Randomized placebo-controlled trial of metformin for adolescents with polycystic ovary syndrome.

To determine whether metformin or placebo could, in conjunction with healthy lifestyle counseling, decrease serum testosterone levels and related aberrations in adolescents with hyperandrogenism, hyperinsulinemia, and polycystic ovarian syndrome. Randomized, placebo-controlled, double-blind trial. Pediatric university teaching hospital. Twenty-two adolescents aged 13 to 18 years with hyperinsulinemia and polycystic ovarian syndrome. Participants were randomly assigned to take a 12-week course of either metformin or placebo. Pretreatment and posttreatment oral glucose tolerance tests, fasting lipid profiles, and clinical measurements. There was a significant decline in mean serum testosterone concentration with metformin (-38.3 ng/dL) compared with placebo (-0.86 ng/dL) (95% confidence interval, -infinity to -0.29 for the mean difference between groups). At completion, the relative risk of menses was 2.50 times higher in the metformin group compared with the placebo (95% confidence interval, 1.12 to 5.58). Measures of insulin sensitivity, including insulin area under the curve and HOMA (homeostasis model assessment), demonstrated improvement only with metformin, but these did not reach statistical significance. High-density lipoprotein cholesterol levels increased by 6.98 mg/dL with metformin vs a decrease of -2.33 mg/dL with placebo (95% confidence interval, 0.78 to 18.23 for the mean difference between groups). There were no significant changes in body mass index, hirsutism, triglyceride levels, or total and low-density lipoprotein cholesterol levels. Metformin significantly lowered total testosterone concentrations, increased the likelihood of menses, and improved high-density lipoprotein cholesterol levels without affecting measures of insulin sensitivity or body weight.