Imperial College London
Portrait Picture

ProfessorAlexanderComninos

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Professor of Practice (Endocrinology)
 
 
 
//

Contact

 

+44 (0)20 3313 3242a.comninos

 
 
//

Location

 

Commonwealth BuildingHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Thurston:2022:10.1172/JCI152341,
author = {Thurston, L and Hunjan, T and Mills, E and Wall, M and Ertl, N and Phylactou, M and Muzi, B and Patel, B and Alexander, E and Suladze, S and Modi, M and Eng, P and Bassett, P and Abbara, A and Goldmeier, D and Comninos, A and Dhillo, W},
doi = {10.1172/JCI152341},
journal = {Journal of Clinical Investigation},
pages = {1--12},
title = {Melanocortin 4 receptor agonism enhances sexual brain processing in women with hypoactive sexual desire disorder},
url = {http://dx.doi.org/10.1172/JCI152341},
volume = {132},
year = {2022}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND. Hypoactive sexual desire disorder (HSDD) is characterized by a persistent deficiency of sexual fantasies and desire for sexual activity, causing marked distress and interpersonal difficulty. It is the most prevalent female sexual health problem globally, affecting approximately 10% of women, but has limited treatment options. Melanocortin 4 receptor (MC4R) agonists have emerged as a promising therapy for women with HSDD, through unknown mechanisms. Studying the pathways involved is crucial for our understanding of normal and abnormal sexual behavior.METHODS. Using psychometric, functional neuroimaging, and hormonal analyses, we conducted a randomized, double-blinded, placebo-controlled, crossover clinical study to assess the effects of MC4R agonism compared with placebo on sexual brain processing in 31 premenopausal heterosexual women with HSDD.RESULTS. MC4R agonism significantly increased sexual desire for up to 24 hours after administration compared with placebo. During functional neuroimaging, MC4R agonism enhanced cerebellar and supplementary motor area activity and deactivated the secondary somatosensory cortex, specifically in response to visual erotic stimuli, compared with placebo. In addition, MC4R agonism enhanced functional connectivity between the amygdala and the insula during visual erotic stimuli compared with placebo.CONCLUSION. These data suggest that MC4R agonism enhanced sexual brain processing by reducing self-consciousness, increasing sexual imagery, and sensitizing women with HSDD to erotic stimuli. These findings provide mechanistic insight into the action of MC4R agonism in sexual behavior and are relevant to the ongoing development of HSDD therapies and MC4R agonist development more widely.TRIAL REGISTRATION. ClinicalTrials.gov NCT04179734.FUNDING. This is an investigator-sponsored study funded by AMAG Pharmaceuticals Inc., the Medical Research Council (MRC) (MR/T006242/1), and the National Institute for Health Research (NIHR) (C
AU  - Thurston,L
AU  - Hunjan,T
AU  - Mills,E
AU  - Wall,M
AU  - Ertl,N
AU  - Phylactou,M
AU  - Muzi,B
AU  - Patel,B
AU  - Alexander,E
AU  - Suladze,S
AU  - Modi,M
AU  - Eng,P
AU  - Bassett,P
AU  - Abbara,A
AU  - Goldmeier,D
AU  - Comninos,A
AU  - Dhillo,W
DO  - 10.1172/JCI152341
EP  - 12
PY  - 2022///
SN  - 0021-9738
SP  - 1
TI  - Melanocortin 4 receptor agonism enhances sexual brain processing in women with hypoactive sexual desire disorder
T2  - Journal of Clinical Investigation
UR  - http://dx.doi.org/10.1172/JCI152341
UR  - https://www.jci.org/articles/view/152341
UR  - http://hdl.handle.net/10044/1/99507
VL  - 132
ER  -
Download