Hormone Abuse in Sport

1
Hormone Abuse in Sport

• Alan D. Rogol, MD, Ph.D
• University of Virginia

2
Historical perspectives

• 3rd century BC. Galen described use of
  stimulants by athletes
• Romans gladiators and stimulants
• 19th century use of caffeine, strychnine,
  alcohol, cocaine
• 1904 Olympic marathon Thomas Hicks strychnine
  and brandy
• W.W.II. increased availability of amphetamines

3
SEMINAL EVENTS

• 1967 death of Tommie Simpson in Tour de France
  amphetamines and alcohol
• 1960-70s anabolic steroids
• 1990s peptides growth hormone and
  erythropoietin

4
IOC DEFINITION OF DOPING

• The use of an expedient (substance or method)
  which is potentially harmful to athletes health
  and/or capable of enhancing their performance, or
• The presence in the athletes body of a
  Prohibited Substance or evidence of the use
  thereof or evidence of the use of a Prohibited
  Method

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DOPING

• dop stimulant drink used in tribal ceremonies
  in South Africa during 18th century

6
Sir Arthur Porritt (1965)(first chairman of the
IOC Medical Commission)

• To define doping is, if not impossible, at best
  extremely difficult, and yet everyone who takes
  part in competitive sport or who administers it
  knows exactly what it means. The definition lies
  not in words but in integrity of character.

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ETHICAL ISSUES - AGAINST

• Cheating
• Drug use in sport is contrary to the very
  principles upon which sport is based. Sport is
  considered as character building, teaching the
  virtues of dedication, perseverance, endurance
  and self-discipline.
• Health risks to athlete

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ETHICAL ISSUES - FOR

• Pressure to win
• Attitude that doping is necessary to success
• Expectations about success (individual, coach,
  family, spectators, advertisers)
• Financial rewards
• Desire to be the best

9
DRUG ABUSERS IN SPORT

• Adolescent athletes
• Elite athletes
• Body builders
• Semi-professionals e.g. bouncers, policemen

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CLASSES OF PROHIBITED SUBSTANCES

• Stimulants e.g. amphetamines
• Narcotics
• Anabolic androgenic steroids (AAS)
• Diuretics
• Peptide hormones, mimetics and analogues
• e.g. GH, EPO, IGF-I, insulin

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ANABOLIC ANDROGENIC STEROIDS (AAS)

• Synthetic derivatives of testosterone
• Modified to enhance anabolic effects vs
  androgenic effects

• Depo-testosterone esters
• Enanthate
• Decanoate
• Nandrolone
• Methenolone

• C-17 ?-alkylated
• Methyltestosterone
• Oxymethalone (Anadrol?)
• Stanazol (Winstrol?)
• Oxandrolone

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ERGOGENIC AIDS

• From the Greek, ergon, work.

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ERGOGENIC EFFECTS OF AAS

• Increase lean body mass
• Decrease total body fat
• Enhance recovery time (anti-catabolic)
• Increase aggression
• Enhanced exercise performances
• dependent on skeletal muscle

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ERGOGENIC AIDS (1)

• Enhance energy utilization
• Production
• Control
• Efficiency

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ERGOGENIC AIDS (2)

• True athletic success stems primarily from the
  combination of genetic endowment, training,
  technique, equipment, and proper nutrition

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What athletes want from anabolic supplements

• Citius
• Altius
• Fortius

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What athletes want from anabolic supplements

• Increased strength
• Increased endurance
• Alteration in body composition
• Increased muscle mass
• Reduced fat
• Faster recovery from exercise
• Enhanced athletic performance

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Dietary Supplement Health and Education Act of
1994

• A food supplement is .any product that contains
  a vitamin, a mineral, an amino acid, an herb or
  other botanical or a concentrate, metabolite,
  constituent, extract or combination of any of
  these ingredients.

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ANABOLIC STEROID CONTROL ACT OF 2004

• The amendments clarified the definition of
  anabolic steroids and provided for research and
  education activities relating to steroids and
  steroid precursors.

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ANABOLIC-ANDROGENICSTEROIDS

• Rationale
• Clear differential in athletic performance
  between males and females
• Anabolic effects of the physiologic increases in
  testosterone during male puberity
• Anabolic and ergogenic effects of physiological
  doses of testosterone in hypogondal men

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ANABOLIC-ANDROGENICSTEROIDS

• Rationale (cont)
• Assumption that use of supraphysiologic doses of
  T or more potent synthetic analogs will increase
  muscle bulk and improve athletic performand in
  Eugonadal men
• Assumption that anabolic effects can be separated
  from virilizing effect by use of pure anabolic
  agents
• No changes in gondotropin levels
• No increase in muscle protein metabolism

22
ANDROGENS

• Physiological regulators of lipoproteins,
  particularly the HDL density faction
• Oral and non-aromatizable androgens have a
  greater suppressive effect on HDL, particularly
  HDL2, than do aromatizable androgens

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PATTERNS OF AAS ABUSE

• cycling
• pyramiding
• stacking
• oral and injectable
• Doses

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PATTERNS OF AAS ABUSE

• Concomitant drugs
• Tamoxifen
• diuretics
• hCG
• GH
• IGF-I
• insulin
• thyroid hormone

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SIDE EFFECTS OF AAS ABUSE (1)

