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


ABSTRACT: OBJECTIVE: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. METHODS: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 (Clinicaltrials.gov 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. RESULTS: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?

SUBMITTER: Prague JK 

PROVIDER: S-EPMC6092106 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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

Prague Julia K JK   Roberts Rachel E RE   Comninos Alexander N AN   Clarke Sophie S   Jayasena Channa N CN   Mohideen Pharis P   Lin Vivian H VH   Stern Theresa P TP   Panay Nicholas N   Hunter Myra S MS   Webber Lorraine C LC   Dhillo Waljit S WS  

Menopause (New York, N.Y.) 20180801 8


<h4>Objective</h4>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  ...[more]

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