Metabolism and excretion of anabolic steroids in doping control-New steroids and new insights

Journal of Steroid Biochemistry and Molecular Biology

Volumn 101, Issue 4-5, 2006, Pages 161-178

  Van Eenoo, Peter ^a   Delbeke, Frans T ^a  

^a GHENT UNIVERSITY   (Belgium)

Author keywords

Anabolic steroid; Doping; Metabolism; Prohormone; Sport

Indexed keywords

1 TESTOSTERONE; 3BETA ANDROSTANEDIOL; 4 HYDROXYTESTOSTERONE; ANABOLIC AGENT; ANDROSTANOLONE; ANDROSTENEDIOL; ANDROSTENEDIONE; BOLDIONE; DANAZOL; ESTR 4 ENE 3,17 DIONE; ETHYLESTRENOL; FORMESTANE; GESTRINONE; HORMONE PRECURSOR; HYDROXYSTEROID; LYNESTRENOL; NANDROLONE DERIVATIVE; NORBOLETONE; NORETHANDROLONE; NORETHISTERONE; NORSTEROID; OXABOLONE; OXOSTEROID; PRASTERONE; QUINBOLONE; STENBOLONE; STEROID HORMONE; TESTOLACTONE; TESTOSTERONE; TIBOLONE;

CHEMICAL STRUCTURE; CHROMATOGRAPHY; DOPING; DRUG MISUSE; KIDNEY CONCENTRATING CAPACITY; MASS SPECTROMETRY; NUCLEAR MAGNETIC RESONANCE; REVIEW; SPORT; STEROID ANALYSIS; STEROID EXCRETION; STEROID METABOLISM; STEROID RELEASE; URINALYSIS;

ANABOLIC AGENTS; ANDROGENS; BIOLOGICAL TRANSPORT; DOPING IN SPORTS; KETOSTEROIDS; MOLECULAR STRUCTURE; NORSTEROIDS; STEROIDS; SUBSTANCE ABUSE DETECTION; TESTOSTERONE;

EID: 33750032249     PISSN: 09600760     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jsbmb.2006.06.024     Document Type: Review

References (151)

1. Chen W.C., Thiboutot D., and Zouboulis C.C. Cutaneous androgen metabolism: basic research and clinical perspectives. J. Invest. Derm. 119 (2002) 992-1007
2. David K., Dingemanse E., Freud J., and Laqueur E. Über krystallinisches männliches Hormon aus Hoden (Testosteron) wirksamer als aus Harn oder Cholesterin bereites Androsteron. Z. Physiol. Chem. 233 (1935) 281-282
3. Butenandt A., and Hanisch G. Über testosterone. Umwandlung des Dehydro-Androsterons in Androstendiol und Testosteron; ein Weg zur Darstellung des Testosterons aus Cholesterin. Z. Physiol. Chem. 237 (1935) 89-97
4. Ruckzika L., Wettstein A., and Kaehgi H. Sexualhormone VIII Darstellung von Testosterone unter Anwendung gemischter Ester. Helv. Chim. Acta 18 (1935) 1478
5. Brown-Sequard C.E. The effects produced on man by subcutaneous injections of a liquid obtained from the testis of animals. Lancet 2 (1889) 105-107
6. Wade N.A. Anabolic steroids: doctors denounce them, but athletes aren't listening. Science 176 (1972) 1399
7. Delbeke F.T. From Amanita Muscaria to somatropine: the doping story. Biol. Sport 17 (2000) 81-86
8. Kicman A.T., and Gower D.B. Anabolic steroids in sport: biochemical, clinical and analytical perspectives. Ann. Clin. Biochem. 40 (2003) 321-356
9. Donike M., Bärwald K.R., Klostermann K., Schänzer W., and Zimmermann J. Nachweis von exogenem Testosteron. In: Heck H., Hollman W., Liesen H., and Rost R. (Eds). Sport: Leistung und Gesundheit (1983), Deutsche Ärzte Verlag, Köln 293-298
10. Donike M., Adamietz B., Opfermann G., Schänzer W., Zimmermann J., and Mandel F. Die Normbereiche für Testosteron- und Epitestosterone Urinspiegel sowie des Testosteron-/Epitestosteron-Quotienten. In: Franz I.W., Mellerowicz H., and Noack W. (Eds). Training und Sport zur Prävention und Rehabilitation in der technisierten Umwelt (1985), Springer Verlag, Berlin, Heidelberg 503-507
11. Donike M., Rauth S., and Wolansky A. Reference ranges of urinary endogenous steroids determined by gas chromatography/mass spectrometry. In: Donike M., Geyer H., Gotzmann A., Mareck-Engelke U., and Rauth S. (Eds). Proceedings of the 10th Cologne Workshop on Dope Analysis (1993), Sport und Buch Strauβ, Cologne, Germany 69-86
12. S. Rauth, Referenzbereiche von urinären Steroidkonzentrazionen und Steroidquotienten - Ein Beitrag zur Interpretation des Steroidprofils in der Routinedopinganalytik. Thesis Deutsche Sporthochschule Köln, 1994.
