Effect of synthetic oestrogens and progestagens in oral contraceptives on bile lipid composition

The prevalence of cholesterol gall stones in young women has increased since the introduction of oral contraceptives. The synthetic female sex hormones used in these preparations, increase the degree of cholesterol saturation in bile. To determine whether oestrogens, progestagens, or both, are responsible for the change in biliary cholesterol saturation index, a prospective randomised, controlled study was performed. A significant increase in the cholesterol saturation index of bile was observed when either 30 micrograms ethinyloestradiol plus 150 micrograms norgestrel (p = 0.01) or 50 micrograms ethinyloestradiol plus 250 micrograms norgestrel (p less than 0.01) were ingested daily for two months. No change in the cholesterol saturation index was observed when 30 micrograms ethinyloestradiol alone, or 30 micrograms ethinyloestradiol plus 2.5 mg norethisterone were used. The mechanism for the increase in cholesterol saturation index did not appear to involve bile acid metabolism. These results indicate that the progestagen, norgestrel, and not as previously thought the oestrogen, ethinyloestradiol, is responsible for the increase in cholesterol saturation of bile which accompanies the use of oral contraceptives.