For hot flushes, oestrogen still reduces both how often and how badly; non-hormonal options mostly reduce how often

Design

Systematic review and meta-analysis of randomised trials, for the American College of Physicians

Population

90 trials in perimenopausal and postmenopausal women with vasomotor symptoms

Primary outcome

Frequency and severity of vasomotor symptoms, quality of life, sleep, harms

Effect

Oestrogen reduced frequency and severity vs placebo; SSRIs, SNRIs, neurokinin antagonists reduced frequency only; low to moderate certainty

This systematic review was commissioned by the American College of Physicians to inform its guideline on menopausal vasomotor symptoms. It included 90 randomised trials of at least eight weeks, searched to March 2026. Certainty of evidence was low to moderate for most comparisons.

Against placebo, oestrogen with or without a progestogen, conjugated oestrogen with bazedoxifene, and oxybutynin reduced both the frequency and severity of hot flushes. Neurokinin receptor antagonists such as fezolinetant, SNRIs, SSRIs, gabapentin and progestogens reduced frequency but not severity. Oestrogen's effect depended on dose, not route. Several drug classes, including the non-hormonal ones, improved quality of life and sleep. On cost, oestrogen was judged high value with high certainty; fezolinetant low value.

The review could not assess long-term harms well: most trials were short and not designed to capture serious adverse events, and observational studies were excluded. That leaves the established risk discussion around oestrogen unchanged. For women without contraindications, oestrogen remains the most effective and most economical option; for those who cannot or prefer not to take it, several non-hormonal drugs help, mainly by reducing how often flushes occur.

• Offer oestrogen as first-line for troublesome hot flushes in women without contraindications, with a progestogen if the uterus is intact.
• For women who cannot take oestrogen, an SSRI, SNRI, gabapentin or a neurokinin receptor antagonist can reduce flush frequency.
• Tell patients that non-hormonal options mainly cut how often flushes occur, rather than how severe each one is.
• Ask about sleep; several options improved sleep quality as well as flushes.
• Use the lowest oestrogen dose that controls symptoms; route did not change efficacy.

Why it matters

It gives a cost and efficacy ranking that puts oestrogen back at the front for women who can take it.

Don't overread it

The review was not designed to weigh long-term harms such as breast cancer or thrombosis; it does not settle safety.

The statistics, in plain English

Certainty of evidence rated low to moderate means future trials could well change the size of these effects. The distinction between frequency and severity matters: a drug can reduce how many flushes occur without making each one milder.

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