Neurokinin 3 receptor antagonism – the magic bullet for hot flushes?

Abstract

Hot flushes affect 70% of menopausal women and are reported as being the most bothersome symptom by the majority. Hormone replacement therapy and other currently available alternative therapies are not without side-effects and/or have variable efficacy, and so an effective novel therapy could be practice-changing. Over the last 20 years, numerous studies in animal and human models have implicated neurokinin B, a hypothalamic neuropeptide, together with its receptor (NK3R) in the etiology of menopausal hot flushes. Most recently, a randomized, placebo-controlled trial of an NK3R antagonist in symptomatic menopausal women has proven concept suggesting a new therapeutic that can safely and effectively reduce hot flush frequency, severity, bother, and interference without the need for estrogen exposure. Here we review the physiology and neurocircuitry of the reproductive axis, hot flushes, and the evidence that supports this potential new therapeutic approach.

Keywords:

• Neurokinin 3 receptor
• hot flushes
• randomized controlled trial

Conflict of interest

J.K.P. is funded by the MRC. W.S.D. is funded by the NIHR [NIHR Imperial BRC grant reference P61244], is an inventor on a patent application 14762086.8-1453 (which is registered to Imperial Innovations), and was previously an investigator for a separate study of MLE4901 in polycystic ovarian syndrome, for which a consultancy fee was paid.

Source of funding

This work was supported by the UK Medical Research Council [grant reference MR/M024954/1], a National Institute for Health Research Professorship to WSD [grant reference RP-2014-05-001], and the National Institute for Health Research Imperial Biomedical Research Centre.