TRT and Atrial Fibrillation Risk What TRAVERSE Means for Monitoring

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Key takeaways

TRAVERSE found more atrial fibrillation with TRT (3.5%) vs placebo (2.4%) while MACE did not increase; deaths were numerically lower with TRT.
The AF signal was a secondary finding with important limitations; a 2025 observational analysis did not confirm a statistically significant AF increase.
In February 2025, the FDA removed the boxed MACE warning and added a class-wide blood pressure warning, emphasizing ambulatory BP monitoring (ABPM).
Early, individualized monitoring can mitigate non-MACE risks like AF and acute kidney injury (AKI), especially in higher-risk men.
Physiologic dosing and avoiding supraphysiologic peaks are linked with better outcomes; VA data associate normalized testosterone with lower AF incidence.

Introduction
What TRAVERSE actually found
How strong is the AF signal?
What newer data say
The 2025 FDA label update
Practical risk stratification before starting TRT
Monitoring that matches the evidence
The early months: why AF might appear—and how to reduce risk
If you’re already on TRT
Men with prior AF or higher cardiovascular risk
What this means for safety—and for you
Open questions we’re watching
Conclusion

Introduction

Testosterone replacement therapy (TRT) has long carried debate around cardiovascular safety. The 2023 TRAVERSE trial added a new wrinkle: a higher rate of atrial fibrillation (AF) in men assigned to TRT compared with placebo, even as major adverse cardiovascular events (MACE) did not increase. In 2025, the FDA removed the boxed warning for MACE across testosterone products, while adding a class-wide warning about increases in blood pressure—shifting the focus from broad cardiovascular risk to targeted monitoring. Here’s what the latest evidence means if you’re considering TRT, already on therapy, or supporting someone who is.

What TRAVERSE actually found

TRAVERSE was a large, randomized, placebo-controlled trial enrolling 5,246 symptomatic men aged 45–80 with confirmed hypogonadism and preexisting or high cardiovascular risk. Over a median of 33 months:

MACE (cardiovascular death, nonfatal MI, nonfatal stroke) was not increased with TRT—the primary safety endpoint was met.
TRT recipients experienced more atrial fibrillation: 91 cases (3.5%) vs 63 (2.4%) with placebo (p=0.02).
Non-fatal arrhythmias overall were more frequent (p=0.001).
AKI occurred more often (60 vs 40 cases; p=0.04).
Pulmonary embolism events were numerically higher (0.9% vs 0.5%).
Paradoxically, there were 16 fewer deaths in the TRT group, a reassuring if exploratory signal.

This pattern reframes risk: while catastrophic endpoints were not elevated, certain non-MACE events—AF, AKI, and perhaps thromboembolism—merit attention during treatment, especially early on.

How strong is the AF signal?

Important context tempers the AF finding:

AF was a secondary outcome without mandated baseline ECGs or protocol-driven rhythm monitoring. Events relied on clinical diagnoses, which can vary in detection and documentation.
The study population skewed older with substantial cardiovascular comorbidity—men who already carry higher baseline AF risk.
Investigators and commentators have raised the “early mobilization” hypothesis: previously under-active, frail men may abruptly increase activity after TRT initiation (improved energy and anemia correction), transiently unmasking AF before longer-term cardiovascular gains accrue.
TRAVERSE did not provide dose-stratified AF analyses, so we cannot link events to supraphysiologic peaks or suboptimal titration.

Bottom line: the AF signal is real in this trial but methodologically limited and may not generalize to younger, lower-risk men or to care settings with tight dose control and proactive monitoring.

What newer data say

Since TRAVERSE, two complementary evidence streams inform interpretation:

A 2025 retrospective analysis found an increased risk of AKI with TRT (RR 1.53, 95% CI 1.07–2.18) but did not confirm a statistically significant AF increase (RR 1.48, 95% CI 0.93–2.37). While observational and confounded by design, it suggests AF risk may not be uniform across populations or practice styles.
Longitudinal observational data from the Veterans Affairs system indicated AF incidence was lowest in men whose testosterone was normalized to physiologic levels on TRT, compared with men whose levels were not normalized or who remained untreated. This aligns with clinical experience that careful titration and stable physiologic dosing correlate with better rhythm and vascular outcomes.

TRAVERSE also documented correction of anemia in many TRT recipients. Anemia is a recognized cardiovascular risk factor; its improvement could contribute to longer-term benefit that isn’t immediately visible in early safety signals.

The 2025 FDA label update: from broad warnings to targeted monitoring

In February 2025, the FDA removed the boxed warning about MACE from testosterone product labels and added a class-wide warning for increases in blood pressure based on ambulatory blood pressure monitoring data. The shift emphasizes:

No demonstrable increase in MACE when TRT is used as indicated in appropriately selected men.
Focused vigilance for non-MACE signals—especially blood pressure, arrhythmias, kidney function, and thromboembolic symptoms.
The practical value of ABPM and structured follow-up to catch manageable changes before they escalate.

Practical risk stratification before starting TRT

No article can assess your personal risk; that’s the role of your clinician. Still, it helps to understand how many practices approach stratification.

Factors that generally raise baseline AF or complication risk:

Prior AF or atrial flutter; known structural heart disease
Hypertension, obesity, diabetes, sleep apnea, thyroid disease
Chronic kidney disease or borderline renal function
Elevated hematocrit at baseline or prior erythrocytosis on TRT
Active smoking, heavy alcohol use, stimulant use
Age 65+ with multiple cardiovascular comorbidities

Reasonable baseline evaluations to discuss with your care team:

Confirmation of biochemical hypogonadism with morning testosterone on two days
Cardiovascular review, blood pressure measurement or ABPM
Hematocrit/hemoglobin, creatinine/eGFR, electrolytes
Consider a baseline ECG if arrhythmia risk is elevated or symptoms suggest palpitations; targeted cardiac evaluation as indicated
Sleep apnea screening if snoring, daytime sleepiness, or high STOP-BANG score

At Taurus Meds, we prioritize physiologic dosing and evidence-based monitoring tailored to a patient’s risk profile—particularly in the first few months when most non-MACE signals surface.

