Association of testosterone therapy with disease progression in older males with COVID-19

Importance: Low testosterone levels in males have been linked with increase in proinflammatory cytokines—a primary culprit in COVID-19 disease progression—and with adverse COVID-19 outcomes. To date, however, no published studies have assessed the effect of testosterone therapy on COVID-19 outcomes in older men. Objective: To examine whether testosterone therapy reduced disease progression in older men diagnosed with COVID-19. Design, setting, and participants: Nested within a national cohort of older (aged ≥50 years) male patients diagnosed with COVID-19 between January 1, 2020 and July 1, 2021 from the Optum electronic health record COVID-19 database, two matched case–control studies of COVID-19 outcomes were conducted. Cases—defined, respectively, as persons who (a) were hospitalized ≤30 days after COVID-19 diagnosis (n = 33,380), and (b) were admitted to the intensive care unit or received mechanical ventilation during their COVID-19 hospitalization (n = 10,273)—were matched 1:1 with controls based on demographic and clinical factors. Exposures: Testosterone therapy was defined based on receipt of prescription at ≤60, ≤90, or ≤120 days before COVID-19 diagnosis. Main outcomes and measures: Adjusted odds ratios (ORs) for the risk of hospitalization within 30 days of COVID-19 diagnosis and intensive care unit admission/mechanical ventilation during COVID-19 hospitalization. Results: The use of testosterone therapy was not associated with decreased odds of hospitalization (≤60 days: OR = 0.92, 95% confidence interval [CI] = 0.70–1.20; ≤90 days: OR = 0.87, 95% CI = 0.68–1.13; ≤120 days: OR = 0.97, 95% CI = 0.72–1.32) or intensive care unit admission/mechanical ventilation (≤60 days: OR = 0.67, 95% CI = 0.37–1.23; ≤90 days: OR = 0.63, 95% CI = 0.36–0.11; ≤120 days: OR = 0.58, 95% CI = 0.29–1.19). Conclusions and relevance: This study showed that testosterone therapy was not associated with decreased risks of COVID-19 adverse outcomes. These findings may provide clinically relevant information regarding testosterone treatment in older men with COVID-19 and other respiratory viral infections with similar pathogenesis.