Objective: To determine the clinical, hormonal, and biochemical effects of metformin therapy in obese and nonobese patients with polycystic ovary syndrome (PCOS). Design: Controlled clinical study. Setting: Department of Gynecology of Federal University of Sao Paulo, Sao Paulo, Brazil. Patient(s): Twenty-nine patients with PCOS. Intervention(s): Patients were treated with 500 mg of p.o. metformin t.i.d. for 6 months. Main Outcome Measure(s): Clinical data as well as serum concentrations of sex steroids, sex hormone-binding globulin (SHBG), gonadotropins, leptin, GH, lipids, insulin, and glucose levels were assessed before and after treatment. Result(s): In the metformin group of nonobese patients, the mean fasting serum insulin concentration decreased from a pretreatment value of 12.1 +/- 2.4 to 6.3 +/- 0.6 muU/mL after treatment, and the area under the curve of insulin decreased from 5,189.1 +/- 517.4 to 3,035.6 +/- 208.9 muU/mL per minute. Also in the metformin group of nonobese patients, the mean basal serum total testosterone, free testosterone, and androstenedione concentrations decreased by 38%, 58%, and 30%, respectively. In the obese patients treated with metformin, only free testosterone showed a statistically significant decrease (1.7 +/- 0.2). Conclusion(s): Our data suggest that nonobese patients respond better than obese patients to a 1.5 g/day metformin regimen. (C)2004 by American Society for Reproductive Medicine.