Metformin therapy decreases hyperandrogenism and hyperinsulinemia in women with polycystic ovary syndrome

Objective: To evaluate the effects of 12 weeks of metformin therapy on hormonal and clinical indices in polycystic ovary syndrome (PCOS). Design: Prospective study. Setting: University hospital. Patient(s): Thirty-nine women with PCOS and fasting hyperinsulinemia. Intervention(s): Twelve weeks of therapy with oral metformin (500 mg three times per day). Main Outcome Measure(s): Levels of insulin, T, DHEAS, insulin-like growth factor-I (IGF-I), gonadotropins, and sex hormone-binding,globulin (SHBG); and clinical symptoms including acne, hirsutism, and length of the menstrual cycle were assessed before and after treatment with metformin. Result(s): Metformin therapy resulted in a significant decrease in fasting insulin and total T and an increase in SHBG, leading to a decrease in the free T index. In addition, there was a significant decline in mean body mass index, waist-hip ratio, hirsutism, and acne, as well as an improvement in the menstrual cycle. No changes in LH and LH-FSH ratio were observed. Multiple regression analysis demonstrated that the greatest decline of T and free T index in response to metformin was observed among patients with the most pronounced hyperandrogenemia. Subjects with elevated DHEAS differed from those with normal DHEAS in their responses to metformin treatment. Women with high DHEAS exhibited less improvement of menstrual cycle regularity, no change in hirsutism, and an increase in levels of IGF-I after treatment. Conclusion(s): Metformin treatment of women with PCOS results in a decline of insulin as well as total and bioavailable T, leading to significant improvement of clinical manifestations of hyperandrogenism. Responses to metformin are related to the severity of hyperandrogenemia and to adrenal function. (C) 2000 by American Society for Reproductive Medicine.