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  • Androgenes et Sport
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Utilisation illégale d’androgènes

Drug abuse for synthetic anabolic androgenic steroids

Andrologie volume 5, pages 347–360 (1995)Cite this article

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Le dopage par les androgènes est l’utilisation de substances dérivées ou apparentées à la testostérone à des fins d’amélioration de la performance sportive. Toute prise d’androgène est illégale de par la Loi du 28 Juin 89 relative au sport. Il n’existe pas, pour cette classe de substances, de justification thérapeutique possible. Le Comité Médical d’Éthique a confirmé cette décision légale en 1993.

Les moyens utilisés actuellement pour mettre en évidence cette utilisation illégale sont revus ici. En bref, le dépistage de l’utilisation illégale d’an-drogènes commence par la recherche des différents anabolisants de synthèse dans un échantillon d’urine d’un compétiteur. La seule technique utilisée et reconnue officiellement dans le cadre du dépistage du dopage est la chromatographie gazeuse couplée à la spectrométrie de masse (GC/MS).

Abstract

Drug abuse for synthetic anabolic androgenic steroids in order to ameliorate sports results is illegal since the law of june 89 in France. No exception whatsoever, therapeutical purpose(s) included, is accepted. Means for controlling such abuse are reviewed briefly here together with data from our research on epitestosterone modifications following physical exercise and testosterone undecanoate controled administration in 15 nor In France the national body responsible for doping analysis in sports is the «Laboratoire National de Dépistage du Dopage» (LNDD).

In fact, the control of drug abuse in sports requires laboratory means enabling the detection of banned substances with unlimited certainty. Briefly, untimed urine samples are analyzed for such purpose by gas (liquid or high pressure) chromatography coupled to mass spectrometry (GC/MS) which is the only technique accepted by the medical commission of I.O. C. and relevant bodies world-wide.

However, since testosterone itself can now be used as a mean of steroid abuse in man, detection has to solve new problems arising from such manipulation. After considering various approches in order to prove the offense, such as the isotopic ratio for testosterone and different urinary metabolites, and indirect technique, based on the ratio of testosterone to epitestosterone glucuronides, has proved valuable but is now questionned.

Epitestosterone is the 17α epimere of testosterone. It is not readily known to clinicians as it has no androgenic potency [5] and does not bind to the specific plasma protein TeBG (26) or androgen receptor [5, 26]. Epitestosterone was first isolated from human urines, simultaneously, by Brooks [6] and Korenman [18]. Wilson and Lipsett [30] among others demonstrated, in man, that this steroid originated both from adrenals and testis, results confirmed recently by Dehennin [8]. Dray et al. and studied its production and circadian rythm in man pointing out that epitestosterone is found in the sulphate fraction of plasma steroids and in the glucuronide fraction of urinary androgen metabolites [12, 20]. Epitestosterone is recovered as such in urines. It is not metabolized [12, 28]. However the pathway for epitestosterone biosynthesis is still uncertain today. The best (for it’s the only one!) hypothesis at present being that of Weustein et al. [30] who reported that epitestosterone could be synthesyzed in man from Δ5 androstène- 3 β, 17α-diol through a possible non enzymic modification of Δ5 androstène-3β, 17β- diol.

Donike et al. [10] showed, in man, that the mean GT/GEPIT ratio in urines was 1,5±0,9 (±SD) using epitestosterone as a marker for endogenous androgens. This added index has being implemented, as an official test for androgen abuse’s detection in sports, since the Los Angeles Olympic Games in 1982. All other parameters being normal the definition of a positive androgen doped case is based on GT/GEPIT values over 6. This value of 6 was obtained by adding 6 SD to the mean obtained in man. However, is the use of this parameter justified and 100% safe?

Some have questioned its used arguing that epitestosterone, not a well known substance, can not be reliable and could lead to false positive results. We summarize here the results of the French Research Network to which we participated.

Mathian et al. [22] showed that epitestosterone production follows testosterone production whatever the age of the subject. The ratio GT/GEPIT doesn’t vary according to age, even over puberty, it remains at 1,40±0,86 from Tanner Stade II to Tanner Stade V. It doesn’t vary significantly after exercise or with fatigue.

We also report our study of 15 young men (18–45 year old) over a year. Extensive blood (T, Δ4, DHT, DHA, SDHA, E2, TeBG, FSH, LH) and urinary parameters (GT, DHT, GEPIT, ADIOL, BDIOL) were measured before, during and after a 21 days course of testosterone undecanoate (TU). Whatever the technique used (GC/MS or RIA) results are identical. We confirmed that GT/GEPIT was very stable for each individual and could be considered as a personnal marker. After TU, at the dosage of 40 to 80 mg/day, GT/GEPIT increased significantly in all instances (athletes and sedentary subjects alike), but not permanently. This change resulted from an increase in testosterone excretion wheras epitestosterone remained non statistically changed. However at the dosage used no permanent modification was found and most of the time GT/GEPIT returned to basal values rapidly.

The analysis of the results of our study, according to the limit set by the I.O.C. at 6 for GT/GEPIT, pointed out a lot of false negative (over 50%). Values for GT excretion rate corrected with the creatinine content in the same urinary sample (GT/mg creatinine) have therefore been considered together with GT/GEPIT values. In our opinion, a more suitable and reliable index is thus obtained. The setting of a new limit at 3 for GT/GEPIT (Mean ± 3 SD) together with values under 75 ng/mg creatinine for GT is analyzed. It is also stressed that only a medical commission (aware of the significance of epitestosterone) can interpret the results obtained by analytical chemistry. This is the case in France.

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  1. Faculté de Médecine Pitié-Salpêtrière, Service de Biochimie Médicale, Université Paris VI, 91 Boulevard de l’Hôpital, 75634, Paris Cedex 13, France

    F. Wright, E. Godefroy, M. Bongini, F. Bozzolan & A. Doukani

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Le travail de recherche présenté ici a été subventionné par le «Ministère Jeunesse et Sport», «Cellule Vie de l’Athlète» Conventions 91–94.

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Wright, F., Godefroy, E., Bongini, M. et al. Utilisation illégale d’androgènes. Androl. 5, 347–360 (1995). https://doi.org/10.1007/BF03034340

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Basic and Clinical Andrology

ISSN: 2051-4190