13. Oftebro H. Evaluating an abnormal urinary steroid profile. Lancet 339 (1992) 941-942
14. Kicman A.T., Oftebro H., Walker C., Norman N., and Cowan D.A. Potential use of ketoconazole endocrine test to differentiate between biological outliers and testosterone use by athletes. Clin. Chem. 39 (1993) 1798-1803
15. Franke W.W., and Berendonk B. Hormonal doping and androgenization of athletes: a secret program of the German Democratic Republic Government. Clin. Chem. 43 (1997) 1262-1279
16. United States Food & Drug Administration, Drug Supplement Health and Education Act, http://www.cfsan.fda.gov/-dms/dietsupp.html.
17. Anabolic Steroid Control Act P.L.N. 1990, XIX:104 Stat 4851, amended in 2004 as Anabolic Steroid Control Act of 2004. Section 102 of the Controlled Substances Act (21 U.S.C. 802).
18. Catlin D.H., Sekera M.H., Ahrens B.D., Starcevic B., Chang Y.-C., and Hatton C.K. Tetrahydrogestrinone: discovery, synthesis, and detection in urine. Rapid Commun. Mass Spectrom. 18 (2004) 1245-1249
19. World Anti-Doping Agency (WADA). Prohibited list of substances 2006. http://www.wada-ama.org/.
20. Schänzer W., and Donike M. Metabolism of anabolic steroids in man: synthesis and use of reference substances for identification of anabolic steroid metabolites. Anal. Chim. Acta 275 (1993) 23-48
21. Schänzer W. Metabolism of anabolic androgenic steroids. Clin. Chem. 42 (1996) 1001-1020
22. Saugy M., Cardis C., Robinson N., and Schweizer C. Test methods: anabolics. Best Pract. Res. Clin. Endoc. Metab. 14 (2000) 111-133
23. Wolthers B.G., and Kraan G.P.B. Clinical applications of gas chromatography and gas chromatography-mass sspectrometry of steroids. J. Chromatogr. A 843 (1999) 247-274
24. Ayotte C., Goudreault D., and Charlebois A. Testing for natural and synthetic anabolic agents in urine. J. Chromatogr. B 687 (1996) 3-25
25. Kazlauskas R. Effects of dehydroepiandrosterone on urinary steroids. In: Schänzer W., Geyer H., Gotzmann A., and Mareck-Engelke U. (Eds). Recent Advances in Doping Analysis (5) (1997), Sport und Buch Strauβ, Cologne, Germany 83-90
26. Bowers L. Oral dehydroepiandrosterone supplementation can increase the testosterone/epitestosterone ratio. Clin. Chem. 45 (1999) 295-297
27. Bosy T.Z., Moore K.A., and Poklis A. The effect of oral dehydroepiandrosterone on the urinary testosterone/epitestosterone (T/E) ratio in human male volunteers. J. Anal. Toxicol. 22 (1998) 455-459
28. Dehennin L., Ferry M., Lafarge P., Pérès G., and Lafarge J.-P. 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. Steroids 63 (1998) 80-87
29. Van Eenoo P., Delbeke F.T., Desmet N., and De Backer P. Excretion studies with 4-androstene-3 17-dione. In: Schänzer W., Geyer H., Gotzmann A., and Mareck-Engelke U. (Eds). Recent Advances in Doping Analysis (6) (1998), Sport und Buch Strauβ, Cologne, Germany 171-180
30. Garle M., and Palonek E. Androstenedione: excretion studies from single and multiple dose experiments. In: Schänzer W., Geyer H., Gotzmann A., and Mareck-Engelke U. (Eds). Recent Advances in Doping Analysis (6) (1998), Sport und Buch Strauβ, Cologne, Germany 181-184
31. Catlin D.H., Leder B.Z., Ahrens B., Starcevic B., Hatton C.K., Green G.A., and Finkelstein J.S. Trace contamination of over-the-counter androstenedione and positive urine test results for a nandrolone metabolite. JAMA 284 (2000) 2618-2621
32. Uralets V.P., and Gilette P.A. Over-the-counter anabolic steroids 4-androsten-3,17-dione; 4-androsten-3beta,17beta-diol; and 19-nor-4-androsten-3. 17-dione: excretion studies in men. J. Anal. Toxicol. 23 (1999) 357-366
33. Uralets V.P., and Gilette P.A. Over-the-counter anabolic delta5 anabolic steroids 5-androsten-3,17-dione; 5-androsten-3beta,17beta-diol; dehydroepiandrosterone and 19-nor-5-androsten-3. 17-dione: excretion studies in men. J. Anal. Toxicol. 24 (2000) 188-193
34. Geyer H., Schänzer W., Schindler U., and Donike M. Changes of the urinary steroid profile after sublingual application of dihydrotestosterone. In: Donike M., Geyer H., Gotzmann A., and Mareck-Engelke U. (Eds). Recent Advances in Doping Analysis (3) (1995), Sport und Buch Strauβ, Cologne, Germany 215-229
35. 3]-5α-dihydrotestosterone. In: Donike M., Geyer H., Gotzmann A., and Mareck-Engelke U. (Eds). Recent Advances in Doping Analysis (3) (1995), Sport und Buch Strauβ, Cologne, Germany 201-213
36. Southan G.J., Brooks R.V., Cowan D.A., Kicman A.T., Unnadkat N., and Walker C.J. Possible indices for the detection of the administration of dihydrotestosterone to athletes. Steroid Biochem. Mol. Biol. 42 (1992) 87-94
37. Kicman A.T., Coutts S.B., Walker C.J., and Cowan D.A. Proposed confirmatory procedure for detecting 5α-dihydrotestosterone doping in male athletes. Clin. Chem. 41 (1995) 1617-1627
38. Lévesque J.F., and Ayotte C. Criteria for the detection of androstenedione oral administration. In: Schänzer W., Geyer H., Gotzmann A., and Mareck-Engelke U. (Eds). Recent Advances in Doping Analysis (7) (1999), Sport und Buch Strauβ, Cologne, Germany 169-179
39. Lévesque J.F., Gaudreault M., Houle R., and Chauret N. Evaluation of human hepatocyte incubation as a new tool for metabolism study of androstenedione and norandrostenedione in a doping control perspective. J. Chromatogr. B 780 (2002) 145-153
