Anderson Garnet L, Limacher Marian, Assaf Annlouise R, Bassford Tamsen, Beresford Shirley A A, Black Henry, Bonds Denise, Brunner Robert, Brzyski Robert, Caan Bette, Chlebowski Rowan, Curb David, Gass Margery, Hays Jennifer, Heiss Gerardo, Hendrix Susan, Howard Barbara V, Hsia Judith, Hubbell Allan, Jackson Rebecca, Johnson Karen C, Judd Howard, Kotchen Jane Morley, Kuller Lewis, LaCroix Andrea Z, Lane Dorothy, Langer Robert D, Lasser Norman, Lewis Cora E, Manson JoAnn, Margolis Karen, Ockene Judith, O'Sullivan Mary Jo, Phillips Lawrence, Prentice Ross L, Ritenbaugh Cheryl, Robbins John, Rossouw Jacques E, Sarto Gloria, Stefanick Marcia L, Van Horn Linda, Wactawski-Wende Jean, Wallace Robert, Wassertheil-Smoller Sylvia
Fred Hutchinson Cancer Research Center, Seattle, Wash 98109-1024, USA.
JAMA. 2004 Apr 14;291(14):1701-12. doi: 10.1001/jama.291.14.1701.
Despite decades of use and considerable research, the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain.
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 10 739 postmenopausal women, aged 50-79 years, with prior hysterectomy, including 23% of minority race/ethnicity.
Women were randomly assigned to receive either 0.625 mg/d of conjugated equine estrogen (CEE) or placebo.
The primary outcome was coronary heart disease (CHD) incidence (nonfatal myocardial infarction or CHD 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.
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: CHD, 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 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years. The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years.
The use of CEE increases the risk of stroke, decreases the risk of hip fracture, and does not affect CHD 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.
尽管已使用数十年且进行了大量研究，但雌激素在预防绝经后女性慢性病方面的作用仍不明确。
评估美国最常用的绝经后激素疗法对主要疾病发病率的影响。
设计、地点和参与者：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]的单用雌激素部分），于1993年在美国40个临床中心开展。纳入10739名50 - 79岁、既往有子宫切除术的绝经后女性，其中少数种族/族裔占23%。
女性被随机分配接受每日0.625毫克结合马雌激素（CEE）或安慰剂。
主要结局为冠心病（CHD）发病率（非致命性心肌梗死或CHD死亡）。浸润性乳腺癌发病率为主要安全性结局。一个包括这些主要结局以及中风、肺栓塞（PE）、结直肠癌、髋部骨折和其他原因导致的死亡的风险和效益综合指数，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）决定提前结束试验的干预阶段。截至2004年2月29日（平均随访6.8年），CEE与安慰剂相比，主要临床结局的估计风险比（HRs）（95%置信区间[CIs]）为：冠心病，0.91（0.75 - 1.12），病例数376例；乳腺癌，0.77（0.59 - 1.01），病例数218例；中风，1.39（1.10 - 1.77），病例数276例；肺栓塞，1.34（0.87 - 2.06），病例数85例；结直肠癌，1.08（0.75 - 1.55），病例数119例；髋部骨折，0.61（0.41 - 0.91），病例数102例。综合结局的相应结果为：总心血管疾病，1.12（1.01 - 1.24）；总癌症，0.93（0.81 - 1.07）；总骨折，0.70（0.63 - 0.79）；总死亡率，1.04（0.88 - 1.22），以及综合指数，1.01（0.91 - 1.12）。对于受CEE显著影响的结局，每10000人年额外有12例中风的绝对超额风险，每10000人年髋部骨折绝对风险降低6例。综合指数中所有监测事件的估计超额风险为每10000人年2例，无统计学意义。
在平均6.8年的时间里，使用CEE会增加中风风险，降低髋部骨折风险，且不影响既往有子宫切除术的绝经后女性的冠心病发病率。乳腺癌风险可能降低需要进一步研究。CEE组和安慰剂组的发病事件负担相当，表明无总体益处。因此，不建议使用CEE预防绝经后女性的慢性病。
