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Joseph W. McNutt, M.D. Frisco Orthopedics and Sports Medicine

Joseph W. McNutt, M.D. Frisco Orthopedics and Sports Medicine

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Joseph W. McNutt, M.D. Frisco Orthopedics and Sports Medicine

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  1. Joseph W. McNutt, M.D.Frisco Orthopedics and Sports Medicine

  2. Performance Enhancing Drugs

  3. Performance EnhancingDrugs • Anabolic Steroids • Androstenedione • Human Growth Hormone • Beta–2 Agonists • Stimulants • Beta Blockers • Erythropoitin • Creatine • HMB

  4. Anabolic Steroids • 1995 poll – 198 Olympic level power athletes • Given following scenario: you offered a banned substance with two guarantees • You will not be caught • By taking the substance you will win your event • Only 3 said no

  5. Anabolic Steroids • Same poll, new scenario: • The substance will allow you to win every competition you enter over the next 5 years • However the substance will then kill you • More than 50 % would still use the substance!

  6. This is why performance enhancing drugs remain in the spotlight of sports

  7. Anabolic Steroids • Class of steroid hormones related to the male hormone – testosterone • Increase protein synthesis within cells which results in growth of muscle • Also have androgenic properties which include the development and maintenance of males characteristics • Have both medical and sport performance uses

  8. Anabolic Steroids • AS have been modified many times to maximize the anabolic effects and minimize the androgenic affects • Alkylation of the 17-alpha position (oral) • Esterfication of the 17-beta hydroxyl group (IM)

  9. Anabolic Steroids • All AS possess both anabolic and androgenic properties • None are absolutely selective • Testosterone anabolic:androgenic ratio: 1 • Nandrolone: 10 • Stanozolol: 30 • Anabolic effect dose dependent (300 mg per week required)

  10. Anabolic SteroidsHistory • 1931 – male hormone androstenone isolated • 1934 – androstenone synthesized • 1935 – testosterone identified and synthesized • 1937 – clinical trials on humans with testosterone began

  11. Anabolic SteroidsHistory • WWII – German scientist synthesized other anabolic steroids and experimented on concentration camp inmates to treat chronic wasting • Also given to German soldiers hoping to increase their aggression • Adolf Hitler rumored to take anabolic steroids

  12. Anabolic SteroidsHistory • 1940s - Soviet Union and Eastern Bloc Countries (East Germany) established steroid programs in Olympic and amateur weight lifters • 1958 – Dianabol (methandrostenolone) approved in U.S. by the FDA

  13. Anabolic SteroidsHistory • 1972 – study showed no difference in performance enhancement in participants compared to ones given placebo • Remained unchallenged for 18 years • Poor study with inconsistent controls and insignificant doses • 2001 – study showed clear increase in muscle mass and decrease in fat associated with high doses of anabolic steroids

  14. Anabolic SteroidsAnabolic Effects • Two different, but overlapping effects • Anabolic – promote cell growth. Increased protein synthesis, appetite, bone remodeling and growth, and production of red blood cells • Increase the size of muscle fibers (hypertrophy) leading to increase in muscle mass and strength • Decrease the amount of fat in muscle

  15. Anabolic SteroidsAndrogenic Effects • Androgenic (virilizing) - development and maintenance of male characteristics: • Increased growth of pubic, beard, chest and limb hair • Enlargement of vocal cords • Increased libido • Enlargement of clitoris • Suppression of natural sex hormones

  16. Anabolic SteroidsAdverse Effects • Most side effects are dose dependent • Elevated blood pressure (most common) • Increase LDL cholesterol and decrease HDL • Increase risk of CV disease and coronary artery disease, arrhythmias, and heart attacks (chronic use)

  17. Anabolic SteroidsAdverse Effects • Accelerate the rate of premature baldness (male and female) • Acne – stimulates the sebaceous glands • Liver damage (cancer) – increased demand on liver as oral steroids are changed (increase bioavailability and stability)

  18. Anabolic SteroidsAdverse Effects • Tendon rupture has been linked to AS • Stiffer and less elastic tendon • No consistent AS –induced ultrastructural or biochemical alterations • Probably tendon does not adapt as fast (weak link

  19. Anabolic SteroidsGender Specific Effects • Gynecomastia – development of breast tissue in males • Conversion of testosterone to estrogen by an aromatase enzyme

