Application of the Athlete Biological Passport approach to the detection of growth hormone doping

Context Because of its anabolic and lipolytic properties, growth hormone (GH) use is prohibited in sport. Two methods based on population derived decision limits are currently used to detect human GH (hGH) abuse: the hGH Biomarkers Test and the Isoforms Differential Immunoassay. Objective Test the hypothesis that longitudinal profiling of hGH biomarkers through application of the Athlete Biological Passport (ABP) has the potential to flag hGH abuse. Design IGF-1 and P-III-NP distributions were obtained from 7 years of anti-doping data and applied as priors to analyse individual profiles from an hGH administration study in recreational athletes. Setting Academic and anti-doping laboratories. Elite (n=11,455) and recreational athletes (n=35). Intervention(s) An open-label, randomized, single site, placebo-controlled administration study was carried out with individuals randomly assigned to 4 arms: placebo, or 3 different doses of recombinant hGH. Main Outcome Measure(s) Serum samples were analyzed for IGF-1, P-III-NP, and hGH isoforms and the performance of a longitudinal, ABP-based approach was evaluated. Results An ABP-based approach set at a 99% specificity level flagged 20/27 individuals receiving hGH treatment, including 17/27 individuals after cessation of the treatment. ABP sensitivity ranged from 12.5-71.4 % across the hGH concentrations tested following 7 days of treatment, peaking at 57.1-100 % after 21 days of treatment, and was maintained between 37.5-71.4 % for the low and high dose groups one week after cessation of treatment. Conclusions These findings demonstrate that longitudinal profiling of hGH biomarkers can provide suitable performance characteristics for use in anti-doping programs.

Factors Confounding the Athlete Biological Passport: A Systematic Narrative Review

Background Through longitudinal, individual and adaptive monitoring of blood biomarkers, the haematological module of the athlete biological passport (ABP) has become a valuable tool in anti-doping efforts. The composition of blood as a vector of oxygen in the human body varies in athletes with the influence of multiple intrinsic (genetic) or extrinsic (training or environmental conditions) factors. In this context, it is fundamental to establish a comprehensive understanding of the various causes that may affect blood variables and thereby alter a fair interpretation of ABP profiles. Methods This literature review described the potential factors confounding the ABP to outline influencing factors altering haematological profiles acutely or chronically. Results Our investigation confirmed that natural variations in ABP variables appear relatively small, likely—at least in part—because of strong human homeostasis. Furthermore, the significant effects on haematological variations of environmental conditions (e.g. exposure to heat or hypoxia) remain debatable. The current ABP paradigm seems rather robust in view of the existing literature that aims to delineate adaptive individual limits. Nevertheless, its objective sensitivity may be further improved. Conclusions This narrative review contributes to disentangling the numerous confounding factors of the ABP to gather the available scientific evidence and help interpret individual athlete profiles.

Chinese Herbal Medicine Significantly Impacts the Haematological Variables of the Athlete Biological Passport

In the fight against sports doping, the Athlete Biological Passport (ABP) system aims to indirectly unveil the doping incidents by monitoring selected biomarkers; however, several unexplored extrinsic factors may dampen a fair interpretation of ABP profiles. Chinese herbal medicine (CHM) plays a pivotal role in the health care system, and some remedies have a long history of being used to treat anaemia. In this study, we addressed the concerns of whether the CHM administration could yield a measurable effect on altering the ABP haematological variables. Forty-eight healthy volunteers were randomly assigned to receive two-week oral administration of one of the six selected CHM products that are commonly prescribed in Taiwan (eight subjects per group). Their blood variables were determined longitudinally in the phases of baseline, intervention, and recovery over 5 weeks. Blood collection and analyses were carried out in strict compliance with relevant operating guidelines. In the groups receiving Angelicae Sinensis Radix, Astragali Radix, and Salviae Miltiorrhizae Radix et Rhizoma, a significant increased reticulocyte percentage and decreased OFF-hr Score were manifested during the intervention, and such effects even sustained for a period of time after withdrawal. All other variables, including haemoglobin and Abnormal Blood Profile Score, did not generate statistical significance. Our results show that the use of CHM may impact the ABP haematological variables. As a consequence, we recommend athletes, particularly those who have been registered in the testing pool, should be aware of taking specific Chinese herbal-based treatment or supplementation, and document any of its usage on the anti-doping forms.

