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Polycystic Ovary Syndrome

A Little-Known Complaint Affecting Many Women

David Edelberg, M.D., Chief Medical Advisor

Since her early teens, Jane had been plagued by several annoying but seemingly unrelated problems -- acne, irregular menstrual periods, weight gain, and excessive hair growth on her face, arms and legs. Following her doctors' advice, she had coped with these problems individually, using medication for her acne, oral contraceptives to regulate her periods, electrolysis to zap the unwanted hair and various diets to lose weight.

Years later when she was having trouble conceiving, Jane started taking fertility drugs. After several rounds of treatments proved unsuccessful, she visited a new gynecologist who finally put all the pieces of the puzzle together and diagnosed her condition as polycystic ovary syndrome. Much to her surprise, Jane discovered that many of her problems probably stemmed from a single underlying defect: her body's resistance to insulin, the hormone that helps cells absorb sugar from the bloodstream.

Jane learned that the syndrome, believed to be the leading cause of infertility in women, also placed her at risk for high blood pressure, heart disease, diabetes and uterine cancer. Although the news was disturbing, it also carried a message of hope: Lowering insulin levels might reduce her future disease risk and alleviate many of her existing problems.

She also learned that drug therapy isn't the only answer for women with this syndrome. Alternative approaches, such as specific diets, exercise, acupuncture and herbal therapy, also have much to offer.

Insulin: The Prime Culprit?
Women with polycystic ovary syndrome overproduce androgens, or male hormones, including testosterone. All women produce some testosterone, but excessive amounts can prevent the egg from being expelled from the ovary, disrupting the menstrual cycle and leading to infertility.

The retained eggs form small cysts that encircle the ovary, giving the syndrome its name. The high testosterone levels also account for the weight gain, acne, excessive body hair and male-pattern hair thinning often seen in affected women.

Exactly what causes the high testosterone levels is still not completely clear, but one clue emerged in 1980 when researchers identified insulin resistance as a key feature of the syndrome. When the body fails to use insulin properly, the pancreas releases more and more insulin. In affected women, this insulin surplus apparently triggers the ovaries to boost their androgen production.

Dr. Andrea Dunaif, chief of the division of women's health at Brigham and Women's Hospital in Boston, believes that "multiple genes may contribute to polycystic ovary syndrome." She notes that her research is picking up strong evidence that a marker near the insulin receptor may be associated with the disorder.

1 in 10 Women?
Some 5 percent to 10 percent of women of reproductive age -- perhaps as many as 5 million women in the United States -- have polycystic ovary syndrome. Left untreated, the condition can lead to life-threatening illnesses. For example, affected women have a sevenfold increased risk for adult-onset diabetes, and they are also more likely to develop hypertension and abnormal lipid levels, both of which increase their risk for cardiovascular disease. Also, because women with polycystic ovaries do not menstruate regularly, they are at higher risk for uterine cancer.

Drug Therapy
Many researchers now believe that for many women, lowering insulin resistance may help restore fertility and alleviate problems caused by excessive androgens. Even more important, this approach offers hope for reducing the risk of serious future disease.

Measures for improving insulin sensitivity include weight loss, dietary changes, increased physical activity, and the use of insulin-sensitizing medications such as metformin (Glucophage), rosiglitazone (Avandia), and pioglitazone (Actos).

Several recent studies with insulin-sensitizing drugs showed that lowering insulin resistance can, in fact, correct the hormonal imbalances. In one controlled study, metformin induced ovulation either when given alone or together with the fertility drug clomiphene in 89% of affected women who had previously failed to respond to clomiphene alone (New England Journal of Medicine, 6/25/98). The insulin-lowering agent troglitazone produced similar results in women resistant to clomiphene (Human Reproduction, 11/99). (Troglitazone, however, was withdrawn from the market in March 2000 because of life-threatening side effects. Rosiglitazone and pioglitazone, which are members of the same class of drugs as troglitazone, appear to be safer alternatives.)

