A randomised controlled trial of ursodeoxycholic acid and S-adenosyl-L-methionine in the treatment of gestational cholestasis Nadia Roncaglia, Anna Locatelli * , Alessandra Arreghini, Francesca Assi, Irene Cameroni, John C. Pezzullo, Alessandro Ghidini Objective To compare the efficacy of S-adenosyl-L-methionine and ursodeoxycholic acid in improving serum biochemical abnormalities in gestational cholestasis. Design Randomised clinical trial. Setting University hospital. Population All women at <36 weeks of gestation with severe gestational cholestasis during June 1996 to December 2001. Methods Enrolled women were randomly assigned oral S-adenosyl-L-methionine 500 mg twice daily or oral ursodeoxycholic acid 300 mg twice daily until delivery. Main outcome measures Reduction in the concentration of serum bile acids. Other variables considered included obstetric and neonatal outcome, clinical symptoms and other laboratory measurements (serum levels of transaminases and bilirubin). The two groups were compared using Student’s t test, Wilcoxon’s signed rank sum test and Fisher’s exact test, with a two-tailed P < 0.05 being considered significant. Results Of the 46 women enrolled, 24 received ursodeoxycholic acid and 22 S-adenosyl-L-methionine. At enrolment, gestational age, duration of therapy, rate of nulliparity, pruritus score and biochemical characteristics were similar between the groups. Both therapies significantly and equally improved pruritus. Women receiving ursodeoxycholic acid had a significantly greater improvement in the concentration of serum bile acids ( P ¼ 0.001), aspartate aminotransferase ( P ¼ 0.01), alanine aminotransferase (<0.001) and bilirubin ( P ¼ 0.002) compared with those receiving S-adenosyl-L-methionine. Duration of therapy was significantly greater in women receiving ursodeoxycholic acid compared with S-adenosyl-L- methionine ( P ¼ 0.04), whereas gestational age at delivery and rate of prematurity were similar in the two groups. Conclusions In women with intrahepatic cholestasis of pregnancy, ursodeoxycholic acid is more effective than S-adenosyl-L-methionine at improving the concentration of serum bile acids and other tests of liver function, whereas both therapies are equally effective at improving pruritus. INTRODUCTION Gestational cholestasis, an intrahepatic form of chole- stasis that occurs during the second half of pregnancy, is characterised by intense pruritus and abnormalities of liver function tests and bile acids. In most cases, the onset is in the last weeks of pregnancy and the women do not require treatment, either because the symptoms are mild or because the pregnancy is terminated. Onset of cholestasis early in pregnancy gestation with severe symptoms and serum biochemical abnormalities is often considered an indication for treatment. Of the several therapies proposed for this condition, ursodeoxycholic acid and S-adenosyl-L- methionine have been shown in several studies to have a beneficial effect on serum biochemical abnormalities. Their mechanism of action is thought to be enhancement of excretory hepatocyte function and choleretic activity, sta- bilisation of hepatocyte cell membrane and dilution of the more toxic bile acids in the enterohepatic circulation. 1 Ursodeoxycholic acid normalises the ratio of 3a to 3h hydroxysteroid in women with obstetric cholestasis and decreases the accumulation of bile acids in the fetus. 2,3 S-Adenosyl-L-methionine is implicated in methylation reactions, and in animal experiments, it protects against hormone-induced cholestasis by facilitating the trans- sulphuration of bile salts into excretory forms. 4 Anecdotal evidence suggests that improvement in serum biochemical DOI:10.1046/j.1471-0528.2003.00029.x BJOG: an International Journal of Obstetrics and Gynaecology January 2004, Vol. 111, pp. 17–21 D RCOG 2004 BJOG: an International Journal of Obstetrics and Gynaecology www.blackwellpublishing.com/bjog Department of Obstetrics and Gynecology, University of Milano-Bicocca, Monza, Italy Department of Pharmacology and Biostatistics, Georgetown University Medical Center, Washington, DC, USA * Correspondence: Dr A. Locatelli, Divisione di Ostetricia e Ginecologia, ISBM San Gerardo, Via Solferino, 16, 20052 Monza, Italy.