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A 24 weeks, randomized, two-period, placebo controlled study was conducted to compare the effects of continuous transdermal 17 beta-estradiol replacement therapy (0.05 mg/day once a week) with placebo on systemic hemodynamics and blood pressure in postmenopausal women. Twenty-nine postmenopausal women (47-62 years) free of hormone replacement therapy were randomized in two groups; group 1 received estradiol patches for the first 12 weeks and placebo patches for the second, and group 2 received the same treatments in the reverse order. The effect of combined estradiol plus oral norethisterone acetate (NETA) 1 mg was also evaluated in the subset of women with intact uteri (n = 24). Crossover analysis showed that stroke volume and cardiac output were significantly higher (P < 0.05) and blood pressure was significantly lower (P < 0.05) with estradiol, irrespective of the order in which the treatments were administered. Although correlations between plasma estradiol levels during active treatment and hemodynamic changes were not significant, hemodynamic changes were significantly greater above 63 pg/ml than below this level (P < 0.05). Oral norethisterone acetate administration either during transdermal placebo or estradiol arms tended to modify systemic hemodynamics in the same direction than estradiol but the changes did not attained statistical significance. In summary compared with placebo, transdermal 17 beta-estradiol, replacement to postmenopausal women, increased cardiac output and decreased blood pressure. Although the average magnitude of changes was small, the results suggest that plasma estradiol levels could be a source of individual variability in the hemodynamic response. Oral NETA administration tended to enhance rather than reverse the estradiol-induced changes.