Performance-enhancing drugs: implications for insurance

Marianne E. Cumming The use of performance enhancers by otherwise healthy individuals may influence their overall well-being for better; or possibly, as a result of unintended side effects, for worse. It could also influence an individual’s insurance status; but it is very challenging for insurers to make an accurate risk assessment.

Medical enhancement, the use of pharmaceutical agents to enhance performance, may be physical or cognitive enhancement or both. Performance-enhancing drugs or enhancers are commonly drugs approved to treat medical conditions; or alternatively they are used ‘off-label’ to improve performance or appearance.

Modern pharmacy has made significant contributions to society through medical innovations and drug development. Early discoveries, such as insulin and penicillin, that some athletes consider enhancers Neuroenhancement drugs contributed to the emergence of a huge necessary to perform at an elite level. Cognitive enhancing drugs, also called pharmaceutical industry. Drug research ‘smart drugs’ or ‘nootropics’, include and development has focused primarily Use of enhancers may be even more amphetamine, methyphenidate, on treatments for diseases, with common in sports without doping modafanil and caffeine. Use in normal exceptions, notably oral contraceptives controls and in recreational sports. healthy individuals is reportedly in 1960. More recently we have seen the Additionally, pharmaceutical increasing with a prevalence reported in increasing medicalisation of conditions, enhancement for non-athletic purposes the range of 5% to 35% (Smith and such as anxiety or minor skin complaints, is increasingly found in the wider Farah, 2011). Although improved which would previously be seen as population. The pursuit of improved cognitive abilities with the use of within the normal remit of human performance in academia, business and stimulants have been reported, available circumstance. This trend has evolved into social environments has led to this data is limited. Benefits are most the use of pharmaceuticals for increase. This may have been driven by consistently reported in clinical enhancement, in the absence of disease competitive pressures; the relative populations; while evidence for benefit in and without a medical condition. performance of peers; and the perceived healthy individuals is mixed. Some efficacy and safety of marketed drugs. studies report enhancement with Performance-enhancing drugs are improved memory and possibly commonly associated in competitive Population surveys suggest use of drug executive functions; but others report sports. Doping, the use of performance- enhancement, particularly for cognitive impairment or detrimental effects. (Smith enhancing drugs in sports, is banned by performance, is gaining acceptance. and Farah, 2011) the majority of sports governing bodies. Reasons for the use of enhancers are Anti-doping campaigns have intensified various: they include increased Amphetamines have been used for over the recent years with coordinated concentration; reduced fatigue; improved medical and non-medical reasons for eradication campaigns; the founding of physical performance; competitive almost 100 years, including enhancing the World Anti-Doping Agency (WADA) advantage; and improved appearance by alertness in military settings, treating in 1999; and more reliable testing increased muscle mass and decreased depression and for athletic competition. methods. As testing has improved, body fat. Use of performance enhancing More recently, amphetamines and however, many believe that the ability to drugs among insurance applicants and methylphenidate, both common cheat the tests has also improved. It is policy holders may influence their health treatments for attention-deficit tacitly acknowledged that doping may and well-being. hyperactivity disorder (ADHD), have been continue to thrive in certain sports; and extensively used off-label to increase

