Andrologia. 2018;e13026. wileyonlinelibrary.com/journal/and | 1 of 10 https://doi.org/10.1111/and.13026 © 2018 Blackwell Verlag GmbH 1 | INTRODUCTION Tramadol is one of the most effective prescriptions for treating pain (Ahmad et al., 2017; Awadalla & Salah-Eldin, 2016). It is an opioid analgesic, modifies the pain centrally, through mu receptor agonistic action, and inhibiting serotonin and norepinephrine reuptake in neu- rons, and locally by increase in nitric oxide (NO) level (Dal, Salman, Salman, Iskit, & Aypar, 2006; Grond & Sablotzki, 2004; Oliva et al., 2002). O-desmethyl-tramadol, an active tramadol metabolite, is 2–4 times as potent as tramadol (Grond & Sablotzki, 2004; Matthiesen, Wohrmann, Coogan, & Uragg, 1998; Tao et al., 2002). Tramadol’s half-life (t1/2) is around 6.3 hr; following cessation of intake, it stays 1.44 days for tramadol and 1.7 days for O-desmethyltramadol. Although tramadol is still considered as a nonaddictive drug, reports showed withdraw effects and physical dependence for its long use (Manivannan, Mittal, Goyal, Ansari, & Lohiya, 2009; McDiarmid, Mackler, & Schneider, 2005; Senay et al., 2003). United Nation reported that middle east and north Africa re- gions were among highest areas of tramadol/opiate abuse over the world (International-Narcotics-Control-Board, 2013). Tramadol Accepted: 20 March 2018 DOI: 10.1111/and.13026 ORIGINAL ARTICLE Tramadol (opioid) abuse is associated with a dose- and time-dependent poor sperm quality and hyperprolactinaemia in young men A. G. A. Farag 1 | M. A. Basha 1 | S. A. Amin 2 | N. F. Elnaidany 3 | N. G. Elhelbawy 4 | M. M. T. Mostafa 1 | S. A. Khodier 5 | R. A. Ibrahem 6 | R. Z. Mahfouz 5,7 1 Dermatology, Andrology and STDs, Menoufia University, Shebin El Kom, Egypt 2 Forensic Medicine & Clinical Toxicology, Menoufia University, Shebin El Kom, Egypt 3 Faculty of Pharmacy, Clinical Pharmacy, MSA University, 6 October City, Egypt 4 Faculty of Medicine, Medical Biochemistry, Menoufia University, Shebin El Kom, Egypt 5 Faculty of Medicine, Clinical Pathology, Menoufia University, Shebin El Kom, Egypt 6 Faculty of Medicine, Public Health and Community Medicine, Menoufia University, Shebin El Kom, Egypt 7 Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio Correspondence Reda Z. Mahfouz, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, USA. Emails: mahfour@ccf.org; reda.mahfouz@med.menofia.edu.eg Summary Tramadol, one of the most commonly abused drugs in Middle East, impacts sper- matogenesis and disturbs reproductive hormones in animal studies. We aimed to in- vestigate tramadol impact on sperm quality and on levels of testosterone, prolactin and gonadotropins, in tramadol abusers (n = 30) to age-matched control (n = 30). Abusers had significantly low percentages of sperm motility, normal forms and vital- ity compared with control (95% CI −40.7 to −19.3, −13.5 to −9.3 and −31.9 to −9.7 respectively). Hypoandrogenism (95% CI −4.5 to −2.8), hyperprolactinaemia (CI (95%) 4.9 to 9.4) and hypergonadotropinaemia (95% CI 2.9 to 7.2 for FSH and 2.0 to 7.8 for LH) were observed in tramadol abusers vs controls. Smokers (26 of 30), concurrently abusing other drugs (11 of 30) and asymptomatic leucocytospermic (15 of 30) pa- tients subgroups significantly abused tramadol beyond 3 years ( p = .02, <.001, = .03 respectively) and in excess >450 mg/day ( p = .02, = .01, = .005 respectively). Progressive motility (a + b%) was significantly low in young men <25 years old ( p = .03) subgroup. Tramadol abuse is associated with poor sperm quality, hyperprol- actinaemia and hypergonadotropic hypogonadism. We recommend semen analysis for tramadol long-intakes, question sperm donors and follow-up studies to prevent and reverse tramadol-induced testicular damage. KEYWORDS opioids, prolactin, sperm quality, testicular function, tramadol