Abstract
Purpose
Previous studies have indicated an increased risk of gallbladder disease with hormonal contraceptives although with discordant results. The potential increased risk of gallbladder disease with hormonal contraceptives is concerning given that women are at increased risk of this disease. Thus, the aim of this study was to examine risk of surgery-confirmed gallbladder disease (cholecystectomy) with oral contraceptives, intrauterine devices, and injectable hormonal contraceptives.
Methods
We conducted a retrospective cohort study. Females aged 15–45 who initiated hormonal contraceptive use were identified in the United States IQVIA Ambulatory electronic medical record database between 2008 and 2018. Cox proportional hazards models were used to estimate adjusted hazards ratios and 95% confidence intervals for cholecystectomy with eight formulations of contraceptives compared with levonorgestrel and ethinyl estradiol combined oral contraceptive. Sensitivity analysis was conducted by lagging exposure by 90 days and by excluding patients with history of gallbladder disease. Secondary analyses were conducted by cumulative duration of use.
Results
We identified 1,425,821 females who initiated the use of hormonal contraceptives and generated 4417 cholecystectomy events. Overall, the use of medroxyprogesterone acetate (HR: 1.22, 95% CI: 1.07–1.40) and at least 1 year of levonorgestrel intrauterine device use (HR: 1.74: 95% CI: 1.19–2.54) were associated with increased risk of cholecystectomy when compared with levonorgestrel and ethinyl estradiol combined oral contraceptive. However, we did not observe an increased risk with other hormonal contraceptives. Consistent results were observed across sensitivity analyses.
Conclusion
In this large population-based study, there was an increased risk of cholecystectomy with medroxyprogesterone acetate and intrauterine device but not other hormonal contraceptives. Additional large observational studies are required to corroborate these findings.
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Data availability
The data that support the findings of this study are available from IQVIA. Restrictions apply to the availability of these data, which were used under license for this study.
Code availability
The codes generated for the current study are available from the corresponding author upon reasonable request.
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Funding
This study was supported by a project grant from Canadian Institutes of Health Research.
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ME is the guarantor of this study. ME and FK conceptualized the research question and study design. ME was involved in acquisition of data. All authors were involved in data interpretation. FK and ME drafted the manuscript, while all others were involved in the critical revision of the manuscript for important intellectual content. Statistical analysis was conducted by FK and ME. ME obtained the funding and was the study supervisor. FK and ME provided technical and material support.
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This is an observational study. The University of British Columbia Research Ethics Committee has confirmed that no ethical approval is required.
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The authors declare no competing interests.
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Khosrow-Khavar, F., Sodhi, M., Ganjizadeh-Zavareh, S. et al. Association between the use of hormonal contraceptives and risk of cholecystectomy in women of reproductive age. Eur J Clin Pharmacol 77, 1523–1529 (2021). https://doi.org/10.1007/s00228-021-03137-6
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DOI: https://doi.org/10.1007/s00228-021-03137-6