{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:14:10Z","timestamp":1790806450076,"version":"4.1.0"},"reference-count":33,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T00:00:00Z","timestamp":1701648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objective<\/jats:title>\n<jats:p>To determine whether menopausal hormone therapy (MHT) increases the risk of gallstones and gallbladder cancer.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Design<\/jats:title>\n<jats:p>A retrospective cohort study.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Patients or other participants<\/jats:title>\n<jats:p>Data from the Korea National Health Insurance Corporation was obtained between January 1, 2002, and December 31, 2019.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Interventions<\/jats:title>\n<jats:p>Participants were divided into MHT and non-MHT groups; the MHT group was analyzed in detail by dividing participants into tibolone, combined estrogen plus progestin by the manufacturer (CEPM) or physician (CEPP), oral estrogen alone, and topical estrogen subgroups.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Main outcome measures<\/jats:title>\n<jats:p>The incidence of gallstones and gallbladder cancer was compared between the two groups.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec006\">\n<jats:title>Results<\/jats:title>\n<jats:p>This study enrolled 1,004,034 and 381,711 patients in the non-MHT and the MHT groups, respectively. The incidence of gallstones was 2.6% in the non-MHT group and 3.4%, 2.6%, 3.4%, 3.2%, and 4.4% in the tibolone, CEPM, oral estrogen alone, CEPP, and topical estrogen groups, respectively. Cox proportional hazard analysis revealed that all hormones increased the risk of gallstones ([tibolone] hazard ratio [HR]: 1.347, 95% confidence interval [CI]: 1.309\u20131.387, [CEPM] HR: 1.146, 95% CI: 1.1\u20131.19, [oral estrogen alone] HR: 1.241, 95% CI: 1.18\u20131.305, [CEPP] HR: 1.164, 95% CI: 1.01\u20131.341, [topical estrogen] HR: 1.602, 95% CI: 1.295\u20131.983). However, the risk of gallbladder cancer did not change with any hormone therapy.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec007\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>All types of MHT including tibolone, increased the risk of gallstones. This risk was the highest with topical estrogen, which may be a result of selection bias due to concerns regarding the adverse effects of CEE and MPA.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0294356","type":"journal-article","created":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T18:25:35Z","timestamp":1701714335000},"page":"e0294356","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Menopausal hormone therapy increases the risk of gallstones: Health Insurance Database in South Korea (HISK)-based cohort study"],"prefix":"10.1371","volume":"18","author":[{"given":"Jin-Sung","family":"Yuk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5299-3820","authenticated-orcid":true,"given":"Ji 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