Published in Risk Dialogue Magazine No 16, September 2013: Human enhancement alertness, energy or concentration in is a major focus of anti-doping Despite being marketed as anabolic healthy individuals. This has especially campaigns. While use in elite athletes is steroids, androstenedione and been the case with university students, in often highly publicised, most use occurs dehydroepiandrosterone (DHEA), a trend dubbed ‘academic doping’. The in recreational athletes, body builders androgen precursors, have not been adverse effects of amphetamine and and non-athletes, with estimated use in shown to increase testosterone levels, methylphenidate are similar and include one percent of the population (Sjöqvist et strength or performance. Adverse effects insomnia, nervousness, rare cases of al. 2008) include increases in serum levels of psychosis, anorexia, elevations in blood oestrogen and lutenising hormone (LH) pressure, sudden cardiac death, and The frequency of adverse effects of AAS which are of unknown significance, and addiction potential. use in healthy individuals is not clearly negative effects on serum lipids have identified. Risks may be underestimated been reported. Modafinil, a novel stimulant approved for in the medical literature due to under- use in the treatment of excessive daytime reporting of illicit use. Equally, use could Human growth hormone (HGH), sleepiness associated with narcolepsy, be overestimated given an anti-doping relatively common as enhancer for sleep apnea and shift work sleep environment or due to other factors such athletes, increases lean body mass but disorder, has been used non-medically as combination drugs or adverse training has no demonstrated beneficial effect on by military personnel to manage fatigue effects without established causality. strength or exercise capacity in trained and increasingly is used in academic and athletes (Liu 2008). HGH was evaluated business settings. Modafinil has been Cardiovascular adverse effects, including in a randomised controlled trial with shown to have modest enhancing effects hypertension, left ventricular recreational athletes. HGH significantly on several aspects of cognitive hypertrophy, myocardial ischemia, increased lean body mass and decreased performance (Repantis et al., 2010, arrhythmias, thromboembolism and fat mass in both men and women; and Müller et al., 2013) Modafinil may be blood lipid abnormalities, have been increased sprint capacity in men also better tolerated than amphetamines but reported (Angell et al. 2012, Urhausen et administered testosterone (Meinhardt et may still cause anorexia, elevations in al.2004 D’Andrea et al., 2007). AAS al., 2010). Adverse effects are significant, blood pressure and tachycardia. have been associated with psychiatric including insulin resistance, diabetes, abnormalities including disorders of soft tissue edema, hypertension, Caffeine, the most widely used stimulant, mood and aggressive behaviour. cardiomegaly, myopathy, and carpal is known to increase mental alertness, Associations between AAS use and risky tunnel syndrome. Cases of Creutzfeldt- energy, and the ability to concentrate. Its behaviours including illicit drug use, Jakob disease, a fatal neurodegenerative use as a cognitive enhancer is alcohol or opioid misuse, drinking and disease, have been associated with the widespread, including use of caffeine- driving, or violent or criminal activities use of cadaveric human HGH. containing energy drinks. Caffeine’s have been reported (McCabe et al. 2007, cognitive enhancing effects are likely Buckman et al 2009). Oral synthetic Other performance enhancing drugs indirect through its action on arousal 17-alpha-alkylated androgens have been The list of drugs considered enhancers mood and concentration (Nehlig, 2010). associated with liver toxicity including continues to expand as available drugs, It also has analgesic properties and has elevated liver enzymes, cholestatic developed and approved for disease been associated with possible decreased jaundice, and peliosis hepatitis. Cases of entities, are being used as enhancers. risk of type 2 diabetes, Parkinson’s hepatocellular adenomas or carcinomas Antidepressants, anxiolytics, disease, Alzheimer’s disease, certain have been reported with long-term use antipsychotics, and certain cancers and even all-cause mortality in (Gorayski et al. 2008). Increased risk of anticonvulsants may improve mood and some studies (Lopez-Garcia et al., 2008). benign prostatic hypertrophy and anxiety when used by individuals without Risks include headache, anxiety, tremors, prostate cancer with AAS use has been any diagnosed condition. Similarly, oral insomnia, depression, possible suggested but not conclusively proven hypoglycemics, antihypertensives and substance misuse, elevated blood and tendon rupture has also been particularly cholesterol lowering HMG- pressure and potentially coronary or reported. Additionally, AAS users may CoA reductase inhibitors (statins) may be arrhythmic events. use other substances to gain muscle used in cardiovascular risk factor mass, lose fat mass or to otherwise prevention outside of thresholds for Androgens and other hormones enhance physical appearance with recommended treatment guidelines. Anabolic androgenic steroids (AAS) are added adverse effects. synthetic analogs of the naturally Beta blockers, a class of medications occurring hormone testosterone known Human chorionic gonadotropin (hCG) approved for treatment of several for their anabolic (muscle-building) and stimulates testosterone production in cardiovascular and other conditions, may androgenic (masculising) effects. Their males and may be used in place of be used to reduce performance anxiety primary clinical use is as androgen testosterone or anabolic steroids. hcG is or tremors in normal or anxious replacement therapy in men with a not easily differentiated from normal individuals. They are banned for specific testosterone deficiency. Other clinical secretion which makes its detection with sports that require steadiness such as uses may include treatment for delayed drug testing more difficult. Adverse archery, gymnastics and shooting. Beta puberty, muscle-wasting associated with effects include edema and blockers slow the heart rate, decrease chronic disease and occasionally other gynecomastia. hand tremor and help reduce anxiety. conditions. More commonly, AAS use is They may be used for performance associated with competitive athletes and anxiety associated with presentations or

