Testosterone Therapy and Atrial Fibrillation Risk
Testosterone therapy may increase the risk of atrial fibrillation, particularly in men with high-normal or elevated testosterone levels, and should be used with caution in patients with existing cardiovascular risk factors or a history of arrhythmias.
Evidence on Testosterone and Atrial Fibrillation
The relationship between testosterone and atrial fibrillation (AFib) appears complex and potentially contradictory:
Risk Factors and Mechanisms
- AFib is the most common cardiac arrhythmia, associated with significant morbidity and mortality 1
- Multiple clinical risk factors for AFib include increasing age, hypertension, diabetes, obesity, and structural heart disease 1
- Drug-induced AFib (DIAF) is increasingly recognized as a potential adverse effect of various medications 1
Testosterone Levels and AFib Risk
- Recent evidence suggests a non-linear relationship between testosterone levels and AFib risk:
- Low testosterone levels in men are associated with increased risk of AFib 2
- However, high-normal or elevated testosterone levels also appear to increase AFib risk 3, 4
- In the ASPREE study of healthy older men, those in the highest quintiles of testosterone concentration had approximately twice the risk of developing AFib compared to those with mid-range levels 4
Testosterone Replacement Therapy (TRT) and AFib
- The evidence regarding TRT and AFib risk is mixed:
- A 2017 study found that normalization of testosterone levels after TRT was associated with decreased incidence of AFib compared to non-normalized TRT or no TRT 5
- However, a recent cardiovascular safety trial noted more AFib events in testosterone-treated men 4
- A 2024 meta-analysis of randomized controlled trials did not find a significant increase in non-fatal arrhythmias or AFib with TRT, though the authors noted limitations in the available data 6
Clinical Recommendations
Patient Assessment and Risk Stratification
- Before initiating testosterone therapy, assess for existing cardiovascular risk factors and history of arrhythmias 1
- Consider waiting 3-6 months after any cardiovascular event before initiating testosterone therapy 1
Monitoring and Dosing
- Target testosterone levels in the middle tertile of the normal reference range (450-600 ng/dL) rather than maximizing levels 1
- Use the minimal effective dose necessary to achieve symptom improvement 1
- Monitor for cardiovascular symptoms during follow-up visits, including palpitations, chest pain, shortness of breath, or dizziness 1
Special Considerations
- Use particular caution when considering testosterone therapy in:
- Men with existing cardiovascular disease
- Older men (>65 years)
- Patients with a history of arrhythmias
- Men with multiple cardiovascular risk factors
Important Caveats and Pitfalls
- The FDA has required manufacturers of testosterone products to conduct controlled clinical trials evaluating cardiovascular outcomes, indicating ongoing safety concerns 1
- Counsel patients that the current evidence cannot definitively state whether testosterone therapy increases or decreases cardiovascular risk 1
- Lifestyle modifications (weight loss, increased physical activity) should be recommended alongside any consideration of testosterone therapy 1
- Avoid using 17-alpha-alkylated oral testosterone due to liver toxicity risks 1
- Use commercially manufactured testosterone products rather than compounded formulations to ensure consistent dosing 1
The relationship between testosterone and AFib appears to follow a U-shaped curve, with both low and high levels potentially increasing risk. Clinicians should aim for mid-range testosterone levels when treating testosterone deficiency and remain vigilant for signs of arrhythmias in patients receiving testosterone therapy.