Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity
Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity
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DOI：
10.1016/j.fertnstert.2004.02.127
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发表时间：
2004-10-01
影响因子：
6.7
通讯作者：
Nestler, JE
中科院分区：
文献类型：
--
作者：
Baillargeon, JP;Jakubowicz, DJ;Nestler, JE
目的：探讨胰岛素增敏药物是否能改善无胰岛素抵抗临床或生化指标的多囊卵巢综合征(PCOS)患者的排卵和T水平，以及两种不同的胰岛素增敏药物联合用药是否比单独用药有任何益处。设计：随机对照双盲试验。地点：委内瑞拉加拉加斯的一家转诊中心。患者(S)：128名胰岛素敏感指数正常的非肥胖PCOS妇女，即正常糖耐量、空腹、口服葡萄糖耐量试验胰岛素峰值和空腹葡萄糖/胰岛素比值。干预(S)：100名女性在6个月内每天接受两次治疗：二甲双胍(850 Mg)、罗格列酮(4 Mg)、两种药物联合使用或至少一种安慰剂。主要观察指标(S)：6个月后排卵频率和血清游离T水平。结果(S)：胰岛素增敏药物治疗后排卵频率(每个受试者6个月内排卵量：二甲双胍3.3；罗格列酮2.4；联合使用3.4)高于安慰剂(0.4)。与罗格列酮相比，二甲双胍显著增加排卵频率，而且两者的联合作用并不更强。治疗后，各主动治疗组(二甲双胍：2.34pg/mL，罗格列酮：3.06pg/mL，联合用药：2.39pg/mL)的血清游离T水平接近，明显低于安慰剂组(7.26pg/mL)。与安慰剂相比，服用二甲双胍或联合用药后，空腹胰岛素水平、OGTT中胰岛素曲线下面积、胰岛素敏感性的稳态模型评估和OGTT衍生的胰岛素敏感指数显著改善，但罗格列酮治疗后改善不明显。结论：这些发现提示胰岛素增敏药物增加排卵频率和改善高雄激素血症，即使在胰岛素敏感性正常的非肥胖PCOS女性中也是如此。(C)2004年，由美国生殖医学会提供。
Objective: To determine whether insulin-sensitizing drugs would improve ovulation and T levels in women with polycystic ovary syndrome (PCOS), without clinical or biochemical criteria indicating insulin resistance and whether the combination of two distinct insulin-sensitizing drugs would be of any benefit over either drug alone.Design: Randomized controlled double-blind trial.Setting: A referral center in Caracas, Venezuela.Patient(s): One hundred twenty-eight nonobese PCOS women with normal indices of insulin sensitivity-that is, normal glucose tolerance, fasting insulin, peak insulin during an oral glucose tolerance test (OGTT), and fasting glucose-to-insulin ratio. Twenty-eight women were lost to follow-up initially and did not receive any intervention.Intervention(s): One hundred women received twice daily one of the following for 6 months: metformin (850 mg), rosiglitazone (4 mg), combination of both drugs, or at least one placebo.Main Outcome Measure(s): Frequencies of ovulation and serum free T after 6 months.Result(s): Frequencies of ovulation were higher after treatment with an insulin-sensitizing drug (ovulations per subject in 6 months: metformin, 3.3; rosiglitazone, 2.4; and combination, 3.4) than with placebo (0.4). Ovulatory frequencies increased significantly more with metformin than rosiglitazone, and the combination was not more potent. After treatment, serum free-T levels were comparable among all active treatment groups (metformin: 2.34 pg/mL, rosiglitazone: 3.06 pg/mL, and combination: 2.39 pg/mL) and were significantly lower than in the placebo group (7.26 pg/mL). Compared with placebo, fasting insulin levels, area under the insulin curve during OGTT, the homeostatic model assessment of insulin sensitivity, and OGTT-derived insulin sensitivity index improved significantly after metformin or combination therapies but not after rosiglitazone.Conclusion(s): These findings suggest that insulin-sensitizing drugs increase ovulatory frequency and ameliorate hyperandrogenemia, even in nonobese women with PCOS who appear to have normal insulin sensitivity. (C) 2004 by American Society for Reproductive Medicine.