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Association between the use of hormonal contraceptives and risk of cholecystectomy in women of reproductive age

  • Pharmacoepidemiology and Prescription
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

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.

Author information

Authors and Affiliations

  1. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada

    Farzin Khosrow-Khavar

  2. Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada

    Farzin Khosrow-Khavar

  3. Department of Ophthalmology and Visual Sciences, Medicine and Pharmacology, Faculty of Medicine, The Eye Care Center, University of British Columbia, Room 323-2550 Willow Street, Vancouver, BC, V5Z 3N9, Canada

    Mohit Sodhi & Mahyar Etminan

  4. Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada

    Saeed Ganjizadeh-Zavareh

Authors
  1. Farzin Khosrow-Khavar
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  2. Mohit Sodhi
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  3. Saeed Ganjizadeh-Zavareh
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  4. Mahyar Etminan
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Contributions

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.

Corresponding author

Correspondence to Mahyar Etminan.

Ethics declarations

Ethics approval

This is an observational study. The University of British Columbia Research Ethics Committee has confirmed that no ethical approval is required.

Competing interests

The authors declare no competing interests.

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Cite this article

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

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