Biochemical and Pharmacological Assessments of Tramadol Abuse on Human Male Fertility: Relation to Seminal Plasma 8-Hydroxyguanosine and Zinc

Indian J Clin Biochem. 2024 Oct;39(4):489-505. doi: 10.1007/s12291-023-01141-4. Epub 2023 Jun 24.

Abstract

Tramadol is a pain killing drug highly used worldwide. There is a knowledge gap for fertility consequences of analgesic addiction in men. In this observational study, we investigated the hazards of tramadol abuse on human male reproductive function. A total of 30 tramadol addicts and 30 healthy controls have participated in the study. History and clinical examination of the included subjects were performed. Biochemical and molecular assays were measured in all participants include serum reproductive hormones (calculated free testosterone, FSH, LH, prolactin and estradiol) using ELISA techniques, semen analysis, seminal plasma zinc and selenium assays using colorimetric kits, seminal plasma tramadol concentrations using Gas Chromatography-Mass Spectrometry (GC-MS), and seminal plasma 8-hydroxyguanosine (8-OHG) using high performance liquid chromatography were measured. Tramadol abuse significantly decreased semen parameters quality. Additionally, tramadol abuse significantly decreased testosterone (P = 0.001) and increased prolactin serum levels (P = 0.000). Tramadol abusers showed significantly higher levels of 8-OHG (P < 0.0001) with significantly lower levels of zinc and selenium in their seminal plasma compared with the controls (P < 0.0001, and 0.0002 respectively). Also, tramadol addicts displayed positive correlations between seminal plasma levels of 8-OHG (r = 0.905, P = 0.00) and sperm abnormal forms (r = 0.610, P = 0.000) with seminal plasma tramadol levels. Seminal plasma levels of zinc (r = - 0.815, P = 0.00), sperm motility (r = - 0.484, P = 0.007), and vitality (r = - 0.430, P = 0.018) were negatively correlated with seminal plasma levels of tramadol. Our data suggest that tramadol abuse may impair male fertility by increasing oxidative damage of sperms and reducing testosterone and the antioxidants trace elements in testicular tissues.

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-023-01141-4.

Keywords: 8-Hydroxyguanosine; Antioxidant trace elements; Gas chromatography; HPLC; Male fertility; Mass spectrometry; Reproductive hormones; Tramadol abuse.