28-JAN-1350 - Dr. Doug Richards

Doping 101: “Doping is for Dopes”
Doug Richards MD Dip Sport Med
OMA SportMed 2017
DAVID L. MACINTOSH SPORT MEDICINE CLINIC
UNIVERSITY of TORONTO
No
Conflicts
of
Interest
Outline / Learning Goals
 WADA 101: some history leading to creation of WADA
 Review of WADA-prohibited substances and methods:
 Patterns of use in recreational settings
 Health risks associated with anabolic steroid use
What is “Doping”?
 Etymology: from the use of “dope”
as a colloquial term for illicit drugs
 [from Dutch: dop psychoactive concoction from
grape skins from doop sauce from doopen to dip]
 Current precise definition depends on relevant authorities:
i.e. governments, sport organizations (e.g. pro leagues, WADA)
History Outside of Sport
 Historic use of stimulants to enhance
endurance / power / for other reasons
 Scandinavian Berserkers eating Amanita muscaria
 South Asians eating betel nuts
 South Americans eating coca
 Swiss watchmakers & caffeine (controls tremor in low doses)
 Use of many substances to improve lots of
other types of “performance”:
 social disinhibition
 sexual libido / performance
 etc.
First Use in Sport: Endurance Races
 Endurance races in Britain in 1800’s
 > 500 mile walking “races” in < 140 hours
some participants used opium
 Claimed it kept them awake - not at all logical!
Perhaps it numbed their pain / awareness,
and kept them “euphoric” enough to tolerate the race.
 Six-day bicycle races in USA in late 1800’s
 many riders used cocaine to boost endurance
 this makes more physiological sense
1904 St. Louis Olympic Summer Games
 Thomas Hicks (USA) won gold in marathon despite receiving
2mg of strychnine and a shot of brandy in the last 10 miles
 He only won gold after initial winner
Fred Lorz (USA) was discovered to
have travelled several miles in a car!
Hicks being assisted by trainers
Smithsonian Magazine
Leading Off… Stimulants
 after use of cocaine as outlined above, came…
 benzedrine (racemic amphetamine - Merck 1934)
 RAF in WWII
 Berlin Olympics 1936
 cycling in 1940’s on - one death Olympics 1960
- autopsy found amphetamine
 Tour de France death 1967 - amphetamines
 Premiership Football in UK - 1960’s
 amphetamine use widespread
Tom Simpson dies in le Tour ’67
Total Pro Sports
Next Up… Anabolic Agents
 1950’s - reports of Russian and East German
weightlifters using testosterone
 “Designer” steroids:
 1957 - CIBA invents Dianabol
Metandienone (Dianabol)
 early 1960s - J Zeigler (MD) develops Primobolan
 Became “mandatory” in NFL in early 1960’s
 World records in power events all shattered
(Olympic lifting, 100m sprint, etc.)
 68% of competitors at 1972 Olympics
admitted to steroid use (Jan Silvester, PhD thesis BYU)
Metenolone (Primobolan)
F. Vasconcellos
commons.wikimedia.org
Anti-Doping Programs
 First rules:
 1924 - IAAF prohibited use of “stimulants”
 Other ISFs followed suit, but no testing!
 First tests:
 1966 - UCI (cycling) and FIFA (football/soccer)
 1968 - Olympics (Grenoble / Mexico)
Le Tour de France Dopage

1924 - reports of riders admitting to cocaine (and other drugs) use to survive “le Tour”

1950s and beyond - widespread reports of stimulant use – rider died in 1964

1990s – was Lance doping? Does a bear s__ in the woods?

