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.
It has been reported that intake of (n-3) polyunsaturated fatty acids (PUFA) reduces the risk of coronary heart disease and decreases biliary cholesterol saturation in the bile of gallstone patients. We investigated the effect of n-3 PUFA on cholesterol saturation index (CSI) and nucleation time (NT) in obese subjects who were losing weight. This was a double-blind, placebo-controlled clinical trial. Obese women (n = 35) with a body mass index (BMI) > or = 30 kg/m(2), with no prior history of gallstones or cholecystectomy by ultrasound were first studied to ensure absence of stones or biliary sludge. The women were then assigned to a hypocaloric regimen [5.02 MJ (1200 kcal)/d] and to receive 1200 mg/d of ursodeoxycholic acid (UDCA), 11.3 g/d of (n-3) PUFA or a placebo for 6 wk. BMI, CSI and NT were recorded at baseline and at the end of the experimental period. BMI decreased 5.75 +/- 2.7%/mo (range, 1.5-12.42%/mo) during the experiment. The CSI did not change in any of the groups. Cholesterol NT decreased significantly in the UDCA and placebo groups, but not in the (n-3) PUFA group. None of the women had developed gallstones at 6 wk. These results suggest that (n-3) PUFA maintain the CSI and NT in obese women during rapid weight loss, which probably results in the prevention of cholesterol gallstone formation.
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