Published in Risk Dialogue Magazine No 16, September 2013: Human enhancement speeches, despite lack of evidence of obtain enhancers from alternate sources Co-existing medical conditions and effectiveness. Another apparently without informing their doctor, so prescribed medications are relevant to an common practice with limited evidence medical records do not include this underwriting assessment with of effectiveness is the use of beta information. Dosage of enhancers is also enhancers. Enhancers may exacerbate a blockers to enhance surgeons’ important as these dosages are condition or interact with prescription performance by decreasing anxiety and sometimes higher than recommended medications. The prescribing doctor may tremor, although this has not been medical dosages and may contribute to not be aware of the enhancer or the correlated with patient outcomes (Elman adverse events. Route of administration potential interactions. Some enhancers et al. 1998). Adverse effects of beta may also be important, particularly with may worsen psychiatric conditions, lower blockers with short-term use include the potentially hazardous injection seizure threshold in susceptible bradycardia, increased airway resistance, practices of AAS, and potentially other individuals or promote tumour growth. and decreased endurance. unsafe or unapproved routes. Enhancers may be part of an overall drug-centric approach to medical Creatine, one of the most common The method of procuring of enhancer conditions and the level of adherence to nutritional supplements, has been shown drugs may be relevant in terms of the recommended treatment including non- to enhance short duration, high intensity overall medical care of the applicant. An drug treatments may be helpful in the exercise such as sprinting, with no applicant who obtains an enhancer from overall assessment. apparent benefit for endurance sports. It their doctor is more likely to have is heavily advertised for sports and is not adequate follow-up, and early Motivation to use enhancers may be presently a banned substance by WADA. recognition of adverse effects; whereas relevant to insurance underwriting. An Adverse effects of creatine include weight an applicant whose source of the drug is individual could be engaged in several gain, with reports of acute interstitial a trainer or through internet sales is less positive behaviours and lifestyle choices nephritis and possible renal failure. likely to have adequate follow-up. that may translate into a longer, healthier Physician prescribed medications are life. The individual may have a pattern of Implications for insurance most likely legitimate prescriptions with healthy lifestyle and has gradually underwriting proper manufacture and quality controls, incorporated enhancers into their daily Performance enhancing drug use is whereas other sources could potentially regimen, possibly as part of fitness goals widespread in the general population be less reliable in terms of quality. or anti-aging efforts. In contrast, an and also likely in life and health insurance individual may have an undisclosed or groups. Insurance applicants and policy Regulatory issues may be relevant for occult illness that prompted lifestyle holder groups are diverse, healthier than insurance underwriting. Some enhancers changes and various treatments to the general population and with may be illegal in some markets. For counter, for example, muscle wasting characteristics that may fit with enhancers obtained from an illegal source, associated with disease or frailty in an performance enhancing drug use: highly an applicant may be less likely to disclose older applicant. motivated, well-educated, well-informed, drug use on an application and unlikely to successful, employed, and competitive. tell their doctor. The source of the drug, An overall underwriting risk assessment particularly if not through legitimate is valuable to identify the risk appetite of Reasons for performance enhancing drug prescription and licensed pharmacies, the applicant and any associated risk- use have common themes: improvement may also be important. Some drugs may taking behaviors. Use of enhancers may or maintenance of function, health or be diverted from veterinary manufacture. be associated with use of other drugs, wellness promotion, and competitive Others from illegal sources may be alcohol misuse or substance or illicit drug advantage. The wealth of promotional without quality assurances and may misuse. Additional risk-taking behaviours information related to enhancers and the contain an incorrect amount of the may be identified with information dearth of evidence-based enhancer, harmful contaminants or related to occupations or avocations, recommendations relevant to benefits undisclosed active ingredients. The risks including sports associated with and risks serve to translate wishful associated with obtaining the drug significant injury potential or potentially thinking into widespread and not always illegally and nondisclosure are relevant for criminal activity, particularly where sensible use of these drugs. Individual risk assessment. legitimate drugs sources are not wellness initiatives are generally welcome identified. Sports demanding maximal by insurance companies; although they Risk assessment may be challenging exertion may increase risk for sudden may be misguided through inadequate even with the applicant’s list of types, adverse events, particularly with information. names and dosages of enhancers. enhancers with cardiovascular risk, such Indications, usage guidelines and safety as stimulants. For insurance underwriting, the types, information for several drugs used as names and dosages of enhancers and enhancers are available but developed Performance-enhancing drug use in prescriber details are relevant for risk specifically for drug use to treat a insurance applicants adds to the assessment. Applicants using enhancers particular condition. Evidence-based complexities of underwriting risk frequently take multiple enhancers and research and guidelines for use as assessment. The concept that enhancers may or may not fully disclose all drugs; enhancers are limited or unavailable. may contribute to a shift from a disease while others may not consider Additionally, studies of the long term model, in which a drug is used to treat a supplements to be relevant and effects of enhancers are limited or condition or disease, to a health model, inadvertently omit them. Applicants may unavailable, particularly at older ages. in which a drug is used to enhance

