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: 6810109
• 负责人: Howard Neil Hodis
• 金额: $ 153.25万
• 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/6810109
• 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）：尽管关于年龄依赖性组织对天然激素的反应改变的信息很少，但一些证据强烈表明，年轻和年长绝经后妇女的血管壁对激素的生物反应可能不同。妇女健康倡议表明，绝经后 10 年内随机接受激素治疗的女性患冠心病 (CHD) 的相对风险小于 1，而绝经后 10 年以上的女性患冠心病的相对风险大于 1。健康研究数据表明，绝经后 6 年内开始激素治疗的女性，其冠心病风险明显低于绝经后 6 年或更长时间开始治疗的女性。雌激素预防动脉粥样硬化 试验结果表明，与绝经后 10 年或以上的女性相比，雌激素治疗更能有效地减少绝经 6 年内随机分组的女性亚临床动脉粥样硬化的进展。非人类灵长类动物研究提供的病理生物学证据表明，雌激素治疗干预的最佳时间是绝经后 6 年内。随着进入更年期的女性数量迅速增加以及新的激素产品进入市场，绝经后激素治疗可能会增加。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而及时的公共卫生问题，因为出现更年期症状（主要是潮红）的年轻绝经后女性是最有可能开始激素治疗的女性。由于没有试验直接检验外源性雌激素对动脉粥样硬化进展的影响会随着绝经后时间的推移而变化这一假设，因此我们提出了一项双盲、安慰剂对照试验，采用 2x2 析因设计（治疗 x 自绝经后的时间）更年期），其中 504 名没有心血管疾病临床证据的健康绝经后妇女将被随机分配到 1713-雌二醇 1 毫克/天，对比安慰剂绝经后的年数，<6 年或>10 年。治疗持续时间平均为 3 年（范围为 2 至 5 年），颈动脉内膜中层厚度的变化率（亚临床动脉粥样硬化的公认衡量标准）将是主要试验终点。