40. D.H. van de Kerkhof. Steroid profiling in doping analysis. PhD-thesis, Utrecht University, 2001. 237.
41. Catlin D.H., Leder B.Z., Ahrens B.D., Hatton C.K., and Finkelstein J.S. Effects of androstenedione administration on epitestosterone metabolism in men. Steroids 67 (2002) 559-564
42. Goudreault D., Bhérer P., Lévesque J.F., Poirier D., and Ayotte C. Androstenedione metabolism: end of story. In: Schänzer W., Geyer H., Gotzmann A., and Mareck-Engelke U. (Eds). Recent Advances in Doping Analysis (9) (2001), Sport und Buch Strauβ, Cologne, Germany 73-83
43. In: Parr M.K., Geyer H., Reihart U., and Schänzer W. (Eds). Analytical strategies for the detection of non-labeled anabolic androgenic steroids in nutritional supplements 7 (2004), Food Addit. Contam. 632-640
44. Uralets V.P., and Gilette P.A. New anabolic steroids available as nutritional supplements: 5α-androstan-3β,17β-diol, 1,4-androstadien-3,17-dione and 5α-androst-1-en-17β-ol-3-one. In: Schänzer W., Geyer H., Gotzmann A., and Mareck U. (Eds). Recent Advances in Doping Analysis (10) (2002), Sport und Buch Strauss, Cologne, Germany 73-82
45. Briggs M.H., and Brotherton J. Steroid Biochemistry and Pharmacology (1970), Academic Press Inc., London p. 424
46. de la Torre R., de la Torre X., Alia C., Segura J., Baro T., and Torres-Rodriguez J.M. Changes in androgenic steroid profile due to urine contamination: a prospective study in the context of doping control. Anal. Biochem. 289 (2001) 116-123
47. W. Van Thuyne, F.T. Delbeke. (2006), personal communication.
48. Tóth M., and Zakár T. Relative binding affinities of testosterone. 19-Nortestosterone and their 5a-reduced derivatives to the androgen receptor and to other androgen-binding proteins: a suggested role of 5a-reductive steroid metabolism in the dissociation of "myotropic" and "androgenic" activities of 19-nortestosterone. J. Steroid Biochem. 17 (1982) 653-660
49. Potts GO.., Arnold A., and Beyler A.L. Dissociation of the androgenic and other hormonal activities from the protein anabolic effects of steroids. In: Kochakian D. (Ed). Anabolic-Androgenic Steroids (1976), Springer-Verlag Berlin, Heidelberg 361-406
50. Nandrolone progress report to the UK Sports Council from the expert committee on nandrolone. Int. J. Sports Med. 24 (2003) 620-626
51. Engel L.L., Alexander J., and Wheeler M. Urinary metabolites of administered 19-nortestosterone. J. Biol. Chem. 231 (1958) 159-165
52. Van Eenoo P., Delbeke F.T., de Jong F.H., and De Backer P. Urinary metabolites of endogenous nandrolone in women: a case study. In: Schänzer W., Geyer H., Gotzmann A., and Mareck-Engelke U. (Eds). Recent Advances in Doping Analysis (6). (1998), Sport und Buch Strauss, Cologne, Germany 105-117
53. Van Eenoo P., Delbeke F.T., de Jong F.H., and De Backer P. Endogenous origin of norandrosterone in female urine: indirect evidence for the production of 19-norsteroids as by-products in the conversion from androgen to estrogen. J. Steroid Biochem. Mol. Biol. 78 (2001) 351-357
54. Le Bizec B., Bryand F., Gausin I., Monteau F., Poulain F., and Andre F. Endogenous nandrolone metabolites in human urine: preliminary results to discriminate between endogenous and exogenous origin. Steroids 67 (2002) 105-110
55. Mareck-Engelke U., Schultze G., Geyer H., and Schänzer W. The appearance of urinary 19-norandrosterone during pregnancy. Eur. J. Sports Sci. 2 (2002) 1-7
56. Le Bizec B., Bryand F., Gausin I., Monteau F., Poulain F., and Andre F. Endogenous nandrolone metabolites in human urine, two-year monitoring of male professional. J. Anal. Toxicol. 26 (2002) 43-47
57. Hemmersbach P., Hågensen A.H., and Misund J. Determination of urinary norandrosterone excretion in females during one menstrual cycle by gas chromatography/mass spectrometry. In: Schänzer W., Geyer H., Gotzmann A., and Mareck-Engelke U. (Eds). Recent Advances in Doping Analysis (8) (2000), Sport und Buch Strauβ, Cologne, Germany 141-144
58. Grosse J., Anielski A., Hemmersbach P., Lund H., Müller K., Rautenberg C., and Thieme D. Formation of 19-norsteroids by in situ demethylation of endogenous steroids in stored urine samples. Steroids 70 (2005) 499-506
59. World Anti-Doping Agency. WADA Technical Document TD2004NA. Reporting Norandrosterone findings. Version 1.0. http://www.wada-ama.org/rtecontent/document/nandrolone_aug_04.pdf.
