EVALUATION OF THE ANDROGENIC/ANTIANDROGENIC ACTIVITY OF SELECTIVE SEROTONIN REUPTAKE INHIBITORS

Selective serotonin reuptake inhibitors (SSRIs) are being increasingly prescribed to treat depression, even during pregnancy and postpartum, although recent studies suggest that SSRIs may interfere with sexual steroid signalling, potentially causing adverse effects in exposed children. This study aimed to assess potential SSRIs interactions with the androgen receptors (AR) in vitro, using a firefly luciferase reporter construct in the MDA-kb2 cell line. The tested compounds were fluoxetine and its metabolite, norfluoxetine, sertraline and paroxetine. None of the compounds induced AR-transcriptional activity during individual testing. In mixtures with dihydrotestosterone (DHT), all the compounds induced a significant increase in luciferase expression (compared to the positive control) at low concentrations. This study shows for the first time that SSRIs may potentiate the DHT-induced androgenic activity, and depending on the mechanism underlying this effect, these results could raise concern regarding the endocrine toxicity.