ROSIGLITAZONE IN POLYCYSTIC OVARY SYNDROME

罗格列酮治疗多囊卵巢综合征

• 批准号: 6536264
• 负责人: NICHOLAS A CATALDO
• 金额: $ 5.55万
• 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 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6536264
• 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：（改编自申请人的描述）：多囊卵巢 综合症 (PCOS) 是一种影响约 5% 育龄妇女的疾病 其特征是卵巢不排卵和产生过多的雄激素。 无排卵会导致月经不调和不孕，而排卵过多会导致月经不调和不孕。 雄激素会导致毛发生长，并可能促进痤疮。传统的 多囊卵巢综合症的治疗包括药物刺激排卵，如果 需要生育能力，或者服用药物来抑制或阻断雄激素或恢复 如果生育不是近期目标，则定期月经周期，但这些 治疗方法通常是相互排斥的 PCOS 通常与以下疾病相关： 常见的代谢紊乱、胰岛素抵抗等 单独使用会增加非生殖健康问题的风险，例如 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。近几年来，已发表的报告描述了 用胰岛素增敏剂治疗多囊卵巢综合症，开发治疗药物 糖尿病，可改善胰岛素抵抗。这些药物可以改善 多囊卵巢综合症的荷尔蒙异常，在某些情况下可以恢复正常的月经 和/或排卵。迄今为止测试的两种上市药物中，二甲双胍尚未 一直有效，而曲格列酮虽然有效，但一直有效 发现具有不可接受的肝毒性风险。 该项目将研究罗格列酮，一种新批准的与其密切相关的药物 在结构和作用上与曲格列酮相似，但没有明显的毒性， 开放标签，第二阶段格式。患有多囊卵巢综合症的受试者会出现胰岛素抵抗 通过使用奥曲肽胰岛素抑制试验的动态测试来确定， 在进一步评估激发的胰岛素分泌后，将收到 每天服用罗格列酮三剂中的一剂，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、 将测量罗格列酮的循环血脂并与 受试者的治疗前值。将评估排卵的发生 每周血清孕酮水平。罗格列酮的剂量和时间 其效果发挥所需的时间将被确定。之间的关联 对代谢参数的影响和对生殖参数的影响将是 寻求。 这项研究的假设是罗格列酮可以改善胰岛素 敏感性并降低循环胰岛素，从而恢复排卵 以及纠正升高的 LH 和睾酮。罗格列酮可能是一种 对所有患有 PCOS 和胰岛素的女性进行适当且有益的治疗 无论目标如何，都会抵抗。