- Design
- Systematic review and meta-analysis of randomised trials for the American College of Physicians
- Population
- 90 trials in females with menopausal vasomotor symptoms, at least 8 weeks of treatment
- Primary outcome
- Vasomotor symptom frequency and severity, quality of life, sleep, endometrial outcomes, serious adverse events
- Effect
- Estrogens, estrogen with bazedoxifene and oxybutynin reduced frequency and severity; other classes reduced frequency only; certainty low to moderate
This systematic review and meta-analysis, done for the American College of Physicians, searched to March 2026 and included 90 randomised trials of at least 8 weeks of treatment in females with vasomotor symptoms. Certainty of evidence was low to moderate for most comparisons.
Compared with placebo, estrogens with or without progestogens, conjugated estrogen with bazedoxifene and oxybutynin reduced both the frequency and severity of symptoms. Neurokinin receptor antagonists, SNRIs, SSRIs, gabapentin and progestogens reduced frequency but not severity. Estrogen efficacy varied by dose but not by route.
Estrogens (with or without progestogens), bazedoxifene combinations, neurokinin receptor antagonists, SNRIs and SSRIs improved menopause-related quality of life. Gabapentin, neurokinin receptor antagonists, oxybutynin, SNRIs and SSRIs improved sleep. Few serious adverse events were reported, but most studies were short and not designed to detect long-term harms. Estrogens were judged of high economic value and the neurokinin receptor antagonist fezolinetant of low value.
This is a systematic review that informs guidance; the review itself is not a guideline. Choice of drug still depends on the individual's risks, particularly for estrogen.
- Compared with placebo, estrogens reduced both the frequency and severity of vasomotor symptoms.
- For people who cannot or prefer not to take estrogen, SSRIs, SNRIs, gabapentin and neurokinin receptor antagonists reduced frequency.
- Sleep improved with gabapentin, oxybutynin, SNRIs, SSRIs and neurokinin receptor antagonists.
- Long-term harms were not well studied; review individual risk factors before prescribing estrogen.
- Compare cost: the review rated estrogens high value and fezolinetant low value.
Why it matters
It lets a physician compare treatment classes for hot flushes on benefits, harms and cost in one place.
Don't overread it
Short trials and limited harms data mean this does not establish long-term safety of any option, and the review did not include observational studies of long-term harm.
The statistics, in plain English
Certainty of evidence rated low to moderate means future studies could change the estimates. Most trials ran only a few months, so they say little about long-term safety such as endometrial effects.
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