National Institute on Drug Abuse (NIDA) Steroids and Other ... · approved for these purposes. ... Ephedrine/ephedra used to be included in dietary supplements that ... bodybuilding

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NationalInstituteonDrugAbuse(NIDA)

SteroidsandOtherAppearanceandPerformanceEnhancingDrugs(APEDs)

LastUpdatedFebruary2018

https://www.drugabuse.gov

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TableofContents

SteroidsandOtherAppearanceandPerformanceEnhancingDrugs(APEDs)

Introduction

WhatarethedifferenttypesofAPEDs?

Whatisthehistoryofanabolicsteroiduse?

Whousesanabolicsteroids?

Whyareanabolicsteroidsmisused?

Howareanabolicsteroidsused?

Whatarethesideeffectsofanabolicsteroidmisuse?

Howdoesanabolicsteroidmisuseaffectbehavior?

Whataretherisksofanabolicsteroiduseinteens?

Howdoanabolicsteroidsworkinthebrain?

Areanabolicsteroidsaddictive?

Howareanabolicsteroidstestedinathletes?

Whatcanbedonetopreventsteroidmisuse?

Whattreatmentsareeffectiveforanabolicsteroidmisuse?

WherecanIgetfurtherinformationaboutsteroids?

References

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Introduction

Appearanceandperformanceenhancingdrugs(APEDs)aremostoftenusedbymalestoimproveappearancebybuildingmusclemassortoenhanceathleticperformance.Althoughtheymaydirectlyandindirectlyhaveeffectsonauser’smood,theydonotproduceaeuphorichigh,whichmakesAPEDsdistinctfromotherdrugssuchascocaine,heroin,andmarijuana.However,usersmaydevelopasubstanceusedisorder,definedascontinuedusedespiteadverseconsequences.

Anabolic-androgenicsteroids,thebest-studiedclassofAPEDs(andthemainsubjectofthisreport)canboostauser’sconfidenceandstrength,leadinguserstooverlookthesevere,long-lasting,andinsomecases,irreversibledamagetheycancause.Theycanleadtoearlyheartattacks,strokes,livertumors,kidneyfailure,andpsychiatricproblems.Inaddition,stoppingusecancausedepression,oftenleadingtoresumptionofuse.

Becausesteroidsareofteninjected,userswhoshareneedlesorusenonsterileinjectingtechniquesarealsoatriskforcontractingdangerousinfectionssuchasviralhepatitisandHIV.

Steroidsarepopularlyassociatedwithdopingbyeliteathletes,butsincethe1980s,theirusebymalenon-athleteweightliftershasexceededtheirusebycompetitiveathletes. Theiruseiscloselyassociatedwithdisorderedmalebodyimage—mostspecifically,muscledysmorphia.

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WhatarethedifferenttypesofAPEDs?

Anabolic-androgenicsteroids,oftenshortenedto"anabolicsteroids,""steroids,"or"androgens," arethemostwidelymisusedAPED.Thesearesyntheticsubstancessimilartothemalesexhormonetestosterone.Theypromotethegrowthofskeletalmuscle(anaboliceffects)andthedevelopmentofmalesexualcharacteristics(androgeniceffects)inbothmalesandfemales.

Thesecompoundsaresometimesusedmedicallytotreatdelayedpubertyandmusclelossduetodisease andtotreatlowlevelsoftestosteroneinmenwithanassociatedmedicalcondition. Anabolicandrogenicsteroidscanalsoimprovefeelingsofwell-beingandincreasebonestrength,butarenotapprovedforthesepurposes.However,testosterone-supplementationtherapyisanincreasinglycommontreatmentformoodandsexualperformanceproblemsassociatedwithmaleaging,anditiscontroversiallybeingprescribedevenforyoungermen.

Notethatinthecontextofthisreport,anabolicsteroidsreferonlytothenon-prescribeduse(misuse)oftestosteroneandtestosterone-likesubstancesbyathletesandnon-athletebodybuilders.Thisresearchreportwillnotcoverimageenhancers,suchasdermalfillers,Botox,ortheskintanner,melanotan.

Non-steroidalanabolics,includeinsulin,insulin-likegrowthhormone(IGF),andhumangrowthhormone(HGH)—substancesthatareproducedbythehumanbodyandareprescribedforlegitimatemedicalusesbutalsosometimesmisusedforperformanceenhancement.

Ergo/thermogenicsarecompoundsusedtodecreasebodyfatortopromoteleannessversusmusclemassinenduranceathletes. Thethreemaincategoriesofergo/thermogenicsare:

Xanthines:compoundsthatincreaseattentionandwakefulnessand

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suppressappetite.Examplesarecaffeine,theasthmadrugtheophylline,andtheobromine—asubstancefoundinchocolate,coffee,andtea.

Sympathomimetics:drugsthataresimilarinstructureandactiontoepinephrineandnorepinephrine—naturalchemicalsinthebodythatincreaseheartrate,constrictbloodvessels,andraisebloodpressure.Anexampleisephedrine,whichisderivedfromtheephedraplant.Ephedrine/ephedrausedtobeincludedindietarysupplementsthatpromotedweightloss,increasedenergy,andenhancedathleticperformance. In2004,theFDAbannedtheU.S.saleofdietarysupplementscontainingephedrine/ephedraduetovariouspossiblehealthrisksincludingcardiovascularandnervoussystemeffects.

Thyroidhormones:substancesthatregulatemetabolismbyalteringthefunctionofthethyroid. Cytomelisanexample.

