By Robert W. Rebar, MD
Professor and Chair, Department of Obstetrics and Gynecology, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, MI
Dr. Rebar reports no financial relationships relevant to this field of study.
Menopausal hormone therapy is the most effective treatment for symptoms of the menopause, and benefits may exceed risks for most women within 10 years of menopause.
Stuenkel CA, Davis SA, Gompel A, et al. Treatment of symptoms of the menopause: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2015;100:3975-4011.
The Treatment of Symptoms of the Menopause Task Force appointed by the Endocrine Society developed a consensus document on the role of menopausal hormone treatment (MHT). Based on evidence, the task force concluded MHT is the most effective treatment for vasomotor symptoms (VMS) and improves genitourinary symptoms, sleep disturbance, menopause-associated anxiety and depressive symptoms, and arthralgia. It further concluded that the benefits may exceed the risks for the majority of symptomatic postmenopausal women < 60 years of age or within 10 years of the onset of menopause. The task force further emphasized the need for healthcare providers and their patients to use a shared decision-making approach to choose the most appropriate therapy only after a careful assessment of individual risks and benefits.
Use of MHT is not warranted to prevent coronary heart disease, breast cancer, or dementia. The task force noted there are other, albeit less effective, therapies for individuals with VMS who cannot or choose not to use MHT. Similarly, they noted that low-dose vaginal estrogen and ospemifene are effective in treating the genitourinary syndrome of menopause and that various vaginal moisturizers and lubricants are also effective for those who do not choose hormonal therapy. The task force further emphasized that estrogens alone should be prescribed for women without a uterus, and progestogens should be added only for those with a uterus. Starting dosages generally should be lower than those utilized in the Women’s Health Initiative (WHI, 0.625 mg conjugated equine estrogens with or without 2.5 mg medroxyprogesterone daily) and should be titrated upward until the appropriate clinical response is achieved. The task force also recommended against the use of custom compounded hormones. Although the use of MHT is recommended for the shortest duration possible, strong evidence to support this conclusion is lacking. Thus, clinicians and patients should reassess MHT continuation yearly and consider the risks and individual benefits beyond five years of use. Continuing therapy can be considered for those who become symptomatic after stopping MHT, those at high risk of osteoporotic fractures, and those for whom alternative therapies are not appropriate and who have no contraindications to continuing therapy. For young women with premature ovarian insufficiency or premature menopause, MHT can be taken until the time of anticipated natural menopause when the use of continued MHT can be reassessed. The task force concluded its recommendations by noting that the most important question for postmenopausal women is how to balance menopausal symptom relief with the prevention of chronic diseases of aging and by emphasizing the need for further research.
COMMENTARY
Publication of the initial results of the WHI in 2002 changed the use of hormone therapy for menopausal women dramatically.1 In some sense, the changes were warranted: Provide no therapy to any individual without a specific indication, as clinicians were administering MHT to women who had no reason to initiate therapy. Simultaneously, the report and ensuing publicity led to a marked reduction in usage of MHT even by symptomatic menopausal women who might well have benefited greatly. That the initial findings of the WHI were misleading and are more complex and difficult to interpret than initially reported was the subject of a recent commentary.2 In fact, in a recent reanalysis of the data from the WHI for women 50 to 59 years of age, benefits for women using estrogen alone or estrogen and progestin seemed to outweigh the risks.3 To be sure, the WHI was not powered for age-related subset analyses, and none of the data were significant, but the data indicated that all-cause mortality was favorably influenced in both arms of the study for women initiating MHT close to menopause. When these data are analyzed over a five-year period, there seems to be similarly beneficial effects.4
This guideline is a powerful statement recommending consideration of use of MHT — and it has been provided to a group consisting largely of internist-endocrinologists. Moreover, despite the reanalysis of the WHI data, most clinicians remain wary of the use of MHT, and the majority of symptomatic women in the United States who might benefit from MHT are, in fact, not receiving therapy. Women’s healthcare providers have an obligation to educate other clinicians about the responsible use of MHT and a responsibility to provide accurate and appropriate information to patients.
While this guideline hardly provides all the answers, it does provide a framework for discussing the use of MHT with other clinicians and patients. There is clearly a balance that must be struck between ruling out MHT for all women and providing MHT to all. It is now clear that MHT should not be provided to women to prevent chronic diseases, such as cardiovascular disease, but it continues to play a critical role in treating women with VMS. This is particularly relevant in light of recent data from the Study of Women Across the Nation (SWAN), which noted that frequent VMS, defined as experiencing hot flushes or night sweats for six days in the two weeks before an exam, lasted more than seven years during the menopausal transition and persisted for four and a half years following the final menstrual period in women who exhibited such symptoms.5 Women who were premenopausal or early postmenopausal when they first reported frequent VMS had the longest total VMS duration (median > 11.8 years) and persistence following the final menstrual period (median 9.4 years). Interestingly, the SWAN noted differences among various ethnic groups, with African-American women experiencing the longest total duration (median 10.1 years). Earlier SWAN data showed that experiencing frequent VMS is highly related to anxiety, depression, sleep disturbances, quality of life, cardiovascular risk, bone health, and how much VMS bother women. Thus, MHT should be of significant benefit to women with frequent VMS, and frequent VMS can be expected to last for several years. However, such therapy should be provided only after appropriate risk assessment and counseling.
Over time, as the information about MHT becomes more widely disseminated, one can only hope MHT will be used more appropriately when it should and avoided when usage is inappropriate. One also should recognize that a single large, randomized trial, which was inappropriately analyzed, deprived an entire generation of women from receiving potential benefits of MHT. Clinicians should remain vigilant to ensure this never happens again.
REFERENCES
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Roussouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002;288:321-333.
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Brewer MA. Hormone replacement therapy controversies: Have we harmed women? OB/GYN Clinical Alert 2016;32:68-70.
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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;310:1353-1368.
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Santen RJ, Allred DC, Ardoin SP, et al. Postmenopausal hormone therapy: an Endocrine Society scientific statement. J Clin Endocrinol Metab 2010;95:s1-s66.
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Avis NE, Crawford SL, Greendale G, et al. Duration of menopausal vasomotor symptoms over the menopausal transition. JAMA Intern Med 2015;175:531-539.
