Therapeutic levels of short-term tramadol administration negatively affect testis function in rats

Objective: To investigate the effects of 30-day treatment with therapeutic dose equivalent levels of tramadol on serum testosterone level, sperm parameters, and testicular histology in rats. Methods: Thirty-five Wistar rats were equally divided into seven groups. Group 1 (the control group) received distilled water (0.5 mL) daily for 30 days. Groups 2-4 were gavaged with therapeutic dose equivalent levels of tramadol (1.25, 2.50 and 5.00 mg/kg/day body weight, respectively) in two equal divided doses for 30 consecutive days, and sacrificed on day 31. Groups 5-7 received similar tramadol treatments as above but they were allowed for another 30 days to recover after receiving the last dose and sacrificed on day 61 for reversibility study. Serum testosterone level and epididymal sperm were analyzed, and histopathological examination of the testis was carried out. Results: Tramadol treatment significantly decreased serum testosterone levels compared with the control group. Furthermore, tramadol treatment inhibited sperm motility and significantly and dose-dependently decreased sperm count and viability compared with the control group. In addition, tramadol significantly increased morphological abnormalities in sperm (P<0.05). The above effects of tramadol were reduced in the reversible groups. Testis histopathological examination revealed disintegrated cell architecture, eroded and atrophied seminiferous tubules, and a marked decrease in the number of spermatogenic cells in the tramadol treated groups. The histopathological changes were restored in the reversible groups, but improvement was not complete in the 5.00 mg/kg tramadol treated reversible group. Conclusions: Long term treatment with tramadol at clinical dose levels may adversely affect testosterone level, sperm parameters, and testicular histology, but they are reversible at lower doses.