Codeine influences the serum and urinary profile of endogenous androgens but does not interact with the excretion rate of administered testosterone

Abstract

Today's doping tests involve longitudinal monitoring of urinary steroids including the testosterone glucuronide and epitestosterone glucuronide ratio (T/E) in an Athlete Biological Passport (ABP). The aim of this study was to investigate the possible influence of short-term use of codeine on the urinary excretion of androgen metabolites included in the steroidal module of the passport prior to and after the co-administration with testosterone. The study was designed as an open study with the subjects being their own control. Fifteen healthy male volunteers received therapeutic doses of codeine (Kodein Meda) for 6 days. On Day 3, 500 mg or 125 mg of testosterone enanthate (Testoviron®-Depot) was administered. Spot urine samples were collected for 17 days, and blood samples were collected at baseline, 3, 6, and 14 days after codeine intake. The circulatory concentration of total testosterone decreased significantly by 20% after 3 days' use of codeine (p = 0.0002) and an atypical ABP result was noted in one of the subjects. On the other hand, the concomitant use of codeine and testosterone did not affect the elevated urinary T/E ratio. In 75% of the individuals, the concentration of urinary morphine (a metabolite of codeine) was above the decision limit for morphine. One of the participants displayed a morphine/codeine ratio of 1.7 after codeine treatment, indicative of morphine abuse. In conclusion, our study shows that codeine interferes with the endogenous testosterone concentration. As a result, the urinary steroid profile may lead to atypical findings in the doping test.

Testicular toxicity following chronic codeine administration is via oxidative DNA damage and up-regulation of NO/TNF-α and caspase 3 activities

“…The reduction in testicular weight following codeine use explains the associated reduction of testosterone bioavailability and disrupted spermatogenesis observed in this study. The decline in the circulatory concentrations of testosterone seen in codeine treatment aligns with previous reports [15][16][17][18]. The decline in serum and testicular levels of androgen and cessation of spermatogenesis observed in codeine-treated animals could be partly due to codeine-induced loss of testicular tissues, and impairment of testicular metabolism and function.…”

“…Chronic use of opioids is associated with androgen deficiency [15][16][17][18]. Findings of Rubinstein and Carpenter [15] demonstrated that the highest odds of androgen deficiency are associated with opioids that maintain the most stable serum drug concentrations.…”

Testicular toxicity following chronic codeine administration is via oxidative DNA damage and up-regulation of NO and caspase 3

“…The reduction in testicular weight following codeine use explains the associated reduction of testosterone bioavailability and disrupted spermatogenesis observed in this study. The decline in the circulatory concentrations of testosterone seen in codeine treatment aligns with previous reports [15][16][17][18]. The decline in serum and testicular levels of androgen and cessation of spermatogenesis observed in codeine-treated animals could be partly due to codeine-induced loss of testicular tissues, and impairment of testicular metabolism and function.…”

Assessment of sexual behaviour and fertility indices in male rabbits following chronic codeine use

“…Surprisingly, despite the enhanced sexual activity observed in rabbits administered with codeine, serum levels of testosterone were lower in them. Although no study has documented the effects of codeine or any opioid on sexual performance, findings from this study corroborate those that reported the anti‐androgenic activity of opioids (Eichenbaum et al , ; Daniell, ; Rubinstein & Carpenter, ; Lehtihet et al , ). Studies have reported a decline in serum levels of testosterone in tramadol‐treated rats via oxidative stress‐mediated testicular damage (Nna & Osim, ; Nna et al , ).…”