Polycystic Ovarian Syndrome
(Also see the related topic of Hirsuitism)

Thomas Higgins, M.D.
1/31/99

 Definition

Originally termed Stein Leventhal Syndrome after the investigators who first described it, the disorder is now more commonly known as polycystic ovarian syndrome or PCOS. Most physicians would agree that PCOS can be diagnosed clinically in a woman who has hirsutism, irregular menstrual cycles, obesity, and a classic ovarian morphology. However, there is considerable controversy about diagnostic criteria for other women with less florid manifestations. After considerable debate at a 1990 National Institutes of Health Conference on PCOS, two minimal criteria were proposed:

• Menstrual irregularity.
• Evidence of hyperandrogenism, whether clinical (hirsutism, acne, or male pattern balding) or biochemical (elevated serum androgen level).

The diagnosis of the PCOS also requires the exclusion of women with other known causes of female hyperandrogenism. Disorders such as the use of some drugs, congenital adrenal hyperplasia, androgen-secreting tumors, ovarian hyperthecosis and hyperprolactinemia should be considered.

Clinical Manifestations

It is important to appreciate that PCOS is a syndrome reflecting multiple potential etiologies and variable clinical presentations. A familial pattern occurs in some cases, suggesting a genetic component to the disorder.

Menstrual dysfunction: Although menstrual dysfunction is a defining characteristic of PCOS, it can be manifested in several different ways. Probably most common is erratic menstruation due to anovulation.

The menstrual irregularity may also be manifest as oligomenorrhea (fewer that nine menstrual periods in a year) or amenorrhea (no menstrual periods for three or more months).

The menstrual disturbances in PCOS classically have a peripubertal onset.

Hyperandrogenism: Hyperandrogenism is the second defining characteristic of PCOS. This may be manifested clinically by hirsutism, acne, male pattern balding or hair loss, increased muscle mass, deepening voice, or clitoromegaly.

Depending upon the androgen measured and the technique employed, between 50 and 90 percent of PCOS women have elevated serum androgen levels. The excess androgens can be derived from the ovary and/or the adrenal cortex.

Ovarian Morphology: Polycystic ovaries can often be seen on ultrasonography. From the original description of the thickened glistening white capsule of the enlarged multicystic ovary on laparotomy by Stein and Leventhal, it has been clear that PCOS is associated with a classic ovarian appearance. Between 80 and 100 percent of women with PCOS have a classic ultrasound appearance consistent with the histologic findings. The presence of the classic polycystic ovarian morphology alone, however, is insufficient to make the diagnosis in women who have regular ovulatory menstrual cycles or are not hyperandrogenic since this morphology is seen in up to 20 to 25 percent of regularly ovulating normal women.

Infertility: Clinical experience suggests that most affected women ovulate intermittently and therefore may take longer to conceive or may have fewer children. A subset of women with PCOS do have infertility.

Obesity and insulin resistance: At least one-half of women with PCOS are obese. Women with PCOS are also hyperinsulinemic and insulin resistant. It has been estimated that 20 percent of women with PCOS who are obese have either impaired glucose tolerance or non-insulin-dependent diabetes mellitus (NIDDM) by age 40. The presence of obesity and insulin resistance may also predispose women with PCOS to coronary heart disease.

Biochemical Abnormalities

Depending upon the androgen measured, between 50 and 90 percent of PCOS women have elevated serum androgen levels. The excess androgens can be derived from the ovary and/or the adrenal cortex.

Other biochemical findings that may be present include:

• Normal serum estradiol and increased serum estrone concentrations
• Serum luteinizing hormone concentrations that are often slightly high, but serum follicle-stimulating hormone concentrations are normal.
• Although most women have normal glucose tolerance, nearly all – whether obese or not – have insulin resistance and hyperinsulinemia.
• Slightly elevated prolactin.

Treatment

There are several treatments for each of the manifestations of PCOS; the choice among the available treatments for hirsutism, menstrual irregularity, infertility and insulin resistance/obesity depends upon the woman's goals. Most if not all of the manifestations or PCOS can be reversed by weight loss in those women who are obese. The issue of fertility should always be discussed with the woman first, because whether she wants to become pregnant is a major determinant of the choice of therapy.

Hirsutism: hirsutism can be treated by removal of hair by shaving, depilatories or electrolysis. Hair growth may be slowed by administration of oral contraceptives and antiandrogens (e.g., spironolactone), which decrease androgen secretion and action. The latter treatments may also reduce acne.

Menstrual irregularity: Menstrual irregularity is best treated by an oral contraceptive. This therapy also inhibits ovarian androgen. An oral contraceptive, therefore, is the best overall treatment for women with the PCOS who do not wish to become pregnant.

Infertility: It is critical to complete a basic evaluation of the couple before initiating therapy in an infertile woman with PCOS. Initial evaluation should include a semen analysis of the male. Approximately 80 percent of women with the PCOS ovulate in response to clomiphene citrate.

Other methods to induce ovulation are:

• pulsatile administration of gonadotropin-releasing hormone (GnRH)
• exogenous administration of gonadotropins.

These regimens are complex and expensive and are best carried out by experienced physicians.

Obesity and insulin resistance: Any treatment that reduces insulin resistance and therefore diminishes insulin secretion in both obese and lean women with the PCOS can have a variety of beneficial effects. Although the mechanism is unclear, many obese women with PCOS resume more regular menstrual cycles after relatively small amounts of weight loss.

Metformin and troglitazone (Rezulin) are medications used in the treatment of Type 2 diabetes. Both increase insulin sensitivity and, in women with PCOS, may also reduce ovarian androgen production and restore normal menstrual cycles. Studies of metformin in PCOS have been conflicting. Two studies of troglitazone have demonstrated more consistent results. Enthusiasm for the use of troglitazone has been tempered, however, by reports of severe idiosyncratic liver injury.

www.pcosupport.org Link to a non-profit organization dedicated to providing patient & physician education about PCOS and its health effects.