What are the recommendations for Testosterone Replacement Therapy (TRT) in patients with pre-existing cardiac conditions?

Testosterone Replacement Therapy in Patients with Pre-existing Cardiac Conditions

Patients with pre-existing cardiac conditions should be counseled that current scientific literature does not definitively demonstrate that testosterone therapy increases the risk of major adverse cardiovascular events, but caution is warranted and testosterone therapy should not be started for 3-6 months after acute cardiovascular events. 1

Cardiovascular Risk Assessment Before Starting TRT

• Before initiating TRT in patients with cardiac conditions:
  • Inform patients about the uncertain relationship between TRT and cardiovascular events 1
  • Evaluate baseline cardiovascular risk factors
  • Measure baseline hematocrit/hemoglobin (increased risk of polycythemia with TRT) 2
  • Consider cardiac stability (avoid starting TRT within 3-6 months of acute cardiac events) 2

Evidence on TRT and Cardiovascular Risk

The relationship between TRT and cardiovascular risk remains controversial:

• Conflicting Evidence: Studies measuring cardiovascular benefit or harm in men on testosterone therapy have returned inconsistent results 1
• FDA Warning: In 2015, the FDA issued a Safety Announcement cautioning against TRT use for age-related hypogonadism alone, recommending labeling changes to reflect increased risk of heart attack and stroke 1
• Recent Research: The 2023 TRAVERSE trial (n=5246) demonstrated that TRT was noninferior to placebo regarding major adverse cardiac events in men with hypogonadism and pre-existing or high risk of cardiovascular disease (HR 0.96; 95% CI 0.78-1.17) 3
• Potential Benefits: Some evidence suggests TRT may improve angina-free exercise tolerance in men with chronic stable angina and increase coronary artery diameter and blood flow 1

Recommendations for TRT in Cardiac Patients

1. Patient Selection:

   • Confirm testosterone deficiency with two separate morning measurements 2
   • Determine etiology (primary vs. secondary hypogonadism) 2
   • Ensure patient has true hypogonadism, not just age-related decline 1

2. Dosing and Target Levels:

   • Use minimal dosing necessary to achieve total testosterone levels in the middle tertile of normal range (450-600 ng/dL) 1, 2
   • Avoid supraphysiologic levels which may have greater cardiovascular risk 1

3. Monitoring Protocol:

   • Check testosterone levels at 3-6 months initially, then annually once stabilized 2
   • Monitor hematocrit/hemoglobin at baseline, 3-6 months, and then annually 2
   • Advise patients to report any cardiovascular symptoms (chest pain, shortness of breath, dizziness, transient loss of consciousness) 1

4. Specific Cardiac Considerations:

   • Heart Failure: Use with caution in patients with uncontrolled/severe congestive heart failure due to risk of edema 1, 4, 5
   • Recent Cardiac Events: Delay TRT for 3-6 months after myocardial infarction, stroke, or other major cardiovascular events 2
   • Venous Thromboembolism Risk: Monitor for symptoms of DVT/PE; discontinue TRT if suspected 4

5. Concurrent Management:

   • Implement lifestyle modifications (weight loss, physical activity) alongside TRT 1, 2
   • Address metabolic syndrome concurrently with testosterone management 2
   • Consider diuretic therapy if edema develops, particularly in patients with pre-existing cardiac disease 4

Potential Risks and Benefits

Risks:

• Possible increased risk of cardiovascular events in first 2 years of use 6
• Edema with or without congestive heart failure in patients with pre-existing cardiac disease 4, 5
• Potential for increased atrial fibrillation and pulmonary embolism 3

Benefits:

• May improve angina-free exercise tolerance 1
• Potential improvements in coronary blood flow 1
• Neutral or potentially beneficial effects on lipid profiles at physiologic replacement doses 1

Common Pitfalls to Avoid

• Starting TRT based on a single testosterone measurement 2
• Failing to monitor hematocrit regularly during treatment 2
• Not addressing metabolic syndrome concurrently with testosterone management 2
• Initiating TRT too soon after acute cardiovascular events 2
• Using supraphysiologic doses which may have greater cardiovascular risk 1

TRT can be considered for patients with pre-existing cardiac conditions who have confirmed hypogonadism, but requires careful patient selection, appropriate dosing, and vigilant monitoring of cardiovascular parameters to optimize safety and efficacy.