in the mitochondria, sausage-like structures that are the primary source of energy within cells. Some theories suggest that low amounts of complex I may make nerve cells vulnerable to the assault of oxygen free radicals (also called oxidants). Oxidants are unstable molecules that bind to other molecules in the body. They are normally produced by the natural chemical processes in the body. If the body is subjected to environmental stresses, however, they can be over-produced. In excess, they can damage any cell, including nerve cells in the brain, and even interfere with their DNA.

NMDA Receptors. Also of interest in PD are processes that occur in an area of the brain called the subthalamic nucleus. Here, receptors known as glutamatergic N-methyl-D-aspartate (NMDA) become persistently overexcited and produce high levels of calcium ions within brain cells. This in turn leads to a cascade of events that trigger oxygen-free radicals and cell damage.

Immune Factors and the Inflammatory Response. An over-responsive immune system triggered by initial damage may also play a role in perpetuating Parkinson's disease. When the immune system becomes overactive, it produces excessive numbers of potent factors called cytokines, which cause inflammation and further injury in brain cells. Important cytokines under investigation are interleukin-1 and tumor necrosis factor.

Specific genetic factors appear to play a strong role in early-onset Parkinson's disease, an uncommon form of the disease. Research from the last several years suggests that multiple genetic factors may also be involved in late-onset Parkinson’s disease. Several important studies, published in 2005, lay the groundwork for potential genetic screening for this disease. Researchers identified the leukine-rich repeat kinase 2 (LRRK2) gene, located on a region of chromosome 12 known as PARK8, as a key gene involved in inherited forms of Parkinson’s. The researchers estimate that a single gene mutation in LRRK2 may be responsible for 5% of inherited Parkinson’s cases and about 2% of isolated cases.

Early Onset PD. The cases of genetic early-onset Parkinson's disease have most often been detected in specific family groups.

Defective genes that regulate the molecules alpha synuclein and parkin, which are important in the PD disease process, may be responsible for a number of early-onset cases. For example, genetic abnormalities the alpha synuclein protein have been detected in some early-onset Parkinson's patients of European descent.
The parkin gene may be the cause of many cases of early-onset Parkinson's in young adults. (Parkinson's cases associated with this mutation tend to progress slowly and respond well to treatment, even after years of symptoms. Dementia is also rare with this form.)

Late Onset PD. Two landmark studies published in the Journal of the American Medical Association provided the first evidence of a genetic link to late-onset Parkinson’s disease. In these 2001 studies, researchers found that regions on chromosomes 5, 6, 8, 9, and 17 were implicated with Parkinson’s. The parkin gene (located on chromosome 6) and the tau gene (located on chromosome 17) were both found in families that had late onset Parkinson’s. Parkin was previously thought to be responsible only for early-onset Parkinson’s, but this research identified it in families that had both early- and late-onset disease forms. These studies also bolstered the theory that Parkinson’s does have a genetic component and is not caused solely by environmental factors. A 2005 study found that a G2019S mutation in the LRRK gene, located on the PARK8 region of chromosome 12, was definitively associated with late-onset Parkinson’s disease in North American and European families.

Environmental toxins, infections, and other triggers can provoke excessive production in the body of oxygen free-radicals, damaging particles that may play a major role in the deterioration of nerve cells that lead to Parkinson's.

Infectious Organisms. Some research has identified immune factors that suggest a viral presence in the Lewy bodies and swollen nerve pathways of Parkinson's brains. Influenza and other potent viruses have long been known to be a cause of parkinsonism. In one well-known example, a major flu epidemic causing encephalitis in the early twentieth century left many of its victims with parkinsonism.

Environmental and Industrial Chemicals. Intense exposure to certain environmental and industrial chemicals is also being studied.

Pesticides and Herbicides. Some evidence implicates pesticides and herbicides as important factors in many cases of Parkinson's disease. A higher incidence of parkinsonism has long been noted in people who live in rural areas, particularly those who drink private well water or are agricultural workers. A large 2000 study found a strong link between high exposure to insecticides and herbicides at home and a 50 - 70% increase in risk of Parkinson's.
Other Chemicals. Intense exposure to other industrial chemicals and metals (manganese, copper, lead, iron, mercury, zinc, aluminum, and others) has also been linked with parkinsonism, a cause that is often reversible. The role of long-term exposure in the development of Parkinson's disease is unclear. High levels of iron content observed in critical parts of the brain in PD are under particular scrutiny.

Most, but not all, Parkinson's victims are elderly. Some studies indicate that the very elderly are not susceptible to the disease, indicating that the aging process itself is not the major player in the disease. Aging does appear to reduce the concentration of dopamine in structures called dopamine transporters, which carry the neurotransmitter back and forth between nerve cells. Some researchers posit that any excessive stress on these transporters might trigger Parkinson's disease in the aging, and more vulnerable, brain.

Symptoms

Parkinson's disease (PD) symptoms often start with tremor, which may occur in the following ways:

Tremors may first be only occasional, starting in one finger and spreading over time to involve the whole arm. The tremor is often rhythmic, 4 - 5 cycles per second, and frequently causes an action of the thumb and fingers known as pill rolling.
Tremors can occur when the limb is at rest or when it is held up in a stiff unsupported position. They usually disappear briefly during movement and do not occur during sleep.
Tremors can also eventually occur in the head, lips, tongue, and feet. Symptoms can occur on one or both sides of the body. In one study, 44% of patients reported experiencing internal tremors lasting less than half an hour, but occurring several times a week.

In younger patients tremor is usually predominant and often suggests a less aggressive form of the disease. Some evidence suggests that tremor in PD may occur from mechanisms in the brain that are different from those that cause other PD symptoms.

A number of PD symptoms involve motor impairment caused by the abnormalities in the brain that regulate movement:

Slowness of motion (bradykinesia) is one of the classic symptoms of Parkinson's disease. Patients may eventually develop a stooped posture and a slow, shuffling walk. The gait can be erratic and unsteady. After a number of years, muscles may freeze up or stall, usually when a patient is making a turn or passing through narrow spaces, such as a doorway.
Intestinal motility (the ability to swallow, digest, and eliminate) may slow down, causing eating problems and constipation.
Muscles may become rigid (akinesia). This symptom often begins in the legs and neck. Muscle rigidity in the face can produce a mask-like, staring appearance.
Motor abnormalities that limit action in the hand may develop in late stages. Handwriting, for instance, often becomes diminutive.
Normally spontaneous muscle movements, such as blinking, may need to be done consciously.

The traditional view of Parkinson's disease is shifting to reflect growing awareness that it is much more than a motor disease. Many non-motor components and their treatments are now under study. The following symptoms should be carefully monitored by doctors and caregivers:

Depression is the most common psychiatric problem associated with PD, affecting about 40% of patients. Because depression is a common problem in older people, it is likely not to be recognized as a symptom.
Anxiety affects about 30% of patients.
Dementia and paranoia are more common than previously understood.
Orthostatic hypotension -- some patients experience a sudden drop in blood pressure when they stand. This can cause dizziness and fainting.
Changes in sensations of temperature, hot flashes, and excessive sweating.
Daytime sleepiness and other sleep disorders are common.

