Previous studies have suggested that metformin is clinically useful in the treatment of polycystic ovary syndrome (PCOS). The aim of this study was to evaluate whether the improvement of ovarian function achieved by metformin therapy is associated with changes in leptin concentrations. Twenty-six obese women with PCOS were treated with 500 mg metformin, x 3 daily, for 2 months; and 12 women continued the therapy for 4-6 months. A significant decrease in the serum leptin level was observed after 2 months of treatment in the whole study group (29.2 +/- 12.7 ng/mL vs. 25.7 +/- 10.9 ng/mL, P = 0.03). In the 12 women treated for 4-6 months, the mean serum leptin concentration decreased after 2 months (38.6 +/- 9.3 ng/mL vs. 30.2 +/- 8.1 ng/mL; P = 0.004) but slightly increased after 4-6 months of treatment (33.4 +/- 15.7 ng/mL; not significant). These results indicate that insulin sensitizing therapy with metformin decreases the leptin concentrations in obese PCOS women.