60. Schänzer W., Breidbach A., Geyer H., van Kuk C., Nolteernsting E., and Thevis M. Metabolism of nortestosterone, norandrostenedione and norandrostenediol. Identification of 3α-hydroxy-estr-4-en-17-one glucuronide and 3α,16α-dihydroxy-5α-estran-17-one glucuronide and sulphate. In: Schänzer W., Geyer H., Gotzmann A., and Mareck-Engelke U. (Eds). Recent Advances in Doping Analysis (8) (2000), Sport und Buch Strauβ, Cologne, Germany 155-175
61. Colker C.M., Antonio J., and Kalman D. The metabolism of orally ingested 19-nor-4-androstene-3,17-dione and 19-nor-4-androstene-3,17-diol in healthy, resistance-trained men. J. Strength Cond. Res. 15 (2001) 144-147
62. Thieme D., Anielski P., Grosse J., Sachs H., and Mueller K. Identification of anabolic steroids in serum, urine, sweat and hair. Comparison of metabolic patterns. Anal. Chim. Acta 483 (2003) 299-306
63. Tseng Y.L., Kuo F.H., and Sun K.H. Quantification and profiling of 19-norandrosterone and 19-noretiocholanolone in human urine after consumption of a nutritional supplement and norsteroids. J. Anal. Toxicol. 29 (2005) 1-11
64. Baume N., Mahler N., Kamber M., Mangin P., and Saugy M. Research of stimulants and anabolic steroids in dietary supplements. Scand. J. Med. Sci. Sports 16 (2006) 41-48
65. Lévesque J.F., Gaudreault M., Aubin Y., and Chauret N. Discovery, biosynthesis, and structure elucidation of new metabolites of norandrostenedione using in vitro systems. Steroids 70 (2005) 305-317
66. Brooks C.J.W., Thawley A.R., Rocher P., Middleditch B.S., Anthony G.M., and Stillwell W.G. Characterization of steroidal drug metabolites by combined gas chromatography-mass spectrometry. J. Chromatogr. Sci. 9 (1971) 35-43
67. Ward R.J., Lawson M.A., and Schackleton C.H.L. Metabolism of anabolic steroid drugs in man and the marmoset monkey (Callithrix Jacchus)- I Nilevar and Orabolin. J. Steroid Biochem. 8 (1977) 1057-1063
68. Ward R.J., Schackleton C.H.L., and Lawson M.A. Gas chromatographic-mass spectrometric methods for the detection and identification of anabolic steroid drugs. Br. J. Sports Med. 9 (1975) 93-97
