Transcript Steroid Precursors and Prohibited Substances

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.org
2. http://www.usada.org
3. 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 tamperproof 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
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
– 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
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
a
Bench-Press Quadriceps
Strength (kg) Area (mm2)
6
4
2
0
P = 0.02
600
400
200
0
P < 0.001
P = 0.003
c
1200
800
400
0
b
b
P < 0.001
P < 0.001
P < 0.001
a
b
20
10
0
b
P < 0.001
P = 0.005
40
30
20
10
0
b
P = 0.004
P < 0.001
P < 0.001
Placebo Testosterone
Placebo Testosterone
No Exercise
Exercise
P < .05 for the comparison between the change indicated and that in either no-exercise group.
< .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.
bP
b
b
c
Squating
Strength (kg)
Treatment
 600 mg testosterone or
placebo weekly for 10 weeks
 Exercisers lifted weights
3 times/week
Mean Change
Subjects
 43 healthy young men across
4 groups
Triceps
Area (mm2)
Fat-free
Mass (kg)
a
P < 0.001
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.