F-MARC Fight against Doping in Football (part I) - FIFA.com

Fédération Internationale de Football Association
President Joseph S. Blatter
General Secretary Urs Linsi
Address Fédération Internationale de Football Association
FIFA-Strasse 20 P.O. Box 8044 Zurich Switzerland
Tel: +41-(0)43-222 7777 Fax: +41-(0)43-222 7878
www.FIFA.com
F-MARC
Fight against Doping in Football
A comprehensive introduction and overview
FIFA’s strategy, the relevant substances, their effects and detection

SPORTS MEDICAL COMMITTEE | FIGHT AGAINST DOPING IN FOOTBALL FIGHT AGAINST DOPING IN FOOTBALL | FIFA MEDICAL ASSESSMENT AND RESEARCH CENTRE
Sports Medical Committee
Chairman D’HOOGHE Michel, Dr Belgium
Deputy Chairman DIAKITE Amadou Mali
Members PETERSON Lars, Prof. Dr Sweden
O’HATA Nozomu, Prof. Japan
DVORAK Jiri, Prof. Dr Switzerland
GITTENS Rudy, Dr Canada
ZERGUINI Abdelmadjid Yacine, Dr Algeria
MADERO Raul, Dr Argentina
GRAF-BAUMANN Toni, Prof. Dr Germany
TOLEDO Lidio, Dr Brazil
YOON Young Sul, Dr Korea Republic
ABDEL-RAHMAN Hosny, Prof. Egypt
BABWAH Terence, Dr Trinidad and Tobago
SINGH Gurcharan, Dr Malaysia
EDWARDS Tony, Dr New Zealand
Doping Control Sub-Committee
President D’HOOGHE Michel, Dr Belgium
Chairman GRAF-BAUMANN Toni, Prof. Dr Germany
Members DVORAK Jiri, Prof. Dr Switzerland
PETERSON Lars, Prof. Dr Sweden
GUILLEN MONTENEGRO Jorge, Dr Spain
SAUGY Martial, Dr Switzerland
FIFA Medical Assessment and Research Centre (F-MARC)
President D’HOOGHE Michel, Dr Belgium
Chairman DVORAK Jiri, Prof. Dr Switzerland
Members PETERSON Lars, Prof. Dr Sweden
GRAF-BAUMANN Toni, Prof. Dr Germany
JUNGE Astrid, Dr Germany
O’HATA Nozomu, Prof. Japan
GITTENS Rudy, Dr Canada
MADERO Raul, Dr Argentina
ZERGUINI Abdelmadjid Yacine, Dr Algeria
FULLER Colin, Dr England
ROUX Constant-Antoine, Prof. Côte d‘Ivoire
EDWARDS Tony, Dr New Zealand
MANDELBAUM Bert, Dr USA
ABDEL-RAHMAN Hosny, Prof. Egypt
CHOMIAK Jiri, Dr Czech Republic
ROSNOVSKY Mark, Dr Israel

TABLE OF CONTENTS | FIGHT AGAINST DOPING IN FOOTBALL
Table of Contents
Fight against Doping in Football
FIGHT AGAINST DOPING IN FOOTBALL | TABLE OF CONTENTS
Editorial 2
J. S. Blatter
Introduction to FIFA/F-MARC Update on Doping 4
J. Dvorak, M. D’Hooghe
FIFA’s Approach to Doping in Football 6
J. Dvorak, T. Graf-Baumann, M. D’Hooghe, M. Saugy, H. Tännler
Social Drugs: Cannabis 28
M. Saugy
Stimulants 32
L. Mateus-Avois, N. Robinson, Ch. Saudan,
N. Baume, M. Saugy
Testosterone and Synthetic Anabolic Steroids 42
Ch. Saudan, N. Baume, L. Mateus-Avois, N. Robinson, M. Saugy
Nandrolone 48
N. Baume, L. Mateus-Avois, Ch. Saudan, N. Robinson, M. Saugy
Erythropoietin – Blood Doping 54
N. Robinson, Ch. Saudan, N. Baume, L. Mateus-Avois, M. Saugy
Human Growth Hormone 62
M. Saugy, N. Robinson, Ch. Saudan, N. Baume, L. Mateus-Avois
Therapeutical Use Exemption 70
J. Dvorak, D. Kirkendall, M. Vouillamoz
Beta-2 Agonists and Asthma 76
W. Kindermann
Glucocorticosteroids 80
W. Kindermann
Medical Legal Aspects 86
T. Graf-Baumann
FIFA’s Future Activities in the Fight against Doping 94
J. Dvorak, P. McCrory, M. D’Hooghe
Glossary and Abbreviations 100
Note: Please refer to the Glossary at the end for explanation of medical terms and abbreviations.

2 EDITORIAL | FIGHT AGAINST DOPING IN FOOTBALL
FIGHT AGAINST DOPING IN FOOTBALL | EDITORIAL 3
Editorial
Dear Members of the International Football Family
FIFA has a clear vision for its anti-doping strategy in
football: to make the game free of doping. It is our
duty to protect the players from harm and ensure that
they can compete on a level playing field. Since we are
dealing with ambitious and independent professionals,
FIFA’s anti-doping strategy relies on education and
prevention, thereby ensuring their support in our fight
against doping.
Naturally, FIFA aims at interfering as little as possible in
the normal course of matches and tournaments and the
recuperation of players after a game. At the same time,
we demonstrate our respect for the dignity and privacy
of each player who is subjected to testing. A worldwide
network of specially trained physicians therefore ensures
the correct implementation of FIFA’s doping control
procedure, which is straightforward and leaves no room
for cheating or wrong doing.
As far as we can judge from current data, the incidence
of doping in football appears to be very low, and we
have no scientific evidence for systematic doping in
football. As abuse still occasionally occurs, much closer
collaboration with other antidoping organisations
such as WADA, the IOC and international federations
is required regarding banned substances, detection
methods and data collection. At the same time, a
firm stand must be made against the suppression
of symptoms through medication with the sole
objective of meeting the ever-increasing demands on
professional football players.
Since we are dealing with ambitious
and independent professionals,
FIFA’s anti-doping strategy relies
on education and prevention...
FIFA actively acknowledges its responsibility in the
fight against doping through stringent doping control
regulations, data collection of positive samples and
active support of research in the field, complemented
by large-scale prevention promoted by the FIFA Medical
Assessment and Research Centre (F-MARC). FIFA has
proved to be a reliable and supportive partner in the
much-needed worldwide collaboration of all parties
involved in the fight against doping to safeguard the
health of athletes and the spirit of fair competition.
However, the increasing use of recreational drugs
such as marihuana and cocaine is outside the scope
of doping and reveals the need for collaboration far
beyond the capacity of anti-doping agencies and sports
organisations. FIFA is ready to play an active role in this
challenge to the worldwide community and to reach
out to the billions of young people linked to us through
their passion for the game.
By acknowledging this responsibility, we will not only
make the game better, but also contribute to making
the world a better place!
Joseph S. Blatter
FIFA President

4
INTRODUCTION | FIGHT AGAINST DOPING IN FOOTBALL
Introduction
Fight against Doping in Football
The ongoing debate and controversy surrounding
doping has raised public awareness of a problem
that has not been fully appreciated during the rapid
development of various sports disciplines.
FIFA introduced doping controls in 1970 to ensure
that the results of national and international matches
were a fair reflection of the ability of those taking part.
Over the past twelve years, the FIFA Medical Assessment
and Research Centre (F-MARC) has developed a
worldwide network of specialists who are involved in
the educational process within the confederations and
associations as well as in conducting doping controls at
national, international and FIFA competitions.
Over the years, FIFA has developed a close collaboration
not only with the confederations and member
associations, but also with other team sports federations
and particularly with the accredited laboratories. It has
also established its own database. Consequently, FIFA
is able to understand the problems based on facts,
figures and a statistical analysis of the test results, and
draw conclusions for developing a global, harmonised
strategy in the fight against doping in football.
Over 20,000 doping controls are performed each year
on football players worldwide – in fact, in football, more
tests are performed than in any other sport. Based on
that number, the incidence of positive doping cases is
0.4%. The FIFA database shows that the most common
doping cases are on account of so-called recreational or
social drugs, such as cannabis and cocaine. Only 0.07%
are linked to the abuse of anabolic steroids. Analysing
this data in detail, including the distribution of positive
cases among the confederations, has determined the
content of this FIFA/F-MARC update on the strategy in
the fight against doping.
In fact, in football,
more doping tests are performed
than in any other sport
The first part describes the background, historical
perspectives and development of the FIFA strategy in
the fight against doping over the past twelve years.
The articles that follow are in an order that reflects
the frequency of the substances in positive cases, i.e.
cannabis, cocaine, testosterone and synthetic anabolic
steroids as well as nandrolone. The latter is a case
deserving of special attention, as many of the food
supplements sold over-the-counter are contaminated
by undeclared nandrolone or its precursors. As a
result, they might be taken by footballers without
their knowledge, leading to a positive doping test.
However, it is clear that any footballer is responsible
for his or her diet, including the intake of food
supplements and vitamins.
The papers on erythropoietin, blood doping and human
growth hormone offer in-depth information about
substances that are frequently discussed in the media.
However, over the past three years, there has not been
a single positive test for abuse of erythropoietin and/or
blood doping in football.
Football players who suffer from acute or chronic
diseases or physical symptoms and signs following
injury may require specific medication for treatment
that might be on the prohibited list. In these cases, a
therapeutical use exemption (TUE) may be granted if
clinically justified. The most common applications for
TUE in FIFA and the confederations are for the use of
beta-2-agonists to treat asthma and for corticosteroids
to treat acute injuries. Both groups of medications are
presented in separate chapters.
In its management of positive samples, FIFA follows the
rule of separation of power. Medical doctors analyse
the medical circumstances and laboratory results, and
estimate the severity of violation of the FIFA doping
control regulations. It is the duty of the FIFA Doping
Control Sub-Committee to present the medical aspects
of a positive case with background information for
further individual case management in the FIFA
Disciplinary Committee. The last chapter therefore
deals with these particular medical legal aspects of
positive cases.
Prof. Jiri Dvorak and Dr. Michel D’Hooghe
FIGHT AGAINST DOPING IN FOOTBALL | INTRODUCTION
Even though, according to WADA statistics for 2004,
the incidence of positive doping cases among football
players is low in comparison with other sports,
FIFA is convinced that a stringent system of doping
controls adhered to by all member associations is
important. However, the education of players, coaches,
paramedical and medical personnel surrounding the
football players might be even more important. It helps
to underline that doping has no place in football and
FIFA, but also that there is no rational reason to believe
that such abuse would transform a good footballer into
an excellent footballer – or even into a star.
This update on FIFA’s strategy in the fight against doping
should contribute to a better understanding of the
problem and it will be an integral part of the concerted
action in the long-term educational programme of FIFA.
Prof. Jiri Dvorak
FIFA Chief Medical Officer
F-MARC Chairman
Michel D’Hooghe, MD
Chairman of FIFA Sports Medical Committee
FIFA Executive Committee Member
5

FIFA’s Approach
to Doping in Football

8 FIFA’S APPROACH TO DOPING IN FOOTBALL | F-MARC DOPING UPDATE 2006
F-MARC DOPING UPDATE 2006 | FIFA’S APPROACH TO DOPING IN FOOTBALL 9
FIFA’s Approach to Doping in Football
Introduction
The ongoing debate and controversy concerning doping
(i.e. the list of prohibited substances, the procedures and
the sanctions used in amateur and professional sport)
has raised public awareness of a problem that has not
been fully appreciated during the rapid development of
various sports disciplines.
It is only 38 years since drug testing was first introduced
at the1968 Olympic Games in Mexico City following
the amphetamine and nicotinyl tartrate-related deaths
of a number of cyclists at the 1960 summer Olympic
Games in Rome and during the 1967 Tour de France.
Regular doping controls have been conducted since,
but these controls have failed to prevent sportsmen and
women from taking performance enhancing drugs both
during and out of competition. Regrettably, banned and
harmful substances are openly available even without
prescription. Drugs such as nandrolone and others can
be ordered over the internet in unlimited quantities. In
recent years, an increasing number of positive samples
and cases of so-called recreational drugs like marijuana
and cocaine have been observed and need to be addressed
accordingly. In addition, media reports may encourage
those competing at lower levels of sport to experiment
in the use of such substances without considering the
possible side-effects and medical complications, let alone
the legal consequences of their actions.
Sporting associations, including FIFA, have stated that
the fundamental aims of doping controls and antidoping
policies are:
• to uphold and preserve the ethics of sport;
• to safeguard the physical health and mental integrity
of the player;
• to ensure that all competitors have an equal chance.
FIFA introduced doping controls in 1970 to ensure that
the results of national and international matches were a
fair reflection of the ability of those taking part. The FIFA
Sports Medical Committee has the responsibility for
implementing doping controls at all FIFA competitions
and also for coordinating with confederations and
member associations. The overall management of doping
controls is done by the FIFA administration (medical
department and the FIFA Sports Medical Committee).
Over the past twelve years, the FIFA Medical Assessment
and Research Centre (F-MARC) has developed a
worldwide network of specialists who are involved in
the educational process within the confederations and
member associations as well as in conducting doping
controls at national, international and FIFA competitions.
The medical doctors/sports physicians, following their
Hippocratic Oath as well as their professional and ethical
values, play key roles in FIFA’s long-term strategy in the
fight against doping. Many of the doctors are also team
physicians within their associations.
The fight against doping in football focuses on education
and prevention with regular in- and out-of-competition
controls. In years gone by, approximately 15,000 doping
controls were performed annually on footballers, with
over 20,000 performed in both 2004 and 2005. FIFA
has articulated its unyielding position in the fight against
doping prior to the World Cups in 1998 and 2002
(FIFA magazine May 2002) and reinforced its strategy in
FIFA magazine in March 2004.
The physicians demonstrated their strong support
of FIFA’s long-term strategy in the fight against
doping prior to the 2002 FIFA World Cup Korea/
Japan when the team physicians of all 32 finalists
unanimously signed a joint declaration in the fight
against doping, supporting FIFA’s decision to introduce
routine blood sampling to analyse for blood doping
and erythropoietin. This was a firm message to the
football community and demonstrated the excellent
collaboration and cooperation between the FIFA Sports
Medical Committee with the team physicians taking
care of the players prior to and during the competition.
The team physicians of all the finalists of the 2006
FIFA World Cup Germany again reinforced the
fight against doping with a joint declaration signed
on 5 March 2006 to keep this unique event free
of doping.
The fight against doping
in football focuses on
education and prevention
with regular in- and
out-of-competition
controls.
Definition
Doping constitutes an
acute or chronic health
hazard for players
Doping is defined as any attempt either by the
player, or at the instigation of another person such
as manager, coach, trainer, doctor, physiotherapist or
masseur, to enhance mental and physical performance
unphysiologically or to treat ailments or injury – when
this is medically unjustified – for the sole purpose of
taking part in a competition. This includes using (taking
or injecting), administering or prescribing prohibited
substances prior to or during a competition. These
stipulations also apply to out-of-competition testing for
anabolic steroids and peptide hormones as well as to
substances producing similar effects. Other prohibited
methods (e.g. blood doping) or manipulation of
collected samples is likewise classified as doping.
The detailed definition as related to the anti-doping
rule violations is presented in the current FIFA Doping
Control Regulations (January 2006). Doping contravenes
the ethics of sport, constitutes an acute or chronic health
hazard for players and may have fatal consequences.

