The Impact of Oral Contraceptives on Depression: A Meta-Analysis

Corresponding author: liangxuemei, 1105362215@qq.com

DOI: 10.12201/bmr.202601.00058

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  Abstract: Objective Oral contraceptives (OCs) are a widely used method of contraception globally. Observational studies suggest their use may be associated with an increased risk of depressive symptoms in women, but the causal relationship remains unclear due to potential confounding factors. This study aims to quantitatively evaluate the association between oral contraceptive use and the risk of depressive symptoms across multiple clinical trials through a systematic review and meta-analysis.Methods This study systematically searched the PubMed, Web of Science, and Embase databases (from inception to October 18, 2025). A systematic review and meta-analysis of clinical trials were conducted, comparing women randomly assigned to receive any form of oral contraceptives with those randomly assigned to receive any other form of contraception or placebo. A random-effects meta-analysis was used to pool risk ratios. Subgroup analyses based on study origin and the method of depressive symptom assessment were performed to explore sources of heterogeneity.Results A total of 1,661 records were screened, and 14 clinical trials were ultimately included. The random-effects meta-analysis showed that, compared to the control group, oral contraceptive use did not significantly increase the risk of depressive symptoms (RR = 1.09, 95% CI: 0.83–1.42, P = 0.54). However, significant heterogeneity was observed among the studies. Further subgroup analyses indicated that the impact of oral contraceptives on depression risk might vary across different countries, study methodologies, and depression assessment tools.Conclusion Current evidence from clinical trials does not indicate that oral contraceptives significantly cause or increase depressive symptoms in adult women. However, this does not imply that oral contraceptives have no effect on depressive symptoms. Heterogeneity analyses suggest that their effects may vary across different countries, study methodologies, and depression assessment tools. Future research could further investigate this association by considering factors such as first-time users and specific types of contraceptive formulations.

  Key words: Oral Contraceptives，Depression，A Meta-Analysis，Women’s Depression

  Submit time: 20 January 2026

  Copyright: The copyright holder for this preprint is the author/funder, who has granted biomedRxiv a license to display the preprint in perpetuity.
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