Insulin Resistance and the Polycystic Ovary Syndrome: Mechanism and Implications for Pathogenesis

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I. Introduction

A. Background and historical perspective

POLYCYSTIC ovary syndrome (PCOS) is an exceptionally common disorder of premenopausal women characterized by hyperandrogenism and chronic anovulation (1, 2). Its etiology remains unknown. Although there have been no specific population-based studies, a 5–10% prevalence of this disorder in women of reproductive age is probably a reasonable conservative estimate. This is based as an upper limit on studies of the prevalence of polycystic ovaries, which found that∼ 20% of self-selected normal women had polycystic ovary morphology on ovarian ultrasound (3). Many of these women had subtle endocrine abnormalities (3). The lower estimate is based on the reported 3% prevalence rate of secondary amenorrhea for 3 or more months (4) and the fact that up to ∼75% of women with secondary amenorrhea will fulfill diagnostic criteria for PCOS (5). PCOS women can also have less profound disturbances in menstrual function (1, 3, 6).

Since the report by Burghen et al. (7) in 1980 that PCOS was associated with hyperinsulinemia, it has become clear that the syndrome has major metabolic as well as reproductive morbidities. The recognition of this association has also instigated extensive investigation of the relationship between insulin and gonadal function (1, 8–11). This review will summarize our current understanding of insulin action in PCOS, address areas of controversy, and propose several hypotheses for this association. Abnormalities of steroidogenesis and gonadotropin release will not be discussed in detail; these changes have been reviewed recently by Erhmann and colleagues (12) and by Crowley (13), respectively.