Nandrolone! Medicine or Doping Agent?
40
Journal of Exercise Physiologyonline
(JEPonline)
Volume 12 Number 6 December 2009
Managing Editor
Tommy Boone, PhD, MPH
Editor-in-Chief
Jon K. Linderman, PhD
Review Board
Todd Astorino, PhD
Julien Baker, PhD
Tommy Boone, PhD
Eric Goulet, PhD
Robert Gotshall, PhD
Alexander Hutchison, PhD
M. Knight-Maloney, PhD
Len Kravitz, PhD
James Laskin, PhD
Derek Marks, PhD
Cristine Mermier, PhD
Chantal Vella, PhD
Ben Zhou, PhD
Official
Research Journal of
the American Society of
Exercise Physiologists
(ASEP)
ISSN 1097-975
Case Study
Dope Opera: Is Nandrolone a Medicine or Doping Agent?
MICHAEL GRAHAM1,3, PETER EVANS2, BRUCE DAVIES3, NON
THOMAS4, JULIEN BAKER3,5
1
The Newman Centre for Sport and Exercise Research, Newman University
College, Birmingham, UK 2Royal Gwent Hospital, Newport, Gwent, Wales, UK,
3
University of Glamorgan, Pontypridd, Wales, UK 4Centre for Child Research,
Swansea University, Swansea, UK 5Division of Sport, Faculty of Engineering
and Science, University of the West of Scotland, Paisley Campus, Paisley, UK.
ABSTRACT
Graham MR, Evans P, Davies B, Baker JS. Dope Opera: Is
Nandrolone a Medicine or Doping Agent? JEPonline 2009;12 (6):40-43.
The identification of false positive doping tests in sport is pivotal to
administering justice to the athlete. Nandrolone is a performanceenhancing drug. Although Nandrolone and its metabolites are on the
World Anti-doping Agency list of banned substances, the detection of its
abuse may become challenging. Testing positive for Nandrolone is
defined as a concentration in the urine exceeding 2 ng·ml-1. It is a strict
liability offence. An international athlete tested positive for Nandrolone
metabolites in his “A” sample in 2008. The athlete sought immediate
legal and medical advice and was advised to exercise his rights of a B
sample analysis. There was a variation in levels in A (6.2 ng.ml -1) and B
(5.6 ng.ml-1) samples. There are statutory defences which can be argued
on legal or medical grounds. One such medical exemption is an
application for a therapeutic use exemption certificate, for a legitimate
medical condition, to an empowered medical committee before
competition. Such exemption allows the sporting participant to use
certain specified medical products, but urine and or serum levels of
those drugs or its metabolites are required to be within a specified
therapeutic range. Problems arise when the therapeutic range is
unknown and when there may be co-administration of the same drug in
a performance-enhancing design. A recent unique case highlights the
difficulties the enforcement agencies have in securing a conviction
against a deliberate doping offender versus an accidental doping
violation while administering justice and fair-play.
Key Words: Ergogenic Aids, Anabolic Steroids, Androgens.
Nandrolone! Medicine or Doping Agent?
41
CASE STUDY
Nandrolone (19-nortestosterone) is an androgenic-anabolic steroid known to increase muscle mass
and strength. Athletes use it in an oral or injectable form to enhance sporting performance (1). The
metabolites of nandrolone are 19-norandrosterone (19-NA), 19-noretiocholanolone (19-NE) and 19norepiandrosterone. Finding these metabolites in the urine by gas chromatography-mass
spectrometry forms the basis of doping (2, figure 1). While nandrolone still has therapeutic use in
specified diseases, it is rarely used (3). The health risks associated with its abuse led the
International Olympic Committee (IOC) to prohibit its use in sport in 1976.
In 1996, the IOC stated that a critical concentration for Nandrolone metabolites in the urine producing
a doping offence must exceed 2 ng·ml-1 in men and 5 ng·ml-1 in women, with critical variation of 20%.
