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Steroid Precursors and Prohibited Substances

Steroid Precursors and Prohibited Substances. Athletic Drug Testing: What Is It?.

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Steroid Precursors and Prohibited Substances

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  1. Steroid Precursors and Prohibited Substances

  2. Athletic Drug Testing: What Is It? • “Anti-doping programs seek to preserve what is intrinsically valuable about sport. This intrinsic value is often referred to as ‘the spirit of sport,’ it is the essence of Olympism; it is how we play true. The spirit of sport is the celebration of the human spirit, body and mind, and is characterized by the following values • Ethics, fair play and honesty • Health • Excellence in performance • Character and education • Fun and joy • Teamwork • Dedication and commitment • Respect for rules and laws • Respect for self and other participants • Courage • Community and solidarity • Doping is fundamentally contrary to the spirit of sport” World Anti-Doping Agency. The World Anti-Doping Code. Accessed; 12/15/2010. Available at: http://www.wada-ama.org/rtecontent/document/code_v2009_En.pdf.

  3. Athletic Drug Testing: Who Monitors? • World Anti-Doping Agency (WADA)1 • Established in 1999 as an international independent agency composed and funded equally by the sport movement and governments of the world • Key activities include scientific research, education, development of anti-doping capacities, and monitoring of the World Anti-Doping Code, which harmonizes anti-doping policies across all sports and countries     • United States Anti-Doping Association (USADA)2 • Established in 2000 as the national anti-doping organization for the Olympic movement in the United States • The US Congress recognized USADA as "the official anti-doping agency for Olympic, Pan American and Paralympic sport in the United States.“ • National Collegiate Athletic Association (NCAA)3 • When Proposal No. 30 was approved at the 1986 NCAA Convention and Proposal Nos. 52-54 were approved at the January 1990 Convention, NCAA institutions reaffirmed their dedication to the ideal of fair and equitable competition at their championships and postseason certified events • http://www.wada-ama.org • http://www.usada.org • http://www.ncaapublications.com/productdownloads/DT11.pdf

  4. Athletic Drug Testing: How Do They Monitor? • Athletes are selected randomly and may be tested “in season” or “out of season” • A urine sample is given under close scrutiny of a testing officer, and volume, pH, temperature, and in some cases specific gravity of the sample are immediately tested to ensure that there has been no attempt to alter the sample • At least 75 mL must be given under close scrutiny • The urine is split into 2 portions (bottles "A" and "B“) • Only the athlete handles the urine and collection containers until sealed with tamper-proof strips, overwrapped with tamper-evident seals, and coded • In some cases, blood samples are taken and undergo a similar rigorous collection and analysis process • The independent official observing the sample procedure records the information and ensures that a chain-of-custody record is continuous • This guarantees that the sample content is protected and that the sample tested is from the correct athlete • The anonymous samples are analyzed by an independent, accredited laboratory for presence of substances banned for a given sport • In many cases, the unused sample may be stored for future testing http://www.theathlete.org/Drug-Testing-In-Sports.htm.

  5. Athletic Drug Testing: Where Does Liability Lie? • Athletic commissions maintain a “strict liability” policy regarding drug testing • Athletes are responsible for any prohibited substance, metabolites, or markers in their body, whether intentional or accidental • Some brands of dietary supplements can contain unknown contaminants that may contain trace amounts of banned substances • A 2007 study of dietary supplements found that 12.5% contained banned substances not declared on the label • NSF International certification program • Provides assurance to athletes that the supplements they use will not contain a banned substance Abbreviation: NFL, National Football League. Martello S, et al. Food Addit Contam. 2007;24(3):258-365.

  6. Permissible and Nonpermissible Substances • Agents prohibited at all times • Anabolic agents • Steroids, steroid precursors • Hormone antagonists and modulators • Erythropoeitin (EPO) • Chemical and physical manipulation • Intravenous fluids or blood products, unless exempted • Specified substances • Beta blockers, masking agents, or diuretics • Major sources of information on prohibited substances • NCAA Banned Substance List • World Antidoping Agency (WADA) • United States Antidoping Association (USADA) Abbreviation: NCAA, National Collegiate Athletic Association. http://www.NCAA.org.

  7. NCAA Rules Regarding Nutritional Supplements (1) • Colleges and coaches are limited in what nutritional supplements can be provided to athletes • No muscle-building supplements and products with unproven or potentially unsafe ingredients can be provided • Institutional staff cannot sell supplements to athletes • Over-the-counter and prescription products may also be prohibited1 • Decongestants and weight loss products that contain phenylpropanolamine (a stimulant) • Beta-2 agonists (asthma medications) • Ephedrine • Alcohol • Caffeine (urinary levels ≥ 15 μg/mL are not allowed) • ~5 regular cups of coffee within a few hours of testing for a healthy and average-sized man2 Abbreviation: NCAA, National Collegiate Athletic Association. http://grfx.cstv.com/photos/schools/domi/genrel/auto_pdf/ncaa-banned-substance-list.pdf. http://www.drugfreesport.com/newsroom/insight.asp?VolID=50&TopicID=7.

