S-adenosyl-l-methionine antagonizes ethynylestradiol-induced bile cholesterol supersaturation in humans without modifying the estrogen plasma kinetics

Abstract

Previous investigations have shown that S-adenosyl-l-methionine antagonizes both cholestasis and bile lipid alterations induced by ethynylestradiol in the rat. Since it is still unknown whether S-adenosyl-l-methionine prevents ethynylestradiol-induced cholesterol supersaturation of bile in humans also and how methylation interferes with plasma ethynylestradiol disappearance, the present study has been carried out. On different days, 5 nonobese subjects with indwelling biliary drainage and reestablished enterohepatic bile circulation received 200 μg of intravenous ethynylestradiol or ethynylestradiol plus 200 mg of S-adenosyl-l-methionine intramuscularly. S-adenosyl-l-methionine administration prevented any ethynylestradiol-induced changes in hepatic bile saturation index. Moreover, S-adenosyl-l-methionine did not affect ethynylestradiol pharmacokinetics which was evaluated in a group of 6 nonobese women receiving 100 μg of intravenous ethynylestradiol or ethynylestradiol plus 100 mg of S-adenosyl-l-methionine intramuscularly. These findings indicate that S-adenosyl-l-methionine prevents ethynylestradiol-induced bile lipid changes without interfering with ethynylestradiol kinetics in humans.