HEMODYNAMIC-EFFECTS OF TRANSDERMAL ESTRADIOL ALONE AND COMBINED WITH NORETHISTERONE ACETATE

A 24 weeks, randomized, two-period, placebo controlled study was condu cted to compare the effects of continuous transdermal 17 beta-estradio l replacement therapy (0.05 mg/day once a week) with placebo on system ic hemodynamics and blood pressure in postmenopausal women. Twenty-nin e postmenopausal women (47-62 years) free of hormone replacement thera py were randomized in two groups; group 1 received estradiol patches f or the first 12 weeks and placebo patches for the second, and group 2 received the same treatments in the reverse order. The effect of combi ned estradiol plus oral norethisterone acetate (NETA) 1 mg was also ev aluated in the subset of women with intact uteri (n = 24). Crossover a nalysis showed that stroke volume and cardiac output were significantl y 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 leve ls during active treatment and hemodynamic changes were not significan t, hemodynamic changes were significantly greater above 63 pg/ml than below this level (P < 0.05). Oral norethisterone acetate administratio n either during transdermal placebo or estradiol arms tended to modify systemic hemodynamics in the same direction than estradiol but the ch anges did not attained statistical significance. In summary compared w ith placebo, transdermal 17 beta-estradiol, replacement to postmenopau sal women, increased cardiac output and decreased blood pressure. Alth ough the average magnitude of changes was small, the results suggest t hat plasma estradiol levels could be a source of individual variabilit y in the hemodynamic response. Oral NETA administration tended to enha nce rather than reverse the estradiol-induced changes. (C) 1997 Elsevi er Science Ireland Ltd.