Transcript Performance Enhancing Drugs in Sports

Performance Enhancing Drugs in
Sports
An Overview
Disclosures : None
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Overview of Presentation Topics
• Major types of PEDs and how they work
• Side effects, methods of testing, evasion
• Incidence
• Safety issues with supplements
• MD/ATC approach to the athlete using PEDs
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Many Ways to Enhance Performance
Enhancement Strategy
• Hormonal methods
Sub-topics
• Mechanism
• Medicinal methods
• Effects and side-effects
• Blood doping
• Permissibility and testing
• Nutritional methods
• Training methods
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Steroid synthesis starts with
cholesterol
Most athletic benefit from
testosterone and
dihydrotestosterone
Glucocorticoids and
mineralocorticoids have shortterm benefits
Estrogens cause side-effects
Steroidogenesis
Wikimedia Commons: steroidogenesis
Testosterone
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All the same
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Differs by attached ester
Testosterone analogs
Testosterone precursors
Pathway modifiers
Antiestrogens
Steroidogenesis
Wikimedia Commons: steroidogenesis
Testosterone: Original and Best PED
• Effects
• Increases strength & lean muscle mass
• Reduces fat mass
• Reduces recovery time
• Increases RBC mass
• Types: Testosterone is Testosterone
• “Types” differ by the attached ester
• Propionate, enanthate, cypionate, testosterone suspension, sustanon-250, omnadren
• Molecules that emulate testosterone
• Dihydrotestosterone
• Testosterone analogs
• Testosterone precursors
• Steroidogenesis pathway modifiers
Testosterone
Testosterone analogs
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Stanozolol (Winstrol)
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Nandrolone (Durabolin)
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Tetrahydrogestrinone (the
Clear)
Testosterone precursors
Pathway modifiers
Antiestrogens
Steroidogenesis
Wikimedia Commons: steroidogenesis
Testosterone Analogs
Molecules with similar structure to testosterone
• Testosterone esters are injected
• Stanozolol (Winstrol) depot
• Nandrolone (19-nortestosterone)
• Enanthate (Primobolan)
• Cypionate
• 17α-alkylated androgens are usually taken orally
• Stanozolol (Winstrol)
• Selective Androgen Receptor Molecules (SARMs)
• Andarine most well-known example
• Designed to have greater anabolic than androgenic effects
– No clear evidence any drug is anabolic without being androgenic
• Designer steroids, designed to evade testing
• No pharmacologic use, FDA regulation, safety data
• Poorly characterized, potentially dangerous
Marion Jones, Jason Giambi, Barry Bonds
Implicated for transactions with
Balco (Bay Area Laboratory CoOperative), which supplied designer
androgen tetrahydrogestrinone (the
Clear)
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Testosterone and Analogs
• Water retention
Suppression of endogenous testosterone and • Tendon rupture
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Often biceps and triceps
gametogenesis, testicular atrophy
• Infections from needle use
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Usually recovers in 4 months
Gynecomastia
• ? Prostatic hypertrophy / cancer
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Not seen at replacement doses but not studies at PED doses
Premature physeal closure
Left ventricular hypertrophy (data conflicting) Side Effects in Women
Lower HDL, higher LDL (esp 17a-alkylated) • Virilization
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Hirsutism
Hypertension
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Clitoromegaly
Changes in concentrations of clotting factors,
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Male pattern baldness
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Deepening of voice
but unclear clinical import
• Acne
Roid rage in retrospective surveys, but not
• Oligomenorrhea / amenorrhea
seen in controlled studies
• Muscle dysmorphia
Erythrocytosis
Side Effects
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Hepatotoxicity
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Abnormal LFTs, cholestasis, peliosis hepatis. Probably not
hepatomas.
