Distribution of Neuroendocrine Cells and Hormone Receptors in the Male Proximal Urethra: Implications for Sensory Function and the Impact of Aging

PURPOSE: To assess the distribution of neuroendocrine cells in the male penile urethra and the influence of age and estrogen therapy. MATERIALS AND METHODS: A retrospective immunohistochemical cohort study was conducted on 26 penile urethras obtained during feminizing genitoplasty. Three anatomical regions were analyzed: bulbar, distal, and glans urethra. Neuroendocrine cells were identified by double immunohistochemistry and quantified as chromogranin A-positive cells per mm² of epithelium. RESULTS: Patients were divided according to estrogen exposure: Group 1 (n=12, median age 23.5 years, estrogen 5.5 years) and Group 2 (n=14, median age 43.0 years, estrogen 18.0 years). A clear gradient of neuroendocrine cell density was observed, with the bulbar urethra showing the highest values compared to distal urethra and glans. Group 2 had significantly higher bulbar urethral cell density than Group 1 (p<0.005). A negative correlation between age and bulbar density was observed. CONCLUSIONS: This study provides evidence of a neuroendocrine cell gradient in the human male urethra, concentrated in the bulbar region. Cell density declines with age but is preserved by long-term estrogen therapy. These findings underscore the bulbar urethra as a key sensory structure that should be preserved during surgery and suggest that hormone therapy may mitigate age-related sensory decline.