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

Objective: To 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. Design: Randomized, blinded, placebo-controlled study. Setting: Outpatient 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.