akn
Musclechemistry Member
Naturally occurring steroids have hypertrophic capacities for muscle tissue and can accordingly increase the athlete’s strength. Therefore, these performance-enhancing substances are listed as prohibited compounds by the World Anti-Doping Agency (WADA). Their detection has subsequently been implemented in routine procedures of doping control laboratories. Nowadays, endogenous steroids are believed to be among the most widespread doping substances misused in sports. In 2008, more than 40% of the total adverse analytical findings and atypical findings reported by WADA-accredited testing laboratories were attributed to endogenous steroids.
The detection of misuse with naturally occurring steroids remains challenging since analytical screening methods cannot differentiate between synthetic and natural compounds. The costly and laborious confirmation analysis with gas chromatography/ combustion/isotope ratio mass spectrometry has been applied
since the end of the 1990s to differentiate exogenous from endogenous steroids in suspicious urine samples, but today availability of synthetic steroids with the same C13/C12 ratio as endogenous ones can seriously limit this approach.
Supplementation with endogenous steroids alters basal steroid concentrations. In the early 1990s, population-based reference ranges were established for testosterone (T), epitestosterone (E), androsterone (Andro), etiocholanolone (Etio), 5?-androstane-3?, 17?-diol (5???-Adiol), 5?-androstane-3?,17?-diol (5???-Adiol) and a number of steroid ratios i.e. T/E, Andro/Etio, Andro/T. These reference values were applied to screen for outlying values characteristic of doping with steroids. At that period, the studies mainly focused on the administration of T.
To defeat doping control tests in the early 1990s, athletes started to use new endogenous steroids which alter the steroid profile in different ways than T. 5?-dihydrotestosterone (DHT or androstanolone), a direct metabolite of T, was suited for this purpose as it leaves the T/E ratio unchanged just after administration. Indeed, the enzymatic 5?-reductase conversion of T to DHT is considered as an irreversible process. Moreover, DHT was known to be a 3-times more potent androgen than its precursor as it shows greater affinity for the androgen receptor complex. As DHT misuse was investigated and detection criteria were established in the mid 1990s, the endogenous 5?-androstane-3?,17?-diol was marketed as a prohormone of DHT to obtain the same effects and was sold as a nutritional supplement.
From 1996 onwards, DHEA has been marketed as a freely available food supplement. Together with androstenedione (Adion) and andostenediol, DHEA became an over-the-counter product in the United States. Elsewhere in the world, DHEA could be obtained via the Internet or as pharmaceutical preparations from local drug stores with a medical prescription. DHEA is known to be the most abundant androgen circulating in the body and its sulfate ester acts as a reservoir or buffer for steroid genesis of androgens. As the high concentrations decline during lifespan, it was believed that DHEA had anti-ageing effects and was marketed accordingly. Although DHEA is generally claimed to be a weak androgen, the anabolic nature of DHEA has been proven using DNA micro arrays to compare its genomic expression profile with that of DHT. DHEA metabolises via Adion to T and is therefore considered a prohormone of T. Both DHT and DHEA have been misused by athletes. Consequently, several groups have reported on the detection of both DHT and DHEA misuse and proposed decision criteria based upon population statistics.
Although it was already known in the 1990s that subject based reference ranges are more reliable than population-based reference ranges for androgens and their ratios, it is only in 2007 that an evaluation method was proposed for this purpose. In that model, Bayesian inference techniques are used to switch the focus from comparison with a population to the determination of individual reference values as the number of individual records grows. Today, following the Athlete Biological Passport (ABP) paradigm, individual records comprising results from blood and/or urine analyses acquired in different doping control laboratories are stored over time to reveal the biological response of doping or effects of a medical condition requiring a closer examination. The Athlete Steroidal Passport (ASP) is the endocrine module of the ABP that collects steroid profiling data obtained from urine samples. The ASP records some steroids and metabolites which are routinely monitored in steroid profiling for doping control purposes. The ASP currently includes T, E, Andro, Etio, 5???-Adiol, 5???-Adiol, DHEA, and DHT. In addition to the T/E ratio, relevant steroid ratios such as Andro/Etio, 5???-Adiol/5???-Adiol, 5???- Adiol/Etio, and Andro/T are also evaluated. In its present form, the ASP remains mainly operational for the alteration of the steroid profile induced by different routes of T administration.
