Oral contraceptives and the risk of rheumatoid arthritis in women: A systematic review and meta-analysis

ObjectivesThe relationship between the use of oral contraceptives and the risk of rheumatoid arthritis remains unclear. The objective of this meta-analysis was to comprehensively evaluate the association between oral contraceptive use and rheumatoid arthritis risk.MethodsA systematic search was conducted in PubMed, EMBASE, and Cochrane Library databases for cohort studies published from 1980 to July 2024. Studies were assessed for bias using the Newcastle-Ottawa Scale. Two investigators independently screened abstracts and full-text articles and graded the certainty of evidence according to the Grading of Recommendations Assessment, Development and Evaluation approach. Data were analyzed using random effects models, and publication bias was evaluated using funnel plots and Egger test. A leave-one-out sensitivity analysis was performed, which demonstrated the robustness of the overall pooled estimate.ResultsTwelve cohort studies (1989-2024) with 1,126,554 participants were included. There was no significant overall association between oral contraceptive use and rheumatoid arthritis risk (relative risk = 0.96, 95% confidence interval: 0.93-1.00, <i>I</i>² = 0.0%, <i>p</i> = 0.920). However, subgroup analysis revealed that oral contraceptive use for ≤5 years was associated with a higher risk of rheumatoid arthritis (relative risk = 1.08, 95% confidence interval: 1.01-1.16, <i>I</i>² = 59.4%, <i>p</i> = 0.043). Current oral contraceptive use was linked to a reduced risk of rheumatoid arthritis (relative risk = 0.86, 95% confidence interval: 0.77-0.95, <i>I</i>²<i> = </i>0.0%, <i>p</i> = 0.840), while past oral contraceptive use showed no such association (relative risk = 0.94, 95% confidence interval: 0.87-1.02, <i>I</i>² = 0.0%, <i>p</i> = 0.961). No publication bias was detected in the included studies (<i>p</i> = 0.183, Egger test).ConclusionsThis meta-analysis found no overall protective effect of oral contraceptive use on the risk of rheumatoid arthritis but suggested that current oral contraceptive use may lower the risk. Caution must be exercised while interpreting these results, particularly in studies with shorter follow-up periods, wherein the association might be stronger.