Insulin resistance is a common feature of polycystic ovary syndrome (PCOS) regardless of whether patients are obese. There is evidence that the associated hyperinsulinemia contributes to development of the condition, suggesting that insulin-sensitizing drugs, such as metformin, might have therapeutic value. Reduced serum androgen levels have been reported in women with PCOS who were given metformin. The present randomized, double-blind, placebo-controlled study evaluated a 6-month course of metformin in 23 women aged 18 to 35 years with PCOS but normal glucose tolerance. A large majority were overweight. Women were assigned to receive either placebo capsules or metformin in a daily dose of 500 mg the first week, 1000 mg the second, and 1500 mg (three 500-mg capsules) for the next 24 weeks. Eighteen of these women and 14 others then participated in an open trial of metformin, the dose being increased stepwise as in the double-blind phase. Insulin sensitivity was estimated by the euglycemic hyperinsulinemic glucose clamp technique.
Serum levels of free testosterone declined significantly with metformin treatment in the double-blind study. Both groups had a slight fall in body mass index, and there was no substantial change in hirsutism scores. Only one patient required dose reduction because of an adverse reaction. Menstruation was significantly more frequent during metformin therapy. Treatment correlated with a lower serum 17-hydroxyprogesterone response to buserelin. Fasting plasma insulin levels decreased, and serum high-density lipoprotein cholesterol rose significantly. Insulin levels declined in women given metformin but remained unchanged in women given a placebo. In the open study, 40 percent of women had some discomfort. Menstrual bleeding became totally regular in 13 of 32 subjects and improved markedly in 4 others, and most cycles in these women became ovulatory. Regression analysis showed that responders tended to be women with lower serum androstenedione levels, higher plasma insulin levels, and less marked menstrual abnormalities. The insulin-sensitizing drug metformin brings substantial improvement in menstrual function and other aspects of PCOS, apart from changes in body weight, to many affected women.
J Clin Endocrinol Metab 2000;85:139–146