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Effect of the Insulin Sensitizer Pioglitazone on Insulin Resistance, Hyperandrogenism, and Ovulatory Dysfunction in Women with Polycystic Ovary Syndrome

Division of Gynecological Endocrinology and Reproductive Medicine, University Women’s Hospital Basel (N.B., C.D.G.); and Department of Central Laboratories (P.R.H.) and Division of Endocrinology, Diabetes, and Clinical Nutrition (U.K.), University Hospital Basel, CH-4031 Basel, Switzerland

Address all correspondence and requests for reprints to: Dr. Christian De Geyter, University Women’s Hospital Basel, Spitalstrasse 21, CH-4031 Basel, Switzerland. E-mail: cdegeyter{at}uhbs.ch.

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.

This work was supported in part by a grant from the Medical Faculty of University of Basel and in part by an unrestricted educational grant from Takeda Pharma, Switzerland. N.B. was supported by a scholarship from the Schweizerische Eidgenössische Stipendienkommission.

Abbreviations: BMI, Body mass index; oGTT, oral glucose tolerance test; PCOS, polycystic ovary syndrome.

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