Performance enhancing drugs

Performance enhancing drugs

Performance enhancing drugs Athletics, academics, anti-aging and aesthetics Marianne E. Cumming, BSc (Pharm), MSc, MD, DBIM, AALU September 11, 2014 Table of Contents / Agenda Performance enhancement: definitions User characteristics Enhancer characteristics Neuro-enhancers Anabolic-androgenic steroids Other enhancers

Underwriting considerations Dr. Marianne Cumming | MUC | September 11, 2014 2 Performance enhancement: definitions Dr. Marianne Cumming | MUC | September 11, 2014 3 Performance enhancement Performance:

action or process of carrying out or accomplishing an action, task, or function Enhance: intensify, increase, or further improve the quality, value, or extent of Performance-enhancing drug: "any substance taken to perform better athletically" most commonly associated with elite competitive sports Dr. Marianne Cumming | MUC | September 11, 2014 4 Performance enhancement: medical models

The foundation of modern pharmacy is medical innovation and drug development within a disease-based model. Several factors contribute to the increased use of drugs as enhancers Medicalization common conditions formerly not considered "disease" Use of pharmaceuticals in absence of disease or medical condition disease awareness campaigns, direct-toconsumer advertising self-directed medical care,

"lifestyle drugs" physical enhancement, cognitive enhancement or both with or without athleticism accessible health information via internet with or without "performance" increasing "off-label" prescription drug use

("without the work") Dr. Marianne Cumming | MUC | September 11, 2014 5 Enhancer benefits: perceptions or deceptions "Transhumanism": transform human condition by developing & making available technologies to greatly enhance human intellectual, physical, psychological capabilities Improve and maintain

function increase energy, reduce fatigue increase endurance increase strength improve physical performance improve physical appearance increase muscle mass decrease body fat improve concentration Competitiv e advantage

Health and wellness promotion improve cognitive performance financial gain perceived safety and efficacy and so much more.. The wealth of promotional information and the dearth of evidence-based recommendations related to benefits and risks serve to translate wishful thinking into widespread and not always sensible use of 'enhancers' Dr. Marianne Cumming | MUC | September 11, 2014 6

Enhancers: the insurance applicant Increasing acceptance and use in the general population Increasing identification in insured groups motivated, successful, competitive well-educated, well-informed health conscious, perceived benefits peer pressure potential financial and career incentives expanded "indications" for enhancer use, the four A's athletics academics anti-aging appearance

A Dr. Marianne Cumming | MUC | September 11, 2014 7 Medical enhancing drug: definition Any substance taken to feel or look better The list is long; select examples: Athletics Academics Anti-aging Anabolic

steroids Testosterone precursors Human growth hormone (HGH) Human chorionic gonadotropin Erythropoietin Creatine Stimulants Opioids Stimulants Amphetamines Caffeine

Methylphenidat e Modafinil Armodafinil Beta-blockers Athletics list Academics list Aromatase inhibitors Metformin Other hormones thyroid, melatonin Others - statins

Appearance HGH Androgens Mesotherapy Dr. Marianne Cumming | MUC | September 11, 2014 8 38 year old male, professional athlete, life insurance applicant Highly publicized use of performance-enhancing drugs Reported substances include AAS and HGH, dosages unavailable

Dr. Marianne Cumming | MUC | September 11, 2014 9 28 year old female, PhD student, life insurance applicant No diagnosed medical condition Takes methylphenidate during preparation for examinations Prescribed by her regular physician, no evaluation Dr. Marianne Cumming | MUC | September 11, 2014 10 58 year old male, successful entrepreneur, life

insurance applicant Fit, healthy, active, no medical conditions although recent diagnosis "adult growth hormone deficiency" Rx: testosterone, somatotropin (Norditropin), DHEA, finasteride (Propecia), Marine Fish oil, Men's multivitamin Prior omega-3, lycopene, coenzyme Q10, melatonin, indole-3carbinol, glucosamine chondroitin, methylsulfonylmethane (DMSO, MSM) Dr. Marianne Cumming | MUC | September 11, 2014 11 Performance enhancement: user characteristics

Dr. Marianne Cumming | MUC | September 11, 2014 12 The performer Dr. Marianne Cumming | MUC | September 11, 2014 13 Athletics: long history of enhancer use Dr. Marianne Cumming | MUC | September 11, 2014

14 Risk profile: male college athletes using performance enhancers 234 college male athletes PED users (n=73) in past year (stimulants, hormone precursors, supplements) more likely to report problem alcohol and drug use compared to nonusers (n=160)

Buckman et al, J Stud Alc Drugs 2009 Dr. Marianne Cumming | MUC | September 11, 2014 15 Professional athletes: compared to insured groups Pro athletes ages 20-40, 1970-2000 baseball, basketball, football, hockey violent deaths more common

most were motor vehicle accidents medical deaths less common few "high profile" athletes more deaths in off-season overall, no significant difference in athlete mortality vs other insured young males Pinkham, Contingencies 2001 Dr. Marianne Cumming | MUC | September 11, 2014 16

