Testosterone replacement therapy in heart failure: A systematic review of randomized controlled trials

Heart failure (HF), a leading cause of morbidity and mortality, is characterized by a complex pathophysiology involving neurohormonal activation, metabolic dysregulation, and multiple hormonal deficiency syndrome (MHDS). MHDS is common in HF, affecting up to 90% of patients, and is associated with worse outcomes. This systematic review aims to evaluate the efficacy and safety of testosterone replacement therapy (TRT) in the management of HF.

We conducted a comprehensive search of PubMed, the Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) examining TRT in HF patients up to September 15, 2024. Studies were included if they involved human subjects aged 18 or older with a confirmed diagnosis of HF and had a follow-up period of at least 4 weeks. We excluded reviews, animal studies, observational studies, and trials without randomization.

Our search yielded 653 records, of which 12 studies met the inclusion criteria. Key findings include significant improvements in muscle strength and aerobic capacity as well as increases in lean muscle mass and decreases in fat mass in certain trials. Additionally, improvements in insulin sensitivity and shortening of the QT interval were reported. TRT did not consistently affect blood pressure, lipid profiles, or heart rate, nor did it lead to any serious adverse effects.

While TRT has demonstrated potential benefits in HF patients, particularly in improving physical function and metabolic profiles, the current evidence is limited by small sample sizes and short follow-up periods. Larger event-driven RCTs evaluating hard endpoints are needed to determine whether TRT should be integrated into standard HF therapies.