69. P. Mikulcikova, P. Van Eenoo, W. Van Thuyne, F.T. Delbeke. unpublished results.
70. Schindler A.E., Campagnoli C., Druckmann R., Huber J., Pasqualini J.R., Schweppe K.W., and Thijssen J.H.H. Classification and pharmacology of progestins. Maturitas 46S1 (2003) S7-S16
71. De Boer D., de Jong E., Maes R.A.A., and van Rossum J.M. The problems of oral contraceptives in dope control of anabolic steroids. Biomed. Environ. Mass Spectrom. 17 (1988) 127-128
72. Pommier F., Sioufi A., and Godbillon J. Simultaneous determination of norethisterone and six metabolites in human plasma by capillary gas chromatography with mass-selective detection. J. Chromatogr. B 674 (1995) 155-165
73. Mareck-Engelke U., Geyer H., and Schänzer W. 19-Norandrosterone-criteria for the decision making process. In: Schänzer W., Geyer H., Gotzmann A., and Mareck-Engelke U. (Eds). Recent Advances in Doping Analysis (6) (1998), Sport und Buch Strauβ, Cologne, Germany 119-129
74. Cook C.E., and Kepler J.A. 7α 11β-Dimethyl-19-nortestosterone: a potent and selective androgen response modulator with prostate-sparing properties. Bioorg. Med. Chem. Lett. 15 (2005) 1213-1216
75. Segaloff A. The enhanced local androgenic activity of 19-norsteroids and stabilization of their structure by 7α- and 17α-methyl substituents to highly potent androgens by any route of administration. Steroids 1 (1963) 299-315
76. Kumar N., Crozat A., Li F., Caterall J.F., Bardin C.W., and Sundaram K. 7α-Methyl-19-nortestosterone, a synthetic androgen with high potency: structure-activity comparisons with other androgens. J. Steroid Biochem. Mol. Biol. 71 (1999) 213-222
77. Von Eckardstein S., Noe G., Brache V., Nieschlag E., Croxtto H., Alvarez F., Moo-Young A., Sivin I., Kumar N., Small M., and Sundaram K. A Clinical trial of 7α-methyl-19-nortestosterone implants for possible use as a long-acting contraceptive for men. J. Clin. Endocrinol. Metab. 88 (2003) 5232-5239
78. Kazlauskas R. Miscellaneous projects for 2003. In: Schänzer W., Geyer H., Gotzmann A., and Mareck U. (Eds). Recent Advances in Doping Analysis (12) (2004), Sport und Buch Strauβ, Cologne, Germany 261-268
79. World Anti-Doping Agency (WADA). Prohibited list of substances 2005. http://www.wada-ama.org/.
80. Timmer C.J., Verheul H.A.M., and Doorstam D.P. Pharmacokinetics of tibolone in early and late postmenopausal women. Br. J. Clin. Pharmacol. 54 (2002) 101-106
81. Vos R.M.E., Krebbers S.F.M., Verhoeven C.H.J., and Delbressine L.P.C. The in vivo human metabolism of tibolone. Drug Metab. Dispos. 30 (2002) 106-112
82. Purohit A., Malini B., Hooymans C., and Newman S.P. Inhibition of sulphatase activity by tibolone and its metabolites. Horm. Metab. Res. 34 (2002) 1-6
83. Sipoli Marques M.A., Gualberto Pereira H.M., and de Oliveira M.C. Validation of the determination of tibolone in human urine and saliva using GC-MS for doping control and clinical studies. In: Schänzer W., Geyer H., Gotzmann A., and Mareck U. (Eds). Recent Advances in Doping Analysis (12) (2004), Sport und Buch Strauβ, Cologne, Germany 403-406
84. MacNeill F.A., Jacobs S., Dowsett M., Lønning P.E., and Powles T.J. The effects of oral 4-hydroxyandrostenedione on peripheral aromatisation in post-menopausal breast cancer patients. Cancer Chemother. Pharmacol. 36 (1995) 249-254
85. Brodie A.M.H., and Njar V.C.O. Aromatase inhibitors in advanced breast cancer: mechanism of action and clinical implications. J. Steroid Biochem. Mol. Biol. 66 (1998) 1-10
86. Poon G.K., Jarman M., Rowlands M.G., Dowsett M., and Firth J. Determination of 4-hydroxyandrost-4-ene-3, 17-dione metabolism in breast cancer patients using high-performance liquid chromatography-mass spectrometry. J. Chromatogr. Biomed. Appl. 565 (1991) 75-88
87. Poon G.K., Jarman M., McCague R., Davies J.H., Heeremans C.E.M., van der Hoeven R.A.M., Niessen W.M.A., and Van der Greef J. Identification of 4-hydroxyandrost-4-ene-3, 17-dione metabolites in prostatic cancer patients by liquid chromatography-mass spectrometry. J. Chromatogr. Biomed. Appl. 576 (1992) 235-244
88. Lønning P.E., Geisler J., Johannessen D.C., Gschwind H.-P., Waldmeier F., Schneider W., Galli B., Winkler T., Blum W., Kriemler H.-P., Miller W.R., and Faigle J.W. Pharmacokinetics and metabolism of formestane in breast cancer patients. J. Steroid Biochem. Mol. Biol. 77 (2001) 39-47
89. Parr M.K., Opfermann G., and Schänzer W. Analytical properties of 4-hydroxysteroids and some esters. In: Schänzer W., Geyer H., Gotzmann A., and Mareck U. (Eds). Recent Advances in Doping Analysis (12) (2004), Sport und Buch Strauβ, Cologne, Germany 129-138
90. Covey D.F., and Hood W.F. Enzyme-generated intermediates from androst-4-ene-3,6,17-trione and 1,4, 6-androstatriene cause a time-dependent decrease in human placental aromatase activity. Endocrinology 108 (1981) 1597-1599
91. Numazawa M., Tsuji M., and Mitumi A. Studies on aromatase inhibition with androst-4-ene-3,6, 17-trione: its 3β-reduction and time-dependent irreversible binding to aromatase with human placental microsomes. J. Steroid Biochem. 28 (1987) 337-344
92. Numazawa M., Mitumi A., and Tachibana M. Mechanism for aromatase inactivation by a suicide substrate, androst-4-ene-3,6, 17-trione. Biochem. Pharmacol. 52 (1996) 1253-1259
93. Deventer K., Van Eenoo P., Mikulcikova P., Van Thuyne W., and Delbeke F.T. Quantitative analysis of androst-4-ene-3,6, 17-trione and metabolites in human urine after administration of a food supplement by liquid chromatography/ion trap-mass spectrometry. J. Chromatogr. B. 828 (2005) 21-28
94. ®) and its metabolites in urine by gas chromatography-mass spectrometry in relation to doping analysis. Biomed. Chromatogr. 19 (2005) 689-695
95. P. Van Eenoo, P. Mikulcikova, K. Deventer, W. Van Thuyne, F.T. Delbeke. Metabolism, excretion and detection of androst-4-ene-3,6,17-trione, In: W. Schänzer, H. Geyer, A. Gotzmann, U. Mareck (Eds.), Recent Advances in Doping Analysis (13). Sport und Buch Strauβ, Cologne, Germany, 2005.
