Objective: Polycystic ovary syndrome (PcOs) is characterized by obesity and insulin resistance (Ir), which result in elevated plasminogen activator inhibitor-1 (PAI-1) levels. We aimed to assess the changes in PAI-1 levels in PcOs during treatment with metformin and during weight loss. DEsIGN: twenty-three normal weight women with PcOs were given met-formin 850 mg bid for 6 months. Fifty overweight/obese women with PcOs were prescribed an energy-restricted diet, were instructed to exercise and were randomized to orlistat 120 mg tid or sibutramine 10 mg qd for 6 months. Results: In normal weight women, treatment with metformin reduced the body mass index (bMI) and circulating androgens, improved markers of Ir and lowered PAI-1 levels. In overweight/obese women, sibutramine and orlistat yielded comparable reductions in bMI and markers of Ir. In contrast, the effects on the free andro-gen index (FAI) differed (p=0.027): sibutramine reduced the FAI (p=0.005), whereas orlistat had no effect. the effects of sibutramine and orlistat on PAI-1 levels also differed (p=0.042): sibutramine reduced PAI-1 levels (p<0.001), whereas orlistat had no effect. cONcLUsIONs: Metformin and sibutramine, but not orlistat, reduce PAI-1 levels in PcOs. the reduction in circulating androgens during metformin and sibutramine treatment might be implicated in this decline.