Anabolic steroids and anabolic androgenic steroids

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Anabolic steroids and anabolic androgenic steroids
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What are these?

• terms for synthetic substances related to the
  naturally occurring male sex hormone testosterone
• have both muscle building (anabolic) and
  masculinizing effects and are therefore used to
  enhance athletic performance and appearance
• Illicit use occurs among adolescents and adults
  both male and female athletes and nonathletes

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Ns?

• One study
• 55 of 27 year old male and 10 24 year old
  female body builders use anabolic steroids
• More than 1 million Americans have used anabolic
  steroids either to improve athletic ability or to
  improve personal appearance
• 4-12 high school boys have used/abused AAS (many
  starting by age 11)

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Street names

• Juice, Roids, Gym Candy, Pumpers, Stackers, Balls
  or Bulls, Weight Trainers, Arnies, As or
  Anabolics

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How are they taken?

• Swallowed in tablets or liquid, injected or
  patches
• Users take them in patterns called cycling
• take them over a specific period of time, stop,
  then start taking them again
• stacking
• Taking different types of steroids in combination
  with other drugs

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Pharmacokinetics

• Highly lipid soluble
• Implications
• Routes of administration
• Significant 1st pass metabolism
• Risk for liver

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Why are they taken?

• Promote increased muscle mass and enhance
  physical strength
• Increase endurance, physical appearance, and
  athletic performance
• 2003 -
• previously undetectable anabolic steroid
  tetrahydrogestrinione incited furor in media when
  high prof
• High profile professional athletes admitted to
  using this drug.
• March 2004-
• FDA classified them as an illegal substance and
  now tests are available to detect drug in urine.
• Androstenedione Mark McGwire

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Medicinal Uses

• Used to treat delayed puberty
• prevention of weight loss in renal failure
• Muscle wasting in males with HIV/AIDS related
  weight loss.
• Repair of severe muscle loss following trauma,

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How do androgens work?

• T synthesized principally in Leydig cell of
  testes
• Once in bloodstream, T (or the anabolic steroid)
  passes through the cell walls of the target
  tissues and attaches to steroid receptors in the
  cytoplasm of cells
• Hormone receptor complex carried into the nucleus
  of the cell and then attaches to DNA (genetic
  transcription mRNA produced)
• Translation of RNA results in production of new
  proteins that leave the cell and mediate
  biological functions

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• Negative feedback loop

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Consequences

• Effects on negative feedback loop
• abnormally high levels of steroids
• shut off production of GRF FSH and LH
• shut off spermatogenesis

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Adverse Effects

• Cardiovascular
• Increase cardiac risk factors
• Hypertension
• Increase in ldl/hdl ratio
• Increased risk for strokes/cardv event
• Hepatic (if taken orally)
• Elevated liver enzymes
• Liver tumours

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Reproductive system effects

• Males
• Decreased T production
• Abnormal spermatogenesis
• Transient infertility
• Testicular atrophy
• Females
• Altered menstruation

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Endocrine, Immune, Muscular

• Increased thyroid function
• Immune function (decreased immunoglobulin)
• Premature closure of bony growth centers
• Tendon degeneration (so inc risk of tears)

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Cosmetic

• Males
• Gynecomastia
• Testicular atrophy
• Acne
• Acceleration of male-pattern baldness
• Females
• Clitoral enlargement
• Acne
• Increased facial/body hair
• Coarsening of skin
• Male pattern baldness
• Deepened voice

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Psychological

• Severe mood swings
• Aggression (?)
• Psychotic episodes (?)
• Depression
• suicideality

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Specific issues for adolescence

• Adolescence hormonally sensitive developmental
  period
• Organizational vs activation effects of steroids

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Aggression

• Idiosyncratic in adults
• Young males?
• roid rage
• Animal models

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• (Farrell et al 2004)
• Male rats given AAS or T (5 days/week for 5 weeks
  before began testing) and then 4 more weeks
  during testing
• Tested in 3 environments
• Home cage
• Neutral cage
• Opponents cage
• Tested at three time points
• During AAS treatment
• During AAS withdrawal
• After AAS withdrawal

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Other results

• AAS exposed males tested with
• Low threat (smaller male)
• High threat (cage of male w estrus female)
• Aggression toward females
• Estrus vs nonestrus females
• Provoked vs not

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Other approaches with animal models

• AAS cocktails
• Differences in AAS
• Testosterone androgenic and anabolic
• Several effects on numerous nt in adolescent
  brain
• Including 5HT
• Stanozolol high anabolic low androgenic
  affinity
• Seems to inhibit androgen-sensitive behaviors
• Nandrolone highest affinity for androgen
  receptor
• Has both androgenic and anabolic

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• Stacking in rodent studies very limited

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Results

• AAS treated males displayed aggression in home
  cage

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Physical Dependence

• WD from large doses of anabolic steroids can be
  accompanied by moderate to severe depression,
  fatigue, restlessness, insomnia, etc,
  dissatisfaction with body image suicide risk
• Still no defined psychiatric wd system have
  been described

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• Congressional hearings (between 1988-1990) held
  to determine the extent of AAS abuse and whether
  the Controlled Substances Act should be amended
• the reported adverse medical effects of steroid
  use, such as potential liver damage and
  endocrinological problems, were not really
  relevant to the criteria for scheduling under the
  Controlled Substances Act

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. Anabolic Steroid Control Act of 1990

• added anabolic steroids as Schedule III
  controlled substances criminalizing non-medical
  use
• It places steroids in the same legal class as
  barbiturates, ketamine and LSD precursors.