By Robert W. Rebar, MD

Professor and Chair, Department of Obstetrics and Gynecology, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo

Dr. Rebar reports no financial relationships relevant to this field of study.

SYNOPSIS: Recommendations for menopausal hormone therapy were widely publicized and adopted following the original publication of the results of the Women’s Health Initiative, affecting both initiation and continuation of estrogen therapy through at least 2013.

SOURCE: Crawford SL, et al. Menopausal therapy trends before versus after 2002: Impact of the Women’s Health Initiative study results. Menopause 2018; Dec. 21. doi: 10.1097/GME.0000000000001282. [Epub ahead of print].

To better appreciate how to educate patients and providers about menopausal hormone therapy (MHT; generally regarded as estrogen plus progesterone in women with a uterus and as estrogen alone in women without a uterus), Crawford et al analyzed survey data from up to 14 approximately annual visits collected between 1996 and 2013 from 3,018 participants in the NIH’s multicenter Study of Women’s Health Across the Nation (SWAN). Investigators wished to determine the effect of the initial 2002 report1 of data from the Women’s Health Initiative (WHI), which involved administration of estrogen-progestin therapy to postmenopausal women and ended prematurely because of significant concerns about safety on initiation and continuation of MHT. SWAN included women of diverse ethnicities 42-52 years of age with an intact uterus and one or two ovaries to examine the changes that occur longitudinally across the menopausal transition. MHT initiation declined from 8.6% before publication of the WHI results to 2.8% post-WHI (P < 0.0001), with a decrease in continuation as well from 84.0% to 62.0% (P < 0.0001). Although the magnitude of the lower initiation and continuation varied among ethnic groups, it occurred in all and tended to be greater in women who might be expected to benefit more from MHT based on current guidelines, specifically younger women with severe vasomotor flushes. More frequent vasomotor symptoms were associated with greater initiation of MHT, both pre- and post-WHI (P < 0.001 for both), but the largest decrease (9.4% decline) occurred in women who reported the most frequent hot flashes. Similarly, young postmenopausal women were less apt to begin MHT and were more likely to discontinue use despite current guidelines. Reasons for initiating MHT changed after publication of WHI, with the largest declines for use among those who wished to reduce the risk of osteoporosis and heart disease. The most commons reasons for discontinuing MHT were for media reports and provider advice.

COMMENTARY

The initial report that the WHI was ending early because of safety concerns changed our views on MHT forever. MHT should not be used for prevention of coronary heart disease, breast cancer, or dementia. Despite subsequent studies and guidelines promoting appropriate use of MHT in certain symptomatic postmenopausal women, providers who are not gynecologists are significantly less likely to recommend use of MHT (as noted in this report), regardless of patient symptomatology. I have been frustrated when patients who clearly would benefit from MHT were advised not to begin or to discontinue therapy after seeing another provider. Yet, another large cohort study, this time from Denmark, documented that long-term follow-up (median, 17.6 years) of almost 30,000 women between the ages of 50 and 64 years representing 7% of the Danish female population enrolled between 1993 and 1997 showed no association of MHT and overall mortality.2 This squares with a recent reanalysis of the data from the WHI documenting the safety of MHT when begun within five years of menopause and documenting no increase in all-cause mortality.3

American women have had their reproductive lives turned topsy-turvy three times in the last 50 years. In the 1960s, they witnessed the publicity surrounding combination oral contraceptive agents and the higher risks for several significant diseases, including deep venous thrombosis, stroke, and myocardial infarction. The far greater risks of pregnancy compared to the use of oral contraceptives were not emphasized in press releases. Many women discontinued use of this contraception only to suffer unintended pregnancies. Then followed the debacle related to the Dalkon Shield intrauterine device (IUD), which resulted in a dramatic decline in IUD usage in the United States; today, this usage remains lower than in most other industrialized countries. More recently, women were subjected to incompletely analyzed findings from the WHI, which has lowered MHT use rates — even when it is indicated.

Clinicians counseling women on the risks and benefits of MHT should remain positive. We need to emphasize to patients and less-informed providers that MHT is extremely useful in improving quality of life and is warranted for women with vasomotor flushes,4 plays a role in protection against fracture risk,5 and can improve sexual function.6 Moreover, we have long known that MHT is warranted to prevent coronary heart disease,7 as well as to prevent symptoms associated with estrogen deficiency following bilateral oophorectomy in premenopausal women and in those with premature menopause.8

Both the North American Menopause Society and the Endocrine Society have created guidelines for the use of MHT.9,10 Both effectively agree that MHT is the most effective therapy for vasomotor symptoms and the genitourinary syndrome of menopause (GSM) and can prevent bone loss. Both emphasize the need to individualize therapy based on clinical factors and patient preference and note that benefits may exceed risks for most women < 60 years of age. Both note that low-dose vaginal estrogen therapy is effective for treatment of GSM in women without indications for systemic MHT.

For those not desiring local estrogen, several vaginal moisturizers and lubricants are available. Neither guideline recommends a firm age by which MHT must be discontinued, focusing on shared decision-making with the patient. All women should embrace healthy lifestyle measures. It is these recommendations that we must emphasize in counseling patients and in educating other providers.

REFERENCES

  1. Rossouw JE, 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.
  2. Holm M, et al. Pattern of mortality after menopausal therapy: Long-term follow up in a population-based cohort. BJOG 2019;126:55-63.
  3. Manson JE, et al. Menopausal hormone therapy and long-term all-cause and cause-specific mortality. The Women’s Health Initiative randomized trials. JAMA 2017;318:927-938.
  4. Bachmann GA, et al. Lowest effective transdermal 17beta-estradiol dose for relief of hot flushes in postmenopausal women. A randomized controlled trial. Obstet Gynecol 2007;110:771-779.
  5. Jackson RD, et al. Effects of conjugated equine estrogen on risk of fractures and BMD in postmenopausal women with hysterectomy: Results from the Women’s Health Initiative randomized trial. J Bone Miner Res 2006;21:817-828.
  6. Simon JA, et al. Sexual well-being after menopause: An international Menopause Society White Paper. Climacteric 2018;21:415-427.
  7. Colditz GA, et al. Menopause and the risk of coronary heart disease in women. N Engl J Med 1987;316:1105-1110.
  8. Rebar RW. Premature menopause. Semin Repro Endocrinol 1983;1:169-176.
  9. The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. The 2017 hormone therapy position statement of the North American Society Menopause Society. Menopause 2017; Jul. 24. doi: 10.1097/GME.0000000000000921.
  10. Stuenkel CA, et al. Treatment of symptoms of the menopause: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2015;100:3975-4011.