Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol

作者：Howard N. Hodis, Wendy J. Mack, Victor W. Henderson, Donna Shoupe, Matthew J. Budoff, Juliana Hwang-Levine, Yanjie Li, Feng Mei, Laurie Dustin, Naoko Kono, Frank Z. Stanczyk, Robert H. Selzer, Stanley P. Azen · 发表于：New England Journal of Medicine · 年份：2016 · DOI：10.1056/nejmoa1505241 · 被引用次数：769 · 研究领域：Menopause: Health Impacts and Treatments、Cardiovascular Health and Disease Prevention、Estrogen and related hormone effects

BACKGROUND: Data suggest that estrogen-containing hormone therapy is associated with beneficial effects with regard to cardiovascular disease when the therapy is initiated temporally close to menopause but not when it is initiated later. However, the hypothesis that the cardiovascular effects of postmenopausal hormone therapy vary with the timing of therapy initiation (the hormone-timing hypothesis) has not been tested. METHODS: A total of 643 healthy postmenopausal women were stratified according to time since menopause (<6 years [early postmenopause] or ≥10 years [late postmenopause]) and were randomly assigned to receive either oral 17β-estradiol (1 mg per day, plus progesterone [45 mg] vaginal gel administered sequentially [i.e., once daily for 10 days of each 30-day cycle] for women with a uterus) or placebo (plus sequential placebo vaginal gel for women with a uterus). The primary outcome was the rate of change in carotid-artery intima-media thickness (CIMT), which was measured every 6 months. Secondary outcomes included an assessment of coronary atherosclerosis by cardiac computed tomography (CT), which was performed when participants completed the randomly assigned regimen. RESULTS: After a median of 5 years, the effect of estradiol, with or without progesterone, on CIMT progression differed between the early and late postmenopause strata (P=0.007 for the interaction). Among women who were less than 6 years past menopause at the time of randomization, the mean CIMT in...