JoAnn V. Pinkerton, M.D.

N Engl J Med 2020; 382:446-455 DOI: 10.1056/NEJMcp1714787

This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author’s clinical recommendations.

Abstract

A healthy 53-year-old nonobese, menopausal woman presents with an 8-month history of menopausal symptoms, noting worsening hot flashes, soaking night sweats, and sleep disruption with fatigue that is affecting her work. Her mother had breast cancer at 75 years of age. Results of a recent mammogram were negative. The patient has heard that hormone therapy may be harmful but worries about functioning at work. How would you advise this patient?

Guideline

Guidelines from professional societies recommend hormone therapy for symptom relief within 10 years after the onset of menopause4,27,47,49-52 and in women with early menopause or primary ovarian insufficiency, at least until the average age of the onset of menopause.4,27,34,49-52 Vaginal therapies are recommended for genitourinary syndrome of menopause.4,27,34,47,49-52 Recommendations vary regarding the use of hormone therapy to prevent osteoporosis in the absence of vasomotor symptoms. Although some guidelines address the possible cardiovascular benefit of hormone therapy in younger postmenopausal women (Table 2), none recommend hormone therapy for the prevention of heart disease or dementia.4,27,34,48-52 The recommendations in this review are largely concordant with these guidelines.

Conclusions and Recommendations

The woman described in the vignette is healthy, younger than 60 years of age and less than 10 years from the onset of menopause, has an intact uterus, and is seeking therapy for vasomotor symptoms. In line with professional guidelines, discussion with this patient should address the benefits and risks of hormone and nonhormone therapies and the uncertainties regarding the effects of longer-term hormone use.

In this case, an appropriate recommendation would include low-dose oral therapy with estradiol (1 mg or 0.5 mg per day) or a transdermal patch (which delivers a daily dose of ≤0.05 mg), combined with micronized progesterone or a synthetic progestin. If she prefers not to use or has contraindications to hormone therapy, a selective serotonin-reuptake inhibitor could be started (a low dose of escitalopram [10 to 20 mg daily] or the daily dose of 7.5 mg of paroxetine approved by the FDA). Other options are venlafaxine or gabapentin. All these medications are available in generic form.

After 3 to 5 years of hormone therapy, there should be an attempt to taper and eventually discontinue treatment. If symptoms persist, lower doses or transdermal therapy could be offered, with periodic reevaluation of the risks and benefits. If vaginal moisturizers and lubricants are not sufficient for genitourinary symptoms after discontinuation of treatment, low-dose vaginal hormone therapy could be offered.