Does exogenous testosterone therapy increase the risk of atrial fibrillation (AFib)?

From the Guidelines

Exogenous testosterone therapy does not appear to increase the risk of atrial fibrillation, according to the most recent and highest quality evidence. The 2024 guideline for the primary prevention of stroke from the American Heart Association/American Stroke Association suggests that initiation or continuation of transdermal testosterone therapy in individuals with appropriate indications is reasonable and does not increase the risk of stroke 1. This is in line with the findings of a 2020 evidence report for a clinical practice guideline by the American College of Physicians, which found that most studies did not identify an increased risk for death or cardiovascular events associated with testosterone therapy 1.

Key Considerations

• The risk of cardiovascular events, including atrial fibrillation, should be carefully evaluated on an individual basis, taking into account the patient's underlying medical conditions and risk factors.
• Patients considering testosterone therapy should undergo baseline cardiovascular assessment, including ECG evaluation, and regular monitoring of cardiovascular symptoms, blood pressure, and hematocrit levels during treatment.
• The lowest effective dose of testosterone should be employed when therapy is indicated, particularly in men with existing cardiovascular disease or multiple risk factors.
• The biological mechanism of testosterone's effects on cardiac electrophysiology and potential increases in hematocrit levels should be considered when evaluating the risk of atrial fibrillation in patients on testosterone therapy.

Evidence Summary

• A 2020 evidence report found that most studies did not identify an increased risk for death or cardiovascular events associated with testosterone therapy 1.
• The 2024 guideline for the primary prevention of stroke suggests that transdermal testosterone therapy does not increase the risk of stroke 1.
• A 2018 guideline from the American Urological Association recommends counseling patients that the current scientific literature does not definitively demonstrate that testosterone therapy increases the risk of major adverse cardiovascular events (MACE) 1.

From the FDA Drug Label

5.5 Cardiovascular Risk

The FDA drug label does not answer the question.

From the Research

Exogenous Testosterone Therapy and Atrial Fibrillation Risk

• The relationship between exogenous testosterone therapy and the risk of atrial fibrillation (AFib) is complex and has been investigated in several studies 2, 3, 4, 5, 6.
• A study published in EClinicalMedicine found that circulating testosterone concentrations within the high-normal range are independently associated with an increased risk of incident AF amongst healthy older men 2.
• However, a systematic review and meta-analysis published in The American Journal of Medicine found that exogenous testosterone therapy did not show any significant increase in risk of myocardial infarction, stroke, or mortality compared with placebo 3.
• Another study published in Clinical Endocrinology found that injected testosterone was associated with an increased risk of adverse cardiovascular events, including myocardial infarction, stroke, or unstable angina, in older adult men following injection receipt 4.
• A prospective study published in Clinical Cardiology found that low serum androgens, including testosterone and dihydrotestosterone, are associated with an increased risk of AF in older men 5.
• A review published in Nature Reviews Cardiology noted that the cardiovascular safety of testosterone replacement therapy remains unclear, and that no trials published to date were designed or adequately powered to assess cardiovascular events 6.

Key Findings

• High-normal total testosterone concentrations may be associated with an increased risk of incident AF in healthy older men 2.
• Exogenous testosterone therapy may not be associated with an increased risk of myocardial infarction, stroke, or mortality 3.
• Injected testosterone may be associated with an increased risk of adverse cardiovascular events in older adult men 4.
• Low serum androgens may be associated with an increased risk of AF in older men 5.
• The cardiovascular safety of testosterone replacement therapy remains unclear due to limited evidence 6.