Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol.
Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol.
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DOI：
10.1056/nejmoa1505241
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发表时间：
2016-03-31
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影响因子：
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通讯作者：
ELITE Research Group
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作者：
Hodis HN;Mack WJ;Henderson VW;Shoupe D;Budoff MJ;Hwang-Levine J;Li Y;Feng M;Dustin L;Kono N;Stanczyk FZ;Selzer RH;Azen SP;ELITE Research Group
数据表明，当雌激素治疗在接近更年期时开始，而在较晚开始时，雌激素激素治疗与心血管疾病的有益效果有关。然而，绝经后激素治疗的心血管效应随着治疗开始时间的不同而不同的假说(激素时机假说)尚未得到检验。643名健康的绝经后妇女根据绝经后的时间(<；6年[绝经后早期]或≥10年[绝经后晚期])进行分层，并随机分配到有子宫的妇女连续服用17β-雌二醇(每天1毫克，加孕酮[45 mg]阴道凝胶)或安慰剂(有子宫的妇女连续服用安慰剂阴道凝胶)。主要结果是颈动脉内膜中层厚度(CIMT)的变化率，每6个月测量一次。次要结果包括心脏计算机断层扫描(CT)对冠状动脉粥样硬化的评估，这是在参与者完成随机分配的方案时进行的。中位数5年后，雌二醇加或不加孕酮对绝经后早期和晚期CIMT进展的影响不同(交互作用P=0.007)。在随机分组时绝经后不到6年的妇女中，安慰剂组的平均CIMT每年增加0.0078毫米，而雌二醇组每年增加0.0044毫米(P=0.008)。在随机分组时绝经10年或以上的妇女中，安慰剂组和雌二醇组的CIMT进展率相似(分别为每年0.0088 mm和0.0100 mm；P=0.29)。在安慰剂组和雌二醇组之间，冠状动脉钙化、总狭窄和斑块的CT测量在绝经后两组中都没有显著差异。在绝经后6年内开始治疗时，口服雌二醇治疗与亚临床动脉粥样硬化(以CIMT衡量)的进展程度低于安慰剂，但在绝经后10年或更长时间内开始治疗时，与安慰剂治疗无关。雌激素对绝经后各层动脉粥样硬化的心脏CT测量均无显著影响。(由国家老龄研究所、国家卫生研究院资助；Elite ClinicalTrials.gov编号，NCT00114517)
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. 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. 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 increased by 0.0078 mm per year in the placebo group versus 0.0044 mm per year in the estradiol group (P = 0.008). Among women who were 10 or more years past menopause at the time of randomization, the rates of CIMT progression in the placebo and estradiol groups were similar (0.0088 and 0.0100 mm per year, respectively; P = 0.29). CT measures of coronary-artery calcium, total stenosis, and plaque did not differ significantly between the placebo group and the estradiol group in either postmenopause stratum. Oral estradiol therapy was associated with less progression of subclinical atherosclerosis (measured as CIMT) than was placebo when therapy was initiated within 6 years after menopause but not when it was initiated 10 or more years after menopause. Estradiol had no significant effect on cardiac CT measures of atherosclerosis in either postmenopause stratum. (Funded by the National Institute on Aging, National Institutes of Health; ELITE ClinicalTrials.gov number, NCT00114517.)