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Testicular and Epididymal Histology of Rats Chronically Administered High Doses of Phosphodiesterase-5 Inhibitors and Tramadol.

Testicular oxidative stress, endocrine disruption and abnormal spermatogenesis in rats exposed to high doses ofphosphodiesterase-5 inhibitors (PDE5i) and opioids, with poor reversibility following withdrawal of treatment had beenreported. In this study, we examined the histopathological effects of high doses of sildenafil, tadalafil, tramadol andsildenafil+tramadol on the testes and epididymis of rats. Seventy male rats (180 - 200 g b.w) were assigned to one of fivegroups (n = 14), namely; A: control (0.2 mL normal saline), B: sildenafil (1 mg/100g b.w), C: tadalafil (1 mg/100g b.w), D:tramadol (2 mg/100g b.w) and E: sildenafil+tramadol group (dose as in groups B and D). The drugs were administered orallyfor 8 weeks. Seven rats were sacrificed per group while the remaining 7/group continued for 8 weeks without treatment.Histopathological examination was carried out at the end of both phases. After 8 weeks of treatment, mean Johnsen'stesticular biopsy score (MJTBS) and Leydig cell count decreased significantly (p=0.001) in all treated groups compared withthe control. The MJTBS and Leydig cell count decreased significantly in tramadol (p = 0.05) and sildenafil+tramadol (p<0.01)groups compared with tadalafil group. After recovery, MJTBS and Leydig cell count were significantly (p<0.05) lower in all the groups compared with the control. Histology of the testes of rats in groups B - E showed reduced germ cell andspermatozoa population in the seminiferous tubules after 8 weeks treatment. Additionally, their epididymis showed decreasedspermatozoa density. There was no complete reversibility of histopathological alterations following withdrawal of treatment.High doses of sildenafil, tadalafil, tramadol or sildenafil+tramadol impact negatively on testicular histology with poorreversal following withdrawal of treatment.