Polycystic Ovary Syndrome, Insulin Resistance, and Molecular Defects of Insulin Signaling

The polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders, affecting 4–6% of unselected women of reproductive age. More recently, it has been recognized that in addition to endocrine abnormalities many patients with PCOS demonstrate metabolic aberrations. Most significant among these is the presence of insulin resistance. Overall, approximately 50–60% of PCOS patients suffer from insulin resistance (1, 2), compared with a prevalence of insulin resistance in the general population of 10–25%, depending on definition and mean population body weight (3–5). Insulin resistance in PCOS leads to the development of compensatory hyperinsulinemia, and this hyperinsulinemia seems to play a major role in the pathogenesis of the hyperandrogenism of PCOS. Hyperinsulinemia stimulates androgen secretion by the ovarian theca, excess growth of the basal cells of the skin resulting in acanthosis nigricans, and abnormal hepatic and peripheral lipid metabolism. That insulin resistance and hyperinsulinemia underlie many of the features of PCOS is supported by the fact that the administration of various insulin-reducing or sensitizing agents, including diazoxide, metformin, troglitazone, and d-chiro-inositol, has been found to improve clinical features in many of these patients.