Factors affecting urinary excretion of testosterone metabolites conjugated with cysteine. Issue 1 (28th April 2015)

• Record Type: Journal Article
• Authors: Fabregat, Andreu; Marcos, Josep; Segura, Jordi; Ventura, Rosa; Pozo, Oscar J.
• Is Part Of: Drug testing and analysis. Volume 8:Issue 1(2016:Jan.)
• Page Start: 111
• Page End: 120
• Publication Date: 2015-04-28
• Subjects: steroid profile -- cysteinyl metabolites -- exogenous influencing factors -- endogenous influencing factors -- doping; Drugs -- Analysis -- Periodicals; Drug testing -- Periodicals; Chemistry, Forensic -- Periodicals; 615.1901
• DOI: 10.1002/dta.1801
• Languages: English
• ISSNs: 1942-7603

Abstract

Abstract : The implementation of the athlete steroidal passport in doping control analysis aims to detect intra‐individual changes in the steroid profile related to the abuse of anabolic steroids. In this context, the study of intrinsic variations associated with each marker is of utmost importance. In the present work, the influence of several factors in the excretion of the recently reported testosterone metabolites conjugated with cysteine (Δ 1 ‐AED; 1, 4‐androstadien‐3, 17‐dione, Δ 6 ‐AED; 4, 6‐androstadien‐3, 17‐dione, Δ 6 ‐T; 4, 6‐androstadien‐17β‐ol‐3‐one, and Δ 15 ‐AD; 15‐androsten‐3, 17‐dione) is evaluated for the first time. Degradation experiments at 37 °C proved that, although the cysteinyl moiety is released, the variation for urinary Δ 1 ‐AED/Δ 6 ‐AED, Δ 1 ‐AED/Δ 6 ‐T ratios is less than 30%. Moreover, freeze/thaw cycle testing resulted in RSDs values below 15% for all the analytes. Regarding infradian variability, moderate variations (below 40%) were observed. Additionally, notable alterations in the excretion of these compounds have been observed in the earliest stages of pregnancy. UGT2B17 polymorphism, responsible for the low T/E ratio found in some population, does not influence the excretion of cysteinyl compounds whereas the intake of exogenous substances (alcohol or 5α‐reductase inhibitors) dramatically affects their excretion. The urinary concentrations of Δ 1 ‐AED, Δ 6 ‐AED, and Δ 15 ‐AD decreased (<50 %) after the ethanol intake, whereas after the administration of dutasteride, an important increase was observed for the concentrations of Δ 6 ‐AED, Δ 6 ‐T and Δ 15 ‐AD. Overall, the presented data describes the stability of the urinary cysteinyl steroids under the influence of many factors, proving their potential as suitable parameters to be included in the steroidal module of the athlete′s biological passport. Copyright © 2015 John Wiley & Sons, Ltd. Abstract : The influence of several factors in the excretion of testosterone metabolites (Δ 1 ‐AED, Δ 6 ‐AED, Δ 6 ‐T and Δ 15 ‐AD) conjugated with cysteine is evaluated. These factors are divided into sample preservation (microbial degradation and freeze/thaw cycles), endogenous factors (gender, ultradian and circadian rhythms, pregnancy and UGT2B17 polymorphism), and exogenous factors (alcohol and 5α‐reductase inhibitors). The results show the stability of the urinary cysteinyl steroids under the influence of many factors, proving their potential as adequate parameters to be included in screening procedures applied in doping control.