Detecting Testosterone & Analogs
• Analogs can be detected directly
• Testosterone
• Testosterone glucuronide : epitestosterone glucuronide ratio (T/E
ratio)
• Ratio of 13C to 12C
• Exogenous testosterone made from plant sterols; have higher 12C
• Detected with liquid-chromatography mass-spectrometry (LCMS) or gaschromatography mass-spectrometry (GCMS)
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Testosterone
Testosterone analogs
Testosterone precursors
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Dehydroepiandrosterone
(DHEA)
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Androstenedione
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Androstenediol
Pathway modifiers
Antiestrogens
Steroidogenesis
Wikimedia Commons: steroidogenesis
Mark McGwire
Admitted to using androstenedione in 1998
Same year he hit 70 home runs
Androstenedione was legal in MLB until 2004
The Andro Project
Archives of Internal Med, 2000
• RCT of 50 men undergoing 12 weeks of high intensity training
• Double blind design
• Branches:
• Androstenedione
• Androstenediol
• Placebo
• Conclusion:
• Androstenedione & androstenediol equal to placebo for strength and body
composition
• Did down-regulate testosterone and raise estrogen levels
Mark McGwire
Admitted to using androstenedione in 1998
In 2010 admitted to using steroids throughout
his career
Testosterone
Testosterone analogs
Testosterone precursors
Pathway modifiers
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Aromatase inhibitors
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Exemestane
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Anastrazole
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Letrozole
5α-reductase inhibitors
Antiestrogens
Steroidogenesis
Wikimedia Commons: steroidogenesis
Testosterone
Testosterone analogs
Testosterone precursors
Pathway modifiers
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Aromatase inhibitors
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5α-reductase inhibitors
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Dutasteride
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Finasteride (Propecia)
Antiestrogens
Steroidogenesis
Wikimedia Commons: steroidogenesis
Testosterone
Testosterone analogs
Testosterone precursors
Pathway modifiers
Antiestrogens
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SERMs
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Tamoxifen
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Clomiphene
Steroidogenesis
Wikimedia Commons: steroidogenesis
Non-Steroidal Hormonal PEDs
Human Chorionic Gonadotropin (HCG)
Function
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Agonizes luteinizing hormone
receptors of Leydig cells
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Stimulates testosterone production
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Often used in testosterone
supplementation off-cycle to prevent
rapid muscle loss
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May kick-start endogenous
testosterone production
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Recommended not to prescribe for that
purpose, since a banned substance in itself
Detection
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Urine test can quantify HCG
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In females also detects pregnancy
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In males also detects certain types of cancers
Manny Ramirez
Suspended for 100 games in April 2011 while on
the LA Dodgers for HCG usage
Growth Hormone
Use
Side-Effects
• Benefits
• Insulin resistance, hyperglycemia,
diabetes
• Sodium retention, hypertension,
cardiomegaly
• Physeal closure (in pediatrics)
• Myopathy
• Carpal tunnel syndrome
• Theoretical risk of
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Increases muscle mass
Decreases fat mass
• Increases fat metabolism
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To reduce atrophy in testosterone offcycle
Liked for difficulty of detection
Thought to promote cartilage
• Insignificant benefit for strength
• Usually taken every other day in ~6
month cycles with 3-6 months off
• Usually taken in cocktails
• Increases IGF-1 production
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Acromegaly
Cancers including prostate
Growth Hormone
• Detection
• Requires blood tests because <0.1% secreted in urine
• IGF-1 levels
• N-terminal extension peptide of procollagen type III levels (P-III-P)
• Ratio of growth hormone isoforms
• Recombinant HGH is 23 kDa
• Pituitary secretes many isoforms of different weights
• Difficult to detect
Erythropoietin
• Aka: EPO, epoietin, darbepoietin, Procrit
• Stimulates hematopoiesis
• Increases hematocrit
• Thus increases v̇O2max
• Side effects:
• Increased blood viscosity
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Team US Postal
Service
George Hincapie, Lance Armstrong (front)
Implicated in EPO use by testimony of cyclists,
not failed tests
Armstrong stripped of 7 Tour de France titles
From 1996-2010 only one Tour de France winner
kept his medal (Carlos Sastre, 2008)
Fausto Coppi
Won Tour de France in 1949 and 1952
"Yes, and those who claim otherwise, it's not
worth talking to them about cycling."
