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JAMA. 2017 Sep 12;318(10):927-938. doi: 10.1001/jama.2017.11217.

Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific Mortality: The Women's Health Initiative Randomized Trials.

Author information

1
Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
2
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
3
National Heart, Lung, and Blood Institute, Bethesda, Maryland.
4
Department of Family Medicine and Public Health, University of California, San Diego, School of Medicine, San Diego.
5
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance.
6
now with City of Hope National Medical Center, Department of Medical Oncology and Therapeutics Research, Duarte, California.
7
MedStar Health Research Institute, Washington DC.
8
Georgetown/Howard Universities Center for Clinical and Translational Sciences, Washington DC.
9
Department of Health Promotion Sciences, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson.
10
HealthPartners Institute for Education and Research, Minneapolis, Minnesota.
11
Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham.
12
Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, California.
13
Department of Medicine, The Ohio State University, Columbus.
14
Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis.
15
Cardiology Division, George Washington University School of Medicine and Health Sciences, Washington DC.
16
Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, North Carolina.
17
Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina.
18
Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, New York.

Abstract

Importance:

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.

Objective:

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.

Interventions:

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).

Main Outcomes and Measures:

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.

Results:

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.

Conclusions and Relevance:

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.

Trial Registration:

clinicaltrials.gov Identifier: NCT00000611.

PMID:
28898378
PMCID:
PMC5728370
DOI:
10.1001/jama.2017.11217
[Indexed for MEDLINE]
Free PMC Article

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