Low Testosterone on Hospital Admission with COVID-19 Infection Is Associated with Increased Mortality

Abstract

Objective: Males, despite equal sex-related susceptibility to COVID-19, appear at a greater risk of poor clinical outcomes and death. This suggests that serum testosterone could be a mediator. The aim of this retrospective study was to evaluate the association between serum total testosterone (TT), other prognostic indicators, and mortality in men with COVID-19. Methods: Of the 110 men consecutively admitted to Walsall Manor Hospital (with COVID-19 related symptoms) tested for SARS-CoV-2, 85 were positive and 27 of these men died. Serum TT was compared (rank-sum test) between men negative and positive for SARS-CoV-2, and this was followed by establishing factors associated with mortality in the latter group (rank-sum, logistic, Cox regression analyses). No patient was on testosterone therapy (TTh). Results: No significant difference (p = 0.12, rank-sum test) in serum TT between men positive [median TT (IQR) = 3.9 (1.9-7.22) nmol/L, 0 days (median) postadmission] and negative [median TT (IQR) = 5.9 (2.69-10.1) nmol/L, 2 days (median) postadmission] for SARS-CoV-2 was observed. Serum TT was lower (p = 0.0011, rank-sum test) in men with COVID-19 who died [median TT (IQR) = 2.0 (1.5-3.6) nmol/L] compared with survivors [median TT (IQR) = 5.0 (2.6-9.4) nmol/L]. Comorbidities obtained via medication history were not associated with mortality. Mortality (logistic regression) was associated with only age and serum TT (odds ratio: 0.77, 95% confidence intervals [CI]: 0.64-0.91). Survival (Cox regression) was inversely associated with serum TT (continuous variable, hazard ratio [HR]: 0.85) (95% CI: 0.74-0.98), stratified by median, TT ≥3.9 nmol/L (reference, TT <3.9 nmol/L), HR: 0.24 (95% CI: 0.089-0.63). Conclusions: Serum TT was inversely associated with mortality in men with COVID-19 and requires measurement at admission and while managing long COVID. Future research should establish whether low serum TT, possibly associated with negative acute phase response, contributes to poorer prognosis and a role for TTh.