In overweight women with polycystic ovary syndrome (PCOS), increased insulin resistance has been observed. Since abdominal obesity is associated with impaired fibrinolytic capacity and elevated levels of plasminogen activator inhibitor (PAI-1) and since PAI-1 seems to be related to insulin resistance, we investigated the possible effects of dietary intervention on lipids, fibrinolysis, coagulation, and insulin sensitivity in obese PCOS women. Nine women aged 22 to 39 years (median weight, 97 kg) ate a protein-rich very-low-calorie diet (VLCD) (Nutrilett, Nycomed Pharma, Oslo, Norway; 421 kcal/d) for 4 weeks (part 1). After significant reductions of body fat (13%, P < .01), two of nine women achieved regular menstruation and became pregnant. Six of the remaining women continued on a conventional low-calorie diet (1,000 to 1,500 kcal/d) for the next 20 weeks (part 2), during which time they were generally able to preserve the body fat loss obtained in part 1 of the study. During part 1, significant reductions of total serum cholesterol (29%, P = .001) and fasting triglyceride ([TG] 31%, P < .05) levels were observed, as well as significant reductions of fasting glucose (6%, P < .05) and insulin (20%, P < .05). Insulin sensitivity (glucose disposal rate [GDR]) was increased by 93% (P < .05). After finishing part 2, insulin sensitivity was still significantly increased (86%, P < .05) and PAI-1 activity was significantly reduced (54%, P < .05). Moreover, overall fibrinolytic activity was significantly improved (serum D-dimer concentration increased by 75%, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)