OBJECTIVE To investigate the effects of transdermal 17 beta-estradiol (E(2)) compared with oral unopposed as well as opposed E(2) on echocardiographic parameters of left ventricular (LV) systolic and diastolic function. METHODS A prospective, randomized, double-blind, placebo-controlled, multi-center study. METHODS Gynecologic and cardiologic outpatient departments. METHODS One hundred fifty-two healthy hysterectomized postmenopausal women. METHODS Participants received daily placebo (n = 49) or transdermal E(2) (50 microg; tE(2) group, n = 33), or oral E(2) (1 mg; oE(2) group, n = 37), or oral E(2) (1 mg) combined with gestodene (25 microg; oE(2)+G group, n = 33) for thirteen 28-day treatment cycles. METHODS M-mode, quantitative two-dimensional, and Doppler echocardiographic measurements were performed at baseline and after 1 year. RESULTS Compared with placebo, tE(2) and oE(2) showed no statistically significant changes in LV function. oE(2)+G resulted in a statistically significant favorable increase in peak flow velocity, flow velocity integral, and mean acceleration. Furthermore, a favorable decrease was observed in interventricular septum thickness and ejection time. CONCLUSIONS After 1 year of unopposed E(2), LV function remained unchanged. The oE(2)+G treatment showed a potential beneficial influence on LV systolic function.