Non-Hormonal Methods
• Stimulants
• Caffeine (legal)
• Herbals
• Red Bull, 5 Hour Energy, other drinks
• Amphetamines
• ADHD drugs
• Decongestants
• Methylhexanamine (DMAA)
• Ephedra (ma huang)
• Old fashioned
• Strychnine
• Nicotinyl alcohol
• Catecholamine modifiers
• β-blockers/agonists
• α-blockers/agonists
• Diuretics
• Weight loss, test evasion
• Analgesics
• All types
• Ketorolac big in NFL
• Superman effect
• Thermogenics
• 2,4-dinitrophenol (no antidote)
• Masking drugs
Cat and Mouse
• Athletes may attempt to defeat urine drug testing by
• Diluting urine with diuretics and high fluid intake
• Putting proteases in urethra to hydrolize proteins / peptides
• Drugs that induce endogenous production of anabolic hormones
• Exogenous epitestosterone
• Whizzinator
Athlete’s Perspective
• Often learn about PEDs from
• Other athletes
• Trainers / Coaches
• Magazines
• Internet
• Advertisements
• Not necessarily forthcoming about use
• Goals often not just being healthy
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Where Athletes Get PEDs
• Sources
• Online
• Prescription
• Foreign
• Domestic black market labs
• BALCO, Biogenesis being high profile examples
• Veterinary
• In supplements sold over the counter
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Dangerous Drugs at Vitamin Stores
USA Today, 7/25/2013, “Sports supplement designer has history of risky products”
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Craze sold at GNC, Walmart, Amazon, Bodybuilding.com among others
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USADA tests revealed it contains several amphetamines not on the label
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New supplement Craze on USADA high risk supplement list
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2012 Bodybuilding.com “Supplement of the Year”
Founder, Matt Cahill, investigated & jailed for previous supplements containing
dinitrophenol (1990s) and 2 designer steroids (2000s)
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Dinitrophenol supplement
• Caused blindness, deaths
• Banned for human use in 1930s for causing blindness
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Designer steroids
• Posed as landscaping company to purchase pesticide from China
• Never tested on humans
• Sold as sports supplement
• Caused hepatic failure, death
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Amy Eichner of USADA: players like Matt Cahill are ubiquitous in supplement industry
Incidence of Doping, NCAA Report
• NCAA 2009 Substance Use Report
• “Anonymous” survey of 20,474 athletes from stratified random sample
of all NCAA schools
• Results indicated
• Very low incidence of PED use
• Declining rates of PED use
• Questionable validity
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NCAA Report
• Overall doping reported as rare, decreasing
• Similar across divisions I, II, III
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Different Results with a Different Survey
Method
• NY Times reported unpublished study of >2000 track & field
athletes
• Anonymously asked: “Have you knowingly violated anti-doping
regulations by using a prohibited substance or method in the past 12
months?”
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Used “randomized response” so athletes knew response was anonymous
Yes from 29% of athletes at 2011 world championships
Yes from 45% of athletes at Pan-Arab Games
<2% of WADA drug tests in 2010 were positive
WADA told researchers not to publish their data
• Sport governing bodies, national organizations, teams often have no
incentive or disincentive to catch dopers
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Signs of Use
• Behavioral
• Secretive actions
• Rapid performance gains
• High dietary supplement
interest / use
• Rapid size / muscularity
increases
• Physique or diet obsession
• Hypermuscularity
• Other high-risk behaviors
• Tendinopathies, ruptures
• Cavalier attitude about
supplements
• Virilization (more females)
• Using the lingo: “stacks,”
“cycles,” names of PEDs
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• Physical
• Acne
Role of the Clinician / Trainer
• What the clinician should know
• More than the athlete
• Can be difficult
• Some basic rules about legality of the substance
• Athlete is responsible for substances / medications taken
• Prescriber liability minimal if prescribing substance for medical purposes
• Prescriber liability high if for performance enhancement
• Possession of many anabolic PEDs is a felony
• There is no legal obligation to report
• Support the health of the patient, monitor:
• Lipids, BP, LFTs, lytes, renal function, coags, Hct, TSH…
• Don’t say it doesn’t work. May lose credibility.
