Prohormones and sport

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Abstract

Several precursors of testosterone and nandrolone introduced on the nutritional supplement market as performance enhancing drugs are banned in sports. Until now they are legally sold without a prescription in the US. Results of excretion studies with related compounds including 7-keto-DHEA and 1-androstenediol are presented. The main metaboliltes of 7-keto-DHEA are 7-hydroxylated compounds. The commercial 1-androstenediol preparation was contaminated with several other anabolic steroids. Oxidation of 1-androstenediol to 1-androstenedione seems to be the major renal metabolic pathway.

Additionally contaminated nutritional supplements containing banned substances not indicated on the label were administered. The results of the excretion studies indicate that after the intake of amounts substantially lower than the recommended dose athletes can fail a doping test for periods up to 120 h.

Introduction

Since the introduction in the 1980s of a general screening method for anabolic steroids in doping analysis, the detection of long acting injectable preparations became rather easy [1], [2], [3]. In order to circumvent a positive test athletes therefore switched to injectable testosterone or oral preparations that were rapidly cleared from the body. It was reported that in the 1980s East German scientists, knowing that a test would soon be adopted to detect the use of testosterone, developed short acting testosterone preparations and nasal sprays containing the testosterone precursor androstenedione [4].

Another way to circumvent the doping tests was the use of prohormones, especially precursors of testosterone, while the orally short acting precursors of nortestosterone also seemed to attract the cheating athlete.

One of the first hormonal supplements that became available in the USA was DHEA around 1996. The list steadily expanded and now includes DHEA, 4-androstenedione, 4-androstenediol and 5-androstenediol as well as the nandrolone precursors 19-norandrostenedione and 19-norandrostenediol. Their introduction on the US market and the internet trade were the direct result of the 1994 Dietary Supplement and Health Education Act. Originally this act was designed to allow people the use of common vitamin supplements. However, through several loop-holes in the law, any substance that is natural to the body can be sold according to this act. In this way consumers including professional athletes and people using substances for cosmetic reasons, are being increasingly provided with untested, unproven and potentially lethal products. A strong indication of this trend comes from the increased sales of dietary supplements which have surged in the US from 8.3 billion in 1994 to 14 billion in 1999. Moreover these supplements place athletes at sanctions from international sports authorities.

In this work results of excretion studies with prohormones including 1-androstenediol and 7-keto-DHEA will be presented.

Another problem with prohormones and sport is related to nutritional supplements contaminated with prohormones [5], [6], [7]. The aim of this study was to determine detection times for doping substances not listed on the product labels after the ingestion of two contaminated supplements.

Section snippets

Prohormones

The prohormone 7-keto-DHEA (7-keto®) was manufactured by Enzymatic Therapy® (Green Bay, WI, USA) and was purchased in the Netherlands. The lot number was 25740.

The other prohormone 1-AD was manufactured by LPJ Research Inc. (Seymour, IL, USA) and was labelled to contain 100 mg 1-androstene-3β-17β-diol. A jar containing 60 capsules of this supplement (lot number: DC25301EX04) was purchased via internet.

Contaminated nutritional supplements

Two different supplements were purchased. The manufacturer’s recommended dose for supplement X

Prohormones

Analysis of the 7-keto dietary supplement did not reveal the presence of other anabolic steroids.

The ion chromatograms (m/z 374 and 358) obtained after the analysis of extracts from a 4 h post-administration sample after TMS-ether derivatisation are shown in Fig. 1.

The main metabolites of 7-keto-DHEA are 7-hydroxylated-DHEA compounds. Mass spectra of TMS-ether derivatives of 7α-OH-DHEA and 7-keto-DHEA are shown in Fig. 2, Fig. 3, respectively. Besides 7-hydroxy-DHEA metabolites a number of other

Prohormones

The main metabolites of 7-keto DHEA are the 7-hydroxylated-DHEA compounds. 7-Hydroxy DHEA isomers were previously identified as metabolites of DHEA and are endogenously present in very small amounts [8]. After ingestion of 7-keto DHEA, however, these substances are abundantly present. Regarding doping analysis more quantitative analyses on a wide range of samples from excretion studies will be necessary to determine appropriate threshold values.

Besides the 7-hydroxy-DHEA metabolites, one

Conclusion

Except in very special circumstances requiring medical care nutritional supplements are not required in addition to a normal balanced diet. Athletes needing supplements should be very careful as some supplement may contain prohormones not declared on the label. Moreover following international rules athletes remain responsible for what is found in their bodyfluids, irrespective the origin.

As long as initiatives to legally control the production and distribution of prohomones are not instigated

Acknowledgements

The authors wish to thank T. Demey, D. Dhaenens and K. Roels for technical assistance. A grant by the Flemish Ministry is acknowledged.

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