JU INSIGHT: Addressing the Relationship Between Testosterone Levels and Urethral Stricture: A Case-control Study

By: Ignacio Puche-Sanz, MhD, MD; Almudena Sabio-Bonilla, MD; Pedro Vila-Braña, MD; Juan Manuel Guardia-Baena, MhD, MD; Mercedes Nogueras-Ocaña, Mhd, MD; Francisco Javier Contreras-Matos, MD; Laura Entrena-Ureña, Mhd, MD; Ana Jimenez-Domínguez, MD; Alba Tamayo-Gomez, MD; Javier Vicente-Prados, Mhd, MD; Pablo Lardelli-Claret, Mhd | Posted on: 01 Nov 2022

Puche-Sanz I, Sabio-Bonilla A, Vila-Braña P, et al. Addressing the relationship between testosterone levels and urethral stricture: a case-control study. J Urol. 2022;208(5):1098-1105.

Study Need and Importance

The biological mechanisms underlying the development of urethral stricture (US) are still unknown. Recent studies have shown that low testosterone levels are associated with decreased periurethral vascularization and that hypoandrogenism is a frequent condition in men with anterior US that also seems to correlate with the severity of the stricture. However, the role of testosterone in the etiopathogenesis of US is uncertain. We designed this study with the objective of identifying and, where appropriate, quantifying the magnitude of the association between testosterone levels and US.

What We Found

Our multivariate analysis demonstrated that low testosterone levels are associated with US, independent of other potential confounding factors such as age, body mass index, hypertension, diabetes, or smoking (Table 1). Each 100-unit increase in total testosterone (ng/dL) was related to a 34% decrease in the odds of US (adjusted OR 0.66, 95% CI: 0.51-0.86). A strong direct relationship was observed between hypoandrogenism and US (adjusted OR 4.01, 95% CI: 1.37-11.7; Table 2).

Limitations

The main limitation of our study is its cross-sectional nature. Although it was designed as a case-control study, the measurement of the exposure variable was performed after the diagnosis of US. Another limitation is the known variability (both circadian and throughout life) in testosterone levels. Nevertheless, our results are consistent with previously reported evidence and are biologically plausible. Taken together, all suggest that testosterone plays an important role in the pathophysiological process of US.

Interpretation for Patient Care

Our results encourage continuing research on the role of testosterone as a prognostic and/or predictive biomarker in US. The integration of this information together with other clinical variables may allow the development of predictive models with the ultimate goal of individualizing the different therapeutic options that currently exist for these patients.

Table 1. Comparative Analysis

	Controls (n = 67)	Cases (n = 149)	P value
HA rate, Total-T <300 ng/dL, %	7.5	26	.002
HA rate, Free-T <6 ng/dL, %	22	33	.15
Total-T, mean±SD, ng/dL	488±188	394±141	< .001
Free-T, mean±SD, ng/dL	8.3±3	7.4±3.1	.08
Bio-T, mean±SD, ng/dL	196±74	172±76	.046
Abbreviations: Bio-T, bioavailable testosterone; Free-T, free testosterone; HA, hypoandrogenism; Total-T, total testosterone.

Table 2. Multivariate Analysis Estimates^a

	aOR	CI 95%	P value
HA, Total-T <300 ng/dL	4.01	1.37-11.7	.011
HA, Free-T <6 ng/dL	2.11	0.94-5.19	.07
Total-T (× 100)^b	0.66	0.51-0.86	.002
Free-T	0.82	0.70-0.94	.006
Bio-T (× 10)^c	0.90	0.85-0.96	.002
Abbreviations: aOR; adjusted odds ratio; Bio-T, bioavailable testosterone; Free-T, free testosterone; HA, hypoandrogenism; Total-T, total testosterone. ^aThe following variables were also included in each model: age, body mass index, diabetes, smoking status, hypertension, and thyroxine levels. ^bOR of urethral stricture for each 100 units of increase in total testosterone values. ^cOR of urethral stricture for each 10 units of increase in bioavailable testosterone values.