TRT and Atrial Fibrillation: Understanding the Cardiac Rhythm Risk

Written by Adam Maggio | Medically reviewed by Dr. Sarah Chen, PharmD, BCPS

Atrial fibrillation (AFib), an irregular and often rapid heart rate, has been observed with a higher incidence in men undergoing testosterone replacement therapy (TRT) in some large studies, notably the TRAVERSE trial. While the exact mechanisms are still being investigated, this finding underscores the importance of careful cardiac assessment and monitoring for AFib symptoms in men on TRT, especially those with pre-existing cardiovascular risk factors.

TRT and Atrial Fibrillation: Navigating the Cardiac Rhythm Landscape

Atrial fibrillation (AFib) is the most common type of cardiac arrhythmia, characterized by an irregular and often rapid heart rate that can lead to symptoms like palpitations, shortness of breath, and fatigue. More importantly, AFib significantly increases the risk of stroke and other heart-related complications. For men considering or undergoing testosterone replacement therapy (TRT), the potential link between TRT and AFib has emerged as a significant area of clinical interest and concern.

The TRAVERSE Trial: A Key Finding

One of the most impactful findings regarding TRT and AFib comes from the landmark TRAVERSE trial (Lincoff et al., 2023). This large, randomized, placebo-controlled study, designed to assess the cardiovascular safety of TRT, reported a statistically significant higher incidence of atrial fibrillation in the testosterone group (3.5%) compared to the placebo group (2.4%). This observation was one of the unexpected adverse event signals identified in the trial, alongside acute kidney injury and pulmonary embolism.

This finding from TRAVERSE is particularly noteworthy because of the trial's robust design and large patient population, which provides a high level of evidence. It suggests that while TRT may be noninferior to placebo for major adverse cardiovascular events (MACE), it might carry a specific risk for AFib in the population studied (men with hypogonadism and pre-existing cardiovascular disease or high risk).

Nuance and Conflicting Data

The relationship between testosterone and AFib is not entirely straightforward, and some other research presents a more complex picture. For instance, some studies have suggested that normalization of testosterone levels after TRT might actually be associated with a decreased incidence of AFib (Yassin et al., 2017). Conversely, other research indicates that naturally circulating testosterone concentrations within the high-normal range might be independently associated with an increased risk of incident AFib in older men (Tran et al., 2024).

This apparent conflict highlights several important points:

• Endogenous vs. Exogenous Testosterone: The effects of naturally occurring (endogenous) testosterone at different levels might differ from the effects of externally administered (exogenous) testosterone in TRT.
• Patient Population: The TRAVERSE trial focused on men with pre-existing cardiovascular risk, a population that is already at higher risk for AFib.
• Mechanisms: The mechanisms linking testosterone to AFib are still under investigation. Potential pathways include testosterone's effects on cardiac electrophysiology, inflammation, and blood pressure regulation. Unlike polycythemia, which has a clear mechanistic link to clotting, the connection to AFib is less clear-cut.

Clinical Implications and Monitoring

Given the TRAVERSE trial's findings, clinicians must be particularly vigilant for AFib in men on TRT, especially those with existing cardiovascular risk factors. Key considerations include:

• Pre-TRT Cardiac Assessment: A thorough cardiac history and physical examination, including an electrocardiogram (ECG), should be performed before initiating TRT.
• Symptom Awareness: Patients should be educated about the symptoms of AFib, such as palpitations, irregular heartbeat, dizziness, shortness of breath, and chest discomfort, and instructed to report them immediately.
• Regular Follow-up: Routine follow-up appointments should include inquiries about cardiac symptoms. For high-risk individuals, more frequent monitoring or even Holter monitoring might be considered.
• Risk-Benefit Analysis: The decision to initiate or continue TRT in men with a history of AFib or those who develop it on therapy requires a careful risk-benefit discussion, potentially involving a cardiologist.

Unlike the overall MACE risk, which appears neutral, the specific signal for AFib with TRT is a concern that requires proactive management. It's not a reason to avoid TRT if indicated, but a reason to be vigilant.

Practical Takeaway

Atrial fibrillation is a serious cardiac arrhythmia that has been observed more frequently in men on TRT in some major studies. While the overall cardiovascular safety of TRT for major events appears reassuring, you'll need to be aware of the symptoms of AFib, such as a racing or irregular heartbeat, and report them to your doctor immediately. Your physician will assess your cardiac health before and during TRT, especially if you have other cardiovascular risk factors. Don't dismiss new or unusual heart sensations; prompt evaluation is essential to manage this potential risk effectively.