Association between antidepressant use and gynecological cancer risk: a systematic review and meta-analysis

The potential carcinogenic effects of antidepressants (ADs) have been debated, with some preclinical studies suggesting associations with tumor promotion. However, clinical evidence regarding their impact on the risk of gynecological cancers remains limited and inconclusive, necessitating further investigation. Therefore we conducted a comprehensive search in PubMed, Embase, and Web of Science for studies examining the correlation between AD use and the risk of gynecological cancers.

The DerSimonian and Laird random-effects model was applied to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity was assessed using the I-squared and Tau-squared statistics. Statistical analyses were performed using R software (version 4.4.1), with a significance threshold of p < 0.05.

Our meta-analysis included 10 case-control studies, with a total of 965,834 participants, of whom 45,998 were AD users. The findings revealed a significant association between AD use and a reduced overall risk of gynecological cancers (OR = 0.9518; 95% CI: 0.9206 to 0.9841; P = 0.004; I² = 19%). Subgroup analyses demonstrated a decreased risk for ovarian cancer (OR = 0.9316; 95% CI: 0.9105 to 0.9531; P < 0.001; I² = 0%) and endometrial cancer (OR = 0.9264; 95% CI: 0.8683 to 0.9927; P = 0.030; I² = 19%). Additionally, selective serotonin reuptake inhibitors (SSRIs) were associated with a lower risk compared to non-AD users (OR = 0.9216; 95% CI: 0.8855 to 0.9591; P < 0.001; I² = 18.2%), as well as for ovarian cancer (OR = 0.9377; 95% CI: 0.8991 to 0.9780; P = 0.003; I² = 16%) and endometrial cancer (OR = 0.9078; 95% CI: 0.8251 to 0.9989; P = 0.047; I² = 35%).

Our meta-analysis indicates that AD use may serve as a protective factor against the development of gynecological cancers. However, potential biases and confounders should be considered, highlighting the need for balanced prescribing, taking into account the potential side effects of each AD and its suitability for individual patients.