Serum Estradiol-Binding Profiles in Postmenopausal Women Undergoing Three Common Estrogen Replacement Therapies: Associations With Sex Hormone-Binding Globulin, Estradiol, and Estrone Levels*

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Objective:To compare the effects of three commonly prescribed estrogen replacement therapies—oral conjugated equine estrogens (CEE; n = 37), oral micronized estradiol (ME; n = 25), and transdermal estradiol (TE; n = 24)—on the binding characteristics of plasma estradiol as related to the concentrations of blood sex hormone-binding globulin (SHBG), estradiol, and estrone.Design:Menopausal volunteers, opting for estrogen replacement therapy, gave blood at 0, 2, and 4 months. SHBG was assayed by automated immunoabsorbent technology. Estradiol and estrone were determined by quantitative gas chromatography/mass spectrometry. After tritiated estradiol was added to serum, the percentage of estradiol not bound to protein was determined by ultrafiltration and the percentage of estradiol bound to SHBG was measured by a method exploiting that this protein, even when bound to estradiol, binds avidly 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% (nonsignificant) for subjects who were receiving CEE, ME, and TE regimens, respectively. Decreases in the percentage of estradiol not bound to protein and increases 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∽TE >> CEE, whereas for estrone, the 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 intermediary circulation and metabolism of the hormones introduced in these regimens. (Menopause 2000;7:243-250. © 2000, The North American Menopause Society.)

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