Anabolic steroids and anabolic androgenic steroids

1. Anabolic steroids and anabolic androgenic steroids

2. 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

3. N’s? • 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)

6. Street names • Juice, Roids, Gym Candy, Pumpers, Stackers, Balls or Bulls, Weight Trainers, Arnies, A’s or Anabolics

7. 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

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

9. 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 –

10. 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,

11. 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

12. Negative feedback loop

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

15. 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

16. Reproductive system effects • Males • Decreased T production • Abnormal spermatogenesis • Transient infertility • Testicular atrophy • Females • Altered menstruation

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

18. 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

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

20. Specific issues for adolescence • Adolescence –hormonally sensitive developmental period • Organizational vs activation effects of steroids

21. Aggression • Idiosyncratic in adults • Young males? • “roid rage” • Animal models

22. (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

24. 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

25. 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

26. Stacking in rodent studies very limited

27. Results • AAS treated males displayed aggression in home cage

28. 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

29. 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

30. . 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.