Genotype-dependent metabolism of exogenous testosterone - new biomarkers result in prolonged detectability
Abstract
Testosterone (T) misuse still represents a major problem in sports drug testing. Many strategies have been developed and applied to routine doping controls in recent years to enable both to identify suspicious samples in initial testing procedures and to confirm the exogenous origin of urinary T by means of carbon isotope ratio (CIR) determinations. Depending on the tested individual's genotype of UGT2B17, significantly different amounts of T are glucuronidated and excreted, which results in unaffected T/epitestosterone ratios after T misuse in those subjects with the deletion/deletion polymorphism (del/del). The aim of this study was to investigate differences in metabolic pathways of orally administered T between persons of del/del and insertion/insertion (ins/ins) genetic polymorphism. Therefore, a recently established method using hydrogen isotope ratios together with high-resolution and high-accuracy mass spectrometry was applied after administration of deuterated T to n = 4 subjects including both genotypes. Participants collected urine specimens directly before and for up to 8 days after the application. Urine aliquots were prepared to yield unconjugated, glucuronidated, and sulphoconjugated fractions of urinary steroids. Besides the significant difference in the excretion of T-glucuronide, all measured metabolites varied rather on an individual basis than due to a genotype difference. New T metabolites (both methylated and de-methylated) were detected and investigated regarding their potential to enhance the screening for T misuse. Sulphoconjugated epiandrosterone was further identified as the biomarker allowing for a prolonged retrospective detection of T misuse by means of CIR determinations for up to 5 days compared to 1 day if currently applied sports drug testing procedures were used. Copyright © 2016 John Wiley & Sons, Ltd.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Genetic variations of UGTs can change the glucuronidation efficiency for an androgen and alter its excretion.
“Genetic variations of UGTs can change the glucuronidation efficiency for an androgen and alter its excretion (Piper et al., 2016).”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Piper et al., 2016
Cites
Recent Advances in Doping Analysis
Bassindale, T., Cowan, D., Dale, S. E. C., Hutt, A., Leeds, A., Kicman, A. T., Schanzer, H., Geyer, H., Gotzmann, A., & Mareck, U. (2002) · Cited by 547 · see citing works
Jakobsson, J., Ekström, L., Inotsume, N., Garle, M., Lorentzon, M., Ohlsson, C., Roh, H., Carlström, K., & Rane, A. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-1643 · Cited by 282 · see citing works
Factors influencing the steroid profile in doping control analysis
Mareck, U., Geyer, H., Opfermann, G., Thevis, M., & Schänzer, W. (2008) · Journal of Mass Spectrometry · doi:10.1002/jms.1457 · Cited by 261 · see citing works
Self-citationConley, A. J., & Mm, H. (2001) · Reproduction · doi:10.1530/rep.0.1210685 · Cited by 235 · see citing works
Methylation and Inactivation of Estrogen, Progesterone, and Androgen Receptors in Prostate Cancer
Sasaki, M. (2002) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/94.5.384 · Cited by 200 · see citing works
Schulze, J. J., Lundmark, J., Garle, M., Skilving, I., Ekström, L., & Rane, A. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0218 · Cited by 186 · see citing works
Piper, T., Mareck, U., Geyer, H., et al. (2008) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.3601 · Cited by 169 · see citing works
Self-citationBayesian detection of abnormal values in longitudinal biomarkers with an application to T/E ratio
Sottas, P., Baume, N., Saudan, C. M., et al. (2006) · Biostatistics · doi:10.1093/biostatistics/kxl009 · Cited by 153 · see citing works
A review of mechanistic studies on aromatase (CYP19) and 17α-hydroxylase-17,20-lyase (CYP17)
Akhtar, M., Wright, J. N., & Lee-Robichaud, P. (2010) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2010.11.003 · Cited by 126 · see citing works
Sten, T., Bichlmaier, I., Kuuranne, T., et al. (2008) · Drug Metabolism and Disposition · doi:10.1124/dmd.108.024844 · Cited by 108 · see citing works
Studies on Testosterone Metabolism
Baulieu, É.-É., & MAUVAIS-JARVIS, P. (1964) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)91355-4 · Cited by 78 · see citing works
Dehennin, L., Bonnaire, Y., & Plou, P. (1999) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/s0378-4347(98)00480-0 · Cited by 76 · see citing works
Zhang, Y., Tobias, H. J., & Brenna, J. T. (2008) · Steroids · doi:10.1016/j.steroids.2008.10.001 · Cited by 72 · see citing works
Dehennin, L., Lafarge, P., Dailly, P., et al. (1996) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/s0378-4347(96)00131-4 · Cited by 67 · see citing works
Renterghem, P. V., Eenoo, P. V., Sottas, P., et al. (2011) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2011.03992.x · Cited by 57 · see citing works
The identification of C-18 neutral steroids in normal stallion urine