Nutritional/dietarysupplementsaresubstancespurchasedlegallyfromnutritionalstoresorviatheinternetthatareoftentakenincombinationwithotherAPEDS.Creatine,whichboostsexercisecapacity,isonecommonexample.

IntheUnitedStates,dietarysupplementscontainingsteroidprecursorssuchastetrahydrogestrinone(THG)andandrostenedione(streetname"Andro")previouslycouldbepurchasedlegallywithoutaprescription.Athletestooksteroidprecursorsinanefforttoboosttestosteronelevels.Lessisknownaboutthesideeffectsofsteroidprecursors,butiflargequantitiesofthesecompoundssubstantiallyincreasetestosteronelevelsinthebody,thentheyalsoarelikelytoproducethesamesideeffectsasanabolicsteroidsthemselves. Thepurchaseofthesesupplements,withthenotableexceptionofdehydroepiandrosterone(DHEA),becameillegalafterthepassageoftheAnabolicSteroidControlActof2004,whichamendedtheControlledSubstancesAct.

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Whatisthehistoryofanabolicsteroiduse?

TestosteronewasfirstsynthesizedinGermanyin1935 andwasusedmedicallytotreatdepression. Professionalathletesbeganmisusinganabolicsteroidsduringthe1954Olympics,whenRussianweightliftersweregiventestosterone. Inthe1980s,anabolicsteroidusebegantoextendintothegeneralpopulation,andyoungmenbeganusingthesesubstances,sometimestoenhanceathleticperformancebutinmostcasestoimprovepersonalappearance.

Mostanabolicsteroidusersaremalenon-athletesaimingtoimprovetheirappearancebybuildingmuscle,anduseofsteroidsisstronglytiedtoamalebodyimagedisordercalledmuscledysmorphia(see“Whousesanabolicsteroids?"). Justasfemalebodyimagedisordershavebeenlinkedtounrealisticportrayalsofthefemaleforminfashionmagazinesandpopularculture,muscledysmorphiainmalesislinkedtoexaggeratedphysiquesinactionmoviesandothermediaoverthepastthreedecades.

CongresspassedtheAnabolicSteroidActof1990torespondtotheincreasinglevelsofillicittrafficinsteroids.ThisActidentifiedanabolicsteroidsasaseparatedrugclassandcategorizedovertwodozendrugsascontrolledsubstances.TheActalsogaveafour-partdefinitionofthisdrugclass,whichallowedforflexibilityincontrollingnewanabolicsteroidsastheyweresynthesized.In2004,CongressenactedtheAnabolicSteroidControlActof2004,whichbannedover-the-countersteroidprecursors;increasedpenaltiesformaking,selling,orpossessingillegalsteroidprecursors;andprovidedfundsforpreventativeeducationalefforts.

Othercountries,suchasMexicoandsomeEuropeannations,wheresteroidsareavailablewithoutprescription,arethemainsourcesofillegalsteroidssmuggledintotheUnitedStates.Lesscommonillicitsourcesincludediversionfromlegitimatesources(e.g.,theftsorinappropriateprescribing)orproductionwithinclandestinelaboratories.

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Ahistoricaltimelineofanabolicsteroids.Source:Pope,Wood,Rogol,Nyberg,Bowers,Bhasin.EndocrineReviews.2014.

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Whousesanabolicsteroids?

Thevastmajorityofpeoplewhomisusesteroidsaremalenon-athleteweightliftersintheir20sor30s. Contrarytopopularbelief,onlyabout22percentofanabolicsteroidusersstartedasteenagers. Anabolicsteroiduseislesscommonamongfemales,sincefewerwomendesireextrememuscularityandthemasculinizingeffectsofsteroids.

Maleswhoaremorelikelytousesteroidstendtohavepoorself-esteem,higherratesofdepression,moresuicideattempts,poorknowledgeandattitudesabouthealth,greaterparticipationinsportsemphasizingweightandshape,greaterparentalconcernaboutweight,andhigherratesofeatingdisordersandsubstanceuse. Steroidmisuseisassociatedwithmuscledysmorphia,abehavioraldisorderinwhichmenthinkthattheylooksmallandweak,eveniftheyarelargeandmuscular(see“Whyareanabolicsteroidsmisused?”).

Somepeoplewhomisusesteroidshaveexperiencedphysicalorsexualabuse.Inastudyof506maleusersand771malenonusersofanabolicsteroids,usersweresignificantlymorelikelythannonuserstoreportbeingsexuallyabusedinthepast. Similarly,femaleweightlifterswhohadbeenrapedwerefoundtobetwiceaslikelytoreportuseofanabolicsteroidsoranotherpurportedmuscle-buildingdrug,comparedwiththosewhohadnotbeenraped.Moreover,almostallfemaleswhohadbeenrapedreportedthattheymarkedlyincreasedtheirbodybuildingactivitiesaftertheattack.Theybelievedthatbeingbiggerandstrongerwoulddiscouragefurtherattacksbecausemenwouldfindthemeitherintimidatingorunattractive.

ItisdifficulttoestimatethetrueprevalenceofsteroidmisuseintheUnitedStatesbecausemanysurveysthataskaboutillicitdrugusedonotincludequestionsaboutsteroids.However,theannualMonitoringtheFuturestudy,aNIDA-fundedsurveyofdruguseandattitudesinmiddleandhighschoolstudentsacrosstheUnitedStates,showsthatpast-yearuseofsteroidshasgenerallydeclinedamong8thand10thgraders,afterpeakingin2000.Past-yearsteroiduseamong12thgradersincreasedfrom2011to2015,althoughusesignificantlydeclinedfrom2015to2016.The2017rateofuseamong12th

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gradersholdsrelativelysteady.

