Oral contraceptives for the risk of endometriosis: a systematic review and meta-analysis

ABSTRACT

Objective: This systematic review and meta-analysis aimed to evaluate the effects of oral contraceptive pills(OCPs) on the risk of endometriosis among nulliparous women, with a focus on the potential influence of geographical location and OCP type on treatment efficacy. Methods: A comprehensive literature search was conducted in PubMed, Embase, Scopus, and the Cochrane Library up to July 10, 2025, to identify relevant cohort and case-control studies. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Data extraction and quality assessment were performed using a pre-designed form and the revised Cochrane Risk of Bias Tool. A fixed-effect model was used for meta-analysis when heterogeneity was low (I2≤50%, p≥0.1); otherwise, a random-effects model was adopted. Additionally, another model was employed for validation, and the results from both models were compared to derive more reasonable conclusions. Publication bias was assessed using funnel plots and the Egger test. Results: A total of six studies (three cohort and three case-control studies) involving 683,590 participants were included. The overall quality of the studies was high, with an average Newcastle-Ottawa Scale score of 8.0 (range: 5-9). The meta-analysis revealed that OCPs were significantly associated with a reduced risk of endometriosis (OR=1.956; 95% CI: 1.573-2.430; z=6.041; p<0.001). Subgroup analysis showed that the protective effect of OCPs was more pronounced in Asia (OR=2.586; 95% CI: 1.730-3.870; z=4.626; p<0.001) and among nulliparous women (OR=1.850; 95% CI: 1.471-2.378; z=5.245; p<0.001). Additionally, the combined use of OCPs and gonadotropin-releasing hormone agonists (GnRHa) further enhanced the efficacy of OCPs in reducing endometriosis risk (OR=2.282; 95% CI: 1.492-3.490; z=3.845; p<0.001). Conclusions: Oral contraceptives significantly reduce the risk of endometriosis, particularly among nulliparous women in East Asia. The combination of OCPs with GnRHa appears to provide additional benefits. These findings highlight the potential for personalized treatment strategies based on geographical location and patient characteristics. Future research should focus on elucidating the underlying mechanisms and exploring the impact of individual genetic and lifestyle factors on the efficacy of OCPs in endometriosis management.