Responses of serum androgen and insulin resistance to metformin and pioglitazone in obese, insulin-resistant women with polycystic ovary syndrome.

Severe insulin resistance is a key abnormality in obese women with polycystic ovary syndrome (PCOS). The purpose of this study was to evaluate whether pioglitazone decreases insulin resistance (IR) and hyperandrogenism to the same extent as metformin in obese women with PCOS who have not received any previous treatment. Fifty-two women with PCOS were randomly allocated to receive either pioglitazone (30 mg/d, n = 25) or metformin (850 mg three times daily, n = 27) and were assessed before and after 6 months. Body weight, body mass index, and waist to hip ratio increased significantly (P </= 0.05) after pioglitazone treatment but not after metformin treatment. Fasting serum insulin concentration (P < 0.001 for both drugs) and the area under the insulin curve during a 2-h oral glucose tolerance test decreased after pioglitazone (P < 0.002) or metformin (P < 0.05) treatment. IR (homeostasis model of assessment-IR index) decreased and insulin sensitivity (elevation of the quantitative insulin sensitivity check index and the fasting glucose to insulin ratio) increased (P </= 0.008) after treatment with either drug. Hirsutism (P < 0.05) and serum concentrations of free testosterone (P < 0.02) and androstenedione (P < 0.01) declined to a similar extent after treatment with the drugs. Treatment with pioglitazone or metformin was associated with the occurrence of pregnancy (n = 5 and n = 3, respectively). These results suggest that pioglitazone is as effective as metformin in improving insulin sensitivity and hyperandrogenism, despite an increase in body weight, body mass index, and the waist to hip ratio associated with pioglitazone.