96. Faredin I., Fazekas A., Toth I., Kokai K., and Julesz M. Transformation in vitro of [4-C14]-dehydroepiandrosterone into 7-oxygenated derivatives by normal human male and female skin. J. Invest. Derm. 52 (1969) 357-361
97. Doostzadeh J., Cotillon A.-C., Benalychérif A., and Morfin R. Inhibition studies of dehydroepiandrosterone 7α- and 7β-hydroxylation in mouse liver microsomes. Steroids 63 (1998) 608-614
98. Fukushima D.K., Kemp A.D., Schneider R., Stokem M.B., and Gallagher T.F. Steroid metabolism XXV. Isolation and characterization of new urinary steroids. J. Biol. Chem. 210 (1954) 129-137
99. Van Eenoo P., Delbeke F.T., Desmet N., and De Backer P. Excretion studies with 7-keto-dehydroepiandrosterone. In: Schänzer W., Geyer H., Gotzmann A., and Mareck U. (Eds). Recent Advances in Doping Analysis (9) (2001), Sport und Buch Strauβ, Cologne, Germany 91-98
100. Delbeke F.T., Van Eenoo P., and Van Thuyne W. Prohormones and sports. J. Steroid Biochem. Mol. Biol. 83 (2003) 245-251
101. Sala G. Biological properties of 4-hydroxy-3-keto-Δ4-steroids. In: Martini L., and Pecile A. (Eds). Hormonal Steroids vol. I (1964), Academic Press, New York 67-75
102. Grosse J., Lang R., Müller R.K., Thieme D., and Wahl A. Appearance of an oxabolone metabolite after administration of OTC 19-norsteroids-metabolite or artefact. In: Schänzer W., Geyer H., Gotzmann A., and Mareck-Engelke U. (Eds). Recent Advances in Doping Analysis (8) (2000), Sport und Buch Strauβ, Cologne, Germany 227-232
103. Barbarulo M.V., Buiarelli F., Ciardi M., Giarrusso A., and Rosati F. Capillary GC-MS investigation of the metabolism and excretion of oxabolone in man. J. High Resolut. Chromatogr. 18 (1995) 705-708
104. Counsell R.E., Klimstra P.D., and Colton F.B. Anabolic agents. Derivatives of 5α-androst-1-ene. J. Org. Chem. 27 (1962) 248-253
105. Galetti F., and Gardi R. Metabolism of 1-dehydroandrostanes in man. I. Metabolism of 17β-hydroxyandrosta-1,4-dien-3-one (quinbolone) and androsta-1,4-diene-3,17-dione. Steroids 18 (1971) 39-50
106. Schänzer W., and Donike M. Metabolism of boldenone in man: gas chromatographic-mass spectrometric identification of urinary excreted metabolite and determination of excretion rates. Biol. Mass Spectrom. 21 (1992) 3-16