This changed in females to 2 ng·ml-1 in 2005. Urinary 19-NA was identified as being present in
laboratory staff, free of exogenous nandrolone, using isotope dilution mass spectrometry, in 1982 (4).
In 1988, the presence of endogenous urinary 19-NA, by radioimmunoassay, free of exogenous
nandrolone, was identified (5). The level ranged from 3.8 to 49.4 ng·ml-1. In 1999, individual
endogenous 19-NA urine excretion in a male athlete varied by 680% over a three month period (6). In
another male subject, individual endogenous 19-NA urine excretion varied by 72% over a 24-hour
period (7).
In a doping control situation, the excretion kinetics of labelled nandrolone showed inter-individual
variability in two individuals treated with the same dosage at the same time (8). In spot-urine
analyses, the urinary volume is influenced by various factors: glomerular filtration, tubular secretion
and re-absorption, alimentary regimen, fluid intake and perspiration, which affect urinary dilution and
the concentrations of excreted substances leading to under- or over-estimation (8).
An international athlete recently presented with metabolites of urinary nandrolone >2 ng·ml -1. There
was a variation in levels in A (19-NA: 6.2 ± 0.18, ng·ml-1 19-NE: 2.6 ± 0.08, ng·ml-1) and B (19-NA:
5.6 ± 1.1, ng·ml-1; 19-NE: not measured) samples. The medico-legal defence prepared an argument
based on physiological grounds of endogenous production. They also prepared a defence that the
World Anti-Doping Agency (WADA)-accredited testing laboratory had incorrectly applied the 2005
WADA explanatory technical note, mandate, as per a study which identified that active, unstable
urines could have 19-NA and 19-NE levels >2 ng·ml-1, but <10 ng·ml-1 (9). At the eleventh hour a
witness statement from the prosecution, identified that he had been taking eye drops for an
ophthalmic condition.
When questioned by his own team he admitted to having an eye condition 7 weeks before the
tournament. His ophthalmology notes were requested and identified that he had been prescribed
“Keratyl” eye drops (containing nandrolone sodium sulphate) for an anterior uveitis and corneal
abrasion (figure 2). He had been administering the eye drops while being scrutinized in an anti-doping
procedure. A WADA-accredited laboratory study administered therapeutic levels of Keratyl eye drops
to 4 male volunteers, for 3 days, and produced positive urinary nandrolone metabolites >2 ng·ml -1
(10).
The urinary concentrations reached 450 ng·ml-1 and 70 ng·ml-1 for 19-NA and 19-NE, respectively.
The study demonstrated that concentrations >2 ng·ml -1 could be found in samples, 15 days after the
last administration of the drug, depending on individual metabolism. Due to poor bioavailability of
ophthalmic solutions, it was not expected to obtain such high urinary concentrations and such
discrepancies between individuals. Poor bioavailability of ocular drugs has been documented in the
literature (11). Quantification has indicated a great variability in terms of inter- and intra-individual
Nandrolone! Medicine or Doping Agent?
42
excretion of nandrolone metabolites, with respect to this medication. Ophthalmic pharmaceuticals are
often considered harmless. Physicians are not always aware they can lead to a positive urine even
several weeks after the last administration, and they do not warn athletes against using this kind of
medication. Medical treatments cannot and should not be discounted when drug testing regimes are
in process. Can an ophthalmic delivery elevate the serum levels of nandrolone to an extent where
they increase muscle development? The urinary levels that can be achieved cannot discount this as
a real possibility, and cannot be differentiated from levels achieved by injection. Where does this
leave WADA if they wish to admonish or acquit an athlete for doping offences? Further research is
required to quantify whether the nandrolone levels detected in urine are being used for medical or
performance-enhancing purposes.
Address for correspondence: : Graham MR, PhD, The Newman Centre for Sport and Exercise
Research, Newman University College, Birmingham, UK. Phone (+4401214831181 extn 2516);
Email. drgraham.ac.uk@live.co.uk.
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