Environmental hazards and the risk of development of idiopathic urethral strictures.

Background: Though idiopathic urethral strictures are a common form of strictures, little is understood about the pathophysiology leading to their development. This retrospective cohort study sought to analyze the risk of environmental toxins on the development of stricture disease. Methods: Using the Utah Population Database (UPDB), we identified patients with idiopathic urethral strictures born between 1996-2021. Each case was matched 1:1 with controls, based on year of birth and location. Models compared historical air pollution exposure data between the cohorts. Environmental exposures were analyzed in the prenatal period, the first year of life, and the 5 years prior to diagnosis and individual exposures were weighted by the risk of stricture development. Results: We identified 2,048 patients with urethral strictures, diagnosed between 1996 and 2021 and were matched to 1,939 controls for a total cohort of 3,987 men. There was no difference in risk of stricture development for exposure prenatally and within the 5 years prior to diagnosis. The relative risk of cumulative exposures in the first year of life was 1.21 (1.07-1.36, P=0.002) in the development of stricture disease. On univariate analysis, the toxins most associated with stricture development within the first year of life were ethylbenzene, tetrachloroethylene, and molybdenum trioxide. Conclusions: Idiopathic urethral stricture is a common presentation of anterior urethral stricture disease (aUSD) but the mechanism is not well understood. Environmental exposures within the first year of life were associated with an increased risk of the development of a stricture, indicating a potential role within broader inflammatory pathways associated with urethral strictures.