The concentrations in serum of sulfated metabolites of pro-Intrahepatic cholestasis of pregnancy (ICP) is charactergesterone are known to be elevated in patients with intraheized by skin pruritus appearing in late pregnancy, coinciding patic cholestasis of pregnancy (ICP). The profiles of these with a moderate or mild increase in serum bile acids (mainly metabolites and conjugated bile acids were analyzed in serum cholic acid), a mild rise in serum aminotransferases and bilifrom 11 patients with ICP before and during administration rubin, and a subclinical steatorrhea, all of them subsiding of ursodeoxycholic acid (UDCA) (8 patients) or placebo (3 soon after delivery. [2][3] Its main clinical consequences are the patients). The clinical condition of 7 of the patients given disturbed maternal status caused by pruritus and the risk of UDCA improved markedly, and 1 patient given placebo had stillbirths and premature deliveries. The pathogenesis of the a spontaneous remission of the disease. The total concentradisease and of its clinical consequences is still obscure, altion of conjugated bile acids in the 11 patients was 25 { 6 though a role of female sex hormones and/or their metabommol/L (mean { SEM) and decreased to 6.3 { 3.5 mmol/L lites is suggested by several studies. [7][8] While estrogens have in the 7 patients responding to treatment with UDCA. The received most attention as potential inducers of ICP, it is of level of 7a-hydroxy-4-cholesten-3-one was significantly lower interest that 10 of the 13 patients studied by Bacq et al. 4 had (7.2 { 2.2 ng/mL) in patients with ICP than in healthy pregbeen given daily doses of 0.2 to 1 g of progesterone shortly nancy (18 { 4.6 ng/mL) (P Γ΅ .05). The concentrations of 5abefore the development of ICP.
pregnane-3a,20a-diol mono-and disulfates decreased by 52%
The daily synthesis of progesterone in late pregnancy is { 7.9% and 68% { 5.5%, respectively, in the patients reapproximately 250 to 350 mg/d. The hepatic metabolism of sponding to treatment. Similar decreases were observed for progesterone involves 5a and 5b reduction of the 4,5-double the mono-and disulfates of 5a-pregnane-3a,20a,21-triol and bond and reduction of the 3-and 20-oxo groups to yield a 5b-pregnane-3a,20a-diol. The disulfate of 5a-pregnanenumber of isomeric pregnanolones and pregnanediols. The 3b,20a-diol showed a smaller decrease, while glucuronidated 5b-isomers are mostly glucuronidated, while 5a-isomers are steroids were not affected. The 3a-/3b-hydroxysteroid ratio sulfated. [11][12] The monosulfates may be hydroxylated in the and di-/monosulfate ratio decreased significantly during 16 or 21 positions. 11 The sulfated pregnanolones, preg-UDCA. The magnitudes of the changes of bile acid and steroid nanediols and 5a-pregnane-3a,20a,21-triol are present in concentrations during UDCA were not correlated to each mmolar concentrations in plasma, and the concentrations inother. The results suggest that UDCA stimulates the biliary crease with time of gestation. 12 Women with ICP have markexcretion of steroids with a 3a-sulfoxy group and disulfates. edly elevated levels of many of these sulfates. [13][14][15] It is not This effect seems to be independent of the effect on bile acid clear whether this abnormality is primary or secondary to excretion, indicating the use of different transport proteins. the cholestasis. Sulfated and glucuronidated progesterone The possibility of an effect of UDCA on the formation of the metabolites are excreted in bile in late pregnancy, 16 and the steroid sulfates cannot be excluded. (HEPATOLOGY 1997; concentrations in bile, 17 as well as the excretion of steroids 26:1573-1579.)
in feces, 18 are lower in ICP than in normal pregnancy. Oral administration of ursodeoxycholic acid (UDCA) to patients with ICP of early onset (before week 33 of pregnancy) results in an amelioration of pruritus and the correction of some serum liver tests. A recent double-blind study comparing the effects of UDCA and a placebo in patients with ICP of Abbreviations: ICP, intrahepatic cholestasis of pregnancy; UDCA, ursodeoxycholic early onset has confirmed the beneficial effects of this bile acid.