ROSIGLITAZONE IN POLYCYSTIC OVARY SYNDROME

描述：（改编自申请人的描述）：多囊卵巢 多囊卵巢综合征是一种影响约5%育龄妇女的疾病 以不排卵和卵巢产生过多的雄激素为特征。 不排卵导致月经不调和不孕，而过量 雄激素引起不需要的毛发生长并可能促进痤疮。传统 PCOS的治疗包括药物刺激排卵，如果 生育能力是期望的，或药物抑制或阻止雄激素或恢复 正常的月经周期，如果生育不是一个直接的目标，但这些 治疗往往是相互排斥的PCOS往往与一个 常见的代谢紊乱、胰岛素抵抗和类似的胰岛素抵抗 单是这一项就增加了非生殖健康问题的风险， 糖尿病或动脉粥样硬化的发展。胰岛素抵抗导致 胰岛素分泌过多，这可能会刺激卵巢分泌过多 雄激素在过去的几年里，发表的报告描述了 用胰岛素增敏剂治疗PCOS， 糖尿病，可以改善胰岛素抵抗。这些药物可以改善 PCOS的激素异常，在某些情况下可以恢复正常的月经 和/或排卵。在迄今为止测试的两种上市药物中，二甲双胍没有 一直有效，而曲格列酮是有效的，但一直 发现具有不可接受的肝毒性风险。 本项目将研究罗格列酮，一种新批准的药物密切相关 在结构和作用上与曲格列酮相似，但无明显毒性， 开放标签、II期形式。多囊卵巢综合征患者会有胰岛素抵抗 通过使用奥曲肽胰岛素抑制试验的动态试验鉴定， 在进一步评估激发的胰岛素分泌后， 罗格列酮每日一次，三次剂量之一，持续12周。胰岛素抵抗和 胰岛素分泌、葡萄糖耐量、血清总睾酮和游离睾酮、LH 将测量罗格列酮和循环脂质，并与 受试者的治疗前值。将评估排卵的发生情况 每周血清孕酮水平。罗格列酮的剂量和时间 将确定其效果发展所需的时间。之间的关联 对代谢参数的影响和对生殖参数的影响， 寻找。 本研究的假设是罗格列酮可以提高胰岛素 敏感性和降低循环胰岛素，从而恢复排卵， 以及正确升高的LH和睾酮。罗格列酮可能是一种 适当和有益的治疗所有妇女与PCOS和胰岛素 不分目标的抵抗。

DESCRIPTION: (Adapted from applicant's description): Polycystic ovary syndrome (PCOS) is a disorder affecting about 5% of reproductive-age women characterized by anovulation and excess production of androgens by the ovary. Anovulation causes menstrual irregularity and infertility, while excess androgens cause unwanted hair growth and may promote acne. Traditional treatments for PCOS have consisted of medication to stimulate ovulation if fertility is desired, or medication to suppress or block androgents or restore regular menstrual cycles if fertility is not an immediate goal, but these treatments are often mutually exclusive PCOS is frequently associated with a common metabolic disorder, insulin resistance, and like insulin resistance alone carries an increased risk of non-reproductive health problems such as the development of diabetes or atherosclerosis. Insulin resistance leads to excessive insulin secretion, and this may stimulate the ovary to hypersecrete androgens. In the last few years, published reports have described the treatment of PCOS with insulin sensitizers, medications developed to treat diabetes which can improve insulin resistance. These drugs can improve the hormonal abnormalities in PCOS and in some cases can restore regular menses and/or ovulation. Of the two marketed drugs tested to date, metformin has not been consistently effective, while troglitazone is effective but has been found to have an unacceptable risk of liver toxicity. This project will study rosiglitazone, a newly approved drug closely related to troglitazone in structure and action but without apparent toxicity, in an open-label, Phase II format. Subjects with PCOS wiII have insulin resistance identified by dynamic testing using the octreotide insulin suppression test, and after further evaluation of provoked insulin secretion will receive rosiglitazone daily in one of three doses for 12 weeks. Insulin resistance and insulin secretion, glucose tolerance, serum total and free testosterone, LH, and circulating lipids will be measured on rosiglitazone and compared to subjects' pretreatment values. The occurrence of ovulation will be evaluated by weekly serum progesterone levels. The dose of rosiglitazone and the time needed for its effect to develop will be determined. Associations between effects on metabolic parameters and effects on reproductive ones will be sought. The hypothesis of this study is that rosiglitazone can improve insulin sensitivity and lower circulating insulin, and thereby restore ovulation as well as correct elevated LH and testosterone. Rosiglitazone is potentially an appropriate and beneficial treatment for all women with PCOS and insulin resistance regardless of goals.