10 FIFA’S APPROACH TO DOPING IN FOOTBALL | F-MARC DOPING UPDATE 2006 F-MARC DOPING UPDATE 2006 | FIFA’S APPROACH TO DOPING IN FOOTBALL 11
The Extent and Scope of Doping in
Football
FIFA is a global organisation that unifies over 250 million
footballers in 207 countries with around 40 million of
these players being female.
Currently, confederations, members associations or both
that fall under FIFA’s management carry out their own
doping controls at competitions that they stage. Urine,
blood samples or both must, however, be analysed at
FIFA/WADA-accredited laboratories. These laboratories
send reports on any “chemically positive” A samples to
the member associations, as well as to FIFA headquarters
for management and to WADA for information. Once
the FIFA medical department has received a positive
A sample report, follow up information is required by
the member association, the confederation in question,
or both to receive the results of the possible B sample
and the particular disciplinary committee decision. If
the information is not provided, the FIFA Disciplinary
Committee takes appropriate action. Since the 1994
FIFA World Cup in the United States, the FIFA
medical department has been stringently registering all
performed samples.
The true extent of the
problem is unknown
A new doping control policy for FIFA competitions was
introduced at the FIFA U-17 World Championship in
New Zealand in 1999. Ever since, during tournaments,
two players from each team have been randomly selected
to undergo doping tests after each match.
Between 1994 and 2005, 3,327 doping controls (men
and women) were performed during three consecutive
FIFA World Cup competitions (USA, France, Korea/
Japan), two consecutive Olympic Games (Sydney, Athens)
as well as at the most recent Women’s World Cup, the
FIFA U-19 Women’s World Championship in Thailand,
the FIFA U-17 World Championship in Peru, the FIFA
Confederations Cup in Germany, the FIFA Club World
Championship in Japan, the FIFA Beach Soccer World
Cup in Brazil, the FIFA U-20 World Championship in
Netherlands and the FIFA Futsal World Championship in
Chinese Taipei as well as at the 2006 FIFA World Cup
preliminaries. Only four samples tested positive during
this period: one for ephedrine and pseudoephedrine in
1994, one for cannabis and one for nandrolone during
the 2003 FIFA World Youth Championship in the
United Arab Emirates, and one for ephedrine in Angola.
This reflects an overall incidence of 0.12% positive cases
over the past eleven years. The extremely low incidence
of positive cases during FIFA competitions indirectly
confirms FIFA’s long-term strategy in the fight against
doping, that education and prevention are key issues in
keeping high-profile competitions free of doping.
Number of Cases
50
45
40
35
30
25
20
15
10
5
0
It can only be assumed that team sports such as football are
not as prone to abuse of performance enhancing substances
in comparison to individual sports. When looking at
positive doping cases during the 2004 Olympic Games in
Athens, 27 positive cases were detected; all in individual
athletes and none in any team sport participants. It might
be claimed that the close collaboration of the team sport
medical committees has, since the 2000 Olympic Games
in Sydney, positively influenced the team sports’ fair play
attitude during the Olympic Games in Athens.
Close collaboration with accredited laboratories, the
reporting system and the central control system are
important tools to continue to statistically record the
extent of doping in football in the future. Although
several prominent footballers have tested positive for
drugs in recent decades, the true extent of the problem
is unknown. Even if we assume that doping is still
not a major issue in team sports such as football, any
estimation of the problem can be considered to be merely
an unscientific hypothesis or speculation. To meet the
challenge brought about by this situation, FIFA has
taken action to develop closer collaboration between
the medical committees of the various confederations.
In October 1999, the FIFA Sports Medical Committee
and the UEFA Medical Committee met to discuss the
latest sports medicine issues, not only with the aim
of combating doping, but also to develop educational
programmes designed to meet the fundamental aims and
objectives outlined above.
Similar meetings have been conducted between a
representative of the FIFA Sports Medical Committee
and the medical committees of CONCACAF (North,
38
47
Figure 1: FIFA doping statistics per substance for 2004 and 2005 (excl. T/E)
30
16
2004
13
Central America and the Caribbean in 2000, 2001), AFC
(Asia, 2001, 2002, 2005) and CAF (Africa, 2003, 2004).
During 2005, meetings with the newly established OFC
(Oceania) Sports Medical Committee and CONMEBOL
(South America) were held with the aim of harmonising
doping control procedures, improving the understanding
of the scientific background of doping and enhancing the
FIFA network of doping control officers (DCOs) who
fulfil educational duties as a part of their responsibilities.
According to IOC statistics (until 2003) and WADAaccredited
laboratories (as of 2004), approximately
20,750 doping controls are performed annually on
football players. The majority of tests are performed
in Europe, North and South America. The number
of doping controls continues to increase in the other
confederations.
In this respect, FIFA has developed its own database
to keep records on the substances reported as positive
to allow an online control of the management of these
samples within the different confederations and member
associations. During 2004 and 2005, there were 88
(0.42% based on the assumption of 20,750 samples
per year) and 78 (0.37%) positive samples respectively
registered at FIFA (see Figure 1). This increase is
probably a result of improved reporting systems by the
laboratories as a result of the implemented World Anti-
Doping Code (March 2004).
Most of these cases were detected or reported by the
European Laboratories that receive most of their samples
from European associations (see Figures 2 and 3).
Cannabis Cocaine Anabolic Steroids Stimulants Miscellaneous
2005
9
3
0
4
6

12 FIFA’S APPROACH TO DOPING IN FOOTBALL | F-MARC DOPING UPDATE 2006 F-MARC DOPING UPDATE 2006 | FIFA’S APPROACH TO DOPING IN FOOTBALL 13
Number of Cases
Figure 2: FIFA positive doping samples per confederation in 2004 and
2005 (excl. T/E)
Following FIFA’s meeting in Zurich with medical
representatives of the Olympic Team Sports Federations
and representatives from the WADA accredited
laboratories in 2003, it has been possible to receive
reliable data on performed analyses of doping samples
from the WADA-accredited laboratories (Figure 4).
It was observed that samples performed for football
(FIFA) showed quite a discrepancy between laboratories
in Seoul (42 analyses) and Rome (4,159 analyses). The
analysis of this data might influence the future strategy
of the distribution of the samples to the laboratories.
The total number of football samples analysed during
the year 2004 allows the calculation of incidents for the
positive samples in total (0.42%), the distribution and
Positive Doping Samples
70
60
50
40
30
20
10
0
18
16
14
12
10
8
6
4
2
0
4
0
AFC
10 10
Belgium
2
7
CAF
0
Croatia
0
CONCACAF
1 1
2004
2005
17
2 1 0
CONMEBOL
0
England
Figure 3: FIFA positive doping samples for Europe in 2004 and 2005 (excl. T/E)
11
13
17
France
OFC
1
64
0
Greece
UEFA
58
13
8
Italy
calculation of incidents in the different confederations
(Table 1), and the calculation for the most commonly
detected prohibited substances (Table 2).
It should be stated that these statistical analyses do not
include the applications for Therapeutic Use Exemption
(TUE) or the pending T/E (Testosterone/Epitestosterone)
ratio cases. These cases are extremely difficult to manage
and have motivated F-MARC to develop a new research
study in collaboration with the WADA-accredited
laboratory in Lausanne for direct proof of testosterone in
urine. This study is currently on the way.
The relatively low incidence of positive doping samples,
especially for the true performance enhancing drugs
such as anabolic steroids and stimulants, support the
assumption that there is no evidence of systematic
doping. Other important support for the assumption for
no evidence of systematic doping was provided by UEFA
during the 2005/2006 Champions League competition.
All 32 participating teams underwent unannounced
doping controls in their training camps. Ten players
per team were tested by UEFA medical doctors. All
320 samples were declared negative.
The newly developed FIFA database for management
of all samples collected worldwide allows doping
control officers’ records to be tracked and it has proven
to be an extremely useful tool for following up on
cases, particularly for less experienced FIFA member
associations. As of January 2006, this database has
2
0
Malta
3
5
Netherlands
8
2
Norway
9
12
Portugal
2
0
Spain
2
2004
2005
3
Turkey
Samples Positive Incidence%
AFC 1058 4 0.38
CAF 715 2 0.28
CONCACAF 275 0 0.00
CONMEBOL 3993 17 0.42
OFC 226 1 0.44
UEFA 14483 64 0.44
Total 20’750 88 0.42
Table 1: WADA-accredited laboratories’ doping statistics for 2004 per
confederation (excl. T/E)
Samples Incidence%
38 Cannabis 0.18
30 Cocaine 0.14
13 Anabolic Steroids 0.07
3 Stimulants 0.01
4 Miscellaneous 0.02
88 Total 0.42
Table 2: Substance per positive sample of WADA-accredited
laboratories in 2004
Doping Samples
4500
4000
3500
3000
2500
2000
1500
1000
500
0
42 45 45 84 86 96 107 108 134 152 199 226 257
Figure 4: Samples analysed in 2004 per WADA-accredited laboratory
allowed each positive sample to be tracked, with the aim
of having the final decision of the member association’s
disciplinary committee no later than 90 days after the
analysis of the B sample.
The FIFA database will allow a continuous cross-check
with the WADA database (ADAMS – Anti-Doping and
Management System) once operational, not only in order
to control the reporting system of the WADA-accredited
laboratories, but also to allow prospective studies on
sanctions related to the different substances, the severity
of the violation, or both.
List of Prohibited Substances
Like most major sports governing bodies and the
IOC, FIFA has drawn up a list of prohibited doping
substances and methods. The categories of prohibited
substances and methods have been approved by the FIFA
Sports Medical Committee and follows the Prohibited
List International Standards in the World Anti-Doping
Code. The most recent Doping Control Regulations
and list of banned substances (Jan 2006) are divided
into three main sections containing different categories
of prohibited drugs and methods (table 3). Additional
substances and methods such as stimulants, narcotics,
cannabinoids and glucocorticosteroids are included for
in-competition testing. The 2006 list includes specific
402 405 421 421 470 473 516 529 565 572
Seoul
Havanna
Prague
Barcelona
Penang
Los Angeles
Bangkok
Helsinki
Montral
Seibersdorf
Bloemfontain
Sydney
Moscow
Tokyo
Lausanne
Ankara
Beijing
Oslo
Stockholm
Tunis
Genf
Athens
Kreischa
Bogota
Paris
Lisbon
London
Cologne
Rio de Janeiro
Rome
881
994
1165
1536
2548
3112
4159

