Effects of conjugated, equine estrogen in postmenopausal women with hysterectomy - The women's health initiative randomized controlled trial
Effects of conjugated, equine estrogen in postmenopausal women with hysterectomy - The women's health initiative randomized controlled trial
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DOI：
10.1001/jama.291.14.1701
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发表时间：
2004-04-14
影响因子：
120.7
通讯作者：
Wassertheil-Smoller, S
中科院分区：
文献类型：
--
作者：
Anderson, GL;Limacher, M;Wassertheil-Smoller, S
尽管几十年的使用和大量的研究，雌激素单独在预防绝经后妇女慢性疾病中的作用仍然不确定。目的评价美国最常用的绝经后激素治疗对主要疾病发病率的影响。设计、环境和参与者一项随机、双盲、安慰剂对照的疾病预防试验（妇女健康倡议[WHI]的雌激素单独成分），从1993年开始在美国40个临床中心进行。纳入10739名绝经后妇女，年龄50-79岁，既往子宫切除术，包括23%的少数民族/民族。妇女被随机分配接受0.625 mg/d的共轭马雌激素（CEE）或安慰剂。主要结局指标主要结局指标为冠心病（CHID）发病率（非致死性心肌梗死或CHID死亡）。浸润性乳腺癌发病率是主要的安全性指标。风险和收益的全球指数，包括这些主要结局加上中风、肺栓塞（PE）、结直肠癌、髋部骨折和其他原因的死亡，用于总结总体效果。2004年2月，在审查了截至2003年11月30日的数据后，美国国立卫生研究院（NIH）决定提前结束该试验的干预阶段。截至2004年2月29日（平均随访6.8年）的主要临床结果中，CEE与安慰剂的估计风险比（95%可信区间[ci]）为：CHID， 376例，0.91 (0.75-1.12)；乳腺癌218例，0.77 (0.59 ~ 1.01)；卒中276例，1.39 (1.10 ~ 1.77)；85例，PE为1.34 (0.87-2.06)；结直肠癌119例，1.08 (0.75 ~ 1.55)；髋部骨折102例，0.61例（0.41 ~ 0.91）。综合结局对应的结果为：总心血管疾病，1.12 (1.01-1.24)；总癌，0.93 (0.81-1.07)；骨折总数，0.70 (0.63-0.79)；总死亡率为1.04(0.88-1.22)，全球指数为1.01（0.91-1.12）。对于受CEE显著影响的结果，每10000人年有12例额外卒中的绝对超额风险，每10000人年有6例髋部骨折的绝对风险降低。全球指数中所有监测事件的估计超额风险为每10000人年2次。结论：在平均6.8年的子宫切除术后绝经妇女中，CEE的使用增加了卒中的风险，降低了髋部骨折的风险，并且对CHID的发生率没有影响。降低乳腺癌风险的可能性需要进一步调查。在CEE组和安慰剂组中，疾病事件的负担相当，表明没有总体获益。因此，不建议将CEE用于绝经后妇女的慢性疾病预防。
Context Despite decades of use and considerable research, the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain.Objective To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States.Design, Setting, and Participants A randomized, double-blind, placebo-controlled disease prevention trial (the estrogen-alone component of the Women's Health Initiative [WHI]) conducted in 40 US clinical centers beginning in 1993. Enrolled were 10739 postmenopausal women, aged 50-79 years, with prior hysterectomy, including 23% of minority race/ethnicity.Intervention Women were randomly assigned to receive either 0.625 mg/d of conjugated equine estrogen (CEE) or placebo.Main Outcome Measures The primary outcome was coronary heart disease (CHID) incidence (nonfatal myocardial infarction or CHID death). Invasive breast cancer incidence was the primary safety outcome. A global index of risks and benefits, including these primary outcomes plus stroke, pulmonary embolism (PE), colorectal cancer, hip fracture, and deaths from other causes, was used for summarizing overall effects.Results In February 2004, after reviewing data through November 30, 2003, the National Institutes of Health (NIH) decided to end the intervention phase of the trial early. Estimated hazard ratios (HRs) (95% confidence intervals [CIs]) for CEE vs placebo for the major clinical outcomes available through February 29, 2004 (average follow-up 6.8 years), were: CHID, 0.91 (0.75-1.12) with 376 cases; breast cancer, 0.77 (0.59-1.01) with 218 cases; stroke, 1.39 (1.10-1.77) with 276 cases; PE, 1.34 (0.87-2.06) with 85 cases; colorectal cancer, 1.08 (0.75-1.55) with 119 cases; and hip fracture, 0.61 (0.41-0.91) with 102 cases. Corresponding results for composite outcomes were: total cardiovascular disease, 1.12 (1.01-1.24); total cancer, 0.93 (0.81-1.07); total fractures, 0.70 (0.63-0.79); total mortality, 1.04 (0.88-1.22), and the global index, 1.01 (0.91-1.12). For the outcomes significantly affected by CEE, there was an absolute excess risk of 12 additional strokes per 10000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10000 person-years. The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10000 person-years.Conclusions The use of CEE increases the risk of stroke, decreases the risk of hip fracture, and does not affect CHID incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years. A possible reduction in breast cancer risk requires further investigation. The burden of incident disease events was equivalent in the CEE and placebo groups, indicating no overall benefit. Thus, CEE should not be recommended for chronic disease prevention in postmenopausal women.