Effect of the insulin sensitizer pioglitazone on insulin resistance, hyperandrogenism, and ovulatory dysfunction in women with polycystic ovary syndrome

Polycystic ovary syndrome ( PCOS) is characterized by hyperandrogenism, chronic anovulation, and insulin resistance; long-term consequences include diabetes mellitus type 2. The aim of this randomized, double-blind, controlled trial was to investigate whether the thiazolidinedione derivative pioglitazone diminishes insulin resistance and hyperandrogenism and enhances ovulation rates in women with PCOS. Forty premenopausal women with PCOS were randomly allocated to treatment with either pioglitazone (30 mg/d) or placebo for periods of 3 months. Administration of pioglitazone resulted in a remarkable decline in both fasting serum insulin levels (P < 0.02) and the area under the insulin response curve after an oral glucose load ( P < 0.02). This represented an increase in insulin sensitivity and a decrease in insulin secretion ( P < 0.05). Furthermore, pioglitazone increased serum SHBG ( P < 0.05), resulting in a significant decrease in the free androgen index ( P < 0.05 compared with placebo). Treatment with pioglitazone was also associated with higher ovulation rates (P < 0.02). Thus, pioglitazone significantly improved insulin sensitivity, hyperandrogenism, and ovulation rates in women with PCOS, thereby providing both metabolic and reproductive benefits.