Real-World Data on the Associations of Tricyclic Antidepressants and Selective Serotonin Reuptake Inhibitors with Gynecologic Cancer Risk

<b>Background</b>: While the potential anti-cancer effects of antidepressants have been investigated, limited research has been conducted incorporating age-specific analyses for individual tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). This study aims to elucidate the associations between TCAs and SSRIs with gynecologic cancers and to identify specific age groups and cancer types that may benefit from the chemopreventive effects of these medications. <b>Methods</b>: A case-control study comprised 97,736 female patients diagnosed with gynecologic cancers between 2002 and 2016. Each newly diagnosed case of cervical, ovarian, or uterine cancer was matched with four controls. Both cases and controls were then stratified by age to perform subgroup analyses. Associations between antidepressant use and cancer risk were evaluated using multivariable conditional logistic regression models. <b>Results</b>: The TCA class was significantly associated with reduced risks of cervical, ovarian, and uterine cancers, displaying adjusted odds ratios (aORs) of 0.799, 0.775, and 0.813, respectively. The SSRI class also indicated reduced risks, with aORs of 0.736, 0.638, and 0.567 for the same cancer types. Particularly noteworthy were females aged 40-64, who demonstrated the most significant associations between gynecologic cancers and using TCAs or SSRIs. <b>Conclusions</b>: TCAs and SSRIs are associated with reduced risks of developing cervical, ovarian, and uterine cancers. The middle-aged population may have the most significant potential for future research on drug repurposing against gynecologic cancers, and both cervical and uterine cancers are potential targets for drug repurposing involving TCAs or SSRIs.