Toxicology Letters 158 (2005) 167175

Mini Review

Adverse effects of anabolic steroids in athletesreat

C. Maravelias, A. Dona, M. Stefanidou , C. SpiliopoulouDepartment of Forensic Medicine and Toxicology, University of Athens, Medical School,

75 Mikras Asias Street, Goudi, Athens 115 27, Greece

Received 7 April 2005; received in revised form 8 June 2005; accepted 8 June 2005Available online 6 July 2005

Abstract

Anabolic-augmentinggenerally dodamage. Ammasculinizahepatic neopthe reproducpsychologicemphasizing 2005 Else

Keywords: A

Contents

1. Introdu2. Mecha3. Advers

3.1.3.2.3.3.3.4.

CorresponE-mail ad

0378-4274/$doi:10.1016/jandrogenic steroids (AAS) are used as ergogenic aids by athletes and non-athletes to enhance performance bymuscular development and strength. AAS administration is often associated with various adverse effects that arese related. High and multi-doses of AAS used for athletic enhancement can lead to serious and irreversible organong the most common adverse effects of AAS are some degree of reduced fertility and gynecomastia in males and

tion in women and children. Other adverse effects include hypertension and atherosclerosis, blood clotting, jaundice,lasms and carcinoma, tendon damage, psychiatric and behavioral disorders. More specifically, this article reviewstive, hepatic, cardiovascular, hematological, cerebrovascular, musculoskeletal, endocrine, renal, immunologic andeffects. Drug-prevention counseling to athletes is highlighted and the use of anabolic steroids is must be avoided,that sports goals may be met within the framework of honest competition, free of doping substances.

vier Ireland Ltd. All rights reserved.

nabolic-androgenic steroids (AAS); Testosterone; Adverse effects; Athletes; Doping

ction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168nism of action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169e effects of AAS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169Reproductive effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170Hepatic effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170Cardiovascular, cerebrovascular and hematological effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171Musculoskeletal effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171

ding author. Tel.: +30 210 7716098; fax: +30 210 7716098.dress: mstefan@med.uoa.gr (M. Stefanidou).

see front matter 2005 Elsevier Ireland Ltd. All rights reserved..toxlet.2005.06.005A constant th

168 C. Maravelias et al. / Toxicology Letters 158 (2005) 167175

3.5. Endocrine effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1713.6. Renal effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1723.7. Immunologic and infectious effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1723.8. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172

4. Conclu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172Refere . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173

1. Introdu

Since thous derivatand studielife of theterone hasas androgenon-reprodresponsibleand develowhereas anand increas

The potanabolic aled to syntately calledthe goals oparent molegens, and dand moreof testosternot been aanabolic acity (Shahid

The anatives is primwhich resuin conjuncton the braeuphoria anwidespreadwell as bylimited to pfocusing onand significletes and nand Dumitrate of useical risks,

medical and athletic organizations as well as byidual scientists (American Academy of Pediatrics,). These statements condemn the use of anabolicids but confirm that they enhance strength veryitively (Bhasin et al., 1996a,b). It has become evi-that prohibitions against anabolic steroid use ands that steroids lack efficacy or produce harm haveinsufficient to curtail their use (Marshall, 1988;berg et al., 1990). In addition, anabolic steroidslong ago been available on the black market andare easy to obtain in many gyms or health clubshaine, 1989).is an uone stred to

inclut. Theased g

on or

etholzolol.rolone

1lic ster

nabolicic nameetholonroloneandrostestrenololola

ymesterandrolnolonePsychologic effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .sions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .nces . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

ction

e discovery of testosterone in 1935, numer-ives of testosterone have been synthesizedd in order to prolong the metabolic half-parent molecule and its efficacy. Testos-been found to exert its effects; designatednic and anabolic, on both reproductive anductive target tissues. Androgenic effects arefor growth of the male reproductive system

pment of secondary sexual characteristics,abolic effects stimulate nitrogen fixationed protein synthesis (Kuhn, 2002).ential therapeutic value of testosteronesctivity in various catabolic situations hashesis of many derivatives, more appropri-, anabolic-androgenic steroids (AAS) withf prolonging the biological activity of thecule in vivo, producing orally active andro-eveloping products that are less androgenicanabolic. Although complete dissociationones androgenic and anabolic effects havechieved, the AAS have shown significanttivity with somewhat reduced androgenic-i, 2001).bolic activity of testosterone and its deriva-

arily manifested in its myotrophic action,lts in greater muscle mass and strength. This,ion to the stimulatory effects of androgensin, which frequently result in a feeling ofd increased aggressiveness, has led to theuse of AAS by athletes at all levels, as

recreational drug users. Such use is notrofessional and Olympic athletes. Studies

manyindiv1997sterodefindentclaimbeenGoldhavethey(Duc

Itthanreferoftenagenincrecomm

oxymstanonand

TableAnabo

Oral a(generOxymOxandMethaEthyleStanozFluoxNorethMetheanabolic steroids have shown a continuingant increase of use among adolescent ath-on-athletes alike (Wagner, 1989; Windsorru, 1989). In response to the alarming highof anabolic steroids and the attendant med-policy statements have been published by

