Incidence of Chest Pain with Testosterone Therapy
The incidence of chest pain associated with testosterone therapy is not precisely quantified in current literature, but patients should be counseled that cardiovascular symptoms such as chest pain are potential adverse effects that warrant immediate medical attention. 1
Cardiovascular Risk Profile of Testosterone Therapy
Current Evidence on Cardiovascular Risk
- The American Urological Association (AUA) guidelines state that the current scientific literature does not definitively demonstrate whether testosterone therapy increases or decreases the risk of cardiovascular events 1
- The FDA has noted in drug labeling that some postmarketing studies have shown an increased risk of myocardial infarction and stroke associated with testosterone replacement therapy 2
- The most recent large-scale randomized controlled trial (TRAVERSE, 2023) demonstrated that testosterone therapy was noninferior to placebo regarding major adverse cardiac events in men with hypogonadism and preexisting or high risk of cardiovascular disease 3
Specific Chest Pain Risk
- While specific incidence rates of chest pain are not well-documented, cardiovascular symptoms including chest pain are important enough to be mentioned in clinical guidelines as symptoms that patients should report during follow-up visits 1
- The FDA recommends that healthcare providers evaluate patients with signs or symptoms consistent with cardiovascular events, including chest pain 2
Risk Factors for Chest Pain with Testosterone Use
Patient-Specific Risk Factors
- Men with pre-existing cardiac disease appear to have higher risk
- In men under 65 with pre-existing diagnosed heart disease, the risk of myocardial infarction following initiation of testosterone therapy was substantially increased (RR 2.90) 4
- Older men (≥65 years) have shown a higher risk ratio (2.19) for myocardial infarction after testosterone prescription compared to younger men 4
Formulation Considerations
- Oral formulations of testosterone are associated with greater risk of blood pressure elevation, which may contribute to chest pain symptoms 5
- Injectable testosterone may have intermediate effects on blood pressure 5
- Transdermal preparations generally have minimal effects on blood pressure 5
Monitoring and Management
Recommended Monitoring
- Men on testosterone therapy should be advised to report any possible cardiovascular symptoms, including chest pain, shortness of breath, dizziness, or transient loss of consciousness during routine follow-up visits 1
- Regular monitoring of blood pressure and hematocrit is essential, particularly in the first 3-6 months of therapy 5
Risk Mitigation Strategies
- Clinicians should adjust testosterone therapy dosing to achieve a total testosterone level in the middle tertile of the normal reference range (450-600 ng/dL) 1
- Use the minimal dosing necessary to achieve therapeutic goals 1
- Lifestyle modifications (weight loss, increased physical activity) should be recommended concurrently with testosterone therapy 1
- Patients with pre-existing hypertension, obesity, or higher baseline hematocrit values require closer monitoring 5
Clinical Approach to Patients Reporting Chest Pain
Immediate Assessment
- Any report of chest pain in patients on testosterone therapy should be taken seriously and evaluated promptly
- Evaluate for signs or symptoms consistent with myocardial infarction, as the FDA notes increased risk in some postmarketing studies 2
- Consider temporarily discontinuing testosterone therapy until cardiovascular evaluation is complete
Long-term Management
- For patients with confirmed cardiovascular disease who experience chest pain on testosterone therapy, consider alternative treatments for hypogonadism
- For patients with risk factors but no confirmed disease, consider formulation changes (e.g., from oral to transdermal) and dose adjustments 5
The evidence regarding testosterone therapy and cardiovascular risk remains mixed, with some studies showing increased risk 4 and others showing no significant association 6, 3. The most recent high-quality evidence suggests testosterone therapy is noninferior to placebo regarding major cardiovascular events 3, but clinicians should remain vigilant about monitoring for chest pain and other cardiovascular symptoms in patients receiving testosterone therapy.