Imperial College London
Alternate

Dr. Channa Jayasena MA PhD MRCP FRCPath

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Reader in Reproductive Endocrinology
 
 
 
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Contact

 

c.jayasena Website

 
 
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Location

 

6N5CCommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Prague:2020:jendso/bvz009,
author = {Prague, J and Abbara, A and Comninos, A and Jayasena, C and higham, C and adaway, J and keevil, B and veldhuis, J and Dhillo, W},
doi = {jendso/bvz009},
journal = {Journal of the Endocrine Society},
title = {Neurokinin 3 receptor antagonists do not increase FSH or estradiol secretion in menopausal women},
url = {http://dx.doi.org/10.1210/jendso/bvz009},
volume = {4},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background: Neurokinin 3 receptor (NK3R) antagonism is a promising novel treatment for menopausal flashes. However, to avoid adverse hormonal effects it is clinically important to first confirm whether gonadotropin and estradiol concentrations change as a result of their administration. Methods: Single-center, randomized, double-blind, placebo-controlled, crossover trial of an oral NK3R antagonist (MLE4901) in 28 women aged 40-62yrs, experiencing >7 hot flashes/24h; some bothersome or severe (Clinicaltrials.gov NCT02668185). Weekly serum gonadotropins and estradiol levels were measured using commercially available automated immunoassays a priori. Serum estradiol was also measured post hoc using a highly sensitive direct assay by liquid chromatography tandem mass spectrometry. Hormone levels were compared by the paired sample t-tests or by the Wilcoxon matched-pairs signed rank test, as appropriate for the distribution of the data. Results: Mean (SD) serum FSH concentration was not significantly increased when taking MLE4901 (72.07 ±19.81iU/L) compared to placebo (70.03 ±19.56iU/L), p=0.26. Serumestradiol was also not significantly altered, irrespective of which assay method was used (median IQR of serum estradiol by immunoassay: placebo 36 ±3pmol/L, MLE4901 36 ± 1pmol/L, p=0.21; median serum highly sensitive estradiol: placebo 12 ± 16pmol/L, MLE4901 5 13 ± 15pmol/L, p=0.70). However, mean (SD) serum LH concentration significantly decreased with MLE4901 (27.63 ± 9.76iU/L) compared to placebo (30.26 ± 9.75iU/L), p=0.0024. Implication: NK3R antagonists do not increase serum estradiol or FSH despite their reduction in hot flashes. This is clinically significant; and highly reassuring for women who have a contraindication to conventional hormone therapy such as prior/existing breast cancer and/or thromboembolism.
AU  - Prague,J
AU  - Abbara,A
AU  - Comninos,A
AU  - Jayasena,C
AU  - higham,C
AU  - adaway,J
AU  - keevil,B
AU  - veldhuis,J
AU  - Dhillo,W
DO  - jendso/bvz009
PY  - 2020///
SN  - 2472-1972
TI  - Neurokinin 3 receptor antagonists do not increase FSH or estradiol secretion in menopausal women
T2  - Journal of the Endocrine Society
UR  - http://dx.doi.org/10.1210/jendso/bvz009
UR  - http://hdl.handle.net/10044/1/74330
VL  - 4
ER  -
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