Metformin effects on ovarian ultrasound appearance and steroidogenic function in normal-weight normoinsulinemic women with polycystic ovary syndrome: a randomized double-blind placebo-controlled clinical trial

Objective: To investigate metformin effects on the endocrine-metabolic parameters and ovarian morphology in normoinsulinemic women with polycystic ovary syndrome (PCOS). Design: Randomized double-blind study. Setting: Operative Division of Endocrinological Gynecology, Universita Cattolica del Sacro Cuore. Patient(s): Twenty-eight normal-weight normoinsulinemic PCOS women. Intervention(s): Patients were randomized to receive metformin 500 mg twice a day (group A, 15 subjects) or placebo (group B, 13 subjects) for 6 months. Ultrasonographic pelvic exams, hormonal and lipid features, and oral glucose tolerance test were performed at baseline and after 3 and 6 months of treatment. Main Outcome Measure(s): Hormonal and glycoinsulinemic assessment, ovarian ultrasound appearance. Result(s): Glycoinsulinemic assessment remained unvaried in both groups. About 70% of patients in group A experienced a restoration of menstrual cyclicity. Metformin significantly decreased testosterone levels at 3 and 6 months) and 17-hydroxyprogesterone levels at 6 months, and improved hirsutism score at 6 months. No clinical or hormonal modifications occurred in group B. Metformin, but not placebo, reduced ovarian volume and stromal/total area ratio at 3 and 6 months. Conclusion(s): Metformin seems to improve the menstrual pattern and ultrasonographic ovarian features in normoinsulinemic PCOS women. These effects seem to be, at least in part, independent of the insulin-lowering properties of the drug. (Fertil Steril (R) 2010; 93: 2303-10. (C) 2010 by American Society for Reproductive Medicine.)