ROSIGLITAZONE IN POLYCYSTIC OVARY SYNDROME

罗格列酮治疗多囊卵巢综合征

• 批准号: 6232505
• 负责人: NICHOLAS A CATALDO
• 金额: $ 5.58万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6232505
• 关键词: blood lipid; blood tests; drug administration rate /duration; drug screening /evaluation; female; fertility promoting drug; glucose tolerance; human middle age (35-64); human subject; human therapy evaluation; hypoglycemic agents; insulin sensitivity /resistance; luteinizing hormone; morphometry; ovulation; patient oriented research; personal log /diary; pharmacology; polycystic ovary syndrome; reproductive hormone; reproductive system disorder chemotherapy; testosterone; women's health; young adult human (21-34)

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.

描述：(改编自申请者的描述)：多囊卵巢 综合征(PCOS)是一种影响大约5%的育龄妇女的疾病 以无排卵和卵巢分泌过多的雄激素为特征。 无排卵会导致月经不调和不孕，而月经过多会导致月经不调和不孕。 雄激素会导致不想要的毛发生长，并可能促进粉刺。传统型 多囊卵巢综合征的治疗包括药物刺激排卵，如果 想要生育，或者用药物来抑制或阻止雌雄同体或恢复 如果生育不是一个直接的目标，那么有规律的月经周期，但这些 治疗通常是相互排斥的，多囊卵巢综合征经常与 常见的代谢紊乱、胰岛素抵抗以及类似的胰岛素抵抗 仅此一项就会增加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，这可能会刺激卵巢过度分泌 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多囊卵巢综合征，开发治疗药物 糖尿病可以改善胰岛素抵抗。这些药物可以改善心脏功能。 多囊卵巢综合征患者的激素异常，在某些情况下可以恢复正常月经 和/或排卵。到目前为止，在测试的两种上市药物中，二甲双胍没有 曲格列酮一直有效，而曲格列酮有效，但 被发现有不可接受的肝脏毒性风险。 该项目将研究与罗格列酮密切相关的新药罗格列酮。 曲格列酮在结构和作用上无明显毒性，在 开放标签，第二阶段格式。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测试来鉴定， 在进一步评估刺激的胰岛素分泌后，将收到 罗格列酮每天服用三种剂量中的一种，持续12周。胰岛素抵抗和 胰岛素分泌、糖耐量、血清总睾酮和游离睾酮、黄体生成素、 循环血脂将在罗格列酮上进行测量并与 受试者的前置值。将评估排卵的发生情况。 通过每周的血清孕酮水平。罗格列酮的剂量和时间 将确定其效果发展所需的条件。两者之间的关联 对代谢参数的影响和对生殖参数的影响 被追寻。 本研究的假设是罗格列酮可以改善胰岛素。 敏感性和较低的循环胰岛素，从而恢复排卵 以及正确升高的黄体生成素和睾丸素。罗格列酮是一种潜在的 对所有患有多囊卵巢综合征和胰岛素的妇女进行适当和有益的治疗 不管目标是什么，都要抵抗。