Joseph W. McNutt, M.D.
Frisco Orthopedics
and
Sports Medicine
Performance Enhancing
Drugs
Performance Enhancing
Drugs
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Anabolic Steroids
Androstenedione
Human Growth Hormone
Beta–2 Agonists
Stimulants
Beta Blockers
Erythropoitin
Creatine
HMB
Anabolic Steroids
•
1995 poll – 198 Olympic level power
athletes
• Given following scenario: you offered a
banned substance with two guarantees
1. You will not be caught
2. By taking the substance you will win your
event
• Only 3 said no
Anabolic Steroids
•
Same poll, new scenario:
1. The substance will allow you to win every
competition you enter over the next 5
years
2. However the substance will then kill you
•
More than 50 % would still use the
substance!
This is why performance
enhancing drugs remain in the
spotlight of sports
Anabolic Steroids
• Class of steroid hormones related to the
male hormone – testosterone
• Increase protein synthesis within cells
which results in growth of muscle
• Also have androgenic properties which
include the development and maintenance
of males characteristics
• Have both medical and sport performance
uses
Anabolic Steroids
• AS have been
modified many times
to maximize the
anabolic effects and
minimize the
androgenic affects
• Alkylation of the 17alpha position (oral)
• Esterfication of the
17-beta hydroxyl
group (IM)
Anabolic Steroids
• All AS possess both anabolic and
androgenic properties
• None are absolutely selective
• Testosterone anabolic:androgenic ratio: 1
• Nandrolone: 10
• Stanozolol: 30
• Anabolic effect dose dependent (300 mg
per week required)
Anabolic Steroids
History
• 1931 – male hormone androstenone
isolated
• 1934 – androstenone synthesized
• 1935 – testosterone identified and
synthesized
• 1937 – clinical trials on humans with
testosterone began
Anabolic Steroids
History
• WWII – German scientist
synthesized other
anabolic steroids and
experimented on
concentration camp
inmates to treat chronic
wasting
• Also given to German
soldiers hoping to
increase their aggression
• Adolf Hitler rumored to
take anabolic steroids
Anabolic Steroids
History
• 1940s - Soviet Union
and Eastern Bloc
Countries (East
Germany) established
steroid programs in
Olympic and amateur
weight lifters
• 1958 – Dianabol
(methandrostenolone)
approved in U.S. by
the FDA
Anabolic Steroids
History
• 1972 – study showed no difference in
performance enhancement in participants
compared to ones given placebo
• Remained unchallenged for 18 years
• Poor study with inconsistent controls and
insignificant doses
• 2001 – study showed clear increase in muscle
mass and decrease in fat associated with high
doses of anabolic steroids
Anabolic Steroids
Anabolic Effects
• Two different, but overlapping
effects
• Anabolic – promote cell
growth. Increased protein
synthesis, appetite, bone
remodeling and growth, and
production of red blood cells
• Increase the size of muscle
fibers (hypertrophy) leading to
increase in muscle mass and
strength
• Decrease the amount of fat in
muscle
Anabolic Steroids
Androgenic Effects
• Androgenic (virilizing) - development and
maintenance of male characteristics:
• Increased growth of pubic, beard, chest
and limb hair
• Enlargement of vocal cords
• Increased libido
• Enlargement of clitoris
• Suppression of natural sex hormones
Anabolic Steroids
Adverse Effects
• Most side effects are
dose dependent
• Elevated blood pressure
(most common)
• Increase LDL cholesterol
and decrease HDL
• Increase risk of CV
disease and coronary
artery disease,
arrhythmias, and heart
attacks (chronic use)
Anabolic Steroids
Adverse Effects
• Accelerate the rate of
premature baldness
(male and female)
• Acne – stimulates the
sebaceous glands
• Liver damage (cancer) –
increased demand on
liver as oral steroids are
changed (increase
bioavailability and
stability)
Anabolic Steroids
Adverse Effects
• Tendon rupture has been
linked to AS
• Stiffer and less elastic
tendon
• No consistent AS –
induced ultrastructural or
biochemical alterations
• Probably tendon does not
adapt as fast (weak link
Anabolic Steroids
Gender Specific Effects
• Gynecomastia –
development of
breast tissue in males
• Conversion of
testosterone to
estrogen by an
aromatase enzyme
Anabolic Steroids
Gender Specific Effects
• Temporary infertility
(decreased
production of sperm)
• Testicular atrophy
(caused by decrease
levels in natural
testosterone)
Anabolic Steroids
Female-Specific Effects
• Increase in body hair
• Male-pattern baldness
• Deepening of voice
(permanent)
• Enlarged clitoris
(permanent)
• Temporary decrease in in
menstrual cycle
• Affect fetal development
during pregnancy
Anabolic Steroids
Adolescent Effects
• Stunted growth –
Premature growth plate
shut down as a result of
increased levels of
estrogen
• Premature sexual
development
• Anabolic steroid use in
adolescence has been
correlated with poorer
attitudes related to health
Anabolic Steroids
Adverse Effects
• Risk of mortality among chronic AS users
repoted to be 4.6 times higher than nonAS users
• Weekly doses of 600 mg ot testosterone
