Manson JoAnn E, Aragaki Aaron K, Rossouw Jacques E, Anderson Garnet L, Prentice Ross L, LaCroix Andrea Z, Chlebowski Rowan T, Howard Barbara V, Thomson Cynthia A, Margolis Karen L, Lewis Cora E, Stefanick Marcia L, Jackson Rebecca D, Johnson Karen C, Martin Lisa W, Shumaker Sally A, Espeland Mark A, Wactawski-Wende Jean
Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
JAMA. 2017 Sep 12;318(10):927-938. doi: 10.1001/jama.2017.11217.
Health outcomes from the Women's Health Initiative Estrogen Plus Progestin and Estrogen-Alone Trials have been reported, but previous publications have generally not focused on all-cause and cause-specific mortality.
To examine total and cause-specific cumulative mortality, including during the intervention and extended postintervention follow-up, of the 2 Women's Health Initiative hormone therapy trials.
DESIGN, SETTING, AND PARTICIPANTS: Observational follow-up of US multiethnic postmenopausal women aged 50 to 79 years enrolled in 2 randomized clinical trials between 1993 and 1998 and followed up through December 31, 2014.
Conjugated equine estrogens (CEE, 0.625 mg/d) plus medroxyprogesterone acetate (MPA, 2.5 mg/d) (n = 8506) vs placebo (n = 8102) for 5.6 years (median) or CEE alone (n = 5310) vs placebo (n = 5429) for 7.2 years (median).
All-cause mortality (primary outcome) and cause-specific mortality (cardiovascular disease mortality, cancer mortality, and other major causes of mortality) in the 2 trials pooled and in each trial individually, with prespecified analyses by 10-year age group based on age at time of randomization.
Among 27 347 women who were randomized (baseline mean [SD] age, 63.4 [7.2] years; 80.6% white), mortality follow-up was available for more than 98%. During the cumulative 18-year follow-up, 7489 deaths occurred (1088 deaths during the intervention phase and 6401 deaths during postintervention follow-up). All-cause mortality was 27.1% in the hormone therapy group vs 27.6% in the placebo group (hazard ratio [HR], 0.99 [95% CI, 0.94-1.03]) in the overall pooled cohort; with CEE plus MPA, the HR was 1.02 (95% CI, 0.96-1.08); and with CEE alone, the HR was 0.94 (95% CI, 0.88-1.01). In the pooled cohort for cardiovascular mortality, the HR was 1.00 (95% CI, 0.92-1.08 [8.9 % with hormone therapy vs 9.0% with placebo]); for total cancer mortality, the HR was 1.03 (95% CI, 0.95-1.12 [8.2 % with hormone therapy vs 8.0% with placebo]); and for other causes, the HR was 0.95 (95% CI, 0.88-1.02 [10.0% with hormone therapy vs 10.7% with placebo]), and results did not differ significantly between trials. When examined by 10-year age groups comparing younger women (aged 50-59 years) to older women (aged 70-79 years) in the pooled cohort, the ratio of nominal HRs for all-cause mortality was 0.61 (95% CI, 0.43-0.87) during the intervention phase and the ratio was 0.87 (95% CI, 0.76-1.00) during cumulative 18-year follow-up, without significant heterogeneity between trials.
Among postmenopausal women, hormone therapy with CEE plus MPA for a median of 5.6 years or with CEE alone for a median of 7.2 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years.
clinicaltrials.gov Identifier: NCT00000611.
妇女健康倡议组织的雌激素加孕激素试验和单独使用雌激素试验的健康结果已有报道，但以往的出版物一般未关注全因死亡率和特定原因死亡率。
研究妇女健康倡议组织的两项激素治疗试验的全因和特定原因累积死亡率，包括干预期间和干预后延长随访期间的死亡率。
设计、设置和参与者：对1993年至1998年参加两项随机临床试验的50至79岁美国多民族绝经后妇女进行观察性随访，并随访至2014年12月31日。
结合马雌激素（CEE，0.625毫克/天）加醋酸甲羟孕酮（MPA，2.5毫克/天）（n = 8506）与安慰剂（n = 8102），为期5.6年（中位数）；或单独使用CEE（n = 5310）与安慰剂（n = 5429），为期7.2年（中位数）。
汇总两项试验以及每项试验单独的全因死亡率（主要结局）和特定原因死亡率（心血管疾病死亡率、癌症死亡率和其他主要死亡原因），并根据随机分组时的年龄按10岁年龄组进行预先设定的分析。
在27347名随机分组的女性中（基线平均[标准差]年龄为63.4[7.2]岁；80.6%为白人），超过98%的女性有死亡率随访数据。在累计18年的随访期间，发生了7489例死亡（干预阶段1088例死亡，干预后随访期间6401例死亡）。在总体汇总队列中，激素治疗组的全因死亡率为27.1%，安慰剂组为27.6%（风险比[HR]，0.99[95%置信区间，0.94 - 1.03]）；使用CEE加MPA时，HR为1.02（95%置信区间，0.96 - 1.08）；单独使用CEE时，HR为0.94（95%置信区间，0.88 - 1.01）。在汇总队列的心血管死亡率方面，HR为1.00（95%置信区间，0.92 - 1.08[激素治疗组为8.9%，安慰剂组为9.0%]）；总癌症死亡率方面，HR为1.03（95%置信区间，0.95 - 1.12[激素治疗组为8.2%，安慰剂组为8.0%]）；其他原因方面，HR为0.95（95%置信区间，0.88 - 1.02[激素治疗组为10.0%，安慰剂组为10.7%]），试验之间结果无显著差异。在汇总队列中按10岁年龄组比较年轻女性（50 - 59岁）和年长女性（70 - 79岁）时，干预阶段全因死亡率的名义HR比值为0.61（95%置信区间，0.43 - 0.87），累积随访18年期间该比值为0.87（95%置信区间，0.76 - 1.00），试验之间无显著异质性。
在绝经后女性中，中位5.6年的CEE加MPA激素治疗或中位7.2年的单独CEE激素治疗在18年的累积随访期间与全因、心血管或癌症死亡率风险无关。
clinicaltrials.gov标识符：NCT00000611。
