Menopausal hormone therapy and risk of cholecystectomy: a prospective study based on the French E3N cohort

Studies in the United States and the United Kingdom have reported an increased risk of cholecystectomy among women exposed to menopausal hormone therapy, but with substantial heterogeneity between types of hormone treatments. We evaluated the risk of cholecystectomy associated with different regimens of menopausal hormone therapy in a large prospective cohort study.

Between 1992 and 2008, 70 928 menopausal women from the French E3N study cohort were sent questionnaires assessing their use of menopausal hormone therapy, medical history and lifestyle characteristics. The primary outcome was cholecystectomy. We analyzed the risk of cholecystectomy associated with use of menopausal hormone therapy using Cox proportional models, with age as time-scale.

During follow-up, 45 984 (64.8%) of the participants were exposed to menopausal hormone therapy, and 2819 cholecystectomies were recorded. The use of menopausal hormone therapy was associated with an increased risk of cholecystectomy (adjusted hazard ratio [HR] 1.10, 95% confidence interval [CI] 1.01-1.20) compared with women who were not exposed to menopausal hormone therapy. The association was restricted to unopposed oral estrogen therapy (adjusted HR 1.38, 95% CI 1.14-1.67). Over 5 years, about 1 cholecystectomy in excess would be expected in every 150 women using oral estrogen therapy without progestogens, compared with women not exposed to menopausal hormone therapy.

The risk of cholecystectomy was increased among women exposed to oral estrogen menopausal hormone therapy, especially oral regimens without a progestagen. Complicated gallstone disease should be added to the list of potential adverse events to be considered when balancing the benefits and risks associated with menopausal hormone therapy.