14 FIFA’S APPROACH TO DOPING IN FOOTBALL | F-MARC DOPING UPDATE 2006
F-MARC DOPING UPDATE 2006 | FIFA’S APPROACH TO DOPING IN FOOTBALL 15
substances that are examined for monitoring purposes
and are particularly susceptible to unintentional antidoping
violations because of their general availability
in medical products or because they are less likely to be
successfully abused as doping agents. A doping violation
involving such substances may result in a reduced
sanction provided that the “athlete can establish that
the use of such specified substances was not intended
to enhance sports performance” (FIFA Doping Control
Regulations p. 33).
An extensive list of examples for each category of
prohibited substances is provided by FIFA in the annual
Doping Control Regulations. These lists are always
followed by the words “and other substances“ to include
all related substances with a similar chemical structurr or
biological effect.
Even though the majority of the drugs described are
banned in football, some categories are more capable
of enhancing a player’s performance than others and, as
such, may well be used within our sport.
Two categories are not commonly used by players:
narcotic analgesics and diuretics. Narcotic analgesics
are mainly from the opiate family such as morphine.
Diuretics are used as masking agents in certain sports.
Both of these categories are contraindicated for the type
of exercise that footballers have to perform on the field
over 90 minutes. Three categories that could involve
footballers are stimulants, anabolic agents and peptide
hormones.
Current Doping Control Regulations
Cooperation within the Confederations and
Associations
In 1999, a comparative study of the Doping Control
Regulations issued by the confederations showed a high
level of agreement as far as the lists of banned substances
and methods were concerned. This was because the
confederations simply decided to adopt the FIFA
Doping Control Regulations that were in force.
A detailed survey of the doping control regulations
issued by associations, however, revealed some
differences in the procedure and concerning the
inclusion of certain substances in the categories of
prohibited substances (1999).
Following this comparative study, the FIFA Sports
Medical Committee and F-MARC proposed to the
Executive Committee that the doping control regulations
of all associations be harmonised and that they adopt the
list of prohibited substances and methods. Following the
FIFA Executive Committee decision, the FIFA Ordinary
Congress ratified this decision in Seoul (May 2002),
thereby paving the way for the decision of the FIFA
Extraordinary Congress in Doha/Qatar (December
2003), i.e. following the method of individual case
management, expulsion sanctions by the disciplinary
committees of associations will be extended for all
international matches and vice versa.
Prohibited Substances Prohibited Methods Substances and Methods
Prohibited in Competition
Anabolic Agents Enhancement of Oxygen Transfer Stimulants
Hormones and related substances Chemical and Physical Manipulation Narcotics
BETA-2-Agonists Gene Doping Cannabinoids
Agents with Anti-Estrogenic Activity Glucocorticosteroids
Diuretics and Other Masking Agents
Table 3: Categories of banned substances and methods from FIFA Doping Control Regulations
Stringent Rules of Procedure
While the in-competition Doping Control Regulations
outline a clear procedure, the out-of-competition
controls have not been performed routinely in football,
mainly because the professional football player is
“in competition” for almost the entire year with the
exception of brief seasonal breaks (2-4 weeks) or when
rehabilitating after severe injury.
For the first time, FIFA and UEFA produced a joint set
of regulations for out-of-competition doping controls
prior to EURO 2000. About one month before the
tournament, all competing countries were informed
that unannounced doping controls might be carried out
at training camps and were instructed on the procedure
to be followed.
After lots had been drawn to select four national teams,
two doping control co-ordinators (one from UEFA and
one from FIFA) visited the training camps in question
at around 11 a.m. and immediately reported to the
national team’s head of delegation.
The head of delegation was requested to find a suitable
location for collecting the required samples. The players
to be tested – four per team – were then drawn by lots
and the doping control procedure was carried out by the
UEFA and FIFA doctors immediately thereafter.
FIFA Doping Control Officers are
physicians for confidentiality reasons
and educational purposes
The experience of these out-of-competition tests
showed the need for a much greater level of cooperation
between associations, confederations and FIFA to
ensure that procedures for standard doping controls and
unannounced out-of-competition controls were brought
more closely into line.
A similar procedure for out-of-competition controls
was performed during the training camps prior to the
2002 FIFA World Cup (Korea/Japan) and Euro 2004
(Portugal). The procedure proved to be feasible and the
compliance of involved teams and individual players
was 100%. Out-of-competition, unannounced controls
are also planned prior to the 2006 FIFA World Cup
Germany.
Using Medical Doctors as Doping Control Officers
Although some sporting organisations and anti-doping
agencies continue to employ coordinators who are
not medical doctors for doping controls, FIFA and
its member confederations insist on physicians. This
question requires closer analysis.
Players from teams selected to undergo a doping test
are required to provide details of any treatment with
medication from seven weeks to 72 hours before the test
or the competition in question.

16 FIFA’S APPROACH TO DOPING IN FOOTBALL | F-MARC DOPING UPDATE 2006 F-MARC DOPING UPDATE 2006 | FIFA’S APPROACH TO DOPING IN FOOTBALL 17
All medications that a player has received must be listed
together with details of the method of administration,
dosage and medical indications. The information
declared on the forms used for this purpose is covered by
patient confidentiality and may not be communicated to
non-medical persons (for example, the general secretary
of the football association concerned, the player’s coach
or his club’s general manager) unless the A sample tests
positive. For confidentiality reasons alone, it is essential
that the doping control officer is a physician with
appropriate qualifications for this position.
Clinical studies show that until recently, most of
the doping substances were, as a general rule, drugs
developed for therapeutic purposes that are primarily
used for medical therapy. Today, however, an increasing
number of substances are being developed for the sole
purpose of doping and no studies have been conducted
into their clinical effectiveness.
This is a final reason why specially trained physicians,
working in close co-operation with laboratory specialists,
should serve as doping control officers. The doctor not
only has to carry out the control procedure, but also has
an educational function before, during and after the
doping control.
In case of Therapeutic Use
Exemption, strict confidentiality is
necessary and guaranteed
Prohibited Substances Prescribed for
Medical Reasons
(TUE – Therapeutic Use Exemption)
If there is doubt surrounding the appropriate therapeutic
treatment of a player who has a medically confirmed
pathological condition, drugs containing prohibited, or
partially prohibited, substances could be permitted in
exceptional cases if:
• the player’s health would be impaired if the prohibited
drug were withheld;
• no performance enhancement could result from the
prohibited substance being administered as medically
prescribed;
• no permitted or practical alternative drug is available
in place of the prohibited substance.
In such a situation, a player or his doctor must request
an exemption by submitting a formal application to
the FIFA Doping Control Sub-Committee. Strict
confidentiality is necessary and guaranteed.
FIFA has become part of an international network
in this field, initiated by the Australian Sports Drug
Medical Advisory Committee (ASDMAG), and will be
able to draw upon the accumulated body of knowledge
from other team sports, WADA and individual cases.
The TUE applications are managed by the FIFA
Doping Control Sub-Committee. The copy of
approval or rejection is sent automatically to WADA
for information and possible appeal. If requested, the
complete medical file is submitted to WADA medical
staff for further investigation, following the rules of
medical confidentiality.
Laboratory Analyses of Samples
Chain of Custody
The laboratories throughout the world that are in charge
of doping analyses are all specialised and well equipped
institutions, empowered by their national sporting
authorities to perform analyses on urine samples
received from sporting authorities.
WADA has established an accreditation system for such
laboratories. A total of 33 are fully accredited for 2005
(table 4). This accreditation is based on quality control
checks performed annually on each laboratory. The
main objective of accreditation is to guarantee uniform
quality of analysis at laboratories all over the world.
International federations, including FIFA, use
these official laboratories for their major events and
competitions. The laboratory is requested by the
governing body concerned to analyse the samples and is
obliged to comply strictly with the rules laid down in
their medical codes.
Table 4: FIFA/WADA accredited laboratories in 2006
The laboratories treat all samples anonymously with
each sample being labelled with a code number known
only to the player and the committee in charge of the
controls. This is essential to assure the player that the
analyses are completely objective and avoid any undue
pressure on the laboratory when analysing the samples.
The results (negative or positive) are communicated to
the committee in charge of the controls. If the A sample
is positive, the test is performed a second time before the
result is sent to the relevant committee. A copy from the
report of any positive case is simultaneously sent to the
international federation (if the latter is not in charge of
the controls), to FIFA and to WADA. The committee in
charge then informs the player, who then has a limited
time to request an analysis of the B sample.
Analyses
The analyses are carried out with the aim of identifying
all detectable banned substances. The equipment used
is state-of-the-art technology designed to generate a
“molecular fingerprint”. The techniques of choice are gas
(or liquid) chromatography controlled with detectors
based on mass spectrometry. Chromatography is the
first step in the analysis, consisting of a preliminary
separation in the mixture of several natural or nonnatural
substances contained in each urine extract. After
the substances have been sorted, a mass spectrometer
provides a picture of the molecular structure that can be
compared with others stored in the chemical databases
of the computer that controls the entire system.
Ankara (Turkey) Warsaw (Poland) Bogota (Colombia)
Athens (Greece) Bangkok (Thailand) Barcelona (Spain)
Beijing (China) Bloemfontein (South Africa) Cologne (Germany)
Gent (Belgium) Helsinki (Finland) Seibersdorf(Austria)
Havana (Cuba) Kreischa (Germany) Lausanne (Switzerland)
Lisbon (Portugal) London (England) Los Angeles (USA)
Madrid (Spain) Montreal (Canada) Moscow (Russia)
Oslo (Norway) Paris (France) Penang (Malaysia)
Prague (Czech Republic) Rome (Italy) Seoul (Korea)
Sydney (Australia) Tokyo (Japan) Stockholm (Sweden)
Tunis (Tunisia) Rio De Janeiro (Brazil) Cambridge (England)

18 FIFA’S APPROACH TO DOPING IN FOOTBALL | F-MARC DOPING UPDATE 2006 F-MARC DOPING UPDATE 2006 | FIFA’S APPROACH TO DOPING IN FOOTBALL 19
The aim of all these analyses is to prove that no banned
substances are present in the urine samples provided
by “clean” players (the vast majority: a true negative),
so that the player can then be declared negative. In
positive cases, the same technology must also deliver
absolute chemical proof that a banned substance or its
degradation products (called metabolites) are present in
the urine (a true positive). Every possible step is taken
to prevent samples from erroneously being declared
positive (a false positive); in general, the purpose of B
sample analysis is to provide confirmation of the result
obtained during the first test in presence of the player or
one of the player’s representatives.
The purpose of B sample analysis is to provide confirmation of the
A result
Unfortunately, not all banned substances used in sport
can be detected using this technology (a false negative).
In addition, some of them have exactly the same
structure as their natural endogenous forms and are
quite difficult to tell apart.
The T/E Ratio
Widespread use of anabolic steroids in doping began
in the 1980s and testosterone was one of the preferred
androgenic anabolic agents. Until recently, it was
difficult to differentiate between synthetic and natural
testosterone in the body. The only method available was
a quantitative one involving the establishment of a ratio
with another steroid called epitestosterone that is similar
to testosterone and is very stable in its concentration.
The normal Caucasian and African population has a
mean ratio (testosterone to epitestosterone = T:E) of
1.5:1 (for males) with some variability, rising to 4:1
in very rare cases. The mean ratio for Asian people is
generally lower than 1:1. A player with excessive levels
of testosterone will show a much higher ratio, resulting
from an increase in testosterone concentration. It was
later decided that the maximum permissible T:E ratio
would be 6:1, and that any ratio over this limit would
be declared positive. Currently, the limit for an adverse
finding has been fixed at 4:1.
In addition to the T:E ratio, monitoring of the
complete steroid profile of the athlete over time can
be a demonstration of manipulation. The latter can
also be due to the consumption of other steroids
like testosterone precursors that are easily purchased
over the internet. Moreover, a laboratory’s use of new
instrumentation, the isotope ratio mass spectrometer
(IRMS), allows a differentiation between steroids of
endogenous origin from those of exogenous origin in
urine. This tool, together with the retrospective values
of the player, if they exist, and in some cases, additional
endocrinologic investigations, provide the disciplinary
committees with the opportunity to make the most
accurate decision in a timely manner.
A 2004 FIFA-initiated validation study conducted
jointly with LAD (WADA-accredited laboratory in
Lausanne) is in progress.
Nandrolone
Just before the FIFA World Cup in France in 1998,
a number of well-known players tested positive for
small amounts of nandrolone metabolites in their
urine. Nandrolone (chemical name: nortestosterone) is
an anabolic steroid that often occurs in body-building
doping cases. In general, this compound is taken in high
doses and its degradation products (metabolites) remain
detectable in urine for up to several months.
Prior to the 1998 World Cup, FIFA commissioned an
independent anti-doping laboratory (University of
Lausanne) to carry out a collaborative study to obtain
a true picture of the situation in football. With the
agreement of national and international bodies, every
player from every team in the top national leagues in
Switzerland (A and B Leagues) was tested after a game
(356 players in total over two weekends) in collaboration
with the Swiss anti-doping committee. The results
were compared with those obtained by testing amateur
footballers and students.
Without revealing anything about the origin of these
products, the study showed that some players had
nandrolone metabolites in their urine after the game.
The traces of metabolites in those players’ urine samples
were very small and all were below the limits of a
positive reading.
On the basis of the study, FIFA was able to organise
the anti-doping programme for the World Cup with
a degree of assurance to provide reliable information
to the competing teams to rule out any occurrence of
false positive tests. With FIFA’s support, this study
into nandrolone and its derivate substances continued.
Extraordinary variability in the excretion was
demonstrated, making the relationship between dosage,
time delay and the urine concentration very critical.
The involvement of the world governing body in such
a research programme is essential if any worthwhile
progress is to be made in this area. The players can also
be given the assurance that, scientifically and ethically,
they start a match on a level “playing field” with their
opponents as far as doping is concerned.
Peptide hormones
There are several peptide hormones in the list, of which
the two most important are erythropoietin and human
growth hormone.
Erythropoietin (EPO)
The use of erythropoietin (EPO) in sport can be detected
in urine by a novel method based on biochemical
properties of the substance. EPO and analogues are too
large to be filtered by the kidney and easily eliminated in
urine. Their concentrations in urine are so low that there
was a need for improvement in biochemical technology
to allow the detection of this product in urine.
Thus, in 2000, the laboratory in Paris implemented a
method based on a small structural difference between
recombinant and natural EPO to determine whether
doping had taken place. This method is now applied in
several accredited laboratories in the world.
Every possible step is taken
to prevent samples from being
erroneously declared positive

