Clinical Pearls & Morning Reports

Posted by Carla Rothaus

Published January 29, 2020


What nonhormonal pharmacologic therapies are available to reduce the frequency and severity of hot flashes?

In the absence of contraindications, systemic hormone therapy remains the most effective therapy for vasomotor symptoms related to menopause. Read the Clinical Practice article here.

Clinical Pearls

Q: What subset of women with menopausal hot flashes are most likely to benefit from hormone therapy?

A: Women younger than 60 years of age or within 10 years after the onset of menopause who have symptomatic menopausal hot flashes or night sweats are most likely to benefit from hormone therapy. Initiating systemic hormone therapy in women older than 60 years of age in general is not recommended. Controversy exists regarding how long hormone therapy can be safely used and when it should be discontinued. Discontinuation is typically suggested after 5 years or by the age of 60. Vasomotor symptoms return in approximately 50% of women after discontinuation; data are lacking to directly compare the effects of stopping “cold turkey” with those of tapering over 3 to 6 months.

Q: Does transdermal estrogen therapy confer a lower risk of thromboembolism than oral therapy?

A: The risk of venous thromboembolism was twice as high among women in the Women’s Health Initiative trial who received oral combination therapy as it was among those assigned to placebo. Similar results have been reported in observational studies involving women taking oral estrogen, although no elevated risk was reported in those taking transdermal estrogen. Data are needed to determine whether transdermal therapy confers a lower risk of thromboembolism than oral therapy.

Morning Report Questions

Q: How are women with early menopause managed?

A: Observational studies involving women with early surgical menopause or primary ovarian insufficiency show increased risks of cardiovascular disease, osteoporosis, and fracture. There is also a higher risk of affective disorders, Parkinson’s disease, cognitive dysfunction, and sexual dysfunction than in women with later menopause. Despite the lack of long-term randomized trials, hormone therapy is recommended — at least until the expected age of natural menopause (approximately 51 years) — to reduce long-term health risks. Higher-dose hormone therapy may be needed to provide symptom relief or protection against bone loss. Alternatively, in young women, oral contraceptive pills (ethinyl estradiol and progestin) provide the benefits of regular cycles and contraception should spontaneous ovulation resume.

Q: What nonhormone therapies are available to reduce the frequency and severity of hot flashes?

A: Nonhormone pharmacologic therapies that have been shown to reduce the frequency and severity of hot flashes in randomized trials include selective serotonin-reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, gabapentinoids, and clonidine. Effective doses of antidepressants for the relief of hot flashes are lower than those commonly used for the treatment of depression, with onset of relief generally occurring within 2 to 3 weeks. Paroxetine mesylate (7.5 mg per day) is the only nonhormonal treatment for vasomotor symptoms that has been approved by the FDA. Paroxetine, a cytochrome CYP2D6 inhibitor, decreases the conversion of tamoxifen to its active metabolite, endoxifen, which may increase the risk of cancer recurrence. Consequently, paroxetine is not recommended for women taking tamoxifen. Limited data from randomized trials associate reductions in hot flashes with weight loss, stress-reducing therapies that involve mindfulness, hypnosis, and cognitive behavioral therapy. Trials of acupuncture, exercise, and yoga for relief of vasomotor symptoms have shown inconsistent or negative results.

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