Serum estradiol-binding profiles in postmenopausal women undergoing three common estrogen replacement therapies: Associations with sex hormone-binding globulin, estradiol, and estrone levels

Objective: To compare the effects of three commonly prescribed estrogen rep lacement therapies-oral conjugated equine estrogens (CEE; n = 37), oral mic ronized estradiol (ME; n = 25), and transdermal estradiol (TE; n = 24)-on t he binding characteristics of plasma estradiol as related to the concentrat ions of blood sex hormone-binding globulin (SHBG), estradiol, and estrone. Design: Menopausal volunteers, opting for estrogen replacement therapy, gav e blood at 0, 2, and 4 months. SHBG was assayed by automated immunoabsorben t technology. Estradiol and estrone were determined by quantitative gas chr omatography/mass spectrometry, After tritiated estradiol was added to serum , the percentage of estradiol not bound to protein was determined by ultraf iltration and the percentage of estradiol bound to SHBG was measured by a m ethod exploiting that this protein, even when bound to estradiol, binds avi dly to Concanavalin A-Agarose, Results: In each study, 2- and 4-month data were similar. Increases in SHBG concentrations were 100% (p <0.001), 45% (p < 0.001), and 12% (nonsignific ant) for subjects who were receiving GEE, ME, and TE regimens, respectively . Decreases in the percentage of estradiol not bound to protein and increas es in the percentage of estradiol bound to SHBG correlated with changes in the concentrations of this protein mediated by the therapies. The order for increases in estradiol was ME similar to TE >> GEE, whereas for estrone, t he order was ME > CEE >> TE, divergent from the SHBG responses. Conclusions: The diverse responses observed can be explained by differences in the estrogen load delivered to target tissues as controlled by the inte rmediary circulation and metabolism of the hormones introduced in these reg imens. (Menopause 2000;7:243-250, (C) 2000, The North American Menopause So ciety.).