05Non-Hormonal Therapy for Vasomotor Symptoms
For the women who cannot, or will not, take oestrogen — and there are many.
Key takeaways
- —NK3/NK1-NK3 antagonists are the first genuinely mechanism-targeted non-hormonal class, with effect sizes approaching but not matching oestrogen.
- —Paroxetine and fluoxetine are potent CYP2D6 inhibitors and reduce conversion of tamoxifen to endoxifen — use venlafaxine or citalopram instead.
- —CBT does not reduce flush frequency much but reliably reduces the bother and interference score — a legitimate outcome.
- —Placebo response in VMS trials runs at 30–50%, which is why uncontrolled testimonials for supplements are so persuasive and so unreliable.
- —Fezolinetant requires baseline and periodic liver function monitoring following post-marketing hepatic injury reports.
Graded claims
Fezolinetant reduces moderate-severe VMS frequency and severity vs placebo
Established — RCT / guideline-gradeSKYLIGHT 1 and 2, replicated.
Elinzanetant improves VMS and sleep disturbance vs placebo
Established — RCT / guideline-gradeOASIS 1–3.
Venlafaxine and escitalopram reduce VMS frequency vs placebo
Supported in defined populationsMsFLASH network trials — modest but consistent.
Paroxetine should be avoided in women on tamoxifen
Established — RCT / guideline-gradeCYP2D6 inhibition reduces endoxifen; associated with worse breast cancer outcomes in cohort data.
CBT reduces the bother and impact of hot flushes
Supported in defined populationsMENOS trials — impact scores improve more than objective frequency.
Black cohosh reduces moderate-severe VMS
Popular, weak or conflicting supportHeterogeneous, largely null vs placebo; hepatotoxicity case reports.
Evening primrose oil relieves VMS
Refuted or actively misleadingNo convincing controlled evidence.
Supporting references
- The 2023 Nonhormone Therapy Position Statement of The North American Menopause Society — Menopause 2023 https://pubmed.ncbi.nlm.nih.gov/37252752/
- Efficacy and safety of fezolinetant (SKYLIGHT 1) — Lederman et al., Lancet 2023 https://pubmed.ncbi.nlm.nih.gov/36924778/
- Cognitive behavioural therapy for menopausal symptoms (MENOS trials) — Ayers et al., Menopause 2012 https://pubmed.ncbi.nlm.nih.gov/22334056/