Association of oral contraceptives with depression symptoms, diagnosis, and treatment in healthy women: A meta-analysis

BACKGROUND: Oral contraceptives are a popular choice of contraception globally. OBJECTIVE: The objective was to assess whether oral contraceptive use is associated with diagnosis, treatment, and symptoms of depression in healthy women. DESIGN: Databases (MEDLINE, EMBASE, and PsycINFO databases via OvidSP for relevant studies, from database inception to 01 July 2025) were searched for prospective and observational studies comparing users of any currently prescribed oral contraceptives to non-users. Binary outcomes were summarised via relative risks (RR) with 95% confidence intervals (95% CI). Continuous outcomes were evaluated via standardised mean differences (SMD) along with 95% CI. Main outcomes and measures included incident depression diagnosis, antidepressant initiation, and depressive symptom scores measured with externally validated depression scales. RESULTS: Out of 438 screened references, 14 (2,425,648 participants) were included in the analysis. Of the five studies (1,607,461 participants) that examined depression diagnoses, oral contraceptives were associated with a 31% increased relative risk of being diagnosed with depression compared to non-users (RR: 1.31; 95% CI: 1.07 to 1.61, I2 = 94.18%, moderate certainty, high heterogeneity). Three studies (2,150,352 participants) with incidence of antidepressant use showed oral contraceptive users were 25% more likely to take antidepressants than non-users (RR: 1.25; 95% CI: 1.20 to 1.30 I2 = 75.4%, moderate certainty). Eight studies (2,525 participants) measuring depressive symptom scores found oral contraceptive users had statistically significantly higher, but clinically small, differences in depressive symptom scores than non-users (SMD: 0.12, 95% CI: 0.05 to 0.20). Subgroup analyses of depressive symptom scores showed no evidence of group differences by study design, follow-up length or progestogen content. CONCLUSION: Evidence from this meta-analysis suggests oral contraceptive use is associated with increased risks of depression diagnoses, antidepressant initiation, and higher depressive symptom scores. The findings, which reflect the association between hormonal oral contraceptives and depression in women without pre-existing psychological or gynaecological conditions, suggest that adverse effects on mood should be closely monitored by contraception prescribers.