Risk Factors

Parkinson's disease affects about 3% of Americans over 65 years old. Experts estimate that this percentage could double in the next 30 - 40 years. The symptoms of parkinsonism (tremor, gait disturbance, bradykinesia, and rigidity) occur in even more people, estimated to be 8 million over age 65. In a study that included very mild symptoms, parkinsonism occurred in about 15% of people 65 - 74 years of age, about 30% in those 75 - 84, and over half of people older than age 85.

The average age of onset of Parkinson's disease is 55. About 10% of Parkinson's cases are in people younger than 40 years old. Older adults are at higher risk for both parkinsonism and Parkinson's disease. There is some evidence, however, that the risk declines significantly after age 75 and that the very elderly are at low risk.

Some research indicates that men may face up to twice the risk as women. Estrogen may offer some protection for women up until menopause. A 2001 study, for example, reported a higher rate of Parkinson's disease in women who had undergone hysterectomy. Other studies suggest that the disease also progresses more rapidly in men than women. Older women seem to be more at risk for gait disturbance and men for rigidity and tremor.

People with siblings or parents who developed Parkinson's at a younger age are at higher risk for Parkinson's disease, but relatives of those who were elderly when they had the disease appear to have an average risk.

African- and Asian-Americans have a lower risk than Caucasians. Some evidence suggests that non-Caucasians may be more vulnerable to an atypical form of PD, which causes early impairment in thinking and has a poor response to levodopa, the primary PD treatment.

Increasing weight gain in middle age was associated with a higher risk of PD in a 2002 study.

Complications

Parkinson's disease (PD) is not fatal, but it can reduce longevity. The disease progresses more quickly in older than younger patients, and may lead to severe incapacity within 10 - 20 years. Older patients also tend to experience freezing and greater declines in mental function and daily functioning than younger people. If PD starts without signs of tremor, it is likely to be more severe than if tremor had been present. Having other family members with PD does not appear to have any effect on the severity of the disease.

Parkinson's disease can seriously impair the quality of life in any age group. The physical and emotional impact on the family should not be underestimated as the patient becomes increasingly dependent on their support.

Treatment advances are increasingly effective in alleviating symptoms and even slowing progression of the disease. Taking many of the medications over time, however, can produce significant side effects. Newer drugs may help reduce these occurrences.

The negative effect of overall motor and muscle impairment on daily life can be considerable. Some motor complications can be life-threatening.

Disturbed gait and unstable posture are common and serious problems in elderly patients, since they increase the risk for falling and injury. Some studies have suggested that the appearance of these symptoms early in the course of the disease predict a faster decline than having tremor as the predominant symptom.
Swallowing problems (dysphagia). The presence of dysphagia is associated with shorter survival time. Motor impairment of the muscles in the throat not only impairs swallowing but it also poses a risk for aspiration pneumonia.
Constipation is a major problem and occurs both as a result of the disease and a side effect of its treatment. Laxatives, stool softeners, and other medications may be prescribed.
Bladder control and urinary incontinence are also important complications of PD.
Speech problems occur in more than 70% of patients, by some estimates. Speech difficulty can be caused by rigidity of the facial muscles, loss of motor control, and impaired breath control. Tone can become monotonous, words may be repeated over and over, or the rate of speech may even be very fast.

Depression is extremely common, affecting up to 40% of patients with Parkinson's. PD poses multiple threats on the emotional health:

The disease process itself causes changes in chemicals in the brain that affect mood and well-being.
The complications of its symptoms have a profound impact on daily life that can be emotionally devastating without help and support.
Some drug treatments (levodopa combined with a dopamine agonist) can cause compulsive behavior, such as gambling, shopping, and increased sexuality. Patients who have pre-existing tendencies to novelty-seeking behavior, or a family or personal history of alcohol abuse, may be more likely to develop compulsive gambling. Deep brain stimulus (DBS) surgery may also increase the risk for compulsive gambling in patients who have a history of gambling.

Impaired Thinking (Cognitive Impairment). Defects in thinking, memory, language, and problem solving skills may occur early on in untreated patients or late in the course of the disease. Medications may play a role in thinking problems. In one study, for example, patients with PD were slower in detecting associations, although (unlike in Alzheimer's disease) once they discovered them they were able to apply this knowledge to other concepts. After they were taken off medication, however, they had no problems with the tasks.

Dementia. Dementia is three to six times more common in the elderly Parkinson patient than in the average older adult. It is most likely to occur in older patients who have had major depression. PD marked by muscle rigidity (akinesia), rather than tremor, and early hallucinations also increase the risk for dementia. (Visual hallucinations can also occur in about a third of patients from PD medication.) Unlike in Alzheimer's, language is not usually affected in Parkinson's related dementia.

A number of other problems associated with Parkinson's disease affect daily life:

Vision Problems. Vision is also affected, including impaired color perception and contrast sensitivity. These problems progress and can impair motor functioning.

Sleep Disorders. Excessive daytime sleepiness and other sleep disorders are common in PD, both from the disease itself and from the drugs that treat it. In general, patients have a 25% higher risk for daytime sleepiness, including suddenly falling asleep, than patients with other neurologic diseases.

Restless legs syndrome, an irresistible urge to move the calves, which often occurs at night, affects many patients. However, Parkinson's disease itself does not seem to increase the risk for RLS. Nor does RLS early in life predispose to Parkinson's later on. The common connection between RLS and Parkinson's disease may derive from iron deficiencies that can play a role in both conditions.

Many patients also suffer from nighttime leg cramps. And, some of the medications cause vivid dreams as well as waking hallucinations.

Impaired Sexuality. Although Parkinson's disease and its treatments can cause compulsive sexual behavior, the disease can also affect patients' self-esteem and inhibit sexuality. This is an area not often studied but which is important for many patients' well-being. A 2000 study reported that not only did sexual dysfunction occur, but also affectionate touching and expression of feelings were reduced, even though both partners maintained a desire for intimacy.

Worsened Sense of Smell. The sense of smell is impaired in about 70% of patients.

Osteoporosis. Parkinson’s disease may increase the risk for low bone density and osteoporosis. Both men and women are at risk. Experts recommend that patients with Parkinson’s disease get tested for osteoporosis, especially if they have problems with walking.

Diagnosis

It is difficult to diagnose Parkinson's in early stages. The disease is primarily diagnosed by its symptoms, and studies indicate that doctors make an incorrect initial diagnosis of Parkinson's disease in 8 - 35% of cases. Even neurologists have difficulties in correctly identifying the disease.

A medical and personal history should include any relevant symptoms as well as any medications taken, and information on exposure to environmental toxins.

