Glueck Charles J, Moreira Andrew, Goldenberg Naila, Sieve Luann, Wang Ping
Cholesterol Center, Jewish Hospital, ABC Building, 3200 Burnet Avenue, Cincinnati, OH 45229, USA.
Hum Reprod. 2003 Aug;18(8):1618-25. doi: 10.1093/humrep/deg343.
In an observational study of 13 women with polycystic ovary syndrome (PCOS) not optimally responsive to metformin diet, we assessed the efficacy and safety of addition of pioglitazone. We also compared these 13 women to 26 women with PCOS, who were responsive to metformin diet, matched by age and by pre- treatment menstrual history and not different by obesity categories.
Prospectively, as outpatients, with diet constant [1500-2000 calorie (depending on entry body mass index), 26% protein, 44% carbohydrate, 30% fat], metformin (2.55 g/day) was given for 12 months to 39 women, 13 not optimally responsive, 26 responsive to metformin diet, followed by addition of pioglitazone (45 mg/day) for 10 months in the 13 non-responders. Outcome measures included changes in sex hormones, insulin, insulin resistance (IR), insulin secretion, high density lipoprotein cholesterol, weight, and menstrual status.
In 13 non-responders, on metformin diet, median serum insulin fell (21 to 16 microIU/ml, P<0.05) and insulin secretion fell from 251 to 200 (P<0.01); weight, dehydroepiandrosterone sulphate (DHEAS), testosterone and IR were unchanged (P> or =0.07). Compared with 14% pre- treatment, on metformin diet, expected menses occurred 46% of the time at 3 months (P=0.05), 38% at 6 months (P=0.07), 27% at 9 months, and 24% at 12 months. In 26 responders, on metformin diet, median weight fell (93 to 87 kg), testosterone fell (50 to 32 ng/dl), insulin fell (26 to 16 microIU/ml), IR fell (5.32 to 3.45) and insulin secretion fell (351 to 271) (P< or =0.017 for all). The occurrence of expected menses in the 26 responders was 2.5-fold higher than in the 13 non-responders (P<0.0001). In 11 non-responders, on pioglitazone + metformin diet over 10 months versus antecedent metformin diet, DHEAS fell (211 to 171 microg/dl, P=0.02), insulin fell (16 to 10 microIU/ml, P= 0.001), IR fell (3.37 to 1.73, P=0.002), insulin secretion fell (217 to 124, P=0.004), sex hormone-binding globulin rose (31 to 43 nmol/l, P=0.006), and HDL cholesterol rose (38 to 42 mg/dl, P=0.003). On pioglitazone + metformin diet, the occurrence of expected menses was 2-fold higher than on metformin diet (P<0.0001).
In women with PCOS who failed to respond optimally to metformin, when pioglitazone was added, insulin, glucose, IR, insulin secretion, and DHEAS fell, HDL cholesterol and sex hormone-binding globulin rose, and menstrual regularity improved, without adverse side-effects.
在一项针对13名对二甲双胍饮食反应欠佳的多囊卵巢综合征（PCOS）女性的观察性研究中，我们评估了添加吡格列酮的疗效和安全性。我们还将这13名女性与26名对二甲双胍饮食有反应的PCOS女性进行了比较，这26名女性在年龄、治疗前月经史方面相匹配，且在肥胖类别上无差异。
前瞻性地，作为门诊患者，保持饮食恒定[1500 - 2000卡路里（取决于入院时的体重指数），26%蛋白质，44%碳水化合物，30%脂肪]，39名女性服用二甲双胍（2.55克/天）12个月，其中13名反应欠佳，26名对二甲双胍饮食有反应，随后13名无反应者添加吡格列酮（45毫克/天）服用10个月。观察指标包括性激素、胰岛素、胰岛素抵抗（IR）、胰岛素分泌、高密度脂蛋白胆固醇、体重和月经状况的变化。
在13名无反应者中，服用二甲双胍饮食时，血清胰岛素中位数下降（从21降至16微国际单位/毫升，P<0.05），胰岛素分泌从251降至200（P<0.01）；体重、硫酸脱氢表雄酮（DHEAS）、睾酮和IR无变化（P≥0.07）。与治疗前的14%相比，服用二甲双胍饮食时，预期月经在3个月时出现的时间为46%（P = 0.05），6个月时为38%（P = 0.07），9个月时为27%，12个月时为24%。在26名有反应者中，服用二甲双胍饮食时，体重中位数下降（从93降至87千克），睾酮下降（从50降至32纳克/分升），胰岛素下降（从26降至16微国际单位/毫升），IR下降（从5.32降至3.45），胰岛素分泌下降（从351降至271）（所有P≤0.017）。26名有反应者中预期月经的发生率比13名无反应者高2.5倍（P<0.0001）。在11名无反应者中，与之前的二甲双胍饮食相比，服用吡格列酮+二甲双胍饮食10个月后，DHEAS下降（从211降至171微克/分升，P = 0.02），胰岛素下降（从16降至10微国际单位/毫升，P = 0.001），IR下降（从3.37降至1.73，P = 0.002），胰岛素分泌下降（从217降至124，P = 0.004），性激素结合球蛋白升高（从31升至43纳摩尔/升，P = 0.006）以及高密度脂蛋白胆固醇升高（从38升至42毫克/分升，P = 0.003）。服用吡格列酮+二甲双胍饮食时，预期月经的发生率比服用二甲双胍饮食时高2倍（P<0.0001）。
在对二甲双胍反应欠佳的PCOS女性中，添加吡格列酮后，胰岛素、血糖、IR、胰岛素分泌和DHEAS下降，高密度脂蛋白胆固醇和性激素结合球蛋白升高，月经规律性改善，且无不良副作用。
