COCs have a variety of effects on the liver. Estrogen influences the hepatic synthesis of DNA, RNA, enzymes, plasma proteins, lipids, and lipoproteins. It also influences the hepatic metabolism of carbohydrates and intracellular enzyme activity. Progestins have less, if any, effect on the liver. Although the liver is affected in a variety of ways by COCs, many of these changes have proved to be of no clinical significance, and others remain incompletely understood. Virtually all phase II and phase III studies of COCs have evaluated the effects of COCs on liver function tests, and have shown no effect.75 Some studies have shown an increased incidence of gallbladder disease and gallstones among current COC users.76 Other studies77 and a metaanalysis78 of the effect of COCs on biliary disease showed that COCs initially did increase the risk of biliary disease (RR = 1.36, 95% CI 1.15–1.62),78 but over time the risk returns to baseline. This suggests that, under the influence of COCs, susceptible (or asymptomatic) women become symptomatic from biliary disease shortly after starting the pill, whereas nonsusceptible women do not develop biliary disease over time with continued use.