  8. NCAA Rules Regarding Nutritional Supplements (2) • Permissible to provide to athletes • Vitamins/minerals • Energy bars • May contain no more than 30% of kcals from protein • Calorie replacement drinks • Shake-type protein drinks with no more than 30% of kcals from protein • Electrolyte replacement drinks • Not permissible to provide to athletes • Amino acids (including amino acid chelates) • Chondroitin • Chrysin • CLA • Creatine/creatine-containing compounds • Garcinia cambogia (hydroxycitric acid) • Ginkgo biloba • Ginseng • Glucosamine • Glycerol • Green tea • HMB (hydroxy-methylbutyrate) • Melatonin • MSM (methyl sulfonyl methane) • Protein powders • St. John’s Wort • Tribulus • Weight gainers • Yohimbe Adapted from NCAA bylaw 16.5.2.g. Available at: http://fs.ncaa.org/Docs/NCAANewsArchive/2005/Association-wide/ncaa+issues+notice+about+nutritional-supplement+provision+-+5-23-05+ncaa+news.html.

  9. Substance Classes of Concern • Testosterone and its structural analogues (anabolic steroids) • Precursors of testosterone (prohormones) • Human growth hormone (HGH)/insulin-like growth factor 1 (IGF-1) • Human chorionic gonadotropin (HCG) • Clenbuterol • Aromatase inhibitors

  10. Testosterone and Anabolic Steroids • Testosterone and its analogues work mainly by interacting with androgen receptors • 2 main sites of androgen receptors are muscle myonuclei and satellite cells • Once testosterone or its analogues dock with the receptors, processes are set in motion that can increase muscle protein synthesis • Effectiveness of anabolic steroids was debated and questioned for a long time • Many studies used dosages much lower than typically used by athletes • To discourage steroid use, the efficacy/activity of steroids was not communicated

  11. Benefit/Risk of Anabolic Steroid Use Benefits • Increased muscle mass and strength • Improved recovery after workouts • Increased aggressiveness, which may intensify training Risks • Cardiovascular disease • Dramatic decreases in HDL • LDL may increase • Liver damage • Peliosis hepatitis, esophageal varices resulting from portal hypertension • Sexual side effects • In males: gynecomastia, testicular atrophy, and decreased sperm count • In females: masculinization • Reduced tendon and ligament flexibility (more tears) • Aggressiveness (‘roid rage) and withdrawal symptoms • Acne The American College of Sports Medicine issued a position statement in 1984 deploring the use of anabolic steroids by athletes (based on health risks and ethics)1 1. American College of Sports Medicine. Med Sci Sports Exerc. 1987;19(5):534-539.

  12. Testosterone Increases Muscle Size and Strength With or Without Exercise • Subjects • 43 healthy young men across 4 groups • Treatment • 600 mg testosterone or placebo weekly for 10 weeks • Exercisers lifted weights 3 times/week aP < .05 for the comparison between the change indicated and that in either no-exercise group. b P < .05 for the comparison between the change indicated and that in the group assigned to placebo with no exercise. cP < .05 for the comparison between the change indicated and the changes in all 3 other groups. Reprinted from Bhasin S, et al. N Engl J Med. 1996;335(1):1-7.

  13. Testosterone Precursors/Prohormones • Androstenedione/androstenediol • 19-Norandrostenedione/19-norandrostendiol • Dehydroepiandrosterone (DHEA) • Others

  14. Summary of Prohormones • Reasons for not using prohormone supplements • Poor quality control • Study of 16 DHEA products found that only 7 were within 90% to 110% of stated label claim • 3 had no DHEA at all, 1 was 150% of label claim • Uncertainty regarding optimal doses • Potential safety concerns • Possible stimulation of the growth of cancers or hypertrophy of tissues such as the prostate • Androgenic effects (eg, facial hair in females) • Research on possible health benefits of prohormones (eg, bone density, cognition) is sketchy at best • Similar lack of efficacy for the nor- versions of androstenediol/androstenedione at 156 mg/day (combination) for 8 weeks in resistance-trained men Abbreviation: DHEA, 5-dehydroepiandrosterone. Parasrampuria J, et al. JAMA. 1998;280(18):1565; Van Gammeren D, et al. Eur J Appl Physiol 2001;84:426.

