What are the considerations for testosterone therapy in a patient with atrial fibrillation (Afib)?

Testosterone Therapy in Patients with Atrial Fibrillation

Testosterone replacement therapy (TRT) can be used in patients with atrial fibrillation, but requires heightened monitoring for incident AF episodes, acute kidney injury, and venous thromboembolism, while maintaining standard rate control and anticoagulation strategies per established AF guidelines.

Key Safety Concerns with TRT in AF Patients

The most recent large-scale TRAVERSE trial (2023) demonstrated that while TRT was noninferior for major adverse cardiac events in hypogonadal men with cardiovascular disease, there was a significantly higher incidence of new-onset atrial fibrillation in the testosterone group 1. Additionally, acute kidney injury and pulmonary embolism occurred more frequently with TRT 1. A 2025 real-world analysis confirmed increased risks of atrial fibrillation (HR 1.27) and venous thromboembolism (HR 1.26) in cis men receiving testosterone therapy 2.

However, the 2024 TriNetX analysis found increased AKI risk but did not confirm increased AF risk, suggesting the relationship may be context-dependent 3.

The Testosterone-AF Relationship

Low endogenous testosterone appears protective against AF in men, while TRT normalization shows mixed effects:

• A 2018 population study found that naturally low testosterone levels predicted incident AF and stroke in men (HR 0.98 per nmol/L increase, meaning lower T = higher risk) 4
• Paradoxically, a 2017 Veterans Affairs study showed that normalization of testosterone levels after TRT was associated with decreased AF incidence (HR 0.79 vs no treatment) compared to men who remained hypogonadal 5
• Men receiving TRT without achieving normal testosterone levels showed no AF benefit 5

Rate Control Management During TRT

Continue standard rate control medications without interruption when initiating TRT:

• Beta-blockers or non-dihydropyridine calcium channel antagonists remain first-line for rate control in AF patients receiving TRT 6, 7
• Never discontinue rate control medications to accommodate opioids or other sedating medications including testosterone-related therapies 6
• Monitor for bradycardia when combining TRT with rate-controlling agents, with atropine 0.5-1 mg IV available for acute hemodynamically unstable bradycardia 6
• Digoxin should not be used as sole agent for rate control in paroxysmal AF, as sedation or other effects may mask inadequate rate control during activity 6, 7

Anticoagulation Strategy

Maintain anticoagulation based on stroke risk stratification regardless of TRT use:

• Continue warfarin (target INR 2.0-3.0) or direct oral anticoagulants according to CHA₂DS₂-VASc score 6, 7
• The increased venous thromboembolism risk with TRT (HR 1.26) 2 makes anticoagulation adherence even more critical
• No adjustment to anticoagulation intensity is needed specifically for TRT, but ensure compliance given dual thrombotic mechanisms 6

Monitoring Protocol for AF Patients on TRT

Implement intensified surveillance during TRT initiation and titration:

• Assess heart rate and rhythm at each follow-up visit, particularly during testosterone dose adjustments 6
• Monitor for new-onset AF episodes in patients without prior AF, as risk increases within the first 3 years of therapy 3, 1
• Check renal function regularly given increased AKI risk (RR 1.53) 3
• Evaluate for signs/symptoms of venous thromboembolism 2, 1

Clinical Decision Algorithm

For hypogonadal men with existing AF considering TRT:

1. Confirm hypogonadism with two fasting testosterone levels <300 ng/dL 1
2. Ensure optimal rate control is achieved with beta-blockers or non-dihydropyridine calcium channel antagonists 7, 6
3. Verify appropriate anticoagulation for stroke prevention based on CHA₂DS₂-VASc score 7, 6
4. Initiate TRT with transdermal 1.62% testosterone gel, targeting levels 350-750 ng/dL 1
5. Monitor heart rate/rhythm, renal function, and thrombotic symptoms monthly for first 3 months, then quarterly 6, 3
6. If symptomatic bradycardia develops, reduce rate-control medication doses rather than stopping them, or consider pacemaker placement for persistent symptoms 6

Critical Pitfalls to Avoid

• Do not withhold TRT solely due to AF diagnosis - the TRAVERSE trial showed noninferiority for major adverse cardiac events 1
• Do not use IV non-dihydropyridine calcium channel antagonists in decompensated heart failure patients receiving any therapy, as combined hemodynamic effects are catastrophic 6, 7
• Do not assume TRT will worsen existing AF - normalization of testosterone may actually reduce AF burden in some patients 5
• Do not ignore the 27% increased AF risk - counsel patients about new palpitations and monitor accordingly 2
• Do not overlook AKI risk - maintain adequate hydration and avoid nephrotoxic combinations 3, 1

Special Populations

In transgender men receiving TRT, reassuring data shows no increased cardiovascular events compared to untreated cisgender men, with the added benefit of reduced suicide attempts (HR 0.52) 2. Standard AF management principles apply equally to this population.