The Influence of Pregnancy and Contraceptive Steroids on the Biliary Tract and Its Reference to Cholesterol Gallstone Formation

The evidence that pregnancy and the use of contraceptive steroids are associated with increased risk of cholesterol gallstones is reviewed from a physiologic viewpoint. Hepatobiliary functions known to be involved in gallstone formation are physical and chemical composition of bile; nucleation retention and crystal growth; decreased gallbladder motility; enterohepatic circulation of bile acids; speed of gastric emptying and intestinal transit time. In pregnancy many changes in bile acid concentration and pool size have been documented in animals and women with conflicting results. Late pregnant women have enlarged gall bladders that empty slowly in response to food and prolonged intestinal transit time but not gastric emptying has been reported. Cholesterol saturation of bile is increased. Estrogens are known to bind to receptors in hepatocytes and gall bladder. During estrogen administration cholesterol saturation in bile increases the bile acid pool size decreases synthesis of bile acids declines and recycling of bile acids increases with increased fecal losses of bile acids. Progestins have the opposite effects favoring bile acid synthesis. Progesterone has a quieting effect on smooth muscle possibly causing some of the complaints of pregnancy and oral contraception such as heartburn and constipation. These changes with the possibility that emptying of the gall bladder is incomplete give cause for the association between oral contraception and gallstones.