John Hatzenbuehler MD, FACSM ACSM Team Physician Course

Jacksonville, FL February 2016

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There is no room for second place. There is only one place in my game, and that’s first place. Vince Lombardi

I play to win, whether during practice or a real game. And I will not let anything get in the way of me and my competitive enthusiasm to win. Michael Jordan

Winning isn’t everything; it’s the only thing. ‘Red’ Sanders, UCLA football coach, 1950

”If you’re not First, you’re Last.”

- Ricky Bobby

“If you could take a pill that would guarantee you the Olympic gold medal, but would kill you within a year, would you take it?”

How many said “YES”? A. <10% B. 18% C. 25% D. >50%

Mirkin G. Eating for competing. Semin Adolesc Med. 1987;3:177-183.

“If you could take a pill that would guarantee you the Olympic gold medal, but would kill you within a year, would you take it?”

How many said “YES”? A. <10% B. 18% C. 25% D. >50%

Mirkin G. Eating for competing. Semin Adolesc Med. 1987;3:177-183.

“If you were offered a banned performance-enhancing substance that guaranteed that you would win an Olympic medal, and you could not be caught, would you take it?”

How many said “YES”?

195 out of 198 athletes

Goldman B. Death in the locker room II. Chicago. Elite Sports Medicine Publications. 1992; 23-24.

“Would you take a banned performance enhancing drug with a guarantee that you will not be caught; you will win every competition for the next 5 years, but then die from the side effects of the substance?”

How many said “YES”? >50% of the athletes willing to take

the risk Goldman B. Death in the locker room II. Chicago. Elite Sports Medicine Publications. 1992; 23-24.

“Would you take a banned performance enhancing drug with a guarantee that you will not be caught; you will have unlimited medical knowledge, work <20 hours per week and make sweet cash for 5 years, but then die from the side effects of the substance?”

A. Yes, definitely B. No way C. I would consider it if it helped my golf

game

1. Identify commonly used/abused ergogenic substances

2. Describe the testing processes for common ergogenic aids

3. Become familiar with WADA and TUE

Definition Any substance taken into the body or used by the

body with the intention of increasing performance Ergogenic: Derived from Greek ‘to work’ and ‘to produce’ Ergogenic= Increasing the ability to do work

Common terms to know Cycling- use for a time, then discontinue for a

time and restart ▪ Often surrounds anticipated drug testing

Stacking- using multiple agents simultaneously Pyramiding- regimen of increasing and

decreasing dosages

Why is the use of performance enhancing substances so prevalent?? Simply put: they WORK ▪ Or at least the athlete/coach/parent/fan thinks they do…

Tough to convince an athlete not to take when it makes them faster and stronger

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Widespread use Anabolic steroids now illegal but can still be

found via the internet, black market Use increasing in adolescent population Main classes of agents Anabolic steroids Steroid precursors Blood doping (EPO) Stimulants (Ephedra, Caffeine) Growth hormones Amino acids (Creatine)

Anti-Drug Abuse Act of 1988 Prohibited distribution of AAS for any use other

than disease treatment Placed AASs in Schedule III classification for

controlled substances (same as morphine, amphetamines, etc)

Possession or use= Jail

World Anti-Doping Agency (WADA) established 1999

Initially foundation with support from International Olympic Committee (IOC)

Publishes a banned substances list yearly

Illegal substances Determined by FDA eg. anabolic steroids, androstenedione (steroid

precursor) Legal but banned substances Published list by US Anti-Doping Agency eg. diuretics, caffeine

Dietary supplements eg. protein supplements

US Anti Doping Agency Has to meet 2 of 3 criteria for banning:

▪Enhances sport performance ▪Has inherent health risk to athlete ▪Violates the spirit of sport

Enhanced versions of testosterone Altered to enhance protein synthesis and muscle

growth First introduced in 1950s Illegal in US since 1988

Anabolic and anti-catabolic AKA: ‘roids’ ‘juice’ ‘hype’ ‘pump’

Presumed effects Build muscle mass and strength Enhance athletic performance Improve self-esteem

How do adolescents obtain them? Available legally by prescription ONLY Internet based companies sell designer steroid

that have anabolic effects

Both male and female athletes use Estimated 3 million users in USA 1 in 4 adult users began as teens 1 in 10 users is adolescent age

Medical indications HIV wasting, male hypogonadism, palliative

breast Ca, refractory anemia, hereditary angioedema

Adverse Side Effects Liver

▪ Hepatotoxicity ▪ Glucose intolerance

Cardiovascular ▪ Cardiomyopathy ▪ Lipid metabolism

Psych ▪ Aggressive behavior ▪ Depression ▪ Sleep disturbance

Sexual maturation ▪ Infertility ▪ Testicular atrophy ▪ Impotence ▪ Menstrual irregularities ▪ Gynecomastia ▪ Often NOT reversible

