Effect of duration of hormonal contraceptive use on breast cancer risk: a systematic review and meta-analysis of cohort studies

Abstract

We conducted a systematic review and meta-analysis on the prospective evidence for the association between use of hormonal contraceptives for 5 years or more and the subsequent incidence of breast cancer. We systematically searched all cohort studies published in English, Spanish, Italian, French, or Portuguese on PubMed or Web of Science up to September 8, 2025. We used Covidence software to manage most review activities. We extracted relative risks, odds ratios, or hazard ratios from each individual study to generate pooled results using a random-effects meta-analysis, and a dose–response meta-analysis to calculate relative risks and their 95 % confidence intervals for each additional year of use of hormonal contraceptives. The Newcastle-Ottawa Scale was applied to assess the quality of included studies. Several subgroup and sensitivity analyses were conducted. Twenty independent cohorts and 23 reports with a total of 5,572,683 women and 72,350 incident cases of breast cancer were included in the systematic review, while 3,920,319 women with 68,508 incident cases were included in the meta-analysis. The pooled adjusted relative risk for the association between hormonal contraceptive use for 5 years or more and breast cancer risk was 1.20 (95 % confidence interval, 1.09–1.32) compared with never users. Further meta-analyses on the dose–response relationship showed a nonlinear association, with risk progressively increasing during the first 5 years of use, after which the risk remained stable until the 10th year, when it increased again. This meta-analysis provides evidence of a detrimental association between duration of exposure to oral contraceptives and breast cancer risk.