Published in Risk Dialogue Magazine No 16, September 2013: Human enhancement health or possibly in some instances, Liu H, Bravata DM, Olkin I, et al. Systematic About the author: prevent a condition is an interesting one. review: the effects of growth hormone on Dr Marianne Cumming is Vice President, However, pharmaceutical companies will athletic performance. Ann Intern Med. Medical Director with Swiss Re America likely continue to focus on drug 2008;148(10):747-758. where she provides medical development for recognized medical consultation, and is involved in Lopez-Garcia E, van Dam RM, Li TY et al. conditions rather than invest in the underwriting and claims education, Relationship coffee consumption with mortality. development of enhancers or lifestyle Swiss Re’s Life Guide Underwriting Ann Intern Med 2008; 148:908–914 drugs. With both healthy and unhealthy Manual development, and mortality applicants using medications, and at Maher B. Poll results: look who’s doping. research. times the same medications, the ability Nature 2008; 452:674–5. to differentiate these groups in an She has published in the Journal of McCabe SE, Brower KJ, West BT, et al. Trends underwriting setting becomes more Insurance Medicine, North American in non-medical use of anabolic steroids by challenging. Evidence supporting use of Actuarial Journal, and On the Risk and is U.S. college students: results from four performance enhancing drugs is limited author of the Academy of Life national surveys. Drug Alcohol Depend and despite the connotations of the term Underwriting (ALU) examination series 2007; 90:243. ‘enhancer’, drug use in the healthy may Build and Blood Pressure chapter as well or may not equate with health. Meinhardt U, Nelson AE, Hansen JL, et al. as three Non-coronary Heart Disease The effects of growth hormone on body chapters. Her research interests include composition and physical performance in obesity, cardiology, psychiatry and References recreational athletes: a randomized trial. Ann substance misuse, chronic pain and Angell PJ, Chester N, Sculthorpe N et al. Intern Med 2010; 152:568. pharmacy topics. Performance enhancing drug abuse and Müller U, Rowe JB, Rittman T et al. Effects of cardiovascular risk in athletes: implications Dr Cumming is board certified in modafinil on non-verbal cognition, task for the clinician. Br J Sports Med 2012; insurance medicine, serves on the enjoyment and creative thinking in healthy 46(Suppl I):i78–i84. American Academy of Insurance volunteers. Neuropharmacology 2013; 64; Medicine Executive Council and the Buckman JF, Yusko DA, White HR, Pandina (2013) 490–495 Board of Insurance Medicine. She was RJ. Risk Profile of Male College Athletes Who Nehlig A, Is Caffeine a Cognitive Enhancer? Program Chair for the AAIM 2012 Use Performance-Enhancing Substances. J Alzheimer’s Dis 2010; 20: S85–S94 Annual Meeting and Triennial Course, is J. Stud. Alcohol Drugs 2009; 70: 919-923, past-Chair of the American Council of 2009 Okudan N, Gokbel H. The effects of creatine Life Insurers Medical Section and past- supplementation on performance during the D’Andrea A, Caso P, Salerno G et al. Left President of the Midwestern Medical repeated bouts of supramaximal exercise. ventricular early myocardial dysfunction after Directors Association. J Sports Med Phys Fitness 2005; 45:507. chronic misuse of anabolic androgenic steroids: a Doppler myocardial and strain Repantis D, Schlattmann P, Laisney O, Heuser Dr Cumming received her Bachelor of imaging analysis. Br. J. Sports Med I. Modafinil and methylphenidate for Science in Pharmacy, Master of Science 2007;41:149–155. neuroenhancement in healthy individuals: in Pharmacology, and Doctor of Medicine A systematic review. Pharmacol Res. 2010 all from the University of Manitoba in Elman MJ, Sugar J, Fiscella R, et al. The effect Sep;62(3):187-206. Winnipeg, Canada. of propranolol versus placebo on resident surgical performance. Tr Am Ophth Soc. Sepkowitz KA. Energy drinks and caffeine- 1998 ( XCVI); 283–294 related adverse effects. JAMA 2012 Dec 19; [e-pub ahead of print] Gorayski P, Thompson CH, Subhash HS, Thomas AC. Hepatocellular carcinoma Sjöqvist F, Garle M, Rane A. Use of doping associated with recreational anabolic steroid agents, particularly anabolic steroids, in Swiss Re use. Br. J. Sports Med 2008;42:74–75. sports and society. Lancet 2008; 371:1872. Centre for Global Dialogue

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Published in Risk Dialogue Magazine No 16, September 2013: Human enhancement