• Cardiovascular disease
• cardiomyopathy
• lipid disorders - ?LDL, ?HDL (esp. 17
  ?-alkylated)
• ? platelet aggregation
• ? hematocrit
• ?hypertension

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SIDE EFFECTS OF AAS ABUSE (2)

• Cosmetic
• gynecomastia
• acne
• hirsutism
• breast atrophy
• voice deepening
• virilization (cliteromegaly)
• menstrual disturbance
• hair loss

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SIDE EFFECTS OF AAS ABUSE (3)

• Liver disease (esp with oral and 17?-alkylated
  AAS)
• cholestasis
• steatosis
• tumors
• Reproductive
• testicular atrophy
• infertility
• prostate disease

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SIDE EFFECTS OF AAS ABUSE (4)

• Infection
• HIV, hepatitis
• skin
• Psychological
• aggression (roid rage)
• mood swings

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ANDROSTENEDIONE

• An anabolic steroid
• Direct precursor of estradiol and testosterone
• Dietary supplement

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ANDROSTENEDIONE

• Weak androgen poorly converted to T and E2
• Oral Adione raises Adione concentrations
• Increase in T (30) increase in E2(150)
• Large inter-subject variability
• Increase in circulating steroid metabolites far
  out of proportion to circulating levels of T

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ANDROSTENEDIONE

• No credible studies in adolescent athletes
• Not ethically possible
• Unknown doses and products of unknown purity with
  some contaminants on banned list
• Expensive urine

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ANDROSTENEDIONE

• Short and long term supplementation does not
  increase testosterone levels in young men
• Increase in estrone and estradiol
• LH/FSH not affected
• Gains in muscle mass and strength not affected by
  supplementation

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DEHYDROEPIANDROSTERONE SULFATE (DHEA-S)

• Most abundant human steroid hormone
• Secretory rate- 30mg/day
• Conversion and metabolism in peripheral tissues
  and act locally

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DHEA-S

• Levels change over normal life-cycle
• Fetus-precursor for placental estrogen
• Adrenarche
• Peak as young adult
• Decline with aging

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DHEA-S

• Decline with aging
• Causative of ills of aging
• Paraphenomenon
• Most data in animals who normally make much less
  DHEA-S than primates

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DHEASupplementation

• To alleviate age-associated metabolic/hormonal
  changes and related sequelae
• Decreased immune function
• Decreased lean body mass
• Decreased strength levels
• Increased body fat
• Increased insulin resistance
• Increased coronary artery disease

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DHEA Supplementation

• Discrepancies among studies may relate to
• Basal physiologic milieu
• Body composition
• Nutritional status
• Training protocol
• Closing criteria
• age

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• Im convinced that anyone interested in winning
  Olympic Gold Medals must select his parents
  carefully.
• P.O. Astrand

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• That which is used develops, and that which is
  not used wastes away.
• Hippocrates

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GH abuse

• Increasing prevalence
• Anecdotal reports
• Increasing information re benefits on the
• Internet
• Favorable write-up in The Underground
• Steroid Handbook
• Increasing number of seizures from athletes,
  cyclists, swimmers

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Growth Hormone

• 191 amino acid protein
• Pituitary origin
• 75 22kD 10-15 20kD 10-15 glycosylated/
  sulphated isoforms
• Pulsatile secretion
• Influenced by numerous physiological stimuli
• sleep
• exercise
• nutrition (amino acids, glucose)
• stress

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Growth Hormone Actions

• Direct metabolic effects
• increase glucose availability
• regulate free fatty acids
• increase amino acid uptake
• Long-term anabolic effects
• mediated via IGF-I
• endocrine
• paracrine

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Growth Hormone/ IGF-I axis
Hypothalamus
GHRH
somatostatin
ghrelin
GH secretagogues
Pituitary
Growth Hormone
IGF-I
Anabolism
IGF-I
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GH Deficiency

• leanfat ratio
• exercise tolerance
• muscle strength
• Effect of physiological doses of rhGH in fully
• reversing these changes is controversial

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Ergogenic effects of rGH

• Very few controlled double-blind trials
• Non-exercising young men Yarasheski et al 1992
• 12 weeks rGH - Daily resistive weight training -
• GH ?x6
• IGF-I ?x3 No benefit
• Power athletes - training 14 hrs/week Deyssig et
  al 1993
• GH ?x3
• IGF-I ?x3 No benefit

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Possible reasons for lack of detectable GH
ergogenic effect

• dose of rhGH used
• duration of studies
• GH studied in isolation
• crude efficacy variables

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Current progress

• GH 2000 project
• Aim to develop sensitive and specific tests for
• detection of GH abuse
• combinations of GH, IGF-I, BP-3, ALS
• markers of bone turnover
• Two specific sandwich-type immunoassays
• ratio of levels detected by Abs against
• (i) 22 kD only
• (ii) 22 kD, 20 kD and all other isoforms

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Detection of GH abuse

• Extremely difficult to prove
• structure of rGH is identical to natural GH
• GH is secreted in pulsatile manner
• exercise is potent stimulus to GH release
• release may be modified by variations in
  nutrition and nutritional supplements

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Other GH-related ergogenic substances

• IGF-I
• oral GH secretagogues

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Conclusions

• AAS and GH abuse by elite athletes and
  bodybuilders is widespread
• Scientific evidence of GH efficacy as an
  ergogenic aid is lacking
• Rarely abused in isolation

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THANK YOU