Jenifer Sassarini, Karolina Skorupskaite, John McLean, Mary Ann Lumsden, Richard A Anderson
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引用次数: 0
Abstract
Objective: Kisspeptin/neurokinin/dynorphin (KNDy) signaling links reproductive and thermoregulatory systems, and improvements in menopausal flushing are reported with neurokinin 3 receptor (NK3R) antagonists. A rise in brainstem activity preceding a flush has been proposed as its functional origin, with subsequent activity in the insula and prefrontal cortices reflecting individual perception. Using functional magnetic resonance imaging (fMRI), this study investigated the central effect of the NK3R antagonist MLE4901 during a flush, particularly functional connectivity changes in the salience network.
Method: Five postmenopausal women with flushes completed a 1-week flush diary prior to baseline fMRI, during which hot flushes were triggered by heating. Diaries were continued during 7 days of treatment with the NK3R antagonist MLE4901, with repeat fMRI on day 7. Sternal monitors recorded objective flushing before each fMRI. Connectivity changes in the salience network post flush were assessed.
Results: Treatment with MLE4901 reduced the subjective flush frequency (from median 6.9 to 1.1 per day; p = 0.02) without changes in objective flushes. Treatment decreased right anterior insula connectivity, which correlated significantly with decreased subjective flushing.
Conclusion: This pilot study demonstrates decreased connectivity in the salience network during NK3R antagonist treatment. This may indicate areas of interest for further targeted fMRI studies and mechanistic investigation of this novel treatment for flushing.
期刊介绍:
Climacteric is the official journal of the International Menopause Society (IMS). As an international peer-reviewed journal it publishes original research and reviews of all aspects of aging in women.
Climacteric was founded by the IMS in 1998 and today has become a leading journal in the publication of peer-reviewed papers on the menopause, climacteric and mid-life health. Topics covered include endocrine changes, symptoms attributed to the menopause and their treatment, hormone replacement and alternative therapies, lifestyles, and the counselling and education of peri- and postmenopausal women. Climacteric, published bimonthly, also features regular invited reviews, editorials and commentaries on recent developments.
The editorial review board of Climacteric includes leading scientific and clinical experts in the field of midlife medicine and research and is headed by its Editor-in-Chief, Professor Rod Baber of Australia. He and his team of Associate Editors act independently to set a clear editorial policy, co-ordinate peer review, and ensure a rapid response to submitted papers.