Biologic Response of Menopausal Women to 17B-Estradiol

更年期妇女对 17B-雌二醇的生物反应

• 批准号: 7086895
• 负责人: Howard Neil Hodis
• 金额: $ 184万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7086895
• 关键词: aging; atherosclerosis; cardiovascular disorder prevention; chemoprevention; clinical research; clinical trials; estradiol; female; hormone regulation /control mechanism; hormone therapy; human subject; human therapy evaluation; pathologic process; patient oriented research; placebos; postmenopause; therapy design /development; women' s health

DESCRIPTION(provided by applicant):Although there is little information available regarding age-dependent altered tissue responses to natural hormones, several lines of evidence strongly suggest that the biologic response of the vascular wall to hormones may differ in younger and older postmenopausal women. The Women's Health Initiative showed that women randomized to hormone therapy within 10 years of menopause had a relative risk less than 1 for coronary heart disease (CHD) compared with women more than 10 years postmenopausal who had a relative risk for CHD greater than 1. Nurse's Health Study data indicate that women who initiated hormone therapy within 6 years of menopause had a significantly lower CHD risk than did women who initiated therapy 6 or more years after menopause. Estrogen in the Prevention of Atherosclerosis Trial results show that estrogen therapy more effectively reduced the progression of subclinical atherosclerosis in women who were randomized within 6 years of menopause relative to those women who were 10 years or more postmenopausal. Non-human primate studies provide pathobiological evidence that the optimal time for intervention with estrogen therapy is within 6 years of menopause. With the rapidly growing number of women entering menopause and introduction of new hormonal products into the marketplace, postmenopausal hormone therapy is likely to increase. Understanding the effects of estrogen on the progression of subclinical atherosclerosis continues to be an important and timely public health issue since young postmenopausal women who have climacteric symptoms, predominantly flushing, are the women who are most likely to initiate hormone therapy. Since there are no trials designed to directly test the hypothesis that the effect of exogenous estrogen on the progression of atherosclerosis will vary by time since menopause, we propose a double-blind, placebo-controlled trial with a 2x2 factorial design (treatment x time since menopause) in which 504 healthy postmenopausal women without clinical evidence of cardiovascular disease will be randomized to 1713-estradiol 1 mg/day versus placebo according to their number of years since menopause, <6 years or >10 years. Treatment duration will average 3 years (,range, 2 to 5 years) and the rate of change _ carotid artery intima-media thickness, a well-established measure of subclinical atherosclerosis, will be the primary trial end point.

描述（由申请人提供）：尽管几乎没有有关年龄依赖性组织对天然激素的反应的信息，但有几条证据强烈表明，血管壁对激素对激素的生物学反应在绝经后妇女中可能有所不同。妇女的健康计划表明，与绝经后10年以上的女性相比，妇女的冠状动脉疾病（CHD）的相对风险小于1。护士对1的相对风险的相对风险相对10年。护士的健康研究数据在6年内启动了6年妇女的妇女在培训中造成的妇女较少，而较少的妇女在培训中造成了6年的培训，这些妇女的相对风险高于1。雌激素在预防动脉粥样硬化试验结果中表明，雌激素疗法更有效地降低了在绝经后6年内与十年或更多绝经后的女性在6年内随机分组的亚临床动脉粥样硬化的进展。非人类灵长类动物研究提供了病理生物学证据，表明雌激素治疗的最佳干预时间在更年期的6年内。随着进入更年期的妇女数量迅速增长，并将新的荷尔蒙产品引入市场，绝经后激素疗法可能会增加。了解雌激素对亚临床动脉粥样硬化进展的影响仍然是一个重要且及时的公共卫生问题，因为年轻的绝经后妇女患有更高的症状，主要是潮红，是最有可能启动激素治疗的妇女。 Since there are no trials designed to directly test the hypothesis that the effect of exogenous estrogen on the progression of atherosclerosis will vary by time since menopause, we propose a double-blind, placebo-controlled trial with a 2x2 factorial design (treatment x time since menopause) in which 504 healthy postmenopausal women without clinical evidence of cardiovascular disease will be randomized to 1713-estradiol 1 mg/day与安慰剂相比，根据他们更年期以来的年限，<6年或> 10年。治疗持续时间平均为3年（，范围为2至5年），变化率_颈动脉内膜膜厚度（对亚临床动脉粥样硬化的衡量标准）将是主要试验终点。