Monitoring that matches the evidence

Although schedules vary, the data and FDA update point to a few themes that many clinicians adopt:

Blood pressure: Incorporate ABPM or home BP checks, especially during dose titration and after any formulation change.
Serum testosterone: Monitor to maintain levels in the mid-normal physiologic range for age; avoid supraphysiologic peaks.
Hematocrit: Check periodically; address rising levels promptly to minimize thrombotic risk.
Renal function: Reassess creatinine/eGFR after initiation and with dose changes, particularly in men with preexisting kidney risk.
Symptoms review: Ask about palpitations, rapid or irregular heartbeat, dizziness, chest discomfort, decreased urine output, leg swelling, or sudden shortness of breath.

Cleveland Clinic authors have noted that outcomes depend on indication-based prescribing and vigilant monitoring to avoid excessive dosing—something that may not be consistently practiced in all settings. If care is fragmented, advocate for a clear follow-up plan.

The early months: why AF might appear—and how to reduce risk

If AF events cluster early, several modifiable factors may help reduce risk:

Gradual activity ramp-up: Rising energy is a common early benefit; a measured increase in physical activity may be safer than an abrupt jump from sedentary to vigorous exercise in men with underlying heart disease.
Dose and formulation: Avoid supraphysiologic peaks. Discuss whether your formulation’s pharmacokinetics align with stable levels for you.
Blood pressure and volume status: Monitor BP closely; manage salt intake prudently; maintain hydration, particularly with exercise or heat exposure.
Sleep and alcohol: Treat sleep apnea when present; moderate alcohol and avoid binge drinking, which can precipitate AF.
Interacting substances: Review decongestants, stimulants, and supplements with your clinician.

These are not substitutes for medical care but practical levers that, combined with individualized follow-up, may blunt early arrhythmia risk.

If you’re already on TRT

Do not stop therapy abruptly without talking to your prescriber. Sudden changes can cause symptom rebound and complicate evaluation.
Report new palpitations, irregular heartbeat, chest discomfort, shortness of breath, lightheadedness, decreased urination, or leg swelling promptly.
Keep lab and monitoring appointments. Dose adjustment to maintain physiologic levels is a safety feature, not merely a “check-the-box” task.
Share any ER or urgent care visits with your TRT clinician so findings (e.g., ECGs) inform your ongoing plan.

Men with prior AF or higher cardiovascular risk

TRAVERSE included men at elevated cardiovascular risk, and still showed no increase in MACE. However, for those with established AF, heart failure, advanced kidney disease, or multiple risk factors, conversations typically include:

Cardiology co-management, especially if AF has been symptomatic or difficult to control
Baseline ECG and, when indicated, rhythm monitoring
Early and more frequent follow-up during the first 3–6 months
Clear thresholds for contacting the care team if symptoms arise

TRT may still be appropriate in select patients when hypogonadism is confirmed and benefits justify risks; this is a nuanced, shared decision-making process.

What this means for safety—and for you

The weight of evidence now supports a refined message:

When TRT is prescribed for true hypogonadism and carefully titrated, MACE does not appear elevated, which the FDA recognized by removing the boxed warning.
Non-MACE safety signals—including AF, AKI, and potential thromboembolism—are real but manageable with patient selection, physiologic dosing, and proactive surveillance.
Long-term, steady, physiologic testosterone levels may even relate to lower AF incidence in real-world cohorts, underscoring the value of dose control and adherence.

For men exploring TRT, the practical question is less “Is TRT categorically safe or unsafe?” and more “What is my individual risk, and how will my care team monitor and mitigate it—especially early on?”

At Taurus Meds, we approach TRT as a longitudinal partnership: confirm the diagnosis, personalize dosing to physiologic targets, use ABPM and lab monitoring where it adds value, and keep communication open if symptoms evolve.

Open questions we’re watching

Mechanism: Why did TRAVERSE show more AF while normalized testosterone in observational data corresponded to less AF? Is early unmasking the key, or is there a biological threshold effect?
Early vs. long-term risk: What intensity and duration of early monitoring best minimize AF and AKI without overburdening patients?
Dose-response: Which serum levels or pharmacokinetic patterns best separate benefit from risk in diverse populations?
Real-world practice: How often are indication-based prescribing and titration achieved outside of clinical trials?
Subgroups: Which baseline characteristics most strongly predict secondary safety signals, and can we tailor follow-up accordingly?
AKI and PE: What are the dominant mechanisms, and how reversible are these events with dose adjustment or discontinuation?

Conclusion

TRAVERSE reshaped the conversation: MACE risk is not the main barrier to TRT for appropriately selected men, but non-MACE events—especially AF and AKI—deserve targeted, early vigilance. The 2025 FDA label update aligns with this nuance, emphasizing blood pressure monitoring and individualized follow-up rather than blanket warnings.

For patients and clinicians, the path forward is practical: confirm true hypogonadism, stratify risk thoughtfully, titrate to physiologic levels, and monitor early and consistently. Done this way, TRT can be both effective and responsibly managed—minimizing transient risks while pursuing durable benefits.

Disclaimer

This article is for informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare professional about your specific health questions and before making changes to your medications or treatment plan.

TRT and Atrial Fibrillation Risk What TRAVERSE Means for Monitoring