Biologic Response of Menopausal Women to 17B Estradiol

描述（由申请人提供）：本申请是最近资助的临床试验的补充，绝经妇女对17b -雌二醇的生物学反应（R01-AG024154），该试验评估了17b -雌二醇对两组无心血管疾病证据的妇女的亚临床颈动脉粥样硬化进展的影响：绝经6年以内的年轻妇女和绝经10年以上的老年妇女。这篇补充文章关注的是雌二醇对这两组人的认知作用。母体研究是一项随机、双盲、安慰剂对照试验，旨在验证雌二醇对动脉粥样硬化进展的影响自绝经后随时间变化的假设。在妇女健康倡议的结果广为人知后，激素疗法的使用大幅下降，但仍有近1000万美国人使用激素，主要是年轻女性治疗更年期症状。妇女健康倡议记忆研究（WHIMS）评估了64岁以后开始激素治疗的认知结果，但没有长期临床试验数据说明年轻激素使用者的认知结果。鉴于许多观察性研究（主要是绝经后早期的激素暴露，提示有益，容易存在偏差）和WHIMS（绝经后晚期的激素暴露，有害或无益处，方法学更严格）之间的结果存在差异，确定年轻女性的认知结果很重要。母试验的设计、持续时间和规模使其成为实现这一目的的理想平台。由于试验的中心部分得到了资助，因此将以相当大的节省获得一个健全的数据库。目前的目的是在一项为期两年的随机对照试验中调查雌二醇对504名绝经后妇女认知能力的影响。为了解决主要的研究假设，主要的分析将包括绝经后两个时间层之间治疗效果的比较。认知功能（特别是情景性言语记忆）的纵向变化将采用2 × 2因子设计进行评估，第一因素为治疗分配的随机化，第二因素为绝经后的时间。我们还将评估记忆和其他认知变化与颈动脉粥样硬化进展、生殖因素（如绝经期症状、先前接受激素治疗、子宫切除术状态）以及其他可能混淆或改变治疗分配与认知结果之间关联的变量之间的关联。

DESCRIPTION (provided by applicant): This application is a supplement to a recently funded clinical trial, Biologic Response of Menopausal Women to 17B-Estradiol (R01-AG024154) that assesses effects of 17B-estradiol on subclinical carotid atherosclerosis progression in two groups of women without evidence of cardiovascular disease: younger women within 6 years of menopause and older women 10+ years after menopause. This supplement focuses on cognitive effects of estradiol in these two groups. The parent study is a randomized, double-blind, placebo-controlled trial to test the hypothesis that estradiol effects on atherosclerosis progression vary by time since menopause. After results of the Women's Health Initiative became widely known, hormone therapy use declined substantially, but almost 10 million Americans still use hormones, primarily younger women for menopausal symptoms. The Women's Health Initiative Memory Study (WHIMS) assessed cognitive outcomes for hormone therapy initiation after age 64, but no long-term clinical trial data address cognitive outcomes in younger hormone users. Given discrepant results between many observational studies (hormone exposure primarily in early postmenopause, suggestion of benefit, prone to bias) and WHIMS (hormone exposure in late postmenopause, harm or no benefit, methodologically more rigorous), it is important to determine cognitive outcomes for younger women. The design, duration and size of the parent trial make it an ideal platform for this purpose. Since the central portion of the trial is funded, a robust database will be obtained at considerable savings. The present objective is to investigate estradiol effects on cognition in 504 postmenopausal women in a two year randomized controlled trial. To address the main study hypothesis, the primary analysis will consist of a comparison of treatment effects between the two strata of time since menopause. Longitudinal changes in cognitive function (particularly episodic verbal memory) will be assessed in a 2 x 2 factorial design, with randomization on treatment assignment as the first factor and time since menopause as the second. We will also assess associations between memory and other cognitive changes and carotid atherosclerosis progression, reproductive factors (e.g., menopausal symptoms, prior exposure to hormone therapy, hysterectomy status), and other variables that might confound or modify associations between treatment assignment and cognitive outcomes.