Testosterone replacement therapy in heart failure patients demonstrated significant improvements in muscle strength, aerobic capacity, lean muscle mass, fat mass, insulin sensitivity, and QT interval shortening, without serious adverse effects, but evidence is limited by small sample sizes and short follow-up periods.
Key Findings
Background
Multiple hormonal deficiency syndrome (MHDS) is common in heart failure, affecting up to 90% of patients and is associated with worse outcomes.
MHDS is characterized by neurohormonal activation and metabolic dysregulation in HF patients.
The prevalence of MHDS in HF is reported as up to 90% of patients.
MHDS is associated with worse clinical outcomes in HF.
Methods
A systematic review of randomized controlled trials on TRT in heart failure identified 12 eligible studies from 653 records.
Databases searched included PubMed, the Cochrane Library, and ClinicalTrials.gov.
Search covered records up to September 15, 2024.
653 records were initially identified, of which 12 studies met the inclusion criteria.
Inclusion criteria required human subjects aged 18 or older with confirmed HF diagnosis and at least 4 weeks of follow-up.
Reviews, animal studies, observational studies, and non-randomized trials were excluded.
Results
TRT produced significant improvements in muscle strength and aerobic capacity in certain trials of heart failure patients.
Improvements in muscle strength were among the key findings across the included RCTs.
Aerobic capacity improvements were also reported as significant findings.
These improvements in physical function represent a potential benefit of TRT in HF management.
Results
TRT was associated with increases in lean muscle mass and decreases in fat mass in certain trials of heart failure patients.
Changes in body composition, including increased lean muscle mass and decreased fat mass, were reported in certain included trials.
These findings suggest potential metabolic benefits of TRT in HF patients.
Results
TRT was associated with improvements in insulin sensitivity and shortening of the QT interval in heart failure patients.
Improvements in insulin sensitivity were reported among the key findings of the included RCTs.
Shortening of the QT interval was also reported as a finding associated with TRT.
These findings suggest potential cardiometabolic benefits of TRT in HF.
Results
TRT did not consistently affect blood pressure, lipid profiles, or heart rate in heart failure patients.
Blood pressure was not consistently altered by TRT across the included trials.
Lipid profiles showed no consistent change with TRT.
Heart rate was also not consistently affected by TRT in HF patients.
Results
TRT did not lead to any serious adverse effects in the included heart failure trials.
No serious adverse effects were reported across the 12 included RCTs.
This safety profile supports the potential for TRT use in HF management.
The absence of serious adverse effects was noted despite the inclusion of a cardiac patient population.
Conclusions
The current evidence base for TRT in heart failure is limited by small sample sizes and short follow-up periods.
Small sample sizes were identified as a key limitation of the existing RCT evidence.
Short follow-up periods were also cited as a limitation, constraining conclusions about long-term efficacy and safety.
The authors concluded that larger event-driven RCTs evaluating hard endpoints are needed to determine whether TRT should be integrated into standard HF therapies.