Joseph W. McNutt, M.D. Frisco Orthopedics and Sports Medicine : Joseph W. McNutt, M.D. Frisco Orthopedics and Sports Medicine
Performance Enhancing Drugs: Performance Enhancing Drugs
Performance Enhancing Drugs: Performance Enhancing Drugs 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 Steroids: 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!
This is why performance enhancing drugs remain in the spotlight of sports: This is why performance enhancing drugs remain in the spotlight of sports
Anabolic Steroids: 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: 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 Steroids: 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 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: Anabolic Steroids Adverse 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 Steroids Behavioral Effects Controversial
Mood swings
Aggression (roid rage)
Mania
Depression
Withdrawal
Dependence
Anabolic Steroids Biochemical Mechanisms: Anabolic Steroids Biochemical 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 Mechanisms: 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: Anabolic Steroids Biochemical 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 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: 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: 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: 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: 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: 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: 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 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: Anabolic Steroids Post 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 Therapy: 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: 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: 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: 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: Anabolic Steroids Status in Sports AS are banned by all major sporting bodies:
IOC
NBA
NHL
NFL
MLB
NCAA
Anabolic Steroids Status in Sports: 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: 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: 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: 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: 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): 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: 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: 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: 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: Androstenedione Side Effects Similar to AS
Decrease HDL
Increase estrogen levels (gynecomastia)
Androstenedione Testing and Policy: 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: 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 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: 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: 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: 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: 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: 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: Caffeine Adverse 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: 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: 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: 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: 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 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: Erythropoitin and Blood Doping Adverse 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 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: 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: 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: 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: 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: 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: 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: 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: 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: HMB Basic 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: 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: 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: HMB Testing 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
Thank You!: Thank You!