Early Symptoms. Early treatment may help slow progression, so an early diagnosis of Parkinson's is highly desirable. Early symptoms are often mild, however, so Parkinson's disease can be missed, particularly in young adults. Repeated assessment of symptoms over time is important for improving the accuracy of diagnosis. Too often a younger person with Parkinson's may be diagnosed with mental illness, because the doctor associates the disease only with older people.

Parkinson's may be suspected in patients with the following symptoms:

Slowness and difficulty of movement. These are usually the first symptoms. The patient will be asked to walk and to get out of a chair, preferably a deep one. Early gait disturbance, however, often indicates a disease other than Parkinson's disease.
A tremor when their limb is relaxed. (As many as 25% of patients, however, will not have a tremor.)
Symptoms on one side of the body.

Later Symptoms. In later stages of Parkinson's disease, the symptoms are usually unmistakable, and the problem can often be diagnosed using simple physical tests and a medical and personal history.

The loss of smell is associated with loss of dopamine receptors in the brain. “Scratch and sniff” smell tests can help a doctor diagnose Parkinson’s disease. Smell tests can help differentiate Parkinson’s disease from other conditions with similar symptoms. Some patients with a very similar condition called multiple system atrophy will have a good initial response to levodopa, but it is not usually sustained.

Levodopa and apomorphine can confirm a diagnosis of Parkinson’s disease. If patients’ symptoms improve when they take these drugs, they likely have Parkinson’s, ruling out other neurological diseases.

According to 2006 guidelines from the American Academy of Neurology, there is not enough evidence to recommend for or against the use of imaging techniques such as computerized tomography (CT), magnetic resonance imaging (MRI), or positron-emission tomographic (PET) to diagnose PD.

When symptoms resemble Parkinson's disease but have an identifiable cause, the syndrome is known as parkinsonism. People who have parkinsonism, but not Parkinson's disease, often have additional neurologic symptoms. A number of conditions can also have similar or some of these symptoms.

Other Neurologic Conditions. Many medical conditions may cause symptoms of Parkinson's disease:

Hardening of the arteries (arteriosclerosis) in the brain can cause multiple small strokes, which can produce loss of motor control.

Click the icon to see an image of plaque in an artery.

Alzheimer's disease can be very similar. In one study 23% of people with Alzheimer's also met the criteria for Parkinson's disease. The two diseases often coexist, and research suggests that Alzheimer's and Parkinson's disease may sometimes share a common biologic origin, the accumulation of the protein alpha synuclein and Lewy bodies in the brain.
Lewy bodies variant (LBV), also called dementia with Lewy bodies, is a separate disease from both Alzheimer's and Parkinson's disease. It has similar symptoms to both but is marked by early dementia.
Encephalitis caused by influenza has been known to cause parkinsonism.
Primary progressive freezing gait is a progression condition, in which freezing gait occurs at the onset. Other Parkinson-like features, such as slow movement, often develop. Although very similar to PD, this condition does not respond to L-dopa or other PD medications.
Essential tremor, unlike the tremor of Parkinson's disease, often occurs in the head and voice and is usually worse during motion, as opposed to rest.
Progressive supranuclear palsy has similar symptoms, but involves less tremor and earlier rigidity, and it tends to affect both sides of the body symmetrically. Magnetic resonance imaging scans that measure parts of the midbrain may be a reliable method for distinguishing between PD and progressive supranuclear palsy.
Multiple system atrophy (previously called Shy-Drager syndrome) is a degenerative nerve disease that also affects movement and blood pressure and has many of the symptoms of Parkinson's disease. Some research suggests that a trial using the drug apomorphine may help differentiate between the two.
Other problems that may mimic Parkinson's disease include Wilson's disease, thyroid abnormalities, hydrocephalus, tumors, having the fragile X trait (but not the full disorder), and a number of degenerative neurologic diseases.

Drugs. Certain drugs or medications account for about 4% of all cases of parkinsonism. According to some studies, patients who experience drug-induced parkinsonism may actually be at an increased risk of developing Parkinson's disease later in life. A number of drugs can cause these symptoms, including antipsychotic and antiseizure drugs. Anyone with parkinsonism should discuss their medications with their doctor.

The American Academy of Neurology (AAN) recommends the Beck Depression Inventory or the Hamilton Depression Rating Scale to screen for depression in patients with Parkinson’s disease. The AAN recommends the MMSE and CAMCOG tests to screen for dementia. During these tests, the patient answers a series of questions.

Treatment

Drugs, physical therapy, and surgical interventions can manage Parkinson's disease. The goals of treatment for Parkinson's disease are to:

Relieve disabilities
Balance the problems of the disease with the side effects of the medications

Treatment is very individualized for this complicated disease. Patients must work closely with doctors and therapists throughout the course of the disease to customize a program suitable for their particular and changing needs. Patients should never change their medications without consulting their doctor, and they should never stop taking their medications abruptly.

The American Academy of Neurology recommends the following therapies for the initial treatment of Parkinson’s disease:

Levodopa (L-dopa). Levodopa, or L-dopa, has been used for years and is the gold standard for treating Parkinson's disease. The drug increases brain levels of dopamine. It is used in nearly all phases of the disease. The standard preparations (Sinemet, Atamet) combine levodopa with carbidopa, a drug that slows the breakdown of levodopa. Levodopa is better at improving motor problems than dopamine agonists but increases the risk of involuntary movements (dyskinesia).

Dopamine Agonists. Dopamine agonist drugs mimic dopamine to stimulate the dopamine system in the brain. These drugs include pramipexole (Mirapex), ropinirole (Requip), bromocriptine (Parlodel), and rotigotine (Neupro). The Food and Drug Administration (FDA) pulled the dopamine agonist pergolide (Permax) from the market in March 2007 over safety concerns that included potentially fatal heart valve damage.

Selegiline (Eldepryl) and rasagiline (Azilect). Selegiline is a monoamine oxidase B (MAO-B) inhibitor that may have some mild benefit as an initial therapy. However, unlike levodopa, it does not slow the progression of Parkinson’s disease. Another MAO-B inhibitor, rasagiline (Azilect), was approved in May 2006. Unlike selegiline, which needs to be taken by mouth twice a day, rasagiline needs to be taken only once a day.

Drug treatments for Parkinson disease do not consistently control symptoms. At certain points during the day, the beneficial effects of drugs wear off, and patients can experience a return of symptoms, such as uncontrolled muscular motor function, difficulty walking, and loss of energy. In 2006, the American Academy of Neurology (AAN) reviewed evidence for the various drugs used to treat “off time.” The AAN found that the following drugs had the strongest evidence for controlling off time symptoms:

Entacapone (Comtan) belongs to a class of drugs called catechol-o-methyl transferase (COMT) inhibitors. COMT inhibitors help prolong the effects of levodopa by blocking an enzyme that breaks down dopamine.
Rasagiline (Azilect) belongs to a class of drugs called monoamine oxidase (MAO) inhibitors. These drugs slow the breakdown of dopamine that occurs naturally in the brain and dopamine produced from levodopa.

