Polycystic ovary syndrome: Current and future treatment paradigms

Polycystic ovary syndrome is characterized by excess levels of circulating androgens and by chronic anovulation. Although the fundamental pathophysiologic defect has not been determined, women with polycystic ovary syndrome are known to be uniquely insulin resistant. Obesity in polycystic ovary syndrome aggravates the underlying predisposition towards insulin resistance. Diagnostic criteria that focus on menstrual irregularity are more likely to discriminate insulin-resistant women than are such criteria as abnormal gonadotropin secretion or ovarian morphologic characteristics. About 40% of patients with polycystic ovary syndrome demonstrate glucose intolerance (either impaired glucose tolerance or type 2 diabetes) in response to an oral glucose challenge. The lack of a clear causal mechanism in the syndrome has led to a multitude of symptom-oriented treatments, with few therapies improving all aspects of the endocrine abnormalities associated with polycystic ovary syndrome. Many of these therapies - such as ovulation induction with medical agents - hold increased risks for women with polycystic ovary syndrome, including ovarian hyperstimulation syndrome and multiple gestation. Empirical studies of interventions that improve insulin sensitivity in polycystic ovary syndrome (either weight loss and diet programs or pharmaceutical agents) have been shown to improve the endocrine abnormalities in the syndrome. Initial results with antidiabetic agents (specifically insulin-sensitizing agents) are promising but need to be confirmed with larger, randomized studies.