S-adenosylmethionine for the treatment of intrahepatic cholestasis of pregnancy. Results of a controlled clinical trial.

Previous studies have shown that S-adenosylmethionine (SAMe) counteracts oestrogen-induced bile secretion failure. In order to confirm this anticholestatic activity, we conducted a single-blind clinical trial comparing SAMe with placebo in the treatment of women with intrahepatic cholestasis of pregnancy (ICP). Thirty patients in the last trimester of pregnancy were randomly assigned to receive either SAMe (800 mg/day i.v.) or placebo until delivery for a mean period of 18 days. After SAMe, the women exhibited significantly (p less than 0.01) lower levels of total bile acids, serum conjugated bilirubin and aminotransferases with respect to pretreatment levels as well as to the corresponding values of the placebo group. In addition, SAMe significantly reduced pruritus whereas placebo was ineffective. No adverse reactions on mother or child were recorded during SAMe treatment, and the follow-up of these cases showed an incidence of premature labour (earlier than 37 weeks of gestation) in 2 out of 15 vs 5 out of 15 cases in the placebo group. In conclusion, these findings document that SAMe is more effective than placebo in ameliorating subjective and objective parameters of ICP.

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

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 methynation 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 micrograms 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 ethylnylestradiol pharmacokinetics which was evaluated in a group of 6 nonobese women receiving 100 micrograms 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.

Cicloxilic acid and the bile lipids in oral contraceptive users.

Cholesterol supersaturation of gallbladder bile induced by oral contraceptives is significantly reduced by the administration of cis-2-hydroxy-2-phenyl-cyclohexane-carboxilic acid (cicloxilic acid), a choleretic substance which has been demonstrated to exert an antilithogenic effect in the rat and in man.