激素疗法与绝经后女性冠状动脉粥样硬化的进展

Hormone therapy and the progression of coronary-artery atherosclerosis in postmenopausal women.

作者信息

Hodis Howard N, Mack Wendy J, Azen Stanley P, Lobo Roger A, Shoupe Donna, Mahrer Peter R, Faxon David P, Cashin-Hemphill Linda, Sanmarco Miguel E, French William J, Shook Thomas L, Gaarder Thomas D, Mehra Anilkumar O, Rabbani Ramin, Sevanian Alex, Shil Asit B, Torres Mina, Vogelbach K Heiner, Selzer Robert H

机构信息

Atherosclerosis Research Unit, Keck School of Medicine, Los Angeles, CA 90033, USA.

出版信息

N Engl J Med. 2003 Aug 7;349(6):535-45. doi: 10.1056/NEJMoa030830.

DOI:10.1056/NEJMoa030830

PMID:12904518

Abstract

BACKGROUND

In postmenopausal women with coronary artery disease, conjugated equine estrogen with or without continuous administration of medroxyprogesterone acetate has failed to slow the progression of atherosclerosis. Whether 17beta-estradiol (the endogenous estrogen molecule) alone or administered sequentially with medroxyprogesterone acetate can slow the progression of atherosclerosis is unknown.

METHODS

We conducted a double-blind, placebo-controlled trial in 226 postmenopausal women (mean age, 63.5 years) who had at least one coronary-artery lesion. Participants were randomly assigned to usual care (control group), estrogen therapy with micronized 17beta-estradiol alone (estrogen group), or 17beta-estradiol plus sequentially administered medroxyprogesterone acetate (estrogen-progestin group). In all patients the low-density lipoprotein (LDL) cholesterol level was reduced to a target of less than 130 mg per deciliter. The primary outcome was the average per-participant change between base-line and follow-up coronary angiograms in the percent stenosis measured by quantitative coronary angiography.

RESULTS

After a median of 3.3 years of follow-up, the mean (+/-SE) change in the percent stenosis in the 169 participants who had a pair of matched angiograms was 1.89+/-0.78 percentage points in the control group, 2.18+/-0.76 in the estrogen group, and 1.24+/-0.80 in the estrogen-progestin group (P=0.66 for the comparison among the three groups). The mean difference in the percent stenosis between the estrogen group and the control group was 0.29 percentage point (95 percent confidence interval, -1.88 to 2.46), and the mean difference between the estrogen-progestin group and the control group was -0.65 (95 percent confidence interval, -2.87 to 1.57).

CONCLUSIONS

In older postmenopausal women with established coronary-artery atherosclerosis, 17beta-estradiol either alone or with sequentially administered medroxyprogesterone acetate had no significant effect on the progression of atherosclerosis.

摘要

背景

在患有冠状动脉疾病的绝经后女性中，结合马雌激素联合或不联合持续使用醋酸甲羟孕酮均未能减缓动脉粥样硬化的进展。单独使用17β-雌二醇（内源性雌激素分子）或与醋酸甲羟孕酮序贯给药是否能减缓动脉粥样硬化的进展尚不清楚。

方法

我们对226名患有至少一处冠状动脉病变的绝经后女性（平均年龄63.5岁）进行了一项双盲、安慰剂对照试验。参与者被随机分配至常规治疗组（对照组）、单独使用微粒化17β-雌二醇的雌激素治疗组（雌激素组）或17β-雌二醇加序贯使用醋酸甲羟孕酮的治疗组（雌激素-孕激素组）。所有患者的低密度脂蛋白（LDL）胆固醇水平均降至目标值每分升低于130毫克。主要结局是通过定量冠状动脉造影测量的每位参与者在基线和随访冠状动脉造影之间狭窄百分比的平均变化。

结果

在中位随访3.3年后，169名有配对血管造影的参与者中，对照组狭窄百分比的平均（±SE）变化为1.89±0.78个百分点，雌激素组为2.18±0.76，雌激素-孕激素组为1.24±0.80（三组间比较P = 0.66）。雌激素组与对照组之间狭窄百分比的平均差异为0.29个百分点（95%置信区间，-1.88至2.46），雌激素-孕激素组与对照组之间的平均差异为-0.65（95%置信区间，-2.87至1.57）。