(683) Neurosex and Male Sexual Function: Neural Circuitry, Endocrine Modulation and Novel Therapeutic Strategies

Introduction Male sexual function depends on the integration of reward, cognitive, autonomic, and neuroendocrine pathways. Advances in neuroimaging and molecular neuroscience have revealed central mechanisms driving male sexual desire, arousal, and erectile responses. Kisspeptin signaling, neuromodulation, and virtual reality (VR) erotic stimulation have demonstrated potential to modulate limbic networks, enhance erotic processing, and improve sexual outcomes in men. Current treatments for hypoactive sexual desire disorder (HSDD) and erectile dysfunction (ED) remain predominantly peripheral, underscoring the need for brain-directed strategies. Objective To assess the impact of an integrated neurosex approach-combining kisspeptin administration, neuromodulation, and VR-based erotic stimulation-on central and clinical markers of male sexual function. Methods A randomized controlled pilot design was applied. Adult males diagnosed with HSDD using validated sexual desire instruments and stable hormonal profiles were randomized 1:1 to either an integrated neurosex intervention (kisspeptin, non-invasive neuromodulation, and VR erotic audiovisual stimulation) or placebo/sham control. Primary outcomes included changes in sexual desire scores and limbic activation on functional MRI during erotic cues. Secondary outcomes included erectile responses during VR stimulation, standardized erectile function scores, and variations in circulating neuroendocrine markers. Statistical significance was defined as p < 0.05 Results The integrated neurosex intervention produced significantly greater improvements in sexual desire than placebo, with higher standardized desire scores (p < 0.01) and increased limbic activation on functional MRI (p < 0.05). VR-assisted stimulation enhanced erectile responses and increased engagement of reward-motivation pathways compared with sham exposure. Neuromodulation demonstrated additive benefits, improving erectile function scores and autonomic-arousal markers. No major adverse events were reported. The findings suggest that coordinated modulation of central networks can potentiate functional outcomes in male sexual dysfunction. Conclusions This pilot investigation supports a paradigm shift ttoward central brain-focused strategies in male sexual medicine. A combined neurosex approach-leveraging kisspeptin signaling, neuromodulation, and VR-based stimulation-may offer superior therapeutic potential compared with conventional peripheral-focused treatments. Larger multicenter trials are warranted to validate efficacy, refine patient selection, and incorporate neurobiologically informed protocols into routine Disclosure No