Key result
Testosterone and TRT show a U-shaped link to AFib where both extremes increase risk.
Why the study?
Historically, low testosterone has been linked to increased AF risk in men, but recent evidence suggests elevated testosterone levels and testosterone replacement therapy may also confer risk.
Does testosterone replacement therapy or abnormal endogenous testosterone levels alter the risk of atrial fibrillation in men?
Does testosterone replacement therapy or abnormal endogenous testosterone levels alter the risk of atrial fibrillation in men?
Both low and high testosterone levels appear to increase atrial fibrillation risk, suggesting clinicians should target mid-physiologic levels and monitor patients on testosterone replacement therapy.
Target mid-physiologic testosterone levels with AF monitoring on TRT; extends observational data and supports prospective trials.
Historically, low testosterone (T) has been linked to increased atrial fibrillation (AF) risk in men, yet recent evidence suggests that elevated T levels and testosterone replacement therapy (TRT) may also confer risk. This review synthesizes emerging literature to characterize the evolving T-AF relationship and inform clinical practice. A structured literature search of MEDLINE/PubMed and Embase, supplemented by hand-searching reference lists of relevant publications, was performed, using terms including "testosterone," "testosterone replacement therapy," and "atrial fibrillation." Findings were heterogeneous. The 2023 TRAVERSE trial reported a higher AF incidence with TRT, contrasting with earlier VA data from Sharma et al. (2017) showing reduced AF risk when T normalized after treatment. A 2024 meta-analysis by Corona et al of 106 randomized placebo-controlled trials found no significant pooled AF signal. Real-world data remained mixed: a TriNetX-based replication did not confirm elevated AF risk, whereas a 5-year cohort study reported a hazard ratio of 1.27 in cisgender hypogonadal men receiving TRT. Population-level studies by Xu et al (2024) and post-hoc ASPREE analyses by Tran et al (2024) demonstrated a nonlinear association in which both low and high T levels increased AF risk. Updated mechanistic data support a U-shaped model: low T disrupts calcium handling, whereas high T alters potassium currents and promotes reentry. Converging evidence thus supports a U-shaped T-AF relationship. Until definitive data emerge, clinicians should prioritize risk-stratified TRT use, mid-physiologic T targets, stable formulations, and structured monitoring.
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Maligireddy et al. (2026) conducted a review in Atrial fibrillation. Testosterone and testosterone replacement therapy was evaluated on Atrial fibrillation. Testosterone and testosterone replacement therapy demonstrate a U-shaped relationship with atrial fibrillation, where both low and high levels increase risk.
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