  15. Summary of Androstenedione (Andro) • One biochemical step away from testosterone • Best study was performed by King et al • 20 weight-training subjects • 8 weeks of weight training • 100 mg andro 3 times/day for 3 different 2-week periods during training (rice flour placebo) • Beyond effect of exercise itself, andro: • Did not increase muscle mass or strength • Did not increase free or total testosterone • Did not decrease body fat • Decreased HDL cholesterol • Increased estradiol and estrone Abbreviation: HDL, high-density lipoprotein. King DS, et al. JAMA. 1999;281(21):2020-2028.

  16. Summary of 5-Dehydroepiandrosterone (DHEA) • DHEA and its sulfated conjugate DHEA-S are the steroids of greatest abundance in the blood • DHEA can be converted to androstenedione, which then can be made into testosterone • Levels of DHEA typically decrease after age 25 • Supplementation of weight lifters with 150 mg DHEA/d for 8 weeks had no effects on testosterone, body composition, or strength beyond the effect of training • Other studies have also generally not shown efficacy for strength or muscle mass in older and non-exercising populations Brown GA, et al. J Appl Physiol. 1999;87(6):2274-2283.

  17. Human Growth Hormone (HGH) • HGH is normally produced by the pituitary gland • Not a steroid, but nonspecifically promotes growth of various tissues (eg, bone, organs) • HGH levels naturally decrease with age • Many of the biologic effects of HGH are from increased production of insulin-like growth factor 1 (IGF-1) • Major effects include reduction in body fat and increased lean mass • Effects are most pronounced in elderly and untrained subjects Blackman MR, et al. JAMA. 2002;288(18):2282-2292; Rudman D, et al. N Engl J Med. 1990;323(1):1-6.

  18. Human Growth Hormone (HGH) • Even though there is evidence for altered body composition, there are a number of concerns associated with HGH • No evidence that HGH actually improves muscle function, strength, or performance in young adults or trained subjects • Inconsistent results for body composition changes • Potential for a wide variety of side effects • Acromegaly/gigantism, organomegaly • Carpal tunnel syndrome • Swollen feet and ankles • Joint pain • Glucose intolerance • Supplementation of HGH is now more prevalent than ever because of easy availability of recombinant HGH • Banned by both WADA and NCAA, and there is now a blood test • May cost ≥ $1,000 per month Abbreviations: NCAA, National Collegiate Athletic Association; WADA, World Anti-Doping Agency. Crist DM, et al. J Appl Physiol. 1988;65(2):579-584; Deyssig R, et al. Acta Endocrinol (Copenh). 1993;128(4):313-318; Yarasheski KE, et al. Am J Physiol. 1992;262(3):E261-E267; Yarasheski KE, et al. J Appl Physiol. 1993;74(6):3073-3076.

  19. Human Chorionic Gonadotropin (HCG) • Peptide hormone that arises in the placenta during pregnancy • Similar in structure to luteinizing hormone • Male steroid users employ HCG after a cycle of steroids to stimulate the testes to restart production of testosterone • May have some anabolic effects • Banned in males by both NCAA and WADA Abbreviations: NCAA, National Collegiate Athletic Association; WADA, World Anti-Doping Agency .

  20. Clenbuterol • Not a steroid, but rather a 2-adrenergic agonist • Human use is illegal in the United States • Some parts of Europe use inhaled (not oral) clenbuterol for humans as a bronchodilator • Clenbuterol is approved for some veterinary applications in the US (eg, horses with lung obstruction) • Popular with bodybuilders because of fat-burning and muscle mass-building properties (no studies of these properties in humans) • Side effects have occurred in people eating the meat of animals that received clenbuterol • Skeletal muscle tremors, agitation, palpitations, dizziness, nausea, muscle cramps, rapid heart rate, and headache • Clenbuterol use carries the risk of toxicity, is illegal in the US, and it is on the WADA and NCAA banned substance lists Abbreviations: NCAA, National Collegiate Athletic Association; WADA, World Anti-Doping Agency.

  21. Summary • WADA, USADA, and NCAA are the primary agencies responsible for establishing requirements for athletic supplements • It is the athlete’s responsibility to ensure that no banned substances are in his/her blood • Although some banned substances may contribute to increased strength, speed, or athletic ability • They are associated with serious adverse effects • They have inconsistent efficacy (if any) • Their detection can result in elimination from sport participation • Nutritional supplements may also be considered prohibited or restricted and may contain traces of banned substances • For supplements, look for certification of the absence of banned substances and other unsafe contaminants by NSF International or other organizations Abbreviations: NCAA, National Collegiate Athletic Association; USADA, United States Anti-Doping Association ; WADA, World Anti-Doping Agency.

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