Abstract
BACKGROUND: Ovarian cancer ranks fourth in terms of incidence among gynecological malignancies and third as a cause of cancer death in the gynecological field, with oral contraceptives (OCs) exhibiting a potential relationship to ovarian cancer chemoprevention. This meta-analysis aimed to investigate the association between exposure to OCs and the incidence of ovarian cancer. METHODS: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, PubMed, Web of Science, Embase, and the Cochrane Library were searched for cohort studies on OCs and ovarian cancer incidence, covering the period from the establishment of each database to May 2025. Hazard ratio (HR) and 95% confidence interval (95% CI) were applied to assess the association between OCs and ovarian cancer incidence, with subgroup analyses performed for duration of use, time since OCs discontinuation, and geographical region. RESULTS: This meta-analysis included a total of 11 cohort studies. The results revealed that the OCs exposure group had a significantly lower ovarian cancer incidence than the control group (HR: 0.80, 95% CI: 0.71-0.89; P < 0.001; I(2) = 53.6%). However, no significant difference in incidence was noted between both groups for individuals with an OCs exposure duration of less than 5 years (HR: 0.98, 95% CI: 0.84-1.16; P = 0.857), and a lower incidence was exclusively observed in the OCs exposure group with use lasting more than 5 years (HR: 0.66, 95% CI: 0.58-0.76; P < 0.001). Subgroup analysis revealed that in both European (HR: 0.74, 95% CI: 0.61-0.91; P = 0.004) and American (HR: 0.83, 95% CI: 0.68-1.01) cohorts, the incidence of ovarian cancer in the exposed group was lower than that in the control group. However, the difference in the latter did not reach statistical significance (P = 0.064), while no difference in ovarian cancer incidence was observed between the two groups in the Asian cohort (HR: 0.93, 95% CI: 0.71-1.23; P = 0.628). CONCLUSION: This study demonstrated that OCs exposure can exert a preventive effect on ovarian cancer, but such prevention necessitates a duration of use of more than 5 years, and the effect is impacted by geographical factors. In the future, OCs may emerge as one of the potential measures for ovarian cancer prevention.