2000 - Festina scandal – Breaking the Chain by Willy Voet

2006 – Operación Puerto – systematic blood doping operation involving many teams

2006 – Floyd Landis – loses his Tour title for testosterone use*

2010 – Alberto Contador loses his Tour title for clenbuterol use**

2012/3 – Lance stripped of titles by USADA & UCI; “confesses” on Oprah

Present – attempts to “clean up” le Tour by use of “biological passports” - circumvented by
“micro-dosing”? But also evidence of significantly slower winning times on historic stages!
Victor Kerlow, NY Times 2011-07-24
UCI - Lance, Andy & Alberto in 2011
ADRVs at Olympic Summer Games
1968 (Mexico)
EtOH in pentathlon!
(1 medal)
1972 (Munich)
7 stimulants
(4 medals)
1976 (Montreal)
8 anabolics, 3 stimulants
(3 medals)
1980 (Moscow)
none (testing was sparse / suspect)
1984 (Los Angeles)
11 anabolics, 1 stimulants
(2 medals)
1988 (Seoul)
3 anabolics, 2 stimulants, 1 ß-blocker, 4 diuretics
(4 medals)
1992 (Barcelona)
2 anabolics, 3 stimulants
1996 (Atlanta)
6 anabolics, 1 stimulant
2000 (Sydney)
8 anabolics, 1 EPO, 1 hGH,1 stimulant, 4 diuretics, Lance
2004 (Athens)
22 anabolics, 2 stimulants, 3 diuretics, 9 procedural, 2 equine (15 medals)
2008 (Beijing)
23 anabolics, 7 EPO, 2 diuretics, 1 ß-blocker, 6 equine
(18 medals)
2012 (London)
16 anabolics, 4 stim, 5 EPO, 2 diur, 1 cannabis, 31 BioPass
(11 medals)
2016 (Rio)
5 anabolics, 2 EPO, 1 GH, 1 diurectic, 1 stim, 3 procedural
(2 medals)
(14 medals)
ADRVs at Olympic Winter Games
1968 (Grenoble)
none
1972 (Sapporo)
1 stimulants
1976 (Innsbruck)
1 stimulants, 1 narcotics, 1 procedural (MD)
1980 (Lake Placid)
none
1984 (Sarajevo)
1 anabolic
1988 (Calgary)
1 anabolic
1992 (Albertville)
none
1994 (Lillehammer)
none
1998 (Nagano)
none (Rebagliati got off for cannabis!)
2002 (Salt Lake)
1 anabolic, 1 stimulant, 4 EPO, 4 blood doping
(9 medals)
2006 (Turin)
1 anabolic, 1 stimulant, 6 procedural (EPO / blood)
(1 medal)
2010 (Vancouver)
1 EPO
2014 (Sochi)
1 anabolic, 6 stimulants, 3 EPO
(1 medal*)
2016 McLaren Report  28+ athletes, 12 suspended
(15 medals**)
(1 medal)
Heterogeneity of Programs
 Prior to 2004, each country and each sport federation
had different rules about doping
 Canada (for example) was toughest on dopers
 random, year-round, unannounced testing programs
 4 year suspension for first offence, life for second
 USA (for example) buried positive test results
 multiple track athletes found guilty allowed to compete
 This led to Lausanne Declaration 1999  WADA
 WADA Code (original 2004; revised 2009, 2015) adopted by:
 International & National Olympic / Paralympic Committees & Sport Orgs
 Some non-Olympic / Paralympic sports
 Few professional sports (none in North America)
 WADA Prohibited List (original 2004, revised annually)
 www.wada-ama.org
WADA’s 9 Definitions of “Doping”
• Presence of a prohibited substance or its
metabolites or markers in an athlete’s body
• Use or attempted use of a
prohibited substance or method
• Refusing or failing to submit to doping control
• Missing a scheduled doping control
• Failure to meet “athlete whereabouts” rules
(only for athletes in registered testing pools)
WADA’s 9 Definitions of “Doping”
• Tampering or attempting to tamper with
any part of the doping control process
• Possession of prohibited
substances or methods
• Trafficking in any prohibited
substances or methods
• Administration or attempted administration of a
prohibited substance or method to an athlete
WADA’s rationale