MesteroloneTestosterone u

a 17-Alphab 19-Nortesc Testosterod Veterinarynfortunate fact that most athletes use moreeroid at one single time. This state is oftenas stacking. The stack or array of drugsdes at least one oral and one injectabledrugs may be taken at low doses initially,radually, and then tapered. Some of theally administered anabolic steroids include

one, oxandrolone, methandrostenolone andSome of the injectable steroids includedecanoate, nandrolone phenpropionate,

oids generally used by athletes

steroids)

Injectable anabolic steroids(generic name)

ea Nandrolone decanoatebNandrolone phenpropionateb

nolonea Testosterone cypionateca Testosterone enanthatec

Testosterone propionateconea Methenolone enanthateone Boldenone undecyclenateacetate Trenbolone acetated

dTrenbolonendecanoate Stanozolol

alkylated steroids.tosterone esters.ne esters.steroids.

C. Maravelias et al. / Toxicology Letters 158 (2005) 167175 169

testosterone cypionate, and boldenone undecylenate(Table 1).

The fact remains that the abuse of androgenicanabolic sproblem inThe goal ovant issuesmechanismThis informpharmacistteenagers,from any d

2. Mechan

Studiesanabolic stecontroversian increaseno increasetocols, as wdrugs takencould explaRovere, 19be effective

1. They coitive onand incthe abilmuscle ctheir effcellularchromaing proding protThe vartype andenzymeorgan. Tto be idand Gri

2. Steroidscausingcocorticthesis d1984).

Table 2Desired effects of anabolic steroids as perceived by sportscompetitorsa

Increased mused streased recsed aggte heal

ain saming a w

apted f

thletescreasetigue80). T

om wod inte

overe,sted (summ

ids in

dvers

is a wof th

ree ofand t

s of litis andeffect). In adcteriae reactlthougts of alinican on adverse reactions is anecdotal, or is assumedknown problems associated with therapeutic usese agents (Lamb, 1984; Yesalis and Bahrke, 1995;

son et al., 1989; Sullivan et al., 1999; Mottrameorge, 2000; Kuhn, 2002; Kutscher et al., 2002;

inen and Seppala, 2002; Juhn, 2003; Bahrke andlis, 2004). Nevertheless, one has to pay attentionconfound these health consequences of AAS withprovoked by other performance enhancing andteroids (AAS) is a remarkably prevalentcompetitive and non-competitive athletes.f this is to summarize the clinically rele-regarding AAS abuse, including prevalence,

of action, efficacy and adverse effects.ation will therefore enable physicians and

s to adequately educate and guide athletes,parents, teachers and coaches to stay awayoping process.

ism of action

performed to determine the effects ofroids on muscle strength and size have beenal, with approximately half of them findingwith steroid use and the other half finding(Johnson, 1990). Differences in study pro-ell as uncontrolled dosages and number ofby athletes, who participate in the studies,in discrepancies in the results (Haupt and

84). Nevertheless, anabolic steroids seem toin three ways:

nvert a negative nitrogen balance to a pos-e by improving the use of ingested proteinreasing nitrogen retention. They also haveity to induce protein synthesis in skeletalells). Anabolic steroids are believed to exert

ects by binding to androgen receptors at thelevel, which translocate to binding sites on

tin, promoting gene transcription, stimulat-uction of mRNA, and ultimately increas-ein synthesis (Bahrke and Yesalis, 2004).ious clinical effects are determined by the

concentrations of androgen receptors ands controlling steroid metabolism in a givenhe structure of androgen receptors appears

entical in muscle and other organs (Wilsonffin, 1980; Snyder, 2001).compete for glucocorticosteroid receptors,

an anti-catabolic effect by blocking the glu-osteroid effects of depressed protein syn-uring stressful training (Haupt and Rovere,

IncreaDecreIncreaPromoMaintObtain

a Ad

3. Ainfa19fran

Rge

Astero

3. A

Ittrialsnot fdose-levelhepathese1990to batissu

Aeffecthat cmatiofromof theHickand GParssYesanot tothosescle massngthovery timeressioning of injuriese advantage as ones opponentinning edge

rom Hough (1990).

often experience a state of euphoria,d aggressive behavior, and diminishedduring steroid use (Wilson and Griffin,hey report that they recover more rapidlyrkouts and they can train more frequentlynsively while using the drugs (Haupt and1984). A placebo effect has also been sug-Ariel and Saville, 1972).

ary of the desired effects of anabolicsports competitors appears in Table 2.