PastYearAnabolicSteroidUseAmongMiddleandHighSchoolStudents,2007-2017

Dataarefromthe2017MonitoringtheFuturesurvey,fundedbytheNationalInstituteonDrugAbuseandconductedannuallybytheUniversityofMichigan'sInstituteforSocialResearch.

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Whyareanabolicsteroidsmisused?

Anabolicsteroidsincreaseleanmusclemasswhenusedinconjunctionwithweighttraining.Theaim,fornon-athleteweightlifters,istypicallyimprovementofappearance.Asmentionedin“Whousesanabolicsteroids?”steroiduseisoftenassociatedwithaformofmalebodydysmorphicdisordercalledmuscledysmorphia,apreoccupationwiththeperceivedinadequatesizeoftheirmuscles.

Asaresult,someusersreporttakinganabolicsteroidstoincreaseconfidenceandbecausetheyfeelthattheyareatapointwheretheycannolongergetbiggerthroughweighttrainingalone.Mostusersreportthatanabolicsteroidshelpthemachievetheiridealbody.

Increasingmusclemassmayalsopromotestrength,whichcanimproveperformanceincertaintypesofsports.Morebenefitisseenforstrength-dependentsports(weightlifting,shot-putthrowing,football)thanforsportsthatrequirespeed,agility,flexibility,and/orendurance.

Anabolicsteroidusersalsoreportthattheirmusclesrecoverfasterfromintensestrainandmuscleinjury. Researchinanimalshasnotconclusivelysupportedthisbelief,withsomeshowingthatanabolicsteroidscanenhancerecoveryfromcertaintypesofmuscledamage, butothersfindingnobenefitintakinganabolicsteroidstoenhancemusclerecovery.

Anabolicsteroidusersreportusinganaverageofabout11APEDsperyear.Theyarealsomorelikelythannon-steroiduserstotakesupplementssuchasproteinpowdersandcreatine;estrogenblockers;ergo/thermogenics,suchascaffeineorephedrine;medicationsforerectiledysfunction;andotherhormonessuchasinsulin,thyroidhormones,andhumangrowthhormone.

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Howareanabolicsteroidsused?

Someanabolicsteroidsaretakenorally,othersareinjectedintramuscularly,andstillothersareprovidedingelsorcreamsthatareappliedtotheskin.Manyusersstartwiththeoralformandthenprogresstoinjectableforms,sincethelattercauseslessliverdamage.However,oralsteroidsclearmorerapidlyfromthebody,oftenmakingthisthepreferredrouteforusersconcernedwithdrugtesting. Dosestakenbypeoplemisusingthesesubstancescanbe10to100timeshigherthanthedosesusedtotreatmedicalconditions.

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CommonlyMisusedSteroids

OralSteroids

Anadrol(oxymetholone)

Anavar(oxandrolone)

Dianabol(methandienone)

Winstrol(stanozolol)

Restandol(testosteroneundecanoate)

InjectableSteroids

Deca-Durabolin(nandrolonedecanoate)

Durabolin(nandrolonephenpropionate)

Depo-Testosterone(testosteronecypionate)

Agovirin(testosteronepropionate)

Retandrol(testosteronephenylpropionate)

Equipoise(boldenoneundecylenate)

Cycling,stacking,pyramiding,andplateauing

Steroidsareoftenusedinpatternscalled"cycling."Thisinvolvestakingmultipledosesofsteroidsoveraspecificperiodoftime,stoppingforaperiod,andstartingagain.Peoplewhomisusesteroidsalsotypically"stack"thedrugs,meaningthattheytaketwoormoredifferentanabolicsteroids,mixoraland/orinjectabletypes,andsometimeseventakecompoundsthataredesignedforveterinaryuse. Thebeliefisthatdifferentsteroidsinteracttoproduceaneffectonmusclesizethatisgreaterthantheeffectsofeachdrugindividually,

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atheorythathasnotbeentestedscientifically.

Anothercommonmodeofsteroidmisuseisreferredtoas"pyramiding,"whichtypicallyinvolvestakingtheminacycleofsixto12weeks,taperinggraduallyratherthanstartingandfinishingacycleabruptly.Atthebeginningofacycle,thepersonstartswithlowdosesofthedrugsbeingstackedandthenslowlyincreasesthedoses.Inthesecondhalfofthecycle,thedosesareslowlydecreasedtozero.Thisissometimesfollowedbyasecondcycleinwhichthepersoncontinuestotrainbutwithoutdrugs.Steroidusersbelievethatpyramidingallowsthebodytimetoadjusttothehighdoses,andthedrug-freecycleallowsthebody'shormonalsystemtimetorecuperate.

Atechniquecalled"plateauing"mayalsobeused,wherebysteroidsarestaggered,overlapped,orsubstitutedwithanothertypeofsteroidtoavoiddevelopingtolerance. Aswithstacking,theeffectsofpyramiding,cycling,andplateauinghavenotbeensubstantiatedscientifically.

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Whatarethesideeffectsofanabolicsteroidmisuse?

Avarietyofsideeffectscanoccurwhenanabolicsteroidsaremisused,rangingfrommildeffectstoonesthatareharmfulorevenlife-threatening.Mostarereversibleiftheuserstopstakingthedrugs.However,othersmaybepermanentorsemi-permanent.

