title: On the origin of physiologically high ratios of urinary testosterone to epitestosterone: consequences for reliable detection of testosterone administration by male athletes.
abstract: Testosterone administration to male athletes can be safely detected in the vast majority of cases by the urinary excretion ratio of testosterone to epitestosterone glucuronides (TG/EG), which may not exceed 6. Some rare cases of physiologically high TG/EG ratios (between 6 and 12) are encountered; these may be attributed to a dysregulation of the testicular secretions of epitestosterone which is decreased, and of epitestosterone sulphate (ES) which is normal or increased. Impaired hydrolysis of circulating epitestosterone sulphate by deficiency of a specific sulphatase acting on 17 alpha-sulphates must also be considered as a possible reason for the decreased availability of epitestosterone for hepatic glucuronidation. Urinary excretions of conjugates and metabolites of testosterone and epitestosterone (expressed in nmol/mmol creatinine) have been determined by gas chromatography-mass spectrometry associated with stable isotope dilution, in a reference population of 90 healthy male subjects and in 12 subjects with chronic TG/EG > 4. Urinary excretion ratios such as TG/(EG+ES), EG/ES and TG/5-androstene-3 beta,17 alpha-diol glucuronide are shown to be efficient criteria which allow discrimination between physiologically high and pharmacologically high TG/EG ratios. A simple oral loading test with deuterium-labelled epitestosterone demonstrates the difference between hepatic and total epitestosterone metabolism clearly, particularly in subjects with physiologically high TG/EG in comparison with subjects with normal TG/EG.
authors.affiliation: Fondation de Recherche en Hormonologie, Fresnes, France.
authors.forename: L
authors.initials: L
authors.lastname: Dehennin
mesh_terms: D000293:Adolescent; D000328:Adult; D003903:Deuterium; D004845:Epitestosterone / Q000008:administration & dosage / Q000378:metabolism / Q000652:urine*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007201:Indicator Dilution Techniques; D007553:Isotope Labeling; D008099:Liver / Q000378:metabolism; D008297:Male; D011863:Radioimmunoassay; D012016:Reference Values; D012680:Sensitivity and Specificity; D013177:Sports; D015813:Substance Abuse Detection; D013739:Testosterone / Q000031:analogs & derivatives / Q000652:urine*
chemical_list: C015529:testosterone glucuronate; D013739:Testosterone; D004845:Epitestosterone; D003903:Deuterium