Derm ▪ Baldness ▪ Acne

Adverse Side Effects Liver

▪ Hepatotoxicity ▪ Glucose intolerance

Cardiovascular ▪ Cardiomyopathy ▪ Lipid metabolism

Psych ▪ Aggressive behavior ▪ Depression ▪ Sleep disturbance

Sexual maturation ▪ Infertility ▪ Testicular atrophy ▪ Impotence ▪ Menstrual irregularities

Psych ▪ Aggressive behavior ▪ Depression ▪ Sleep disturbance

Derm ▪ Baldness ▪ Acne

Withdrawal from steroids Depression Lethargy High risk of returning to using

Drugs that make you suspicious of anabolic steroids use… Males who take Clomid, aromatase inhibitors ▪ To combat estrogen effects

HCG: increase endogenous testosterone after AASs ▪ Used to restore body’s testosterone production

Selective androgen receptor modulators (SARMs) ▪ Bind better to androgen receptors

Drugs that make you suspicious of anabolic steroids use… Males who take: ▪ Clomid: taken to combat estrogen effects ▪ HCG: increase endogenous testosterone after AASs ▪ Used to restore body’s testosterone production

Prohormones Androstenedione (Andro) DHEA Androstenediol

Became available OTC in 1996

Prohormones Androstenedione (Andro) DHEA Androstenediol

Became available OTC in 1996

1998 2005

Marketed as ‘natural substances’….FDA does not monitor safety ‘Steroid supplements’

2004: Andro (not DHEA) added to schedule III listing for controlled substances by FDA, Dept Health/Human Services Illegal to produce in US Black market availability only

Physiology Involved in testosterone production DHEA produced in adrenals and gonads Converts to Andro or androstenediol in steroid

synthesis pathway Andro/androstenediol converted to testosterone in

testes primarily ▪ High doses of precursor needed to raise testosterone levels

Increased circulating Andro/stendiol levels can be converted to ESTRONE and ESTRADIOL

Andro Project in 2000 Healthy men, 35-65 years of age Andro or androstenediol 200mg daily All men took part in 12-week high intensity

resistance-training program Results: Total testosterone increased by 16% after 1 month but

returned to baseline by 12 weeks Estrone and estradiol levels remained significantly

elevated (up 97%) Neither improved lean body mass or increased muscle

strength (placebo controlled) +adverse effect on HDL

Broeder CE, Quindry J, Brittingham K, et al. The andro project. Arch Intern Med 2000;160: 3093–104.

Effects of daily oral supplementation with Andro 300mg or DHEA 150mg

Healthy men, 19-29yo 8 weeks resistance training No significant increases in testosterone No significant increase in strength or change

in body composition

Brown GA, Vukovich MD, Reifenrath TA, et al. Effects of anabolic precursors on serum testosterone concentrations and adaptations to resistance training in young men. Int J Sport Nutr Exerc Metab 2000;10(3):340–59.

Overall summary of studies 2002 Oral ingestion of steroid precursor= Modest transient increase in testosterone in men Elevated estrogen levels (much more potently) No effect on body composition, muscle mass,

performance Significantly decreased HDL

Adolescent use of testosterone precursors 2002 survey 475 high school students 4% admitted to use in the last year ▪ Many NON-athletes!

NCAA survey 2006 5.3% of athletes use DHEA or Andro 33.4% use nutritional supplements 1.2% AAS

Adverse Side Effects Andro Lowers HDL, increases cardiac risk Long term exposure to unopposed estrogen could

lead to hormone-sensitive malignancy of uterus, breast, prostate

DHEA: Virilization (hair loss, deep voice, hirsutism) Gynecomastia in men

Theoretically, increased androgens could lead to same problems as seen with anabolic steroids Liver injury Glucose intolerance Malignancy Menstrual irregularities Infertility Testicular atrophy Impotence Baldness Acne Aggressive behavior

Who needs their hormones MORE than an adolescent???