The AAN also found good evidence for the dopamine agonists ropinirole (Requip) and pramipexole (Mirapex), and the COMT inhibitor tolcapone (Tasmar). Deep brain stimulation is a surgical treatment that may help improve motor fluctuations in some patients.

Both Levodopa and dopamine agonists can cause involuntary movements (dyskinesia). The AAN has not found any strong evidence to recommend any drug for treating dyskinesia. However, weak evidence suggests that the antiviral drug amantadine (Symmetrel) may help reduce stiffness and improve dyskinesia. There is also weak evidence that deep brain stimulation of the subthalamus area may be helpful.

Conditions associated with motor impairment and other symptoms of Parkinson's disease may require a variety of treatments.

Depression. Although depression is very common in PD, there have been surprisingly few controlled studies. Antidepressants used for PD include tricyclics, particularly amitriptyline (Elavil). Some studies have found that selective serotonin-reuptake inhibitors (SSRIs) -- which include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil) -- may worsen symptoms of Parkinson's. Doctors should monitor patients taking SSRIs.

Psychotic Side Effects. Studies indicate that clozapine (Clozaril) and quetiapine (Seroquel), antipsychotic drugs used to treat schizophrenia, may be the best drugs for treating psychosis in patients with Parkinson's disease. A similar drug, olanzapine (Zyprexa), should not be used for patients with PD because it can worsen their psychotic symptoms.

Dementia. The cholinesterase inhibitor drugs donepezil (Aricept) and rivastigmine (Exelon) are used to treat Alzheimer’s disease. Studies suggest that these drugs may also help treat dementia associated with Parkinson’s disease. In 2006, rivastigimine was approved for treatment of mild-to-moderate dementia associated with Parkinson’s disease.

Daytime Sleepiness. Modafinil (Provigil), a drug used to treat narcolepsy, is proving to be very helpful for patients with sleepiness related to their disease.

Drooling. In search of a simple solution for the problem of drooling, scientists have reported that injections of very small amounts of botulinum toxin effectively reduce saliva production and drooling. In such small amounts the toxin is safe.

Voice Loss. A relatively simple procedure using collagen injections in the neck appears to be a safe and effective method of improving the voice and speech disorders caused by PD. The procedure augments the collagen in the vocal fold and works best in patients who can still initiate speech. A 2001 study reported improvements that lasted from 2 - 7 months in 61% of patients.

Erectile Dysfunction. Sildenafil (Viagra) is proving to be very helpful for men who suffer from impotence from Parkinson's disease. However, the drug may worsen orthostatic hypotension, a side effect of some PD medications.

Eventually, symptoms such as stooped posture, freezing, and speech difficulties may not respond to drug treatment. (Total unresponsiveness is unlikely, however, even after 20 years of treatment.) The following approaches may be tried:

Simply increasing the dose of levodopa or its frequency raises an unacceptable risk of the distressing side effects. Some doctors have tried hospitalizing patients, totally withdrawing the levodopa, and then re-administering it. Benefits were seen for only a few months, however, and there were some dangerous risks to the process of withdrawal, including pneumonia and blood clots in the lungs.

An embolus is a blockage of an artery in the lungs by fat, air, tumor tissue, or blood clot.

Surgical treatments, including deep brain stimulation and pallidotomy, may help some patients.
Research is ongoing to develop drugs and procedures that will manage advanced disease and possibly even reverse the process.

Levadopa (L-dopa)

Levodopa, also called L-dopa, which is converted to dopamine in the brain, remains the gold standard for treating Parkinson's disease. The standard preparations (Sinemet, Atamet) combine levodopa with carbidopa, which improves the action of levodopa and reduces some of its side effects, particularly nausea. Levodopa can also be combined with benserazide (Madopar) with similar results, but Sinemet is almost always used in America. Dosages vary, although the preparation is usually taken in three or four divided doses per day. In 2004, the FDA approved a new oral form of carbidopa-levodopa (Parcopa) that dissolves on the tongue.

In general L-dopa has the following effects on Parkinson's disease:

It is most effective against rigidity and slowness.
It produces less benefit for tremor, balance, and gait.

In many patients, levodopa significantly improves the quality of life for many years. If symptoms do not improve after 2 - 3 months, one of the following reasons may account for the failure:

Other neurologic problems may be causing the symptoms.
Some patients have abnormalities in other brain sites that do not respond to L-dopa.
Sometimes patients are so depressed they cannot tell if the drug is beneficial or not. Only a series of physical examinations by the doctor will indicate that the drug is actually helping.

Studies suggest that levodopa may help slow disease progression and protect against brain cell degeneration.

The toxic effects of levodopa with or without carbidopa are considerable.

Physical Side Effects. The physical side effects are as follows:

Low blood pressure. Low blood pressure is a common problem during the first few weeks, particularly if the initial dose is too high. The addition of extra supplements of carbidopa reduces this effect to some degree. The patient should drink lots of fluids and possibly increase salt intake to maintain normal blood pressure.
Arrhythmia. In some cases the drug may cause abnormal heart rhythms.
Gastrointestinal effects. Stomach and intestinal side effects are common even with carbidopa. Taking the drug with food can alleviate the nausea. However, proteins interfere with intestinal absorption of levodopa, and some doctors recommend not eating any protein until nighttime in order to avoid this interference. The drug can also cause gastrointestinal bleeding.
Effects in the lung. Levodopa can cause disturbances in breathing function, although it may benefit patients who have upper airway obstruction.
Hair loss.

Psychiatric and Mental Side Effects. The major adverse effects of the drug are psychiatric. Patients taking levodopa, especially in combination with other drugs, can experience:

Confusion.
Extreme emotional states, particularly anxiety.
Vivid dreams.
Visual and possibly auditory hallucinations. The drug may even unmask dementia that had not been previously noticed.
Effects on learning. L-dopa appears to have mixed effects on learning. It may improve working memory. However, some evidence suggests that it impairs areas of the brain related to other learning functions and social behavior.
Sleepiness and sleep attacks.

Levodopa causes fewer psychiatric side effects than other drugs used for Parkinson's disease, including anticholinergics, selegiline, amantadine, and dopamine agonists. Because psychiatric side effects often occur at night, if they are severe some doctors recommend reducing or stopping the evening dose.