107. World Anti-Doping Agency. 2004 adverse analytical findings reported by laboratories. http://www.wada-ama.org/.
108. Goudreault D., and Massé R. Studies on anabolic steroids - 6, Identification of urinary metabolites of stenbolone acetate (17β-acetoxy-2-methyl-5α-androst-1-en-3-one) in human by gas chromatography/mass spectrometry. J. Steroid Biochem. Mol. Biol. 38 (1991) 639-655
109. Goudreault D., and Massé R. Studies on anabolic steroids-11. 18-Hydroxylated metabolites of mesterolone, methenolone and stenbolone: new steroids isolated fom human urine. J. Steroid Biochem. Mol. Biol. 42 (1992) 399-410
110. Goudreault D., and Ayotte A. Investigation of mesterolone urinary metabolites by GC/MS. In: Donike M., Geyer H., Gotzmann A., and Mareck U. (Eds). Recent Advances in Doping Analysis (3) (1996), Sport und Buch Strauss, Cologne, Germany 55-80
111. Van Puymbroeck M., Kuilman M.E.M., Maas R.F.M., Witkamp R.F., Leysens L., Vanderzand D., Gelan J., and Raus J. In vitro models are important tools to monitor the abuse of anabolic steroids in cattle. Analyst 123 (1998) 2453-2456
112. De Brabander H.F., Poelmans S., Schilt R., Stephany R.W., Le Bizec B., Draisci R., Sterk S.S., van Ginkel L.A., Courtheyn D., Van Hoof N., Macri A., and De Wasch K. Presence and metabolism of the anabolic steroid boldenone in various animal species: a review. Food addit. Contam. 21 (2004) 515-525
113. Kim Y., Jun M., and Lee W. Characterization of boldione and its metabolites in human urine by liquid chromatography/electrospray ionization mass spectrometry and gas chromatography/mass spectrometry. Rapid Commun. Mass Spectrom. 20 (2006) 9-20
114. Van Eenoo P., Desmet N., and Delbeke F.T. Excretion studies with a supplement containing 5α-androst-1-ene-3β,17β-diol. In: Schänzer W., Geyer H., Gotzmann A., and Mareck U. (Eds). Recent Advances in Doping Analysis (10) (2002), Sport und Buch Strauss, Cologne, Germany 61-71
115. Reilly C.A., and Crouch D.J. Analysis of the nutritional supplement 1AD, its metabolites, and related endogenous hormones in biological matrices using liquid chromatography-tandem mass spectrometry. J. Anal. Toxicol. 28 (2004) 1-10
116. Yinong Z., Xin L., Jinghzu W., and Huyue Z. Analytical data of 1-testosterone and the preliminary results of excretion study with 1-testosterone. In: Schänzer W., Geyer H., Gotzmann A., and Mareck U. (Eds). Recent Advances in Doping Analysis (12) (2004), Sport und Buch Strauss, Cologne, Germany 81-90
117. The International Olympic Committee. List of prohibited substances, 1998.
118. Raman J., and Schlegel P.N. Aromatase inhibitors for male infertility. J. Urol. 167 (2002) 624-629
119. Braunstein G.D. Aromatase and gynecomastia. Endocr. Relat. cancer 6 (1999) 315-324
120. Pascucci V.L., Yeager R.L., Sherins R.J., Clark R.V., Gallelli J.F., and Chatterji D.C. Quantitation of testolactone and 4, 5-dihydrotestolactone in plasma and urine using high-performance liquid chromatography. J. Chromatogr. 14 (1983) 79-85
121. Yeager R.L., Pascucci V.L., Chatterji D.C., and Mico B.A. 4, 5-Beta-dihydrotestolactone- metabolite identification with the aid of the attached proton test in C-13 NMR. Drug Metab. Dispos. 13 (1985) 107-109
122. Vitoriano B., de Boer D., Manzoni C., Ajenjo A., and dos Reys L.J.A.L. Preliminary results of the implementation of some metabolites of the anabolic androgenic testolactone in screening procedures. In: Schänzer W., Geyer H., Gotzmann A., and Mareck-Engelke U. (Eds). Recent Advances in Doping Analysis (7) (1999), Sport und Buch Strauss, Cologne, Germany 153-159
123. Catlin D.H., Ahrens B.D., and Kucherova Y. Detection of norbolethone an anabolic steroid never market in athletes urine. Rapid Commun. Mass Spectrom. 16 (2002) 1273-1275
124. Thevis M., Bommerich U., Opfermann G., and Schänzer W. Characterization of chemically modified steroids for doping control purposes by electrospray ionization tandem mass spectrometry. J. Mass Spectrom. 40 (2005) 494-502
125. Catlin D.H., Sekera M.H., Ahrens B.D., Starcevic B., Chang Y.-C., and Hatton C.K. Discovery and detection of a designer steroid. In: Schänzer W., Geyer H., Gotzmann A., and Mareck U. (Eds). Recent Advances in Doping Analysis (12) (2004), Sport und Buch Strauss 139-140
126. Sekera M.H., Ahrens B.D., Chang Y.-C., Starcevic B., Georgakopoulos C., and Catlin D.H. Another designer steroid: discovery, synthesis, and detection of 'madol' in urine. Rapid Commun. Mass Spectrom. 19 (2005) 781-784
127. Tomarelli H.H., and Bernhart F.W. Oral anabolic ativity of (±)-13β, 17α-diethyl-7β-hydroxy-gon-4-en-3-one (norbolethone) in a nitrogen retention assay. Steroids 4 (1964) 451-456
128. Edgren R.A., and Smith H. Wy 3475, a new potent orally active anabolic agent. In: Martini L., and Pecile A. (Eds). Hormonal Steroids (2) (1965), Academic Press, New York 161-171
129. Edgren R.A. A comparative study of the anabolic and androgenic effects of various steroids. Acta Endocr. 44 (1963) 3-21
130. Buzby G.C., Walk C.R., and Smith H. Totally synthetic steroid hormones, X. Some (±)-13-β-ethyl-7α-methyl-gonane derivatives. J. Med. Chem. 9 (1966) 782-784
131. Strike D.P., Herbst D., and Smith H. Totally synthetic hormones, XVI. The conversion of est-4-en-17β-ol to testosterone and the synthesis of some 18-methyl pregnane derivatives. J. Med. Chem. 10 (1967) 446-451
132. Jasjua R., Catlin D.H., Miller A., Chang Y.-C., Herbst K.L., Starcevic B., Artaza J.N., Singh R., Datta G., Sarkissian A., Chandsawangbhuwana Baker M., and Bhasin S. Tetrahydrogestrinone is an anabolic steroid that stimulates androgen receptor-mediated, myogenic differentiation in C3H10T1/2 multipotent mesenchymal cells and promotes muscle accretion in orchiectomized male rats. Endocrinology 46 (2005) 4472-4478
133. Death A.K., McGrath K.C.Y., Kazlauskaz R., and Handelsman D.J. Tetrahydrogestrinone is a potent androgen and progestin. J. Clin. Endocrinol. Metab. 89 (2004) 2498-2500
134. A. Friedel, H. Geyer, M. Kamber, U. Laudenbach-Lechowsky, W. Schänzer, M. Thevis, G. Vollmer, O. Zierau, P. Diel. Tetrahydrogestrinone is a potent but unselective binding steroid and affects glucocorticoid signaling in the liver. Toxicol. Lett., in press, published online.
