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General Information


Insulin Resistance and the Polycystic Ovary Syndrome

The polycystic ovary syndrome (PCOS) is a prevalent disorder affecting ~6-10% of women of reproductive age (i.e., between 3.5-5.0 million women in the U.S.), and is characterized by chronic anovulation and hyperandrogenism. A frequent feature of women with PCOS is insulin resistance accompanied by compensatory hyperinsulinemia, and increasing evidence suggests that hyperinsulinemia plays an important role in the pathogenesis of PCOS.

Hyperinsulinemia produces hyperandrogenism in women with PCOS via two distinct and independent mechanisms: 1) by stimulating ovarian androgen production, and 2) by directly and independently reducing serum SHBG levels. The net result of these actions is to increase circulating free testosterone concentrations. An inherent (genetically determined) ovarian defect likely is present in women with PCOS, which makes the ovary either susceptible to or more sensitive to insulin's stimulation of androgen production. Limited evidence suggests that hyperinsulinemia might also promote ovarian androgen production by influencing pituitary release of gonadotropins, but this has not been critically evaluated.

In addition to promoting hyperandrogenism, recent evidence indicates that hyperinsulinemia contributes to the anovulation of PCOS. Hyperinsulinemia could adversely affect folliculogenesis and impede ovulation by increasing intra ovarian androgen production, altering gonadoropin secretion, or directly affecting follicular development.

The relationship of hyperinsulinemia to PCOS is important from a clinical standpoint, because: 1) it dictates that women with PCOS need to be evaluated for other disorders associated with insulin resistance (type 2 diabetes mellitus, hypertension, dyslipidemia, atherosclerosis), and 2) it suggests that medications that reduce circulating insulin might prove to be effective therapies for PCOS. Indeed, several studies have demonstrated that 30-50% of obese women with PCOS will develop either IGT or Type 2 diabetes by the age of 30. Conversely, in a recent study of the Diabetes Clinic at Virginia Commonwealth University, we found that 28% of premenopausal women with Type 2 diabetes had PCOS, with a quarter of them being undiagnosed. Studies have also documented early (premature) plaques in the coronary arteries of 35-40 year-old women with PCOS.

Confirming the important role of hyperinsulinemic insulin resistance in the pathogenesis of PCOS, insulin reduction, whether achieved by inhibition of pancreatic insulin release (diazoxide or octreotide) or improvement in peripheral insulin sensitivity (metformin, troglitazone or D-chiro-inositol), is associated with a reduction in circulating androgens in women with PCOS, an improvement in ovulatory function, and enhanced fertility.

Limited evidence also suggests that agents that improve insulin sensitivity might also favorably affect those complications of PCOS that may be attributable to insulin resistance for example, such treatments may reduce blood pressure, serum triglycerides and circulating PAI-1 concentrations. The recent results of the NIH-sponsored Diabetes Prevention Project, which showed that either intensive lifestyle modification (diet and exercise) or treatment with the insulin sensitizing drug metformin decreased the development of Type 2 diabetes in individuals at high risk, lends further credence to the idea that treatment of women with PCOS with insulin sensitizing drugs may have long-term salutary effects on general health.

Thus, in the past 16 years, progress in characterizing the relationship between insulin and PCOS has been substantial, pointing the way to new and novel therapy of PCOS. While many questions remain, clearly sufficient evidence has accumulated to justify clinical use of insulin- sensitizing agents in the management of women with PCOS.

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Last Updated: February 01, 2007