or its equivalent for cycles lasting less than
12 weeks appear to cause few side effects
during scientific studies
• Rule: bigger the dose, the bigger the
muscle, the bigger the problem
Anabolic Steroids
Behavioral Effects
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Controversial
Mood swings
Aggression (roid rage)
Mania
Depression
Withdrawal
Dependence
Anabolic Steroids
Biochemical Mechanisms
•
Effect of AS on muscle mass is caused in
at least two ways:
1. Increase the production of proteins
2. Reduce recovery time by blocking the
effects of cortisol (promote the breakdown of
muscles)
•
AS affect the number of cells that
develop into fat storage cells by favoring
cellular differentiation into muscle cells
Anabolic Steroids
Biochemical Mechanisms
• Steroid hormones mainly
interact with cells by
binding to proteins called
steroid receptors
• After binding, proteins
move into the cell nucleus
and can alter the
expression of genes or
activate processes in
other parts of the cell
Anabolic Steroids
Biochemical Mechanisms
The human receptor bound to
testosterone
• Receptors involved with
AS are called Androgen
receptors
• Different types of AS bind
with different affinities
depending on their
chemical structure
• This determines the
characteristic effects of
the AS (anabolic vs
androgenic)
Anabolic Steroids
Medical Uses
• Bone marrow stimulation – aplastic
anemia
• Growth stimulation – use GH now
• Appetite stimulate – AIDS, cancer
• Induction of male puberty – extreme delay
• Reversible male contraceptive - future
• Hormone replacement therapy (men)
• Gender dysmorphia - psyciatric
Anabolic Steroids
Non-medical use and abuse
• Extremely difficult to determine what
percentage of use in the population
• Usually middle class, heterosexual men
with a median age of 25
• 2006 study – 78% noncompetitive
bodybuilders and non-athletes (cosmetic)
• 13% reported unsafe injection practices
(needle sharing)
Anabolic Steroids
Non-medical use and abuse
• Users often stereo-typed
as uneducated or “muscle
heads”
• 1998 study showed
steroid users to be the
most educated drug
users out of all users of
controlled substances
• Research their product
more than any other
group
Anabolic Steroids
Administration
• 3 common forms of AS
administration:
• Oral – most convenient
(dangerous - liver)
• Injectable – intramusclar
not intravenous (HIV and
Hepatitis)
• Transdermal – self
adhesive skin patches
Anabolic Steroids
Methods of Administration
• Athletes who take AS do so typically during the active
years of the careers
• They combine multiple steroid forms (oral and
injectable), a practice called “stacking”
• The drug dosage is progressively increased
(“pyramiding”) during a 4 to 18 week cycle, including a
drug-free period between drug regimens (4-6 weeks).
• The drug quantity far exceeds the recommended
medical dose (200X)
• The athlete then progressively reduces the drug dosage
in the months prior to competition (to avoid detection)
Anabolic Steroids
Methods of Administration
• The cycling of steroids coincides with competition
• Many athletes use the training model – “Periodization”
• An athlete with a yearly training program (macrocycle)
subdivides the year into phases called mesocycles (3
months)
• As competition nears, training volume gradually
decreases while training intensity increases
• Steroid use coincides with the mesocycles, with the goal
of achieving maximum strength and size at competition
Oral Anabolic Steroids
• 17-alpha methyl testosterone
(Android)
• 17-alpha ethyl testosterone
(Maxibolin)
• 1-methyl testosterone
(Primobolan)
• Androstenediol (“Andro” food
supplements)
• Androstenedione
• Dihydroepiandrosterone
(DHEA)
Injectable Anabolic Steroids
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19-nortesterone ester derivitives (Durabolin)
Testosterone ester derivatives (Oreton)
Testosterone cypionate derivatives (Virilon)
Boldenone
Stanozolol (Winstrol) oral form as well
Anabolic Steroids
Minimization of Side Effects
• Several techniques to
minimize side effects both
during cycles and post
cycle
• Increase CV exercise to
counter act effects on left
ventricle
• Estrogen receptor
modulators to reduce
effect of aromatisation of
steroid hormones
(tamoxifen) reduce
gynecomastia
Anabolic Steroids
Post Cycle Therapy
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“PCT” – takes place after each cycle to
combat the natural testosterone
suppression and restore proper function of
numerous glands
Typically consists of a combination of the
following drugs:
1. Clomiphene or tamoxifen (Primary PCT drug)
2. Anastrozole – aromatase inhibitor
3. HCG – restore hormonal balance
Anabolic Steroids
Post Cycle Therapy
• Finasteride (Propecia)
– reduces the
conversion of
testosterone to DHT
(high rate of alopecia)
• The drug is useless in
cases in which the
steroid is not
converted into a more
androgenic derivative
Anabolic Steroids
Legal Status
• Varies from country to country
• U.S. - Schedule III controlled substance
(requires prescription, possession without Rx.
