Human Nutritional Supplements in the Horse. Dehydroepiandrosterone versus Androstenedione: Comparative Effects on the Androgen Profile and Consequences for Doping Analysis

Abstract

Dehydroepiandrosterone (DHEA) and androstenedione are weak androgens, which need conversion to more potent testosterone in order to enhance anabolic action. Consequences of oral dosing at 1 mg/kg on the urinary and plasma androgen profile of mare and gelding have been evaluated with an analytical method involving conjugate fractionation and selective hydrolysis, group separation, and quantitation by gas chromatography-mass spectrometry with selected ion monitoring of trimethylsilyl ethers. Peak levels of testosterone total conjugates in urine (range 300-6000 microg/L) were attained a few hours after dosing. Renal clearance was fast, so the testosterone detection period lasted only 20 to 33 h, the longest time being generated by androstenedione. The urinary testosterone/epitestosterone ratio for detection of exogenous testosterone in the mare was inoperative after DHEA administration because there was a concomitant increase of epitestosterone, which thereby acted as a masking agent. Androstanediols and androstenediols, as well as some 17-ketosteroids, were additional markers. A transient increase of circulating free testosterone has been evidenced, and this would support possible anabolic/androgenic action by supplementation with DHEA and androstenedione along the oral route.

Investigation of urinary steroid metabolites in calf urine after oral and intramuscular administration of DHEA

“…This seems strange, as levels of α-T were increasing, while α-T is considered as the main metabolite of β-T from the action of 3β-hydroxysteroid dehydrogenase. However, these results are in accordance with the findings obtained by administration of DHEA to the gelding and the mare where there was a high conversion to 5-Andro and a much lower conversion to α-and β-T [19]. These results are also confirmed in humans where ingested DHEA was rapidly metabolized to 5-Andro [20].…”

Metabolism of Anabolic Steroids and Their Relevance to Drug Detection in Horseracing

“…Although only weak androgens in their own right, they are regarded as prohormones to testosterone and thus there is potential for their abuse in sport. Following oral administration, the effect on the androgen profile in the horse and the consequences for doping ana lysis have been investigated [13,14]. Administration of 1 mg/kg resulted in significant conversion to testosterone with the threshold values in geldings and mares being exceeded for 24-36 and 19-23 h, respectively.…”

Modern Techniques for the Determination of Anabolic–Androgenic Steroid Doping in the Horse

“…Common derivatization procedures include O-methyloximination followed by trimethylsilylation [6-10, 13,[16][17][18]20,22,23], enol-trimethylsilylation [17,21,[24][25][26][27]45,48,[52][53][54][55], oximination followed by tert-butyldimethylsilylation [29] and perfluoroacylation [30,34,41,47]. The oximination/tert-butyldimethylsilylation approach was the first to be adapted for general equine AAS screening and makes use of the strong [M-57] + fragments exhibited by steroidal tert-butyldimethylsilyl ethers under electron ionization (EI) conditions, corresponding to the loss of a single tert-butyl radical.…”

“…Dehennin et al have investigated the effects of the administration of androgen precursors on concentrations of a range of endogenous steroids in equine blood and urine [52,53]. In the first study, the examined components downstream of the administered steroids on the androgen cascade were all elevated to varying degrees, although the effects on upstream components or parallel cascades were not recorded.…”