2. Three Omnipresent Performance
Enhancing Methods in American
Sports
Anabolic-Androgenic Steroids (AAS)
- i.e. testosterone, oxymetholone, stanozolone, etc.
Human Growth Hormone (HGH)
“Blood Doping”
- i.e. recombinant human erythropoietin (rHuEPO), autologous
and allogeneic blood transfusions, and hemoglobin-based
oxygen carriers (HBOC’s)
3. History of Performance
Enhancement
Ancient Use – Some historians believe that the Greeks used
experimental herbal concoctions and ate a lot of meat prior to
competitions1; ancient Roman gladiators used substances like
strychnine and hydromel in order to stave off fatigue and increase
speed2.
19th Century Use – Athletes have used stimulants such as strychnine,
caffeine, and cocaine since the 1800’s3.
Modern Use – Steroid use has been an acknowledged problem in
America since the 1960’s. Blood doping became a major concern in
sports after the creation of commercial rHuEPO in 1989. HGH became
major concern by 2010.
4. Stimulants in Sports
Amphetamine is the most notorious stimulant in athletics
today
- The MLB is the most infamous institution of amphetamine use
– due to the penalties implemented for amphetamine use, 8-10%
of MLB players receive therapeutic use exemptions (TUE’s) in
order to use them without penalty (compared to the 4.4% of the
general population with symptoms appropriate for amphetamine
use3)
5. Anabolic-
Androgenic
Steroids (AAS)
AAS are probably the
most recognized means
of performance
enhancement, and use
has evolved over time in
order to escape detection
These compounds act on
one intracellular receptor
mostly found in the
reproductive tract, but
also present in non-
reproductive cells in
bone, skeletal muscle,
the liver, and adipocytes
(fat cells)4
7. Testosterone and AAS
Testosterone (T) is the naturally occurring male
hormone that causes all of the desired effects seen in
AAS use
Testosterone is the parent molecule to every
adrenergic steroid, and is itself often utilized in
performance enhancement3
8. Metabolic Effects of AAS
AAS have been shown to increase EPO activity in both
mice and humans, in vivo and in vitro
Molinari and Neri showed that the administration of
the AAS oxymetholone in eight healthy volunteers
increased the concentration of 2,3-diphosphglycerate
(2,3-DPG), which has an important role in the binding
of hemoglobin to oxygen4
9. Anabolic Effects of AAS
In bone, AAS stimulate osteoblast proliferation, bone
matrix protein production, and the syntheses of
growth factor and cytokines4
Steroids and testosterone decrease muscle and protein
breakdown while encouraging lipolysis (fat break-
down) in part due to their nitrogen-retaining
properties
10. Detecting AAS and Testosterone
AAS are typically detected through hyphenated mass
spectrometry, a method that combines
chromatographic techniques with spectroscopic
techniques to more accurately identify a compound5
Synthetic T is identified through the ratio of T to
epitestosterone (E) – an isoform of inactive T only
made through natural T and not through synthetic T.
The current threshold for the T:E ratio is 33.
11. Risks and Adverse Effects of
Steroids
Serious side effects of chronic AAS use include
cholestatic jaundice, peleosis hepatitis, hepatic cancer,
masculinization in women and children (acne,
deepening voice, clitoral enlargement, etc.), and
simultaneously raising low-density lipoproteins (“bad”
cholesterol) while lowering high-density lipoproteins (
good” cholesterol), among others4
13. Benefits of AAS
AAS have become widely used in the
treatment of muscle wasting disorders,
damaged myocardium from heart failure,
growth retardation and malnutrition, bone
marrow failure syndromes, end-stage renal
disease, and angioneurotic edema4
14. Human Growth Hormone
Recently, HGH for performance enhancement in
athletics has become a problem
HGH is a natural occurring hormone, arising from
the anterior pituitary, that has a wide swath of uses
in the human body – in children it aids in growth
and development; while it helps break down fat,
build lean muscle, maintain immunity, and repair
tissue throughout life6
16. HGH in Athletics
HGH was listed in the 2010 Prohibited List
HGH use can start as early as adolescence, with a
survey showing that 5% of American 10th grade boys
had used HGH in the past
A web-based study showed that 25% of AAS users also
used HGH6
17. Detection of HGH
Urinalysis is ineffective at detecting HGH, as its
concentrations in urine are less than 1% their conc. in
blood
A test was developed that can detect the 22 kDa
isoform of the hormone, however, it was found
ineffective at detecting HGH in athletes. This could be
due to the relatively fast excretion of HGH (24-36 hr)3
18. Dangers of HGH Use
HGH use creates significant fluid retention, which can
