Abstract
INTRODUCTION: Testosterone therapy may improve physical capacity and mood in men with chronic heart failure. However, recent findings have raised concerns that testosterone therapy could also increase the risk of atrial fibrillation, pulmonary embolism, and acute kidney injury. METHODS: Leveraging data from the TriNetX platform from January 1, 2014, to December 01, 2024, we conducted a propensity-matched analysis of two cohorts of patients with heart failure with protein-calorie malnutrition, where the only difference between cohorts was testosterone therapy. The primary outcomes were all-cause mortality and the incidence of acute heart failure, with secondary outcomes including major adverse cardiovascular events as well as cardiovascular, kidney, and thrombotic diseases. RESULTS: After propensity matching, 577 patients were compared across the two cohorts. The findings indicated that testosterone therapy reduced the risk of all-cause mortality (hazard ratio [HR] 0.56, 95 % confidence interval [CI] 0.46-0.68), acute heart failure (HR 0.62, 95 % CI 0.49-0.78), and major adverse cardiovascular events (HR 0.77, 95 % CI 0.61-0.97). Additionally, incident peripheral arterial disease (HR 0.52, 95 % CI 0.30-0.91), coronary arterial disease (HR 0.83, 95 % CI 0.69-1.00), acute myocardial infarction (HR 0.65, 95 % CI 0.48-0.89), and atrial fibrillation (HR 0.79, 95 % CI 0.66-0.95) also favored the testosterone-treated cohort. There was a trend toward an increased risk of venous thromboembolism (HR 1.14, 95 % CI 1.03-1.27) and stroke (HR 1.12, 95 % CI 0.81-1.54) associated with testosterone therapy. CONCLUSION: These hypothesis-generating findings support potential beneficial effects of testosterone therapy in patients with heart failure and protein-calorie malnutrition.