Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Dec 4;18(12):e0294356.
doi: 10.1371/journal.pone.0294356. eCollection 2023.

Menopausal hormone therapy increases the risk of gallstones: Health Insurance Database in South Korea (HISK)-based cohort study

Jin-Sung Yuk  1 , Ji Young Park  2
Affiliations

Menopausal hormone therapy increases the risk of gallstones: Health Insurance Database in South Korea (HISK)-based cohort study

Jin-Sung Yuk et al. PLoS One. .

Abstract

Objective: To determine whether menopausal hormone therapy (MHT) increases the risk of gallstones and gallbladder cancer.

Design: A retrospective cohort study.

Patients or other participants: Data from the Korea National Health Insurance Corporation was obtained between January 1, 2002, and December 31, 2019.

Interventions: 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.

Main outcome measures: The incidence of gallstones and gallbladder cancer was compared between the two groups.

Results: 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]: 1.309-1.387, [CEPM] HR: 1.146, 95% CI: 1.1-1.19, [oral estrogen alone] HR: 1.241, 95% CI: 1.18-1.305, [CEPP] HR: 1.164, 95% CI: 1.01-1.341, [topical estrogen] HR: 1.602, 95% CI: 1.295-1.983). However, the risk of gallbladder cancer did not change with any hormone therapy.

Conclusions: 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.

PubMed Disclaimer

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flowchart to select to participants according to the use of menopausal hormones in this study.
MHT, Menopausal hormone therapy.
Fig 2
Fig 2. Risk of gallstone and gallbladder cancer according to the types of menopausal hormones.
HR, Hazard ratio; CI, confidence interval.
See this image and copyright information in PMC

References

    1. Cirillo DJ, Wallace RB, Rodabough RJ, et al.. Effect of estrogen therapy on gallbladder disease. JAMA. 2005;293(3):330–339. doi: 10.1001/jama.293.3.330 - DOI - PubMed
    1. Halldestam I, Kullman E, Borch K. Incidence of and potential risk factors for gallstone disease in a general population sample. Br J Surg. 2009;96(11):1315–1322. doi: 10.1002/bjs.6687 - DOI - PubMed
    1. Huang D, Lee J, Song N, Cho S, Choe S, Shin A. Gallstones, Cholecystectomy and the Risk of Hepatobiliary and Pancreatic Cancer: A Nationwide Population-based Cohort Study in Korea. J Cancer Prev. 2020;25(3):164–72. doi: 10.15430/JCP.2020.25.3.164 - DOI - PMC - PubMed
    1. Di Ciaula A, Wang DQ, Portincasa P. An update on the pathogenesis of cholesterol gallstone disease. Curr Opin Gastroenterol. 2018;34(2):71–80. doi: 10.1097/MOG.0000000000000423 - DOI - PMC - PubMed
    1. Shabanzadeh DM. Incidence of gallstone disease and complications. Curr Opin Gastroenterol. 2018;34(2):81–89. doi: 10.1097/MOG.0000000000000418 - DOI - PubMed