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USPSTF recommends against HT for prevention of chronic conditions in postmenopausal women

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December 12, 2017

Gerald Gartlehner
Gerald Gartlehner

Hormone therapies in menopausal women are associated with some beneficial effects, such as decreased risk for diabetes and fracture, but are also associated with increased risks for stroke, thromboembolic events, gallbladder disease and urinary incontinence, according to an evidence report and systematic review for the U.S. Preventive Services Task Force.

In 2012, the USPSTF recommended against the use of HT for prevention of chronic conditions, and the current update continues to recommend against its use.

“HT in postmenopausal women has benefits and harms,” Gerald Gartlehner, MD, MPH, associate director of RTI International-University of North Carolina at Chapel Hill Evidence-based Practice Center, told Endocrine Today. “Overall, harms appear to outweigh benefits. The evidence whether early initiation of HT (the timing hypothesis) in younger women has a better benefits-harms profile is weak and inconclusive.”

Gartlehner and colleagues evaluated 18 trials published between June 1, 2011, and Aug. 1, 2016, to update evidence for the USPSTF on the benefits and harms of HT in reducing the risks for chronic conditions.

Mean duration of the trials was 3.5 years, the mean age of participants ranged from 53 to 79 years, and the majority were white (from 59% to 99% across the studies). Specifically, the Women’s Health Initiative trials were the only studies included that were powered to assess HT effectiveness for the primary prevention of various chronic conditions and enrolled generally health postmenopausal women aged 50 to 79 years to compare conjugated equine estrogen, with or without medroxyprogesterone, with placebo. The WHI trials had the longest follow-up.

Participants taking estrogen-only therapy compared with placebo had significantly decreased risks for osteoporotic fractures (–53 fractures per 10,000 patient-years) and diabetes (–19 cases per 10,000 patient-years) and a nonsignificantly decreased risk for invasive breast cancer (–7 cases per 10,000 patient-years).

The risks for colorectal cancer, incident diabetes, new diabetes diagnoses and fractures were also decreased with estrogen plus progestin therapy compared with placebo.

Estrogen-only therapy increased risks for gallbladder disease (30 more cases per 10,000 patient-years), stroke (11 more cases per 10,000 patient-years), urinary incontinence (1,261 more cases per 10,000 patient-years) and venous thromboembolism (11 more cases per 10,000 patient-years). Estrogen plus progestin therapy increased the risks for invasive breast cancer (9 more cases per 10,000 person-years), coronary events (8 more cases per 10,000 patient-years), probable dementia (22 more cases per 10,000 patient-years), gallbladder disease (21 more cases per 10,000 patient years), stroke (9 more cases per 10,000 patient-years), urinary incontinence (876 more cases per 10,000 patient-years) and VTE (21 more cases per 10,000 patient-years).

“Don’t use HT to prevent chronic conditions. Overall, risk for harms seems to outweigh the benefits. Besides that, there are better ways to prevent chronic conditions; encourage patients to get exercise and eat better,” Gartlehner said.  

“Treatment of menopausal symptoms, however, is different,” Gartlehner said. “This was not addressed in our report. Research into early initiation that focuses on health outcomes using a more diverse population (80% of women in existing studies were white) and research using different formulations of HT and different routes of application are needed.”

In an accompanying editorial published in JAMA, Cora E. Lewis, MD, MSPH, of the division of preventive medicine, department of medicine at the University of Alabama at Birmingham School of Medicine, and Melissa F. Wellons, MD, MHS, of the division of diabetes, endocrinology and metabolism, department of medicine at Vanderbilt University Medical Center, wrote that the recommendations are based “only on evidence from randomized trials and do not pertain to women considering hormone therapy for vasomotor symptoms, given the USPSTF mandate to consider specific preventive care services for patients without related signs and symptoms of illness.”

They also note that it is appropriate for relatively healthy, younger menopausal women to draw “comfort” from long-term WHI data.

“These women can consider hormone therapy for symptom relief,” they wrote. “Physicians also have more evidence to impart to their patients during discussions about therapies for menopausal symptoms. Symptom relief is distinct from long-term prevention of chronic disease.”

In another editorial published in JAMA Cardiology, Nanette K. Wenger, MD, wrote that although HT is not recommended for preventing chronic conditions, “recent long-term all-cause and cause-specific mortality data from the WHI should offer reassurance to women considering menopausal hormone therapy for menopausal symptoms.”

“After more than 18 years of follow-up, all-cause mortality rates for the overall cohort were not significantly different for the hormone vs. placebo groups,” she wrote. “Menopausal hormone therapy for 5 to 7 years was not associated with a risk of long-term all-cause, cardiovascular or cancer mortality.” – by Amber Cox

For more information:

Gerald Gartlehner, MD, MPH, can be reached at


Lewis CE, et al. JAMA. 2017;doi:10.1001/jama.2017.16974.

Wenger NK. JAMA Cardio. 2017;doi:10.1001/jamacardio.2017.4575.

US Preventive Services Task Force. JAMA. 2017;doi:10.1001/jama.2017.18261.

Disclosures: Lewis reports she served as principal investigator for the WHI Clinical Center and the University of Alabama at Birmingham. Wellons reports she has served as a junior faculty consultant for the WHI Southeast Regional Center and serves for Pfizer on a roundtable for conjugated equine estrogens/bazedoxifene. All members of the USPSTF report they receive travel reimbursement and an honorarium for participating in USPSTF meetings. No other authors report any relevant financial disclosures.

itj+ Perspective

Suzanne Fensle

HT remains a controversial issue. Use of estrogen therapy became popular in the late 1960s to keep women “feminine” even after menopause. In the 1980s, HT was touted for its medical benefits, including prevention of osteoporosis and cardio-protection. A follow-up study by WHI demonstrated increased risks for breast cancer and cardiac disease with HT, but this study included an older population and women who had experienced menopause at least 10 to 15 years prior. After this study, HT lost favor. The data from the WHI study were reinterpreted, and the women in the study were grouped by age, and different outcomes were appreciated. The data demonstrated that there appeared to be some cardio-protective benefit to HT in the population of women near menopause, and the opposite was observed in women who were started on HT remote from menopause.

It had been debated as to whether HT should be used as preventive medicine for women to combat some medical ailments, such as cardiac disease, that afflict women after menopause. Cardiac disease is the No. 1 cause of death in women after menopause. To date, we have no effective preventive medicine for this disease in women. Most recently, the USPSTF has issued recommendations against the use of HT for prevention of chronic conditions, basing its recommendations, again, on the WHI study. The USPSTF has found that HT has some benefit in reducing the risks for fractures and, potentially, diabetes. The USPSTF has found that HT can increase the risk for coronary artery disease, stroke, blood clot, gallbladder disease, urinary incontinence and dementia. With these risks, the USPSTF states the benefits are not enough to support use of HT as preventive medicine. HT remains a beneficial treatment for menopausal symptoms recalcitrant to other treatment as long as the patient is an appropriate candidate and aware of the risks.

These recommendations remain in-line with the recommendations of other governing bodies and most gynecologists. There is no debate as to whether HT may be used in treatment of menopause in women who did not respond to other treatments and whose quality of life is greatly affected, as long as they have no contraindications, are aware of the risks and take the smallest dosage necessary for the shortest period of time necessary.

Suzanne Fenske, MD

Assistant Professor of Obstetrics, Gynecology and Reproductive Science
Icahn School of Medicine at Mount Sinai

Disclosure: Fenske reports no relevant financial disclosures.