Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 28, 2021; 27(20): 2643-2656
Published online May 28, 2021. doi: 10.3748/wjg.v27.i20.2643
Association between oral contraceptive use and pancreatic cancer risk: A systematic review and meta-analysis
Milena Ilic, Biljana Milicic, Irena Ilic
Milena Ilic, Department of Epidemiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia
Biljana Milicic, Department of Medical Statistics and Informatics, Faculty of Dental Medicine, University of Belgrade, Belgrade 11000, Serbia
Irena Ilic, Faculty of Medicine, University of Belgrade, Belgrade 11000, Serbia
Author contributions: All authors equally contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Supported by Ministry of Education, Science and Technological development, Republic of Serbia, 2011–2020, No. 175042.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Milena Ilic, MD, PhD, Professor, Department of Epidemiology, Faculty of Medical Sciences, University of Kragujevac, S. Markovica 69, Kragujevac 34000, Serbia.
Received: February 6, 2021
Peer-review started: February 6, 2021
First decision: February 27, 2021
Revised: March 13, 2021
Accepted: April 23, 2021
Article in press: April 23, 2021
Published online: May 28, 2021

Studies on the association of oral contraceptive (OC) use and pancreatic cancer showed inconsistent findings.


To evaluate the relationship between OC use and pancreatic cancer risk.


A literature search for observational studies (case-control and cohort studies) was conducted up to December 2020. A meta-analysis was performed by calculating pooled relative risks (RRs) and 95% confidence intervals (CIs). Heterogeneity was assessed using Cochran’s chi-square test and I2 statistic. Subgroup analyses were performed by study design, source of controls in case-control studies, number of cases of pancreatic cancers, study quality according to Newcastle-Ottawa Scale score, geographical region and menopausal status. All analyses were performed using Review Manager 5.3 (RevMan 5.3).


A total of 21 studies (10 case-control studies and 11 cohort studies) were finally included in the present meta-analysis, comprising 7700 cases of pancreatic cancer in total. A significant association was observed between the ever use of OC and pancreatic cancer risk in the overall analysis (RR = 0.85; 95%CI = 0.73-0.98; P = 0.03). Duration of OC use (< 1 year, < 5 years, 5-10 years, > 10 years) was not significantly associated with the risk of pancreatic cancer. Subgroup analyses revealed a statistically significant subgroup difference for the geographic region in which the study was conducted (Europe vs Americas vs Asia; P = 0.07). Subgroup analyses showed a statistically significant decrease in pancreatic cancer risk and OC use in high-quality studies, studies conducted in Europe, and in postmenopausal women.


Despite the suggested protective effects of OC use in this meta-analysis, further epidemiological studies are warranted to fully elucidate the association between the use of OC and pancreatic cancer risk.

Keywords: Pancreatic cancer, Oral contraceptives, Risk factors, Risk assessment, Meta-analysis, Review

Core Tip: Although the understanding of the etiology of pancreatic cancer has improved dramatically over the past decades, the link between pancreatic cancer risk and oral contraceptive (OC) use is still insufficiently known. This meta-analysis showed a significant association between OC use and pancreatic cancer risk (overall relative risk = 0.85; 95% confidence interval = 0.73-0.98). A better understanding of the risks of pancreatic cancer occurrence in women who use OC may be relevant for pancreatic cancer prevention strategy.