Send to

Choose Destination
Menopause. 2018 Aug;25(8):862-869. doi: 10.1097/GME.0000000000001090.

Neurokinin 3 receptor antagonism rapidly improves vasomotor symptoms with sustained duration of action.

Author information

Department of Investigative Medicine, Imperial College London, United Kingdom.
Millendo Therapeutics, Inc., Ann Arbor, MI.
TPS Pharmaceutical Consulting, Saline, MI.
Department of Gynaecology, Queen Charlotte's & Chelsea Hospital and Chelsea & Westminster Hospital, London, United Kingdom.
Institute of Reproductive and Development Biology, Imperial College London, United Kingdom.
Institute of Psychiatry, Psychology & Neuroscience, King's College London, United Kingdom.
Emerging Innovations Unit, Scientific Partnering and Alliances, IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom.



Seventy percent of postmenopausal women experience vasomotor symptoms, which can be highly disruptive and persist for years. Hormone therapy and other treatments have variable efficacy and/or side effects. Neurokinin B signaling increases in response to estrogen deficiency and has been implicated in hot flash (HF) etiology. We recently reported that a neurokinin 3 receptor (NK3R) antagonist reduces HF in postmenopausal women after 4 weeks of treatment. In this article we report novel data from that study, which shows the detailed time course of this effect.


Randomized, double-blind, placebo-controlled, single-center, crossover trial of an oral NK3R antagonist (MLE4901) for vasomotor symptoms in women aged 40 to 62 years, experiencing ≥7 HF/24 hours some of which were reported as bothersome or severe ( NCT02668185). Thirty-seven women were randomized and included in an intention-to-treat analysis. To ascertain the therapeutic profile of MLE4901, a post hoc time course analysis was completed.


By day 3 of treatment with MLE4901, HF frequency reduced by 72% (95% CI, -81.3 to -63.3%) compared with baseline (51 percentage point reduction compared with placebo, P < 0.0001); this effect size persisted throughout the 4-week dosing period. HF severity reduced by 38% compared with baseline by day 3 (95% CI, -46.1 to -29.1%) (P < 0.0001 compared with placebo), bother by 39% (95% CI, -47.5 to -30.1%) (P < 0.0001 compared with placebo), and interference by 61% (95% CI, -79.1 to -43.0%) (P = 0.0006 compared with placebo); all continued to improve throughout the 4-week dosing period (to -44%, -50%, and -70%, respectively by day 28, all P < 0.0001 compared with placebo).


NK3R antagonism rapidly relieves vasomotor symptoms without the need for estrogen exposure.

Supplemental Content

Full text links

Icon for Wolters Kluwer Icon for PubMed Central
Loading ...
Support Center