Houghton, E., Copsey, J., DUMASIA, M. C., et al. (1984) · Journal of Mass Spectrometry · doi:10.1002/bms.1200110209 · Cited by 56 · see citing works
Strahm, E., Mullen, J., Gårevik, N., et al. (2015) · Drug Testing and Analysis · doi:10.1002/dta.1841 · Cited by 54 · see citing works
Determination of 13 C/ 12 C ratios of endogenous urinary steroids excreted as sulpho conjugates
Piper, T., Opfermann, G., Thevis, M., et al. (2010) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.4762 · Cited by 50 · see citing works
Self-citationPiper, T., Emery, C., Thomas, A., Saugy, M., & Thevis, M. (2013) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-013-6949-3 · Cited by 45 · see citing works
Self-citationSchänzer, W., Horning, S., & Donike, M. (1995) · Steroids · doi:10.1016/0039-128x(95)00008-e · Cited by 44 · see citing works
Self-citationOkano, M., Ueda, T., Nishitani, Y., Kano, H., Ikekita, A., & Kageyama, S. (2012) · Drug Testing and Analysis · doi:10.1002/dta.1394 · Cited by 42 · see citing works
19-Nor-deoxycorticosterone in the neutral fraction of human urine
Dale, S. L., HOLBROOK, M. M., & Melby, J. C. (1981) · Steroids · doi:10.1016/0039-128x(81)90012-x · Cited by 41 · see citing works
Piper, T., Thomas, A., Thevis, M., & Saugy, M. (2012) · Drug Testing and Analysis · doi:10.1002/dta.1416 · Cited by 37 · see citing works
Self-citationZeranol: doping offence or mycotoxin? A case‐related study
Thevis, M., Fußhöller, G., & Schänzer, W. (2011) · Drug Testing and Analysis · doi:10.1002/dta.352 · Cited by 37 · see citing works
Self-citationStandardization for oxygen isotope ratio measurement - still an unsolved problem
Kornexl, B. E., Werner, R. A., & Gehre, M. (1999) · Rapid Communications in Mass Spectrometry · doi:10.1002/(sici)1097-0231(19990715)13:13 · Cited by 35 · see citing works
Boccard, J., Badoud, F., Jan, N., Nicoli, R., Schweizer, C., Pralong, F. P., Veuthey, J., Baume, N., Rudaz, S. L., & Saugy, M. (2014) · Bioanalysis · doi:10.4155/bio.14.200 · Cited by 32 · see citing works
UDP-Glucuronosyltransferases in Conjugation of 5α- and 5β-Androstane Steroids
Sten, T., Kurkela, M. J., Kuuranne, T., Leinonen, A., & Finel, M. (2009) · Drug Metabolism and Disposition · doi:10.1124/dmd.109.029231 · Cited by 31 · see citing works
Thevis, M., Piper, T., Horning, S. R., et al. (2013) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.6648 · Cited by 29 · see citing works
Self-citationTräger, L. (1977) · Springer eBooks · doi:10.1007/978-3-642-66529-5 · Cited by 28 · see citing works
Piper, T., Thomas, A., Baume, N., Sobolevsky, T. G., Saugy, M., Rodchenkov, G. M., Schänzer, W., & Thevis, M. (2014) · Rapid Communications in Mass Spectrometry · doi:10.1002/rcm.6891 · Cited by 26 · see citing works
Self-citationDegradation of urine samples and its influence on the 13 C/ 12 C ratios of excreted steroids
Piper, T., Geyer, H., & Schänzer, W. (2010) · Drug Testing and Analysis · doi:10.1002/dta.219 · Cited by 26 · see citing works
Self-citationPiper, T., Schänzer, W., & Thevis, M. (2015) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2015.12.013 · Cited by 25 · see citing works
Self-citationComplementary stable carbon isotope ratio and amount of substance measurements in sports anti‐doping
Cawley, A., & George, A. V. (2012) · Drug Testing and Analysis · doi:10.1002/dta.1378 · Cited by 18 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Intracrine androgen biosynthesis, metabolism and action revisited
Schiffer, L., Arlt, W., & Storbeck, K.-H. (2018) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.08.016 · Cited by 217 · see citing works
“metabolite, probably at a hydroxyl functional group, and the demethylation to C19-nor-androgens (Piper et al., 2016).”
Piper, T., Dib, J., Putz, M., Fusshöller, G., Pop, V., Lagojda, A., Kuehne, D., Geyer, H., Schänzer, W., & Thevis, M. (2018) · Drug Testing and Analysis · doi:10.1002/dta.2527 · Cited by 23 · see citing works
Self-citation
- Authors
- Piper, T., Schänzer, W., & Thevis, M.
- Affiliations
- German Sport University Cologne (DE)
- Corresponding author
- Piper, Thomas
- Venue
- Drug Testing and Analysis
- Publisher
- Wiley
- Published
- 2016-10-13
- Volume
- 8
- Issue
- 11-12
- Pages
- 1163-1173
- ISSN
- 1942-7603 (ISSN-L)
- 1942-7611
- OpenAlex
- W2525002452
- Cited by
- 38
- References
- 33
- Citations by year
- 2024: 4 · 2023: 1 · 2022: 2 · 2021: 6 · 2020: 8 · 2019: 5 · 2018: 5 · 2017: 6 · 2016: 1
- FWCI
- 16.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drug Testing and Analysis (publishedVersion)
- PubMed (publishedVersion)
- Funders
- World Anti-Doping Agency
- Topics
- Social Sciences › Sociology and Political Science › Doping in Sports
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Pharmacological Effects and Assays
- Keywords
- glucuronidation, testosterone glucuronide, steroid metabolites, hydrogen isotope ratio, carbon isotope ratio, doping control, biomarkers, testosterone/epitestosterone ratio, methylation
- MeSH terms
- Carbon Isotopes, Doping in Sports, Genotype, Humans, Gas Chromatography-Mass Spectrometry, Mass Spectrometry, Testosterone, Biomarkers, Substance Abuse Detection
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
