Oral contraceptives raise the cholesterol saturation of bile by increasing biliary cholesterol secretion

To discover the mechanism by which oral contraceptives increase the level of cholesterol saturation of human bile, we measured biliary lipid secretion rates, gallbladder and hepatic bile lipid composition, bile acid pool size, bile acid composition, and plasma lipoprotein levels in five healthy women during routine oral contraceptive treatment and again during normal menstrual cycles on no medication. The molar percent cholesterol in both gallbladder and hepatic bile was higher in every subject while taking oral contraceptives (p less than .02). Oral contraceptive usage was accompanied by a significant enhancement of biliary cholesterol secretion (65 versus 46 mg/hr, p less than .01), but there was no significant change in bile acid or phospholipid secretion, total bile acid pool size, or bile acid composition. These findings indicate that oral contraceptive usage increases biliary cholesterol secretion, thereby raising the level of cholesterol saturation of bile and predisposing to cholesterol precipitation and gallstone formation.