Mostdataonthelong-termeffectsofanabolicsteroidsinhumanscomefromcasereportsratherthanformalepidemiologicalstudies.Seriousandlife-threateningadverseeffectsmaybeunderreported,especiallysincetheymayoccurmanyyearslater.Onereviewfound19deathsinpublishedcasereportsrelatedtoanabolicsteroidusebetween1990and2012;however,manysteroidusersalsousedotherdrugs,makingitdifficulttoshowthattheanabolicsteroidusecausedthesedeaths. Oneanimalstudyfoundthatexposingmalemiceforonefifthoftheirlifespantosteroiddosescomparabletothosetakenbyhumanathletescausedahighfrequencyofearlydeaths.

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PossibleHealthConsequencesofAnabolicSteroidMisuse

Cardiovascularsystem

highbloodpressure

bloodclots

heartattacks

stroke

arterydamage

Hormonalsystem

Men

decreasedspermproduction

enlargedbreasts

shrinkingofthetesticles

male-patternbaldness

testicularcancer

Women

voicedeepening

decreasedbreastsize

coarseskin

excessivebodyhairgrowth

male-patternbaldness

Infection

HIV/AIDS

hepatitis

Liver

peliosishepatis

tumors

Musculoskeletalsystem

shortstature(iftakenbyadolescents)

tendoninjury

Psychiatriceffects

aggression

mania

delusions

Skin

severeacneandcysts

oilyscalpandskin

abscessatinjectionsite

jaundice

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CardiovascularSystem

Steroidusehasbeenassociatedwithhighbloodpressure; decreasedfunctionoftheheart’sventricles; andcardiovasculardiseasessuchasheartattacks, arterydamage, andstrokes, eveninathletesyoungerthan30.Steroidscontributetothedevelopmentofcardiovasculardiseasepartlybyincreasingtheleveloflow-densitylipoprotein(LDL) anddecreasingthelevelofhigh-densitylipoprotein(HDL). HighLDLandlowHDLlevelsincreasetheriskofatherosclerosis,aconditioninwhichfattysubstancesaredepositedinsidearteriesanddisruptbloodflow.Ifbloodispreventedfromreachingtheheartorbrain,theresultcanbeaheartattackorstroke,respectively.Steroidsalsoincreasetheriskthatbloodclotswillforminbloodvessels,potentiallydisruptingbloodflowanddamagingtheheartmuscle,sothatitdoesnotpumpbloodeffectively.

HormonalSystem

Steroidusedisruptsthenormalproductionofhormonesinthebody.Changesthatcanbereversedincludedecreasedspermproduction, decreasedfunctionofthetestes(hypogonadism)thatleadstolowtestosteronelevels, andshrinkingofthetesticles(testicularatrophy). Irreversiblechangesincludemale-patternbaldnessandbreastdevelopment(gynecomastia)inmen. Anabolicsteroidsmayalsoactuponthehormonesystemtoincreasetheriskoftesticularcancer,especiallywhensteroidsareusedincombinationwithinsulin-likegrowthfactor.

Infemales,anabolicsteroidscausemasculinization.Specifically,breastsizeandbodyfatdecrease,theskinbecomescoarse,andthevoicedeepens. Womenmayexperienceexcessivegrowthofbodyhairbutlosescalphair. Withcontinuedadministrationofsteroids,someoftheseeffectsbecomeirreversible.Itiscommonlybelievedthatanabolicsteroidswillproduceirreversibleenlargementoftheclitorisinfemales,althoughtherearenostudiesonthis.

Infections

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Manypeoplewhoinjectanabolicsteroidsmayusenonsterileinjectiontechniquesorsharecontaminatedneedleswithotherusers.Thisputsthesesteroidusersatriskforacquiringlifethreateningviralinfections,suchasHIVandhepatitisBandC. Inaddition,animalmodelsindicatethatanabolicsteroidssuppresstheimmunesystem, whichcouldworseninfections.

Liver

Steroidmisusehasbeenassociatedwithliverdamage, tumors, andarareconditioncalledpeliosishepatis,inwhichblood-filledcystsformintheliver. Thecystscanrupture,causinginternalbleedingandevendeathinrarecases.

MusculoskeletalSystem

Risinglevelsoftestosteroneandothersexhormonesnormallytriggerthegrowthspurtthatoccursduringpubertyandadolescence.Theserisinglevelsoftestosteronealsoprovidethesignalstostopgrowth. Whenachildoradolescenttakesanabolicsteroids,theresultingartificiallyhighsexhormonelevelscanprematurelysignalthebonestostopgrowing.

Evidencesuggeststhatweightlifterswhomisuseanabolicsteroidshavestiffertendons,whichcouldleadtoanincreasedriskfortendoninjury.

Skin

Steroidmisusecancauseacne, hairlossonthehead,cysts,andoilyhairandskin. Userswhoinjectsteroidsmayalsodeveloppainandabscessformationatinjectionsites.

Anabolicsteroidscanalsoproducejaundice,oryellowingoftheskinoreyes,asaresultofdamagetotheliver.

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Howdoesanabolicsteroidmisuseaffectbehavior?

Aggression

Casereportsandsmallstudiesindicatethatanabolicsteroidsincreaseirritabilityandaggression, althoughfindingsmaybeconfoundedbypersonalitytraitsthatareoverrepresentedinsteroidusers(i.e.,antisocial,borderline,andhistrionicpersonalitydisorder) anduseofotherdrugs.Peoplewhomisuseanabolicsteroidsreportmoreangerthannonusers, aswellasmorefights,verbalaggression,andviolencetowardtheirsignificantothers, sometimescalled"roidrage."Onestudysuggeststhatthemoodandbehavioraleffectsseenduringanabolic-androgenicsteroidmisusemayresultfromsecondaryhormonalchanges.