Some experts say a natural carbohydrate found in fruits and vegetables called D-chiro-inositol may also be effective for lowering insulin. In a recent small study, six to eight weeks of therapy with this compound restored ovulation in 86 percent of affected women, compared with only 27 percent of those in the control group (New England Journal of Medicine, April 29, 1999). The treatment also improved insulin, triglyceride and testosterone levels, while lowering blood pressure. There were no apparent side effects in this study, but larger clinical trials are needed to establish its effectiveness and safety.

Thus, reducing insulin levels may decrease male hormone levels and the associated symptoms of androgen excess. Although the available insulin-sensitizing drugs appear effective for many women, they are not free of side effects. For instance, metformin can cause diarrhea, nausea and bloating, while troglitazone may produce liver toxicity and requires regular monitoring with liver function tests.

High-Protein Diets and Exercise
Before embarking on drug therapy, affected women who are also overweight may first want to try a simpler, and perhaps safer, approach. Losing weight through diet and stepped-up physical activity can also lower insulin resistance.

According to Dunaif, "Lifestyle modification, such as diet and exercise, is a wonderful approach. A reduction of about 10 percent in body weight will restore ovulation in a lot of women with PCOS and improve their insulin sensitivity."

For many women with this syndrome, high-protein, low-carbohydrate diets have proved more successful than low-fat diets. Dunaif thinks they may do better on a diet that contains a little bit more fat and protein "because it's just more satisfying," but she cautions that high-fat, high-protein diets such as the Atkins diet can be dangerous because "the increased intake of animal fat and protein could worsen the lipid abnormalities" in women with this disorder.

A recent Swedish study found that meaningful weight loss (18 pounds average) improved insulin sensitivity and was as effective as oral contraceptives in lowering androgen levels in women with polycystic ovary syndrome (Journal of Clinical Endocrinology and Metabolism, June 1999). Australian investigators also found that diet and regular exercise improved insulin sensitivity and restored ovulation in affected overweight women (Journal of Clinical Endocrinology and Metabolism, April 1999).

Acupuncture and Herbs
Some of the drugs used to induce ovulation hold increased risks for women with polycystic ovary syndrome, including multiple births and ovarian hyperstimulation syndrome, a serious condition marked by enlarged ovaries that can lead to fluid accumulation in the abdomen and lungs.

For some women seeking to become pregnant, acupuncture might offer a gentler alternative. In a recent Swedish study, electroacupuncture -- in which a small electrical current is applied to acupuncture needles inserted into specific points on the body -- helped restore ovulation in more than one-third of women with the syndrome (Acta Obstetricia et Gynecologica Scandinavica, March 2000). Those who responded tended to have less severe disease than those who did not.

"There's a very strong mind-body connection, and I'm sure that altering stress levels with some of these alternative medicine techniques could be effective in some women," Dunaif said.

Finally, several traditional herbal therapies have reportedly been helpful in inducing ovulation and restoring fertility. A Japanese study showed that the Chinese herbal medicine Sairei-to normalized reproductive hormone levels and induced ovulation in 71 percent of affected women (Endocrine Journal, Feb. 1999). The traditional herbal medicine Shakuyaku-Kanzo-To and the Chinese herbal medicine for replenishing Kidney-Yin have also proved effective in restoring fertility in women with polycystic ovaries. However, these herbs have not been studied extensively. You should seek your physician's advice before starting to use any of these herbal remedies.

Do you have PCOS?
According to Dunaif, "Most of the time, if women have irregular menstrual cycles and evidence of male hormone excess, they're going to have polycystic ovary syndrome."

However, many women with polycystic ovary syndrome do not realize they have the disorder. So, if you have two or more symptoms -- erratic menstrual periods, excess hair growth on your face and body, thinning scalp hair, acne, infertility or obesity -- you should see your doctor for an accurate diagnosis.

Appropriate screening tests can determine whether you have the disorder and assess your long-term risks for diabetes, heart disease and uterine cancer. One study reported that a fasting glucose-to-insulin ratio is the best screening measure for detecting insulin resistance in women with polycystic ovary syndrome (Journal of Clinical Endocrinology and Metabolism, Aug. 1998).

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