What is the impact of testosterone replacement therapy on cardiac structure in patients with hypogonadism?

Impact of Testosterone Replacement Therapy on Cardiac Structure in Hypogonadism

Testosterone replacement therapy (TRT) appears to have a neutral or potentially beneficial effect on cardiac structure in patients with hypogonadism, with evidence suggesting it may improve coronary artery diameter and blood flow without increasing cardiovascular risk. 1

Cardiovascular Effects of TRT

Direct Cardiac Effects

• TRT leads to increased mean coronary artery diameter and blood flow compared to baseline, which may have beneficial effects for patients with cardiac disease 1
• In hypogonadal patients, TRT has been shown to improve exercise tolerance in those with chronic stable angina 1
• Short-term TRT has demonstrated improvement in myocardial repolarization phase (Te interval) in hypogonadal males, potentially addressing some electrophysiological abnormalities 2

Cardiovascular Risk and Safety

• The 2024 American Heart Association/American Stroke Association guidelines state that TRT is reasonable in men 45-80 years with confirmed hypogonadism and does not increase stroke risk 1
• The recent TRAVERSE trial (2023) demonstrated that TRT was noninferior to placebo regarding major adverse cardiac events in men with hypogonadism who had preexisting or high risk of cardiovascular disease 3
• Studies have not demonstrated an increased incidence of cardiovascular disease events such as myocardial infarction, stroke, or angina with TRT 1

Effects on Cardiovascular Risk Factors

• TRT has shown neutral effects on lipid profiles when physiologic replacement doses are used 1
• Most studies show no change in total cholesterol, LDL, or HDL with physiologic TRT doses 1
• Only supraphysiologic doses (600 mg/week) have been associated with significant reductions in HDL 1
• TRT may have beneficial effects on insulin resistance and metabolic parameters in men with hypogonadism 1

Potential Cardiac Structural Concerns

Heart Failure Considerations

• TRT may be beneficial for men with heart failure, with studies showing improvements in exercise capacity and New York Heart Association class 4
• Low testosterone correlates with heart failure severity, exercise functional capacity, and worse clinical prognosis 4
• Caution is warranted in patients with severe, uncontrolled, or poorly controlled congestive heart failure 1
• Due to sodium and water retention, edema with or without congestive heart failure may be a complication in patients with preexisting cardiac disease 5

Monitoring Recommendations

• Regular monitoring of cardiovascular parameters is recommended during TRT 1
• Dose adjustment may be necessary if fluid retention occurs 5
• If TRT is restarted after discontinuation due to complications, a lower dose should be used 5

Clinical Implications and Pitfalls

Important Caveats

• Dosage matters: physiologic replacement doses appear safe, while supraphysiologic doses may increase cardiovascular risk 1
• Route of administration may affect cardiovascular outcomes, with transdermal formulations showing minimal effects on lipid profiles 1
• The 2023 TRAVERSE study found a higher incidence of atrial fibrillation and pulmonary embolism in the testosterone group, highlighting the need for monitoring 3
• Proper patient selection is crucial - TRT should be considered only in men with confirmed hypogonadism (symptoms plus testosterone levels <300 ng/dL) 1

Monitoring Algorithm

1. Establish baseline cardiovascular status before initiating TRT 1
2. Target testosterone levels between 350-750 ng/dL 3
3. Monitor for fluid retention, especially in patients with preexisting cardiac disease 5
4. Assess lipid profiles periodically during treatment 1
5. Consider cardiac structure and function evaluation in patients with preexisting cardiovascular disease 4

While definitive long-term data are still needed, current evidence suggests that properly administered TRT in appropriate candidates does not negatively impact cardiac structure and may even provide cardiovascular benefits in men with hypogonadism 1, 3.