INSULIN AND OVARIAN/METABOLIC RESPONSES IN PCOS

多囊卵巢综合征（PCOS）是一种严重的健康问题， 影响了大约6%的育龄妇女。PCOS是 以男性生殖过多和无排卵为特征，是主要原因 美国女性不孕症的最高纪录有证据表明胰岛素 抵抗伴随代偿性高胰岛素血症是常见的 PCOS的特点，高胰岛素血症是部分原因， 雄激素过多症然而，临床研究没有 评估了高胰岛素血症在促进慢性 PCOS的无排卵，他们也没有检查是否改善胰岛素 选择性改变了PCOS相关的发病率， 胰岛素抵抗和/或高胰岛素血症，如葡萄糖耐受不良， 高血压、血脂异常和动脉粥样硬化。因此，我们建议：（1） 评估长期（12个月）胰岛素减少对 激素、代谢（葡萄糖耐量、血压、脂质、派-1、tPA 抗原）和排卵概况的妇女与PCOS，以及时间 过程中的任何变化，2）以确定是否改善 克罗米芬抵抗的PCOS妇女的胰岛素敏感性增加， 自发和/或氯米芬诱导排卵率，以及3）至 确定高胰岛素血症是否改变24小时前后 给予克罗米酚加安慰剂或二甲双胍）。如果我们的研究 证实了高胰岛素血症在PCOS发病机制中的重要作用， 它们具有重大的实际意义。 也就是说，他们将提供 有令人信服的证据表明， PCOS应进行测量，旨在改善胰岛素敏感性， 降低血清胰岛素--包括使用“胰岛素增敏剂”。 此外，他们会建议，在那些没有达到标准的妇女中， 促排卵措施，相对便宜，非侵入性 “胰岛素增敏”技术应在 启动昂贵和更复杂的技术。最后我们 研究结果将揭示胰岛素增敏是否有益于 PCOS合并症也可能与胰岛素抵抗相关，或 高胰岛素血症

The polycystic ovary syndrome (PCOS) is a major health problem that affects approximately 6% of women of reproductive age. PCOS is characterized by hyperandogenism and anovulation, and is the leading cause of female infertility in the United States. Evidence suggests that insulin resistance accompanies by compensatory hyperinsulinemia is a common features of PCOS, and that hyperinsulinemia is responsible in part for the hyperandrogenism of the disorder. However, clinical studies have not assessed the possible role of hyperinsulinemia in promoting the chronic anovulation of PCOS, nor have they examined whether improving insulin selectivity alters PCOS-associated morbidities that may also be linked to insulin resistance and/or hyperinsulinemia, such as glucose intolerance, hypertension, dyslipidemia and atherosclerosis. Therefore, we propose 1) to assess the effects of chronic (12 month) insulin reduction on the hormonal, metabolic (glucose tolerance, blood pressure, lipids, PAI-1, tPA antigen) and ovulatory profiles of women with PCOS, as well as the time course of any changes, 2) to determine whether pharmacologically improving the insulin sensitivity of clomiphene-resistant PCOS women increase the rates of spontaneous and/or clomiphene-induced ovulation, and 3) to determine whether hyperinsulinemia alters 24 hours before and after administration of clomiphene plus placebo or metformin). If our studies confirm an important role of hyperinsulinemia in the pathogenesis of PCOS, they have significant practical implications. That is, they will provide compelling evidence that the first-line treatment of anovulation due to PCOS should be measured aimed at improving insulin sensitivity and reducing serum insulin--including the use of "insulin-sensitizing" agents. Moreover, they will suggest that in women who have failed standard ovulation induction measures, the relatively inexpensive and non-invasive technique of "insulin sensitization" should be employed prior to the initiation of expensive and more complicated technology. Finally, our findings should reveal whether insulin sensitization beneficially affects PCOS co-morbidities that may also be related to insulin resistance or hyperinsulinemia.