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Joseph W. McNutt, M.D. Frisco Orthopedics and Sports Medicine. Performance Enhancing Drugs. Performance Enhancing Drugs. Anabolic Steroids Androstenedione Human Growth Hormone Beta–2 Agonists Stimulants Beta Blockers Erythropoitin Creatine HMB. Anabolic Steroids.

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performance enhancing drugs1
Performance EnhancingDrugs
  • Anabolic Steroids
  • Androstenedione
  • Human Growth Hormone
  • Beta–2 Agonists
  • Stimulants
  • Beta Blockers
  • Erythropoitin
  • Creatine
  • HMB
anabolic steroids
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
anabolic steroids1
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!
anabolic steroids2
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 steroids3
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)
anabolic steroids4
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
Anabolic SteroidsHistory
  • 1931 – male hormone androstenone isolated
  • 1934 – androstenone synthesized
  • 1935 – testosterone identified and synthesized
  • 1937 – clinical trials on humans with testosterone began
anabolic steroids history1
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
anabolic steroids history2
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
anabolic steroids history3
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
anabolic steroids anabolic effects
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
anabolic steroids androgenic effects
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
anabolic steroids adverse effects
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)
anabolic steroids adverse effects1
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)
anabolic steroids adverse effects2
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
anabolic steroids gender specific effects
Anabolic SteroidsGender Specific Effects
  • Gynecomastia – development of breast tissue in males
  • Conversion of testosterone to estrogen by an aromatase enzyme
anabolic steroids gender specific effects1
Anabolic SteroidsGender Specific Effects
  • Temporary infertility (decreased production of sperm)
  • Testicular atrophy (caused by decrease levels in natural testosterone)
anabolic steroids female specific effects
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
anabolic steroids adolescent effects
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
anabolic steroids adverse effects3
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
anabolic steroids behavioral effects
Anabolic SteroidsBehavioral Effects
  • Controversial
  • Mood swings
  • Aggression (roid rage)
  • Mania
  • Depression
  • Withdrawal
  • Dependence
anabolic steroids biochemical mechanisms
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
anabolic steroids biochemical mechanisms1
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
anabolic steroids biochemical mechanisms2
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

anabolic steroids medical uses
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
anabolic steroids non medical use and abuse
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)
anabolic steroids non medical use and abuse1
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
anabolic steroids administration
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
anabolic steroids methods of administration
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)
anabolic steroids methods of administration1
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
oral anabolic steroids
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
Injectable Anabolic Steroids
  • 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
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
anabolic steroids post cycle therapy
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
anabolic steroids post cycle therapy1
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
anabolic steroids legal status
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
anabolic steroids u s legislation on as
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)
anabolic steroids prohormones
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)
anabolic steroids status in sports
Anabolic SteroidsStatus in Sports
  • AS are banned by all major sporting bodies:
  • IOC
  • NBA
  • NHL
  • NFL
  • MLB
  • NCAA
anabolic steroids status in sports1
Anabolic SteroidsStatus 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 sports2
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 6:1, unless there is evidence that this ratio is due to a physiological or pathological condition.

anabolic steroids illegal trade
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
anabolic steroids counterfeit drugs
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
anabolic steroids production and distribution
Anabolic SteroidsProduction 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 distribution1
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)
androstenedione
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
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)
androstenedione performance studies
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
androstenedione side effects
AndrostenedioneSide Effects
  • Similar to AS
  • Decrease HDL
  • Increase estrogen levels (gynecomastia)
androstenedione testing and policy
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
human growth hormone
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
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
human growth hormone performance studies
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
human growth hormone side effects
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
human growth hormone testing and policy
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
beta 2 agonists
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 agonists1
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
Stimulants
  • Caffeine
  • Nicotine
  • Ephedrine
  • Amphetamines
caffeine
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
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
caffeine adverse effects
CaffeineAdverse Effects
  • Diuretic – can result in dehydration
  • Diminished muscular strength
  • Diminished endurance
  • Increased risk of heat-related injury or sickness
nicotine
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
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
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
amphetamines
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
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
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
beta blockers
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
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
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
erythropoitin and blood doping adverse effects
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
erythropoitin and blood doping testing and policy
Erythropoitin and Blood DopingTesting 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
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)
creatine1
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%
creatine basic science
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
creatine basic science1
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
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 – 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
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)
creatine testing and policy
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)
slide91
HMB
  • Beta-hydroxy-beta-methylbutyrate
  • Leucine metabolite that has gained popularity as an “anticatabolic”
  • Marketed to suppress protein breakdown in recovery phase after workout
hmb basic science
HMBBasic Science
  • Mechanism not truly known but several theories:
  • Increase testosterone levels (similar to AAS)
  • Delay anaerobic metabolism
  • Prevent exercise-induced muscle damage
hmb performance studies
HMBPerformance Studies
  • Some evidence that HMB may act to suppress protein breakdown
  • Little evidence in the literature to support any ergogenic advantage
hmb side effects
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
hmb testing and policy
HMBTesting and Policy
  • Available in many over-the-counter supplements
  • Not banned by any sporting organization to date
what can we do
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
Proper Training
  • Sleep
  • Hydration
  • Stretching
  • Nutrition (timing, whey protein, creatine)
  • Proper form and technique (especially in skeletally immature athletes)
  • Goals