Background: Fluoxetine is one of the most prescribed selec- tive serotonin reuptake inhibitors (SSRIs), widely used to treat depression and anxiety disorders. However, its potential impact on the male reproductive system warrants careful investigation. Emerging evidence suggests that fluoxetine can induce oxida- tive stress in various cell types, including ovarian epithelial and hippocampal cells. Given the frequent and long-term use of fluoxetine among men of reproductive age, it is particularly important to evaluate its effects on sperm cells in vitro. Materials and Methods: Semen samples were collected from thirty fertile men. Each sample was divided into three groups: Fresh group analyzed immediately without any treatment; Con- trol group incubated at 37°C for 1 hour without treatment; and Fluoxetine group treated with 5 μm fluoxetine and incubated under the same conditions for 1 hour. In all groups, the param- eters including progressive motility, non-progressive motility, total motility, and sperm viability were evaluated. Additionally, levels of catalase (CAT), glutathione (GSH), superoxide dis- mutase (SOD), and reactive oxygen species (ROS) were meas- ured. Data were analyzed using repeated measures analysis. Results: The mean percentage of total and progressive motility and sperm viability, CAT, Glu and SOD levels in the fluoxetine group showed a significant decrease compared to the fresh and control groups (P˂0.001). While the mean percentage of non-progressive motility and ROS in the fluoxetine group was sig- nificantly increased compared to the fresh and control groups (P˂0.001). Conclusion: The findings of the present study indicated that fluoxetine at 5 μm impairs sperm quality by reducing motility, viability, and antioxidant enzyme levels while increasing oxida- tive stress. These effects may impact male fertility, highlighting the need for further research on fluoxetine’s reproductive risks.
