For decades, the conversation about treating moderate to severe vasomotor symptoms in women who can’t take HRT has been a short one. SSRIs, SNRIs, gabapentin, clonidine. All borrowed from other indications. None designed for the underlying mechanism. NICE has now recommended the first drug in a genuinely new class.
In TA1143, published on 31 March 2026, NICE recommends a neurokinin 3 (NK3) receptor antagonist as an option for treating moderate to severe vasomotor symptoms associated with menopause when HRT is unsuitable.¹ The accompanying NICE announcement estimated that around 500,000 women in England could be eligible to benefit.²
The mechanism is genuinely new for this indication. KNDy neurons (kisspeptin, neurokinin B, dynorphin) sit in the hypothalamic thermoregulatory centre and are normally inhibited by oestrogen. When oestrogen falls at menopause, neurokinin B signalling becomes unopposed. KNDy activity increases. Thermoregulation destabilises. Hot flushes follow.³ Blocking the NK3 receptor reverses that signalling cascade directly.
The phase 3 SKYLIGHT 1 trial, published in The Lancet, demonstrated rapid reductions in both frequency and severity of moderate to severe vasomotor symptoms, with separation from placebo evident within the first weeks of treatment.⁴
The clinical caveats matter. Hepatotoxicity is a known class effect. The MHRA-approved label requires baseline liver function tests before initiation, then monthly monitoring for the first three months, with further checks at six and nine months. Treatment is contraindicated in cirrhosis, severe renal impairment, and concomitant use with CYP1A2 inhibitors.⁵
For UK primary care, this is positioned as second-line. NICE NG23 still recommends HRT as first-line for vasomotor symptoms in women without contraindications.⁶ The new class is for women in whom HRT is unsuitable: those with hormone-sensitive cancer history, prior thromboembolism, or personal preference against hormonal therapy. The British Menopause Society welcomed the decision but noted that integration into primary and secondary care will take time.⁷
One important caveat. Many integrated care boards are still working through local implementation and formulary integration. At least one ICB has explicitly asked primary care prescribers not to initiate until local guidance is issued.⁸ Check your own ICB position before acting on a request.
For the women who fit the criteria, this is the first time in twenty years a genuinely new mechanism has reached the NHS. The first prescription requests will come quickly. Familiarity with the monitoring schedule, and with your local formulary position, is the practical priority.
References
National Institute for Health and Care Excellence. Fezolinetant for treating moderate to severe vasomotor symptoms associated with menopause. Technology appraisal guidance TA1143. Published 31 March 2026. Available at: https://www.nice.org.uk/guidance/ta1143
National Institute for Health and Care Excellence. 500,000 eligible to benefit from new non-hormonal treatment for hot flushes caused by menopause. News release, March 2026. Available at: https://www.nice.org.uk/news/articles/500-000-eligible-to-benefit-from-new-non-hormonal-treatment-for-hot-flushes-caused-by-menopause
Rance NE, Dacks PA, Mittelman-Smith MA, Romanovsky AA, Krajewski-Hall SJ. Modulation of body temperature and LH secretion by hypothalamic KNDy neurons: a novel hypothesis on the mechanism of hot flushes. Front Neuroendocrinol. 2013;34(3):211-227. doi:10.1016/j.yfrne.2013.07.003
Lederman S, Ottery FD, Cano A, et al. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study. Lancet. 2023;401(10382):1091-1102. doi:10.1016/S0140-6736(23)00085-5
Electronic Medicines Compendium. Veoza 45 mg film-coated tablets: Summary of Product Characteristics. Available at: https://www.medicines.org.uk/emc/product/15222
National Institute for Health and Care Excellence. Menopause: identification and management. NICE guideline NG23. Last updated November 2024. Available at: https://www.nice.org.uk/guidance/ng23
British Menopause Society. NICE supports NHS prescribing of fezolinetant. March 2026. Available at: https://thebms.org.uk/2026/03/nice-supports-nhs-prescribing-of-fezolinetant/
North Central London ICB. Awaiting local guidance on Fezolinetant (Veoza) for menopause hot flush symptoms. Available at: https://gps.northcentrallondon.icb.nhs.uk/news/awaiting-local-guidance-on-fezolinetant-veoza-r-for-menopause-hot-flush-symptoms
Medicine Central is a clinical evidence review for UK primary care clinicians. Content reflects evidence current at time of publication and should be read alongside local formulary and clinical guidance. For healthcare professionals only.
