Hormonal Atrial Fibrillation: Pathophysiological Mechanisms That Trigger and Sustain the Arrhythmic Circuits

Atrial fibrillation (AF) is the supraventricular tachy-arrhythmia most commonly detected in the general population, with significant sex-related differences in epidemiology, pathophysiology, and treatment outcomes. Emerging evidence highlights the role of sex hormones-particularly estrogen and testosterone-in modulating left atrial electrophysiologic substrate, structural remodeling, inflammation, and thromboembolic risk. Hormonal fluctuations across different lifespan influence AF onset, progression, and therapeutic response, yet current management approaches largely overlook such determinants. This narrative review integrates data from basic, translational, and clinical research to examine hormonal effects on atrial substrate, disease progression, and differential results of treatments, including stroke prevention, pharmacological options, and transcatheter ablation. It also explores the potential of hormone-targeted interventions, antifibrotic therapies, and precision strategies tailored to hormonal status. Addressing these mechanisms could optimize patient-specific management, improve outcomes and guide future clinical practice recommendations. Advancing toward sex-specific, hormone-informed AF care requires further mechanistic studies, hormonal profiling, and sex-stratified clinical trials.