Markedly elevated levels of estrone sulfate after long-term oral, but not transdermal, administration of estradiol in postmenopausal women

Objective: To compare serum estrone sulfate (E1S) revels in postmenopausal women during long-term treatment with commonly prescribed doses of oral and transdermal estradiol (E-2). Design: A retrospective study performed in a University setting in the Unit ed States involving 33 healthy postmenopausal women. Two groups of postmeno pausal women were studied: group 1 (n = 10) received 1 mg oral micronized E -2 daily for 16 months; blood was drawn at 0, 7, and 15 months. Group 2 (n = 23) was randomized into three subgroups. Two of the subgroups (n = 8; n = 7) received E-2 delivered at a rate of 0.05 mg/day and 0. 1 mg/day, respec tively, by transdermal patch, changed twice weekly; the third subgroup rece ived a placebo (without E-2) patch for 9 continuous months. Blood samples w ere drawn at 0, 6, and 9 months. Serum E1S and E-2 were quantified by speci fic radioimmunoassays. Statistical analysis was performed by analysis of va riance. Results: After oral E-2 treatment, E1S levels increased significantly (p < 0.01) from baseline, reaching an average level of 38.8 ng/mL at 15 months. After transdermal E-2 treatment, E1S levels increased significantly, yet to a much lesser extent, reaching levels of 1.8 ng/mL and 3.2 ng/mL after 9 m onths of treatment with the 0.05 mg/day and 0.1 mg/day patches, respectivel y. Conclusions: Markedly elevated levels of E1S were found after long-term ora l estrogen treatment. In comparison to the increase in E1S levels after lon g-term oral estrogen treatment, there was only a small increase in E1S leve ls after transdermal E-2 therapy. This difference may be attributed to the higher dosage of oral E-2 that is required because of the low bioavailabili ty compared with the transdermal dosages.