Estrogens in intrahepatic cholestasis of pregnancy

Objective: To determine whether estrogen production and excretion are impai red in gravidas with intrahepatic cholestasis. Methods: Plasma and urine samples were collected from 13 women from the Uni ted States and Chile at 35-38 weeks' gestation with mild (n = 9) or severe (n = 4) intrahepatic cholestasis of pregnancy. Urinary and plasma steroid l evels from women with cholestasis were compared with levels from 27 normal pregnant women within the same gestational age range. Urinary concentration s of dehydroepiandrosterone (DHEA), estrone (E1), estradiol (E2), estriol ( E3), estetrol, progesterone, and 16-hydroxy-pregnenolone were measured by g as chromatography mass spectrometry, and plasma concentrations of DHEA sulf ate, progesterone, unconjugated E1, unconjugated E2, unconjugated E3, sulfa ted E3 derivatives, glucuronidated E3 derivatives, and total E3 were measur ed by radioimmunoassay. Results: Compared with normal pregnant women, women with cholestasis had si gnificantly lower plasma levels of estrogens and DHEA sulfate, the precurso r to placental estrogen production synthesized by the fetal adrenal gland ( Hotelling-Lawley trace = 0.81; F-4,F-19 = 3.9; P = .02). The mean plasma DH EA sulfate, unconjugated E2, unconjugated E3, and total E3 concentrations w ere 0.271, 10.21, 9.80, and 99.53 ng/mL, respectively, in women with choles tasis compared with 0.802, 18.98, 16.28, and 145.07 ng/mL for controls. Conclusion: Fetal adrenal production of DHEA sulfate, and in response, down stream placental production of estrogens, was compromised by intrahepatic c holestasis of pregnancy. (Obstet Gynecol 2000;95:372-6. (C) 2000 by The Ame rican College of Obstetricians and Gynecologists.).