Hormone therapy should not be used for the primary prevention of chronic conditions in women, according to the U.S. Preventive Services Task Force (USPSTF).
With “moderate certainty,” (level D) the USPSTF recommended against combined estrogen and progestin therapy in postmenopausal women with an intact uterus for the primary prevention of chronic conditions, such as coronary heart disease, dementia, stroke, fractures, and breast cancer.
Estrogen therapy alone in postmenopausal women who have undergone a hysterectomy also should not be prescribed for the primary prevention of chronic conditions (level D recommendation), according to the task force statement in the Journal of the American Medical Association.
The statement is an update to the USPSTF’s 2012 recommendation and confirms their draft statement released earlier in 2017.
“These recommendations remain in line with the recommendations of other governing bodies and most gynecologists,” noted Suzanne Fenske, MD, of the Icahn School of Medicine at Mount Sinai in New York, who was not involved with the USPSTF. “Hormone replacement therapy should not be used for prevention, but 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.”
The recommendations strictly pertain to the primary prevention of chronic medical conditions, and not for the treatment of menopause-related symptoms, including vasomotor and genitourinary symptoms. The recommendations also exclusively apply to asymptomatic, postmenopausal women and not to women who have undergone premature menopause or surgically induced menopause, according to USPSTF member David C. Grossman, MD, MPH, of Kaiser Permanente Washington Health Research Institute in Seattle, and colleagues.
Current FDA-approved indications for hormone therapy include the treatment of vasomotor symptoms, prevention of bone loss, premature hypoestrogenism, and genitourinary symptoms. Approved systemic hormone therapies also carry an FDA-issued black box warning, noting that therapy should be prescribed for the shortest duration at the lowest effective dose in line with treatment goals.
In an evidence report by Gerald Gartlehner, MD, MPH, of University of North Carolina at Chapel Hill, and colleagues, the task force systematically reviewed 18 fair- or good-quality trials — the largest being the Women’s Health Initiative (WHI) — including 40,058 participants, ages 53-79, using systemic hormone therapy, including oral and transdermal treatments, but not local hormones such as rings and creams.
Among the literature reviewed regarding combined estrogen and progestin use in women with an intact uterus, there were a few benefits recognized that were associated with hormone use when compared with placebo among postmenopausal women. These benefits includes a lowered risk for diabetes (-14 per 10,000 women-years absolute event rate difference, 95% CI -24 to -3), all fractures (-44, 95% CI -71 to -13), as well as colorectal cancer (-6, 95% CI -9 to -1).
However, the risks per 10,000 person-years were significantly increased for:
- Invasive breast cancer: 9 more cases (95% CI 1 to 19)
- Coronary heart disease: 8 more cases (95% CI 0 to 18)
- Dementia (probable): 22 more cases (95% CI 4 to 53)
- Gallbladder disease: 21 more cases (95% CI 10 to 34)
- Stroke: 9 more cases (95% CI 2 to 19)
- Venous thromboembolism: 21 more cases (95% CI 12 to 33)
- Urinary incontinence: 876 more cases (95% CI 606 to 1,168)
There were also some benefits associated with estrogen use alone in women without an intact uterus, which included a lowered estimated event rate for invasive breast cancer (-7 per 10,000 person-years absolute event rate difference, 95% CI -14 to 0.4), all fractures (-53, 95% CI -69 to -39), and diabetes (-19, 95% CI -34 to -3).
However, these benefits were similarly outweighed by several possible associated harms:
- Dementia (probable): 12 cases/10,000 person-years event rate difference (95% CI -4 to 41)
- Gallbladder disease: 30 (95% CI 16 to 48)
- Stroke: 11 (95% CI 2 to 23)
- Venous thromboembolism: 11 (95% CI 3 to 22)
- Urinary incontinence: 1,261 (95% CI 880 to 1,689)
‘Women of Average Risk’
In an email to MedPage Today, Michael S. Irwig, MD, vice chair of the American Association of Clinical Endocrinologists (AACE) Reproductive Scientific Committee emphasized that the recommendations “are consistent with those in the AACE Clinical Practice Guideline on Menopause.”
“It should be stressed that the USPSTF recommendations and the AACE guideline recognize that broad recommendations apply to women of average risk and without certain chronic diseases,” noted Irwig, who is at George Washington University in Washington.
“Depending on their medical and family histories, long-term hormone therapy should be considered for certain women as the benefits may outweigh the potential harms in certain scenarios,” he added. Irwig was not involved in the USPSTF recommendations.
In a JAMA Internal Medicine editorial, Deborah Grady, MD, MPH, of the University of California San Francisco, agreed with the recommendations with regard to chronic conditions. However, she warned against the potential for clinicians to “fail to distinguish the use of [hormone therapy] for prevention of chronic diseases from its use for relatively short-term treatment to relieve menopausal symptoms.” She added that “this fear of [hormone therapy] is overblown,” a sentiment echoed by the North American Menopause Society.
In another accompanying editorial in JAMA, Cora Lewis, MD, MSPH, of the University of Alabama at Birmingham, and Melissa Wellons, MD, MSH, of Vanderbilt University Medical Center in Nashville, agreed, writing that “symptom relief [for menopausal symptoms] is distinct from long-term prevention of chronic disease.” They also recommended a future trial testing the timing hypothesis — which suggests a benefit of hormone therapy if initiated closer to the time of menopause — would be beneficial, although unlikely due to the need for “extremely large sample sizes.”
Although there is “no evidence” that the risk-benefit profile for hormone therapies may vary between race, ethnicity, and age groups, the USPSTF highlighted that the majority of women in the WHI were white, and therefore the trial may not have fully parsed out any potential differences. The task force suggested a meta-analysis of individual patient information could be helpful in identifying said differences.
The USPSTF offered alternative approaches to chronic disease prevention in postmenopausal women, such as daily, low-dose aspirin to reduce colorectal cancer and cardiovascular disease risk, and behavioral counseling for cardiovascular disease risk reduction in those who are overweight, obese, or carry other risk factors.
The USPSTF recommendations by Grossman’s group was supported by the Agency for Healthcare Research and Quality (AHRQ). Grossman disclosed no relevant relationships with industry.
The evidence report by Gartlehner’s group was supported by the AHRQ, the U.S. Department of Health and Human Services, and USPSTF. Gartlehner and co-authors disclosed no relevant relationships with industry.
Lewis disclosed serving as principal investigator for the WHI Clinical Center at the University of Alabama at Birmingham. Wellons disclosed serving as a junior faculty consultant for the WHI Southeast Regional Center and a relevant relationship with Pfizer.
Grady disclosed no relevant relationships with industry.