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  • Title: Serum bile acids and the bile acid tolerance test under oral contraception.
    Author: van Berge Henegouwen GP, van der Werf SD.
    Journal: Hepatogastroenterology; 1992 Apr; 39(2):177-80. PubMed ID: 1634184.
    Abstract:
    Oral contraceptives (OC) have lithogenic properties as shown by a rise in biliary cholesterol secretion and cholesterol saturation index. Since we noted not only a rise in saturation index, but also a reduction in chenodeoxycholate (CDC) pool size and an increase in cholate (C) pool size during oral contraception (30 micrograms ethinylestradiol + 150 micrograms desogestrel), we investigated the endogenous bile acid tolerance test as a potential predictor of this effect on bile acid pool sizes using a cholecystokinin infusion of 55 min duration (1.2 U.kg-1.hr-1) as stimulus of the enterohepatic bile acid circulation in 12 healthy females before and during oral contraception for 3-5 months. Serum C and CDC conjugates were measured at 5-10 min intervals over a period of 150 min and analysed by two specific RIA's. Although no significant correlations between the serum CDC and C measurements and CDC and C pool sizes were found, a significant reduction of nearly 40% for both serum peak levels and the integrated area under the serum curve of CDC conjugates during oral contraception, but not of C conjugates was found. The reduction in serum levels of CDC conjugates during OC using the present model is best explained by both a reduction in CDC pool size and more efficient hepatic uptake of CDC conjugates (consisting of considerably more taurine conjugates during OC use), as well as by an intestinal effect on bile acid absorption under OC. Gastroenterologists analyzed data on 12 19-30 year old, healthy hospital nurses and medical school students in either Utrecht or Arnhem, the Netherlands to study the endogenous bile acid tolerance test before and after oral contraceptive (OC) use and to examine likely changes in the enterohepatic circulation of each bile acid during OC use. The OCs contained 30 mcg ethinyl estradiol and 150 mcg desogestrel. The study did not reveal a strong correlation between serum chenodeoxycholate (CDC) measurements and CDC pool size, thus clinicians should not use them to monitor changes in CDC pool sizes in individuals. They could use serum CDC measurements, however, to monitor CDC pool size changes as a result of pharmacological manipulation with bile acid therapy or estrogen treatment in larger groups of people. During the study, the area under the curve (AUC) of CDC conjugates and serum CDC peak levels was 40% lower during OC use than it was when the women did not use OCs (p.01 and p.02, respectively). The reduction in the AUC of serum CDC peak levels may have been a result of a sharp increase in taurine conjugates of all bile acid classes during OC use. The even stronger reduction in the AUC of CDC conjugates may be because hepatic extraction of taurine conjugates are more efficient than of glycine conjugates. Glycine amidated CDC is somewhat passively absorbed at the proximal small intestinal level while taurine CDC is not. Thus more distal absorption of taurine-enriched CDC in the small intestine occurs. They very small increase in CDC conjugates after cholecystokinin infusion during OC use is somewhat like what happens during pregnancy.
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