【 “Side Effects” of “Doping drugs” 】

By : Prof. Keun-Youl KIM, M.D. (OCA-MC & Chair of OCA-TUE Subcomm.)

( Handout for Education Symposium – Macau. October 2005)

⊙ Prohibited Substances

[1] Anabolic-Androgenic Steroids

* Widely abused drug. Estimated 1-3 million athletes in US alone have

used anabolic steroids, with annual black market sales well in excess of

$100 million. (Silver M. 2001) (Buckley WE et al. 1988) (Haipt HA et al,1984)

* Among American adolescents, use rate generally range between 4-12%

among young men and are as high as 2% among young women.(Bahrke,1998)

* Recently, there has been increasing concern over so-called “ designer

steroids “. Most popular of these is “ tetrahydrogestrinone (THG) “.

(Tokish JM et al. 2004)

≪ SIDE EFFECTS ≫

* Studying the side effects and health risks of anabolic steroid use is diffi-

cult. Because the drugs are illegal & there is paucity of well-controlled

studies available for review.

Nevertheless, a number of studies have investigated the health

consequences associated with these drugs and have provided strong

evidence of their risks, including hepatic cellular damage, testicular

atrophy, cardiovascular disease, and psychological disturbance, musculo-

Skeletal effects and even increased mortality.

(1) Cardiovascular effects:

(a) Elevated blood pressure, decreased high-density lipoprotein,

Erythrocytosis, Myocardial hypertrophy, Arrhythmia, Thrombosis.

(b) Association between Endothelial dysfunction with an atherogenic

blood lipid profile, and may pose an increased risk of atherosclerosis.

(Ebenbichler CF et al, 2001)

(c) Decrease (25% - 27%) in HDL cholesterol & increase in diastolic

blood pressure after 8 weeks of anabolic steroid use. (Kuipers,1991)

(d) Associated with hypertension, myocardial ischemia, and sudden

cardiac death.

( Fieschi V et al. 2001)(Sillivan ML et al.1998)(Parssinen M et al. 2002)

( Wight JN et al. 1995) (Meichert RB et al: 1995)

(2) Hepatic effects (functional / structural)

(a) Hepatotoxicity (elevated liver function tests) / jaundice

(b) Neoplasm

(3) Reproductive- Endocrine effects

(a) Libido changes, Subfertility, Decreased Luteinizing hormone and

follicle-stimulating hormone.

(b) Increased aggressiveness and sexual appetite, sometimes resulting

in aberrant sexual and criminal behavior.

(c) In Males Only : Impotence with chronic or repeated use, testicular

shrinkage(atrophy), breast enlargement (gynecomastia), prostatic

enlargement, reduction of sperm production, premature baldness.

(d) In Female Only : Masculinization/Hirsutism, excessive hair growth on

the face & body, deepening of the voice, enlargement of clitoris,

abnormal menstrual cycles (suppression of ovarian function and

menstruation), reduced breast size. Polycystic ovarian syndrome.

(e) Childrn: Premature epiphyseal closure of the growth center of long

bones (in adolescents) which may result stunted growth.

Premature puberty among female child.

(4) Psychological effects / Behavioral effects

(a) Mood swings, Aggression, Mania, Depression, Withdrawal,

Dependence.

(b) Direct cause of significant disturbances in personality profiles.

(Cooper CJ et al, 1996)

(c) Significantly less in control of their aggression than did controls.

(Midgley et al, 2001)

(5) Dermatologic effects

(a) Acne, Striae, Alopecia

(b) Gynecomastia

(c) Hursutism (male pilosis)(Too many body-hari as male)

(d) Collagen reducing skin elasticity

(6) Musculo-skeletal system effects:

(a) Muscle tightness and cramp.

(b) Stiff tender, resulting in an increased potential for muscle strains or

rupture.

(7) Mortality rates:

(a) The most severe consequences of long-term AAS use many be on the

cardiovascular system. (Parssinen M, 2002)

(b) Mortality rates among elite power lifters during the years of follow

up was 12.9% in the body-builders compared with 3.1 % in the con-

troll population. The causes of death among the power lifters

include suicide, acute myocardial infarction, hepatic coma, non-

Hodgkin’s lymphoma. ( Parssinen M et al, 2000)

(c) Investigation on cause of death of steroid abusers among the demise

of 34 known users of anabolic steroid, investigator found: 9; victim of

homicide, 11; committed suicide, 12; judged accidental, 2; not determ-

mined. And concluded that anabolic steroid use was associated with

increased risk of violent death from impulsive, aggressive behavior or

depressive symptoms. Chronic cardiac changes were observed in 12

cases (35%)

(8) Injection associated with needle sharing: (Rich JD et al,1999)

(a) Bruising, Infection, Fibrosis, Neuro-vascular injury.

(b) Risk of acquirig AIDS, hepatitis(B,C), and other blood-borne diseases,

abscesses increase greatly with the use of injectable forms.

