Trace Contamination of Over-the-Counter Androstenedione and Positive Urine Test Results for a Nandrolone Metabolite | Urology | JAMA | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 18.204.227.34. Please contact the publisher to request reinstatement.
1.
 Herbal treatments: the promises and pitfalls.  Consumer Reports.1999;64:44-48.Google Scholar
2.
Zorpette G. Sports supplements: bigger muscles without the acne.  Scientific American Presents.1999;10:52.Google Scholar
3.
 Dietary Supplement Health and Education Act of 1994. Pub L No. 103-417, 1994. 103rd Congress, 2nd sess, S784.
4.
Angell M, Kassirer JP. Alternative medicine: the risks of untested and unregulated remedies.  N Engl J Med.1998;339:839-841.Google Scholar
5.
Catlin DH, Murray TH. Performance-enhancing drugs, fair competition, and Olympic sport.  JAMA.1996;276:231-237.Google Scholar
6.
Uralets VP, Gillette PA. 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.1999;23:357-366.Google Scholar
7.
Dehennin L, Bonnaire Y, Plou PH. Urinary excretion of 19-norandrosterone of endogenous origin in man: quantitative analysis by gas chromatography-mass spectrometry.  J Chromatogr B Biomed Sci Appl.1999;721:301-307.Google Scholar
8.
Le Bizec B, Monteau F, Gaudin I, Andrae F. Evidence for the presence of endogenous 19-norandrosterone in human urine.  J Chromatogr B Biomed Sci Appl.1999;723:157-172.Google Scholar
9.
Leder BZ, Longcope C, Catlin DH, Ahrens B, Schoenfeld DA, Finkelstein JS. Oral androstenedione administration and serum testosterone concentrations in young men.  JAMA.2000;283:779-782.Google Scholar
10.
Catlin DH, Kammerer RC, Hatton CK, Sekera MH, Merdink JM. Analytical chemistry at the Games of the XXIIIrd Olympiad in Los Angeles, 1984.  Clin Chem.1987;33:319-327.Google Scholar
11.
Fishman J. Biochemical mechanism of aromatization.  Cancer Res.1982;42(8 suppl):3277s-3280s.Google Scholar
12.
Dehennin L, Jondet M, Scholler R. Androgen and 19-norsteroid profiles in human preovulatory follicles from stimulated cycles: an isotope dilution-mass spectrometric study.  J Steroid Biochem.1987;26:399-405.Google Scholar
13.
Reznik Y, Herrou M, Dehennin L, Lemaire M, Leymarie P. Rising plasma levels of 19-nortestosterone throughout pregnancy: determination by radioimmunoassay and validation by gas chromatography-mass spectrometry.  J Clin Endocrinol Metab.1987;64:1086-1088.Google Scholar
14.
Ciardi M, Ciccioli R, Barbarulo MV, Nicoletti R. Presence of norandrosterone in "normal" urine samples. In: Schänzer W, Geyer H, Gotzmann A, Mareck-Engelke U, eds. Recent Advances in Doping Analysis. Köln, Germany: Sport & Buch Strauss; 1999:97-104.
15.
US Department of Health and Human Services.  Guidance for Industry ANDAs: Impurities in Drug Substances. Washington, DC: US Dept of Health and Human Services, Food and Drug Administration; 1999.
16.
 United States Pharmacopoeia DI 2000, Micromedex, Vol III . Englewood, Colo: The United States Pharmacopoeial Convention Inc; 1998.
17.
Coppen JJW. Steroids: from plants to pills: the changing picture.  Trop Sci.1979;21:125-141.Google Scholar
18.
Merkli A, Christen P, Kapetanidis I. Production of diosgenin by hairy root culture of Trigonella foenum-graecum L.  Plant Cell Rep.1997;16:632-636.Google Scholar
Clinical Investigation
November 22/29, 2000

Trace Contamination of Over-the-Counter Androstenedione and Positive Urine Test Results for a Nandrolone Metabolite

Author Affiliations

Author Affiliations: Departments of Molecular and Medical Pharmacology (UCLA Olympic Analytical Laboratory) (Drs Catlin and Hatton and Messrs Ahrens and Starcevic), Medicine (Dr Catlin), and Family Medicine (Dr Green), University of California, Los Angeles; and Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston (Drs Leder and Finkelstein).

JAMA. 2000;284(20):2618-2621. doi:10.1001/jama.284.20.2618
Abstract

Context Several anabolic steroids are sold over-the-counter (OTC) in the United States, and their production is not regulated by the US Food and Drug Administration. Reports have suggested that use of these supplements can cause positive urine test results for metabolites of the prohibited steroid nandrolone.

Objectives To assess the content and purity of OTC androstenedione and to determine if androstenedione and 19-norandrostenedione administration causes positive urine test results for 19-norandrosterone, a nandrolone metabolite.

Design Randomized controlled trial of androstenedione, open-label trial of 19-norandrostenedione, and mass spectrometry of androstenedione preparations, conducted between October 1998 and April 2000.

Setting Outpatient facility of a university hospital.

Participants A total of 41 healthy men aged 20 to 44 years.

Intervention Participants were randomly assigned to receive oral androstenedione, 100 mg/d (n = 13) or 300 mg/d (n = 11) for 7 days, or no androstenedione (n = 13); in addition, 4 patients received 10 µg of 19-norandrostenedione.

Main Outcome Measures Content of OTC androstenedione preparations; level of 19-norandrosterone in urine samples, determined by mass spectrometry, compared among the 3 randomized groups at day 1 and day 7, and among the participants who received 19-norandrostenedione from October 1998 to April 2000.

Results All urine samples from participants treated with androstenedione contained 19-norandrosterone, while no samples from the no-androstenedione group did. Urinary concentrations were averaged for day 1 vs day 7 measurements; mean (SD) 19-norandrosterone concentrations in the 100-mg/d and 300-mg/d groups were 3.8 (2.5) ng/mL and 10.2 (6.9) ng/mL, respectively (P = .006). The 19-norandrosterone content exceeded the cutoff for reporting positive cases (>2.0 ng/mL) in 20 of 24. The androstenedione preparation used was pure at a sensitivity of 0.1%, but at 0.001% 19-norandrostenedione was found. For the 4 participants to whom 10 µg of 19-norandrostenedione was administered, 19-norandrosterone was found in all urine samples. Of 7 brands of androstenedione analyzed at the 1% level, 1 contained no androstenedione, 1 contained 10 mg of testosterone, and 4 more contained 90% or less of the amount stated on the label.

Conclusion Our study suggests that trace contamination of androstenedione with 19-norandrostenedione is sufficient to cause urine test results positive for 19-norandrosterone, the standard marker for nandrolone use. Oral steroid doses as small as 10 µg are absorbed and excreted in urine. Some brands of androstenedione are grossly mislabeled. Careful analysis of androstenedione preparations is recommended in all studies of its biological effects.

×