135. Karpesiuk W., Lehner A.F., Hughes C.G., and Tobin T. Preparation and chromatographic characterisation of tetrahydrogestrinone a new "designer" anabolic steroid. Chromatographia 60 (2004) 359-363
136. Knight J. Drugs bust reveals athletes' secret steroid. Nature 425 (2003) 752
137. Vogel G. A race to the starting line. Science 305 (2004) 632-635
138. Knight J. No dope. Nature 426 (2003) 114-115
139. Lévesque J.F., Templeton E., Trimble L., Berthelette C., and Chauret N. Discovery, biosynthesis, and structure elucidation of metabolites of a doping agent and a direct analogue, tetrahydrogetsrinone and gestrinone, using human hepatocytes. Anal. Chem. 77 (2005) 3164-3172
140. WADA press conference, February 1st 2005, entitled: WADA announces discovery of a new designer steroid, http://www.wada-ama.org/en/newsarticle.ch2?articleId=3115089, consulted on October 25th 2005.
141. Tsivou M., Kioukia-Fougia N., Lyris E., Aggelis Y., Fraagkaki A., Kiousi X., Simitsek Ph., Dimopoulou H., Leontiou I.-P., Stamou M., Spyridaki M.-H., and Georgakopoulos C. An overview of the doping control analysis during the Olympic Games of 2004 in Athens, Greece. Anal. Chim. Acta 555 (2005) 1-13
142. A. Shipley. Chemists stay a step ahead of drug testers. The Washington Post, October 18th 2005.
143. Spooner J.B. Classification of side-effects to danazol therapy. J. Int. Med. Res. 55 S5 (1979) 40-43
144. De Boer D., de Jong E.G., and Maes R.A.A. The detection of danazol and its significance in doping analysis. J. Anal. Toxicol. 16 (1992) 14-18
145. Chrostowski K., Kwiatkowska D., Partyka E., and Wojcikowska-Wojcik B. Danazol detection in doping analysis in urine. In: Schänzer W., Geyer H., Gotzmann A., and Mareck-Engelke U. (Eds). Recent Advances in Doping Analysis (6) (1998), Sport und Buch Strauss, Cologne, Germany 53-64
146. Montes de Oca R., Rodriguez A., Martinez D., and Correa T. Excretion study with danazol. New metabolites proposed for doping control. In: Schänzer W., Geyer H., Gotzmann A., and Mareck U. (Eds). Recent Advances in Doping Analysis (12) (2004), Sport und Buch Strauss, Cologne, Germany 389-393
147. Montes de Oca R., Rodriguez Fernandez A., Martinez Brito D., Correa Vidal T., and Lopez Diaz A. Gas chromatography/mass spectrometry characterization of urinary metabolites of danazol after oral administration in human. J. Chromatogr. B 830 (2006) 178-183
148. Kim Y., Lee Y., Kim M., Kim Y.-H., and Lee W. Determination and excretion study of gestrinone in human urine by high performance liquid chromatography/mass spectrometry. Rapid Commun. Mass Spectrom. 14 (2000) 1293-1300
149. Kim Y., Lee Y., Kim M., Kim Y.-H., and Lee W. Determination of the metabolites of gestrinone in human urine by high performance liquid chromatography/mass spectrometry and gas chromatography/mass spectrometry. Rapid Commun. Mass Spectrom. 14 (2000) 1717-1726
150. Salmon J., Cousty C., and Mouren M. Gestrinone pharmacokinetics and metabolism. In: Raynaud J.P. (Ed). Medical Managagement of Endomitriosis (1984), Raven Press, New York 193-205
151. Shipley A. Steroids detected in dietary tablets. The Washington Post, November 30th 2005.