Within 4 - 6 years of treatment with levodopa, the effects of the drug in many patients begin to last for shorter periods of time (called the wearing-off effect) and the following pattern may occur:

Patients may first notice slowness (bradykinesia) or tremor in the morning before the next dose is due.
Less commonly, some experience painful dystonia, muscle spasms that can cause sustained contortions of various parts of the body, particularly the neck, jaw, trunk, and eyes and possibly the feet.
Patients must increase the frequency of levodopa doses. This puts them at risk for dyskinesia (the inability to control muscles), which usually occurs when the drug level peaks. Dyskinesia can take many forms, most often uncontrolled flailing of the arms and legs or chorea, rapid and repetitive motions that can affect the limbs, face, tongue, mouth, and neck. Dyskinesia is not painful, but it is very distressing.
In some people, eventually L-dopa is effective only for 1 - 2 hours and most patients start to experience motor fluctuations. In about 15 - 20% of patients such fluctuations become extreme, a phenomenon known as the on-off effect, which consists of unpredictable, alternating periods of dyskinesia and immobility. Sometimes the symptoms switch back in forth within minutes or even seconds. (The transition may follow such symptoms as intense anxiety, sweating, and rapid heartbeats.)

Reasons for the Wearing-Off Effect. Debate is ongoing about the cause of the wearing-off effect and dyskinesia. Some theories suggested for these effects are:

The disease progresses beyond the ability of levodopa to control it.
Some patients become tolerant to prolonged exposure to dopamine and, at the same time, the disease is progressing.
The brain's own dopamine neurons become incapable of storing dopamine. When the levodopa wears off, little or no natural dopamine remains.
Levodopa itself accelerates the disease by producing oxygen free radicals, unstable particles that increase injuries to the brain and dopamine degradation.

Preventing the Wearing-Off Effect. To reduce the effects of fluctuation and the wearing-off effect, it is important to maintain as consistent a level of dopamine as possible. Unfortunately, levodopa is poorly absorbed and may remain in the stomach a long time. A number of strategies are being developed to take care of these problems:

Some patients take multiple small doses on an empty stomach, crushing the pills and mixing them with a lot of liquid.
A liquid form of Sinemet may produce fewer fluctuations and a prolonged "on" time compared with the tablet.
A prolonged release version of levodopa and carbidopa (Sinemet CR) is also available to control fluctuations for some people. (Some evidence suggests that there is no actual difference in symptom control between the sustained and immediate release forms, but patients on Sinemet CR tend to experience a better quality of life.)

Other Medications

Selegiline (Eldepryl, Movergan, Zelepar), also known as deprenyl, is an antioxidant drug that blocks monoamine oxidase B (MAO-B), an enzyme that degrades dopamine. Until recently, selegiline was the drug most commonly used in early-onset disease and in combination with levodopa for maintenance. A major 2002 study reported, however, that although selegiline delays the need for L-dopa by a few months, it has no effect on long-term progression.

Rasagiline (Azilect), another MAO-B inhibitor, was approved in May 2006 for the initial treatment of Parkinson’s disease. It is used alone during early-stage PD and in combination with L-dopa for moderate-to-advanced PD. Unlike selegiline, which is taken twice a day, rasagiline is taken once a day.

Other Adverse Effects. MAO-B inhibitors may have severe side effects:

One of the most important side effects is orthostatic hypotension, particularly in people taking Sinemet plus selegiline. This condition is a sudden drop in blood pressure that causes dizziness and lightheadedness when a patient stands up. Orthostatic hypotension can also occur with other Parkinson's drugs.
Can cause high blood pressure (hypertension) if combined with drugs that increase serotonin levels -- such drugs include nearly every major antidepressant. Patients suffering from depression and taking selegiline should discuss all treatment options with their doctor.
Can also cause a dangerous increase in blood pressure if patients eat foods rich in the amino acid tyramine. Patients should avoid the following foods while taking selegiline or rasagiline and for 2 weeks after stopping medication: aged cheeses, air-dried meats, pickled herring, yeast extract, aged red wines, draft beers, sauerkraut, and soy sauce

Debate over Mortality Rates. Some major studies have reported higher mortality rates in patients with advanced PD. Such findings may be due to adverse effects on the heart and blood vessels. Although other studies have not reported lower survival rates, some experts believe that, given its modest effects, selegiline may be a poorer drug choice than others, particularly in patients with risk factors for heart disease.

Dopamine agonists stimulate dopamine receptors in the substantia nigra, the part of the brain in which Parkinson's is thought to originate. Dopamine agonists are effective in delaying motor complications during the first 1 or 2 years of treatment.

Newer Dopamine Agonists. The most commonly prescribed dopamine agonists are pramipexole (Mirapex) and ropinirole (Requip). They are used either alone or in combination with L-dopa. Pramipexole appears to work better and have fewer side effects than ropinirole.

Studies still report, however, that L-dopa is superior for improving motor function. In one study, motor function was no different in disease progression among all of the drugs by the third year of treatment. Recent research suggests that L-dopa is better at improving motor disability and dopamine agonists are better at reducing motor complications. L-dopa has a higher risk for dyskinesia side effects than dopamine agonists, but dyskinesia can also occur with dopamine agonists.

Side Effects. Side effects of pramipexole and ropinirole vary but can be severe and include:

Gastrointestinal side effects (nausea and constipation). Nausea can be controlled by drugs, such as domperidone.
Headache
Orthostatic hypotension (sudden drop in blood pressure upon standing up)
Nasal congestion
Nightmares, hallucinations, and psychosis (more severe than with L-dopa for both drugs)
Sudden sleep attacks. These can be very serious, particularly if patients are driving. (Sleep attacks may occur -- although less commonly -- with other PD drugs.)

Other Dopamine Agonists.

Specific dopamine agonists that contain ergot alkaloids include bromocriptine (Parodel), pergolide (Permax), cabergoline (Dostinex), and lisuride (Dopergin). As of 2007, bromocriptine is the only ergot dopamine agonist approved for Parkinson’s treatment in the United States. In January 2007, the New England Journal of Medicine (NEJM) published two studies indicating that pergolide and cabergoline are associated with heart valve damage. In March 2007, due to these safety concerns, the FDA withdrew pergolide from the U.S. market. Cabergoline and lisuride are not approved in the U.S. for Parkinson’s disease treatment but are used for this purpose in other countries. The NEJM studies did not find any heart valve problems associated with bromocriptine or lisuride.
Rotigotine transdermal (Neupro) is a dopamine agonist that is delivered through a skin patch that is changed daily. In 2007, the FDA approved rotigotine transdermal for treatment of symptoms of early Parkinson’s disease. It is the first skin patch approved for Parkinson’s disease. Side effects are similar to those of other dopamine agonists.
Apomorphine is a dopamine agonist used as a "rescue" drug in people experiencing on-off effects severe enough to require going off L-dopa for a few days. In 2004, the FDA approved apomorphine for treating off-time episodes of Parkinson’s disease. Apomorphine is given by injection. Because it causes severe nausea and vomiting, it must be taken with an anti-nausea drug.

