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Endocrine Abstracts (2022) 86 OP3.1 | DOI: 10.1530/endoabs.86.OP3.1

1Imperial College London, London, United Kingdom; 2Invicro London, London, United Kingdom; 3Statsconsultancy, Amersham, United Kingdom; 4Imperial College Healthcare NHS Trust, London, United Kingdom

Background: Hypoactive Sexual Desire Disorder (HSDD) is associated with a deficiency of sexual desire with marked distress. It affects up to 8% of men, but has no licensed treatments. The reproductive neuropeptide kisspeptin offers a putative therapeutic target owing to its emerging role in modulating reproductive behaviour in animal models and healthy men. However, there are no studies examining its effects in HSDD. To address this, we performed the first clinical study of kisspeptin in men with HSDD.

Methods: We examined the effects of kisspeptin administration (vs placebo) on brain activity during short and long erotic video tasks using functional MRI in 32 men with HSDD (mean±SEM age 37.9±1.5 y, BMI 24.9±1.0 kg/m2). To provide functional relevance for the fMRI brain responses during the long erotic video, simultaneous penile tumescence and subjective arousal were recorded. Participants also completed psychometric questionnaires. Standard analysis methods were used for fMRI data from the short videos task, and the long videos task used regressors derived from the subjective arousal and penile tumescence data.

Results: In response to visual erotic stimuli, kisspeptin significantly increased penile tumescence during the long video task compared to placebo, with kisspeptin increasing penile tumescence by 56% (P=0.02). Kisspeptin also increased participant-reported happiness about sex (P=0.02). During both video tasks, kisspeptin significantly modulated brain activity, compared to placebo, in key structures of the sexual-processing network (P<0.05). Additionally, we observed positive correlations between kisspeptin’s effects on aforementioned brain activity and psychometric parameters of sexual desire and arousal (all P<0.01).

Conclusion: Collectively, we demonstrate for the first time that kisspeptin in men with HSDD increases penile tumescence and psychometric measures of sexual desire and arousal by modulating sexual brain processing. Our data suggest that kisspeptin-based therapeutics may offer a novel, effective and much-needed clinical strategy for men with HSDD.

Volume 86

Society for Endocrinology BES 2022

Harrogate, United Kingdom
14 Nov 2022 - 16 Nov 2022

Society for Endocrinology 

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