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Metabolic and Hormonal Changes Induced by Pioglitazone in Polycystic Ovary Syndrome: A Randomized, Placebo-Controlled Clinical Trial

Veterans Affairs San Diego Healthcare System (V.R.A., T.P.C., P.B., P.C., S.P., S.M., R.R.H.), San Diego, California 92161; Department of Medicine (V.R.A., T.P.C., S.P., S.M., R.R.H.), University of California, San Diego, La Jolla, California 92093; MedStar Research Institute (V.R.A.), Washington, D.C. 20003; and Department of Reproductive Medicine (R.J.C.), University of California, San Diego, La Jolla, California 92093

Address all correspondence and requests for reprints to: Vanita R. Aroda, M.D., MedStar Research Institute, 650 Pennsylvania Avenue #50, Washington, D.C. 20003. E-mail: vanita.aroda{at}medstar.net.

Context: Polycystic ovary syndrome (PCOS) is characterized by insulin resistance, compensatory hyperinsulinemia, increased prevalence of impaired glucose tolerance, and increased ovarian androgen biosynthesis.

Objective: The aim of the study was to evaluate effects of pioglitazone on whole body insulin action and ovarian androgen biosynthesis in PCOS.

Design: We performed a randomized placebo-controlled trial.

Setting: The study was conducted at the Special Diagnostic and Treatment Unit of the Veterans Affairs Medical Center, San Diego, and the University of California, San Diego, General Clinical Research Center.

Patients or Other Participants: A total of 23 subjects with PCOS were evaluated at baseline and end of treatment. Six age- and body mass index-matched women without PCOS were normal controls for baseline evaluation.

Intervention: Subjects with PCOS were randomized to oral placebo or pioglitazone 45 mg daily for 6 months.

Main Outcome Measure(s): The primary outcome measures were whole body insulin action as measured by hyperinsulinemic euglycemic clamp and ovarian androgen biosynthesis as measured by leuprolide-stimulated production of 17-hydroxyprogesterone (17-OHP).

Results: Compared with placebo, pioglitazone treatment significantly improved multiple measures of insulin action, including glucose disposal rate (P < 0.01), 2-h glucose during 75-g oral glucose tolerance test (P < 0.01), area under the curve glucose during oral glucose tolerance test (P < 0.01), serum adiponectin (P < 0.01), and fasting hyperinsulinemia (P < 0.01). Compared to placebo, pioglitazone treatment reduced the increment of leuprolide-stimulated 17-OHP (P < 0.02). Improvements in glucose disposal rate correlated with reductions in 17-OHP stimulation (P < 0.02).

Conclusions: Compared to placebo, pioglitazone treatment in PCOS was associated with improvements in insulin action and glucose homeostasis and ameliorated the hyperandrogenic ovarian response.