Catechol-O-methyl transferase (COMT) inhibitors increase concentrations of existing dopamine in the brain. Entacapone (Comtan, Stalevo) is the current standard COMT inhibitor. (Stalevo combines entacapone and levodopa into a single pill.) It improves motor fluctuations related to the wearing-off effect and has shown good results in improving on time and reducing the requirements for L-dopa. If the patient does not respond to the drug within 3 weeks, it should be withdrawn. No one should withdraw abruptly from these drugs.

Side Effects. Side effects include:

Involuntary muscle movements
Mental confusion and hallucinations
Cramps, nausea, and vomiting
Insomnia
Headache
Urine discoloration (a harmless side effect but should be reported to the doctor)
Diarrhea
Less commonly, constipation, susceptibility to respiratory infection, sweating, dry mouth

Of major concern are reports of a few deaths from liver damage in patients taking the COMT inhibitor tolcapone (Tasmar). The drug has been taken off the market in many countries and is recommended in the U.S. only for patients who cannot tolerate another other drugs. Entacapone does not appear to have the same effects on the liver and does not require monitoring. A 2003 3-year study suggested that the drug is safe and effective over the long term. Still, patients should watch out for symptoms of liver damage, including jaundice (yellowish skin), fatigue, and loss of appetite.

Jaundice is a condition produced when excess amounts of bilirubin circulating in the bloodstream dissolve in the subcutaneous fat (the layer of fat just beneath the skin), causing a yellowish appearance of the skin and the whites of the eyes. With the exception of normal newborn jaundice in the first week of life, all other jaundice indicates overload or damage to the liver, or inability to move bilirubin from the liver through the biliary tract to the gut.

Anticholinergics were the first drugs used for PD, but have largely been replaced by dopamine drugs. They are generally used only against tremor in the early stages. They are not as effective against bradykinesia and posture problems and may increase the risk for dementia in late stages. Among the many anticholinergics are trihexyphenidyl (Artane, Trihexy), benztropine (Cogentin), biperiden (Akineton), procyclidine (Kemadrin), and ethopropazine (Parisdol). Orphenadrine (Norflex) is a drug with anticholinergic properties, but is also a muscle relaxant and does not cause urinary retention.

Side effects of Anticholinergics. Anticholinergics commonly cause dryness of the mouth (which can actually be an advantage in some people who experience drooling). Other side effects are nausea, urinary retention, blurred vision, and constipation. These drugs can also increase heart rate and worsen constipation. Anticholinergics can sometimes cause significant mental problems, including memory loss, confusion, and even hallucinations. People with glaucoma should use these drugs cautiously.

Amantadine (Symadine, Symmetrel) stimulates the release of dopamine and may be used for patients with early mild symptoms. It has some benefit against muscle rigidity and slowness and may help some patients in advanced stages who are unresponsive to other drugs. It is less powerful than levodopa and may lose its effectiveness after 6 months. It may also reduce motor fluctuations brought on by levodopa, however, and these benefits appear to persist for at least a year. Large, well-conducted studies are still needed to determine its true benefits and safety.

Side Effects. Side effects are similar to those of anticholinergic drugs and also may include swollen ankles and mottled skin. It can also cause visual hallucinations. Overdose can cause serious and even life-threatening toxicity. Patients with Parkinson's should not withdraw from this drug abruptly. In rare instances, it can cause acute delirium or a life-threatening condition called neuroleptic malignant syndrome. Pregnant or nursing women should not use this drug.

Anticonvulsants. Zonisamide (Zonegran), a drug used to treat epilepsy, is showing promise in treating tremors, motor problems, and involuntary movements in patients with Parkinson’s disease.

Budipine and Other Glutamate Blockers. A number of experimental drugs are being investigated for Parkinson's disease because they block the actions of glutamate, an amino acid that is a particularly potent nerve cell killer. Some of these drugs block a receptor group to glutamate called N-methyl-D-aspartate (NMDA). Investigational NMDA antagonists include remacemide, memantine, riluzole, and budipine.

Stem Cell Transplantation. Scientists are investigating whether transplanting embryonic stem cells into the brain may help treat Parkinson’s disease. Researchers hope that the transplanted stem cells may be able to stimulate dopamine production. However, stem cell transplantation research is still in its very early stage. It will be many years before clinical trials will be conducted in humans.

Surgery

Surgical procedures are recommended for specific patients with advanced Parkinson’s disease who no longer respond to drug treatments. Surgical treatment cannot cure Parkinson's disease, but it may help control symptoms such as motor fluctuations and dyskinesia. Pallidotomy and thalamotomy are older procedures that destroy tissue in certain parts of the brain. Deep brain stimulation, the current standard surgical practice for Parkinson’s disease, has largely replaced the older operations.

In deep brain stimulation (DBS), also called neurostimulation, an electric pulse generator controls symptoms. The generator is similar to a heart pacemaker. It sends electrical pulses to specific regions of the brain. Candidates for surgery are generally patients who have responded well to levodopa drug treatment. Patients who have had PD for fewer than 16 years may experience greater benefit from DBS than patients who have had the disease longer.

Evidence indicates that DBS improves motor function and reduces dyskinesia best when the procedure targets the subthalamic nucleus (STN) of the brain. Many studies demonstrate the effectiveness of STN stimulation. Procedures that target the globus pallidus interna or ventral intermediate nucleus of the thalamus can also sometimes treat rigidity and tremors. However, there is not yet enough evidence to support stimulation of these parts of the brain.

The procedure is performed as follows:

The surgeon implants a tiny pulse generator near the collarbone, which is connected to four electrodes that have been implanted in the target area in the brain.
The generator delivers programmed pulses to this area, which the patient can turn on and off using a magnet held over the skin.
When on, the pulses suppress symptoms. Complications occur in 2 - 4% of operations. The most serious ones are bleeding in the brain and infection. Depression is common.

In a 2006 study of patients with advanced Parkinson’s disease and severe motor symptoms, patients who received DBS had better improvement in symptoms and quality of life than those who received only drug therapy. However, patients in the neurostimulation group had more serious side effects than those who were treated only with medications. Researchers are also studying whether DBS can benefit patients with earlier-stage Parkinson’s disease.

Pallidotomy and thalamotomy are surgical procedures that destroy brain tissue in regions of the brain associated with Parkinson’s symptoms such as dyskinesia, rigidity, and tremor. In these procedures, a surgeon drills a small hole in the patient’s skull and inserts an electrode to destroy brain tissue. Pallidotomy targets the global pallidus area. Thalamotomy targets the thalamus. Because these procedures permanently eliminate brain tissue, most experts now recommend deep brain stimulation instead of pallidotomy or thalamotomy.

Surgical complications may include behavioral or personality changes, trouble speaking and swallowing, facial paralysis, and vision problems. Weight gain after surgery is also common.

Scientists are investigating whether stem cells may eventually help treat Parkinson disease. Experimental surgery has shown promise using fetal brain cells rich in dopamine implanted in the substantia nigra area of the brain. Because the use of embryonic stem cells is controversial, researchers are studying alternative types of cells, including stem cells from adult brains and cells from human placentas or umbilical cords. Studies are also using gene therapies and other advanced treatments for transplanting dopamine-producing cells or nerve-protecting cells into the brain. All of this research is still in preliminary stages.

