Low Free Testosterone Is Independently Associated With Long-Term Mortality in Men With Chronic Spinal Cord Injury.

Abstract

Background: Testosterone deficiency is highly prevalent in men with chronic spinal cord injury (SCI) and is associated with obesity, sarcopenia, systemic inflammation, and metabolic dysfunction. However, the independent prognostic role of low testosterone in long-term mortality in this population remains unclear.

Objectives: To investigate whether baseline calculated free testosterone (cFT) independently predicts all-cause mortality in men with chronic SCI.

Materials and methods: We conducted a retrospective cohort study including 152 men with chronic SCI admitted to a rehabilitation center between 2017 and 2023. Participants were followed until death or December 2024 (median follow-up 62 months). Severe hypogonadism was defined according to European Male Ageing Study criteria. Cox proportional hazards models were used to assess the association between testosterone and mortality. Fully adjusted models included age, comorbidities, inflammatory status, functional independence, injury duration, age at injury, autonomic dysreflexia, body mass index (BMI), HDL, and testosterone-binding factors, including albumin. Prespecified parsimonious models (age + CCI or albumin) were also tested. Kaplan-Meier curves were compared by log-rank test and model discrimination was evaluated using Harrell's C-index.

Results: Twenty-four deaths (15.8%) occurred. Deceased patients had significantly lower cFT (48.9 vs. 85.4 pg/mL; p < 0.001) and lower serum albumin levels. In fully adjusted Cox models, lower cFT independently predicted mortality (HR 0.97 per pg/mL increase; 95% CI 0.95-0.98; p = 0.0139). Serum albumin was also strongly associated with mortality in multivariable models, confirming its role as a marker of nutritional and clinical frailty. The association between cFT and mortality remained robust in parsimonious models (HR 0.82 per 10 pg/mL increase; p = 0.001), including those adjusted for albumin. The age-cFT-CCI model showed good discrimination (Harrell's C-index 0.85). ROC analysis identified an internally derived threshold of 59.55 pg/mL (AUC 0.839), with significantly lower survival in men below this threshold (log-rank p < 0.0001).

Discussion and conclusion: Low cFT independently predicts all-cause mortality in men with chronic SCI. These findings suggest that cFT may represent an integrative biomarker of systemic frailty beyond markers of nutritional and clinical status in this high-risk population and warrant confirmation in prospective multicenter studies.