The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome
The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome
复制标题
DOI：
10.1210/jc.81.9.3299
复制
发表时间：
1996-09-01
影响因子：
5.8
通讯作者：
Whitcomb, R
中科院分区：
文献类型：
--
作者：
Dunaif, A;Scott, D;Whitcomb, R
我们进行这项研究的目的是调查胰岛素抵抗在多囊卵巢综合征 (PCOS) 女性生殖异常的发病机制中发挥作用的假设。 25 名患有 PCOS 的女性参加了一项为期 3 个月的双盲随机试验，试验使用两种剂量的胰岛素增敏剂曲格列酮，其中 21 人完成了研究：200 毫克，n = 10； 400 mg，n = 11。将基线激素参数和葡萄糖耐量与 12 名年龄和体重匹配的排卵对照女性进行比较。研究期间体重指数没有显着变化。在曲格列酮治疗期间，空腹（P < 0.01）和 75 g 葡萄糖负荷后 2 小时胰岛素水平（P < 0.05）以及对葡萄糖负荷的综合胰岛素反应下降（P < 0.05），并且通过频繁采样的静脉内葡萄糖耐量试验评估的胰岛素敏感性显着增加（P < 0.001）。与此同时，非性激素结合球蛋白结合睾酮（P < 0.01）、硫酸脱氢表雄酮（P < 0.001）、雌二醇（P < 0.01）和雌酮（P < 0.001）水平显着下降。逐步回归分析表明，非性激素结合球蛋白睾酮水平的降低与胰岛素对葡萄糖负荷的综合反应的降低显着相关（r(2) 0.44，P < 0.01）。 200 mg曲格列酮剂量下唯一显着的变化是胰岛素敏感性增加（P < 0.05）以及硫酸脱氢表雄酮（P < 0.01）和雌酮（P < 0.05）水平降低。在 400 mg 剂量下，除了整个曲格列酮治疗组中注意到的变化外，处置指数（胰岛素敏感性和分泌的乘积）显着增加，雄烯二酮 (P < 0.01) 和 LH (P < 0.05) 水平降低，性激素结合球蛋白水平增加 (P < 0.01)。两名 PCOS 女性有排卵期月经。我们的结论是：1) 曲格列酮改善 PCOS 患者的全身胰岛素作用，导致循环胰岛素水平降低； 2) 胰岛素抵抗，可能通过高胰岛素血症，导致 PCOS 中类固醇生成和 LH 释放普遍增加； 3）胰岛素增敏剂，如曲格列酮，可能为多囊卵巢综合征提供一种新的治疗方法。
We performed this study to investigate the hypothesis that insulin resistance plays a role in the pathogenesis of reproductive abnormalities in women with the polycystic ovary syndrome (PCOS). Twenty-five women with PCOS were enrolled in a double-blind randomized 3-month trial of two doses of the insulin-sensitizing agent, troglitazone, 21 of whom completed the study: 200 mg, n = 10; 400 mg, n = 11. Baseline hormonal parameters and glucose tolerance were compared with 12 age- and weight-matched ovulatory control women. There were no significant changes in body mass index during the study. Fasting (P < 0.01) and 2-h post-75-g glucose load insulin levels (P < 0.05), as well as integrated insulin responses to the glucose load, decreased (P < 0.05), and insulin sensitivity assessed by a frequently sampled iv glucose tolerance test increased significantly (P < 0.001) during troglitazone treatment. This was accompanied by significant decreases in the levels of nonsex hormone-binding globulin-bound testosterone (P < 0.01), dehydroepiandrosterone sulfate (P < 0.001), estradiol (P < 0.01), and estrone (P < 0.001). Stepwise regression analysis indicated that decreases in nonsex hormone-binding globulin testosterone levels were significantly correlated with decreases in integrated insulin responses to the glucose load (r(2) 0.44, P < 0.01). The only significant changes at the 200-mg troglitazone dose were an increase in insulin sensitivity (P < 0.05) and decreases in dehydroepiandrosterone sulfate (P < 0.01) and estrone (P < 0.05) levels. At the 400-mg dose, in addition to the changes noted in the entire troglitazone treatment group, increases in the disposition index (the product of insulin sensitivity and secretion) achieved significance, as did decreases in androstenedione (P < 0.01) and LH (P < 0.05) levels and increases in sex hormone-binding globulin levels (P < 0.01). Two PCOS women had ovulatory menses.We conclude that 1) troglitazone improves total body insulin action in PCOS, resulting in lower circulating insulin levels; 2) insulin resistance, probably via hyperinsulinemia, results in a general augmentation of steroidogenesis and LH release in PCOS; and 3) insulin-sensitizing agents, such as troglitazone, may provide a novel therapy for PCOS.