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 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 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 ?
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