Polycystic Ovarian Syndrome

PCOS is a common disorder of premenstrual women characterized by hyperandrogenism, chronic anovulation, menstrual irregularity, hyperinsulin-emia, and often (for which it is a major cause) infertility (106,107). Prevalence estimates range from 5 to 10% of menstruating females. It was first reported in 1980 that women with PCOS had hyperinsulinemia, suggesting the presence of insulin resistance (108-110). Subsequently, many women with PCOS were found to have subtle acanthosis nigricans, a skin darkening often associated with insulin resistance. Women with chronic anovulation and hyperandrogenemia (111,112) without secondary causes were found to have glucose intolerance and elevated insulin levels (55). That PCOS is associated with insulin resistance and hyperglycemia following an oral glucose tolerance test (OGTT) was first demonstrated by Dunaif in 1987 (109). Forty percent of PCOS patients who are also obese have IGT or frank type 2 diabetes, and this remains consistent despite ethnic or geographic variation. Most of these PCOS patients are diagnosed in their third and fourth decades of life. PCOS-related insulin resistance accounts for 20-40% of IGT and type 2 diabetes in reproductive age women (113). The percentage of occurrence of IGT or diabetes is further increased by the presence of obesity or a family history of type 2 diabetes. Screening patients with PCOS, especially in the presence of other risk factors for IGT (Table 1), should clearly be done. Again, screening should include fasting glucose with the diagnosis of IGT confirmed by 2-h glucose after ingestion of 75 g glucola.

Treatment of PCOS, especially if fertility is desired, should probably consist of metformin (113-117) and possibly lifestyle changes in diet and exercise (118). Drugs that improve insulin sensitivity, such as metformin and the glitizones (rosiglitizone and pioglitazone), are thought to reverse not only the metabolic features of PCOS but also the excess ovarian steroidogenesis and gonadotropin stimulation (119). Treatment with metformin or a thiazolidinedione can often normalize menses and can result in conception in a previously infertile woman. Metformin inhibits glycogenolysis, decreasing hepatic glucose output and also improving peripheral insulin sensitivity. Metformin was first used for PCOS in 1994 by Velazquez et al. (120). Their study in 26 women with PCOS used metformin at 1500 mg/d for 8 wk. Not only did the women have significant improvement in hyperglycemia, but there was a 52% drop in testosterone levels and several spontaneous pregnancies. Subsequently, at least eight publications have shown the positive effects of metformin in decreasing androgen levels, improving metabolic profiles, and increasing fertility in PCOS (121).

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