Randomized Trial Evaluation of the Benefits and Risks of Menopausal Hormone Therapy Among Women 50–59 Years of Age
Open Access
- 7 October 2020
- journal article
- research article
- Published by Oxford University Press (OUP) in American Journal of Epidemiology
- Vol. 190 (3), 365-375
- https://doi.org/10.1093/aje/kwaa210
Abstract
The health benefits and risks of menopausal hormone therapy among women aged 50–59 years are examined in the Women’s Health Initiative randomized, placebo-controlled trials using long-term follow-up data and a parsimonious statistical model that leverages data from older participants to increase precision. These trials enrolled 27,347 healthy postmenopausal women aged 50–79 years at 40 US clinical centers during 1993–1998, including 10,739 post-hysterectomy participants in a trial of conjugated equine estrogens and 16,608 participants with a uterus in the trial of these estrogens plus medroxyprogesterone acetate. Over a (median) 18-year follow-up period (1993–2016), risk for a global index (defined as the earliest of coronary heart disease, invasive breast cancer, stroke, pulmonary embolism, colorectal cancer, endometrial cancer, hip fracture, and all-cause mortality) was reduced with conjugated equine estrogens with a hazard ratio of 0.82 (95% confidence interval: 0.71, 0.95), and with nominally significant reductions for coronary heart disease, breast cancer, hip fracture, and all-cause mortality. Corresponding global index hazard ratio estimates of 1.06 (95% confidence interval: 0.95, 1.19) were nonsignificant for combined estrogens plus progestin, but increased breast cancer risk and reduced endometrial cancer risk were observed. These results, among women 50–59 years of age, substantially agree with the worldwide observational literature, with the exception of breast cancer for estrogens alone.Keywords
Funding Information
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HHSN268201100046C, HSN268201600001C, HHSN268201600002C, HHSN268201600003C, HHSN268201600004C, HHSN271201600004C)
- National Cancer Institute (R01 CA119171, R01 CA210921)
This publication has 25 references indexed in Scilit:
- Menopausal Hormone Therapy and Health Outcomes During the Intervention and Extended Poststopping Phases of the Women’s Health Initiative Randomized TrialsJAMA, 2013
- Evolution of postmenopausal hormone therapy between 2002 and 2009Menopause, 2012
- Breast Cancer Risk in Relation to the Interval Between Menopause and Starting Hormone TherapyJNCI Journal of the National Cancer Institute, 2011
- Benefits and Risks of Postmenopausal Hormone Therapy When It Is Initiated Soon After MenopauseAmerican Journal of Epidemiology, 2009
- Effects of Conjugated Equine Estrogen in Postmenopausal Women With HysterectomyJAMA, 2004
- Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women: Principal Results From the Women's Health Initiative Randomized Controlled TrialJAMA, 2002
- Marginal Regression Models for Multivariate Failure Time DataJournal of the American Statistical Association, 1998
- Design of the Women’s Health Initiative Clinical Trial and Observational StudyControlled Clinical Trials, 1998
- Cox regression analysis of multivariate failure time data: The marginal approachStatistics in Medicine, 1994
- Regression Analysis of Multivariate Incomplete Failure Time Data by Modeling Marginal DistributionsJournal of the American Statistical Association, 1989