Effect of pioglitazone on glucose metabolism and luteinizing hormone secretion in women with polycystic ovary syndrome

ObjectiveTo thoroughly examine the mechanisms for insulin resistance in polycystic ovary syndrome (PCOS) and to evaluate the effects of pioglitazone treatment on insulin resistance, β-cell function, LH secretion, and glucose metabolism.DesignRandomized, blinded, placebo-controlled study.SettingOutpatient clinic, at a university hospital in Denmark.Patient(s)Thirty obese women with PCOS and 14 weight-matched healthy females.Intervention(s)Sixteen weeks of blinded treatment with pioglitazone (30 mg/d) or placebo.Main Outcome Measure(s)Fasting blood samples, 24-hour 20-minute integrated blood sampling (LH, insulin, and C-peptide), euglycemic hyperinsulinemic clamps including 3-3H glucose, and indirect calorimetry were performed before and after the intervention period.Result(s)Patients with PCOS had significantly lower insulin sensitivity compared with controls, including significantly decreased insulin-stimulated oxidative and nonoxidative glucose metabolism. Pioglitazone treatment resulted in significantly lower levels of fasting insulin and significantly higher insulin sensitivity, increased insulin-stimulated glucose oxidation, and increased insulin-stimulated inhibition of lipid oxidation. During 24-hour blood sampling, significantly lower area under-the-curve insulin and lower median insulin levels were observed. Secretion profiles of LH and E2 and T levels did not change significantly.Conclusion(s)Insulin resistance in PCOS was characterized by hyperinsulinemia, impaired insulin-stimulated oxidative and nonoxidative glucose metabolism, which was partly reversed by pioglitazone treatment.