e effects of AAS

ell known fact that the clinical-therapeutice main AAS often used by physicians areadverse effects. These adverse effects areype of steroid-related and include elevatedver enzymes, cholestatic jaundice, peliosisvarious neoplastic lesions. An overview ofs is outlined in Table 3 (Landry and Primos,dition, deep IM injections of AAS may lead

l and fungal abscesses and exuberant localions (Shahidi, 2001).h many excellent reviews on the adversenabolic steroids are available, due to the factl trials are not feasible, much of the infor-

170 C. Maravelias et al. / Toxicology Letters 158 (2005) 167175

Table 3Possible adverse effects of anabolic steroidsa

ReproductiveMale

Decreased reproductive hormonesTesticular atrophyOligospermia/azoospermiaImpotenceProstatic hypertrophyProstatic carcinomaGynecomastiaPriapism

FemaleMenstrual irregularitiesClitoral hypertrophyUterine atrophyBreast atrophyTeratogenicity

LiverHepatocellular damageCholestasisPeliosis hepatisHepatoadenomaHepatocarcinoma

Cardiovascular and hematologic effectsIncreased cholesterolDecreased HDL cholesterolHypertensionThrombosis

MusculoskeletalEarly epiphyseal closure in childrenIncreased rate of muscle strains/rupturesIncreased risk of musckulotendinous

Endocrine (other than reproductive)Decreased glucose tolerance

LarynxDeepening of the voice

IntegumentAcneAlopeciaHirsutismMale pattern baldnessEdema

UrinaryElevated BUN, creatinineWilms tumor

Immunologic and Infectious effectsDecreased IgA levelsHepatitis B or C; HIV infection

PsychologicMood swingsAggressive behaviorDepressionPsychosisAddictionWithdrawal and Dependency Disorders

a Adapted from Landry and Primos (1990).

illicit drugs co-administered with AAS (Bahrke andYesalis, 2004).

3.1. Repro

Use of sing hormonleads to detion, decrephy. The tazoospermthe drugs, bmay be abn2000; Dohhypertrophprostate caHolden etthe peripheestrone. Thsons with lhepatic clemetabolitesprominentsteroids instrual abnowell. Thessutism, acnphy, and mgenic effecof Pediatric

3.2. Hepat

Elevatioaminotranstate dehydruse steroidbe elevated(Hough, 19associated2000; Snydsionally wi3 monthsboth benigadministrat1993; SoeAlter, 2004steroid useductive effects

teroids in men decreases levels of luteiniz-e and follicle-stimulating hormones, whichcreased endogenous testosterone produc-

ased spermatogenesis, and testicular atro-esticular atrophy and the oligospermia oria usually resolve after discontinuation ofut the count and morphology of the spermormal for up to 6 months (Boyadjiev et al.,

le et al., 2003; Eklof et al., 2003). Prostaticy, priapism, and, rarely, carcinoma of then be associated with steroid use (Wemyss-al., 1994). Gynecomastia may result fromral conversion of androgens to estradiol andis side effect can be pronounced in per-

iver disease, probably because of decreasedarance of the parent steroid or estrogenic. The breast tissue becomes softer and lessafter steroid use stops. Use of anabolicwomen, is not only associated with men-rmalities but with masculinizing effects ase effects of AAS in women include hir-e, deepening of the voice, clitoral hypertro-ale-pattern baldness. Some of these andro-ts may be irreversible (American Academys, 1997; Elliot and Goldberg, 2000).

ic effects

ns in levels of liver enzymes (aspartateferase, alanine aminotransferase, and lac-ogenase) are also common in athletes whos. Nevertheless, these enzymes can oftenin weightlifters who are not using steroids

90). Hepatic dysfunction is most commonlywith the 17-alpha alkylated steroids (Friedl,er, 2001). Cholestatic jaundice occurs occa-th steroid use and typically resolves withinof discontinuing the drugs. Liver tumors,n and malignant, have been linked to theion of steroids (Watanabe and Kobayashi,et al., 1994; Friedl, 2000; Velazquez and). Several athletes with extensive histories ofhave died of hepatocellular carcinoma or of

C. Maravelias et al. / Toxicology Letters 158 (2005) 167175 171

hepatic tumor rupture. Hepatocellular carcinomas weremore often associated with oxymetholone and methyltestosterone (Velazquez and Alter, 2004). There is anincreased ris a rare foof multiplecan be fataPavlatos et

3.3. Cardihematologi

Anabolilipid profilopment ofdeterminedanabolic stetions and liAdelman, 1

A signitein (HDLlow-densitysteroid useatherosclerreturn or nuse and norabuse (CohHartgens e

Hyperteand myocaathletes whtime (Ferenthe actual fden death areported inrelationshipeffect is pRockhold,al., 2004).to irreversicentric left2004).