(c) 25% rate of needle sharing among adolescent anabolic steroid users.

★ (9) Other anabolic agents, including but not limited to:

Clenbuterol, tibolone, Zeranol, zilpaterol. (Kim KY,2000)

(Beta-2 Agonist < Clenbuterol, Bambuterol, Salbutamol, Salmeterol,

Formoterol, Terbutaline, Reproterol etc >

: permitted only by inhalation : Formoterol, Salbutamol, Salmeterol

Terbutaline. )

(a) Headache, insomnia, nausea, nervousness, tremor, muscle cramps

(b) Increased heart rate and blood pressure

(c) Withdrawal symptoms, physiologic dependence, habituation.

(d) Tachyphylaxis (become refractory to the protective effects)

(Cheung D.et al. 1992. Ramage L, et al: 1994. Chong et al,1995)

(e) Association with an increased risk of the combined outcome of

fatal and near-fatal asthma, as well as of death from asthma alone.

(Spitzer WO et al. 1992. Sears MR et al. 1990)

(10) Long-Term Health Risks

(a) The health risks associated with long-term therapeutic doses of

testosterone and chronic supraphysiologic doses of AAS are unknown.

(b) The most severe consequences of long-term AAS use many be on the

cardiovascular system. ( Parssinen M et al, 2002)

* Left ventricular hypertrophy, Impaired diastolic filling, Arrhythmia,

* Increased risk of myocardial infarction and sudden death.

(Melchert RB, Welder AA, 1995) (Wight JN, Salem D., 1995)

(c) As etiologic factors for some cancers. (Parssinen M et al, 2002)

* Hepatic tumor (Nako A. et al.: 2000)

* Renal cell carcinoma (Bryden AAG, 1995) (Martorana G et al,1999)

* Testicular tumor (Froehner M et al, 1999)

* Prostatic cancer (Heikkila R et al, 1999)

(d) The risk of mortality among chronic AAS users is reported to be 4.6

times higher than non-AAS users. (Parssinen M et al, 2000)

≪ Physical Signs of Anabolic-Androgenic Steroid Use ≫

(Evans NA, 2004)

1. Appearance : Muscular hypertrophy,

Hirsutism and voice deepening (female)

2. Skin : Acne

Cutaneous striae in delto-pectoral region

Needle marks in buttocks, thigh, deltoids, baldness.

3. Chest : Gynecomastia (males)

Breast tissue atrophy (females)

4. Genitourinary : Testicular atrophy (male)

Clitoral hypertrophy (females)

[2] Stimulants

(1) Increased heart rate, palpitation, cardiac irregularities

(2) Insomnia, Anxiety, Tremor, Aggressiveness.

(3) Inhibited judgement / decision making.

(4) Increased potential for dehydration.

(5) Amphetamines: Anxiety, ventricular dysrhythmias, hypertension,

hallucinations, addiction, death

(6) Ephedrine: Anxiety, ventricular dysrhythmias, hypertension,

hallucinations, addiction.

[3] Narcotics

(1) Increased pain threshold and failure to recognize injury.

(2) Loss of balance and coordination.

(3) Illusion of athletic prowess beyond inherent ability.

(4) A false feeling of invincibility

(5) Sedation

[4] Peptide Hormones

{1} Erythropoietin (EPO)

(1) Thickening of the blood clots (increases blood viscosity)

(2) Increased the risk of heart attacks, myocardial infarction and

strokes, pulmonary embolism.

{2} Growth Hormone (GH)

(1) Overgrowth of hand, feet and face (Acromegaly)

(2) Heart diseases, myopathic muscle

(3) May develop resistance to long-term use

(4) Carpal tunnel syndrome

(5) Increased oil gland production in the skin & increased sweating.

{3} Insulin-like Growth Factor (IGF-1)

(1) Hypoglycemia

(2) Musculoskeletal changes such as enlargement of the heart,

headaches and joint pains. Muscles may at first becomes

stronger, but ultimately are weakened due to degenerative

changes in the joints.

{4} Insulin

(1) Hypoglycemia (low blood sugar)

(2) Nausea, weakness, shortness of breath

(3) Drowsiness, coma, brain damages and death.

{5} Chorionic Gonadotrophins (HCG)

(Stimulate Testosterone production in male)

(1) Same effects as Anabolic steroids

(2) Gynecomastia may be more common.

{6} Corticotrophins (ACTH)

(1) Stomach irritation & ulcer

(2) Softening of connective tissue

(3) Osteoporosis

(4) Cataracts.

⊙ Prohibited Methods

[1] Blood Doping

(1) Allergic reaction (rash, fever, shock, etc)

(2) Acute hemolytic reactions with kidney damage if incorrectly typed

blood is used.

(3) Delayed transfusion reactions resulting in fever and jaundice.