20 FIFA’S APPROACH TO DOPING IN FOOTBALL | F-MARC DOPING UPDATE 2006
F-MARC DOPING UPDATE 2006 | FIFA’S APPROACH TO DOPING IN FOOTBALL 21
Human Growth Hormone (hGH)
The chemical structure of bioengineered human growth
hormone is almost identical to the natural hormone
produced by the body. Consequently, it is particularly
difficult to differentiate between injected and natural
hormone. Recently developed methods use blood as
a biological sample for the determination of a specific
ratio diagnostic for the use of recombinant hGH. This
new approach clearly demonstrates the necessity to
implement blood sampling for anti-doping purposes in
future.
Blood Sampling
Recently, blood has been introduced as an alternative
biological matrix to urine for anti-doping purposes.
Since 2004, blood has been recognised as absolutely
necessary for reliable results for some forbidden
substances and methods. The list of these substances and
methods is not definitive, but currently, hGH, synthetic
haemoglobins and homologous blood transfusions can
be reliably detected with several blood matrices.
Some other blood tests are also carried out in certain
sports, not for the purpose of determining the presence
of doping, but rather as general health checks conducted
in the context of medical screening of the competitors.
This has potential for the future and could easily be
introduced by some national or international federations
depending on their structural organisation. However,
this concept is more difficult to implement in larger
federations where there are players on every continent.
FIFA Network of Doping Control Officers
In cooperation with the confederations and associations,
FIFA has established a worldwide network of more than
250 specially trained physicians who act as FIFA Doping
Control Officers. With regard to medical confidentiality
and the necessity for specific knowledge in the field,
FIFA only accepts physicians as doping control officers.
Doping Control Officers (DCO) all have attended
instructional seminars conducted by F-MARC (Prof.
Jiri Dvorak, Chairman) and FIFA Doping Control Sub-
Committee (Prof. Toni Graf-Baumann, Chairman) in
order to secure “unity of doctrine”. Such seminars were
held in Tunis in November 2000 for CAF, in Penang in
January 2001 for AFC, in Zurich in January 2001 for
UEFA, in Miami in February 2001 for CONCACAF,
in March 2001 for OFC, in Tunis in January 2004 and
in Marrakech in November 2004, in Buenos Aires in
March 2005, in Oman in May 2005, in Port of Spain in
December 2005, in Auckland in February 2006 and in
Buenos Aires in April 2006. The DCOs, as members of
the FIFA network, are currently distributed around the
world. In order to make doping control cost-effective,
the FIFA Congress followed the recommendation of
the Sports Medical Committee that DCOs should be,
by profession, physicians who follow the Hippocratic
Oath and their professional law. DCOs perform doping
controls on their national team in their country when
playing a team from other countries. The FIFA doping
control procedure is straight forward and transparent,
leaving no place for cheating or wrong-doing when all
FIFA doping control procedure is straight
forward and transparent, leaving no
place for cheating or wrong doing
steps are performed in the presence of representatives
from both teams. This makes the logistics easier and
significantly reduces the costs involved, particularly for
qualifying matches for major competitions.
Research
The current list of banned substances contains a number
of drugs for which there is no conclusive scientific
evidence to justify inclusion on the list. Research on
selected substances has highlighted some performanceenhancing
effects while other references are doubtful.
In view of the potentially enormous repercussions (as
demonstrated at the Sydney Olympic Games) there are
several ways of improving the current situation:
• A database containing all currently listed substances
should be set up. This should give details on the
pharmacological background, research findings
and clinical papers documenting the effects of the
particular substance;
• Borderline substances should be reconsidered on
the basis of research studies that provide a scientific
analysis of their effect on physical and psychological
performance as well as their effect on metabolism;
• A standard study design (double-blind, randomised
trials) should be set up for the substances under
scrutiny, proven in pilot projects and implemented
multi-centrically;
• The results of such studies should form the basis for a
future discussion on the list of prohibited substances;
• Tracing and identification of masking agents.
Such initial research work might help to reduce the
list of banned substances to focus concentration on
the major problem areas like anabolic steroids, peptide
hormones and related substances, such as hGH and
EPO and others.
Research into nandrolone metabolism in footballers,
conducted with FIFA’s support, eloquently documents
the complexity of the problem. The study showed
that current laboratory methods cannot distinguish
between endogenous metabolism and exogenous intake
of nandrolone. Although the cut-off level of 2 ng/ml
would appear rational, it has not been scientifically
proven, leaving the window wide open for discussion.
Further double-blind studies are being conducted to
obtain the scientific evidence needed to end the ongoing
speculation. Nevertheless, this cut-off level is valid and
will remain in effect.
FIFA has realised and documented its responsibility by
supporting research studies that promise to enhance
current medical knowledge. A combined effort with
other international sports federations, the IOC and antidoping
agencies might, however, accelerate the process.
Educating the Football Public about
Doping and Performance
Cooperation with Team Doctors
Supplements and Special Nutrition
Continuous and close contact with team doctors is
necessary in countries where sports medicine is still
developing and where team doctors may not have special
training on doping issues. In view of the rapid changes
in doping with regard to substances and methods of
application, a constant exchange of information with all
team doctors is essential.
Apart from the facts of the problem, effective procedures
against doping cannot be put into practice unless a close,
trusting relationship has been established between the
team doctors and the Doping Control Officers.
A trusting relationship has been established between the team doctors
and the Doping Control Officers

22 FIFA’S APPROACH TO DOPING IN FOOTBALL | F-MARC DOPING UPDATE 2006 F-MARC DOPING UPDATE 2006 | FIFA’S APPROACH TO DOPING IN FOOTBALL 23
Players should use foods that optimise training and match performance
In this regard, particular attention must be paid to food
supplements and special diets that might be prescribed
for an athlete. Supplements or diets may contain banned
substances, meaning the athlete may be taking substances
(or using food supplements) without realising that it may
contain a banned substance. If the athlete tests positive,
it is difficult to prove that the substance(s) in question
originated in the athlete’s food or food supplements.
From a legal point of view, players testing positive in
such situations must bear the responsibility themselves.
Here, too, a constant exchange of information between
Doping Control Officers and team doctors will help
everyone keep abreast of developments in the “market”
and prevent problems arising for players.
The recently published summary of “Nutrition for
Football: the FIFA/F-MARC Consensus Conference”
(www.FIFA.com, Sept 2005) clearly states that there is
no evidence to support the current widespread use of
dietary supplements in football. Supplements should
be used only on the advice of qualified sports nutrition
professionals.
Football players can stay healthy, avoid injury and achieve
their performance goals with good dietary habits. Players
should choose foods that support and optimise training
and match performance. What a player eats and drinks
in the days and hours before a game, as well as during
the game, can influence the result by reducing the effects
of fatigue and optimise performance. Food and fluid
ingested soon after a game and training can accelerate
recuperation. All players should have a nutrition plan
that takes account of individual needs.
FIFA`S Cooperation with WADA
On 4 February 1999, a Lausanne declaration on Doping
in Sport was presented to the IOC and international
sport federations that an independent International
Anti-Doping Agency should be established and fully
operational by the Olympic Games in Sydney 2000 in
order to coordinate the various programmes necessary
to realise the objectives.
The medical and legal representatives of FIFA have
developed a close collaboration since 1999 based upon
numerous meetings with the representatives of the
World Anti-Doping Agency, particularly following the
meeting of FIFA President Mr Joseph Blatter and the
Chairman of WADA, Mr Richard Pound in Montreal
in December 2001.
FIFA’s medical legal experts contributed significantly
to the improvement of the World Anti-Doping Code
particularly in versions 1 and 2. They insisted on having
independent expert opinion by prominent European
judges and lawyers, including the International
Sports Lawyers Association, on individual case
management regarding positive cases. This individual
case management has been confirmed as a strategy by
internal studies of the medical legal aspects of the Team
Sports Federations based upon 184 positive samples and
cases between 1998 and 2003 in different sports.
After intensive discussions with Mr Pound, the
management of WADA and a historic speech delivered
by Mr Pound (54th Ordinary FIFA Congress in
Paris on 19 May 2004), a informal agreement on
collaboration between FIFA and WADA was signed
by the respective presidents and confirmed by the
IOC President, Dr Jacques Rooge. Based upon this
agreement and adaptation of the FIFA Doping Control
Regulations, changes have been incorporated in the
FIFA Disciplinary Code.
Legal Background
In this regard, the legal background should be briefly
illustrated. FIFA is a private association in accordance
with Article 60 ff. Swiss Civil Code with headquarters
in Zurich, Switzerland. Consequently, FIFA is a legal
person in accordance with Swiss Private Law and
has to comply with it when setting up its statues and
regulations.
The principles of fault and individual case management
are essentials of Swiss Sanction Law and therefore have
to be considered when imposing private sanctions. Every
sanction contains a distinctive individual component,
because every sentence has to take into account the
International sports federations
are free to establish disciplinary
regulations and sanctioning as they
deem appropriate
fault of the delinquent. FIFA has been following these
principles in his Doping Control Regulations from the
beginning.
In order to base its decisions on expertise, FIFA itself
sought a legal opinion by the Court of Arbitration for
Sport (CAS) as to the extent to which the World Anti-
Doping Agency‘s code complied with Swiss law in
September 2005. In its submission, WADA claimed
that FIFA‘s provisions regarding the fight against
doping and the sanctioning of doping offences showed
significant deviations from the World Anti-Doping
Code. In its legal opinion published in April 2006,
CAS explicitly confirmed FIFA‘s practice of individual
case management when sanctioning doping offences.
In addition, CAS noted that FIFA‘s principle of

24 FIFA’S APPROACH TO DOPING IN FOOTBALL | F-MARC DOPING UPDATE 2006
F-MARC DOPING UPDATE 2006 | FIFA’S APPROACH TO DOPING IN FOOTBALL 25
individual case management complies with the World
Anti-Doping Code. At the same time, the independent
sports arbitration body, with headquarters in Lausanne
(Switzerland), has also ruled that FIFA‘s provisions with
regard to the fight against doping and the sanctioning
of doping offences are, to the greatest possible extent, in
line with the World Anti-Doping Code, and that they
are also fully in line with Swiss law.
CAS also compared FIFA‘s provisions with those of
the World Anti-Doping Code in 22 main areas. In 16
points, including the definition of doping, the strict
liability principle, the list of prohibited substances,
therapeutic use exemptions, testing and analysis,
hearings, commencement of the ineligibility period,
and disqualification provisions regarding teams,
CAS stated that there were no material differences
between the two sets of regulations. Furthermore, CAS
confirmed FIFA`s attitude by stating that neither the
IOC President, Dr Jacques Rooge, FIFA President Mr. Joseph Blatter and Chairman of WADA, Mr Richard Pound
International Olympic Committee (IOC) nor WADA
has the right to dictate to FIFA as regards the latter‘s
disciplinary regulations for the fight against doping and
the sanctioning of doping offences. According to CAS,
international sports federations are free to establish such
provisions as they deem appropriate, especially as CAS
also noted that the World Anti-Doping Code is not
legally binding per se.
CAS reported differences in six areas between FIFA‘s
provisions and the World Anti-Doping Code, although
it only highlighted significant deviations in three of
these points. CAS came to the general conclusion that
with regard to the approach used to determine the level
of punishment to be imposed, there are no considerable
differences between the two sets of regulations. With
regard to the two-year punishment that the World
Anti-Doping Code regards as the standard and FIFA
as the maximum punishment, and in terms of the
minimum punishment of six months (FIFA) and
one year (WADA), CAS also noted that there was a
difference that cannot be resolved solely by recourse
to jurisprudence. With regard to possibly eliminating
a sanction in cases in which an athlete proves that he
did not act with fault or negligence, CAS recommended
that FIFA incorporate an appropriate provision in
its regulations and not impose sanctions on athletes
who prove that a prohibited substance entered his
body through no fault or negligence of his own. FIFA,
however, already follows such a practice by applying the
principle of guilt when sanctioning doping offences.
In addition, FIFA was advised by CAS to adapt its
regulations to clarify WADA‘s right of appeal against
procedures followed in final-instance decisions.
Conversely, it was noted that with its provision
regarding the statute of limitations, the World Anti-
Doping Agency‘s code is not in line with Swiss law.
This legal opinion from CAS has laid the foundations
for FIFA to make the necessary adjustments to the
relevant provisions independently. FIFA will, however,
invite the CAS panel to join a working group and assist
to make these adjustments.
Beyond that, after being operational for two years,
it seems reasonable to reflect on the feasibility and
applicability of the World Anti-Doping Code based
upon the analysis of positive doping cases as related to
the incidence and management amongst the different
member associations. Such analysis is foreseen within
the revision of the World Anti-Doping Code which has
been initiated by WADA in April 2006.
Occupational Medicine in Football –
a Vision
Occupational medicine deals with all work-related
health aspects that have an effect on the employee’s
ability to function effectively; the workplace itself,
the type of work, the state of health of the employee.
In addition to purely physical aspects, social and
psychological influences must also be considered.
It is easy to see that a construction worker who is paid
according to how much work he completes will be
subject to greater stress factors than, say, a gardener or
office worker employed on standard terms.
Moreover, within any occupation there are those – often
a considerable percentage – who will regularly need
medication to function properly, e.g. those suffering
from diabetes, high blood pressure, allergies, rheumatic
disorders etc. In such cases, any extra stress in the
work environment can easily lead to a situation where
the ability of the person to function is close to the
borderline of what can be physically expected, and these
people can often become incapable of continuing in the
job or of only doing so under medical supervision and
with the prescription of suitable medication.
There are definite limits to the level of stress under
which such people can function and it is the concern
of occupational medicine to recognise and deal with
these limits. Occupational medicine aims to point out
to both employer and employee that only under certain
specified conditions will optimum performance be
possible. The conditions that could be recommended
in such cases might include changes in the workplace,
in working hours, in the pressure of the job, or might
specify regular medical treatment for the employee, e.g.
prescribed medication to protect the employee from the
effects of workday stress, such as beta blockers.
If we now turn to sports like football, a number of
examples can be identified:
The proportion of players who suffer from allergies
is similar to that in the general population, and the
treatment will be the same, i.e. appropriate therapy
often involving the taking of medication, especially
during those times of the year when the allergen count
is high. But when we are dealing with open-air sports,
the treatment prescribed could lead to problems since
many of the drugs normally prescribed are on the list of
banned substances (such as corticosteroids) even though
their prescription is medically justified.
A case that makes the situation very clear is that of an
American professional international female player. She
suffers from a relatively rare disease that makes her
blood pressure and fluid balance subject to extreme
variations; this in turn makes it impossible for her,
without medical help, to pursue her profession at the
required level. She needs ongoing treatment with a socalled
mineralocorticoid (Fludrocortisone). However, in
contrast to those mentioned above, this medication has
neither an anabolic nor an anti-phlogistic effect and is
thus not technically a doping substance in the true sense
of the term.

