Insomnia and Benzodiazepine Use as Risk Factors for Erectile Dysfunction: Clinical Evidence and In Silico Analysis of Physicochemical Properties

Background/Objectives: Erectile dysfunction (ED) is a prevalent and multifactorial condition influenced by psychological and sleep-related factors. This study aimed to evaluate the independent and combined associations of insomnia and benzodiazepine use with the risk of ED. Methods: An analytical cross-sectional study was conducted in adult men with and without ED. Logistic regression was used to estimate crude and adjusted odds ratios (ORs). Effect modification was assessed through stratified analyses. Additionally, an in silico analysis of 17 active compounds was performed using SwissADME and Molinspiration to explore physicochemical properties. Results: Insomnia (adjusted OR 2.05; 95% CI 1.13–3.74; p = 0.019) and benzodiazepine use (adjusted OR 2.14; 95% CI 1.10–4.15; p = 0.025) were each independently associated with ED. In contrast, antidepressant use was not significantly associated with ED in the sample analyzed. Participants with both insomnia and benzodiazepine use had a markedly higher risk (adjusted OR 3.96; 95% CI 1.51–10.40; p = 0.005). The joint association of insomnia and benzodiazepine use was consistent with the combined effect expected from their individual associations. The in silico analysis showed an overlapping profile, suggesting benzodiazepine properties may underline their link to ED, supporting the results of the cross-sectional study. Conclusions: Both insomnia and benzodiazepine use independently increased the odds of ED. Their co-occurrence was linked to a substantially higher likelihood of ED, highlighting the clinical importance of assessing both conditions concurrently in patients with sexual dysfunction.