- Design
- Systematic review and meta-analysis of randomised trials (≥8 weeks)
- Population
- 90 trials in perimenopausal and postmenopausal women with vasomotor symptoms
- Primary outcome
- Vasomotor symptom frequency and severity
- Effect
- Oestrogen, CE/BZA and oxybutynin cut frequency and severity; NKRAs, SSRIs, SNRIs, gabapentin cut frequency only
This systematic review and meta-analysis, done for the American College of Physicians, pooled 90 randomised trials of at least eight weeks in women with menopausal vasomotor symptoms. It was published in Annals of Internal Medicine on 6 October. 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 how often and how severely flushes occurred. Neurokinin receptor antagonists such as fezolinetant, SSRIs, SNRIs, gabapentin and progestogens reduced frequency but not severity. Oestrogen effect varied by dose, not route. Oestrogens, the neurokinin antagonists, SSRIs and SNRIs improved menopause-related quality of life; several non-hormonal options improved sleep. On cost-effectiveness, oestrogen was of high value with high certainty; fezolinetant was of low value.
The review excluded observational studies and most trials were short, so it says little about long-term harms such as breast cancer, venous thrombosis or stroke — which remain the core of the individual risk discussion. It does not replace that discussion, and the formal ACP recommendation is a separate document.
For practice, this supports offering oestrogen as the first consideration in women without contraindications, with non-hormonal drugs as real alternatives, not afterthoughts, when oestrogen is unsuitable or unwanted. In India, oestrogen and the SSRI/SNRI and gabapentin options are inexpensive; fezolinetant's availability and approval status here are uncertain.
- Ask about hot flushes and night sweats in women aged 45–55; many do not raise them.
- In women without contraindications, consider oestrogen first; add a progestogen if the uterus is intact.
- Screen for contraindications before oestrogen: past breast cancer, venous thrombosis, stroke, active liver disease, unexplained vaginal bleeding.
- Where oestrogen is unsuitable, an SSRI, SNRI or gabapentin can reduce flush frequency; oxybutynin also reduced severity.
- Before an SSRI in a woman taking tamoxifen, check for interaction; paroxetine and fluoxetine inhibit its activation.
Why it matters
It reframes oestrogen as the most effective and best-value option, not a treatment of last resort.
Don't overread it
The trials were short and excluded long-term observational data, so the review does not settle long-term breast or vascular risk.
The statistics, in plain English
Most findings rest on low to moderate certainty evidence, meaning further research could change the size of the effects. 'Reduced frequency but not severity' means fewer flushes, but each one about as intense.
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