The WADA Code (2009) stipulates that a
substance or method should be prohibited in sport if:
1. It meets two of these three criteria:
A. It is performance enhancing;
B. Its use represents an actual or potential health risk;
C. Its use “violates the spirit of sport”;
OR
2. Its use has the potential to mask the use of another
prohibited substance or method.
WADA-Prohibited Substances and Methods
 Substances and methods
prohibited at all times
 Substances and methods
prohibited only in competition
Substances Prohibited At All Times
 S0 – Non-Approved Substances
 S1 – Anabolic Agents
 S2 – Peptide Hormones
 S3 – β-2 Agonists
 S4 – Hormone & Metabolic Modulators
 S5 – Diuretics & Masking Agents
Prohibited at ALL times!
S0 – Non-Approved Substances
 Drugs not approved for human therapeutic use
 Experimental drugs
 Veterinary drugs
 “Designer” drugs
 Anything not yet invented!
S1 - Anabolic Agents
 Anabolic Steroids:
 testosterone, DHEA,
THG, androstenedione,
nandrolone, stanozolol,
et cetera
 Other Anabolic Agents:
 clenbuterol, zeranol, SARMs
No “juice” required!
S2 - Peptide Hormones, etc.
 All peptide hormones, growth factors, & related compounds
 Erythropoietic agents (EPO, etc.) – endurance sports
 Growth Hormone (hGH) – anabolic or other effects?
 Many others including:
 IGF-1 (Insulin-like Growth Factor 1)
 gonadotropins (LH, FSH - males only)
 corticotropins (ACTH)
 growth factors (FGF, HGF, MGFs, PDGF, VEGF, …)
 Any substance that mimics or elevates levels of any of these
S3 – β-2 Agonists
 Bronchodilators used to treat asthma
 3 are permitted* by inhalation:
 salbutamol (Ventolin) , formoterol (Oxeze)
and salmeterol (Serevent)
 *only at normal doses
 All others prohibited
S4 – Hormone & Metabolic Modulators
 3 categories of estrogen modulators:
 aromatase inhibitors, SERMs, other anti-estrogens
 used to avoid gynaecomastia induced by estrogenic anabolics
 myostatin modulators (follistatin, etc.) – available on internet?
 metabolic modulators (insulins, PPARδ, AMPK, etc.)
S5 – Diuretics & Masking Agents
 Substances used to alter excretion of drugs, hide their presence
in urine or blood, or alter physiologic parameters used to detect doping
 Examples (not an exhaustive list):
 Diuretics (speed up excretion)
 Epitestosterone (confounds testing if high testosterone levels)
 Probenicid (alters excretion)
 Plasma expanders (dilute drugs)
Prohibited Methods (M1 – M3)
 M1 – Manipulation of Blood & Blood Components
 blood doping (non-therapeutic transfusion)
 artificial oxygen carriers
 M2 – Chemical & Physical Manipulation
 e.g. - catheterization / urine substitution
 all IV infusions > 50 mL / 6 hrs unless in hospital / medically necessary
 M3 – Gene Doping
 transfer of polymers of nucleic acids or analogues;
use of normal or genetically-modified cells
Whizzinator
Baby The
with anti-myostatin
mutation
Autonomic Dysreflexia & Boosting (IPC 2016)
 Sympathetic overdrive caused by
noxious stimulus in lower body
of quadriplegic (Bhambhani et al 2009 WADA)
 Spontaneous (e.g. full bladder) or
deliberate stimuli (“boosting”)
 Systolic BP > 160mmHg not allowed
Prohibited In Competition Only
 S6 – Stimulants
 S7 – Narcotics
 S8 – Cannabinoids
 S9 – Glucocorticosteroids
Jamaica loses 4x100m relay gold medal from Beijing 2008 Olympics after
Nesta Carter (second from left) retro-tests positive for methylhexanamine.
Photo credit AP
S6 - Stimulants
 Medical and “Party Drug” stimulants – cocaine, amphetamines, adrenaline, ephedrine,
related compounds (MDA, MDMA / ecstasy / e, special k, methylhexanamine, etc.)
 Oral decongestants:
 some prohibited at high dosage (e.g. - pseudoephedrine)
 some permitted (e.g. – phenylephrine, phenylpropanolamine, synephrine)
 Problems with supplements – many contain stimulants; e.g.:

e.g. - “geranium oil”, Jack3d, OxyELITE Pro, Hemo-Rage Black Ultra Concentrate, C4 Extreme

Power sports (sprints, lifting, etc.) and “Recreational” use (sports < otherwise?)

Risks – arrhythmias, MI, CVA, psychosis, etc.
Toronto Star, May 2013
S7 - Narcotic Analgesics
 Opiates and congeners
other than codeine and meperidine
 May be used to allow
competition while injured
 Risks well-known to medical community
S8 - Cannabinoids
 Cannabis sativa and Cannabis indicis plants:
 marijuana, hashish, hash oil, etc.
 Synthetic cannabimimetics:
 “Spice”, JWH018, JWH073, etc.
 Social / recreational use / abuse
 Health risks – evolving knowledge
Who, me? I’m from Whistler!
S9 - Glucocorticosteroids
 cortisone / cortisol / related compounds
 NOT permitted
 injection into a vein or muscle
 oral ingestion
 rectal suppository
 Permitted
 inhalation or injection of tendons / joints / bursae
 topical - on skin, in nose, eyes, around anus
Prohibitions in Particular Sports
 Individual sport governing bodies may choose to prohibit these
substances for reasons particular to their sports
 P1 – Alcohol (prohibited in competition only)
 motor sports (flying, auto, motorcycle, powerboat)
 archery, karate
 P2 – Beta-blockers (prohibited in competition only)
 shooting sports (guns, archery, darts), billiards, golf
 automobile, skiing & snowboarding (some disciplines only)
“Recreational” Use of Anabolic Steroids
 Prevalence / Patterns of use
 Health Risks
Tenner et al

