Endocrine Abstracts

Seventy percent of menopausal women experience vasomotor symptoms (hot flushes/night sweats), which can be highly disruptive and persist for years; 10% describe them as intolerable. Hormone replacement therapy (HRT) and other available treatments have variable efficacy and/or side effects. A novel therapeutic could therefore benefit 10 million in the UK alone, and particularly those who have a contraindication or aversion to HRT. Neurokinin B signalling is upregulated in menopausal women secondary to oestrogen deficiency, and over recent years, together with its receptor (the neurokinin 3 receptor (NK3R)), has increasingly been implicated as an important mediator of menopausal hot flushes. We recently completed the first clinical trial of an NK3R antagonist in a randomised, placebo-controlled, double-blind, crossover study, and showed that hot flush frequency can be reduced by 73% compared to baseline as early as day 3 of treatment (51 percentage point reduction compared to placebo) as well as reducing hot flush severity, bother, and interference. Subsequent work investigating LH pulsatility in a sub-group using mathematical modelling has challenged the long held scientific dogma regarding the hormonal aetiology of vasomotor symptoms; and investigating single nucleotide polymorphisms in the NK3R gene has uncovered further mechanistic detail of hot flush experience and aetiology.