Potentially irreversible sex hormone effects Virilizing to females Feminizing to males Also possible precocious puberty stunted growth premature closing of epiphyseal growth plates

WADA uses two main methods for testing Testosterone/epitestosterone ratio ▪ Urine – T/E > 4:1 abnormal

Carbon 13(13C) to Carbon 12(12C) ratio ▪ Urine – plant sterols vs endogenous

Tests not offered clinically

More ways that you can imagine.. Cycling off prior to competition Taking epitestosterone Diuretics – dilute urine Using someone else’s urine Synthesize a new compound with no test

Recent popularity, in part, due to knowledge of use in professional sports Prevalence of usage in 10th grade boys found to be

5% (11 of 224 males, 1992 data) High association of usage if also using anabolic

steroids Low awareness of side effect profile

Polypeptide produced in the anterior pituitary Naturally increases with: sleep, strength

training, hypoglycemia, serotonin Effects Skeletal muscle hypertrophy (not strength) Lipolysis Protein building

Medical uses Growth hormone deficiency Short stature Prader-Willi Syndrome Turner’s Syndrome

Adverse side effects: Creutzfeldt-Jakob disease Fluid retention, mild increases in blood pressure Gigantism in children Acromegaly in adolescents and adults ▪ Concentric cardiac hypertrophy ▪ Diastolic dysfunction ▪ With lipolysis, releases FFA in high enough quantity to

produce arrhythmias ▪ HTN, DMII, HLP, respiratory disease, OA, breast CA,

colorectal CA

Adverse side effects: Creutzfeldt-Jakob disease Fluid retention, mild increases in blood pressure Gigantism in children Acromegaly in adolescents and adults ▪ Concentric cardiac hypertrophy ▪ Diastolic dysfunction ▪ With lipolysis, releases FFA in high enough quantity to

produce arrhythmias ▪ HTN, DMII, HLP, respiratory disease, OA, breast CA,

colorectal CA

Cost prohibitive Studies have not demonstrated ergogenic

properties Muscles bigger but not stronger or faster

Athletes may be taking for lipolytic effect

Reputation among athletes (not proven): Enhances performance Decreases fat Quickens recovery from injury Safe- ie. can’t be caught

No reliable blood or urine test exists

Hormone that stimulates RBC production Mechanism of ergogenic effect Higher levels of hemoglobin, hematocrit result in

higher oxygen-carrying capacity Medical uses Anemia with renal failure, AIDS, malignancy

Efficacy Improves endurance Improved aerobic performance

Recombinant EPO banned by IOC in 1990 Only recently have tests become available for

drug testing purposes Test hinges on two factors: rEPO has single peak molecular weight and EPO

has more variable molecular weight rEPO has short half-life of 20 hours, effects last for

2 weeks

Adverse Side Effects Red cell aplasia

secondary to antibodies to EPO

Thrombotic vascular events (hemoconcentration)

Hypertension

Individual biological variables that indirectly detect doping

Hematological Module (2009 ▪ H/H, epo, transfusions

Steroid Module (2014) Exogenous steroids, SARMs

Most commonly used nutritional supplement $400 million dollar industry

Creatine is a naturally occurring substance formed by liver, pancreas, kidneys Complex amino acid (arginine, glycine,

methionine) Found in meat and fish

Involved in creation of ATP in muscle Muscle energy source

Builds muscle mass Increases strength Weight gain Enhances recovery after workout

PCr + ADP + H+ ------ Cr + ATP Creatine Kinase

Prevalence of use in adolescents Large study in Wisconsin 1349 high school football players ▪ 10.4% freshmen ▪ 23.8% sophomores ▪ 41.1% juniors ▪ 50.5% seniors

Dosing regimen A. Loading with 5 grams 4xday for one week then

2-5 grams/day to maintain intramuscular creatine B. 2-3 grams/day (no loading) Mixed with insulin-releasing carbs (ie. fruit drink)

facilitates absorption

Side effects Gastrointestinal distress Muscle cramps Weight gain (up to 2kg consistently seen) Potential to overload kidneys ▪ 2 case reports of acute renal failure from creatine

Use in adolescents very concerning Lack of well designed studies evaluating the

effects in <18 year olds ‘Gateway substance’ 30% non-responders Anaerobic sports best

Recommendations for athletes taking creatine:

Drink large amounts of water Take daily dose without loading doses Do not use during periods of intense exercise

(dehydration) or with high heat and humidity

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Sympathomimetic amine used for years for respiratory ailments, asthma, weight loss, energy

Performance studies- RAND report ▪ Meta-analysis ▪ 52 controlled trials of use ▪ Findings: modest weight loss – 2 pounds ▪ Short term athletic performance improvement if taken

with caffeine

Vast majority of research shows no significant effect of ephedra in relation to: Strength Oxygen uptake Time to exhaustion