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This raises the question of whether it really constitutes
doping if a player can perform at the expected level only
after taking such medication. We suggest that this is a
problem that would fall within the scope of occupational
medicine. If such treatment is prescribed for genuine
medical reasons and involves taking a drug that in itself
has no doping effect, then we cannot be talking about a
case of doping, rather merely of enabling a professional
athlete to exercise his or her normal profession.
Occasional treatment with banned substances for “bona
There are limits of stress under
which people can function and
occupational medicine recognises
and deals with these limits.
fide” medical reasons should be permitted if the facts of
the case are presented openly to the doctors in charge of
the doping control.
A quite different question is whether the ever-increasing
demands made on professional footballers, in terms of
the number of matches and tournaments in which they
are expected to play, can be compensated for by taking
medication so that the required level of performance can
be achieved over and over again.
Playing so frequently, in football as in other sports,
under circumstances necessitating more or less continual
treatment with painkillers and anti-inflammatory
agents can have serious long-term consequences that
really cannot be justified on the basis of occupational
medicine or medical ethics. In this case, the limits of
doping are recognisable.
Admittedly, there is no doping in these cases in terms of
performance-enhancing drugs being taken. However, in
the sense of medical treatment being used to suppress
the symptoms of injuries and over-exertion, there is
clearly an aspect of doping involved. The workplace
pressure being placed on players in the short term leads
to the long-term effects being ignored.
As long as the players in question and their associations
all have the same approach, only a firm stand taken by
sports and occupational medicine will have the effect
of providing the players with at least partial protection
from such long-term damage. This is yet another reason
why the campaign against real doping must be actively
pursued.
Contributing Authors:
Prof. Jiri Dvorak
Michel D’Hooghe, MD
Prof. Toni Graf-Baumann
Don Kirkendall, PhD
Martial Saugy, PhD
Heinz Tännler

Social Drugs: Cannabis

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F-MARC DOPING UPDATE 2006 | SOCIAL DRUGS: CANNABIS 31
Social Drugs: Cannabis
Introduction
Marijuana, or cannabis, refers to the dried leaves and
flowers of the Cannabis sativa plant. Hashish is the dried
juice (resin) that is extracted from the leaves. The active
ingredient in hashish and marijuana is THC (delta9-
Tetrahydrocannabinol) and causes subjective effects of
relaxation and contentment.
Objective tests of psychological or physical performance
all show impairment. Driving ability and memorisation
declines. Other effects include a rapid heart rate,
dilatation of small blood vessels of the eye and reduction
of blood pressure.
Absorption and Metabolism
Absorption and metabolism of THC vary as a function
of route of administration. Pulmonary assimilation of
inhaled THC causes a maximum plasma concentration
within minutes with a peak of effect within 15 to 30
minutes and returning to baseline after 2-3 hours.
Oral ingestion leads to later and longer effects with a
maximum of between 2-3 hours.
THC is metabolised mainly by hydroxylation and
oxidation. The main metabolite is the 11-nor-9-carboxy-
THC (THC-COOH), which may be glucuronated.
Urine Excretion
After smoking cannabis, urine starts to test positive for
THC-COOH after an average of 4 hours (range = 2 to
8 hours). The long-term excretion of cannabis
metabolite is due to the high lipophility of THC, which
binds to fat tissues. This leads to a great inter-individual
variability of the excretion of this product.
Several studies have shown that the urine excretion
pattern is strongly dependent on the status of the
individuals. After taking a single dose of THC, the
metabolite can be detectable for 3 to 5 days, but some
authors showed detection for up to 12 days.
Huestis et al., 1998, reported an average urinary half-life
of THC-COOH of about 45 to 60 hours while other
groups have reported wider times of 0.9 to 9.8 days. It is
clear that heavy users will show the first negative result
in urine after stopping THC consumption much later
than infrequent users. In one study, the average time to
the first negative result in screening for THC metabolite
(cut-off level 20 ng/ml) was 8.5 days (range 3 to 18)
for infrequent users and 19.1 days (range 3 to 46) for
regular users.
Urinary concentration of between 20 and 50 ng can
then often be attributed to a late excretion of cannabis
consumption and hardly related to any recent intake.
15 ng/ml Cut-off
This limit of 15 ng/ml has been chosen in forensic science
to avoid any false positive cases due to passive inhalation.
It has been demonstrated that passive inhalation will not
lead to a urinary result above this limit.
References
Kurzthaler I, Hummer M, Miller C, Sperner-Unterweger B,
Gunther V, Wechdorn H, Battista HJ, Fleischhacker WW
Effect of cannabis use on cognitive functions and driving ability.
[Clinical Trial. Journal Article. Randomised Controlled Trial]
Journal of Clinical Psychiatry. 60(6):395-9, 1999
Niedbala RS, Kardos KW, Fritch DF, Kardos S, Fries T, Waga J,
Robb J, Cone EJ
Detection of marijuana use by oral fluid and urine analysis following
single-dose administration of smoked and oral marijuana.
[Journal Article] Journal of Analytical Toxicology. 25(5):289-303, 2001
Huestis MA, Cone EJ
Differentiating new marijuana use from residual drug excretion in
occasional marijuana users. [Clinical Trial. Controlled Clinical Trial.
Journal Article] Journal of Analytical Toxicology. 22(6):445-54, 1998
Heather Ashton C
Pharmacology and effects of cannabis. A brief review.
British Journal of Psychiatry 178: 101-106, 2001
Contributing Author:
Martial Saugy, PhD
The active ingredient in hashish and marijuana
is THC and causes subjective effects of relaxation
and contentment.
Leaf of the cannabis plant

Stimulants

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Stimulants
Introduction
This class of drugs stimulates the central nervous system
(CNS) and may be used to reduce tiredness and increase
alertness, competitiveness and aggression. For this reason,
they are considered to have a performance enhancing
effect in explosive power activities and endurance events,
since the capacity to exercise strenuously is increased
and sensitivity to pain is reduced. Stimulants are more
likely to be used on the day of a competition; however,
they may be used in training, to allow the intensity of
the training session to be increased. Since stimulants
could increase an athlete’s aggression towards other
competitors or officials, there are potential dangers
involved in their misuse in contact sports. Relatively
high doses are needed to reduce fatigue and performance
can be reduced by side-effects, such as tremors for
example.
The stimulants class includes psychomotor stimulants,
sympathomimetics and miscellaneous central nervous
system stimulants. Examples of this class include caffeine,
amphetamines, ephedrines and cocaine. Caffeine is the
pharmacologically active substance found in tea, coffee
and cola. The amount of caffeine present varies according
to the type of drink and the way it has been prepared.
In addition, caffeine may be a constituent of some
Amphetamine Ephedrine Cocaine
H
NH 2
C
CH 2
CH
3
H CH3 N
H3C C H
H
C OH
Amphetamine
Ephedrine
Cocaine
Figure 1: Chemical structure of amphetamine, ephedrine and cocaine
common medications such as cold preparations and pain
relief treatments, usually in quantities of less than 100
mg per dose. Caffeine produces mild central nervous
system stimulation, similar to that of amphetamines,
reducing fatigue and increasing concentration and
alertness. Physiological effects include increased heart
rate and output, increased metabolic rate and urine
production. High doses can cause anxiety, insomnia
and nervousness. In 2004, caffeine was removed from
the list of prohibited substances and is now part of the
monitoring programme.
Amphetamines are controlled substances under general
drugs legislation, although they have been prescribed as
appetite suppressants and for the treatment of narcolepsy.
Amphetamines are known to produce dependence,
often in increasing doses. Athletes are likely to use
amphetamines to sharpen reflexes and reduce tiredness.
However, athletes have died as a result of amphetamine
misuse, since the increase in blood pressure combined
with increased physical activity and peripheral
vasoconstriction makes it difficult for the body to cool
down. If the body overheats, it dehydrates and blood
circulation decreases, and the heart and other organs are
unable to work normally.
The sympathomimetic drug, ephedrine, is used to treat
the symptoms of the cold virus, and was originally
O
O
C
C
O
CH 3
N
CH 3
prescribed as a bronchodilator for asthma, although it
is now regarded as less suitable for this use since it has
been linked with cardiac arrhythmia. Ephedrine is likely
to be misused for its stimulant effect but could also be
ingested inadvertently because of its wide availability in
over-the-counter medications.
Cocaine has been used as a medication for many years.
It was an original ingredient in Coca-Cola until it was
removed in 1903. Its therapeutic indication is as a local
anaesthetic, though misuse would be linked to its euphoric
effects and a feeling of decreased fatigue. Its potential for
use as a recreational drug emphasises the lifestyle pressures
faced by some athletes. In some disciplinary sports, like
sprint athletes, cocaine is likely to increase heat and lactic
formation, which, coupled with vasoconstriction, could
contribute to fatal cardiac damage.
Amphetamine
Amphetamine was synthesised in 1920 and used to
reduce fatigue and increase alertness during World War
II. Since then, many derivatives have been elaborated,
such as f. e. methamphetamine, dimethamphetamine,
methylendioxyamphetamine (MDA), methylendioxy
methamphetamine (MDMA, “ecstasy”) or selegiline,
and they are all forbidden in the practice of sport.
Annual statistics for drug testing by IOC accredited laboratories
Year Total A-samples analysed Number of positive samples with
stimulants
Amphetamine was prescribed unsuccessfully as a nasal
decongestant, anti-depressant and appetite suppressant,
but rapidly appeared to be a powerful central nervous
system stimulant acting primarily by enhancing the brain
activity of norepinephrine and dopamine, intensifying
psychological sensations of alertness, concentration and
self-confidence.
Metabolism of Amphetamines
2003 ** 151,210 516 0.35
2002 * 131,373 392 0.30
2001 * 125,701 352 0.28
2000 * 117,314 453 0.39
1999 * 118,243 532 0.45
1998 * 105,250 412 0.39
1997 * 106,561 356 0.33
1996 * 96,454 281 0.29
1995 * 93,938 310 0.33
1994 * 93,680 347 0.37
1993 * 89,166 331 0.37
1992 * 87,808 277 0.32
1991 * 84,088 221 0.26
1990 * 71,941 340 0.47
1989 * 52,371 508 0.97
1988 * 47,069 420 0.89
Table 1: Annual statistics for drug testing by IOC-accredited laboratories * Data from IOC, ** Data from WADA
Amphetamine is readily absorbed, mainly from the
small intestine, and the peak plasma concentration
occurs 1-2 hours following administration. Absorption
is usually complete in 2.5-4 hours and is accelerated by
food intake. The metabolism of amphetamine has been
difficult to investigate because of the wide variation
between species in its metabolic effects. The principal
amphetamine metabolites are p-hydroxy ephedrine
and p-hydroxy amphetamine. Amphetamine is lost
from the body by renal filtration. For the detection of
amphetamine use in sport, the urine is analysed for the
parent compound amphetamine.
After a single dose of amphetamine, it has been shown
that detection can be achieved in urine in the first urine
void and can be seen for at least 48 hours after the intake
of the drug. The peak concentration in urine is strongly
% positive samples with stimulants