cause feelings of “pins and needles”, carpel tunnel
syndrome, and arthralgias
A possibly serious complication of long term HGH use
is acromegaly, which often presents with hypertrophic
but weaker muscles, hypertension and other cardiac
problems, joint pathology, and an increased risk of
diabetes and cancer6
20. Results of HGH Use
Some studies suggest that HGH does not even enhance
performance much at all
The increase in lean body mass associated with HGH
comes mostly in the form of fluid retention, and most
of those who experience fat loss and muscle gain are
those with HGH deficiency to begin with6
However, one study by Meinhardt et al juxtaposed
these results with their own data showing that HGH
therapy increased sprint capacity by 3.9%3
21. Blood Doping
Three different types of blood doping are primarily
engaged in athletics – the use of rHuEPO, autologous
(or rarely allogeneic) blood transfusions, and
hemoglobin-based oxygen carriers
22. Human Recombinant
Erythropoeitin
The most common form of blood-doping, rHuEPO
must be used consistently (i.e. injections every 2-3
days over a 4 week period) in order to see its full
benefits
Many different forms of rHuEPO already exist in the
market or are currently being created/researched,
including the α-, β-, and ω- isoforms as well as gene-
activated and EPO and adeno-associated viral vectors
able to deliver the EPO gene7
23. Blood Transfusions
Blood transfusions offer an immediate increase in red
blood cells (RBC’s) and oxygen-carrying capacity
The newly injected RBC’s are exactly like any other
RBC’s, and so they are alive for 120 days
The biggest drawback to this method is inconvenience,
as the drawn RBC’s must be stored in a container at no
more than 4 degrees Celsius in order to survive long
enough to be of use7
24. Hemoglobin-Based Oxygen Carriers
HBOC’s are synthesized from hemoglobin taken from
bovine or human sources, which is sterilized, cross-
linked, modified, and micro-encapsulated to stabilize
the molecule and provide a basis for a range of
subsitutes
These compounds have the advantage of causing no
toxicity
The major disadvantage of this method is the rapidity
of excretion – usually taking place in 12-24 hours7
25. Detection of Blood Doping
Currently there is no accurate way of detecting blood
transfusions directly
HBOC’s are relatively new, and no method of
accurately detecting them is around either7
rHuEPO can be detected using a test that involves the
use of chemiluminescence and electric fields in order
to separate different isoforms of the compound along a
gradient3
26. Adverse Effects of Blood Doping
Blood doping increases blood volume within a
constant container, thus increasing viscosity – this has
been shown to cause problems ranging from
hypertension to increased platelet reactivity to general
inflammation
One study described how EPO use needed to be
discontinued in breast cancer patients due to an
increase in thrombotic events8
27. Is Blood Doping Worth It?
A review by Jules Heuberger et al showed little
scientific evidence that blood doping, particularly with
EPO, objectively boosts performance in cycling
Many studies reviewed in this publication were flawed,
as many only tested moderately trained cyclists with
untrained controls
EPO was found to increase hematocrit and VO2max,
but there is no evidence that this improves
performance8
28. Legal and Ethical Concerns
Numerous organizations across the globe exist solely
to condemn, prohibit, and discourage the use of
performance enhancing drugs in sports
Players can and often are sued when it is discovered
that they have been “doping”
The major ethical problem of these drugs comes in the
destruction of any sort of fairness – rules are in place
for the purpose of leveling the playing field
29. Bibliography
1) Bowers, L.D. “Athletic Drug Testing," Clinics in Sports Medicine, Apr. 1, 1998
2) Aziz, R.A. “History of Doping," Presented at the WADA Asia Education
Symposium, Aug. 29, 2006
3) Werner, T.C.; Hatton, Caroline “Performance Enhancing Drugs in Sports”
Journal of Chemical Education, 88, 34-41, 2011
4) Shahidi, N. “A Review of the Chemistry, Biological Action, and Clinical
Applications of Anabolic-Androgenic Steroids” Clinical Therapeutics, 23, 2001
5) Patel, K. “Introduction to Hyphenated techniques and their Application in
Pharmacy” Pharmaceutical Methods, 1, 2-13, 2010
6) Birzniece, V.; Nelson, A.; Ho, K. “Growth Hormone and Physical
Performance” Trends in Endocrinology and Metabolism, 22, 2011
7) Ashenden, M. “A Strategy to Deter Blood Doping in Sport” Haematologica,
87, 225-234, 2002
8) Heuberger, J.; Tervaert, J.M.C. “Erythropoeitin Doping in Cycling: Lack of
Evidence for Efficacy and a Negative Risk-Benefit” British Journal of Clinical
Pharmacology, 75, 1406-1421, 2012