Minor steroid metabolites are important markers for specific determination of the misuse in sports with other naturally occurring steroids, for example, 7-keto-dehydroepiandrostenendione, DHEA and Adion which can be easily purchased as food supplements. Together with traditionally monitored steroids, these hydroxylated steroid metabolites provide important information on how the steroid profile is altered after misuse of particular endogenous steroids. Hence, additional markers may provide useful information regarding the administration of other steroids like DHT and DHEA. This work aims to identify novel biomarkers for DHT and DHEA administration in sports, with a selection among a large set of potential markers based on the results obtained by the Bayesian framework of the ASP.
Van Renterghem P, Van Eenoo P, Sottas P-E, Saugy M, Delbeke F. Subject-based steroid profiling and the determination of novel biomarkers for DHT and DHEA misuse in sports. Drug Testing and Analysis 2010;2(11-12):582-8. Subject-based steroid profiling and the determination of novel biomarkers for DHT and DHEA misuse in sports - Van Renterghem - 2010 - Drug Testing and Analysis - Wiley Online Library
Doping with natural steroids can be detected by evaluating the urinary concentrations and ratios of several endogenous steroids. Since these biomarkers of steroid doping are known to present large inter-individual variations, monitoring of individual steroid profiles over time allows switching from population-based towards subject-based reference ranges for improved detection. In an Athlete Biological Passport (ABP), biomarkers data are collated throughout the athlete's sporting career and individual thresholds defined adaptively. For now, this approach has been validated on a limited number of markers of steroid doping, such as the testosterone (T) over epitestosterone (E) ratio to detect T misuse in athletes. Additional markers are required for other endogenous steroids like dihydrotestosterone (DHT) and dehydroepiandrosterone (DHEA). By combining comprehensive steroid profiles composed of 24 steroid concentrations with Bayesian inference techniques for longitudinal profiling, a selection was made for the detection of DHT and DHEA misuse.
The biomarkers found were rated according to relative response, parameter stability, discriminative power, and maximal detection time. This analysis revealed DHT/E, DHT/5?-androstane-3?,17?-diol and 5?-androstane-3?,17?-diol/5?-androstane-3?,17?-diol as best biomarkers for DHT administration and DHEA/E, 16?-hydroxydehydroepiandrosterone/E, 7?-hydroxydehydroepiandrosterone/E and 5?-androstane-3?,17?-diol/5?-androstane-3?,17?-diol for DHEA. The selected biomarkers were found suitable for individual referencing. A drastic overall increase in sensitivity was obtained. The use of multiple markers as formalized in an Athlete Steroidal Passport (ASP) can provide firm evidence of doping with endogenous steroids.
The detection of misuse with naturally occurring steroids remains challenging since analytical screening methods cannot differentiate between synthetic and natural compounds. The costly and laborious confirmation analysis with gas chromatography/ combustion/isotope ratio mass spectrometry has been applied
since the end of the 1990s to differentiate exogenous from endogenous steroids in suspicious urine samples, but today availability of synthetic steroids with the same C13/C12 ratio as endogenous ones can seriously limit this approach. Supplementation with endogenous steroids alters basal steroid concentrations. In the early 1990s, population-based reference ranges were established for testosterone (T), epitestosterone (E), androsterone (Andro), etiocholanolone (Etio), 5?-androstane-3?, 17?-diol (5???-Adiol), 5?-androstane-3?,17?-diol (5???-Adiol) and a number of steroid ratios i.e. T/E, Andro/Etio, Andro/T. These reference values were applied
to screen for outlying values characteristic of doping with steroids. At that period, the studies mainly focused on the administration of T.To defeat doping control tests in the early 1990s, athletes started to use new endogenous steroids which alter the steroid profile in different ways than T. 5?-dihydrotestosterone (DHT or androstanolone), a direct metabolite of T, was suited for this purpose as it leaves the T/E ratio unchanged just after administration. Indeed, the enzymatic 5?-reductase conversion of T to DHT is considered as an irreversible process. Moreover, DHT was known to be a 3-times more potent androgen than its precursor as it shows greater affinity for the androgen receptor complex. As DHT misuse was investigated and detection criteria were established in the mid 1990s, the endogenous 5?-androstane-3?,17?-diol was marketed as a prohormone of DHT to obtain the same effects and was sold as a nutritional supplement.
