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Health Consequences of Performance Enhancing Drugs

Health Consequences of Performance Enhancing Drugs. Shalender Bhasin, MD Director, Boston Claude D. Pepper Older Americans Independence Center Director, Research Program in Men’s Health: Aging and Metabolism Brigham and Women’s Hospital Harvard Medical School.

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Health Consequences of Performance Enhancing Drugs

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  1. Health Consequences of Performance Enhancing Drugs Shalender Bhasin, MD Director, Boston Claude D. Pepper Older Americans Independence Center Director, Research Program in Men’s Health: Aging and Metabolism Brigham and Women’s Hospital Harvard Medical School

  2. The Endocrine Society’s Expert Panel:Scientific Statement on Health Consequences of PED Use Dr. Ruth Woods Dr. Fred Nyberg Dr. Harrison Pope Dr. Shalender Bhasin Dr. Jag Khalsa Dr. Larry Bowers Dr. Alan Rogol

  3. Historical Evolution of PED Use by Athletes • 1950s Russian weight lifters use AAS • 1952 Olympics, John Ziegler learns of their use and tries dianabol • 1968 IOC introduces first testing • 1980s First edition of “Steroid handbook” • 1990 US Congress passes Controlled Substances Act • 1999 WADA established • 2003 World anti-doping code adopted • 2012 Lance Armstrong stripped of titles Stepanov 1952 Ziegler at York Club Pope et al, Endocr Rev 2013 in press

  4. How Can We Explain the Androgen Use by Elite Athletes, especially Endurance Athletes and Sprinters? • Motivational effects • Androgens promote recovery • Androgens decrease reaction time and promote hand-eye coordination • Increased O2 delivery: • Increase in hemoglobin and hematocrit • Increase in 2, 3 BPG • Increased capillarity • Effects on mitochondrial biogenesis and quality Guo et al, Aging Cell 2013; Pope et al, 2013

  5. The State-Sponsored Program of Doping in the Former GDR in 1970s • The development of a centralized drug distribution and documentation program • Establishment of a monitoring program • Organization of systematic research into new doping products and avoidance of detection • A comprehensive educational program which trained coaches and physicians about doping • Classification of the doping program as a state secret Franke and Beredonk 1997; Ungerleider 2001 High gold medal count

  6. Two Distinct Populations of PED Users Athletes • Use PEDs to gain competitive advantage in sports • The type of PED used varies with the nature of athletic event • Use often limited to the period of athletic career • Focus of intense detection efforts Non-athlete Weightlifters • Use PEDs mostly to improve personal appearance – look leaner and more muscular • Use mostly AAS • Long term continuous use • Largely invisible Pope et al, Endocr Rev 2013 in press

  7. Categories and Prevalence of PED Use • AAS use uncommon before age of adolescence • About 1/5 of all AAS users have started use by age 18-19 • Median age: 23 years • > 90% by age 35 • Prevalence of lifetime use: about 5% or 3 million persons • Categories of PEDs • Lean mass builders • Stimulants and tranquilizers • Painkillers • Diuretics • Blood boosters • Masking drugs Pope et al, Endocr Rev 2013 in press

  8. The PEDs Used by Athletes and Non-athlete Weightlifters WADA Survey Pope Survey: Substances identified in recreational weightlifters • Pattern of abuse: • IM route used by >80% • Large doses: 50% >500 mg TE, 25% >1000 mg TE • Stacking and cycling • Accessory drugs

  9. Why has PED Use by Non-athlete Weightlifters Remained Hidden as a Public Health Problem? • The public views AAS use largely as a cheating problem among elite athletes. • Most AAS users are not athletes at all • AAS users do not trust physicians; 56% of AAS users had never disclosed their AAS use to their physician (Pope et al 2004). • Unlike alcohol, heroin, and cocaine users, AAS users do not come to the ER. • AAS use became widespread only in the early 1980s.

  10. Roots of Academic Dogma and Controversy Contradictory Position Statements Problems of Study Design in Clinical Trials • Use of relatively low PED doses • Blinding and randomization • Inclusion of competitive athletes • Failure to control protein and energy intake, and exercise stimulus • Methodological limitations Wilson 1988; Bhasin et al 1996, 2003, 2005, 2008, 2013

  11. No Exercise Exercise Placebo Testosterone Placebo Testosterone Effects of A Supraphysiologic Dose of Testosterone on Fat–Free Mass in Healthy Men 6 - 4 - 2 - 0 - Change in Fat Free Mass (Kg) 0.8±0.7 3.2±1.4 1.9±0.6 6.1±0.6 Bhasin S, Storer TW, et al, N Engl J Med 1996;335:1-7

  12. New Challenges in Detection of Designer Steroids • Synthesis and distribution of novel androgens that • have no medicinal properties • have not been previously tested, and • which are produced solely for abuse. • Precursor Molecules: • Converted to active compounds in body • Based on modifications of structures or novel structures • Detection and regulation a challenge for regulatory agencies

  13. BALCO, Barry Bonds, and THG: 73 Home Runs and the “’Clear’ and the ‘Cream’ for my arthritis and fatigue” Bonds’ Trainer Greg Anderson BALCO’s Victor Conte Don Catlin of UCLA Barry Bonds

  14. THG Binds AR, Upregulates AR and MyoD, Stimulates MHC+ Myotubes, and Increases Muscle Mass Jasuja et al Endocrinology 2005

  15. Difficulties in Accurately Assessing Adverse Effects Associated with PED Abuse • Surreptitious nature of abuse • Based on self report of abuse • Variability in types of drugs, dose, frequency, and duration of PED use, and age at initiation • Accessory drugs • High risk behaviors Therefore, randomized trials of PEDs at the high doses used by athletes and non-athlete weightlifters will never be ethically permissible.

