Prevention by S-Adenosylmethionine of estrogen-induced hepatobiliary toxicity in susceptible women

Women with past histories of intrahepatic cholestasis of pregnancy (ICP) exhibit a congenital exaggerated sensitivity to estrogens, which may express as abnormal hepatic reactivity to oral contraceptive intake and increased risk of developing gallbladder disease. Since previous investigations have shown that S-adenosylmethionine (SAMe) is effective in antagonizing ICP, we wondered whether its administration to subjects with previous ICP could 1) protect them from a challenge with ethynylestradiol (EE) or 2) normalize the cholesterol saturation index (CSI). To test the first hypothesis, six women volunteered to receive EE (0.1 mg/day orally for 1 wk) and, after 3 months, the same EE dose plus oral SAMe (800 mg/day for 1 wk). EE significantly increased serum values of transaminases, conjugated bilirubin, and total bile acids with respect to basal values. In the rechallenge with EE plus SAMe, liver function tests did not differ from basal levels and were significantly lower than the values obtained after EE. In the second experiment, we gave oral SAMe (800 mg/day for 2 wk) to seven women with previous ICP who exhibited cholesterol supersaturation of duodenal bile. Both subjects were nonpregnant and nonobese and had cholecystograms negative for gallstones. Bile CSI decreased from a basal value of 1.35 +/- 0.07 to 0.98 +/- 0.08 after SAMe (p less than 0.01). These findings indicate that SAMe protects women with previous ICP from EE-induced liver toxicity and normalizes bile CSI in the same subjects who secrete lithogenic bile. The data support the belief that SAMe acts as a physiological antidote against estrogen hepatobiliary toxicity in susceptible women