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F-MARC DOPING UPDATE 2006 | STIMULANTS 37
dependent on the individuals, but occurs between 3 and
12 hours after the intake of the drug. Amphetamine
excretion is enhanced by an acidic urine, and treatments
that increase the acidity of urine enhance amphetamine
loss – a reaction that is useful in the treatment of
amphetamine overdose.
Amphetamine Action
The positive effects of amphetamines include an increase
in physical energy, mental aptitude, talkativeness,
restlessness, excitement and good humour. Subjects
taking amphetamine also report that they feel confident,
efficient, ambitious and that their food intake is reduced.
Some negative effects of amphetamine (that can be
dose-dependant) are anxiety, indifference, slowness in
reasoning, irresponsible behaviour, irritability, dry mouth,
tremors, insomnia and, following withdrawal, depression.
Tolerance develops rapidly to many of the effects of
the amphetamines. Tolerance is said to be present
when, over a period of time, increasing doses of a drug
are required to maintain the same response. There is
significant evidence to show that amphetamines induce
drug dependence and the amphetamine-dependant
person may become psychotic, aggressive and anti-social.
Withdrawal of amphetamines is associated with mental
and physical depression.
The major side-effects of amphetamine administration
include confusion, delirium, sweating, palpitations,
dilation of the pupil and rapid breathing as well as
hypertension, tachycardia, tremors, muscle and joint
pain. Chronic amphetamine administration is associated
with myocardial pathology and with growth retardation
in adolescents. In most cases, the personality changes
induced by chronic low doses of amphetamine are
reversed gradually after the drug is stopped. High chronic
doses may lead to a variety of persistent personality
changes, paranoid delusions and tactile hallucinations
called amphetamine psychosis.
Amphetamines in Sport
Amphetamines induce drug dependence
and the dependant person may become
psychotic, aggressive and anti-social
The effect of amphetamines on sporting performance
was first investigated in 1959. It has been concluded
that amphetamines enhance anaerobic performance
while having little or no effect on aerobic performance.
Amphetamines might enhance sports performance from
a supplemental mental stimulant effect as well as the
effects on physical power derived from all three human
energy systems – the anaerobic (ATP-CP, lactic acid)
and oxygen energy systems. Depending on the type of
effect or effort the athlete has to do, the dosage might
be important for the user. Aggressiveness seems to be
increased by high dosage, when alertness is stimulated
by lower quantities. To summarise, amphetamines
might improve reaction time when fatigued, increase
muscular strength and endurance, increase acceleration,
raise lactic acid levels at maximal exercise, increase
aerobic endurance capacity and stimulate metabolism by
inducing a loss of body fat.
All amphetamines are banned by the WADA and IOC
codes. Laboratory analysis is qualitative only, verifying
the presence of metabolites in urine. It is sufficient to
demonstrate the substance is present in the urine to
declare the case as an analytical adverse finding. The
presence of amphetamine in urine can be described as
a severe doping offence because amphetamines are no
longer used therapeutically. Many countries prohibit
their use because of their adverse effects. Amphetamines
are part of the S6 category of the prohibited substances
in competition.
Amphetamine Side-Effects in Relation to Sport
Side-effects of amphetamine beyond headaches,
sleeplessness and anxiety are particularly important to
athletes. Indeed, amphetamine use may carry significant
health risks for the sportsman as evidenced by several
amphetamine-linked deaths in sport. Two of the major
risks are amphetamine-induced heatstroke and cardiac
arrest that have caused several fatalities in cyclists during
arduous effort. Amphetamines obscure painful injuries
and have enabled athletes in some sports to continue to
compete and exacerbate their injuries. The side-effects of
amphetamine on behaviour are also important in sport.
Amphetamine administered to promote aggression and
weaken fatigue has led to misjudgements and major fouls
on the pitch, due to its euphoric effects.
Cocaine
Cocaine is the most potent stimulant of natural origin.
As opposed to amphetamines, which are pure synthetic
compounds, cocaine is primarily obtained from coca
species and its notoriety belies the fact that the drug has
been used as a stimulant for thousand of years. Incas used
to chew coca leaves to fight against tiredness; cocaine was
used in a number of patent medicines and even in soft
drinks. In its pure form, cocaine is a white crystalline
powder extracted from the leaves of the South American
coca plant. Pure cocaine was first used medicinally in
the 1880s as a local anaesthetic in eye, nose and throat
surgery because of its ability to provide anaesthesia as
well as to constrict blood vessels and limit bleeding.
Many of its therapeutic applications are obsolete though
due to the development of safer drugs.
Cocaine can be snorted, smoked or injected. When
snorted, cocaine powder is inhaled through the nose and
absorbed into the bloodstream through the nasal tissues.
When injected, a needle is used to release the drug
directly into the bloodstream. Smoking involves inhaling
cocaine vapour or smoke into the lungs where absorption
into the bloodstream is as rapid as by injection. Each
of these methods of administration pose great risks to
the user. Crack is cocaine that has been processed from
cocaine hydrochloride to a free base for smoking. The
most popular route of administration is snorting, which
produces peak effect from 5-15 minutes and lasts for up
to one hour. Inhalation of free-base cocaine produces
peak effects in less than 1 minute and a short-lived
physiological effect measured in minutes.

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Cocaine Action
Cocaine is a strong central nervous system stimulant
and is probably the most addictive agent known. Its
recreational use is widespread, and it is highly addictive
with its effect mediated through dopamine release. For
ethical and practical reasons, most of the knowledge of
the pharmacology of cocaine comes from animal studies
or from addict reports. Physical effects of cocaine use
include constricted blood vessels, increased temperature,
heart rate and blood pressure. It also increases motor
activity, talkativeness and is a strong agent to reach
euphoria. The duration of cocaine’s immediate euphoric
effects (hyper-stimulation, reduced fatigue and mental
clarity) depends on the route of administration. The
faster the absorption, the more intense the effects and
the shorter the duration of action. The effects from
snorting may last 15 to 30 minutes while the effects from
smoking may last 5 to 10 minutes. Increased use can
reduce the period of time a user feels high and increases
the risk of addiction.
Cocaine users usually feel an initial “rush” or sense of
well-being, of having more energy and being more
alert. This effect quickly wears off, often leaving the
user feeling more “down” or depressed than before.
This down feeling leads the addict to use more cocaine,
sometimes just to feel “normal”. Over a period of time,
the amount of cocaine needed and the frequency of use
to achieve a “high” have to be increased. Classic physical
effects of cocaine use include constricted blood vessels,
dilated pupils and increased temperature, heart rate and
blood pressure.
Cocaine is more highly addictive than amphetamine and
the increasingly higher doses addicts are using may lead
to a state of irritability, restlessness, anxiety and paranoia.
Other complications associated with cocaine use include
disturbances in hearth rhythm and heart attacks,
chest pain and respiratory failure, strokes, seizures and
headaches and gastrointestinal complications such as
abdominal pain and nausea. Cocaine abuse is strongly
associated with cerebrovascular accidents arising either
from the rupture or spasm of cerebral blood vessels.
Different means of taking cocaine can produce different
adverse effects. Regular snorting, for example, can lead
to loss of sense of smell, nosebleeds, problems with
swallowing, hoarseness, and a chronically runny nose.
Ingesting cocaine can cause severe bowel gangrene due
to reduced blood flow. People who inject cocaine can
experience severe allergic reactions and, as with any
injecting drug user, are at increased risk of contracting
HIV and other blood borne diseases.
The initial “rush“ quickly wears off,
often leaving the user feeling more
“down” or depressed than before
Cocaine in Sport
Contrary to popular belief, cocaine does not really enhance
performance, whether in the job, in sport, at school or
with a sexual partner. On the contrary, long-term use can
lead to loss of concentration, irritability, loss of memory,
paranoia, loss of energy, anxiety and a loss of interest in
sex. In particular, several studies have demonstrated that
cocaine has no beneficial effect on running times and
reduces endurance performance. Furthermore, at all doses,
cocaine significantly increases glycogen degradation while
increasing plasma lactate concentration without producing
consistent changes in plasma catecholamine levels. The
controlling effect cocaine has on an addict’s life can lead
to exclusion of all other facets of life. Nevertheless, despite
these apparently detrimental effects, cocaine continues
to be abused in sport. It may be that cocaine only affects
activities of short duration requiring a burst of highintensity
energy output. It is possible that the central
nervous stimulatory effect may be more important than
its action on peripheral metabolism. It has been suggested
that the heightened arousal and increased alertness effects,
achieved principally at low doses, drew athletes to cocaine.
Cocaine was federally regulated in December 1914.
This act banned non-medical use of cocaine, prohibited
its importation and sale. Cocaine can currently be
administered by a doctor for legitimate medical use,
such as local anaesthetic for some eye, ear and throat
surgeries. Cocaine is banned by both WADA and
the IOC, including its use as a local anaesthetic.
Like amphetamines, it is part of category S6 of the
prohibited substances in competition and the presence
of cocaine and/or its metabolites (benzoylecgonine and
methylecgonine) in urine can be described as a severe
doping offence.
Cocaine Side-effects in Relation to Sport
A number of dramatic fatalities associated with coronary
occlusion have occurred in cocaine-abusing athletes,
usually those who have been exercising intensely
following drug administration. Many sports people who
abuse cocaine complain of negative central effects such
as perceptual misjudgements and time disorientation
that sometimes reduces their athletic performance.
Furthermore, cocaine addicts frequently turn to other
drugs to relieve the “down” feeling when more cocaine
is not available. When used together, these drugs and
cocaine can prove even more deadly than when used alone.
Some fatalities have also occurred when cocaine abuse has
been mixed with alcohol or anabolic steroids. Joint abuse
of alcohol and cocaine is extremely cardiotoxic. These
practices increase the risk of sudden death by cardiac arrest
or seizures followed by respiratory arrest.
Ephedrines
Ephedra alkaloids which are popular components of
many nutritional supplements are naturally occurring
central nervous system stimulants obtained from
several ephedra plant species. Purified forms of these
substances include ephedrine, pseudoephedrine,
norephedrine, methylephedrine, norpseudoephedrine
and methylpseudoephedrine. Phenylpropanolamine is a
synthetic compound functionally similar to the ephedra
alkaloids in effect and use. Ephedrine, which is now
also produced by chemical synthesis, is closely related in
structure to metamphetamine, although its CNS actions
are much less potent and also longer-acting than those
of amphetamines. Its peripheral stimulant actions are
similar to, but less powerful than, those of epinephrine
(also called adrenaline), a hormone produced in the body
by the adrenal glands.
Ephedrines Action
Of the ephedra alkaloids, ephedrine is the most
potent thermogenic agent. Ephedrine is a mixed
sympathomimetic agent, which acts as a stimulant in
the central nervous system by enhancing the release
of norepinephrine from sympathetic neurons and
stimulating alpha and beta receptors. Ephedrine
stimulates heart rate and thereby increases cardiac
output, but also causes peripheral constriction, resulting
in an increase in peripheral resistance that can lead to a
sustained rise in blood pressure. Ephedrine relaxes the
bronchial smooth muscle and is used as a decongestant
and for temporary relief of shortness of breath caused by
asthma.
Historically, ephedra alkaloids have been used for both
asthma and allergies in China for more than 5,000 years.
Ephedrine has moderately potent bronchial muscle
relaxant properties and has been used clinically for the
treatment of asthma. Currently, ephedrine is found in
various pharmaceuticals mainly as decongestants and
in numerous nutritional and dietary supplements as
energy stimulants and anorexic agents. Pseudoephedrine
can be found in many prescription and over-thecounter
preparations (mostly for the treatment of
congestion) that may be used for treating respiratory
infections or allergies. Until its recent voluntary removal

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F-MARC DOPING UPDATE 2006 | STIMULANTS 41
from the market because of reports of
increased risk of strokes in women,
phenylpropanolamine was also used
similarly to pseudoephedrine and in overthe-counter
diet pills.
Ephedrine is excreted in a largely unchanged
form in urine and the usual elimination halflife
is 3 to 6 hours, which can be prolonged with
increased urine pH.
Common side-effects of ephedrine are qualitatively
similar to those produced by amphetamines,
but are generally milder: headache, dizziness,
irritability, anxiety, tremor and psychosis. Higher
doses (overdose) can cause restlessness and anxiety,
dizziness, insomnia, tremor, rapid pulse, sweating,
respiratory difficulties, confusion, hallucinations,
delirium and convulsions. The most dangerous
symptoms of overdose are abnormally high blood
pressure and rapid, irregular heartbeat. A dose of
ephedrine only two or three times the therapeutic
maximum can cause a significant increase in blood
pressure. Finally, a number of instances of psychosis,
clinically similar to amphetamine psychosis, have
resulted from chronic high-dose abuse.
Regarding food supplements containing ephedra
alkaloids, there are serious doubts concerning their safety.
Because supplements are not considered therapeutic, they
are not held to the same level of rigor in claiming efficacy
and safety as that required of prescribed and over-thecounter
medications. Since the 1994 deregulation, an
increased number of reports of adverse events, including
hypertension, arrhythmia, myocardial infarction, seizure,
cerebrovascular accidents and death, has prompted
the FDA to recommend a limit on the use of ephedra
alkaloids. Furthermore, the joint use of ephedrine and
caffeine can augment adverse cardiovascular and CNS
effects.
Ephedrine in Sport
With their stimulant properties and sympathomimetic
actions, ephedra alkaloids have been perceived as
products that can potentially be used to enhance athletic
performance and lending unfair advantages to athletes,
even if used in supplement forms. Research has shown
that the isolated use of ephedrine, pseudoephedrine
and phenylpropanolamine alone at usual dosages has
an inconsistent, and probably insignificant, ergogenic
benefit for power, endurance, strength or speed. Other
studies looking at the use of ephedrine combined with
vitamins, minerals or caffeine have supported potential
ergogenic effects. Indeed, many athletes use food
supplements containing ephedra alkaloids because of
perceived benefits of increased energy, increased time
to exhaustion and potential thermogenic properties
with increased metabolism, increased fat loss and
improved muscle strength. In particular, a series of
studies evaluated the effects of ephedrine in combination
with caffeine, showing an increased time to exhaustion
and decreased rating of perceived exhaustion on cycle
ergometry compared with either the drug alone or a
placebo. The medical use of ephedrine is tolerated by
WADA and the IOC at therapeutic levels. Nevertheless,
urine concentrations of greater than 10 µg/ml are
considered positive. Ephedrine is a category S6 prohibited
substance.
Ephedrine Side-Effects in Relation to Sport
Because of recent highly publicised tragedies, various
athletic associations have focused on further evaluations
of the use of these substances and on trying to educate
athletes about potential health risks associated with their
use. Continued evaluation of the use of these substances
is necessary, as is continued education of athletes,
parents, coaches and trainers regarding the health risks
associated with ephedrine alkaloids and corresponding
supplements.
References
Bohn AM, Khodaee M, Schwenk TL
Ephedrine and other stimulants as ergogenic aids.
Current Sports Medicine Reports, 2(4): pp 220-225, 2003.
George AJ
Central nervous system stimulants. Best Practice & Research
Clinical Endocrinology & Metabolism, 14(1): pp 79-88, 2000.
Verroken M
Drug use and abuse in sport. Best Practice & Research Clinical
Endocrinology & Metabolism, 14(1): pp 1-23, 2000.
Contributing Authors:
Lidia Mateus-Avois, PhD
Neil Robinson, PhD
Christophe Saudan, PhD
Norbert Baume, PhD
and Martial Saugy, PhD
Regarding food supplements containing
ephedra alkaloids, there are serious doubts
concerning their safety