  16. Adverse Effects of AAS Abuse • Suicidal, homicidal, and sudden unexplained deaths • Prolonged suppression of HPT axis • Mood and psychiatric disorders • Cardiovascular and metabolic adverse effects • Liver toxicity with 17-alpha alkylated, oral androgens • Gynecomastia (bitch tits) • Risks associated with IM injections: abscesses, HIV • Risks associated with the use of accessory drugs • Risks associated with excessive muscle hypertrophy • Growth retardation in children Choong, Lakshman, Bhasin 2008; Greene et al 2005; Pope and Katz 1994

  17. Suicidal, homicidal, and sudden unexplained deaths • Case reports of sudden coronary and CV deaths • Parssinen et al. (2000) • 62 power lifters who achieved top 5 positions in weight lifting and age-matched control during 1977-1982 period • 13% of power lifters and 3% of controls died • RR 4.6, median age of death 24.5 years • Thiblin et al. (2000) • Cause of death among 34 androgen users • 32% suicides, 26% homicides, 35% “accidental” • Petersson et al. (2006) • Retrospective review of patient records • Higher standardized mortality among steroid users than non-users

  18. Mood and Behavior Disorders • High frequency of mania, hypomania, and major depression (Pope and Katz) • Mania and hypomania more frequently during use • Depression more frequently after withdrawal • Anecdotal reports of “roid rage” • 5 Placebo controlled studies in eugonadal men report inconsistent changes in anger or aggression scores • Self-reporting “paper pencil” instruments lack sensitivity • Pre-existing psychopathology or personality disorder • Higher frequency of use among doormen, bouncers, or those convicted of weapons offence Tricker 1997; Su 1993; Daly 2003; Yates 1999; Pope 2000

  19. Prolonged Suppression of Hypothalamic-Pituitary-Testicular Axis • Universal suppression of HPT axis • Infertility • Prolonged period of testicular suppression upon discontinuation of androgen use • Symptoms of androgen deficiency • Increased risk of relapsing AAS use or of using other psychoactive drugs • Unproven use of hCG, clomiphene and aromatase inhibitors to promote recovery

  20. Androgen Abuse and Cardiovascular Risk • Strong evidence: • Proatherogenic dyslipidemia, particularly with oral 17-alpha alkylated, oral androgens • Decrease HDLC • Increase LDLC • Weak or inconclusive evidence: • Increased LV mass: impairment of both systolic and diastolic function (Dickerman, 1996; De Piccolli, 1991; Urhausen, 2004) • Increased risk of thrombosis • Vasospasm through vascular NO Melchert and Welder Med Sci Sports Med 1995;27:1252; Bhasin et al, 2008

  21. LV Systolic and Diastolic Dysfunction Among AAS Users Baggish et al, Circulation: Heart Failure 2010; 3: 472-476

  22. Adverse Effects of rhGH and Erythropoietin rhGH Erythropoietin Increased risk of thrombosis, cardiovascular events, and stroke Implicated in the deaths of 18 European professional bicycle racers (1987-81) Meta-analyses of RCTs in cancer and ESRD: increased risk of death, thromboembolic events, CV events • Edema • Excessive sweating • Myalgias and arthralgias • Carpal tunnel syndrome • Diabetes • Hypertension • Cardiomyopathy • Increased frequency of neoplasms • Arthropathy

  23. The Endocrine Society’s Scientific Statement • PED use is associated with serious health consequences including the increased risk of death, as well as cardiovascular, psychiatric, metabolic, endocrine, neurologic, infectious, hepatic, renal, and musculoskeletal disorders. • PED abuse is an important public health problem that has largely remained subterranean so far. • Vast majority of PED users are not athletes, but rather non-athlete weigt lifters who use PEDs to look lean and muscular. • Singular attention on doping in sports has detracted attention from the larger public health problem of long-term PED use by non-athlete weightlifters. • The current focus on detecting and punishing elite athletes has had limited impact on PED abuse by non-athlete weightlifters Pope et al, Endocr Rev 2013 in press

  24. The Endocrine Society’s Scientific Statement: Unmet Needs and Opportunities • Observation studies, implemented by establishing a registry, are needed to monitor long term health consequences of PEDs, and may be the only feasible method of collecting scientifically meaningful outcome data. • RCTs of interventions to facilitate recovery of HPT axis in men whose endogenous axis is suppressed by long term AAS use • Mechanisms by which PEDs improve physical performanceand contribute to adverse health effects need examination. • Innovative approaches to enhance public awareness of the serious health consequences of PEDs. Pope et al, Endocr Rev 2013 in press

  25. Questions?

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