TY - JOUR
T1 - Menopausal hormone therapy and long-term all-cause and cause-specific mortality
T2 - The Women’s Health Initiative randomized trials
AU - WHI Investigators
AU - Manson, Jo Ann E.
AU - Aragaki, Aaron K.
AU - Rossouw, Jacques E.
AU - Anderson, Garnet L.
AU - Prentice, Ross L.
AU - LaCroix, Andrea Z.
AU - Chlebowski, Rowan T.
AU - Howard, Barbara V.
AU - Thomson, Cynthia A.
AU - Margolis, Karen L.
AU - Lewis, Cora E.
AU - Stefanick, Marcia L.
AU - Jackson, Rebecca D.
AU - Johnson, Karen C.
AU - Martin, Lisa W.
AU - Shumaker, Sally A.
AU - Espeland, Mark A.
AU - Wactawski-Wende, Jean
N1 - Funding Information:
completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Drs Anderson and Prentice report receipt of a grant from the National Heart, Lung, and Blood Institute (NHLBI) during the conduct of the study. Dr LaCroix reports receipt of grants from NHLBI and the National Institutes of Health (NIH) during the conduct of the study; receipt of personal fees from Sermonix for serving on a scientific advisory board and from Pfizer for a consultancy. Dr Chlebowski reports receipt of consulting fees or honoraria from Novartis, Genentech, Amgen, and Astra-Zeneca, Novo Nordisk, and Genomic Health; fees for participation in review activities from Pfizer; payment for lectures from Novartis; and payment for educational activities from Educational Concepts Group. Dr Howard reports receipt of other fees from NIH for a contract for field work. Dr Margolis reports receipt of grants from NHLBI and NIH. Dr Lewis reports receipt of grants to her institution from NIH during the conduct of the study. Dr Espeland reports receipt of grants from NHLBI during the conduct of the study. Dr Wactawski-Wende reports receipt of grants from NHLBI and NIH. No other disclosures were reported.
Funding Information:
Funding/Support: The Women’s Health Initiative is funded by the NHLBI, NIH, and the US Department of Health and Human Services through contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C. Wyeth Ayerst donated the study drugs.
Publisher Copyright:
© 2017 American Medical Association. All rights reserved.
PY - 2017/9/12
Y1 - 2017/9/12
N2 - 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.
AB - 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.
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U2 - 10.1001/jama.2017.11217
DO - 10.1001/jama.2017.11217
M3 - Article
C2 - 28898378
AN - SCOPUS:85029557031
VL - 318
SP - 927
EP - 938
JO - JAMA - Journal of the American Medical Association
JF - JAMA - Journal of the American Medical Association
SN - 0002-9955
IS - 10
ER -