Performance enhancement: enhancer characteristics Dr. Marianne Cumming | MUC | September 11, 2014 17 Enhancer risk: drug or supplement itself Dr. Marianne Cumming | MUC | September 11, 2014 18 Neuro-enhancers

Dr. Marianne Cumming | MUC | September 11, 2014 19 The universal enhancer: caffeine - health benefits and risks World Anti-Doping Agency (WADA): 2004, caffeine removed from banned list, previous limit >12mcg/mL (8C coffee) until research demonstrated this amount more likely detrimental to performance Dr. Marianne Cumming | MUC | September 11, 2014 20

Cognitive enhancers (CEs) Dr. Marianne Cumming | MUC | September 11, 2014 21 Smart drugs: stimulants: amphetamines, methylphenidate, and more Medical and non-medical uses for 100+ years athletic competition military - enhanced alertness depression attention-deficit hyperactivity disorder (ADHD)

More recently extensive off-label use in healthy individuals: increased alertness, energy or concentration academic and business settings Stimulants: amphetamine, methylphenidate, modafanil Increasing prevalence in normal healthy individuals: 5% to 35% Improved cognitive abilities: most consistent in clinical

populations Mixed results in healthy individuals: some studies - enhancement with improved memory and executive functioning others - report impairment or detrimental effects Smith and Farah, 2011 Dr. Marianne Cumming | MUC | September 11, 2014 22

Cognitive enhancers Dr. Marianne Cumming | MUC | September 11, 2014 23 Modafinil Approved: excessive daytime sleepiness associated with narcolepsy, sleep apnea Non-medical use in military and increasing use in academic, business settings Studies demonstrate cognitive

benefits in healthy individuals May be better tolerated than amphetamines Repantis et al 2010, Mller et al 2013 Dr. Marianne Cumming | MUC | September 11, 2014 24 Anabolic-androgenic steroids Dr. Marianne Cumming | MUC | September 11, 2014

25 Anabolic-androgenic steroids US Anti-Doping Agency (USADA), 2009, 26/8000 tests positive US surveys, androgens: 1% population uses androgens 80% users recreational athletes or body builders Survey: 500 anabolicandrogenic steroid users: 78% - non-competitive body builders or non-athletes 60% - >1000 mg testosterone or

equivalent per week 99% - self injected adolescent users: 3.6% high school students, mostly boys 25% - also used growth hormone more common 95% - polypharmacy cycling, baseball, weightlifting

100% - reported adverse effects with personal or family history of drug misuse Parkinson AB, Evans NA, 2006 Dr. Marianne Cumming | MUC | September 11, 2014 26 Anabolic-androgenic steroids and other hormones Testosterone, and its derivatives: increase muscle mass and strength

Anabolic steroids synthetic derivatives of testosterone Testosterone precursors androstenediol, androstenedione and dehydroepiandrosterone (DHEA) Human chorionic gonadotropin (hCG) stimulates testosterone production Tetrahydrogestrinone (THG) potent androgen "designer steroid", developed to escape urine testing detection Dr. Marianne Cumming | MUC | September 11, 2014

27 Anabolic-androgenic steroids Dr. Marianne Cumming | MUC | September 11, 2014 28 BMJ, January 10, 2014 Dr. Marianne Cumming | MUC | September 11, 2014 29 The fifth "A"? Andropause? or the epidemic of

testosterone deficiency Testosterone in males primarily produced in testes, regulates libido, helps regulate bone mass, fat distribution, muscle mass, strength, erythrocyte and sperm production serum levels decrease with age and with obesity, diabetes mellitus, pituitary disease or trauma, acute illness, nutritional deficiency, certain drugs (opioids, glucocorticoids, other steroids, GnRH analogs) some studies demonstrate benefit in aging males (sex drive, muscle mass, well-being) but long-term risks unclear high doses may cause erythrocytosis, increased risk testosteronedependent diseases (prostate cancer, BPH), serum cholesterol and CV risk (mixed reports) FDA approved for hypogonadism, not as anti-aging therapy Dr. Marianne Cumming | MUC | September 11, 2014

30 Dr. Marianne Cumming | MUC | September 11, 2014 Testosterone therapy and cardiovascular risk Dr. Marianne Cumming | MUC | September 11, 2014 32 Testosterone therapy: cardiovascular risk? Dr. Marianne Cumming | MUC | September 11, 2014 33

Androgen precursors: Androstenedione, "andro" bodybuilders, promoted as nutritional supplement until classified as Rx in 2004 may or may not increase testosterone levels and no evidence that it increases muscle strength Dehydroepiandrosterone (DHEA) dietary supplement (not FDA regulated), promoted to increase muscle strength although converted to testosterone, studies show DHEA but not testosterone levels increased mixed results, small study - no differences in lean body mass comparing "andro", DHEA, placebo; another study - increased strength in males with