Anabolimass, hemIncreased fiting factorssteroids. Cein two ster

1988; Kledal et al., 2000; Shahidi, 2001). A case oflethal cerebral oedema has been associated with mas-sive abuse of AAS in a previously healthy 21-year-old

(Kled

Muscu

f partire inase ingens

ve thaous inase inased inr riskshed rugh ethat sndon,n collupture

Endoc

theid usequentdary

lteredance,also

ale poidi, 20cne isult of ts. Le, do nly et amporand whs of twom

d of titism, dies theversiesalisisk of peliosis hepatis with steroid use. Thisrm of hepatitis characterized by formationblood-filled cysts within the liver, which

l (Lamb, 1984; Dourakis and Tolis, 1998;al., 2001).

ovascular, cerebrovascular andcal effects

c steroids may adversely affect the serume, but their long-term effects on the devel-

coronary artery disease have not been. Thrombotic phenomena associated withroid use include strokes, myocardial infarc-

mb loss (Ferenchick, 1990; Ferenchick and992).ficant decrease in high-density lipopro-) cholesterol and, often, an increase in

lipoprotein (LDL) cholesterol occur with, placing the user at increased risk forotic heart disease. Cholesterol levels mayot to normal following cessation of steroidmalization depends on the duration of AASen et al., 1988; Glazer, 1991; Shahidi, 2001;t al., 2004).nsion is associated with anabolic steroid userdial infarction has been reported in severalo used steroids for a prolonged period ofchick, 1990). These case reports reveal thatrequency of myocardial infarction and sud-mong users of AAS is presumably under-medical literature and although a causalhas not yet been established, a pathogenic

lausible (Ferenchick and Adelman, 1992;1993; Ansell et al., 1993; Halvorsen etMoreover, anabolic use has been relatedble changes to myocardium, such as con-ventricular hypertrophy (Urhausen et al.,

c steroids increase red blood cell (RBC)atocrit and RBC count (Snyder, 2001).brinolytic activity and an increase in clot-have been associated with the use of specificrebrovascular accidents have been reported

oid-using athletes (Mochizuki and Richter,

man

3.4.

OclosudecreandrobelietendiincreincrehighepubliAlthogestof teshowdon r

3.5.

Insterosubsesecon

Aresisthavein mShah

Aa res

glandchest(Kira

Temen

lengtIn

periohirsuularitbe irrand Yal et al., 2000).

loskeletal effects

cular concern is the premature epiphysealany child/adolescent, which results in aadult height after prolonged exposure to

(Al-Ismail et al., 2002). Some scientistst there is an increased risk of musculo-juries with steroid use. Tendons may notstrength as muscles do and, when subject totensity and frequency of training, may be atfor rupture according to a small number ofeports (Shahidi, 2001; Battista et al., 2003).xperimental data from animal models sug-teroids alter the biomechanical propertiesultrastructural analysis of tendons has notagen changes that might predispose to ten-

in humans (Evans et al., 1998).

rine effects

prepubertal or pubertal male, prolongedwill result in accelerated maturation withchanges in physique and development of

sexual characteristics.glucose tolerance with increased insulinas well as, decreases of thyroid hormonesbeen reported with anabolic steroid usewer lifters (Cohen and Hickman, 1987;01; Snyder, 2001).a common side effect of steroid use and it ishe androgenic stimulation of the sebaceoussions, most often located on the back andot always respond to routine acne therapyl., 1987).

al hair recession and alopecia can be seen inomen using anabolic steroids for extendedime.en using anabolic steroids for a prolongedme, masculinization may be manifested aseepening of the voice, and menstrual irreg-

at are caused by steroid use, but which mayble once the drugs are discontinued (Bahrke, 2004).

172 C. Maravelias et al. / Toxicology Letters 158 (2005) 167175

3.6. Renal effects

Weightlifters not using anabolic steroids may expe-rience a risskeletal muelevation i(BUN), andmal once tRichter, 19

Acute reolysis in a(Hagelochcreatinineby body budiffuse membeen report

Wilmsreported in(Joyce, 19steroids aregrowth or pcarcinogen1993).

3.7. Immu

There hinfections rneedles forrisks of infand needlealso been reShahidi, 20

3.8. Psych

Some iand behavincluding irsion, mood(Kashkin adleman an2003).

A recen90% of useand violentby steroidsies do not

aggressive behavior (Bhasin et al., 1996a,b; Yates etal., 1999).