Lifestyle Changes

No special diets or natural foods have been shown to slow down the progression of Parkinson's disease, but there are some dietary recommendations.

Protein. High levels of proteins compete with levodopa for transport to the brain and reduce its effectiveness. Avoiding protein altogether is not the solution, since malnutrition can result. Most experts now recommend trying to maintain a carbohydrate-to-protein ratio of 7:1 throughout the day. This may be difficult to calculate and some doctors recommend simply keeping proteins to 12% of total daily calories.

As an aid in calculation, food labels indicate proteins in grams. One gram of protein equals four calories. Good control of protein intake may help minimize fluctuations and wearing-off and may allow some patients to reduce their daily levodopa dosage.

Fruits and Vegetables and Increasing Fiber. Eating whole grains, fresh fruits, and vegetables is the best approach for any healthy life. A diet rich in fruits and vegetables may help protect nerve cell function. Many of these foods are also often rich in fiber, which is particularly important for helping to prevent constipation.

Dietary fiber is the part of food that is not affected by the digestive process in the body. Only a small amount of fiber is metabolized in the stomach and intestine, the rest is passed through the gastrointestinal tract and makes up a part of the stool. There are two types of dietary fiber, soluble and insoluble. Soluble fiber retains water and turns to gel during digestion. It also slows digestion and nutrient absorption from the stomach and intestine. Soluble fiber is found in foods such as oat bran, barley, nuts, seeds, beans, lentils, peas, and some fruits and vegetables. Insoluble fiber appears to speed the passage of foods through the stomach and intestines and adds bulk to the stool. It is found in foods such as wheat bran, vegetables, and whole grains. Fiber is very important to a healthy diet and can be a helpful aid in weight management. One of the best sources of fiber comes from legumes, the group of food containing dried peas and beans.

People whose diets have been low in fiber should increase it gradually. It is best to obtain dietary fiber, soluble or insoluble, in the natural form of whole grains, nuts, legumes, fruits, and vegetables. If it proves difficult to do so, psyllium, a grain naturally found in India, is an excellent soluble fiber supplement (Metamucil, Fiberall, Perdiem Fiber). Fluids are particularly important in preventing constipation.

Fish Oil. Omega-3 fatty acids, which are found in oily fish, are proving to have powerful anti-inflammatory effects and may also be nerve protective.

Click the icon to see an image of foods that contain omega-3 fatty acids.

Dairy Products. A 2002 study reported a higher risk for Parkinson's disease in men (but not in women) who consumed high amounts of dairy products. This association was not linked to fats in dairy foods and high intake of calcium or protein from other sources did not increase the risk. A 2005 prospective study of men found that milk consumption in midlife was associated with increased risk of Parkinson’s disease. As with prior research, the researchers did not find that calcium itself carried a risk. They suggested that some unidentified neurotoxic contaminant in milk may be responsible.

Vitamins.

B Vitamins. Most B vitamins play important roles in the brain and central nervous system. Vitamin B6 (pyridoxine) theoretically has benefits for PD because it is necessary in the production and metabolism of dopamine. Folate deficiency may increase toxic effects against dopamine neural pathways, perhaps by increasing levels of homocysteine, an amino acid that may play a destructive role in many diseases, including heart and neurologic disorders. Some evidence suggests that L-dopa elevates homocysteine levels, so folate supplements may be particularly important for patients. Although the major food sources of B vitamins are meats and dairy products, which are high in protein, these vitamins are also found in whole grains and are added as supplements to commercial cereals.

Click the icon to see an image of the benefits of vitamin B6.

Click the icon to see an image of foods that contain vitamin B6.

Click the icon to see an image of foods that contain folate.

Vitamin E. Researchers have investigated antioxidant vitamins, especially vitamin E, for their effect on the brain. Some, but not all, studies have reported slower mental decline and lower risk for Parkinson's and Alzheimer's disease in people who ate large amounts of foods rich in vitamin E. Such foods include vegetable oils (particularly wheat germ oil), sweet potatoes, turnip greens, mangos, avocados, nuts, sunflower seeds, and soybeans. Vitamin E supplements, however, do not appear to be helpful for slowing disease progression or improving symptoms.

Both smoking and coffee drinking have been associated with lower risk for PD. Researchers are attempting to discover if these substances protect nerve cells. One interesting study suggested that the early disease process in PD produces changes in the dopamine pathway that actually protects an individual from caffeine and nicotine addiction, so that fewer patients have a history of smoking and caffeine. Research is needed to determine why these toxic substances protect against PD.

Smoking and Nicotine Replacement. Cigarette smokers appear to have a 40% lower risk for Parkinson's disease, indicating some protection by nicotine. This finding, of course, is no excuse to smoke, but such protection may help researchers develop new therapies. Studies on nicotine replacement, such as gum or patches, have been conflicting, however, with some short-term studies reporting no benefits. A 2002 study suggested that nicotine replacement may help smokers with early PD, but not nonsmokers.

Coffee Consumption. Studies have indicated that the risk for PD in coffee drinkers is about 30% lower than for non-coffee drinkers. In a 30-year study of Japanese-American men, coffee consumption was associated with a lower risk for Parkinson's disease, and the more coffee they drank, the lower their risk became. Coffee and tea can reduce fluids by increasing urination, however, and so may increase constipation in PD.

Regular use of ibuprofen may reduce the risk of Parkinson’s disease according to research presented at the 2005 annual meeting of the American Academy of Neurology. In this prospective study, people who took at least two ibuprofen tablets per week for at least 1 year lowered their risk of developing Parkinson’s by 35% compared to nonusers or irregular users. For those who took ibuprofen daily, the comparative risk was 38% lower. Other non-steroidal anti-inflammatory drugs (NSAIDS) did not appear to affect disease risk.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

The following dietary supplements are being studied for treatment of Parkinson's disease:

Creatine. Creatine is a nutritional supplement that is sometimes used to improve exercise performance. In 2007, the U.S. National Institutes of Health launched a large-scale clinical trial to study whether creatine can slow the progression of Parkinson’s disease. The trial will enroll patients who have been diagnosed with PD within the last 5 years and who have received levodopa therapy for no more than 2 years.

Coenzyme Q10 (Ubiquinone). Coenzyme Q10 (also called ubiquinone) is an antioxidant being studied for the treatment of Parkinson's disease. This enzyme is important for cellular energy, which may be impaired in PD. In one study, patients who took coenzyme Q10 had slower decline in daily activities and mental and motor skills compared to patients on placebo. However, a 2007 study found that small doses of coenzyme Q10 had no effect on improving Parkinson’s symptoms. Researchers are still investigating whether larger doses given over a long period of time may benefit patients.

