Postmenopausal Hormone Replacement Therapy and the Risks of Calculous Gallbladder Disease

Clinical Geriatrics Volume 14, Number 3 March 2006 Drs. Kalala, Krishna, and Lebovics are from the Division of Gastroenterology; Drs. Shah and Frishman are from the Department of Medicine, New York Medical College/Westchester Medical Center, Valhalla. over $6.5 billion, which is second only to gastroesophageal reflux disease (GERD) among digestive diseases. In 1998, 1143 deaths were attributed to gallbladder disease.7 Age is a major risk factor for gallstones, and this risk increases sharply after age 40. Women have a higher risk of gallbladder disease than men of the same age. The female-to-male ratio of gallbladder disease falls with increasing age, suggesting a possible hormonal effect. Most gallstones are asymptomatic. Complications of gallstones include biliary colic, acute cholecystitis, choledocholithiasis, cholangitis, gallbladder cancer, and acute pancreatitis. Most studies have used the presence of gallstones on ultrasound or cholecystectomy as a marker for gallbladder disease. In humans, 75-80% of gallstones are cholesterol stones, and approximately 10-25% are bilirubin pigment stones. Each type has a particular pathophysiology. The pathophysiology of cholesterol stones has been described in three steps: supersaturation of bile, crystallization, and stone growth. Cholesterol is insoluble in water. It is made soluble in bile by the detergent action of bile salts and phospholipids. Factors that increase cholesterol in bile or decrease bile acids cause supersaturated bile. This tilts the balance toward cholesterol insolubility. In addiINTRODUCTION The average age of onset of menopause in the U.S. population is 51 years.1 Vasomotor instability and hot flashes are among the first symptoms of decline of endogenous estrogen levels. Hormone replacement therapy (HRT), estrogen or estrogen plus progesterone, has been used to alleviate these symptoms. Important to note are the long-term effects of menopause as a risk factor for osteoporosis. One of the documented side effects of HRT is an increased risk of calculous gallbladder disease,2-4 the subject of this review.