DHEA Adverse effects potential for liver damage, estrogen and testosterone dependent cancers, Dr. Marianne Cumming | MUC | September 11, 2014 34 cardiovascular disease Other enhancers Dr. Marianne Cumming | MUC | September 11, 2014 35 Aromatase inhibitors increase testosterone levels in

males Dr. Marianne Cumming | MUC | September 11, 2014 36 Cosmetic mesotherapy Injection of substances locally into subcutaneous tissue "microscopic quantities of homeopathic medications, traditional pharmaceuticals, vitamins, minerals, amino acids into the skin to treat a variety of conditions" local fat reduction, skin rejuvenation, hair restoration, (back pain) Two forms of mesotherapy for local fat reduction Lipolytic: activation of lipolysis in fat cells - aminophylline, isoproterenol,

yohimbine (additive) Ablative: fat cell destruction using a detergent - phosphatidylcholine, deoxycholate Complications, case reports infection (most frequent, atypical mycobacterium), skin reactions, acute psychosis, ischemic colitis, thyrotoxicosis, nephropathy Jayasinghe , Bissoon et al, Obes Rev. 2013 Dr. Marianne Cumming | MUC | September 11, 2014 37 Human growth hormone (HGH) (somatropin): athletics, anti-aging, appearance Decline in serum GH with age is observed yet clinical consequences

are unknown, "replacement" is not recommended, and off-label use in USA is not approved Potential benefits increase in lean body mass (more muscle) decrease in fat mass sprint capacity increased, no effect on strength, power or endurance Adverse effects glucose intolerance, diabetes, edema, hypertension, arthralgias, myopathy possible association with substance misuse, other PEDs (AAS), opioids, cocaine $$$$ US Brand Names: Genotropin, Humatrope, Norditropin, Nutropin, Omnitrope, Saizen, Serostim, Tev-Tropin, Zorbtive

Dr. Marianne Cumming | MUC | September 11, 2014 38 Creatine: athletics Popular nutritional supplement: increase strength, improve high-intensity performance, such as weight lifting (heavy resistance training) not banned BUT supplements containing creatine may be contaminated with banned drugs Sources: endogenous production liver, kidney, pancreas; also dietary meat and fish

Open, 21-month study in college football players, average 5 grams/ day, no detectable adverse effects (Kreider et al, Mol Cell Biochem 2003) Adverse effects, case reports: edema, weight gain, muscle cramps, acute interstitial nephritis (?later chronic renal disease) (Persky & Brazeau, Pharmacol Rev 2001) Dr. Marianne Cumming | MUC | September 11, 2014 39 Dietary supplements: proceed with caution Dr. Marianne Cumming | MUC | September 11, 2014

40 Dr. Marianne Cumming | MUC | September 11, 2014 41 Performance enhancement: underwriting considerations Dr. Marianne Cumming | MUC | September 11, 2014 42

58 year old male, successful entrepreneur, life insurance applicant testosterone cyprionate injection previous 50 mg 2x/weekly, increased to 140 mg weekly (200 mg/ml inject 0.35 ml twice weekly) growth hormone (Norditropin) 0.25 mg/d, increased to 0.3mg/d Dr. Marianne Cumming | MUC | September 11, 2014 43 Enhancers: underwriting considerations Additional factors: age, enhancer properties, reason for use, therapeutic substitute, sportrelated risk

Dr. Marianne Cumming | MUC | September 11, 2014 44 Enhancers: underwriting information underwriting source of drug information, i.e. admitted or from third party indication(s) for drug use current drug(s) and/or dietary supplements, dosage, duration of use prescriber details drug source details any complications resulting from current or previous PED use liver and renal function test results any co-existing medical or psychiatric conditions

any current or history of alcohol or substance misuse or use disorder drug questionnaire Dr. Marianne Cumming | MUC | September 11, 2014 45 Dr. Marianne Cumming | MUC | September 11, 2014 46 Legal notice 2014 Swiss Re. All rights reserved. You are not permitted to create any modifications or derivative works of this presentation or to use it for commercial or other public purposes

without the prior written permission of Swiss Re. The information and opinions contained in the presentation are provided as at the date of the presentation and are subject to change without notice. Although the information used was taken from reliable sources, Swiss Re does not accept any responsibility for the accuracy or comprehensiveness of the details given. All liability for the accuracy and completeness thereof or for any damage or loss resulting from the use of the information contained in this presentation is expressly excluded. Under no circumstances shall Swiss Re or its Group companies be liable for any financial or consequential loss relating to this presentation. Dr. Marianne Cumming | MUC | September 11, 2014 47

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