Testosterone and
Synthetic Anabolic Steroids

44 TESTOSTERONE AND SYNTHETIC ANABOLIC STEROIDS | F-MARC DOPING UPDATE 2006
F-MARC DOPING UPDATE 2006 | TESTOSTERONE AND SYNTHETIC ANABOLIC STEROIDS 45
Testosterone and Synthetic Anabolic Steroids
Introduction
Anabolic steroids are chemical, synthetic derivatives
of testosterone modified to enhance the anabolic
and minimise androgenic actions of the hormone.
Testosterone is a steroid hormone synthesised
in the human body from cholesterol and serves
distinct functions at different stages of life. During
embryonic development, androgen action is central
to the development of the male phenotype. At
puberty, the hormone is responsible for the secondary
sexual characteristics that transform boys into men.
Testosterone regulates many physiological processes in
the adult male including muscle protein metabolism,
sexual and cognitive functions, erythropoiesis, plasma
lipids and bone metabolism.
The purpose of this article is to give an overview
of the use of anabolic-androgenic steroids (AAS) in
sport together with the methods used in anti-doping
laboratories for their detection in urine. In the following
article in this issue, special emphasis is laid on the use
of nandrolone, which is known to be one of the most
widely used AAS by athletes who need power and
muscle strength.
Anabolic steroids are effective in
enhancing athletic performance, but the
side-effects can jeopardise health
Pharmaceutical Action of Anabolic Steroids
Soon after testosterone was isolated in 1935, it was
discovered that it is virtually inactive when taken
orally. After oral ingestion, testosterone is absorbed
from the small intestines and passes via the portal vein
to the liver where it is rapidly metabolised, mostly to
inactive compounds. The discovery of testosterone
has given rise to the synthesis of anabolic steroids.
Chemical modifications of testosterone have been
useful pharmacologically to alter the relative anabolicandrogenic
potency, slow the rate of inactivation and
change the pattern of metabolism. Most oral anabolicandrogenic
steroids preparations are 17-alpha alkylated
derivatives of testosterone that are relatively resistant
to hepatic degradation. Esterification of the 17-beta
hydroxyl group makes the molecule more soluble in
lipid vesicles used for injection and hence slows the
release of the injected steroid into the circulation.
Commonly used 17-α alkyl and 17-β ester derivatives are:
17-α alkyl derivatives:
stanozolol, danazol, fluoxymesterone,
methyltestosterone, methandrostenolone, oxandrolone
and oxymetholone
17-β ester derivatives:
Nandrolone decanoate, boldenone, trenbolone,
methenolone and testosterone enanthate
Evidence suggests that at the normal male physiological
range of plasma testosterone concentrations, the
androgen receptors to which testosterone and
dihydrotesterone (DHT) bind are fully saturated. Invitro
studies have demonstrated that the dose-response
relationship of testosterone on growth of skeletal muscle
reaches a plateau once the physiological concentration
is exceeded. It has been suggested that when anabolic
steroids are abused by athletes, the drugs are producing
their effects by another receptor mechanism, unsaturated
or unaffected by normal plasma testosterone and DHT
concentrations. Indeed, it is supposed that the effect
of a supraphysiological dose of testosterone on muscle
is mediated through an antiglucocorticoid action
independent of androgen receptors. Glucocorticoids
such as cortisol and corticosterone are hormones that
influence glucose synthesis and protein catabolism.
Stimulation of glucocorticoid receptors will lead to
an enhancement of protein breakdown in muscle.
According to one theory, the high doses of anabolic
steroids used by many athletes displace glucocorticoids
from glucocorticoid receptors and inhibit muscle
protein catabolism, leading overall to an anabolic or
muscle-building effect.
Therapeutic Uses of Anabolic-Androgenic Steroids
A number of clinical studies using a variety of
experimental designs have shown that the potent
anabolic effects of AAS have positive benefits to various
patient populations. Physiological replacement doses of
testosterone have been used therapeutically to stimulate
sexual development in cases of delayed puberty and in
cases where the testicles have been surgically removed,
because of either physical injury or testicular tumour.
Anabolic steroids are occasionally used to treat
gynaecological conditions in women, although longterm
usage produces severe side-effects such as erratic
menstruation and the appearance of male secondary
characteristics. They are occasionally used to combat
breast tumours in pre-menopausal women.
The first major clinical use of anabolic steroids was to
inhibit the loss of protein and aid muscle regeneration
after major surgery. Anabolic steroids may be used to
increase growth in prepubescent boys who have failed to
reach the expected height for their age.
Adverse Effects of Anabolic-Androgenic Steroids
Anabolic steroids are effective in enhancing athletic
performance. The trade off, however, is the occurrence
of adverse side-effects that can jeopardise health. Since
AAS have effects on several organ systems, a myriad of
side-effects can be found. In general, orally administered
AAS have more adverse effects than parenterally
administered AAS. In addition, the type of AAS is not
only important for the advantageous effects, but also
for the adverse effects with the AAS containing a 17alkyl
group having potentially more adverse affects,
particularly to the liver. One of the problems with
athletes, in particular strength athletes and bodybuilders,
is the use of oral and parenteral AAS at the same time
(“stacking”), and in dosages that may be several (up to
40 times) the recommended therapeutical dosage. The
frequency and severity of side-effects is quite variable.
This depends on several factors such as the type of drug,
dosage, duration of use and the individual sensitivity
and response.
The potential adverse effects of AAS can be divided
into several main categories, including cardiovascular,
hepatic, endocrine/reproductive, psychological and
tendon injury:
Cardiovascular. Chronic administration of anabolic
steroids causes a reversible reduction in serum highdensity
lipoprotein (HDL) levels. Since HDL binds
cholesterol and renders it inert, reduced HDL levels are
associated with arteriosclerosis, although no long-term
study on athletes has been completed.
Hepatic. AAS may exert a profound adverse effect on
the liver. This is particularly true for orally administered
AAS. Parenterally administered AAS seem to have less
serious effects on the liver. Testosterone cypionate,
testosterone enanthate and other injectable anabolic
steroids seem to have few adverse effects on the liver.
However, lesions of the liver have been reported after
parenteral nortestosterone administration, and also
occasionally after injection of testosterone esters. The
influence of AAS on liver function has been studied
extensively. The majority of the studies involve
hospitalised patients being treated for prolonged
periods for diseases such as anaemia, renal insufficiency,
impotence and pituitary dysfunction. In clinical trials,
treatment with anabolic steroids resulted in a decreased
hepatic excretory function.

46 TESTOSTERONE AND SYNTHETIC ANABOLIC STEROIDS | F-MARC DOPING UPDATE 2006
F-MARC DOPING UPDATE 2006 | TESTOSTERONE AND SYNTHETIC ANABOLIC STEROIDS 47
Endocrine/reproductive. Endogenous AAS lead to
reduced serum testosterone levels that can influence
spermatogenesis and lead to a severe decrease of fertility
in males. In one study, the sperm count fell by 73%,
and in three individuals, azoospermia (complete absence
of sperm cells) was present when high doses of anabolic
steroids were taken chronically. In-depth interviews
with 110 AAS users revealed that 56% of the males
reported testicular atrophy and 62% of the females had
menstrual irregularities. It should be also mentioned
that long-term administration of steroids might lead
to the development of mammary tissue because AAS
can be converted to oestradiol by hepatic aromatase
enzymes, which then induces development of mammary
tissue.
Psychological. Administration of AAS may affect
behaviour. Increased testosterone levels in the blood are
associated with masculine behaviour, aggressiveness and
increased sexual desire. Increased aggressiveness may
be beneficial for athletic training, but may also lead to
overt violence outside the training environment. There
are reports of violent, criminal behaviour in individuals
taking AAS. Other side-effects of AAS are euphoria,
confusion, sleeping disorders, pathological anxiety,
paranoia and hallucinations.
Tendon injuries. Tendon rupture has been linked with
AAS based on a small number of published case reports.
It has been suggested that these drugs predispose tendon
rupture by altering collagen structure. It is possible that
the rapid strength adaptations produced by AAS in
skeletal muscle are not simultaneously matched by the
more slowly-adapting, less vascular tendon structures,
making tendons the weak link in the chain.
Testosterone
Figure 1. Molecular structure of testosterone
Athletic Use of Anabolic-Androgenic Steroids
For many years, the medical community combated
AAS use by denying its effectiveness for promoting
lean body mass. Early studies were flawed and did not
reflect the way AAS are used. Athletes actually “cycle”
on and off compounds, switching from one to another
to avoid developing tolerance. They “stack” AAS, taking
several different steroids at the same time to lower the
dose of each and activate different steroid receptors. The
scientific basis for stacking is highly questionable and
has not been proven.
AAS are generally accepted as having the desired
anabolic effects, provided athletes also consume
adequate protein and exercise intensely. In a randomised
controlled trial, those taking 600mg testosterone
intra-muscular injections weekly for 10 weeks had
significantly increased muscle mass, muscle strength and
fat-free mass compared to the placebo. However, not all
studies have found such strength gains.
Testing for Anabolic-Androgenic Steroids
International organisations have established a list
of substance classes and methods that athletes are
forbidden to use during competition and training. The
latest list established by the World Anti-Doping Agency
(WADA) for 2005 includes two types of steroids:
1. Typically exogenous steroids, whose main examples
have been given previously.
2. Typically endogenous steroids, e.g. androstenediol,
androstendione, dehydroepiandrosterone (DHEA),
dihydrotestosterone (DHT), testosterone and related
substances.
Testing for anabolic agents in the urine of athletes was
implemented on a large scale during the 1976 Montreal
Olympic Games and was mainly based on radioimmunoassay
(RIA) techniques. The techniques for the
identification and characterisation of steroids and their
metabolites in the urine have improved considerably
during the last two decades. This improvement is
largely due to the use of gas chromatography-mass
spectrometry (GC-MS) techniques. Today, most antidoping
laboratories use techniques that are based on
the solid phase extraction of the urine sample followed
by chemical modifications prior to GC-MS analysis.
The confirmation procedure in an anti-doping analysis
consists of demonstrating unequivocally that there is
a correspondence between the GC and MS properties
of the anabolic agent or its metabolite with those of
an authentic pure standard or of a reference excretion
study.
The detection of exogenous substances means identifying
the parent compound or at least one metabolite.
Nevertheless, with substances that are produced
endogenously such as testosterone, the presence of the
substance alone cannot be considered to be an offence
by itself. Moreover, a cut-off value for testosterone
concentration cannot be used because of large interindividual
and intra-individual urinary concentrations of
the steroid. The intake of testosterone, however, causes
characteristic changes in the pattern of steroids excreted
in the urine. Based on studies of athletic populations,
in 1983 the International Olympic Committee (IOC)
adopted a ratio of testosterone to epitestosterone (T/
E) with an authorised upper limit of 6.0 as a criterion
for the administration of testosterone. Epitestosterone
is a minor product of testosterone metabolism and
does not increase after testosterone administration; the
resulting effect is an increase in the T/E ratio. In the
athletic population, the ratio is generally less than 2.0.
The IOC rules clearly indicate that a T/E ratio greater
than 6.0 constitutes an offence unless there is evidence
that this ratio is due to a physiological or pathological
condition, e.g. low epitestosterone excretion, androgenproducing
tumour and enzyme deficiencies. Before
the sample is declared positive, further investigations
are conducted as a longitudinal study. As a first step,
a comparison with previous values should be done.
If no previous values are available, several additional
urine samples are analysed over a short period of time.
This longitudinal study may represent a useful tool for
discriminating the false-positive (naturally elevated T/
E ratios) results from those due to manipulation of the
urine. According to guidance given by the World Anti-
Doping Agency (WADA) in 2004, urine samples should
be now submitted to isotopic ratio mass spectrometry
(IRMS) if the T/E is greater than or equal to 4.0 and
testosterone, testosterone metabolites, epitestosterone
and DHEA concentrations are greater than the fixed
cut-off concentrations.
Even if a longitudinal study gives good quality information
on the potential steroid profile manipulation, there is a
lack of definitive proof for the exogenous application of
natural steroids. One possible solution is the ratio of the
two stable carbon isotopes 13C/12C, which can allow
the differentiation of natural and synthetic steroids. As
exogenous testosterone or precursors contain less 13C
than their endogenous homologues, it is expected that
urinary steroids with a low 13C/12C ratio originate from
pharmaceutical source. The method for determining the
isotopic composition of the relevant analyte includes gas
chromatography, a subsequent combustion to CO2 and
finally, mass spectrometric analysis of this gas in a special
multi-collector mass spectrometer (gas chromatography/
combustion/isotope-ratio-mass-spectrometry, GC/C/
IRMS). The 13C/12C value of testosterone or that
of its metabolites will be measured and compared to
that of urinary reference steroids within the sample. It
should be emphasised that the 13C/12C value of these
endogenous reference compounds should not be affected
by steroid administration. The result will be reported
as consistent with the administration of a steroid if a
significant difference is observed between the 13C/12C
values of testosterone metabolites and the endogenous
reference compound. According to population studies,
a different cut-off for positivity was set in 2004 by the
WADA Laboratory Committee. If the IRMS study
does not readily indicate exogenous administration, the
result should be reported as inconclusive and necessitate
further longitudinal studies.
References
Evans NA
Current concept in anabolic-androgenic steroids.
Am J Sports Med. 2004;32:534-542.
Saugy M, Cardis C, Robinson N, Schweizer C.
Test methods: anabolics. Baillieres Best Pract Res Clin
Endocrinol Metab. 2000;14:111-133.
WADA Technical Document
reporting and evaluation guidance for testosterone, epitestosterone, T/E
ratio and other endogenous steroids, 2004. http://www.wada-ama.org/.
Contributing Authors:
Christophe Saudan, PhD
Norbert Baume, PhD
Lidia Mateus-Avois, PhD
Neil Robinson, PhD
and Martial Saugy, PhD

