Testicular toxicity following separate and combined administration of PDE5 inhibitors and opioid: assessment of recovery following their withdrawal.

We previously observed that PDE5 inhibitors and opioids were widely abused in Nigeria. Here, we examined the effect of high doses of sildenafil, tadalafil, tramadol and sildenafil + tramadol on reproductive toxicity in male rats. Rats were either administered normal saline (0.2 ml), sildenafil (10 mg/kg), tadalafil (10 mg/kg), tramadol (20 mg/kg) or sildenafil + tramadol (10 and 20 mg/kg respectively) p. o. for 8 weeks. The recovery groups were allowed 8-week recovery period before sacrifice. Results showed that body weight change, testicular and epididymal weights, epididymal sperm count and sperm viability were significantly reduced in all treated groups compared with the control. Spermatozoa with abnormal morphology were significantly increased in all treated groups compared with the control. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH) were significantly reduced, while malondialdehyde (MDA) was significantly increased in all treated groups compared with the control. The severity of toxicity was highest in sildenafil + tramadol group. There was no complete recovery from reproductive toxicity following withdrawal of the various treatments. High doses of sildenafil, tadalafil, tramadol or sildenafil + tramadol result in testicular oxidative stress-induced reproductive toxicity with poor reversal following withdrawal.