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: 7146778
• 负责人: Howard Neil Hodis
• 金额: $ 28.53万
• 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/7146778
• 关键词: Biologic; Response; Menopausal; Women; 17B

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.

描述（由申请人提供）：本申请是对最近资助的临床试验的补充，该临床试验评估了17 B-雌二醇对两组无心血管疾病证据的女性亚临床颈动脉粥样硬化进展的影响：绝经6年内的年轻女性和绝经后10年以上的老年女性。本补充侧重于这两个群体中雌二醇的认知影响。母研究是一项随机、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随绝经后时间而变化的假设。在妇女健康倡议的结果广为人知之后，激素治疗的使用大幅下降，但仍有近1000万美国人使用激素，主要是年轻妇女的更年期症状。妇女健康倡议记忆研究（WHIMS）评估了64岁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（主要在绝经早期激素暴露，建议有益，容易产生偏见）和WHIMS（绝经后期激素暴露，有害或无益，方法学上更严格）之间的不一致结果，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已获得资金，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一项为期两年的随机对照试验，探讨雌二醇对504名绝经后妇女认知功能的影响。为了解决主要研究假设，主要分析将包括绝经后两个时间层之间的治疗效果比较。将采用2 x 2析因设计评估认知功能（特别是情景言语记忆）的纵向变化，治疗分配的随机化作为第一个因素，绝经后时间作为第二个因素。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，绝经期症状、既往激素治疗暴露、子宫切除术状态）以及可能混淆或改变治疗分配与认知结果之间关联的其他变量。