Clinical trial NCT00114517
Conditions: Atherosclerosis
Keywords: atherosclerosis CAD cardiac computed tomography cardiovascular disease carotid artery intima-media thickness cognitive function computed tomography coronary artery calcium coronary artery disease coronary artery lesions CVD estrogen estrogen therapy hormone therapy postmenopausal subclinical vascular disease timing hypothesis ultrasonography menopausal hormone replacement therapy menopause prevention intervention
Sponsor: University of Southern California
Start date: 2004-07-01; Completion date: 2013-03-05
Enrollment: 643 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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.

Detailed description:
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.

Arms: arm 1: Oral 17B-estradiol 1 mg daily arm 2: Matching oral 17B-estradiol placebo daily
Interventions: intervention 1: 17B-estradiol intervention 2: Placebo
Intervention descriptions: intervention 1: Oral 17B-estradiol 1 mg daily intervention 2: Matching oral 17B-estradiol placebo daily

Protocol documents: