Sensitivity of doping biomarkers after administration of a single dose testosterone gel

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To detect doping with endogenous steroids, six urinary steroids are longitudinally monitored in the athlete biological passport (ABP). These steroids include testosterone, etiocholanolone, androsterone, 5α‐androstane‐3α,17β‐diol, 5β‐androstane‐3α,17β‐diol, and the testosterone isomer epitestosterone. It is known that the intake of hormonal contraceptives may interfere with the ABP biomarkers. A previous study showed that athletes using hormonal contraceptives (HCs) display lower urinary epitestosterone concentrations than non‐using athletes. In this study, we analyzed the urinary steroid profile prior to and three months after administration of an oral HC including levonorgestrel and ethinylestradiol (n = 55). The urinary concentrations of all the ABP metabolites decreased after three months, with epitestosterone showing the largest decline (median 6.78 to 3.04 ng/mL, p˂0.0001) followed by 5α‐androstane‐3α,17β‐diol (median 23.5 to 12.83 ng/mL, p˂0.0001), and testosterone (median 5.32 to 3.66, p˂0.0001). Epitestosterone is included in two of the five ratios in the ABP (T/E and 5αAdiol/E), and consequently these ratios increased 1.7‐fold (range 0.27 to 8.50) and 1.26‐fold (range 0.14 to 5.91), respectively. Some of these changes may mimic the changes seen after administration of endogenous steroids leading to atypical findings. Notably, even though participants used the same contraceptive treatment schedule, the HC‐mediated epitestosterone change varied to a large extent (median 0.43‐fold, range 0.06 to 6.5) and were associated with a functional T˃C promoter polymorphism in CYP17A1. Moreover, the epitestosterone changes correlated with HC‐induced testosterone and gonadotropins changes in serum, indicating that urinary epitestosterone reflects the androgen load in HC‐using women.

Section: Discussionmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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

Ekström

Knutsson

Mullen

et al. 2019

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“…23,24 Future MS approaches may also include other peptide and proteins with growth-promoting properties. 25,26 An additional endocrine module including IGF-I and P-III-NP would most likely also increase the sensitivity for recGH detection. This has improved the sensitivity to detect administration of low doses of testosterone.…”

Section: Hours and 3 Hours) After An Injection This Results Is In Agrmentioning

confidence: 99%

Longitudinally monitoring of P‐III‐NP, IGF‐I, and GH‐2000 score increases the probability of detecting two weeks’ administration of low‐dose recombinant growth hormone compared to GH‐2000 decision limit and GH isoform test and micro RNA markers

Lehtihet

Bhuiyan

Dalby

et al. 2018

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To detect doping with growth hormone (GH), GH isoform and biomarkers tests are available. Both methods use population-based decision limits. Future testing in anti-doping is progressing toward individual-based reference ranges, and it is possible that with such an approach the sensitivity to detect GH doping may increase. In addition to monitoring different proteins, the use of miRNAs as future GH biomarkers has been discussed. Here we have longitudinally studied the serum concentrations of IGF-I, P-III-NP and the different GH isoforms in nine healthy men prior to, during and after two weeks' administration with low doses (1 and 4 IU/day) of recGH. Moreover, three putative miRNAs were analyzed. The results show that 80% of the participants were identified as atypical findings using the GH isoform test. However, the participants were only positive 1.5-3 hours directly after an injection. Only one of the participants reached a GH-2000 score indicative of doping when a population-based decision limit was applied. When IGF-I and P-III-NP were longitudinally monitored, 88% of the participants were identified above an individual upper threshold arbitrarily calculated as three standard deviations above the mean values of four baseline samples. The miRNA levels displayed large intra-subject variations that did not change in relation to recGH administration. Our results show that the GH isoform test is very sensitive in detecting low doses of recGH but with a short detection window. Moreover, longitudinally monitoring of IGF-I and P-III-NP may be a promising future approach to detect GH doping.

“…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 …”

Section: Discussionmentioning

confidence: 99%

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

Börjesson

Lehtihet

Andersson

et al. 2020

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The use of anabolic androgenic steroids (AAS) and other performance enhancing substances can change over time, so there is a need to constantly update what substances are used and can be detected. Six women and 30 men anabolic androgenic steroid users were recruited who filled out an anonymous questionnaire about their use of performance enhancing substances during the past year. Sampling took place on a single occasion and included blood and urine collection. Our aim was to identify which doping agents can be detected in men and women self‐reporting AAS use. The first choice of substances differed between men (testosterone) and women (oxandrolone). The use of growth hormones was reported among men (10%) and women (50%). Growth hormone releasing factors/secretagogs were reported by about ~ 20% in both genders. Nandrolone was the most frequently detected anabolic androgenic steroid even in those who did not report use in the past year. Of the current male testosterone users, 82% exhibited testosterone/epitestosterone (T/E) ratios of > 4. Men with current testosterone use displayed 4‐fold and 6‐fold higher median T/E, respectively, when compared with recent and previous testosterone users (P = 0.0001). Dermal testosterone use in women (n = 2) was not associated with a T/E ratio of > 4, but with supra‐physiological total serum testosterone concentrations. Changes in gonadotropins and hematological parameters were associated with the time of the last anabolic androgenic steroid intake in men, whereas in women these biomarkers were within the normal range. This highlights gender specific differences and indicates the need for additional biomarkers in female athletes.