Scientistshaveattemptedtotesttheassociationbetweenanabolicsteroidsandaggressionbyadministeringhighsteroiddosesorplacebofordaysorweekstohumanvolunteersandthenassessingbehavioralsymptoms.Inonesuchstudy,researchersfoundthattestosteroneoverasixweekperiodwasassociatedwithincreasedaggression,asassessedbyaquestionnaireandcomputer-basedmodelofaggressivebehavior. Inaddition,highsteroiddosesproducedgreaterfeelingsofirritabilityandaggressionthanplacebo, althoughtheeffectsappeartobehighlyvariableacrossindividuals, andotherstudieshavenotshownthateffect. Onepossibleexplanation,accordingtotheresearchers,isthatsomebutnotallanabolicsteroidsincreaseirritabilityandaggression.

PsychiatricDisorders

Anabolicsteroidusersaremorelikelythannonuserstoreportanxiety.Moderatetohighdosesofanabolicsteroidsarealsoassociatedwithmajormooddisorderssuchasmania,hypomania, andmajordepression. Inonestudy,manicsymptomswerenotuniformacrossindividuals,withmostshowinglittlepsychologicalchange,whereasafewdemonstratedprominenteffects.

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OtherDrugUse

Anabolicsteroidusersaremorelikelytousedrugssuchasmarijuana,prescriptionopioids,cocaine, orheroin. Inastudyofmenadmittedtotreatmentforopioidusedisorders,25percentreportedprioruseofanabolicsteroids.Somedescribedfirstlearningaboutopioidsfromfriendsatthegym,andthattheyfirstpurchasedopioidsfromthesamepersonwhohadsoldthemtheanabolicsteroids. Inastudyofanabolicsteroidusersdependentupontheinjectableopioidanalgesicnalbuphine,mostreportedthattheybeganusingnalbuphinetotreatpainfromweightliftinginjuries.Theyalsodescribedwidespreaduseofnalbuphineintheirgyms.

Researchalsoindicatesthatsomeusersmightturntootherdrugstoalleviatesomeofthenegativeeffectsofanabolicsteroids.Forexample,astudyof227menadmittedin1999toaprivatetreatmentcenterforaddictiontoheroinorotheropioidsfoundthat9.3percenthadpreviouslymisusedanabolicsteroids.Ofthese,mostreportedusingopioidstocounteractinsomnia,irritability,depression,andwithdrawalfromanabolicsteroids.

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Whataretherisksofanabolicsteroiduseinteens?

Unlikemostillicitdruguse,misuseofanabolicsteroidsmostcommonlybeginsinyoungadulthoodratherthanadolescence.Butsteroiduseinteensisofconcern,especiallysincethehormonalsystemstheyinteractwithplayacriticalroleinbraindevelopmentduringtheseyears. Inadolescentrodents,exposuretoanabolicsteroidsincreasedneuronalspinedensitiesinthehippocampusandamygdala—brainregionsinvolvedinlearningandemotions(e.g.,aggression),respectively.Fourweeksafterwithdrawal,theseincreasesinneuronalspinedensitiesreturnedtonormalintheamygdala,butnotinthehippocampus.Thissuggeststhatpubertalsteroidexposurecouldproducelong-lastingstructuralchangesincertainbrainregions.

Teenswhouseanabolicsteroidsmayalsobeatincreasedriskforsomecognitivesideeffectscomparedwithadults.Forexample,maleswhobeginusinganabolicsteroidsduringtheteenyearsshowincreasedimpulsivityanddecreasedattention,comparedtomenwhobeganusingsteroidsintheiradultyears. Inadolescentrats,anabolicsteroidexposureisassociatedwithelectrolyticimbalances,hyperactivity,anxiety,andincreasedsympatheticautonomicmodulation(e.g.,fightorflightresponse)duringadulthood,evenwhensteroidusewasdiscontinuedduringadolescence. Inaddition,adolescentmalehamstersgivenanabolicsteroidsshowincreasedaggression,evenaftersteroiduseisdiscontinued.Theseaggressiveeffectsareparalleledbychangesinlevelsofserotonin andandrogenreceptorsintherodentbrain.

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Howdoanabolicsteroidsworkinthebrain?

Anabolicsteroidsactatandrogenreceptorstoinfluencecellularfunctioningandgeneexpression.Inadditiontoregulatingpathwaysinvolvedinthedevelopmentofmalecharacteristics, activationofandrogenreceptorsalsoproducesrapidincreasesincalciumlevelswithinskeletalmuscle,heart,andbraincells. Calciumplaysimportantrolesinneuronalsignaling.

ResearchwithhumancellsdemonstratesthatanabolicsteroidsalsointeractwithcertaintypesofGABA receptors,whichcouldmediatetheincreasedanxietyreportedbysteroidusers. Inaddition,animalstudiesshowthatanabolicsteroidsincreaseserotoninlevelsinbrainregionsinvolvedinmoodanddopaminelevelsinreward-relatedbrainregions. Chronicuseofanabolicsteroidshasalsobeenshowntocausedysfunctionoftheserewardpathwaysinanimals.Specifically,ratsgiventwicedailynandroloneinjectionsforfourweeksshowedlossofsweetpreference(asignofrewarddysfunction)thatwasaccompaniedbyreductionsofdopamine,serotonin,andnoradrenalineinthenucleusaccumbens,areward-relatedbrainregion.

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Areanabolicsteroidsaddictive?