Anabolic steroid withdrawal and dependency dis-s havr, 199rawalergicnia,

nausea

rtensioalso osychoem ofve psyprior

eroidsing the dep

chanlant dkle e, similrred uids. Mren mal efferity toges. Inl skillangesly thaere h

onshipdal stemotionscentsere re

quenc2003)studi

olled)genic

onclu

tentianue toe in serum creatinine as a result of increasedscle mass. Steroid use may also cause an

n serum creatinine, blood urine nitrogenuric acid. These values often return to nor-

he drugs are discontinued (Mochizuki and88; Juhn, 2003).nal failure as a complication of rhabdomy-body builder using AAS has been reportedet al., 1988). The combination of AAS andsupplement that has been currently abusedilders may cause renal damage. A case ofbranoproliferative glomerulonephritis has

ed (Revai et al., 2003).tumor, uncommon in adults, has beenseveral athletes using anabolic steroids

91). There is evidence suggesting thatweak carcinogens that can initiate tumor

romote such growth in the presence of others (Lamb, 1984; Watanabe and Kobayashi,

nologic and infectious effects

ave been cases of hepatitis B or C and HIVeported in bodybuilders who were sharingsteroid injections in some cases. Increased

ections from improper handling of syringess and from use of impure substances haveported (Rogol and Yesalis, 1992; Wu, 1997;01).

ologic effects

ndividuals may experience mental statusioral changes with anabolic steroid use,ritability, aggressiveness, euphoria, depres-swings, altered libido, and even psychosis

nd Kleber, 1989; Bahrke et al., 1990; Mid-d DuRant, 1996; Clark and Henderson,

t study of health club athletes revealed thatrs reported episodes of over aggressivenessbehavior which were believed to be induced(Tamir et al., 2004), whereas other stud-

support any association between AAS and

orderlowewithdadreninsomgia,hypemayrisk pproblrelatiusers

Stmeetstancgramstimu(Frantomsoccu

sterochildlogicmatuchansociatal chrapid

Threlatigonathe eadoleels wconse

son,

dinalcontrandro

4. C

Pocontie also been reported (Foley and Schyd-3; Bahrke, 2000). Acute anabolic steroid

may produce symptoms of central non-hyperactivity including anxiety, irritability,hot flashes, sweats, chills, anorexia, myal-, vomiting, piloerection, tachycardia, andn. Depression and anabolic steroid cravingccur with withdrawal. Nevertheless, highlogical behaviors may also be the primarythose who take anabolic steroids althoughchiatric disorders may be observed on theseto use (Middleman and DuRant, 1996).may be psychologically addicting, even

e DSM-IV criteria for psychoactive sub-endence in some cases. Electroencephalo-ges similar to those seen with psycho-rugs have been reported with steroid uset al., 1988). Physical withdrawal symp-ar to those seen in opiate withdrawal, havepon cessation of extremely high doses oforeover, the developing nervous system ofay be especially vulnerable to the psycho-cts of steroids. Adolescents may lack the

cope with possible drug-induced moodaddition, the development of appropriate

s and controls necessary to deal with puber-may be made difficult if changes occur moren expected (Snyder, 2001).ave also been reports stating that there is a

between hormone levels (gonadotropins,roid hormones, and adrenal androgens) andal dispositions and aggressive behaviors of. The results indicate that high hormone lev-lated to potentially adverse psychologicales for boys and girls (Clark and Hender-

. Nevertheless, more sophisticated longitu-es (probably placebo and training regimenare required to dissect the role of anabolic-steroids in behavioral disturbances.

sions

l anabolic steroid users have been and willbe involved in sports where strength and

C. Maravelias et al. / Toxicology Letters 158 (2005) 167175 173

muscle mass are at a premium. Endurance athletes andnon-athletes at any age, seeking to add strength, bulk,muscle definition, or to improve their self-image mustalso be con

Anabolibe aware thsteroids msigns. Nevethe risks aning that thiscence aboucated approin internatiticipants, aeffects of astrength trameet theirYesalis, 19niques candrug use (G

Drug-prpreferablya healthy ala way to msteroids. Ahealth, fitntion can beenhancingthat steroidto point outsuccess did

With thand side epharmacistletes, teenaaway fromof the socfree athletiPhysiciansing controlhave alsoand treatinstances. Moanti-dopinga problemauthorities.must fighting the nee

or any other methods known in the long run of sportshistory.

rence

ail, K.uteal mcation ocan Aceroids:l, J., Tiasociated7371.G., Savects ofe, M.S.roids anarmacoe, M.S.one andabolicnetics,e, M.Sd behavabolic-aed. 10,ta, V., Chilles t

ed. 31,, S., Sillips, J96a. Thscle siz

7., S., Stillips, J96b. Thscle siz

7.jiev, N

I., 2000anabolity disor1274.A.S., Hponsesv. 27, 4, J.C., Hcose to

in. End, J.C.,olemiaroids. P, G.R.,ity. Worsidered to be at risk.c steroid users and potential users shouldat many of the adverse effects of anabolic

ight be present without obvious warningrtheless, one should present youth with bothd the benefits of anabolic steroids use, hop-will be more effective in convincing adoles-t steroids negative effects. A more sophisti-ach might be methods that have been used

onal programs, such as ATLAS, where par-part from being informed on the potentialnabolic steroids, they are also informed howining and proper nutrition can help them togoals (Landry and Prinos, 1990, Rogol and92). In addition, proper weightlifting tech-be offered by trainers as an alternative tooldberg et al., 1996, 2000).

