ABSTRACT
Background
Ultram (Tramadol hydrochloride) was initially introduced in Germany in 1977. It has been prescribed extensively, both for patients in the post-operative period and also in pain clinics for more chronic pain syndromes.Tramadol abuse is becoming more and more popular. It also seems that it is not only an Egyptian problem but also in neighboring countries . Objectives: The aim of the present work is to evaluate the effect of tramadol on hypophyseal – gonadal axis {Follicle stimulating hormone (FSH) , Lutenizing hormone (LH) and testosterone } and how it modulates their levels after acute single dose and due to chronic use . Also, if changes in the level of the hormones occurred they will need treatment or not?
Materials and Methods: The present work was conducted on 21 adult male rabbits to study the acute effect of a single toxic doses of Amadol (tramadol hydrochloride) on hypophyseal – gonadal axis {Follicle stimulating hormone (FSH) , Lutenizing hormone (LH) and testosterone }. Also, it was conducted on human (adult male) to study the chronic effect of tramadol on the same hormones. Animals were divided into 3groups. Group I: Is a control group in which rabbits were received only 1ml saline I.M.dose. Group II: Rabbits were treated with tramadol hydrochloride (25 mg single I.M dose ) equal to 1/20 of LD50 of tramadol hydrochloride , Group III: Rabbits were treated with tramadol hydrochloride (50 mg single I.M dose ) equal to 1/10 of LD50 of tramadol hydrochlorid. Blood samples were collected after 4 and 24 hours , Eight adult male persons abused tramadol for more than one year were included in the study. Their ages ranged from 20 to 38 years. The doses ranged from 100 to more than 500 mg/day.Blood samples were collected from human and animals on heparinized tubes, then centrifuged .Plasma were separated and preserved at -20◦C for detection of tramadol level by high performance liquid chromatography-Diodo array detector (HPLC- DAD) and for hormonal assay by test using Monobind Kit.
Results : In acute toxicity by tramadol there was significant decrease in the leves of testosterone hormone as compared with the control group in both 25 mg and 50 mg treated groups after 4 hours .There was a significant correlation between plasma testesterone hormonal levels and plasma tramadol levels.Non significant decrease was observed in the level of the testosterone hormones after 24 hours in both groups. Also non significant decrease was observed in the level of FSH and LH hormones in both 25 mg and 50 mg treated groups.There was non significant correlation between plasma FSH and LH hormonal levels and plasma tramadol levels.In chronic toxicity by tramadol there was significant decrease of testosterone hormon levels and a significant correlation between plasma testosterone levels and plasma tramadol levels. As well as there was a significant increase in the levels of FSH and LH hormones as compared with the control group, P value <0.05. and a significant correlation between plasma FSH & LH hormonal levels and plasma tramadol levels. Conclusion The acute effect of tramadol on the levels of the studied hormones was peripheral. Fortunately, its effect was temporary as the hormones returned to the normal levels within 24 hours without treatment.But the long term use or abuse of tramadol modifies greatly the level of the studied hormones.