federal crime punishable up to 7 yrs)
• Canada – Schedule IV (obtaining or selling
punishable for up to 18 mo., possession not
punishable
• Also illegal without Rx. in Australia, Argentina,
Brazil and Portugal
• Legal in Mexico and Thailand
Anabolic Steroids
U. S. Legislation on AS
• Interest and debate after
1988 Summer Olympics in
Seoul following controversy
of Ben Johnson
• AS added to Schedule III of
the Controlled Substances
Act in the Anabolic Control
Act of 1990
• Prohormones or “Designer
Steroids” not included
(Androstenedione)
Anabolic Steroids
Prohormones
• In 1994 , the Dietary Supplement Health and Education
Act was signed into law.
• This act classified substances derived from natural
sources as food supplements and made many drugs
such as prohormones available over the counter.
• Thus these substances are not regulated under the
same rules and regulations by the FDA. (Loop hole)
• This can result in the dosages and actual quality of these
substances to be in question as they are sold to the
consumer
• Amended in 2004 (Androstenedione)
Anabolic Steroids
Status in Sports
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1.
2.
3.
4.
5.
6.
AS are banned by
all major sporting
bodies:
IOC
NBA
NHL
NFL
MLB
NCAA
Anabolic Steroids
Status in Sports
• Testing in Texas high schools to start this
year (UIL)
• Expensive
• Jurisprudence
• Normal T:ET ratio 1.3:1
• 1 in 1000 men ratio of 4:1
• Positive test result 6:1
Anabolic Steroids
Status in Sports
* For testosterone the definition of positive depends on an adverse
analytical finding (positive result) based on any reliable analytical
method (e.g., IRMS,GCMS, CIR) which shows that the testosterone
is of exogenous origin, or if the ratio of the total concentration of
testosterone to that of epitestosterone in the urine is greater than
6:1, unless there is evidence that this ratio is due to a physiological
or pathological condition.
Anabolic Steroids
Illegal Trade
• The majority of AS are
obtained illegally through
black market trade
• Usually manufactured in
other countries and
smuggled across borders
• Smuggling usually done
in conjunction with other
illegal drugs
• Organized crime is
involved
Anabolic Steroids
Counterfeit Drugs
• Significant health hazard
• Computer and scanning technology as
made it to copy labels
• Product could contain anything (vegetable
oil to toxic substances)
• Users have died of injecting unknown
substances in their body
• Products also diluted to maximize profits
Anabolic Steroids
Production and Distribution
• AS are either manufactured by legitimate
pharmaceutical companies or under ground
laboratories
• In the 1990’s most U.S. producers stopped
making and marketing AS
• Eastern Europe still produce AS in quantity
(most medical grade AS sold illegally in North
America)
• Many illegal AS are veterinary grade (produced
and handled in cruder and less sterile fashion)
Anabolic Steroids
Production and Distribution)
• AS can be obtained
from several sources
• Sold at gyms and
competitions
• Illegal drug dealers
• Mail order
(magazines)
• Internet (websites
posing as oversea
pharmacies)
Androstenedione
• Made famous by
Mark McGuire during
historic 1998 chase
for single season
record of home runs
• Immediate precursor
to testosterone
(prohormone)
• Marketed to raise
testosterone levels
Androstenedione
Basic Science
• Concept of how “Andro” works is based on
knowledge of the effectiveness of testosterone
as an ergogenic aid
• Postulated that the higher the concentration of
“andro” than the more that is converted to
testosterone (debated)
• Majority of studies have shown no increase in
testosterone levels
• Significant increase in estrogen levels (not
marketed)
Androstenedione
Performance Studies
• No studies have
shown any significant
increase in lean body
mass or strength
increase
• No significant
improvement in
athletic performance
has been shown
Androstenedione
Side Effects
• Similar to AS
• Decrease HDL
• Increase estrogen
levels (gynecomastia)
Androstenedione
Testing and Policy
• Was availble over-the-counter until
Anabolic Steroid Act amended in 2004
• Banned by IOC, NCAA, NBA, NFL, and
MLB
• Currently listed as a Schedule III controled
substance
Human Growth Hormone
• Produced in the anterior
lobe of the pituitary gland
• Can be made
synthetically via
recombinant DNA
technology
• Accelerates linear growth
in the skeletally immature
• Increases body weight
and muscle mass in both
the mature and the