evention counseling should be providedat early adolescence which hopefully lead toternative to drug use. Most athletes will findeet their sports goals without using anabolicthletes may need to be reminded that theess and social benefits of sports participa-

readily met without use of performance-substances. For the athlete who is convinceds are essential for success, it may be helpfulrole models in the sports community whosenot depend on the use of drugs.

e appropriate knowledge about the effectsffects of anabolic steroids, physicians ands can adequately educate and guide ath-gers, parents, teachers and coaches to staydoping and help towards the ultimate goal

iety to accomplish not only totally drug-c competitions, but also a drug-free youth.and pharmacists play a key role in dop-programs in a number of ways and they

the obligation when counseling, advisingg athletes to help them avoid banned sub-reover, the challenge of developing a globalprogram requires acceptance of doping as

by sport organizations, athletes and publicAll parties involved in this type of programs

for drug free sports, particularly emphasiz-d to keep away from any doping substance

Refe

Al-IsmGlpli

AmeriSt

Anselas

36Ariel,

effBahrk

stePh

BahrkterAnKi

Bahrkan

an

MBattis

AcM

BhasinPh19mu

1Bhasin

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gluCl

Cohenterste

Dohletils

, Torreggiani, W.C., Munk, P.L., Nicolaou, S., 2002.ass in a bodybuilder: radiological depiction of a com-f anabolic steroid use. Eur. Radiol. 12, 13661369.

ademy of Pediatrics, 1997. Adolescents and Anabolica subject Review. Pediatrics 99, 904908.rks, C., Fairchild, V., 1993. Coagulation abnormalitieswith the use of anabolic steroids. Am. Heart J. 125,

ille, W., 1972. Anabolic steroids: the physiologiacalplacebos. Med. Sci. Sports Excerc. 4, 124126., Yesalis, C.E., 2004. Abuse of anabolic-androgenicd related sub stances in sport and exercise. Curr. Opin.

l. 4, 614620., 2000. Psychological effects of endogenous testos-anabolic-androgenic steroids. In: Yesalis, C.E. (Ed.),

Steroids in Sport and Exercise, second ed. HumanChampaign, pp. 247278.., Yesalis, C.E., Wrigh, J.E., 1990. Psychologicalioral effects of endogenous testosterone levels andndrogenic steroids among males: a review. Sports

303337.ombs, J., Warne, W.J., 2003. Asynchronous bilateral

endon ruptures and androstenediol use. Am. J. Sports10071009.torer, T., Berman, N., Callegari, C., Clevenger, B.,., Bunnell, T.J., Tricker, R., Shirazi, A., Casaburi, R.,e effects of supraphysiologic doses of testosterone one and strength in normal men. N. Engl. J. Med. 335,

orer, T.W., Berman, N., Callegari, C., Clevenger, B.,., Bunnell, T.J., Tricker, R., Shirazi, A., Casaburi, R.,e effects of supraphysiologic doses of testosterone one and strength in normal men. N. Engl. J. Med. 335,

.P., Georgieva, K.N., Massaldjieva, R.I., Gueorguiev,

. Reversible hypogonadism and azoospermia as a resultc-androgenic steroid use in a bodybuilder with person-der A case report. J. Sports Med. Phys. Fitness. 40,

enderson, L.P., 2003. Behavioral and physiologicalto anabolic-androgenic steroids. Neurosci. Biobehav.13436.ickman, R., 1987. Insulin resistance and diminished

lerance in powerlifters ingesting anabolic steroids. J.ocrinol. Metab. 64, 960963.

Noakes, T.D., Benade, A.J., 1988. Hypercholes-in male power lifters using anabolic-androgenic

hys. Sportsmed. 16, 4956.Smit, M., Weber, R.F., 2003. Androgens and male fer-ld J. Urol. 21, 341345.

174 C. Maravelias et al. / Toxicology Letters 158 (2005) 167175

Dourakis, S.P., Tolis, G., 1998. Sex hormonal preparations and theliver. Eur. J. Contracept Reprod. Health Care 3, 716.

Duchaine, D., 1989. Underground Steroid Handbook II. HLR Tech-nical Boo

Eklof, A.C., TThe anti-ding agentsclinical ph

Elliot, D.L., GYesalis, Cond ed. H

Evans, N.A.,analysis o29, 7697

Ferenchick, Gated with aweight lif

Ferenchick, GEngl. J. M

Foley, J.D., Sdrug use b

Frankle, M.AandrogeniPhys. Med

Friedl, K.E.,In: Yesalissecond. H

Glazer, G., 19lipid level

Goldberg, L.,of anaboltudes of h11, 2102

Goldberg, L.,Zoref, L.,A., 1996.vention inAvoid Ste

Goldberg, L.,Cheong, Jsteroids pbehaviors

Hageloch, W.bodybuild2, 12212

Halvorsen, S.infarctionanabolic s

Hartgens, F.,buttel, B.Hapolipopr253259.