Exercise early in adult life may help protect against later development of Parkinson’s disease. Exercise is also an important component of rehabilitation. Physical therapy is extremely important and usually includes active and passive exercise, gait training, practice in normal activities, and if needed, hot or cold treatments, water therapy, and electrical stimulation. Exercise is also essential for well-being and helps patients maintain productive years. To date, no specific approach has been proven to be better than others.

Exercise Programs. Exercise programs are defined as passive or active.

Passive exercise, mostly stretching and manipulation of muscles by a physical therapist, is aimed at preventing muscles from shortening. A passive exercise program that begins with slow and gentle exercises and becomes progressively more intense may improve mobility in patients with early and mid-stage Parkinson's disease.
Active exercises are used to help range-of-motion, coordination, and speed. Patients should continually make efforts to practice movement, even simple ones, such as marching in place, making circular arm movements, and raising the legs up and down while sitting. Patients who enjoy sports or the use of exercise equipment should continue with these activities even if their skills diminish, assuming there are no other medical conditions that would prevent participation.

Gait Training. Practicing new methods for standing, walking, and turning may help retain balance. The following tips may be helpful:

Take large steps when walking forward, raising the toes at the forward step, and hitting the ground with the heel.
Take small steps while turning.
When walking or turning, have the legs 12 - 15 inches apart to provide a wide base.
Do not wear rubber or crepe-soled shoes because they grip the floor and may cause the patient to fall forward.
Using devices that keep a rhythmic beat, such a metronome (a simple device used by musicians to keep time), may be very effective, possibly more than music itself, in helping patients to walk faster and take longer steps. One study found that setting a metronome rhythm to about 10% faster than the patient's fastest gait offers significant improvement over walking to no rhythm at all or to a rhythm that matches the gait.

Reducing Muscle Freezing. The patient should practice regular daily activities that simplify actions and reduce the incidence of muscle freezing. Most often, freezing occurs when a patient begins to move or is presented with an obstacle. The following tips may be helpful:

Rock from side to side.
If the legs feel frozen, lift the toes. This simple action may free spasm in some cases.
Hum marching tunes. In fact, music has been shown to help people move and to get out of bed in the morning. Some studies report that wearing a Walkman and turning music on in situations associated with freezing, such as crossing a street, is helpful.
Divide actions into separate events, which may prevent freezing that occurs from trying to coordinate too many physical operations at one time. For instance, when going through a doorway, approach the door, stop at the door, open it, stop, and then walk through the doorway.
A cane equipped with a laser pointer may be helpful, at least temporarily.
Simply being touched by another person can sometimes release the patient (although a patient with PD should never be pulled or pushed).

Sleep Deprivation Therapy. Sleep deprivation therapy may have a role in treating some cases of depression and some studies are finding some benefits on the depression, tremor, and rigidity experienced by patients. Scientists believe that sleep deprivation produces certain anticholinergic effects, which may improve both depression and Parkinson's symptoms.

Mental Tasks. Mental training may increase dopamine in the brain. Some studies indicate that being mentally fit may be as important for patients as being physically fit. Helpful approaches include:

Select and learn new hobbies that require finger and hand mobility, such as sewing, carpentry, fishing, or playing cards.
Practice deep breathing and relaxation exercises. These may help maintain proper speech control, control tremor, and reduce anxiety.
Both the patient and any caregivers should consider psychological therapy and support for depression and loss of motivation. If psychological therapy is too costly, inexpensive support programs and groups are widely available and can be invaluable for the patient and the family.

Speech Therapy. Speech therapy may help those who develop a monotone voice and lose volume, particularly in combination with medications. There are no well-conducted studies comparing specific speech therapies, but the Lee Silverman Voice Treatment (LSVT) appears to be an example of an effective technique. It has five major components:

Focus on the voice ("think loud/think shout")
High effort (pushes patients to overcome limitations)
Intensive treatment (16 sessions in 1 month)
Calibration (learning to know and accept the amount of effort needed to produce normal sound so it becomes automatic)
Quantification (continuous feedback to objectively document success)

LSVT may help swallowing as well as speech.

Equipment and Devices. A number of devices can be helpful for maintaining stability and preventing falls. The following are some examples:

Rails installed where the patient needs support in getting up or down, such as along the bed and in the bathroom.
Walkers with locking wheels. (Walkers do not appear to be helpful for freezing.)
Chairs with straight backs, firm seats, and arm rests.
Firm mattresses and satin sheets or less expensive sheets with high thread counts. (These are useful for helping patients slide out of bed.)

Resources

www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.aan.com -- American Academy of Neurology
www.apdaparkinson.org -- American Parkinson's Disease Association
www.pdf.org -- Parkinson's Disease Foundation
www.parkinson.org -- National Parkinson Foundation
www.michaeljfox.org -- Michael J. Fox Foundation for Parkinson's Research
www.wemove.org -- Worldwide Education and Awareness for Movement Disorders
www.parkinsonsaction.org -- Parkinson's Action Network

References

Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schafer H, Botzel K, et al. A randomized trial of deep-brain stimulation for Parkinson's disease. N Engl J Med. 2006 Aug 31;355(9):896-908.

Murata M, Hasegawa K, Kanazawa I. Zonisamide improves motor function in Parkinson disease: a randomized, double-blind study. Neurology. 2007 Jan 2;68(1):45-50.

Schade R, Andersohn F, Suissa S, Haverkamp W, Garbe E. Dopamine agonists and the risk of cardiac-valve regurgitation. N Engl J Med. 2007 Jan 4;356(1):29-38.

Schupbach WM, Maltete D, Houeto JL, du Montcel ST, Mallet L, Welter ML, et al. Neurosurgery at an earlier stage of Parkinson disease: a randomized, controlled trial. Neurology. 2007 Jan 23;68(4):267-71. Epub 2006 Dec 6.

Storch A, Jost WH, Vieregge P, Spiegel J, Grelich W, Durner J, et al. Randomized, double-blind, placebo-controlled trial on symptomatic effects of coenzyme Q10 in Parkinson disease. Arch Neurol. 2007 July;64.

Voon V, Thomsen T, Miyasaki JM, de Souza M, Shafro A, Fox SH, et al. Factors associated with dopaminergic drug-related pathological gambling in Parkinson disease. Arch Neurol. 2007 Feb;64(2):212-6.

Watts RL, Jankovic J, Waters C, Rajput A, Boroojerdi B, Rao J. Randomized, blind, controlled trial of transdermal rotigotine in early Parkinson disease. Neurology. 2007 Jan 23;68(4):272-6. Epub 2007 Jan 3.

Zanettini R, Antonini A, Gatto G, Gentile R, Tesei S, Pezzoli G. Valvular heart disease and the use of dopamine agonists for Parkinson's disease. N Engl J Med. 2007 Jan 4;356(1):39-46.

Review Date:
6/4/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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