  20. Anabolic SteroidsGender Specific Effects • Temporary infertility (decreased production of sperm) • Testicular atrophy (caused by decrease levels in natural testosterone)

  21. Anabolic SteroidsFemale-Specific Effects • Increase in body hair • Male-pattern baldness • Deepening of voice (permanent) • Enlarged clitoris (permanent) • Temporary decrease in in menstrual cycle • Affect fetal development during pregnancy

  22. Anabolic SteroidsAdolescent Effects • Stunted growth – Premature growth plate shut down as a result of increased levels of estrogen • Premature sexual development • Anabolic steroid use in adolescence has been correlated with poorer attitudes related to health

  23. Anabolic SteroidsAdverse Effects • Risk of mortality among chronic AS users repoted to be 4.6 times higher than non-AS users • Weekly doses of 600 mg ot testosterone or its equivalent for cycles lasting less than 12 weeks appear to cause few side effects during scientific studies • Rule: bigger the dose, the bigger the muscle, the bigger the problem

  24. Anabolic SteroidsBehavioral Effects • Controversial • Mood swings • Aggression (roid rage) • Mania • Depression • Withdrawal • Dependence

  25. Anabolic SteroidsBiochemical Mechanisms • Effect of AS on muscle mass is caused in at least two ways: • Increase the production of proteins • Reduce recovery time by blocking the effects of cortisol (promote the breakdown of muscles) • AS affect the number of cells that develop into fat storage cells by favoring cellular differentiation into muscle cells

  26. Anabolic SteroidsBiochemical Mechanisms • Steroid hormones mainly interact with cells by binding to proteins called steroid receptors • After binding, proteins move into the cell nucleus and can alter the expression of genes or activate processes in other parts of the cell

  27. Anabolic SteroidsBiochemical Mechanisms • Receptors involved with AS are called Androgen receptors • Different types of AS bind with different affinities depending on their chemical structure • This determines the characteristic effects of the AS (anabolic vs androgenic) The human receptor bound to testosterone

  28. Anabolic SteroidsMedical Uses • Bone marrow stimulation – aplastic anemia • Growth stimulation – use GH now • Appetite stimulate – AIDS, cancer • Induction of male puberty – extreme delay • Reversible male contraceptive - future • Hormone replacement therapy (men) • Gender dysmorphia - psyciatric

  29. Anabolic SteroidsNon-medical use and abuse • Extremely difficult to determine what percentage of use in the population • Usually middle class, heterosexual men with a median age of 25 • 2006 study – 78% noncompetitive bodybuilders and non-athletes (cosmetic) • 13% reported unsafe injection practices (needle sharing)

  30. Anabolic SteroidsNon-medical use and abuse • Users often stereo-typed as uneducated or “muscle heads” • 1998 study showed steroid users to be the most educated drug users out of all users of controlled substances • Research their product more than any other group

  31. Anabolic SteroidsAdministration • 3 common forms of AS administration: • Oral – most convenient (dangerous - liver) • Injectable – intramusclar not intravenous (HIV and Hepatitis) • Transdermal – self adhesive skin patches

  32. Anabolic SteroidsMethods of Administration • Athletes who take AS do so typically during the active years of the careers • They combine multiple steroid forms (oral and injectable), a practice called “stacking” • The drug dosage is progressively increased (“pyramiding”) during a 4 to 18 week cycle, including a drug-free period between drug regimens (4-6 weeks). • The drug quantity far exceeds the recommended medical dose (200X) • The athlete then progressively reduces the drug dosage in the months prior to competition (to avoid detection)

  33. Anabolic SteroidsMethods of Administration • The cycling of steroids coincides with competition • Many athletes use the training model – “Periodization” • An athlete with a yearly training program (macrocycle) subdivides the year into phases called mesocycles (3 months) • As competition nears, training volume gradually decreases while training intensity increases • Steroid use coincides with the mesocycles, with the goal of achieving maximum strength and size at competition

  34. Oral Anabolic Steroids • 17-alpha methyl testosterone (Android) • 17-alpha ethyl testosterone (Maxibolin) • 1-methyl testosterone (Primobolan) • Androstenediol (“Andro” food supplements) • Androstenedione • Dihydroepiandrosterone (DHEA)