Haupt, H.A.,literature.

Hickson, R.Canabolic s271.

Hough, D.O., 1990. Anabolic steroids and ergogenic aids. Am. Fam.Phys. 41, 11571164.

Johnson, D.J., 1990. Anabolic steroid use in adolescent athletes.diatr. C

J.A.,hancingM., 20orts Mein, K.Babolic s, C.L., Aandrogwer athl, S., Clrebral eeger. 16C.M., 21434.her, E.Ciew for

, D.R., 1rk and

y, G.L.,d. 37, 1all, E.,4.eman,d assoc5.izuki, Rovascule. Phys.m, D.R

act. Resnen, M.ks in foos, A.Moxymein. TherT., Sap

inkler, Ging ana25242old, R.nu. Rev

, A.D.,adolesi, N.T.

d clinicer. 23,r, P.J.,odmanerapeut48..L., S

ted wit85258ks, Venice CA.hurelius, A.M., Garle, M., Rane, A., Sjoqvist, F., 2003.oping hot-line, a means to capture the abuse of dop-in the Swedish society and a new service function inarmacology. Eur. J. Clin. Pharmacol. 59, 571577.oldberg, L., 2000. Women and anabolic steroids. In:

.E. (Ed.), Anabolic Steroids in Sport and Exercise, sec-uman Kinetics, Champaign, pp. 225246.Bowrey, D.J., Newman, G.R., 1998. Ultrastructuralf ruptured tendon from anabolic steroid users. Injury73..S., Adelman, S., 1992. Myocardial infarction associ-nabolic steroid use in a previously healthy 37-year-old

ter. Am. Heart J. 124, 507508..S., 1990. Are androgenic steroids thrombogenic? N.ed. 322, 476.chydlower, M., 1993. Anabolic steroid and ergogenicy adolescents. Adolesc. Med. 4, 341352.., Eichberg, R., Zachariah, S.B., 1988. Anabolic-c steroids and a stroke in an athlete: case report. Arch.. Rehabil. 69, 632633.

2000. Effect of anabolic steroids on physical health., C.E. (Ed.), Anabolic Steroids in Sport and Exercise,uman Kinetics, Champaign, pp. 175225.91. Atherogenic effects of anabolic steroids on serums. Arch. Intern. Med. 151, 19251933.Bosworth, E.E., Bents, R.T., Trevisan, L., 1990. Effectic steroid education program on knowledge and atti-igh school football players. J. Adolesc. Health Care14.Elliot, D., Clarke, G.N., MacKinnon, D.P., Moe, E.,

Green, C., Wolf, S.L., Greffrath, E., Miller, D.J., Lapin,Effects of a multidimensional anabolic steroid pre-tervention The Adolescents Training and Learning toroids (ATLAS) Program. JAMA 276, 15551562.MacKinnon, D.P., Elliot, D.L., Moe, E.L., Clarke, G.,., 2000. The adolescents training and learning to avoidrogram: preventing drug use and promoting health. Arch. Ped. Adolesc. Med. 154, 328332., Appell, H.J., Weicker, H., 1988. Rhabdomyolysis in aer using anabolic steroids. Sportverletz Sportschaden.5., Thorsby, P.M., Haug, E., 2004. Acute myocardialin a young man who had been using androgenic

teroids. Tidsskr. Nor. Laegeforen. 124, 170172.Rietjens, G., Keizer, H.A., Kuipers, H., Wolffen-., 2004. Effects of androgenic-anabolic steroids on

oteins and lipoprotein (a). Br. J. Sports Med. 38,

Rovere, G.D., 1984. Anabolic steroids: a review of theAm. J. Sports Med. 12, 469484.., Ball, K.L., Falduro, M.T., 1989. Adverse effects ofteroids. Med. Toxicol. Adverse Drug Exp. 4, 254

PeJoyce,

en

Juhn,Sp

Kashkan

Kiralyofpo

Kledace

LaKuhn,

41Kutsc

rev

Lambwo

LandrPe

Marsh18

Middlan

25Moch

brus

MottraPr

Parssiris

PavlatofCl

Revai,Wtak24

RockhAn

Rogolthe

Shahidan

ThSnyde

GoTh16

Soe, Kcia25lin. North Am. 37, 11111123.1991. Anesthesia for athletes using performance-drugs. AANA J. 59, 139144.

