Vasomotor symptoms: oestrogen cuts frequency and severity; most alternatives cut frequency only

Design

Systematic review and meta-analysis of randomised trials

Population

90 trials in perimenopausal and postmenopausal women with vasomotor symptoms

Primary outcome

Vasomotor symptom frequency and severity, quality of life, sleep and harms

Effect

Oestrogen reduced frequency and severity; NKRAs, SNRIs, SSRIs, gabapentin reduced frequency only

Reviewers for the American College of Physicians pooled 90 randomised trials of at least eight weeks comparing drug treatments for menopausal hot flushes and night sweats with placebo, published in Annals of Internal Medicine on 6 October 2026.

Oestrogen, with or without a progestogen, and conjugated oestrogen with bazedoxifene reduced both how often and how badly symptoms occurred, and improved menopause-related quality of life. Efficacy varied with dose but not route. Neurokinin receptor antagonists such as fezolinetant, SNRIs, SSRIs, gabapentin and progestogens reduced frequency but not severity. Oxybutynin reduced both. Gabapentin, the neurokinin antagonists, oxybutynin and the antidepressants improved sleep. Oestrogen was rated of high economic value and fezolinetant of low value.

Most trials were short and not designed to detect long-term harms such as breast cancer or venous thromboembolism, and the review excluded observational data that address those risks. For a physician managing a woman with cardiovascular risk factors, migraine or a history of thrombosis, the practical value is in the non-hormonal list: each option reduces frequency, each has a different side-effect profile, and head-to-head data are scarce.

• Offer oestrogen as the most effective option for bothersome vasomotor symptoms where there is no contraindication.
• Add a progestogen for women with a uterus to protect the endometrium.
• For women who cannot take hormones, consider an SNRI, SSRI, gabapentin or oxybutynin, matched to comorbidities.
• Check for interactions before an SSRI or SNRI in women on tamoxifen, which needs CYP2D6 activity.
• Use gabapentin at night where sleep disturbance is the main complaint.

Why it matters

Physicians managing women with contraindications to hormones now have a ranked, evidence-graded non-hormonal list.

Don't overread it

Short trials cannot show long-term safety; this review did not weigh breast cancer or thrombosis risk.

The statistics, in plain English

Low to moderate certainty means further trials could change these estimates. The distinction between frequency and severity matters: fewer flushes that are just as intense may or may not feel like improvement to the patient.

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