Anundeterminedpercentageofsteroidusersmaydevelopasteroidusedisorder.Substanceusedisordersaredefinedbycontinuedusedespiteadverseconsequences;forsteroidusers,thesemayincludephysicalorpsychologicalproblemssuchasbreastgrowth(inmen),sexualdysfunction,highbloodpressure,excessivefatsintheblood,heartdisease,moodswings,severeirritability,oraggressiveness.Anabolicsteroidusersalsomaygiveupotherimportantactivitiesforfearthattheywillmissworkouts,violatetheirdietaryrestrictions,orbepreventedfromusingsteroids.Steroidusersalsotypicallyspendlargeamountsoftimeandmoneyobtainingthedrugs,andtheymaytrytoreduceorstopanabolicsteroidusewithoutsuccess—possiblyduetodepression,anxietyaboutlosingmusclemass,orandotherunpleasanteffectsofwithdrawal.

Withdrawalfromsteroidsoccurswhenanindividualdevelopsdependence.Areviewoftheresearchsuggeststhatabout32percentofpeoplewhomisuseanabolicsteroidsbecomedependent. Symptomsofdependencecanincludetolerance,whichisneedingtotakemoresteroidstoachievethesameeffects.Anotherindicatorofdependenceiswithdrawalonceanabolicsteroidusestops. Withdrawalsymptomscanincludefatigue,restlessness,lossofappetite,insomnia,reducedsexdrive,andsteroidcravings. Themostdangerousofthewithdrawalsymptomsisdepression,becauseitsometimesleadstosuicideattempts.

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Howareanabolicsteroidstestedinathletes?

Althoughnon-athleteweightliftersaccountforthebulkofanabolicsteroidmisuse,occasionalsteroidusebyprofessionalandOlympicathletestoimproveperformanceorcheatincompetition("doping")hasdonethemosttoraiseawarenessofsteroidmisuse.TheWorldAnti-DopingAgency(WADA)wasfoundedin1999toconsistentlyapplyanti-dopingpoliciesacrosssportsorganizationsandgovernmentsaroundtheworld.Non-compliantorganizationscanfacesanctionssuchaseventcancellation,lossofWADAfunding,orineligibilitytohostevents.

Refinementsindrugtestinghaveimprovedtheabilitytodetectanti-dopingviolations,resultinginincreasednumbersofreportedviolationsoverrecentyears.Forexample,thediscoveryoflong-termsteroidmetaboliteshaslengthenedthedrugdetectionwindow,makingitmoredifficultforathletestopassdrugtestsbysimplydiscontinuingsteroidusejustpriortoanevent.Inaddition,moresensitivetechnologieshavealloweddetectionoflowermetabolitethresholds.

AlthoughtestingproceduresarenowinplacetodetersteroiduseamongprofessionalandOlympicathletes,newdesignerdrugsconstantlybecomeavailablethatcanescapedetectionandputathleteswillingtocheatonestepaheadoftestingefforts. Todetectearlyuseofdesignersteroidsand

Sportswiththegreatestnumbersofanti-dopingrulesviolationsin2015.Source:WADA.2015Anti-DopingRuleViolations(ADRVs)Report.2017.

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providemoreaccuratebaselinestandardsforeachathlete,testinglaboratoriesstoredatafromeachdrugtestingsample.Thesesamplesarethenusedasreferencepointsforfuturetesting,therebyeliminatingthepossibilitythatapersontestspositivesimplybecauseheorshehasnaturallyelevatedlevelsoftestosteronewhencomparedtothegeneralpopulation. Long-termuseofdesignersteroidssuppresseslevelsendogenoussteroidsinurinesamples,whichcouldbethefirstindicationthatanathleteistakingadesignersteroid.

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DrugTestingandNutritionalSupplements

Athletestakingover-the-counternutritionalsupplementsmaybelievethatsuchproductsaresafe.However,nutritionalsupplementsarenotsubjectedtothesamepre-approvalrequirementsandqualitytestsasFDA-approvedmedications. Forexample,somesupplementsadvertisedtopromoteweightlosshavebeenfoundtocontainbannedstimulantssuchasephedrine orclenbuterol. Otherresearchshowsthatsupplementssometimescontainprohormonesoranabolicsteroids. Inastudylookingat634nutritionalsupplementsfrom13differentcountries,15percentincludedsometypeofprohormonenotlistedonthelabel. Anotherstudyshowedthatsomenon-labeledprohibitedsubstancescouldbedetectedbydrugtestsupto144hourslater.

Nutritionalsupplementssometimescontainbannedsubstancesthatarenotindicatedintheirlabels. TheFDAnotesthatconsumersshouldbewaryifaproductmeetsanyofthesecriteria:

productsclaimingtobealternativestoFDA-approveddrugsortohaveeffectssimilartoprescriptiondrugs

productsclaimingtobealegalalternativetoanabolicsteroids

productsthataremarketedprimarilyinaforeignlanguageorthosethataremarketedthroughmasse-mails

sexualenhancementproductspromisingrapideffectssuchasworkinginminutestohours,orlong-lastingeffectssuchas24hoursto72hours

productsthatprovidewarningsabouttestingpositiveinperformanceenhancementdrugtests

AccordingtoWADA’scodes,athletesareresponsibleforanyprohibitedsubstancefoundintheirsamples,regardlessofwhetheringestionwasintentionalorunintentional.However,sanctionsmaybereducedoravoidediftheathletecandemonstratethatthesubstancewasingestedthroughno

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significantfaultornegligenceonhis/herpart,orinsomecircumstanceswheretheathletedidnotintendtoenhanceperformance.126

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Whatcanbedonetopreventsteroidmisuse?