(can be fatal)

(4) Transmission of infectious diseases (viral hepatitis and AIDS)

(5) Overload of the circulatory system & blood clots

(6) Metabolic shock.

[2] Artificial Oxygen Carriers and Plasma Expanders

(1) Vary significantly and can be extreamly serious, as it is difficult

to measure correct doses.

(2) These include fever, reduced platelet count, hypertension,

Vasoconstriction, kidney damage and iron overload.

[3] Gene Doping

(1) Gene therapy can be used theoretically to build muscle, to alter and

adjust muscle composition.

(2) SIDE REACTION:

* Gene therapy is far from mastered, and the chance of success are

very low and the risks are still very high.

* Gene therapy can be quite dangerous.

(Prof. T. Friedmann, 2005. WADA, Play true. Gene Doping).

* Nevertheless, most experts predict that rogue labs will pop up

in the US, and elsewhere around the world, which willing to

make experimental gene doping, no matter how dangerous,

available to athletes for the right price.

⊙ Food (Nutritional) Supplements

* The field of nutritional supplementation for ergogenic benefit is complex,

constantly changing, and poorly studied. (Schwenk TL et al: 2002)

* A metaanalysis of supplement use, pooling 51 studies involving 10,274

athletes at all level and participating in 15 sports, showed an overall

prevalence of supplement use of 46%, with most studies showing a pre-

valence of greater than 50%, although larger studies found a prevalence

of less than 50%. (Sobal J et al, 1994)

* Very few studies have examined the benefits to performance of long-

term, nonanabolic supplement use.

[1] Copper

(1) Primary benefit is antioxidant protection.

(2) Excessive supplementation can cause gastrointestinal distress,

nausea, vomiting, diarrhea, intravascular hemolysis.

(Lukaski HC,1995)

[2] Zinc (also called “the well-being mineral”)

(1) Supplements of 25-50 mg/day may interfere with the absorption of

iron and copper. (Schwenk TL, 2002)

(2) Higher dose may cause nausea and vomiting.

[3] Magnesium

(1) Excessive intake led to gastrointestinal upset, nausea, vomiting and

diarrhea.

(2) Interference with the absorption of calcium.

[4] B-complex and Multivitamins

(1) Vitamin A, D, B3, and B6 can be toxic at excessive doses.

(2) McDonald R et al, 1988 / Bucci L, 1993)

[5] Vitamin C

(1) Primary adverse effect is its competition for copper bioavailability

(2) Risk of Renal calculi due to urine acidification.

[6] Calcium

(1) Calcium interferes with the absorption of Zinc and Iron.

(2) Can result in the development of renal calculi at high dose.

[7] Iron

(1) Excessive Iron intake may lead to hepatic damage and cirrhosis,

that could be harmful or fatal.

(2) Hemochromatosis (rarely)

(3) Gastrointestinal upset, constipation, black stools which may be

confused with gastrointestinal bleeding.

[8] Chromium

(1) Chromium interferes with iron metabolism and zinc absorption.

(2) Commercial preparations often contain ephedrine, sometimes in the

herbal form “ma huang”.

(3) The concomitant addition of ephedrine to chromium preparations

has been restricted because of significant complications, including

hypertension, stroke, and death, even at lower doses.

[9] Selenium

(1) Supplementation greater than 100 ug/day can cause nausea and

vomiting, abdominal pain, and fatigue.

(2) Williams MH, 1998.

[10] Caffein

(1) There is a wide range of caffeine concentrations in food products,

including 40 to 110 mg in a cup of instant coffee, 60 to 150 mg in

brewed coffee, and 40 to 50 mg in a 12-ownce cola beverage.

(2) The indications for the use of caffeine are still controversial,

despite over 100 years of study.

(* Caffein is almost certainly ergogenic for certain aerobic activities

at dose below the IOC threshold. (Schwenk TL, 2002)

(3) There are several adverse effects of Caffeine, including flushing,

Tachycardia, anxiety, and trembling.

(4) Its known diuretic effect could cause problems in many athletic

events.

[11] Ginseng

(1) Overuse of ginseng leads to hypertension, insomnia, diarrhea and

irritability.

(2) But, some of these effects may be due to coexistent ephedrine or

ma huhung.

[12] Creatine

(1) Increased body weight due to water retention from the intracellular

osmotic effects of creatine supplementation.

(One week of supplementation→ 2-4 pounds of increased body weight)

(2) Intracellular osmotic load can lead to increased muscle cramping,

muscle (such as hamstring) tears, electrolyte dilution due to intra-

muscular water retention, gastrointestinal upset, and dehydration.

[13] Dehydroepiandrosterone (DHEA)

(1) Potential adverse effects such as liver toxicity and prostate cancer

have not been sell characterized to making any formal recommend.

(2) It can cause increased facial hair

(3) Decreased high-density lipoprotein cholesterol in women, further

making recommendation for its use difficult.

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