Intranasal delivery of Natesto® testosterone gel and its effects on doping markers

Abstract

The laboratory profile of intranasal testosterone gel has not been previously reported from an anti-doping perspective. Because intranasal testosterone gel is newly available as a commercial product, we sought to examine the laboratory parameters following administration of this formulation, with particular attention to anti-doping guidelines. Five healthy and active male subjects were administered testosterone intranasal gel three times daily for four weeks, using a pattern of five consecutive days on, two days off. Urine was collected after each five-day round of drug administration and analyzed using a full steroid screen and isotope ratio mass spectrometry (IRMS). Windows of detection for elevated testosterone/epitestosterone (T/E) and other steroid ratios, World Anti-Doping Agency (WADA) athlete biological passport (ABP) findings, and IRMS results were analyzed in this study. In the 0-24 h window post-administration, 70% of samples were flagged with a suspicious steroid profile and 85% were flagged as atypical passport findings according to the WADA ABP steroid module. In the 24-48 h window, 0% of samples displayed suspicious steroid profiles while 40% resulted in atypical passport findings. IRMS testing confirmed the presence of exogenous testosterone in 90% and 40% of samples in the 0-24 h and 24-48 h windows post-administration, respectively. Additionally, IRMS data were analyzed to determine commonalities in the population changes in δ C values of testosterone, androsterone, etiocholanolone, 5αAdiol, and 5βAdiol. Though no discernible metabolic trend of the route of administration was identified, we discovered that intranasal gel testosterone is detectable using conventional anti-doping tests. Copyright © 2016 John Wiley & Sons, Ltd.

IRMS delta values (13C) of nandrolone and testosterone products available in the UK: Implications for anti‐doping

“…collection post-administration22 could also influence a negative or positive outcome since the δ 13 C value will normalize to the athlete's baseline level after a washout time, that is either a normalization of the δ 13 C value back to endogenous in the case of T 27 or a reduction in 19-NA concentration such that it is below the measurement capability of the assay.On the other hand, misuse of steroid preparations that have δ 13 C values further into the exogenous range (less than −29‰) remain easy to detect. For instance, administration of the most 13 C-depleted products (−32.7‰) represent the most likely to yield positive results by GC-C-IRMS analysis as demonstrated in previous studies 28. …”

Studies of athlete biological passport biomarkers and clinical parameters in male and female users of anabolic androgenic steroids and other doping agents

“…It is possible that longitudinal monitoring of the ABP biomarkers in our participants rather than single urine sampling would have resulted in atypical findings. It has been shown that the implementation of ABP has increased the probability of detecting testosterone gel use in men . It is known that basal T/E ratios are higher in men than in women and that the administration of intramuscular testosterone enanthate affects the T/E ratio to a larger degree in men than in women …”

Impact of hormonal contraceptives on urinary steroid profile in relation to serum hormone changes and CYP17A1 polymorphism

“…The ratios monitored are T/E, A/Etio, 5αAdiol/E, 5αAdiol/5βAdiol, and A/T. It has been shown that the use of ABP increases the sensitivity of detecting the administration of testosterone in men …”