Biliary excretion and hepatotoxicity of contraceptive steroids.

Abstract

ABSTRACT The naturally occurring oestrogens and certain synthetic sex hormones, particularly those with a 17α-alkyl function, can interfere with hepatic excretory function by impairment of biliary excretion. This may be manifest in abnormal liver function tests or it may appear as cholestatic jaundice. The naturally occurring and synthetic sex hormones undergo extensive biliary excretion and enterohepatic circulation but the extent to which this occurs varies with species and structure. They appear in bile in the form of conjugates and metabolic conjugation is crucial for their biliary excretion. Impairment of metabolic conjugation, for genetic reasons, or because the presence of an inhibitor may lead to defective biliary excretion of steroids. The natural oestrogens and contraceptive steroids tend to undergo extensive enterohepatic circulation which causes them to persist in the body. This factor has an important bearing on their pharmacokinetics and this has not been adequately considered. The hepatic dysfunction induced by natural and synthetic sex hormones may affect the capacity of the liver to excrete other compounds of endogenous (e. g. bilirubin) and exogenous (e. g. other drugs) origin. The mechanism(s) whereby natural and synthetic sex hormones impair hepatic excretion is not known. These compounds can influence various factors involved in biliary excretion such as metabolic conjugation, hepatic uptake and secretion and permeability of the biliary tree. Steroid induced changes in bile composition may be important in both cholestasis and in the formation of lithogenic bile.