  35. Injectable Anabolic Steroids • 19-nortesterone ester derivitives (Durabolin) • Testosterone ester derivatives (Oreton) • Testosterone cypionate derivatives (Virilon) • Boldenone • Stanozolol (Winstrol) oral form as well

  36. Anabolic SteroidsMinimization of Side Effects • Several techniques to minimize side effects both during cycles and post cycle • Increase CV exercise to counter act effects on left ventricle • Estrogen receptor modulators to reduce effect of aromatisation of steroid hormones (tamoxifen) reduce gynecomastia

  37. Anabolic SteroidsPost Cycle Therapy • “PCT” – takes place after each cycle to combat the natural testosterone suppression and restore proper function of numerous glands • Typically consists of a combination of the following drugs: • Clomiphene or tamoxifen (Primary PCT drug) • Anastrozole – aromatase inhibitor • HCG – restore hormonal balance

  38. Anabolic SteroidsPost Cycle Therapy • Finasteride (Propecia) – reduces the conversion of testosterone to DHT (high rate of alopecia) • The drug is useless in cases in which the steroid is not converted into a more androgenic derivative

  39. Anabolic SteroidsLegal Status • Varies from country to country • U.S. - Schedule III controlled substance (requires prescription, possession without Rx. federal crime punishable up to 7 yrs) • Canada – Schedule IV (obtaining or selling punishable for up to 18 mo., possession not punishable • Also illegal without Rx. in Australia, Argentina, Brazil and Portugal • Legal in Mexico and Thailand

  40. Anabolic SteroidsU. S. Legislation on AS • Interest and debate after 1988 Summer Olympics in Seoul following controversy of Ben Johnson • AS added to Schedule III of the Controlled Substances Act in the Anabolic Control Act of 1990 • Prohormones or “Designer Steroids” not included (Androstenedione)

  41. Anabolic SteroidsProhormones • In 1994 , the Dietary Supplement Health and Education Act was signed into law. • This act classified substances derived from natural sources as food supplements and made many drugs such as prohormones available over the counter. • Thus these substances are not regulated under the same rules and regulations by the FDA. (Loop hole) • This can result in the dosages and actual quality of these substances to be in question as they are sold to the consumer • Amended in 2004 (Androstenedione)

  42. Anabolic SteroidsStatus in Sports • AS are banned by all major sporting bodies: • IOC • NBA • NHL • NFL • MLB • NCAA

  43. Anabolic SteroidsStatus in Sports • Testing in Texas high schools to start this year (UIL) • Expensive • Jurisprudence • Normal T:ET ratio 1.3:1 • 1 in 1000 men ratio of 4:1 • Positive test result 6:1

  44. Anabolic SteroidsStatus in Sports * For testosterone the definition of positive depends on an adverse analytical finding (positive result) based on any reliable analytical method (e.g., IRMS,GCMS, CIR) which shows that the testosterone is of exogenous origin, or if the ratio of the total concentration of testosterone to that of epitestosterone in the urine is greater than 6:1, unless there is evidence that this ratio is due to a physiological or pathological condition.

  45. Anabolic SteroidsIllegal Trade • The majority of AS are obtained illegally through black market trade • Usually manufactured in other countries and smuggled across borders • Smuggling usually done in conjunction with other illegal drugs • Organized crime is involved

  46. Anabolic SteroidsCounterfeit Drugs • Significant health hazard • Computer and scanning technology as made it to copy labels • Product could contain anything (vegetable oil to toxic substances) • Users have died of injecting unknown substances in their body • Products also diluted to maximize profits

  47. Anabolic SteroidsProduction and Distribution • AS are either manufactured by legitimate pharmaceutical companies or under ground laboratories • In the 1990’s most U.S. producers stopped making and marketing AS • Eastern Europe still produce AS in quantity (most medical grade AS sold illegally in North America) • Many illegal AS are veterinary grade (produced and handled in cruder and less sterile fashion)

  48. Anabolic SteroidsProduction and Distribution) • AS can be obtained from several sources • Sold at gyms and competitions • Illegal drug dealers • Mail order (magazines) • Internet (websites posing as oversea pharmacies)

  49. Androstenedione • Made famous by Mark McGuire during historic 1998 chase for single season record of home runs • Immediate precursor to testosterone (prohormone) • Marketed to raise testosterone levels