Biologic Response of Menopausal Women to 17B-Estradiol
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 643
- 试验地点
- 1
- 主要终点
- Progression of Subclinical Atherosclerosis
研究概览
简要总结
The purpose of this study is to examine the effects of oral 17B-estradiol (estrogen) on the progression of early (subclinical) atherosclerosis and cognitive decline in healthy postmenopausal women.
详细描述
The primary hypothesis to be tested is that 17B-estradiol (estrogen) will reduce the progression of early atherosclerosis if initiated soon after menopause when the vascular endothelium (lining of blood vessels) is relatively healthy versus later when the endothelium has lost its responsiveness to estrogen. Ultrasonography will be used to measure the rate of change in the thickness of the carotid artery and cardiac computed tomography (CT) will be used to measure coronary artery calcium and coronary artery lesions. The second hypothesis to be tested is that 17B-estradiol (estrogen) will reduce the progression of cognitive decline if initiated soon after menopause when healthy brain tissue remains responsive to estrogen versus later when brain tissue has lost its responsiveness to estrogen.
A total of 643 (actual; 504 initially proposed) postmenopausal women were randomized according to their number of years since menopause, less than 6 years or 10 years or more, to receive either oral 17B-estradiol 1 mg daily or matching placebo. Women with a uterus will also use vaginal progesterone gel 4% (or placebo gel) the last ten days of each month. The vaginal progesterone will be distributed in a double-blinded fashion along with the randomized treatment so that only women exposed to active treatment will receive active progesterone. As initially proposed, participants will undergo ultrasonography at baseline and every 6 months throughout the 2 to 5 years (average 3 years) of randomized treatment. Participants will also undergo cognitive testing at baseline and after 3 years of randomized treatment. The trial has been extended for an additional 2 to 2.5 years of randomized treatment (overall average randomized treatment of 5 years and range of 2 to 8.5 years). Ultrasonography will continue to be collected every 6 months and upon completion of randomized treatment, participants will undergo cardiac CT for coronary artery calcium and coronary artery lesion measurements. Participants will also undergo a third cognitive testing at the completion of randomized treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Women with a serum estradiol level 25 pg/ml or less
- •No period for 6 months or more
- •Postmenopausal less than 6 years, OR 10 years or longer
排除标准
- •Clinical signs, symptoms, or personal history of cardiovascular disease
- •Women who have had a hysterectomy only and no oophorectomy (since time from menopause cannot be determined)
- •Diabetes mellitus or fasting serum glucose 140 mg/dL or greater
- •Uncontrolled hypertension (diastolic blood pressure 110 mmHg or greater)
- •Thyroid disease (untreated)
- •Serum creatinine greater than 2.0 mg/dL
- •Plasma triglyceride levels greater than 500 mg/dL
- •Life threatening disease with prognosis less than 5 years
- •Cirrhosis or liver disease
- •History of deep vein thrombosis or pulmonary embolism
- •History of breast cancer
- •Current hormone replacement therapy (HRT)
研究组 & 干预措施
17B-estradiol
Oral 17B-estradiol 1 mg daily
干预措施: 17B-estradiol (Drug)
Placebo
Matching oral 17B-estradiol placebo daily
干预措施: Placebo (Other)
结局指标
主要结局
Progression of Subclinical Atherosclerosis
时间窗: Baseline x 2 and then every 6 months up to 6.7 years
Rate of change in distal common carotid artery (CCA) far wall intima-media thickness (mm per year) in computer image processed B-mode ultrasonograms that were obtained at two baseline examinations (averaged to obtain the baseline CIMT value) and every 6 months during trial follow-up.
次要结局
- Change in Neurocognitive Function (Global Cognition)(Baseline and at 2.5 years and 5 years)
- Coronary Artery Calcium(End of randomized treatment, up to 6.7 years)
研究者
Howard N. Hodis, M.D.
Harry J. Bauer and Dorothy Bauer Rawlins Professor of Cardiology, Professor of Medicine, Population and Public Health Sciences, and Molecular Pharmacology and Toxicology, Director, Atherosclerosis Research Unit
University of Southern California