Oral administration of dehydroepiandrosterone to healthy men: alteration of the urinary androgen profile and consequences for the detection of abuse in sport by gas chromatography-mass spectrometry.

Dehydroepiandrosterone (DHEA) replacement therapy as compensation for high age-related decline of DHEA and DHEA sulfate production is a matter of intense investigation, since many beneficial effects have been proven, or are suggested and expected. Therefore, DHEA abuse by athletes has been considered by the International Olympic Committee, which banned the substance recently. As DHEA for oral supplementation is easily available, we decided to investigate the effect on the urinary androgen profile of administration along this route of a single substitution dose of 50 mg. Quantitative analysis by gas chromatography-mass spectrometry with selected ion monitoring demonstrated that the drug was readily absorbed with 50 to 75% recovery of dosing after 24 h, and with glucuro- and sulfoconjugates of DHEA, androsterone, and etiocholanolone as the most abundant metabolites. In agreement with reported data found in blood, conversion of exogenous DHEA to the principal biologically active androgen, testosterone, was low but proven to be real by the administration of deuterium-labeled DHEA and the subsequent identification and quantification of deuterium-labeled testosterone. A concentration threshold of 300 micrograms/L of DHEA glucuronide is proposed for the screening of DHEA abuse in sport, but a single replacement dose can only be detected during 8 h. Such a short detection period is the consequence of considerable first-pass hepatic metabolism and also of the high interindividual variability of circulating and urinary DHEA and DHEA sulfate concentrations.