Treatment with flutamide, metformin, and their combination added to a hypocaloric diet in overweight-obese women with polycystic ovary syndrome: A randomized, 12-month, placebo-controlled study
Treatment with flutamide, metformin, and their combination added to a hypocaloric diet in overweight-obese women with polycystic ovary syndrome: A randomized, 12-month, placebo-controlled study
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DOI：
10.1210/jc.2005-2250
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发表时间：
2006-10-01
影响因子：
5.8
通讯作者：
Pasquali, Renato
中科院分区：
文献类型：
--
作者：
Gambineri, Alessandra;Patton, Laura;Pasquali, Renato
内容：迄今为止进行的少数对照试验表明，在多囊卵巢综合征（PCOS）肥胖女性的低热量饮食中添加二甲双胍和/或氟替卡松可有效影响该综合征的不同表型。然而，所有这些研究的特点都是短期到中期的治疗。目的：我们的目的是调查这些疗法的长期效果。设计和设置：我们在一个医疗中心进行了一项前瞻性、随机、安慰剂对照试验。患者：80名超重肥胖的PCOS妇女中，76名完成了这项研究。干预措施：患者在第一个月接受低热量饮食，然后接受低热量饮食加安慰剂二甲双胍。（850 mg，口服，每日两次），氟替卡松（250 mg，口服，每日两次），或二甲双胍加氟替卡松，持续12个月（每组20名受试者）。主要结果测量：我们评估了临床特征，计算机断层扫描测量脂肪分布，雄激素，血脂，以及基线和治疗6个月和12个月后的空腹和葡萄糖刺激的葡萄糖和胰岛素水平。6个月后，与安慰剂相比，氟替卡松进一步降低了内脏/皮下脂肪量（P = 0.044），雄烯二酮（P < 0.001），硫酸脱氢表雄酮（P < 0.001）和多毛评分（P < 0.001），而二甲双胍进一步增加月经频率（P = 0.039）。12个月后，氟替卡松维持了6个月后观察到的对内脏/皮下脂肪量（P = 0.033）和雄烯二酮（P < 0.001）的影响，而硫酸脱氢表雄酮（P = 0.020）和多毛症评分（P = 0.019）额外降低;二甲双胍进一步改善了月经模式（P = 0.013）。此外，12个月后，氟替卡松改善月经模式（P = 0.008），葡萄糖刺激的葡萄糖水平（P = 0.041），胰岛素敏感性（P < 0.001）和低密度脂蛋白胆固醇水平（P = 0.003），而二甲双胍降低葡萄糖刺激的胰岛素水平（P = 0.014）。这两种药物的组合保持了每种化合物的特定效果，没有任何添加剂或协同效应。结论：这些研究结果增加了二甲双胍和氟西汀在治疗节食超重肥胖PCOS妇女的有用性，并提供了一个理由，针对不同的治疗方案，根据所需的结果在长期。
Context: The few controlled trials performed so far indicate that the addition of metformin and/or flutamide to a hypocaloric diet in obese women with polycystic ovary syndrome ( PCOS) effectively influences different phenotypic aspects of the syndrome. All these studies are, however, characterized by a short to medium period of treatment.Objective: Our objective was to investigate the long-term effects of these therapies.Design and Setting: We conducted a prospective, randomized, placebo-controlled trial at a medical center.Patients: Of 80 overweight-obese women with PCOS, 76 completed the study.Interventions: Patients were placed on a hypocaloric diet for the first month and then on a hypocaloric diet plus placebo, metformin ( 850 mg, orally, twice a day), flutamide ( 250 mg, orally, twice a day), or metformin plus flutamide for the subsequent 12 months ( 20 subjects in each group).Main Outcome Measures: We assessed clinical features, computerized tomography measurement of fat distribution, androgens, lipids, and fasting and glucose-stimulated glucose and insulin levels at baseline and after 6 and 12 months of treatment.Results: After 6 months, compared with placebo, flutamide further decreased visceral/sc fat mass ( P = 0.044), androstenedione ( P < 0.001), dehydroepiandrosterone sulfate ( P < 0.001), and hirsutism score ( P < 0.001), whereas metformin further increased frequency of menstruation ( P = 0.039). After 12 months, flutamide maintained the effects observed after 6 months on visceral/sc fat mass ( P = 0.033) and androstenedione ( P < 0.001), whereas it produced an additional decrease in dehydroepiandrosterone sulfate ( P = 0.020) and hirsutism score ( P = 0.019); metformin further improved the menstrual pattern ( P = 0.013). Moreover, after 12 months, flutamide improved more than placebo the menstrual pattern ( P = 0.008), glucose-stimulated glucose levels ( P = 0.041), insulin sensitivity ( P < 0.001), and low-density lipoprotein cholesterol levels ( P = 0.003), whereas metformin decreased glucose-stimulated insulin levels ( P = 0.014). The combination of the two drugs maintained the specific effect of each of the compounds, without any additive or synergistic effect.Conclusions: These findings add relevance to the usefulness of metformin and flutamide in the treatment of dieting overweight-obese PCOS women and provide a rationale for targeting different therapeutic options according to the required outcomes in the long term.