Nandrolone

50 NANDROLONE | F-MARC DOPING UPDATE 2006
F-MARC DOPING UPDATE 2006 | NANDROLONE 51
Nandrolone
Introduction
Nandrolone, or 19-Nortestosterone (Figure 1), is a
synthetic anabolic-androgenic steroid (AAS), part of
the norsteroids family and derived from the testosterone
molecule – the main sex steroid hormone produced in
man. The small chemical modification (at carbon atom
number 19) makes nandrolone more anabolic than
androgenic. This is a crucial point for medical use and
is at the origin of the widespread misuse of nandrolone
in sport. It is important to minimise the main negative,
androgenic effects of the AAS. For example, testosterone
has an anabolic:androgenic ratio of 1 whereas the same
ratio for nandrolone is 10, indicating that nandrolone
has powerful anabolic properties.
There have been numerous positive doping cases
involving nandrolone over the last decade. These positive
cases have led numerous anti-doping laboratories to
investigate various hypotheses concerning the origin of
the nandrolone metabolites found in urine. In this brief
review, the medical use and misuse by athletes will be
discussed.
The Fédération Internationale de Football Association
(FIFA) participates actively in the research performed in
collaboration with anti-doping laboratories.
Nandrolone as a Xenobiotic
The first synthesis of nandrolone was reported in 1950.
Since then, the pharmaceutical industry has produced
norsteroids for humans and animals for substitutive
(hypogonadism), complementary (osteoporosis and
haematological diseases), contraceptive and growth
stimulating treatment. Nandrolone is commonly
administered as an injectable agent. Deca-Durabolin is
the most widely recognised pharmaceutical formulation.
Because of its potent anabolic properties, nandrolone is
used by athletes as a doping agent to accelerate muscle
growth in order to increase lean body mass, strength and
aggressiveness. Even if scientific data are not conclusive,
nandrolone is also used for faster recovery.
Exogenous application can be either by intra-muscular
injection or oral ingestion of nandrolone itself or precursors
such as 19-norandrostenedione or 19-norandrostenediol.
These latter two components are currently popular
with nutritional supplement manufacturers to produce
prohormone supplements.
Nandrolone Excretion in Urine
Once introduced in the organism, exogenous substances
go through a multitude of metabolic steps that
transform the original molecules into its active forms,
into metabolites that are excreted in urine, or both.
The study of the elimination process relative to time
is called pharmacokinetics. Depending on the method
of administration, urinary nandrolone metabolites can
be detected for several days after oral ingestion or for
months after intra-muscular injection. Elimination and
detection is strongly dose-dependent and individual.
A recent study by the Swiss Anti-Doping Laboratory,
in collaboration with F-MARC (FIFA Medical
Assessment and Research Centre), showed that urinary
nandrolone elimination is a difficult biological process.
A total of 22 volunteers ingested two oral doses of
labelled nandrolone. Urine was collected over five
days after intake and was analysed for 19-NA (19-
Norandrosterone) and 19-NE (19-noretiocholanolone).
A rapid elimination of metabolites in urine, with wide
inter-individual variability, was observed (Figure 2). This
variability could be related to the use of oral ingestion.
Indeed, the rate of absorption through the intestinal
pathway, in particular the first stage through the liver, is
likely to be more variable than through an intramuscular
injection. Nevertheless, this study demonstrated that,
in the case of a positive test for nandrolone, it is very
difficult to know the moment and the method of
administration of the substance.
Nandrolone
Figure 1: Molecular structure of nandrolone or 19-nortestosterone.
Detection of Nandrolone
Nandrolone is transformed in the organism into few
degradation products. The two major metabolites are
19-norandrosterone (19-NA) and 19-noretiocholanolone
(19-NE). The finding of a potential doping offence with
nandrolone is based on the urinary detection of 19-NA
and 19-NE. Nandrolone has been on the banned list
of the International Olympic Committee (IOC) since
the Olympic Games in Montreal in 1976. In 1996,
the IOC set the threshold for 19-NA at 2 ng/mL urine
for males and at 5 ng/mL urine for females. In 2004, a
technical document edited by the World Anti-Doping
Agency (WADA) set the threshold at 2 ng/mL for both
males and females. As with other steroids, nandrolone
metabolites are quantified after being extracted from
urine samples by gas chromatography coupled with mass
spectrometry. Modern analytical instruments used by
anti-doping laboratories are extremely sensitive and can
detect a very low level of urinary 19-NA and 19-NE.
Traces of about 0.2 ng/mL can be detected in urine.
NA concentration [ng/ml]
40000
35000
30000
25000
20000
15000
10000
5000
0
0 10 20 30 40 50 60
Time [h]
Figure 2: Inter-individual variability in pharmacokinetics of 13C 19-NA
following ingestion of two oral doses of 13C nandrolone.
Origin of Nandrolone Metabolites in Urine
Some positive cases of nandrolone in football and judo
were reported just before the 1998 World Cup in France.
This initiated a debate about whether the human body
could produce traces of nandrolone metabolites without
any intake of forbidden substances. FIFA decided then
to support research projects on nandrolone in order to
test the three following hypotheses that were presented
by specialists:
1. The natural production, by the body, of nandrolone
due to enzymatic transformation of endogenous
testosterone to endogenous 19-nortestosterone
(nandrolone).
2. The intake of nutritional supplements which have been
previously voluntary or accidentally contaminated by
nandrolone precursors.
3. The intake of smaller doses (oral) of nandrolone
precursors.
Endogenous Nandrolone
Recent studies have shown that the urine of stallions,
the follicular fluid of mares and the urine of cows
and pregnant boars contain traces of endogenous
nandrolone.
Similarly, nandrolone has been identified in human
ovarian follicular fluid as a possible intermediate in
an enzymatic conversion of androgens to oestrogens.
Moreover, a pregnant woman might be able to produce
nandrolone or 19-NA that has been detected in the urine
of women in their 6th and 14th weeks of pregnancy.
Regarding men, no clear answer to the question of
endogenous production of nandrolone metabolites has
been offered. The discussion on the natural origin, in
very few sportsmen, of sub-nanograms of nandrolone
metabolites in urine has still not been completely
resolved. Analyses performed on a worldwide basis
by all of the WADA-accredited laboratories in recent
years seem to confirm that the urinary concentration of
possible endogenous production, if any, should lie below
the cut-off value of 2 ng/mL in normally concentrated
urine or in over-concentrated urine after correction for
specific gravity.
Nutritional Supplements and Nandrolone
In the last few years, dietary supplements have been
widely used by elite athletes and football players who
believe that products like creatine, prohormones, amino
acids and “mental enhancers” will boost their physical
and psychological abilities. The beneficial effects of
most of these products are not clearly established despite
the numerous studies performed. The widespread
accessibility of supplements is at the root of the use of
these unproven products.

52 NANDROLONE | F-MARC DOPING UPDATE 2006
F-MARC DOPING UPDATE 2006 | NANDROLONE 53
Positive cases with very small urinary concentrations
of forbidden substances like 19-NA have appeared
recently. Anti-doping laboratories investigated the actual
composition of over-the-counter supplements available
on the internet, in shops or in fitness clubs. Many of
these investigations have shown that both hormonal
and non-hormonal dietary supplements are mislabelled
and may contain anabolic-androgenic steroids or
prohormones which could be transformed to compounds
that are produced by the metabolism of banned anabolic
steroids like nandrolone. There is a clear risk, therefore,
of unintentional doping through the use of nutritional
supplements. This danger is not very well understood by
the athletes and a regular education of athletes, coaches
and medical staff is necessary to decrease the abuse of
dietary supplements and their related risks.
In 2000, the Swiss Anti-Doping Laboratory and the
Swiss Federal Office of Sports conducted an initial study
on dietary supplements and informed athletes about the
findings, warning them about products bought from
uncontrolled sources. In 2004, a second investigation
was conducted to learn if the situation had improved (or
worsened) in the supplement marketplace. About 100
nutritional supplements were ordered from different
internet sites and screened for contamination with
anabolic steroid parent compounds, stimulants, traces
of testosterone, nandrolone and their precursors.
The results showed that one creatine product and
three so-called “mental enhancers” contained traces of
hormones not identified on the labels. In addition, 14
prohormones (DHEA, Androstenedione, etc.) products
contained substances other than those indicated by
the manufacturer on the label. These prohormones are
in fact all listed as products forbidden by FIFA. But
the information about ingredients in these products is
generally suppressed in order to deceive sportsmen and
individuals.
More serious is the contamination of creatine products.
It is clear that intake of the recommended daily creatine
dose for three days of a product contaminated with
norandrostenedione, a nandrolone precursor, led to
the presence of nandrolone metabolites in urine with
concentrations near or over the WADA limit of 2 ng/mL.
As creatine phosphate, or any form of creatine, still seems
to be widely used in sport, the obvious contamination of
uncontrolled preparations is a real problem for athletes,
sport federations and anti-doping laboratories.
There are special considerations for female players, as
some contraceptive pills or preparations taken to delay
the onset of menstruation can contain norethisterone
and this product can lead to positive results for
nandrolone metabolites because norandrosterone (19-
NA) is also a minor metabolite of norethisterone.
Nandrolone Intake and Physical Effort
Whatever the origin of nandrolone, another question
worth addressing is the possible increase in norsteroid
excretion and their metabolites during or after strenuous
physical exercise. A possible mechanism could be a
release of these compounds from fat tissues during effort.
A multi-site trial was conducted by the anti-doping
laboratories of Lausanne and Montreal and financed by
F-MARC on a large population of 621 male subjects.
Results from 137 amateur football players did not show
any 19-norsteroid production at rest. After exercise, 128
subjects still had no evidence of 19-NA or 19-NE, while
9 of the 137 players showed traces of 19-NA and 19-NE
after competition. Eight of these 9 players showed 19-
NA and 19-NE values between 0.2-0.5 ng/mL and one a
value between 0.5-1.0 ng/mL.
In the same study, 358 elite football players were
tested after competition. The majority (355 players)
had an undetectable or a value less than 2.0 ng/mL
for urinary metabolites of nandrolone. The other
three players showed values between 2 and 3 ng/mL.
After correction for the specific density, however, all
but one of these results was under the 2 ng/mL limit.
This single result over 2 ng/mL urine is not proof of a
possible endogenous production of norsteroids through
exercise. It could have been due to previous intake of a
contaminated supplement.
To further investigate after the results obtained in the
first project, F-MARC funded a second study on the
effect of exercise on the urinary excretion of nandrolone
metabolites. Thirty-four amateur sportsmen took part
in the test, 22 ingested two caps of nandrolone and
collected urine before and after 8 normalised physical
efforts. The measurements of the 19-NA and 19-NE
urinary concentrations were quite variable and did not
appear to be significantly influenced by exercise.
There are several possible reasons for the absence of a
relationship between the 19-NA and 19-NE urinary
concentrations and physical effort. The most likely
explanation may be related to individual differences
in how the metabolism was affected by the stress of
exercise. Indeed, if the exercise volume, intensity and
caloric expenditure did ensure uniform stress levels,
resistance to such stress could still have varied among
and between different participants. In addition, diet
and energy expenditure were not monitored during the
study. Furthermore, nandrolone elimination could have
been affected by food intake and the type and level of
physical activity outside the exercise sessions.
Thus, physical effort can have different effects on the
excretion of nandrolone metabolites depending on an
individual’s metabolism. These results indicate that
no model can be elaborated and no extrapolation is
possible concerning pre- and post-effort 19-NA and
19-NE urinary levels. The results of this study suggest
that physical exercise cannot be considered as a reliable
parameter that systematically affects nandrolone
metabolite concentrations in urine.
Conclusion
Nandrolone is known to be one of the most widely used
AAS in sports that need power and muscle strength.
Some other beneficial effects (e.g. improvement of
recovery even if they are not scientifically proven) are
argued as a reason for misuse of nandrolone by athletes.
In spite of the numerous investigations conducted,
results demonstrate that individual case management
has to be considered by the disciplinary panels when
making any decision about a sanction to be applied or a
follow-up of the concerned athlete. Nevertheless, in view
of their side-effects, nandrolone and AAS in general are
dangerous substances and athletes remain responsible
for forbidden compounds in their body.
References
Bricout V, Wright F
Update on nandrolone and norsteroids:
how endogenous or xenobiotic are these substances?
Eur J Appl Physiol 2004;92:1-12.
Baume N, Avois L, Schweizer C, Cardis C, Dvorak J,
Cauderay M, Mangin P, Saugy M
[13C]Nandrolone excretion in trained athletes:
interindividual variability in metabolism.
Clin Chem 2004;50:355-364.
Green GA, Catlin DH, Starcevic B
Analysis of over-the-counter dietary supplements.
Clin J Sport Med 2001;11:254-259.
Pipe A, Ayotte C
Nutritional supplements and doping.
Clin J Sport Med 2002;12:245-249.
Contributing Authors:
Norbert Baume, PhD
Lidia Mateus-Avois, PhD
Christophe Saudan, PhD
Neil Robinson, PhD
and Martial Saugy, PhD