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Probably not effective to council that steroids do not work
Natural bodybuilding
restricts certain PEDs
Professional bodybuilding
does not restrict PED use
Elite Natural Bodybuilder:
Rob Riches: 5’10, 180 lbs
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Elite Professional Bodybuilder:
Jay Cutler: 5’9, 310 lbs
Dealing with the Suspected Athlete
• For high school ATCs (4)
• Advantage in knowing athletes,
rapport
• Comment on acne, slowed
growth in height, jaundiced
appearance
• Avoid unfounded scare tactics • Pre-emptive education,
• Acknowledge short-term benefits
• Segue to health, moral, ethical,
legal aspects
• Discuss risks of tainted products
• Support healthy behavior
• Offer good information
• Do not compliment
performance boosts,
appearance
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discussion
• ATLAS
• Athletes Training & Learning to
Avoid Steroids
• ATHENA
• Athletes Targeting Healthy
Exercise & Nutrition Alternatives
References
1.
Antidoping agency delays publication of research: NY Times http://www.nytimes.com/2013/08/23/sports/research-finds-wide-doping-study-withheld.html?_r=0
2.
Broeder et al. The Andro Project: physiological and hormonal influences of androstenedione supplementation in men 35 to 65 years old participating in a highintensity resistance training program. Arch Intern Med. 2000 Nov 13;160(20):3093-104. PubMed PMID: 11074738.
3.
Antidoping agency delays publication of research: NY Times http://www.nytimes.com/2013/08/23/sports/research-finds-wide-doping-study-withheld.html?_r=0
4.
Kersey RD, Elliot DL, Goldberg L, Kanayama G, Leone JE, Pavlovich M, Pope HG Jr; National Athletic Trainers' Association. National Athletic Trainers‘ Association
position statement: anabolic-androgenic steroids. J Athl Train. 2012 Sep-Oct;47(5):567-88. doi: 10.4085/1062-6050-47.5.08. PubMed PMID: 23068595; PubMed Central
PMCID: PMC3465038.
5.
MLB bans use of androstenedione: MLB.com http://mlb.mlb.com/content/printer_friendly/mlb/y2004/m06/d29/c783595.jsp
6.
National Study of Substance Use Trends Among NCAA College Student-Athletes, 2009:
http://www.ncaa.org/sites/default/files/13.%20Substance%20Use%20Report%202009.pdf
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Steroid.com: useful to know what the athletes know, or think they know, about PEDs
8.
Steroids Loom Large Over Programs: Associated Press, 12/20/2012: http://espn.go.com/college-football/story/_/id/8765531/steroids-loom-major-college-football-reportsays
9.
US Anti-Doping Agency High Risk Dietary Supplement List: http://www.usada.org/supplement411/high-risk-list
10.
USA Today, “Sports supplement designer has history of risky products” http://www.usatoday.com/story/news/nation/2013/07/25/bodybuilding-supplement-designermatt-cahill-usa-today-investigation/2568815/
11.
World Anti-Doping Agency prohibited drugs list: http://www.wada-ama.org/en/World-Anti-Doping-Program/Sports-and-Anti-Doping-Organizations/InternationalStandards/Prohibited-List/
12.
Up To Date: “Non-Hormonal Performance Enhancing Drugs,” “Perforance Enhancing Drugs”
13.
Antonio & Stout. “Sports Supplement Encyclopedia” Nutricia Institute of Sports Science, 2001
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