Joseph W. McNutt, M.D. Frisco Orthopedics and Sports Medicine

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Joseph W. McNutt, M.D.Frisco Orthopedics and
Sports Medicine
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Performance Enhancing Drugs
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Performance EnhancingDrugs

• Anabolic Steroids
• Androstenedione
• Human Growth Hormone
• Beta2 Agonists
• Stimulants
• Beta Blockers
• Erythropoitin
• Creatine
• HMB

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Anabolic Steroids

• 1995 poll 198 Olympic level power athletes
• Given following scenario you offered a banned
  substance with two guarantees
• You will not be caught
• By taking the substance you will win your event
• Only 3 said no

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Anabolic Steroids

• Same poll, new scenario
• The substance will allow you to win every
  competition you enter over the next 5 years
• However the substance will then kill you
• More than 50 would still use the substance!

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This is why performance enhancing drugs remain in
the spotlight of sports
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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

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Anabolic Steroids

• AS have been modified many times to maximize the
  anabolic effects and minimize the androgenic
  affects
• Alkylation of the 17-alpha position (oral)
• Esterfication of the 17-beta hydroxyl group (IM)

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Anabolic Steroids

• All AS possess both anabolic and androgenic
  properties
• None are absolutely selective
• Testosterone anabolicandrogenic ratio 1
• Nandrolone 10
• Stanozolol 30
• Anabolic effect dose dependent (300 mg per week
  required)

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Anabolic SteroidsHistory

• 1931 male hormone androstenone isolated
• 1934 androstenone synthesized
• 1935 testosterone identified and synthesized
• 1937 clinical trials on humans with
  testosterone began

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Anabolic SteroidsHistory

• 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

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Anabolic SteroidsHistory

• 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

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Anabolic SteroidsHistory

• 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

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Anabolic SteroidsAnabolic 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

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Anabolic SteroidsAndrogenic 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

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Anabolic SteroidsAdverse 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)

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Anabolic SteroidsAdverse 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)

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Anabolic SteroidsAdverse 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

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Anabolic SteroidsGender Specific Effects

• Gynecomastia development of breast tissue in
  males
• Conversion of testosterone to estrogen by an
  aromatase enzyme

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Anabolic SteroidsGender Specific Effects

• Temporary infertility (decreased production of
  sperm)
• Testicular atrophy (caused by decrease levels in
  natural testosterone)

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Anabolic SteroidsFemale-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

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Anabolic SteroidsAdolescent 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

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Anabolic SteroidsAdverse Effects

• Risk of mortality among chronic AS users repoted
  to be 4.6 times higher than non-AS 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

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Anabolic SteroidsBehavioral Effects

• Controversial
• Mood swings
• Aggression (roid rage)
• Mania
• Depression
• Withdrawal
• Dependence

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Anabolic SteroidsBiochemical Mechanisms

• Effect of AS on muscle mass is caused in at least
  two ways
• Increase the production of proteins
• 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

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Anabolic SteroidsBiochemical 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

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Anabolic SteroidsBiochemical Mechanisms

• 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)

The human receptor bound to testosterone
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Anabolic SteroidsMedical 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

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Anabolic SteroidsNon-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)

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Anabolic SteroidsNon-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

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Anabolic SteroidsAdministration

• 3 common forms of AS administration
• Oral most convenient (dangerous - liver)
• Injectable intramusclar not intravenous (HIV
  and Hepatitis)
• Transdermal self adhesive skin patches

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Anabolic SteroidsMethods 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)

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Anabolic SteroidsMethods 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

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Oral Anabolic Steroids

• 17-alpha methyl testosterone (Android)
• 17-alpha ethyl testosterone (Maxibolin)
• 1-methyl testosterone (Primobolan)
• Androstenediol (Andro food supplements)
• Androstenedione
• Dihydroepiandrosterone (DHEA)

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Injectable Anabolic Steroids

• 19-nortesterone ester derivitives (Durabolin)
• Testosterone ester derivatives (Oreton)
• Testosterone cypionate derivatives (Virilon)
• Boldenone
• Stanozolol (Winstrol) oral form as well

