Work

Effect of estrogen and testosterone on cardiac electrophysiology and atrial fibrillation

Year: 2025

Type: article

Abstract: The prevalence and treatment outcomes of atrial fibrillation (AF) differ between sexes, yet the mechanisms underlying these differences remain poorly understood. Given that estrogen and testosterone are the major sex hormones, they may be involved in altering cardiac electrophysiology and risk of AF. Preclinical studies demonstrate that estrogen and testosterone alter ion currents and cardiomyocyte calcium (Ca 2+ ) handling via receptor-mediated mechanisms, but with opposite effects. Estrogen prolongs action potential duration (APD), whereas testosterone shortens it. A longer APD has antiarrhythmic effects in the atria, whereas a shorter APD is proarrhythmic. Testosterone also accelerates repolarization and enhances contractility, further increasing AF risk. However, most laboratory studies were done in animal ventricular models, limiting direct translation to human atrial physiology owing to species-specific electrophysiological differences. Human population studies suggest that decreased exposure to endogenous estrogen increases AF risk in women. In males, there is no similar consensus for the relationship between endogenous testosterone exposure and AF risk in men. Evidence from hormone replacement, testosterone replacement, and androgen deprivation therapies is similarly inconclusive, reflecting confounding factors, variation in hormone formulations, and reliance on single hormone measurements. This review provides novel insights into how estrogen and testosterone differentially influence cardiac electrophysiology and risk of AF in men and women. These findings underscore the need for personalized sex- and hormone-specific treatment strategies in AF management, addressing a critical gap in current clinical practices.

Source: Heart Rhythm O2

DOI: 10.1016/j.hroo.2025.11.007