Safety of Testosterone Therapy in Chronic Kidney Disease: A Propensity Score-Matched Cohort Study

Testosterone deficiency is highly prevalent in men with chronic kidney disease (CKD) and contributes to frailty, fatigue, and cognitive decline. While testosterone replacement therapy (TRT) may alleviate these complications, concerns persist regarding its cardiovascular and oncologic safety in CKD. Evidence specific to this population is lacking.

We performed a retrospective, propensity score-matched cohort study using the TriNetX Global Collaborative Network. Male patients aged 18-80 years with CKD stages 3-5 and hypogonadism were included. Patients were stratified by TRT exposure within six months of diagnosis. Exclusions were prior transplantation, eGFR <10 mL/min/1.73 m², dialysis or dementia occurring within one month of CKD. Outcomes over five years included all-cause mortality (primary outcome), vascular dementia, Alzheimer's disease, stroke, myocardial infarction, heart failure, and prostate cancer. Propensity score matching (1:1) balanced demographics, comorbidities, and laboratory measures. Cox proportional hazards models estimated hazard ratios (HRs).

After matching, 1,545 patients were included in each of the two cohorts (TRT treated or non-treated) with well-balanced characteristics (mean eGFR 47.7±15.1 mL/min/1.73 m²). Median follow-up was 3.7 years. All-cause mortality was lower in the TRT group (HR 0.78, 95% confidence interval 0.63-0.98). No significant differences were observed for cardiovascular outcomes, prostate cancer or dementia.

In men with CKD and hypogonadism, TRT was associated with improved survival and no excess risk of cardiovascular events, prostate malignancy or dementia. These findings suggest TRT is a safe therapeutic option in this high-risk population, warranting further prospective evaluation.