Biologic Effects of Transdermal Estradiol

We conducted a dose–response study in 23 postmenopausal women to compare the physiologic effects of transdermal estradiol and oral conjugated equine estrogens. The doses studied were 25, 50, 100, and 200 μg of transdermal estradiol per 24 hours, and 0.625 and 1.25 μg of oral conjugated estrogens. Transdermal estradiol increased circulating concentrations of estradiol and estrone. Oral conjugated estrogens also raised the levels of estrogen, particularly estrone. Both preparations lowered gonadotropin levels, decreased the percentages of vaginal parabasal cells, increased the percentage of superficial cells, and lowered urinary calcium excretion. The effects of 0.625 and 1.25 mg of oral estrogens were similar to those of 50 and 100 μg of transdermal estradiol per 24 hours, respectively. Oral estrogens significantly increased circulating levels of renin substrate, sex-hormone–binding globulin, thyroxine-binding globulin, and cortisol-binding globulin; transdermal estradiol had no effect. The higher dose of oral estrogens had favorable effects on concentrations of low-density and high-density lipoproteins, but transdermal estradiol did not. Neither preparation affected any of the four clotting factors studied. These data indicate that transdermal estradiol can elicit many of the desirable actions of estrogen while avoiding the pharmacologic effects of oral estrogens on hepatic proteins. (N Engl J Med 1986; 314:1615–20.) MOST postmenopausal women who undertake estrogen-replacement therapy use oral medications. Oral estrogens have exaggerated effects on hepatic processes, as compared with the nonhepatic actions characteristic of estrogens. 1 2 3 The hepatic effects of oral estrogens are believed to result in several complications of hormone replacement, including hypertension, cholelithiasis, and intravascular clotting. 4 5 6 Other routes of administration might avoid these enhanced hepatic actions. This paper compares the effects of the transdermal administration of estradiol with those of the oral administration of conjugated equine estrogens, the preparation most frequently prescribed for replacement therapy in the United States. The study used a dose–response design and compared . . .