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Effects of Oral and Transdermal Estradiol Administration on Levels of Sex Hormone-Binding Globulin in Postmenopausal Women with and without a History of Intrahepatic Cholestasis of Pregnancy

Departments of Obstetrics and Gynecology (A.R., O.Y.), Clinical Genetics (K.A.), and Medicine (V.V, M.J.T.), Helsinki University Central Hospital, FIN-00029, Helsinki, Finland

Address all correspondence and requests for reprints to: Olavi Ylikorkala, Professor, Department of Obstetrics and Gynecology, Helsinki University Central Hospital, P.O. Box 140, FIN-00029 HUS, Helsinki, Finland. E-mail: olavi.ylikorkala{at}hus.fi.

SHBG, the most important transport protein for sex steroids, is produced in the liver under the control of estrogen action. In a randomized, double-blind, prospective crossover study we compared basal levels of serum SHBG and their responses to increasing doses of oral and transdermal estradiol (E2), followed by E2 plus oral progestin (medroxyprogesterone acetate [MPA]), in 40 postmenopausal women with or without a history of intrahepatic cholestasis of pregnancy (ICP), which could affect the synthesis of SHBG. Serum samples collected at baseline, on the last day of each E2 period, and on the last day of the E2 plus MPA combination were assayed for SHBG and E2. Basal levels of SHBG showed no difference between the study groups. Oral but not transdermal E2 increased SHBG concentrations by 67–171% in the control group, but the response was smaller (42–121%) in the ICP group. Addition of MPA decreased SHBG levels by 14–18% in both groups during both treatments. In conclusion, a history of ICP is associated with blunted responses of SHBG to oral estrogen.

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