Biliary lipids, bile acids, and gallbladder function in the human female: effects of contraceptive steroids

Individuals who take contraceptive steroids or estrogens are at increased risk of developing cholesterol gallstones. The mechanisms of the increased stone formation are incompletely understood. In this study we report biliary lipid composition and secretion, bile acid composition and kinetics, and gallbladder function in a group of healthy, nonobese women taking a contraceptive steroid preparation. A comparable group of healthy women served as controls. Bile-rich duodenal fluid was obtained after stimulation of gallbladder contraction; bile acid, phospholipid, and cholesterol concentrations were determined. Biliary lipid secretion rate was measured by the marker perfusion technique. Bile acid distribution was determined by gas-liquid chromatography. The pool size, FTR, and synthesis rate of each bile acid were measured by using CA and CDCA labeled with the stable isotope of carbon, 13C. In some of the subjects gallbladder storage and emptying were measured during the kinetic study, by real-time ultrasonography. Contraceptive steroid use was associated with a significant increase in biliary cholesterol saturation and in the lithogenic index of bile. The rate of cholesterol secretion in the contraceptive steroid group was 50% greater than in the control (p much less than 0.001) and the rate of bile acid secretion was reduced (p less than 0.02). The total bile acid pool size was significantly increased by contraceptive steroids. The major increase occurred in the CA pool (p less than 0.04). The daily rate of enterohepatic cycles of the bile acid pool was decreased by contraceptive steroids from 6.6 to 4.3 (p less than 0.01). The only effect of contraceptive steroids on gallbladder function was a slower emptying rate in response to intraduodenal amino acid infusion. No index of gallbladder function correlated significantly with any parameter of bile acid kinetics in this small group of subjects. The findings confirm the lithogenic effect of contraceptive steroids and indicate that its causes are an increase in cholesterol secretion and a decrease in bile acid secretion.