Association of sex hormones, aging, and atrial fibrillation in men: the Framingham Heart Study.

Background: Endogenous sex hormones have been related to cardiovascular outcomes and mortality. We hypothesized that sex hormones are related to atrial fibrillation (AF) in a community-based cohort of middle-aged to older men.

Methods And Results: We examined testosterone, estradiol, and dehydroepiandrosterone sulfate in relation to incident AF in men participating in the Framingham Heart Study. We assessed the 10-year risk of AF in multivariable-adjusted hazard models. The cohort consisted of 1251 men (age, 68.0±8.2 years), of whom 275 developed incident AF. We identified a significant interaction between age and testosterone and, therefore, stratified men into age 55 to 69 years (n=786), 70 to 79 years (n=351), and ≥80 years (n=114). In men aged 55 to 69 years, each 1 SD decrease in testosterone was associated with hazard ratio (HR) 1.30 (95% confidence interval [CI], 1.07-1.59) for incident AF. The association between testosterone and 10-year incident AF in men 70 to 79 years did not reach statistical significance. In men≥80 years, a 1 SD decrease in testosterone was associated with HR 3.53 (95% CI, 1.96-6.37) for AF risk. Estradiol was associated with incident AF (HR, 1.12; 95% CI, 1.01-1.26). Dehydroepiandrosterone sulfate had a borderline association with risk of AF that was not statistically significant (HR, 1.12; 95% CI, 0.99-1.28).

Conclusions: Testosterone and estradiol are associated with incident AF in a cohort of older men. Testosterone deficiency in men≥80 years is strongly associated with AF risk. The clinical and electrophysiological mechanisms underlying the associations between sex hormones and AF in older men merit continued investigation.