TY - BOOK
T1 - Improving time- and cost-efficiency in doping analysis
AU - Solheim, Sara Amalie
N1 - CURIS 2019 NEXS 407
PY - 2019
Y1 - 2019
N2 - Testosterone esters and clenbuterol are among the most frequently used doping substances in elite and recreational sports. Direct detection in urine and blood samples is hampered by the costs of collection, transportation and analysis, and the rapid hydrolysis of testosterone esters in blood. Indirect detection of testosterone by the ‘Athlete Biological Passport’ (ABP) steroidal module is limited by both the associated costs and confounding factors. Therefore, the present thesis aimed to improve the time- and cost-efficiency in doping analysis by evaluating 1) the applicability of dried blood spots (DBS) as a complementary sample matrix and 2) whether the hematological module of the ABP can be used to indicate doping of testosterone and thereby increase detection, given the erythropoietic effect of testosterone, and 3) by determining the most cost-efficient anti-doping testing program based on detection windows and performance-enhancing effects. In Paper I-III, DBS, urine and blood samples from men receiving two intramuscular injections of Sustanon® 250 (n = 9) or placebo (n = 10) in a randomized, placebo-controlled design were analyzed for direct and indirect detection of testosterone esters and assessment of serum levels of reproductive hormones. In Paper III, the performances in countermovement jump, 30-s all out cycle sprint and one-arm isometric elbow flexion were measured before and 24 h after the first Sustanon® injection. In Paper IV, DBS and urine samples from 6 healthy men receiving a single oral dose of 80 µg clenbuterol were collected and analyzed for detection of clenbuterol. Paper II and IV demonstrated that the DBS assays allow for detection up to 14 days after an intramuscular injection of 250 mg Sustanon®, and for at least 3 days after an oral ingestion of 80 µg clenbuterol, with 100% specificity. Further, preliminary data suggest that DBS-sampling is well accepted by athletes. Additionally, Paper IV showed that clenbuterol can be detected for at least 10 days in urine after ingestion of 80 µg of drug. Paper I demonstrated that some hematological biomarkers are affected by testosterone administration, and that the largest changes occur 3-10 days after an injection. Paper III showed that a single injection of testosterone esters do not enhance human performance acutely in a countermovement jump test, a one-arm isometric elbow flexion test nor a 30-sec cycle sprint test. In conclusion, the DBS analyses of testosterone esters and clenbuterol appear to have sufficient specificity and sensitivity to be implemented in routine doping control in elite and recreational sports. Given the longer detection windows for clenbuterol in urine, urine is expected to remain as the preferred sample matrix for clenbuterol analysis. However, the implementation of DBS sampling could improve time- and costefficiency while reducing intrusiveness, and thereby allow for higher frequency of testing, or testing of a large number of athletes in a short time, with the aim of increasing detection and deterrence. Further, changes in markers in the hematological module could be indicative of testosterone doping, and should be considered an additional tool for targeted follow-up sample collection and confirmatory analysis. Moreover, since testosterone did not have any acute performance-enhancing effects in power/strength exercises, athletes are likely not to have an advantage if administering a single dose of testosterone esters immediately before or during a competition in power/strength sports.
AB - Testosterone esters and clenbuterol are among the most frequently used doping substances in elite and recreational sports. Direct detection in urine and blood samples is hampered by the costs of collection, transportation and analysis, and the rapid hydrolysis of testosterone esters in blood. Indirect detection of testosterone by the ‘Athlete Biological Passport’ (ABP) steroidal module is limited by both the associated costs and confounding factors. Therefore, the present thesis aimed to improve the time- and cost-efficiency in doping analysis by evaluating 1) the applicability of dried blood spots (DBS) as a complementary sample matrix and 2) whether the hematological module of the ABP can be used to indicate doping of testosterone and thereby increase detection, given the erythropoietic effect of testosterone, and 3) by determining the most cost-efficient anti-doping testing program based on detection windows and performance-enhancing effects. In Paper I-III, DBS, urine and blood samples from men receiving two intramuscular injections of Sustanon® 250 (n = 9) or placebo (n = 10) in a randomized, placebo-controlled design were analyzed for direct and indirect detection of testosterone esters and assessment of serum levels of reproductive hormones. In Paper III, the performances in countermovement jump, 30-s all out cycle sprint and one-arm isometric elbow flexion were measured before and 24 h after the first Sustanon® injection. In Paper IV, DBS and urine samples from 6 healthy men receiving a single oral dose of 80 µg clenbuterol were collected and analyzed for detection of clenbuterol. Paper II and IV demonstrated that the DBS assays allow for detection up to 14 days after an intramuscular injection of 250 mg Sustanon®, and for at least 3 days after an oral ingestion of 80 µg clenbuterol, with 100% specificity. Further, preliminary data suggest that DBS-sampling is well accepted by athletes. Additionally, Paper IV showed that clenbuterol can be detected for at least 10 days in urine after ingestion of 80 µg of drug. Paper I demonstrated that some hematological biomarkers are affected by testosterone administration, and that the largest changes occur 3-10 days after an injection. Paper III showed that a single injection of testosterone esters do not enhance human performance acutely in a countermovement jump test, a one-arm isometric elbow flexion test nor a 30-sec cycle sprint test. In conclusion, the DBS analyses of testosterone esters and clenbuterol appear to have sufficient specificity and sensitivity to be implemented in routine doping control in elite and recreational sports. Given the longer detection windows for clenbuterol in urine, urine is expected to remain as the preferred sample matrix for clenbuterol analysis. However, the implementation of DBS sampling could improve time- and costefficiency while reducing intrusiveness, and thereby allow for higher frequency of testing, or testing of a large number of athletes in a short time, with the aim of increasing detection and deterrence. Further, changes in markers in the hematological module could be indicative of testosterone doping, and should be considered an additional tool for targeted follow-up sample collection and confirmatory analysis. Moreover, since testosterone did not have any acute performance-enhancing effects in power/strength exercises, athletes are likely not to have an advantage if administering a single dose of testosterone esters immediately before or during a competition in power/strength sports.
UR - https://soeg.kb.dk/permalink/45KBDK_KGL/1pioq0f/alma99123523409105763
M3 - Ph.D. thesis
SN - 978-87-7209-334-5
BT - Improving time- and cost-efficiency in doping analysis
PB - Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen
CY - Copenhagen
ER -