Therapeutic effects of metformin on insulin resistance and hyperandrogenism in polycystic ovary syndrome

Abstract

Evidence suggests that insulin resistance and hyperinsulinaemia are associated with ovarian hyperandrogenism and menstrual irregularities in polycystic ovary syndrome (PCOS). Sixteen obese women with PCOS on a weight-maintaining diet were studied before and after 6 months of therapy with the insulin-sensitizing antidiabetic agent metformin at a dose of 1700 mg per day. Compared with baseline values, glucose utilization was markedly enhanced at 6 months using the two-step euglycaemic-hyperinsulinaemic clamp to measure changes in insulin sensitivity (2.56 +/- 0.32 vs 4.68 +/- 0.49 mg/kg per min, P = 0.0001, when 40 mU insulin/m2 per min was infused, and 6.48 +/- 0.58 vs 9.84 +/- 0.72 mg/kg per min, P = 0.0002, when 400 mU insulin insulin/m2 per min was infused). The improvement in insulin action was accompanied by significant increases in the levels of sex hormone-binding globulin (24.5 +/- 7.2 vs 39.8 +/- 16.2 nmol/l, P = 0.003) and decreases in free testosterone (12.8 +/- 5.8 vs 9.0 +/- 3.0 pmol/l, P = 0.03) and androstenedione (12.9 +/- 5.6 vs 7.3 +/- 1.7 nmol/l, P = 0.003). No significant changes were recorded in body weight. Seven subjects resumed normal menstruation and two cases of spontaneous pregnancy occurred during treatment. Metformin was well tolerated except for one case of flatulence. These results confirm that metformin treatment can lead to improvements in insulin resistance and ovarian hyperandrogenism.