Associations between circulating sex hormones and anterior urethral stricture disease

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Background: The pathophysiology of anterior urethral stricture disease (aUSD) is unknown (idiopathic) in the majority of men. Testosterone is required for the in utero development of the male urethra and has been shown to aid in urethral healing. Thus, the purpose of this study was to understand the relationship between circulating sex hormones and aUSD. Methods: This study included 154 males with aUSD undergoing urethroplasty who were enrolled in a prospective, multicenter study evaluating the relationship between inflammation and urethral strictures. This study represents a secondary analysis on serum, measuring circulating levels of total testosterone (TT), free testosterone (fT), estradiol (Es), progesterone (Pr), and cortisol (Co). The control group consisted of males (n=9) lacking urologic pathology undergoing vasectomy. Within the stricture cohort, we looked at differences in sex hormone levels by stricture features and inflammation. T-tests and one-way analysis of variance were used to compare means. Univariate logistic regression was used to assess significant differences followed by multivariable logistic regression to adjust for confounders. Results: fT was lower in the stricture cohort versus control cohort (1.08 vs. 2.13 pg/dL, P=0.05). Adjusting for confounding factors including age, there was a significant decrease in the odds of stricture with increasing fT levels (adjusted odds ratio: 0.33, P=0.02), with a 1-unit increase in fT being associated with a 67% decrease in the adjusted odds of aUSD. Among the stricture cohort, longer strictures were associated with lower fT (P=0.01). Other circulating hormones, including TT, were not statistically different between cohorts or related to aUSD inflammation. Conclusions: We show an association between lower fT, aUSD, and aUSD severity. Bioavailable testosterone is necessary for male urethral development and has anti-inflammatory and anti-fibrotic properties. We hypothesize that fT may contribute to aUSD development by impairing healing to sub-clinical trauma.

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