Contraceptive steroids alter the steady-state kinetics of bile acids.
Contraceptive steroids increase the ratio of cholic acid to chenodeoxycholic acid in bile. This alteration may contribute to the development of cholesterol gallstones. The objective of this study was to measure the effects of contraceptive steroids on bile acid kinetics and to relate them to changes in cholesterol metabolism. Steady-state kinetics of bile acids were measured in 15 healthy women, on and off contraceptive steroids. Cholic acid synthesis increased 30.3% (P less than 0.025) and its pool increased by 37.4% (P less than 0.025). Chenodeoxycholic acid synthesis decreased 6.4% (P = 0.08) and its pool decreased by 11.8% (P less than 0.05) during use of contraceptive steroids. The fractional turnover rates of both primary bile acids did not change. The changes in kinetics of the primary bile acids were related to alterations in biliary lipid and cholesterol metabolism, separately reported. (J. Lipid Res. 1987. 28: 828-839). During use of contraceptive steroids, total bile acid pool and total bile acid synthesis correlated directly with cholesterol synthesis, assayed in mononuclear leukocytes (r = 0.50 and r = 0.54, respectively) but not with the plasma clearance of chylomicron remnants, measured with retinyl palmitate. The data indicate that contraceptive steroids directly alter the hepatic synthesis of bile acids and suggest that newly synthesized cholesterol may be a preferred substrate for bile acid synthesis during use of contraceptive steroids.
Everson
G T
GT
Department of Medicine, University of Colorado Medical School, Denver 80262.
Fennessey
P
P
Kern
F
F
D000328:Adult; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism*; D002635:Chenodeoxycholic Acid / Q000032:analysis; D002784:Cholesterol / Q000378:metabolism; D002793:Cholic Acids / Q000032:analysis; D003280:Contraceptives, Oral, Synthetic / Q000494:pharmacology*; D005260:Female; D006801:Humans; D050356:Lipid Metabolism
D001647:Bile Acids and Salts; D002793:Cholic Acids; D003280:Contraceptives, Oral, Synthetic; D002635:Chenodeoxycholic Acid; D002784:Cholesterol