Association of testosterone and testosterone replacement therapy with atrial fibrillation: an updated review

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.