Biologic Response of Menopausal Women to 17B Estradiol

描述(申请人提供)：本申请是对最近资助的一项临床试验的补充，该临床试验名为更年期妇女对17B-雌二醇的生物反应(R01-AG024154)，该试验评估了17B-雌二醇对两组没有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年内的年轻妇女和绝经10年以上的老年妇女。本补充资料重点介绍了雌二醇对这两组人的认知影响。母公司的研究是一项随机、双盲、安慰剂对照试验，以检验雌激素对动脉粥样硬化进展的影响随绝经后时间的不同而变化的假设。在妇女健康倡议的结果广为人知后，激素治疗的使用量大幅下降，但近1000万美国人仍在使用激素，主要是年轻女性的更年期症状。女性健康倡议记忆研究(WHIMS)评估了年龄后开始激素治疗的认知结果，但没有长期临床试验数据解决年轻激素使用者的认知结果。鉴于许多观察性研究(激素暴露主要发生在绝经后早期，暗示有益，容易产生偏见)和突发奇想(绝经后期激素暴露，有害或无益处，方法更严格)之间的结果存在差异，确定年轻女性的认知结果非常重要。家长试验的设计、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资助，将以相当大的节省获得一个强大的数据库。本研究的目的是通过为期两年的随机对照试验，研究雌激素对504名绝经后妇女认知功能的影响。为了解决主要的研究假设，初步的分析将包括绝经后两个时期的治疗效果的比较。认知功能(特别是情景言语记忆)的纵向变化将以2×2析因设计进行评估，治疗分配的随机化是第一个因素，绝经后的时间是第二个因素。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(例如，更年期症状、以前接受激素治疗的情况、子宫切除状况)以及其他可能混淆或改变治疗分配和认知结果之间关联的变量之间的关系。

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.