Menopausal Hormone Therapy and Health Outcomes

JoAnn E. Manson, MD, DrPH Chief, Division of Preventive Medicine Brigham and Women's Hospital Professor of Medicine and the Michael and Lee Bell Professor of Women's Health Harvard Medical School 900 Commonwealth Avenue , 3rd fl Boston , Massachusetts   02215 Interview with:
JoAnn E. Manson, MD, DrPH
Chief, Division of Preventive Medicine
Brigham and Women’s Hospital
Professor of Medicine and the
Michael and Lee Bell Professor of Women’s Health
Harvard Medical School
Boston , Massachusetts   02215

WHI investigators publish most comprehensive report to date on the two Hormone Therapy Trials and extend follow-up to 13 years: Results inform clinical decision making

Researchers from the Women’s Health Initiative (WHI) Hormone Therapy (HT) Trials provide new information from extended follow-up of postmenopausal women in the two HT trials (estrogen plus progestin and estrogen alone) and the most comprehensive look at the findings to date. The study, published October 2 in the Journal of the American Medical Association, presents information on a wide range of diseases and quality-of-life outcomes, comparisons of the two trials side-by-side, and a full breakdown of results by age and time since menopause onset. The WHI, which enrolled 27,347 women nation-wide in the two hormone therapy trials, is sponsored by the National Institutes of Health.

“Our main goal was to provide as much information as possible from the WHI hormone therapy trials to help women and their clinicians make the most informed decisions about hormone therapy use. The WHI findings, presented in detail by age group and time since menopause onset, help to guide clinical decision making,”, said JoAnn Manson, MD, DrPH, first author of the report and Chief of Preventive Medicine at Brigham and Women’s Hospital. Manson is one of the Principal Investigators of the WHI and the Michael and Lee Bell Professor of Women’s Health at Harvard Medical School .


Key findings of the report are that hormone therapy has a complex pattern of health risks and benefits and that younger women tend to have a more favorable risk-to-benefit profile than older women. The researchers also found that combination estrogen plus progestin (in women with an intact uterus) had more risks than estrogen alone (used in women with hysterectomy), primarily due to an increased risk of breast cancer with the former but not the latter. Both forms of hormone therapy increased the risk of stroke, blood clots in the legs, gallstones, and urinary incontinence, while benefits included decreased risk of hip fractures, other fractures, diabetes, and hot flashes/night sweats. Estrogen plus progestin increased dementia (in women >65 years), but neither treatment affected cognition in younger women. For estrogen alone, younger women (ages 50-59) had more favorable results for all-cause mortality, heart attacks, and colorectal cancer, and their overall risk-to-benefit profile on estrogen alone was more favorable than for older women.  Effects on quality-of-life outcomes with HT were mixed, with improvement in sleep and joint pain but increases in breast tendernes.

After stopping hormone therapy, most risks and benefits of hormone therapy dissipated. However, over the 13-yr cumulative follow-up period, breast cancer risk remained slightly elevated for estrogen plus progestin but became significantly reduced for estrogen alone. For estrogen plus progestin, a significant reduction in uterine (endometrial) cancer emerged during follow up and the risk of hip fracture remained significantly (but modestly) reduced. For both forms of hormone therapy, there was no significant increase or decrease in the rate of total cancer (all types combined), cancer mortality, cardiovascular mortality, or all-cause mortality in the overall study population.


The researchers conclude that the findings from the two WHI trials do not support use of hormone therapy for prevention of chronic disease, but treatment is appropriate for symptom management in some women. The absolute risks of adverse events in younger women are lower than in older women, menopausal symptoms are more common in younger age groups, and the quality-of-life benefits are likely to outweigh the risks for many women who seek treatment for symptoms during the menopause transition.  “Short-term use of hormone therapy to manage moderate-to-severe hot flashes or other symptoms in early menopause remains appropriate,  A clear distinction between the use of hormone therapy for symptom management in women with indications for treatment and its use for the purpose of chronic disease prevention is essential,” added Manson.  “Although studies of other hormone therapy formulations , doses, and routes of delivery are needed to find treatments with fewer risks, these medications are now among the best studied treatments in medical history. Clinicians can share information from the WHI trials with their patients and help them make more informed choices.”


Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal Hormone Therapy and Health Outcomes During the Intervention and Extended Poststopping Phases of the Women’s Health Initiative Randomized Trials. JAMA. 2013;310(13):1353-1368. doi:10.1001/jama.2013.278040.

Last Updated on March 19, 2014 by Marie Benz MD FAAD