Does show modest increase in weight loss

compared to placebo

Adverse Side Effects: 2-3 fold increased odds of developing adverse

psychiatric, autonomic, cardiovascular or gastrointestinal symptoms HTN Tachycardia Impaired thermoregulation DEATH ▪ 26% of adverse events (about 100 events total) resulted

in permanent injury or death

Adverse Side Effects: 2-3 fold increased odds of developing adverse

psychiatric, autonomic, cardiovascular or gastrointestinal symptoms HTN Tachycardia Impaired thermoregulation DEATH ▪ 26% of adverse events (about 100 events total) resulted

in permanent injury or death

Current status BANNED by majority of sporting leagues As of 2004, illegal to manufacture or sell ephedra

in USA (but widely available on internet!!!) Testing for ephedra is randomly done for NCAA

athletes

Methylxanthine alkaloid Well established ergogenic effects Most widely used ergogenic aid Mechanism of action Increases FFA production (spares muscle glycogen) Enhances muscle function and endurance: increases

Calcium release from sarcoplasmic reticulum Antagonizes adenosine receptor resulting in lipolysis

and increase catecholamine release ▪ Decreases perceived fatigue

Question: How much of a caffeinated beverage do you

drink daily?

A. 8 ounces or less B. 9-15 ounces C. 16-23 ounces D. 24 ounces plus E. avoid caffeine most days

Proven ergogenic effects Helps prolong exercise, increase endurance

Question: How much caffeine is in a Tall size Starbucks coffee? A. 100mg B. 240mg C. 400mg D. 600mg

Proven ergogenic effects Helps prolong exercise, increase endurance

Best effect is at lower doses 3 to 6 mg/kg 70 kg person: 210 to 420mg Starbucks coffee: ▪ Tall (12 oz): 260mg ▪ Grande (16oz) : 350mg ▪ Venti (20 oz) : 430mg

Side Effects:

My coffee this morning caused me: A. Gastrointestinal distress (or relief) B. Palpitations C. Dizziness D. Jitteriness or Anxiety E. Coffee makes me feel human

Adverse Side Effects: Gastrointestinal disturbance Palpitations Dizziness Headache Fatigue Tremor Jitteriness Anxiety Loss of concentration No diuretic effect with exercise

IOC has removed from banned list NCAA still restricts use >15ug/mL in urine = positive test Restriction now lifted by USOC because of

variable excretion rates Need to drink 48 oz of Starbucks coffee one hour

before testing to reach this level

Most use in sports relates to those sports that demand strict weight control

Diuresis of free water= acute weight loss Acetazolamide Use with acute mountain sickness May improve athletic performance at high

altitude May be taken to dilute urine to hide discovery

of other substances (‘masking’)

Banned by both IOC and NCAA Adverse Side Effects Dehydration is a significant concern Can occur with as little as 2% loss in body weight Increases risk of heat injury Hypokalemia, renal failure

Confusing to athletes who hear information and recommendations from peers, coaches, parents, medical staff

Struggle to find balance between: society’s praising of athletic prowess medical community’s warnings of performance

enhancing substances

How do you find the users? Most typical patient Male, athlete, involved in sport that demands high

levels of power/speed/strength/size Most common sports: football, weight lifting,

gymnastics, baseball, wrestling, bodybuilding Highly specialized youth athletes

Those being bullied- to gain an advantage Casual athletes or poor self esteem Those with friends who use

Patients feel more educated than their doctors

Health care providers Need to serve as the ‘voice of reason’ Get educated ASK the questions:

Do you take any medicines or vitamins to make you stronger or faster?

Do you take any vitamins that make you a better athlete? Look better?

Are any of your teammates taking medications/vitamins/supplements that make them look different or get stronger?

How important is it for you to excel at your sport?

What are your goals in athletics? What obstacles do you see to attaining your goals in athletics?

Teaching points to athletes Acknowledge effects of steroids, supplements 20-30% non-responders Cosmetic effect may be most important to

patients Discuss contamination and false advertising Offer alternatives to reach desired outcomes Nutrition, Sports Psychology, Personal Trainer

Teach parents about effects and prevalence

Adolescents are using performance enhancing substances….so ASK!

At least 50% of adolescent users ARE NOT athletes.

Anabolic steroids do lead to increased muscle mass and performance

Creatine is associated with improved performance, decreased fatigue Issues of dehydration, dosing

Testosterone precursors (Andro, androstenediol) are more likely to raise estrogen levels than testosterone levels

Testing regulated by sporting agencies Adolescents are largely unaware of risks of

performance enhancing agents

Review: Sjoqvist F, Garle M, Rane A. Use of doping agents, particularly anabolic

steroids, in sports and society. Lancet 2008;371:1872-82.

www.usada.org

www.wada-ama.org