Hyperprolactinemia contributes to reproductive deficit in male rats chronically administered PDE5 inhibitors (sildenafil and tadalafil) and opioid (tramadol)

Objectives: To examine the influence of prolonged use of PDE5 inhibitors and opioids on prolactin among other male reproductive hormones, on the background that hyperprolactinemia has recently been associated with male sterility. Materials and methods: Seventy male Wistar rats with weight 180–200 g were utilized in this study. They were assigned 1 of 5 groups (n = 14) as follows; control (0.2 mL normal saline p.o.), sildenafil (10 mg/kg p.o.), tadalafil (10 mg/kg p.o.), tramadol (20 mg/kg p.o.) and sildenafil + tramadol group (10 mg/kg and 20 mg/kg p.o., respectively). All the animals had ad libitum access to rat chow and water. Administration was done every 2 days, for 8 weeks, after which 7 rats were killed/group while the remaining 7 rats/group were left untreated for additional 8 weeks (recovery period). Serum total cholesterol, low density lipoprotein, testosterone, follicle stimulating hormone, luteinizing hormone and prolactin were assessed in all animals. Results: Serum LDL-c and testosterone concentrations increased significantly (P < 0.001) in the groups administered sildenafil and tadalafil, but reduced (P < 0.001) in tramadol and sildenafil + tramadol groups relative to the control. FSH and LH reduced significantly (P < 0.001) in the treated groups relative to the control, while prolactin concentration was increased (P < 0.001) in the treated groups relative to the control. Reversibility was poor following withdrawal of the various treatments. Conclusion: Serum prolactin concentration correlated negatively with male reproductive hormones and may play a major role in reproductive deficits associated with chronic use of PDE5 inhibitors and opioids