Neurokinin 3 Receptor Antagonists Do Not Increase FSH or Estradiol Secretion in Menopausal Women.
NK3R antagonists
breast cancer
estradiol
flashes
menopause
Journal
Journal of the Endocrine Society
ISSN: 2472-1972
Titre abrégé: J Endocr Soc
Pays: United States
ID NLM: 101697997
Informations de publication
Date de publication:
01 Feb 2020
01 Feb 2020
Historique:
received:
08
07
2019
accepted:
13
11
2019
entrez:
23
4
2020
pubmed:
23
4
2020
medline:
23
4
2020
Statut:
epublish
Résumé
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. Single-center, randomized, double-blind, placebo-controlled, crossover trial of an oral NK3R antagonist (MLE4901) in 28 women aged 40 to 62 years, experiencing >7 hot flashes/24 h; 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 Mean (standard deviation) serum follicle-stimulating hormone (FSH) concentration was not significantly increased when taking MLE4901 (72.07 ± 19.81 IU/L) compared to placebo (70.03 ± 19.56 IU/L), 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.
Sections du résumé
BACKGROUND
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
METHODS
Single-center, randomized, double-blind, placebo-controlled, crossover trial of an oral NK3R antagonist (MLE4901) in 28 women aged 40 to 62 years, experiencing >7 hot flashes/24 h; 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
RESULTS
RESULTS
Mean (standard deviation) serum follicle-stimulating hormone (FSH) concentration was not significantly increased when taking MLE4901 (72.07 ± 19.81 IU/L) compared to placebo (70.03 ± 19.56 IU/L),
IMPLICATION
CONCLUSIONS
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.
Identifiants
pubmed: 32318647
doi: 10.1210/jendso/bvz009
pii: bvz009
pmc: PMC7159071
doi:
Banques de données
ClinicalTrials.gov
['NCT02668185']
Types de publication
Journal Article
Langues
eng
Pagination
bvz009Subventions
Organisme : Department of Health
ID : CS-2018-18-ST2-002
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M024954/1
Pays : United Kingdom
Organisme : Department of Health
ID : PDF-2017-10-098
Pays : United Kingdom
Informations de copyright
© Endocrine Society 2019.
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