7,150 high schools students surveyed, 96.6% response

Reviewed previous studies from 1980s-90s:
 4.0% boys, 1.3% girls,
only slightly higher in
sport participants
Perry et al patterns of use
 Did not look at prevalence, but patterns in 207 self-reported users
 Used a mean of 3.1 agents
 Cycles 5-10 weeks
 Doses 5-29 > max
 Dubious sources of info!
Cohen et al demographics
 surveyed 1,955 USA male users recruited
from weightlifting / bodybuilding gyms
 educated
 white
 employed full time
 occupations widespread
(note execs, health care, self-employed)
Risks of Taking Anabolic Agents
 Hormonal effects
 androgenic (masculinizing) effects
 estrogenic (feminizing) effects
 Non-hormonal toxic effects
 Effects of uncertain mechanism
…or, being kicked out!
“Designer” Steroids 101
 Stereotypical profiles of effect related to side-chain chemistry:
androgenic, estrogenic, and anabolic tendencies
Fragkaki et al Steroids 2009
Gonadal Steroids 101
Androgenic Side-Effects
 Reversible:
 Men - testicular atrophy, low sperm count
 acne
 Irreversible:
 acne scars
 male pattern baldness
 Women - coarse voice, male hair distribution,
clitoral enlargement
 Children - growth arrest, phallic enlargement
Estrogenic Side-Effects
 Reversible:
 breast swelling
(fluid engorgement)
 Women - menstrual irregularities
 Irreversible:
 Men - gynecomastia
Toxic Non-Hormonal Effects
 Reversible:
 liver dysfunction / hepatitis
(usually minimal, sometimes severe)
 Irreversible:
 liver failure?
(hepatic necrosis or hepatocarcinoma)
Effects of Uncertain Mechanism
 Reversible:
 unhealthy cholesterol levels (HDL/LDL)
 decreased glucose tolerance (diabetes)
 dependence / aggression / psychosis / sleep disturbance
 nausea, dizziness
 hypertension
 peptic ulcer (?)
Effects of Uncertain Mechanism
 Irreversible:
 atherosclerosis
 cardiomyopathy
 cancers of lymphatic or
neural tissue (?)
Evidence on Health Effects
 Maravelias et al Toxicology Letters 2005 review
 Korkia et al IJSM 1997 - AAS use in Great Britain
 1,667 @ rec gyms; 6% men, 1.4% women using AAS
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56% testicular atrophy
52% gynecomastia
36% hypertension
26% tendonopathies
22% epistaxis
60% fluid retention
33% clitoral enlargement
65% menstrual abnormalities
Kanayama et al
Canadian Law on Anabolic Steroids
 http://www.rcmp-grc.gc.ca/qc/pub/sens-awar/drogue-drug/steroid-eng.htm
 Post-Dubin enquiry, and after changes to USA law…
 Schedules 1-7 of Controlled Drugs and other Substances Act
 Possession is legal
 Trafficking, import-export, and production are not
Neuropsychiatric Issues
 Dependence / substance abuse syndromes (DSM)
 Aggression / “Roid Rage” / Psychosis
 Yesalis et al JAMA 1993


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use of AAS correlated with:
other drug use including tobacco and alcohol
self-reported aggressive behaviour
crimes against property
 Copeland et al DAD 2000
 100 users interviewed 94 male mean age 27
 75% met 1+ DSM criteria for AAS abuse / dependence
 23% met dependence, 25% met abuse criteria
Conclusions and a Question
 Doping has been and is widespread in competitive sport,
but anti-doping programs may be catching up to the cheaters
 Use of anabolic steroids in non-competitive settings:
 not uncommon
 males, more affluent, educated; focussed on body image
 “Recreational” use of AAS is not benign!
 Issues with info/advice, dosage, injections, patterns of use
 Multiple health risks – variable levels of evidence, but at least some real
 MDs: harm reduction vs. treatment of dependence disorder ?