Effect of estrogen plus progestin on risk for biliary tract surgery in postmenopausal women with coronary artery disease - The heart and estrogen/progestin replacement study

Background: Animal and observational epidemiologic studies have reported th at estrogens may increase the risk for gallstones. No major clinical trials have examined the effect of estrogen plus progestin therapy in postmenopau sal women on the risk for biliary tract surgery. Objective: To determine the effect of estrogen plus progestin on the risk f or biliary tract surgery in postmenopausal women with known coronary artery disease. Design: Randomized, double-blind placebo-controlled trial of postmenopausal hormone therapy for coronary heart disease. Setting: 20 U.S. clinical centers. Participants: 2253 postmenopausal women with a gallbladder, 44 to 79 years of age at baseline, in the Heart and Estrogen/progestin Replacement Study ( HERS). Intervention: conjugated equine estrogens, 0.625 mg, plus medroxyprogestero ne acetate, 2.5 mg, daily in one tablet or identical placebo. Measurements: Documented biliary tract surgery. Results: A total of 147 women (7%) were hospitalized for biliary tract surg ery in HERS. Treatment with estrogen plus progestin resulted in a marginall y significant 38% increase in the relative risk for biliary tract surgery ( P = 0.05). A small absolute difference in risk suggested that for every 185 women treated with estrogen plus progestin, one additional woman had bilia ry tract surgery per year. After adjustment for baseline and in-study stati n use, the association was attenuated further (P = 0.09). After adjustment for treatment assignment and other variables, increased body mass index, fi bric acid use, and a history of nonsurgical gallbladder disease were associ ated with an increased risk for biliary tract surgery, whereas statin use w as associated with a decreased risk (for each comparison, P < 0.05). Conclusion: Estrogen plus progestin therapy among postmenopausal women with known coronary disease resulted in a marginally significant increase In th e risk for biliary tract surgery.