Another major study about the safety of HRT.
Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific Mortality: The Women’s Health Initiative Randomized Trials.
- 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.
- National Heart, Lung, and Blood Institute, Bethesda, Maryland.
- Department of Family Medicine and Public Health, University of California, San Diego, School of Medicine, San Diego.
- Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance.
- now with City of Hope National Medical Center, Department of Medical Oncology and Therapeutics Research, Duarte, California.
- MedStar Health Research Institute, Washington DC.
- Georgetown/Howard Universities Center for Clinical and Translational Sciences, Washington DC.
- Department of Health Promotion Sciences, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson.
- HealthPartners Institute for Education and Research, Minneapolis, Minnesota.
- Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham.
- Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, California.
- Department of Medicine, The Ohio State University, Columbus.
- Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis.
- Cardiology Division, George Washington University School of Medicine and Health Sciences, Washington DC.
- Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, North Carolina.
- Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina.
- Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, New York.
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).
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.
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.
clinicaltrials.gov Identifier: NCT00000611.