Steroid Precursors and Prohibited Substances

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.

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

1. http://www.wada-ama.org2. http://www.usada.org3. http://www.ncaapublications.com/productdownloads/DT11.pdf

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.

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.

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.

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. 1.http://grfx.cstv.com/photos/schools/domi/genrel/auto_pdf/ncaa-banned-substance-list.pdf. 2.http://www.drugfreesport.com/newsroom/insight.asp?VolID=50&TopicID=7.

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.

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

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

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.

Testosterone Increases Muscle Size and Strength With or Without Exercise

Subjects43 healthy young men across 4 groups

Treatment600 mg testosterone or placebo weekly for 10 weeksExercisers lifted weights 3 times/week

a P < .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.c P < .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.

64

Fat-free

Mass(kg)

2P = 0.02

P < 0.001a

a

bb

c

b b

c

b

b

b

0

600400

Triceps

Area(m

m2 )

200

P = 0.003

0

P < 0.001

P < 0.001 P < 0.0011200800

Quadriceps

Area(m

m2 )

4000

P < 0.001

P < 0.001

20

Bench-Press

Strength

(kg)

10

0

P = 0.005P < 0.001

40

Squating

Strength

(kg)

30

Placebo

No Exercise

MeanChange

Exercise

Testos-terone

Placebo Testos-terone

20100

P = 0.004P <

Testosterone Precursors/Prohormones

Androstenedione/androstenediol 19-Norandrostenedione/19-norandrostendiol Dehydroepiandrosterone (DHEA) Others

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.

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.

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.

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.

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.

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 .

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.

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.