skeletally immature
Human Growth Hormone
Basic Science
• 191-residue, 22kDa
peptide hormone
• Release regulated by
GHRH, sleep,
exercise, L-dopa, and
arginie
• Studies show
administration of hGH
leads to muscle
hypertrophy but not
increased strength
Human Growth Hormone
Performance Studies
• Little research has been done with hGH
supplementation
• Most studies deal with endocrine
dysfunction
• Increase in lean body mass but no
increase in strength or performance
Human Growth Hormone
Side Effects
• Insulin resistance (diabetes)
• Increased serum cholesterol
and triglycerides
• Cardiac enlargement
• Hypogonadism (testicular
shrinkage)
• Acromegaly (abnormal
enlargement of appendages)
• Muscles may be myopathic
with long term use
Human Growth Hormone
Testing and Policy
• Available legally only
through physician Rx
• Banned by IOC but
not officially tested
• Testing not available
in professional sports
in the US
Beta-2 Agonists
• Clenbuterol is another drug
with Anabolic effects, but not in
the steroid family
• It is a beta-2 adrenergic
agonist approved for the
treatment of asthma
• Brand names include
Clenasma, Monores, Novegan,
Prontovent, and Spirovent
• It promotes protein synthesis
and increases lean body mass
as well as its medicinal effect
of opening constricted airways
• Bodybuilders switch to the
drug prior to competition to
avoid detection and to achieve
“cut” look
Beta-2-Agonists
• Clenbuterol is not approved for human use in the United
States
• Side effects can include muscle tremor, agitation,
palpitations, muscle cramps, rapid heart rate, and
headache
• No data exist of its effectiveness or safety in long term
use.
• Not justified or recommended for use as an ergogenic
aid.
Stimulants
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Caffeine
Nicotine
Ephedrine
Amphetamines
Caffeine
• Most widely available
ergogenic substances
• Found in coffee, tea,
chocolate, soft
drinks,prescription drugs, and
over the counter drugs (No
Doz, Vivarin, Excedrin, Midol)
• Central Nervous System
stimulus
• Delayed onset of fatigue
• Increased metabolism of free
fatty acids for energy (spares
glycogen stores)
Caffeine
Dosage
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Cup of coffee – 100 mg (small ergogenic effect)
Soft drinks – 70 mg
Over the counter stimulant drugs – 200 mg
Any combination that results in a level of 800 mg is detectable by
current drug tests
Caffeine
Adverse Effects
• Diuretic – can result in
dehydration
• Diminished muscular strength
• Diminished endurance
• Increased risk of heat-related
injury or sickness
Nicotine
• Widely available
• Smokeless tobacco (dip, snuff) or cigarettes
• Any benefit from the stimulant effect is more than
outweighed by the health risks: lung cancer, oral cancer,
emphysema, birth defects
Ephedrine
• Chemical found in the plant genus Ephedra
• Contained in many nonprescription drugs, foods, and
nutritional supplements (greenies)
• Used specifically to attempt to reduce fatigue and to
enhance mental alertness
• Herb teas, Ginseng, gingko, and non prescription cold
medicines
Ephedrine
Side Effects
• With recent death of
NFL lineman, this
class of drugs has
come under scrutiny
• Anxiety, ventricular
dysrythmias (death)
and hypertension
• Possible relationship
with heat stroke
Amphetamines
• Most potent ergogenic drugs in
the stimulant category
• Increase cardiac output and
metabolism of free fatty acids
• CNS stimulation: increased
aggression, increased mental
alertness, decreased
perception of fatigue
Amphetamines
Side Effects
• Illegal (methamphetamines – home labs)
• Heat-related injuries: increased metabolic activity and
altered cardiovascular cooling
• Addiction, withdraw syndrome, depression, marked
reduction of athletic performance
Stimulants
Testing and Policy
• Several amphetamines and stimulants
available over the counter
• Most classes banned by the IOC
• Several forms banned in American
professional sports
• NFL recently banned ephedrine
Beta Blockers
• Propanolol
• Compounds that slow the heart
rate and lower blood pressure
• Little ergonomic potential
except in sports such as
shooting, archery, and
biathalon where fine motor
control and relief of “jitters” are
critical (steady hand)
• These are prohibited in these
sports (IOC)
Erythropoitin and Blood Doping
• Use of exogenous
erythropoietin (EPO) and/or
blood transfusions to increase
blood count
(hemoglobin/hematocrit)
• This improves the availability
of oxygen to the exercising
muscle.