Researchsuggeststhathighschoolathletesarelesslikelytousesteroidsiftheirpeersandparentsdisapprove,indicatingthatpeersandparentscanbestrongpartnersinpreventionefforts.

However,researchshowsthatsimplyteachingstudentsaboutsteroids'adverseeffectsdoesnotconvinceadolescentsthattheywillbeadverselyaffected,nordoessuchinstructiondiscourageyoungpeoplefromtakingsteroidsinthefuture.Presentingboththerisksandbenefitsofanabolicsteroiduseismoreeffectiveinconvincingadolescentsaboutsteroids'negativeeffects,apparentlybecausethestudentsfindabalancedapproachmorecredible.

Researchalsoindicatesthatsomeadolescentsmisusesteroidsaspartofapatternofhigh-riskbehaviorssuchasdrinkinganddriving,carryingagun,drivingamotorcyclewithoutahelmet,andusingotherillicitdrugs.Thissuggeststhatapreventionprogramshouldfocusoncomprehensivehigh-riskbehaviorscreeningandcounselingamongteenswhouseanabolicsteroids.

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NIDA-FundedPreventionResearchHelpsReduceSteroidMisuse

Amoresophisticatedapproachhasshownpromiseforpreventingsteroidmisuseamongplayersonhighschoolsportsteams.TheAdolescentsTrainingandLearningtoAvoidSteroids(ATLAS)programisshowinghighschoolfootballplayersthattheydonotneedsteroidstobuildpowerfulmusclesandimproveathleticperformance.Byeducatingstudentathletesabouttheharmfuleffectsofanabolicsteroidsandprovidingnutritionandweight-trainingalternativestosteroiduse,theATLASprogramhasincreasedfootballplayers'healthybehaviorsandreducedtheirintentionstomisusesteroids.Intheprogram,coachesandteamleadersteachtheharmfuleffectsofanabolicsteroidsandotherillicitdrugsonimmediatesportsperformanceanddiscusshowtorefuseoffersofdrugs.

Studiesshowthatoneyearaftercompletionoftheprogram,comparedwithacontrolgroup,ATLAS-trainedfootballstudentathletesin15highschoolshad:

lessuseofanabolicsteroidsandlessintentiontomisusetheminthefuture

lessmisuseofalcohol,amphetamines,andnarcotics

lessmisuseof"athleticenhancing"supplements

lesslikelihoodofengaginginhazardousbehaviorssuchasdrinkinganddriving

betterknowledgeaboutanabolicsteroid,alcohol,andmarijuanaeffects;betterknowledgeofalternativestosteroidmisuse;greaterconfidenceinathleticabilities;andimprovednutritionalbehaviors

TheAthletesTargetingHealthyExerciseandNutritionAlternatives(ATHENA)programwaspatternedaftertheATLASprogram,butdesignedforadolescentgirlsonsportsteams.EarlytestingofgirlsenrolledintheATHENAprogram

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showedsignificantdecreasescomparedtocontrolsinriskybehaviorssuchasridingwithanintoxicateddriverorengaginginsexualactivitywithnewpartners.ATHENAparticipantswerealsolesslikelytousedietpills,amphetamines,anabolicsteroids,andmuscle-buildingsupplementsduringthesportsseason.Althoughtheprogramhadnoimmediateeffectontobacco,alcohol,ormarijuanause, ATHENA-trainedathletesreportedlesslifetimeuseofthesesubstanceswhensurveyedonetothreeyearsfollowinghighschoolgraduation.Dietpillandsteroidusedeclinedbythisonetothreeyearfollow-upforbothATHENA-trainedandcontrol-groupathletes,sothatthesegroupsnolongerdifferedintheiruseofthesesubstances.

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Whattreatmentsareeffectiveforanabolicsteroidmisuse?

Peoplewhousesteroidsoftendonotseektreatmentfortheiruse,withonestudyreportingthat56percentofusershadnevertoldtheirphysicianabouttheiruse. Thiscouldbebecauseusersfeeltheirphysicianlacksknowledgeaboutanabolicsteroids. Inaddition,manyinternetsitesdevotedtoanabolicsteroidsandotherAPEDschallengetheprofessionalismofhealthcareprovidersandoffertheirownmedicallyquestionableadviceontheuseofAPEDs. Thismakesitimportantforhealthcareproviderstobeeducatedonthesignsandsymptomsofsteroiduseintheirpatients.

Currentviewsrecommendthattreatmentforsteroiduseaddresstheunderlyingcausesofthesteroiduse.Thiscaninclude:

psychologicaltherapies(andpossiblymedications)formuscledysmorphia

endocrinetherapiestorestorefunctioninthosesufferingfromhypogonadismandtoalleviatesymptomsofdepression

antidepressantsforthosewhosedepressiondoesnotrespondtoendocrinetherapies

pharmacologicalandpsychosocialtreatmentsforpatientswhoarealsodependentonopioids,whichappeartoalsobeeffectiveinalleviatingsignsofanabolicsteroiddependence

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WherecanIgetfurtherinformationaboutsteroids?

TolearnmoreaboutSteroids,otherAppearanceandPerformanceEnhancingDrugs(APEDs),andotherdrugsofuseandmisuse,visittheNIDAwebsiteatwww.drugabuse.govorcontactDrugPubsat877-NIDA-NIH(877-643-2644;TTY/TDD:240-645-0228).

