Data from the Third National Health and Nutrition Examination Survey (1) indicate that 11% of U.S. women have a history of clinical gallbladder disease—that is, either previous cholecystectomy or self-reported history of gallstones. Factors associated with gallbladder disease, at least in some studies, include older age, female sex, white ethnicity/race, obesity, rapid weight loss, and, among women, greater parity, use of oral estrogen–containing contraceptives, and postmenopausal estrogen therapy (2). These associations, in general, have been based on observational data and may partly reflect the effects of ascertainment and recall bias, as well as confounding. While some observational studies suggest that estrogens increase the risk for gallbladder disease by as much as twofold to fourfold (3), such an association has not been reported consistently (2–3). The effect of combined estrogen plus progestin therapy has been less well studied, and no recent clinical trial data exist on the relation of such therapy to the risk for biliary tract surgery among postmenopausal women.