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Anabolic SteroidsMinimization 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

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Anabolic SteroidsPost Cycle Therapy

• 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
• Clomiphene or tamoxifen (Primary PCT drug)
• Anastrozole aromatase inhibitor
• HCG restore hormonal balance

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Anabolic SteroidsPost 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

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Anabolic SteroidsLegal 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

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Anabolic SteroidsU. 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)

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Anabolic SteroidsProhormones

• 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)

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Anabolic SteroidsStatus in Sports

• AS are banned by all major sporting bodies
• IOC
• NBA
• NHL
• NFL
• MLB
• NCAA

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Anabolic SteroidsStatus in Sports

• Testing in Texas high schools to start this year
  (UIL)
• Expensive
• Jurisprudence
• Normal TET ratio 1.31
• 1 in 1000 men ratio of 41
• Positive test result 61

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Anabolic SteroidsStatus 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 61,
  unless there is evidence that this ratio is due
  to a physiological or pathological condition.

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Anabolic SteroidsIllegal 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

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Anabolic SteroidsCounterfeit 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

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Anabolic SteroidsProduction and Distribution

• AS are either manufactured by legitimate
  pharmaceutical companies or under ground
  laboratories
• In the 1990s 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)

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Anabolic SteroidsProduction 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)

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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

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AndrostenedioneBasic 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)

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AndrostenedionePerformance Studies

• No studies have shown any significant increase in
  lean body mass or strength increase
• No significant improvement in athletic
  performance has been shown

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AndrostenedioneSide Effects

• Similar to AS
• Decrease HDL
• Increase estrogen levels (gynecomastia)

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AndrostenedioneTesting 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

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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

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Human Growth HormoneBasic 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

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Human Growth HormonePerformance 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

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Human Growth HormoneSide 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

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Human Growth HormoneTesting and Policy

• Available legally only through physician Rx
• Banned by IOC but not officially tested
• Testing not available in professional sports in
  the US

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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

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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.

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Stimulants

• Caffeine
• Nicotine
• Ephedrine
• Amphetamines

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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)

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Caffeine Dosage

• 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

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CaffeineAdverse Effects

• Diuretic can result in dehydration
• Diminished muscular strength
• Diminished endurance
• Increased risk of heat-related injury or sickness

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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

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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

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EphedrineSide 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

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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

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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

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StimulantsTesting 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

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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)

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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

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Erythropoitin and Blood DopingBasic 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

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Erythropoitin and Blood DopingAdverse Effects

• 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

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Erythropoitin and Blood DopingTesting and Policy

• Only available with physicians 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

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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)

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Creatine

• Several studies show up to 50 usage rate in
  male college athletes
• Recent survey of NFL trainers and team
  physicians
• All teams had players actively taking creatine
• Average use 33 and reports as high as 90

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CreatineBasic 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

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Creatine Basic Science

• Provides energy during short-duration maximal
  bouts of anaerobic exercises
• Phosphorylated form provides a phosphorous atom
  to re-synthesize ATP

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CreatinePerformance 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 12 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

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CreatineSide 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)

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CreatineTesting 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)

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HMB

• Beta-hydroxy-beta-methylbutyrate
• Leucine metabolite that has gained popularity as
  an anticatabolic
• Marketed to suppress protein breakdown in
  recovery phase after workout

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HMBBasic Science

• Mechanism not truly known but several theories
• Increase testosterone levels (similar to AAS)
• Delay anaerobic metabolism
• Prevent exercise-induced muscle damage

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HMBPerformance Studies

• Some evidence that HMB may act to suppress
  protein breakdown
• Little evidence in the literature to support any
  ergogenic advantage

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HMBSide 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

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HMBTesting and Policy

• Available in many over-the-counter supplements
• Not banned by any sporting organization to date

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What can we do?

• Education - wealth of information out there
  (internet, books, magazines)
• Your young athlete knows more about it than you
  (and they dont know enough)

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Proper Training

• Sleep
• Hydration
• Stretching
• Nutrition (timing, whey protein, creatine)
• Proper form and technique (especially in
  skeletally immature athletes)
• Goals

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Thank You!