Nonlinear reduction in risk for colorectal cancer by oral contraceptive use: a meta-analysis of epidemiological studies

Cancer Causes Control. 2015 Jan;26(1):65-78. doi: 10.1007/s10552-014-0483-2. Epub 2014 Oct 31.


Purpose: Although the relationship between oral contraceptive (OC) use and colorectal cancer (CRC) risk has been studied extensively, the results of epidemiological studies are controversial. Therefore, we carried out a meta-analysis of epidemiological studies to summarize the available evidence and to quantify the potential dose-response relation.

Methods: We searched PubMed database for studies of OC use and CRC risk that were published until the end of March 2014. Random- and fixed-effects models were applied to estimate summary relative risks (RRs) and 95 % confidence intervals (CIs).

Results: Twelve cohorts and seventeen case-control studies with a total of 15,790 CRC cases were included in the final analysis. The summary RR for the ever versus never category of OC use was 0.82 (95 % CI 0.76-0.88). Similar result was observed when we compared the longest duration of OC use with the shortest duration (RR = 0.86, 95 % CI 0.76-0.96). Furthermore, the results of stratified analysis were comparable to those of overall meta-analysis. In dose-response analysis, significant inverse associations emerged in nonlinear models for the duration of OC use and CRC (P nonlinearity = 0.001). The greatest risk reduction was observed when the duration of OC use was approximately 42 months. There was moderate heterogeneity in the analysis, and no evidence of small-study bias was observed.

Conclusions: Based on the findings of this meta-analysis, ever use of OC is associated with lower risk of CRC. Additionally, there is a statistically significant nonlinear inverse association between the duration of OC use and CRC risk.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Cohort Studies
  • Colorectal Neoplasms / epidemiology*
  • Colorectal Neoplasms / etiology
  • Colorectal Neoplasms / prevention & control
  • Contraceptives, Oral / administration & dosage*
  • Female
  • Humans
  • Risk Factors
  • Time Factors


  • Contraceptives, Oral