Polycystic Ovary Syndrome - Spring 2005

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Polycystic ovary syndrome (PCOS) is a common condition – possibly the most common endocrine disorder of women of reproductive age. Estimates suggest that roughly 5% of women can be classified as having PCOS.

Women with polycystic ovary syndrome usually go to their doctors because they are experiencing a number of problems at once: absent periods or other menstrual irregularities, excess hair growth and/or acne (androgen excess) or infertility problems. Many women with PCOS (particularly in North America) tend also to be overweight or obese.

Of course that’s what a syndrome is – a grouping of symptoms or clinical complaints. However, PCOS is what doctors call a "heterologous" condition, meaning that not all women present the same complaints. And certain other conditions can mimic PCOS. All this has led to disagreements over the past few decades about the criteria for diagnosing this condition.

In May 2003 a group of world experts on PCOS met at Rotterdam, in the Netherlands and worked out the most recent definition for the clinical diagnosis.

To diagnose polycystic ovary syndrome, at least two of the following three symptoms must be present: (1) infrequent ovulation or no ovulation at all (oligo- or anovulation), (2) clinical and/or biochemical signs of hyperandrogenism (high blood levels of male hormones, principally testosterone, or symptoms such as acne or excess hair growth) and/or (3) polycystic ovaries on ultrasound. At the same time, other conditions (such as late onset congenital adrenal hyperplasia, adrenal tumours and Cushing’s syndrome) must be ruled out with appropriate tests.

Treatment is directed at the main complaint. This can include cyclic progestin, progesterone, or oral contraceptives administration for menstrual irregularities, oral contraceptives and other antiandrogen medications for excess hair growth and acne, and ovulation induction medications for infertility.

Over the last 20 years, we have come to recognize that PCOS is associated with other metabolic abnormalities. Women with PCOS have a higher incidence of insulin resistance and secondary hyperinsulinemia (the body’s response to elevated glucose levels in the blood). They are also at much higher risk of developing Type II diabetes at an earlier age than the general population. This is especially true for women with PCOS who are obese and/or have a family history of diabetes, both of which are independent risk factors for developing diabetes.

Similarly, in women with PCOS, and in their family members, we see more illnesses that co-cluster with diabetes, such as abdominal obesity (classic "pear" body shape), elevated blood lipids (high cholesterol and triglyceride), and hypertension. The clustering of these illnesses is often termed the "metabolic syndrome." All these problems tend to place an individual at higher risk for the development of atherosclerotic heart disease and stroke.

PCOS has to be viewed as a potentially long-term health risk. Doctors must make every effort to monitor women at a younger age for the development of the risk factors mentioned above. They should also encourage a lifetime commitment to lifestyle modification – healthy eating, exercise, no smoking – in order to minimize these risks.

When a woman with PCOS presents symptoms such as menstrual irregularity or lack of menses, her condition is often related to failure to establish regular ovulatory cycles, and infertility. Traditionally, treatment of infertility in PCOS has focused on the administration of medications (clomiphene citrate or gonadotropin preparations such as FSH) to stimulate follicular development so as to promote ovulation.

However, our growing body of evidence that insulin resistance is common among women with this disorder opens up a new venue of possible treatment.

Insulin resistance is the body’s subnormal biological response to the tissue action of insulin. We can identify it by measuring the action of insulin at typical target organs, such as muscle and fat. We now know that the ovary is also a target for insulin action. However, there is evidence that "selective insulin resistance" occurs among different target organs in PCOS. This means that insulin is less effective at some target organs, yet maintains action at others.

Elevated insulin levels within the ovary seem to disrupt the normal, carefully orchestrated selection, development, and ovulation of a single mature follicle each month. Ovulation then fails to occur, and infertility results. Insulin within the ovary also stimulates the production of testosterone, and this leads to the increased androgen action on targets in the skin, such as the sebaceous glands and hair follicles, causing acne and excess hair growth (hirsutism).

For some women whose infertility problems are due to PCOS, therapies to lower insulin levels have worked reasonably well in re-establishing ovulatory cycles. In addition to lifestyle modification, an insulin-lowering agent, such as metformin can be prescribed. Recently another class of drugs called thiazolidinediones have been used in women who do not tolerate metformin. These medications improve insulin levels in the same way as weight loss through diet and exercise. For some women this help can re-establish the ovulatory cycle, especially if traditional medications are used as well.

Because ovulation is disrupted in women with PCOS, almost any pattern of menstrual irregularity may occur – long periods of no bleeding, or infrequent and unpredictable bleeding patterns. In women with PCOS who do not ovulate for long episodes (if at all) the ovary continues to produce low levels of estrogen that continue to stimulate the lining of the uterus (endometrium). But because there is no ovulation, the ovary does not produce progesterone. Exposed to chronic estrogen levels, the endometrium can shed unpredictably, leading to irregular menses. Another concern is that over long periods of time, estrogen-only stimulation of the endometrial lining can lead to an over stimulated lining (hyperplasia) which occasionally can progress to endometrial cancer. Because of this, it is important, in women not planning to conceive, to ensure that the endometrium is exposed periodically to progesterone or progesterone-like medications. This can be done by taking a short course (12 to 14 days) of synthetic or natural progesterone every few months, or by taking the oral contraceptive pill. 

ABOUT THE AUTHOR: Dr. Greenblatt completed her medical school (McGill University) and Ob/Gyn Residency (University of Western Ontario) in Canada before moving on to complete a fellowship in Reproductive Endocrinology and Infertility at the University of California, San Francisco. Dr. Greenblatt is a fellow of the Royal College of Surgeons of Canada (Ob/Gyn) as well as a Fellow of the American Board of Obstetrics and Gynecology (ABOG) with ABOG subspecialty certification in Reproductive Endocrinology and Infertility. She is Clinical Director of the Reproductive Biology Unit and IVF Unit in the Department of Obstetrics and Gynaecology, as well as Programme Director of the Reproductive Endocrinology and Infertility fellowship in the Department of Gynecology, University of Toronto. Dr. Greenblatt is an assistant professor in the Department of Obstetrics and Gynaecology, University of Toronto and National Director of the Canadian Fertility Andrology Society. Her research interests focus on polycystic ovary syndrome and optimizing ART treatments.