Endocrine Abstracts

Hot flushes affect 70% of menopausal women and often severely impact physical, psychosocial, sexual, and overall wellbeing. Hormone replacement therapy is effective but is not without risk. Neurokinin B signalling is increased in menopausal women, and has been implicated as an important mediator of hot flushes in animals. We carried out a phase 2, randomised, double-blind, placebo-controlled, single-centre, crossover trial assessed the effectiveness of an oral neurokinin 3 receptor antagonist (NK3R antagonist) on menopausal hot flushes. Participants received 4 weeks of an NK3R antagonist (40 mg, orally, twice daily) and placebo (orally, twice daily) in random order separated by a 2 week washout period. The primary outcome was the total number of hot flushes during the final week of both treatment periods. Analyses were by intention to treat and per protocol using generalised linear mixed models and standard crossover analysis. 28 participants completed the trial and were included in a per-protocol analysis. The NK3R antagonist significantly reduced the total weekly number of hot flushes by 45 percentage points (95% CI 22–67) compared with the placebo (intention-to-treat adjusted means: placebo 49·01 [95% CI 40·81–58·56] vs NK3R antagonist 19·35 [15·99–23·42]; adjusted estimate of difference 29·66 [17·39–42·87], P<0·0001). Treatment was well tolerated. Three participants developed a transaminase rise (alanine aminotransferase 4·5–5·9 times the upper limit of normal) with a normal bilirubin 28 days after starting the NK3R antagonist, which normalised within 90 days (1,2). Treatment with a neurokinin 3 receptor antagonist could be practice changing as it safely and effectively relieves hot flush symptoms without the need for oestrogen exposure.

References: 1. Lancet. 2017 May 6;389(10081):1809–1820.

2. Menopause. 2018 Aug;25(8):862–869.