Important differences exist between women and men with regard to cardiovascular disease. This is likely related to sex steroid (estrogen and testosterone) actions on the heart. However, recent controversies about the use of sex steroid therapies in men and women highlight a lack of understanding of the underlying mechanisms by which sex and sex steroids influence the heart. We have recently shown in humans that both the myocardium and cardiac adipose express the enzyme aromatase – showing that estrogen synthesis can actually occur within the myocardium. As cardiac adipose accumulates in aging/obesity, the influence of this locally synthesised estrogen likely increases. Cardiac adiposity has emerged as an important causative risk factor in cardiac arrhythmia vulnerability by currently unknown mechanisms. Our data indicate a potential role for adipose derived estrogen. This project will use molecular and tissue recording studies of human and rodent tissues to determine how estrogens synthesised within cardiac adipose contribute to the development of cardiac arrhythmias.