Current Insights into the Steroidal Module of the Athlete Biological Passport

For decades, the class of anabolic androgenic steroids has represented the most frequently detected doping agents in athletes’ urine samples. Roughly 50% of all adverse analytical findings per year can be attributed to anabolic androgenic steroids, of which about 2/3 are synthetic exogenous steroids, where a qualitative analytical approach is sufficient for routine doping controls. For the remaining 1/3 of findings, caused by endogenous steroid-derived analytical test results, a more sophisticated quantitative approach is required, as their sheer presence in urine cannot be directly linked to an illicit administration. Here, the determination of urinary concentrations and concentration ratios proved to be a suitable tool to identify abnormal steroid profiles. Due to the large inter-individual variability of both concentrations and ratios, population-based thresholds demonstrated to be of limited practicability, leading to the introduction of the steroidal module of the Athlete Biological Passport. The passport enabled the generation of athlete-specific individual reference ranges for steroid profile parameters. Besides an increase in sensitivity, several other aspects like sample substitution or numerous confounding factors affecting the steroid profile are addressed by the Athlete Biological Passport-based approach. This narrative review provides a comprehensive overview on current prospects, supporting professionals in sports drug testing and steroid physiology.

Factors confounding the athlete biological passport: a systematic narrative review

BackgroundThrough longitudinal, individual and adaptive monitoring of blood biomarkers, the haematological module of the athlete biological passport (ABP) has become a valuable tool in anti-doping efforts. The composition of blood as a vector of oxygen in the human body varies in athletes with the influence of multiple intrinsic (genetic) or extrinsic (training or environmental conditions) factors. In this context, it is fundamental to establish a comprehensive understanding of the various causes that may affect blood variables and thereby alter a fair interpretation of ABP profiles.MethodsThis literature review described the potential factors confounding the ABP to outline influencing factors altering haematological profiles acutely or chronically.ResultsOur investigation confirmed that natural variations in ABP variables appear relatively small, likely—at least in part—because of strong human homeostasis. Furthermore, the significant effects on haematological variations of environmental conditions (e.g. exposure to heat or hypoxia) remain debatable. The current ABP paradigm seems rather robust in view of the existing literature that aims to delineate adaptive individual limits. Nevertheless, its objective sensitivity may be further improved.ConclusionsThis narrative review contributes to disentangling the numerous confounding factors of the ABP to gather the available scientific evidence and help interpret individual athlete profiles.Key pointsThrough longitudinal, individual and adaptive monitoring of blood biomarkers, the haematological module of the athlete biological passport (ABP) has become a valuable tool in anti-doping efforts.This literature review described the potential factors confounding the ABP to outline influencing factors altering haematological profiles acutely or chronically.While our results support the current ABP paradigm as rather robust to delineate adaptive individual limits, our work may contribute to disentangling the numerous confounding factors of the ABP to gather the available scientific

The Influence of Training Load on Hematological Athlete Biological Passport Variables in Elite Cyclists

The hematological module of the Athlete Biological Passport (ABP) is used in elite sport for antidoping purposes. Its aim is to better target athletes for testing and to indirectly detect blood doping. The ABP allows to monitor hematological variations in athletes using selected primary blood biomarkers [hemoglobin concentration (Hb) and reticulocyte percentage (Ret%)] with an adaptive Bayesian model to set individual upper and lower limits. If values fall outside the individual limits, an athlete may be further targeted and ultimately sanctioned. Since (Hb) varies with plasma volume (PV) fluctuations, possibly caused by training load changes, we investigated the putative influence of acute and chronic training load changes on the ABP variables. Monthly blood samples were collected over one year in 10 male elite cyclists (25.6 ± 3.4 years, 181 ± 4 cm, 71.3 ± 4.9 kg, 6.7 ± 0.8 W.kg−1 5-min maximal power output) to calculate individual ABP profiles and monitor hematological variables. Total hemoglobin mass (Hbmass) and PV were additionally measured by carbon monoxide rebreathing. Acute and chronic training loads–respectively 5 and 42 days before sampling–were calculated considering duration and intensity (training stress score, TSSTM). (Hb) averaged 14.2 ± 0.0 (mean ± SD) g.dL−1 (range: 13.3–15.5 g·dl−1) over the study with significant changes over time (P = 0.004). Hbmass was 1030 ± 87 g (range: 842–1116 g) with no significant variations over time (P = 0.118), whereas PV was 4309 ± 350 mL (range: 3,688–4,751 mL) with a time-effect observed over the study time (P = 0.014). Higher acute–but not chronic—training loads were associated with significantly decreased (Hb) (P <0.001). Although individual hematological variations were observed, all ABP variables remained within the individually calculated limits. Our results support that acute training load variations significantly affect (Hb), likely due to short-term PV fluctuations, underlining the importance of considering training load when interpreting individual ABP variations for anti-doping purposes.