Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity.

摘要

The goal of this randomized, controlled, double-blind trial was to learn whether insulin-sensitizing drugs can improve ovulation frequency and serum-free testosterone (T) in nonobese women with polycystic ovary syndrome (PCOS) whose insulin sensitivity was normal. The 100 women enrolled in the study, 17 to 40 years of age, had normal glucose tolerance, fasting insulin, and peak insulin levels during oral glucose tolerance testing (OGTT). The fasting glucose-to-insulin ratio also was normal. Criteria for PCOS were 8 or fewer menstrual periods in the past year and a serum total T exceeding 70 ng/dL. Participants received 850 mg metformin, 4 mg rosiglitazone, a combination of both treatments, or at least 1 placebo twice a day for 6 months. Treatment began when the women were in the equivalent of the follicular phase of the cycle.Only women given rosiglitazone gained significant body weight (1.1 kg), and the posttreatment body mass index was significantly greater in this group. All actively treated women had a significant decline in their waist-to-hip ratio. Systolic blood pressure fell significantly in all actively treated groups but not in placebo recipients. Diastolic pressure decreased and was similar in all groups at the end of the study. Ovulatory cycles were 6- to 8-fold more frequent with treatment and were highest in women given metformin or combination therapy. Ovulation rates at 6 months were markedly increased except in the placebo group. Menstrual bleeding also was greater in treated women. Combination treatment did not yield additive results for either ovulation or menstrual bleeding. Serum total and free T levels decreased significantly with active treatment. Compared with placebo, fasting insulin levels, the area under the insulin curve during an OGTT, and the OGTT-based insulin sensitivity index improved significantly after metformin or combination therapy, but not after rosiglitazone.The investigators concluded that insulin-sensitizing drugs are effective in nonobese women with PCOS even if baseline insulin sensitivity is normal.