PROGESTERONE METABOLITES AND BILE-ACIDS IN SERUM OF PATIENTS WITH INTRAHEPATIC CHOLESTASIS OF PREGNANCY - EFFECT OF URSODEOXYCHOLIC ACID THERAPY

The concentrations in serum of sulfated metabolites of progesterone ar e known to be elevated in patients with intrahepatic cholestasis of pr egnancy (ICP). The profiles of these metabolites and conjugated bile a cids were analyzed in serum from 11 patients with ICP before and durin g administration of ursodeoxycholic acid (UDCA) (8 patients) or placeb o (3 patients), The clinical condition of 7 of the patients given UDCA improved markedly, and 1 patient given placebo had a spontaneous remi ssion of the disease. The total concentration of conjugated bile acids in the 11 patients was 25 +/- 6 mu mol/L (mean +/- SEM) and decreased to 6.3 +/- 3.5 mu mol/L in the 7 patients responding to treatment wit h UDCA, The level of 7 alpha-hydroxy-4-cholesten-3-one was significant ly lower (7.2 +/- 2.2 ng/mL) in patients with ICP than in healthy preg nancy (18 +/- 4.6 ng/mL) (P < .05). The concentrations of 5 alpha-preg nane-3 alpha,20 alpha-diol mono-and disulfates decreased by 52% +/- 7. 9% and 68% +/- 5.5%, respectively, in the patients responding to treat ment, Similar decreases were observed for the mono-and disulfates of 5 alpha-pregnane-3 beta,20 alpha,21-triol and 5 beta-pregnane-3 alpha,2 0 alpha-diol. The disulfate of 5 alpha-pregnane-3 beta,20 alpha-diol s howed a smaller decrease, while glucuronidated steroids were not affec ted. The 3 alpha-/3 beta-hydroxysteroid ratio and di-/monosulfate rati o decreased significantly during UDCA. The magnitudes of the changes o f bile acid and steroid concentrations during UDCA were not correlated to each other. The results suggest that UDCA stimulates the biliary e xcretion of steroids with a 3 alpha-sulfoxy group and disulfates. This effect seems to be independent of the effect on bile acid excretion, indicating the use of different transport proteins, The possibility of an effect of UDCA on the formation of the steroid sulfates cannot be excluded.