6953 Bridging the Gender Gap: Sexually Dimorphic Brain Responses in Distressing Low Sexual Desire

Abstract Disclosure: J. Tsoutsouki: None. N. Ertl: None. E.G. Mills: None. M.B. Wall: None. L. Thurston: None. L. Yang: None. S. Suladze: None. T. Hunjan: None. M. Phylactou: None. B. Patel: None. J. Howard: None. A. Abbara: None. D. Golmeier: None. A.N. Comninos: None. W.S. Dhillo: None. Background: Distressing low sexual desire, termed Hypoactive Sexual Desire Disorder (HSDD), affects 10% of women and 8% of men. The established ‘top-down’ neurofunctional model of HSDD in women suggests that in response to erotic cues, excessive activation of higher-level cognitive brain regions (involved in introspection/self-monitoring) suppresses lower-level sexual brain centres, thereby impeding normal sexual function. By contrast, the neurodysfunction in men with HSDD remains to be fully characterised and crucially unlike in women, there are currently no licensed therapies. Herein, we report the first direct comparison of the neural bases of HSDD in women and men. Methods: 32 premenopausal women with HSDD [mean age±SD (y) 29.2±6.7] and 32 men with HSDD [age 37.9±8.6] underwent a task-based functional MRI (fMRI) measuring sexual brain activity during erotic versus control (exercise) videos. Participants completed psychometric questionnaires before and after the fMRI scan, providing functional relevance for the brain activity changes. Results: Women displayed significantly greater activation in higher-level cortical regions (e.g. inferior frontal gyrus, superior frontal gyrus) and lower-level limbic brain regions (e.g. amygdala, striatum, thalamus) in response to erotic videos, compared to the men. Lower activation in lower-limbic sexual regions in women correlated with more severe HSDD, which along with a hyperactivation in the inferior-frontal gyrus relative to the men, supports the ‘top-down’ mechanism underlying HSDD in women. By contrast, men exhibited lower activation in both higher-cortical and lower-limbic regions, but greater activation than the women in the visual cortex in response to erotic videos. Hence, a heightened sensitivity to visual erotic cues in men might not be effectively relayed to the limbic system. In women only, hypothalamic hyperactivation in response to erotic videos correlated with ‘increased heartbeat’ (r=0.5, P=0.001), and ‘tingling all over’ (r=0.6, P<0.001), while higher striatal activation correlated with feeling more ‘stimulated’ (r=0.4, P=0.001) and ‘genital tingling’ (r=0.6, P<0.001) on the psychometric questionnaires. Crucially, these findings were specific to erotic stimuli as no differences were identified in the control comparison (exercise>baseline contrast). Discussion: This is the first study to directly compare the neural bases of distressing low sexual desire in women and men. While supporting the ‘top-down’ mechanism of HSDD in women, it suggests a different neurodysfunctional process in men with HSDD, highlighting a potential functional disconnection between sensory/attention and sexual centres. Our findings have key clinical implications as they identify a sexual dimorphism in the neural bases of low sexual desire relevant to the escalating development of therapeutics for patients with HSDD. Presentation: 6/3/2024