• Improves aerobic capacity and
muscle endurance
• Detection is difficult and
expensive
• Popular in the cyclists and
other aerobic athletes
Erythropoitin and Blood Doping
Basic Science
• EPO – hormone naturally
produced in the kidney
• Can be created
synthetically via
recombinant DNA
technology
• Once released it
stimulates an increase in
hemoglobin
• Increases oxygen
carrying ability of blood
Erythropoitin and Blood Doping
Adverse Effects
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Increases risk of hyperviscosity syndrome (thick blood)
Increased risk of stroke, heart failure, and even death
Increased risk of dehydration with exercise
HIV or HBV infection from blood transfusions
5 Dutch cyclists died in 1987 in first year release of EPO
Between 1997 and 2000, 18 cyclists have died of stroke,
MI, or Pulmonary embolism
Erythropoitin and Blood Doping
Testing and Policy
• Only available with physician’s Rx
• Not legal in any sport
• Gas and liquid chromatography used for
screening
• Remains difficult to detect
• Some governing bodies use an upper limit
of hemoglobin as their guide
Creatine
• Since its introduction in
1992, it has become the
most popular nutritional
supplement on the
market
• Discovered by Chevreul
in 1832
• First reported use by elite
athletes occurred during
the 1992 Barcelona
Olympics (British track
and field athletes)
Creatine
•
Several studies show up to 50 % usage
rate in male college athletes
• Recent survey of NFL trainers and team
physicians:
1. All teams had players actively taking
creatine
2. Average use 33% and reports as high as
90%
Creatine
Basic Science
• Naturally occuring
compound made from
amino acids: glycine,
arginie, and methionie
• Primarily synthesized in
the liver, pancreas, and
kidney
• 95% stored in skeletal
muscle
• Exogenous sources:
fresh fish and meat
• 2 g daily turnover
Creatine
Basic Science
• Provides energy
during short-duration
maximal bouts of
anaerobic exercises
• Phosphorylated form
provides a
phosphorous atom to
re-synthesize ATP
Creatine
Performance Studies
• Weight lifters – single rep max up 20 -30%
• Cyclists – help maintain muscular force and
power outputs
• Swimming – mixed results (complex
mechanics?)
• Track and field – 1–2 % decrease in times
• Body composition – increase weight and lean
body mass (1-2 kg per short term cycle)
• Summary – effective for simple, short-duration,
maxi-effort anaerobic events
Creatine
Side Effects
• 30% no response rate
• May lead to increase in muscle cramping
(dehydration?)
• As in all supplements – lack of quality
control
• Otherwise short term use safe , long term
use unknown (further studies needed)
Creatine
Testing and Policy
• Available over the counter in several
nutritional supplements
• Not tested for or banned by any major
athletic organization
• NCAA does not allow its member teams to
provide creatine to their players
• Many teams discourage use in season
(cramps)
HMB
• Beta-hydroxy-betamethylbutyrate
• Leucine metabolite
that has gained
popularity as an
“anticatabolic”
• Marketed to suppress
protein breakdown in
recovery phase after
workout
HMB
Basic Science
•
Mechanism not truly known but several
theories:
1. Increase testosterone levels (similar to
AAS)
2. Delay anaerobic metabolism
3. Prevent exercise-induced muscle
damage
HMB
Performance Studies
• Some evidence that
HMB may act to
suppress protein
breakdown
• Little evidence in the
literature to support
any ergogenic
advantage
HMB
Side Effects
• No effect on blood, liver, or kidney function
• No changes seen in urinalysis
• Lowered LDL, total cholesterol, and
systolic blood pressure
• Thus HMB appears to be safe and may be
cardioprotective
HMB
Testing and Policy
• Available in many
over-the-counter
supplements
• Not banned by any
sporting organization
to date
What can we do?
• Education - wealth of
information out there
(internet, books,
magazines)
• Your young athlete
knows more about it
than you (and they
don’t know enough)
Proper Training
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Sleep
Hydration
Stretching
Nutrition (timing, whey protein, creatine)
Proper form and technique (especially in
skeletally immature athletes)
• Goals
Thank You!