03. Popular sports supplements and ergogenic aids.d 33, 921939.., Kleber, H.D., 1989. Hooked or hormones? Anteroid addiction hypothesis. JAMA 262, 31663170.len, M., Rahkila, P., Horsmanheimo, M., 1987. Effect

enic and anabolic steroids on the sebaceous gland inletes. Acta Derm. Venereol (Stockh) 67, 3640.ausen, A.G., Guldager, H., 2000. Fatal outcome withdema following abuse of anabolic steroids. Ugeskr2, 22032204.002. Anabolic steroids. Recent Prog. Horm. Res. 57,

., Lund, B.C., Perry, P.J., 2002. Anabolic steroids: athe clinician. Sports Med. 32, 285296.984. Anabolic steroids in athletics: How well do they

how dangerous are they? Am. J. Sports Med. 12, 3138.Primos Jr., W.A., 1990. Anabolic steroid abuse. Adv.85205.1988. The drug of champions. Science 242, 183

A.B., DuRant, R.H., 1996. Anabolic steroid useiated health risk behaviours. Sports Med. 21, 251

.M., Richter, K.J., 1988. Cardiomyopathy and cere-ar accident associated with anabolic-androgenic steroidSportsmed. 16, 109114.., George, A.J., 2000. Anabolic steroids. Baillieres Best. Clin. Endocrinol. Metab. 14, 5569., Seppala, T., 2002. Steroid use and long-term healthrmer athletes. Sports Med 32, 8394.., Fultz, O., Monberg, M.J., Vootkur, A., 2001. Review

tholone A 17a-alkylated anabolic-androgenic steroid.ap. 23, 789801.i, Z., Benedek, S., Kovacs, A., Kaszas, I., Viranyi, M.,., 2003. Severe nephrotic syndrome in a young man

bolic steroid and creatine long term. Orv. Hetil. 144,7., 1993. Cardiovascular toxicity of anabolic steroids.. Pharmacol. Toxicol. 33, 497520.

Yesalis, C.E., 1992. Anabolic-androgenic steroids andcent. Pediatr. Ann. 21, 175188., 2001. A review of the chemistry, biological action,al applications of anabolic-androgenic steroids. Clin.13551390.2001. Androgens. In: Hardman Limbird, J.G.L.E.,Gilman, A. (Eds.), The pharmacological Basis of

ics, tenth ed. McGraw Hill, New York, pp. 1635

oe, M., Gluud, C.N., 1994. Liver pathology asso-h anabolic-androgenic steroids. Ugeskr Laeger 156,8.

C. Maravelias et al. / Toxicology Letters 158 (2005) 167175 175

Sullivan, M.L., Martinez, C.M., Gallagher, J., 1999. Atrial fibrillationand anabolic steroids. J. Emerg. Med. 17, 851857.

Tamir, E., Ner, Y.Z., Dayan, Y., Tamir, D., 2004. Knowledge and atti-tude regarding use of anabolic steroids among youth exercisingin fitness centers. Harefuah 143, 348352.

Urhausen, A., Albers, T., Kindermann, W., 2004. Are the cardiaceffects of anabolic steroid abuse in strength athletes reversible?Heart 90, 496501.

Velazquez, I., Alter, B.P., 2004. Androgens and liver tumors: Fan-conis anemia and non-Fanconis conditions. Am. J. Hematol.77, 257267.

Wagner, J.C., 1989. Abuse of drugs used to enhance athletic perfor-mance. Am. J. Hosp. Pharm. 46, 20592067.

Watanabe, S., Kobayashi, Y., 1993. Exogenous hormones and humancancer. Jpn. J. Clin. Oncol. 23, 113.

Wemyss-Holden, S.A., Hamdy, F.C., Hastie, K.J., 1994. Steroidabuse in athletes, prostatic enlargement and bladder outflowobstruction: is there a relationship? Br. J. Urol. 74, 476478.

Wilson, J.D., Griffin, J.E., 1980. The use and misuse of androgens.Metabolism 29, 12781295.

Windsor, R., Dumitru, D., 1989. Prevalence of anabolic steroid useby male and female adolescents. Med. Sci. Sports Exerc. 21,494497.

Wu, F.C., 1997. Endocrine aspects of anabolic steroids. Clin. Chem.43, 12891292.

Yates, W.R., Perry, P.J., MacIndoe, J., Holman, T., Ellingrod, V.L.,1999. Psychosexual effects of three doses of testosterone cyclingin normal men. Biol. Psychiatr. 45, 254260.

Yesalis, C.E., Bahrke, M.S., 1995. Anabolic-androgenic steroids.Curr. Iss. Sports Med. 19, 326340.

Adverse effects of anabolic steroids in athletesIntroductionMechanism of actionAdverse effects of AASReproductive effectsHepatic effectsCardiovascular, cerebrovascular and hematological effectsMusculoskeletal effectsEndocrine effectsRenal effectsImmunologic and infectious effectsPsychologic effects

ConclusionsReferences