Abstract
Propofol is a widely used anesthetic that has been associated with post-anesthetic euphoria, particularly among women. Since anhedonia is a core component of female sexual dysfunction (FSD), we aimed to evaluate the clinical incidence of propofol-induced euphoria and explore its potential molecular mechanisms. A total of 300 patients undergoing gastrointestinal endoscopy with propofol anesthesia were assessed postoperatively using the Euphoria Rating Scale, Observer's Assessment of Alertness/Sedation Scale (OAA/S), and the Hospital Anxiety and Depression Scale (HADS). Network pharmacology and molecular docking were applied to identify relevant molecular targets and signaling pathways. Euphoria occurred in 28% (42/150) of female patients compared to 4.4% (6/135) of males (adjusted OR = 6.62; 95% CI, 2.46 to 17.81, p < 0.001). Network pharmacology revealed 37 intersecting targets between propofol and FSD. Functional enrichment highlighted estrogen-related signaling and cGMP-dependent pathways. Molecular docking confirmed strong binding affinities of propofol with ESR1, EGFR, APP, NR3C1, MDM2, and MAOB. Short-term exposure to propofol can induce euphoria more frequently in females and may positively modulate pathways linked to female sexual dysfunction. These findings suggest propofol may have potential therapeutic applications beyond anesthesia.