From 1996 onwards, DHEA has been marketed as a freely available food supplement. Together with androstenedione (Adion) and andostenediol, DHEA became an over-the-counter product in the United States. Elsewhere in the world, DHEA could be obtained via the Internet or as pharmaceutical preparations from local drug stores with a medical prescription. DHEA is known to be the most abundant androgen circulating in the body and its sulfate ester acts as a reservoir or buffer for steroid genesis of androgens. As the high concentrations decline during lifespan, it was believed that DHEA had anti-ageing
effects and was marketed accordingly. Although DHEA is generally claimed to be a weak androgen, the anabolic nature of DHEA has been proven using DNA micro arrays to compare its genomic expression profile with that of DHT. DHEA metabolises via Adion to T and is therefore considered a prohormone of T. Both DHT and DHEA have been misused by athletes. Consequently, several groups have reported on the detection of both DHT and DHEA misuse and proposed decision criteria based upon population statistics.Although it was already known in the 1990s that subject based reference ranges are more reliable than population-based reference ranges for androgens and their ratios, it is only in 2007 that an evaluation method was proposed for this purpose. In that model, Bayesian inference techniques are used to switch the focus from comparison with a population to the determination of individual reference values as the number of individual records grows. Today, following the Athlete Biological Passport (ABP) paradigm, individual records comprising results from blood and/or urine analyses acquired in different doping control laboratories are stored over time to reveal the biological response of doping or effects of a medical condition requiring
a closer examination. The Athlete Steroidal Passport (ASP) is the endocrine module of the ABP that collects steroid profiling data obtained from urine samples. The ASP records some steroids and metabolites which are routinely monitored in steroid profiling for doping control purposes. The ASP currently includes T, E, Andro, Etio, 5???-Adiol, 5???-Adiol, DHEA, and DHT. In addition to the T/E ratio, relevant steroid ratios such as Andro/Etio, 5???-Adiol/5???-Adiol, 5???- Adiol/Etio, and Andro/T are also evaluated. In its present form, the ASP remains mainly operational for the alteration of the steroid profile induced by different routes of T administration.Minor steroid metabolites are important markers for specific determination of the misuse in sports with other naturally occurring steroids, for example, 7-keto-dehydroepiandrostenendione, DHEA and Adion which can be easily purchased as food supplements. Together with traditionally monitored steroids, these hydroxylated steroid metabolites provide important information on how the steroid profile is altered after misuse of particular endogenous steroids. Hence, additional markers may provide useful information regarding the administration of other steroids like DHT and DHEA. This work aims to identify novel biomarkers for DHT and DHEA administration in sports, with a selection among a large set of potential markers based on the results obtained by the Bayesian framework of the ASP.
Van Renterghem P, Van Eenoo P, Sottas P-E, Saugy M, Delbeke F. Subject-based steroid profiling
and the determination of novel biomarkers for DHT and DHEA misuse in sports. Drug Testing and Analysis 2010;2(11-12):582-8. Subject-based steroid profiling and the determination of novel biomarkers for DHT and DHEA misuse in sports - Van Renterghem - 2010 - Drug Testing and Analysis - Wiley Online LibraryDoping with natural steroids can be detected by evaluating the urinary concentrations and ratios of several endogenous steroids. Since these biomarkers of steroid doping are known to present large inter-individual variations, monitoring of individual steroid profiles over time allows switching from population-based towards subject-based reference ranges for improved detection. In an Athlete Biological Passport (ABP), biomarkers data are collated throughout the athlete's sporting career
and individual thresholds defined adaptively. For now, this approach has been validated on a limited number of markers of steroid doping, such as the testosterone (T) over epitestosterone (E) ratio to detect T misuse in athletes. Additional markers are required for other endogenous steroids like dihydrotestosterone (DHT) and dehydroepiandrosterone (DHEA). By combining comprehensive steroid profiles composed of 24 steroid concentrations with Bayesian inference techniques for longitudinal profiling, a selection was made for the detection of DHT and DHEA misuse. The biomarkers found were rated according to relative response, parameter stability, discriminative power, and maximal detection time. This analysis revealed DHT/E, DHT/5?-androstane-3?,17?-diol and 5?-androstane-3?,17?-diol/5?-androstane-3?,17?-diol as best biomarkers for DHT administration and DHEA/E, 16?-hydroxydehydroepiandrosterone/E, 7?-hydroxydehydroepiandrosterone/E and 5?-androstane-3?,17?-diol/5?-androstane-3?,17?-diol for DHEA. The selected
biomarkers were found suitable for individual referencing. A drastic overall increase in sensitivity was obtained. The use of multiple markers as formalized in an Athlete Steroidal Passport (ASP) can provide firm evidence of doping with endogenous steroids.
