Biologic Response of Menopausal Women to 17B-Estradiol

描述(申请人提供)：雌激素早期与晚期干预试验(ELITE)是一项随机、双盲、安慰剂对照的连续动脉成像(颈动脉内膜-中层厚度)试验，旨在测试“时机假说”，该假说假定激素治疗(HT)对动脉粥样硬化进展的影响与与更年期有关的HT何时启动有不同的效果。ELITE是一项2x2因素试验，根据绝经后6年或10年的绝经时间，没有心血管疾病的健康绝经后妇女被随机分为172-雌二醇组或安慰剂组。自从6年前首次提出以来，时间假说的科学证据已经有了很大的增长。精英被提前随机分组，辍学率低于最初的计划，干预措施的依从性保持在94%，不良反应较低。提交本续签申请有两个特殊目的：1)通过对比和非对比心脏计算机断层扫描，将试验成像终点扩大到冠状动脉亚临床动脉粥样硬化，以验证和推广最近的研究结果，即高血压有可能减少年轻绝经后女性的冠状动脉疾病；以及，2)延长Elite的干预期，以充分增加力量，以检测自绝经后月经过后的时间与治疗的相互作用比最初设计的更小，因为Elite仍然是唯一专门为检验计时假设而设计的随机对照试验。确定年轻和老年绝经后妇女对172-雌二醇的生物反应是否不同(定义为绝经后的时间)仍然是这项试验的长期和主要目标。 与公共健康相关：随着越来越多的女性进入更年期(到2015年，大约50%的美国女性将达到45岁)，随着新的荷尔蒙产品进入市场，绝经后激素疗法(HT)的使用将继续下去。因此，了解羟色胺对亚临床动脉粥样硬化进展的影响，特别是在年轻的绝经后妇女中，她们可能会使用这些产品来治疗更年期症状(主要是用于冲洗，因为没有类似有效的替代品)，这仍然是一个重要和及时的公共卫生问题。

DESCRIPTION (provided by applicant): The Early versus Later Intervention Trial with Estradiol (ELITE) is a randomized, double-blind, placebo- controlled, serial arterial imaging (carotid artery intima-media thickness) trial designed to test the "timing hypothesis" which posits that there is a differential effect of hormone therapy (HT) on atherosclerosis progression according to when HT is initiated in relation to menopause. ELITE is a 2x2 factorial trial in which healthy postmenopausal women without pre-existing cardiovascular disease were randomized to 172-estradiol or placebo according to their time since menopause, <6 years or >10 years. Since initially proposed 6 years ago, the scientific evidence for the timing hypothesis has grown substantially. ELITE was randomized ahead of schedule, the dropout rate is lower than initially projected, compliance with the study intervention remains >94% and adverse effects are low. This Renewal Application is submitted for 2 specific purposes: 1) to broaden the trial imaging end point to subclinical atherosclerosis of the coronary arteries through contrast and non-contrast cardiac computed tomography to validate and extend recent findings that HT potentially reduces coronary artery disease in young postmenopausal women; and, 2) to extend the intervention period of ELITE to sufficiently increase power to detect a smaller treatment interaction between time since menopause strata than originally designed since ELITE remains the only randomized controlled trial specifically designed to test the timing hypothesis. To determine whether the biologic response to 172-estradiol is different in younger versus older postmenopausal women (defined as time since menopause) remains the long-term and primary goal of this trial. PUBLIC HEALTH RELEVANCE: With the growing number of women entering menopause (approximately 50% of U.S. women will be >45 years old by 2015) and with the introduction of new hormonal products into the marketplace, use of postmenopausal hormone therapy (HT) will continue. Therefore, understanding the effect of HT on the progression of subclinical atherosclerosis, especially in young postmenopausal women who are likely to initiate these products for menopausal symptoms (primarily for flushing since there are no comparably effective alternatives) continues to be an important and timely public health issue.