EFFECTS OF DECREASED HYPERINSULINEMIA ON THE OVULATORY RESPONSE TO CLOMIPHENE

降低高胰岛素血症对克罗米芬排卵反应的影响

• 批准号: 6304995
• 负责人: DAVID T VANDERMOLEN
• 金额: $ 0.06万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-12-01 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6304995
• 关键词: clinical research; clomiphene; drug screening /evaluation; fertility promoting drug; human subject; human therapy evaluation; hyperinsulinism; ovulation; pharmacokinetics; polycystic ovary syndrome

A trial to determine if taking metformin along with clomiphene will increase the number of women who ovulate in response to clomiphene. The objective of this study is to test the hypothesis that patients with the problem of not ovulating due to polycystic ovary syndrome (PCOS), who are resistant to clomiphene, will have an improved ovulatory response to clomiphene with the correction of the amount of insulin in the blood. Failure to ovulate is estimated to cause 40% of female infertility, with the vast majority of cases due to PCOS. Clomiphene remains the primary therapy to induce ovulation. Yet, 25% of patients on clomiphene don't ovulate. Other inexpensive alternatives have small responses and a more expensive therapy has some undesirable side effects. Evidence supports the role of excess insulin in the blood in causing PCOS and failure to ovulate. It is hoped that reducing the serum insulin levels in clomiphene resistant patients will improve their ovulatory response to clomiphene. This will be a double blind , placebo controlled study of clomiphene resistant women that assesses the ovulatory and hormonal responses to clomiphene treatments after chronic administration of either metformin or placebo. There will be 60 women in the study who will be randomly placed in the metformin group or the placebo group. These women will all have failed to ovulate on clomiphene at the 100mg dose as part of their treatment for not ovulating. An overnight fast is required for the first visit to the CRC. Subjects will be given a glucose drink and several blood tests will be done. Then women will be assigned to groups 1 or 2 and will be given medication to be taken three times a day for seven weeks. During the seven weeks, the subjects will return to have blood tested for ovulation every ten days. If ovulation occurs during the seven weeks, the subject has completed the study. If the subject does not ovulate during the seven weeks, clomiphene at the 50mg dose will be given for five days each month. Blood will be tested during that time for ovulation. After taking each round of clomiphene, an ultrasound will be done of the ovaries. If there is still no ovulation, the clomiphene dose will be raised and will continue to be raised until ovulation occurs. Then, if the subject successfully ovulates, the same dose will be continued for six cycles or until conception. If no ovulation occurs, the study medication will be revealed. Those who were taking metformin will be finished with the study. After six weeks of no medications, those who were in the placebo group will then take metformin for several weeks and will follow the same regimen that the first group followed.

一项试验旨在确定服用二甲双胍和克罗米芬是否会增加因克罗米芬而排卵的女性数量。本研究的目的是检验以下假设：因多囊卵巢综合征 (PCOS) 而出现不排卵问题且对克罗米芬耐药的患者，通过校正胰岛素用量，对克罗米芬的排卵反应会有所改善。血。据估计，40% 的女性不孕症是由于排卵失败造成的，其中绝大多数病例是由多囊卵巢综合症引起的。克罗米芬仍然是诱导排卵的主要疗法。然而，25% 服用克罗米芬的患者没有排卵。其他廉价的替代疗法反应较小，而更昂贵的疗法则有一些不良副作用。有证据表明血液中胰岛素过多会导致多囊卵巢综合症和排卵失败。希望降低克罗米芬耐药患者的血清胰岛素水平将改善他们对克罗米芬的排卵反应。这将是一项针对克罗米芬耐药女性的双盲、安慰剂对照研究，评估长期服用二甲双胍或安慰剂后对克罗米芬治疗的排卵和激素反应。研究中将有 60 名女性，她们将被随机分为二甲双胍组或安慰剂组。作为不排卵治疗的一部分，这些女性在服用 100 毫克克罗米芬后都无法排卵。第一次到 CRC 就诊时需要禁食过夜。受试者将获得葡萄糖饮料，并进行多项血液检查。 然后，女性将被分配到第 1 组或第 2 组，并每天服用 3 次药物，持续七周。在这七周内，受试者将每十天回来进行一次排卵验血。如果在七周内发生排卵，则受试者已完成研究。如果受试者在七周内没有排卵，则每月将给予 5 天 50 毫克剂量的克罗米芬。在此期间将进行血液测试以了解排卵情况。服用每轮克罗米芬后，将对卵巢进行超声波检查。如果仍然没有排卵，克罗米芬剂量将增加，并继续增加直至排卵。然后，如果受试者成功排卵，相同的剂量将持续六个周期或直到受孕。如果没有排卵，将显示研究药物。 那些正在服用二甲双胍的人将完成这项研究。六周不服药后，安慰剂组的患者将服用二甲双胍几周，并遵循与第一组相同的治疗方案。