NIDA'swebsiteincludes:

Informationondrugsofuseandmisuseandrelatedhealthconsequences

NIDApublications,news,andevents

Resourcesforhealthcareprofessionals,educators,andpatientsandfamilies

InformationonNIDAresearchstudiesandclinicaltrials

Fundinginformation(includingprogramannouncementsanddeadlines)

Internationalactivities

Linkstorelatedwebsites(accesstowebsitesofmanyotherorganizationsinthefield)

InformationinSpanish(enespañol)

NIDAwebsitesandwebpages

drugabuse.gov/publications/drugfacts/anabolic-steroids

drugabuse.gov/drugs-abuse/steroids-anabolic

drugabuse.gov

teens.drugabuse.gov

easyread.drugabuse.gov

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researchstudies.drugabuse.gov

irp.drugabuse.gov

Forphysicianinformation

NIDAMED:drugabuse.gov/nidamed

Otherwebsites

InformationontheabuseofSteroidsandotherAppearanceandPerformanceEnhancingDrugs(APEDs)isalsoavailablethroughthefollowingwebsites:

MonitoringtheFuture

ThePartnershipforDrug-FreeKids

WorldAnti-DopingAgency:

LabelinginformationfromtheFDA:Testosteronelabeling

LabelinginformationfromtheFDA:TaintedProductsMarketedasDietarySupplements

Steroidpreventionprogramsforhighschoolathletes:AthletesTraining&LearningtoAvoidSteroids(ATLAS)

Steroidpreventionprogramsforhighschoolathletes:AthletesTargetingHealthyExercise&NutritionAlternatives(ATHENA)

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References

1. KanayamaG,PopeHG.Historyandepidemiologyofanabolicandrogensinathletesandnon-athletes.MolCellEndocrinol.March2017.doi:10.1016/j.mce.2017.02.039

2. RashidH,OrmerodS,DayE.Anabolicandrogenicsteroids:whatthepsychiatristneedstoknow.AdvPsychiatrTreat.2007;13(3):203-211.

3. LipsettMB,KorenmanSG.AndrogenMetabolism.JAMA.1964;190(8):757-762.doi:10.1001/jama.1964.03070210063011

4. ShahidiNT.Areviewofthechemistry,biologicalaction,andclinicalapplicationsofanabolic-androgenicsteroids.ClinTher.2001;23(9):1355-1390.

5. FDA.TestosteroneInformation.https://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm161874.htmPublishedMarch3,2015.AccessedMay26,2017.

6. RaoPK,BouletSL,MehtaA,etal.TrendsinTestosteroneReplacementTherapyUsefrom2003to2013amongReproductive-AgeMenintheUnitedStates.JUrol.2017;197(4):1121-1126.doi:10.1016/j.juro.2016.10.063.

7. BrennanR,WellsJSG,VanHoutMC.Theinjectinguseofimageandperformance-enhancingdrugs(IPED)inthegeneralpopulation:asystematicreview.HealthSocCareCommunity.January2016.doi:10.1111/hsc.12326.

8. HildebrandtT,LangenbucherJW,CarrSJ,SanjuanP.Modelingpopulationheterogeneityinappearance-andperformance-enhancingdrug(APED)use:applicationsofmixturemodelingin400regularAPEDusers.JAbnormPsychol.2007;116(4):717-733.doi:10.1037/0021-843X.116.4.71.

9. GennaroMC,AbrigoC.Caffeineandtheobromineincoffee,teaandcola-beverages.FreseniusJAnalChem.1992;343(6):523-525.

10. NCCIH.Ephedra.NCCIH.https://nccih.nih.gov/health/ephedra.PublishedNovember9,2011.AccessedNovember6,2017.

34

11. OfficeofDietarySupplements.Ephedra.https://ods.od.nih.gov/Health_Information/Ephedra.aspx.Publishedn.d.AccessedDecember13,2017.

12. AmericanThyroidAssociation.ThyroidandWeightFAQ.June2012.http://www.thyroid.org/thyroid-and-weight/.AccessedNovember6,2017.

13. 108thCongressFS.RegulationofDietarySupplements:HearingBeforetheCommitteeonCommerce,ScienceandTransportation.;2003.https://www.gpo.gov/fdsys/pkg/CHRG-108shrg20196/pdf/CHRG-108shrg20196.pdf.AccessedFebruary7,2018.

14. 108thCongress.AnabolicSteroidControlActof2004.VolS.2195.;2004.https://www.congress.gov/bill/108th-congress/senate-bill/2195/all-info.AccessedApril28,2017.

15. FreemanER,BloomDA,McGuireEJ.Abriefhistoryoftestosterone.JUrol.2001;165(2):371-373.doi:10.1097/00005392-200102000-00004.

16. AltschuleMD,TillotsonKJ.Theuseoftestosteroneinthetreatmentofdepressions.NEnglJMed.1948;239(27):1036-1038.doi:10.1056/NEJM194812302392704.

17. WadeN.AnabolicSteroids:DoctorsDenounceThem,butAthletesAren’tListening.Science.1972;176(4042):1399-1403.doi:10.1126/science.176.4042.1399.

18. BuckleyWE,YesalisCE,FriedlKE,AndersonWA,StreitAL,WrightJE.Estimatedprevalenceofanabolicsteroiduseamongmalehighschoolseniors.JAMA.1988;260(23):3441-3445.

19. PopeHG,KouriEM,HudsonJI.Effectsofsupraphysiologicdosesoftestosteroneonmoodandaggressioninnormalmen:arandomizedcontrolledtrial.ArchGenPsychiatry.2000;57(2):133-140;discussion155-156.

20. FDA.SignificantDatesinU.S.FoodandDrugLawHistory.2014.https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm2007256.htm.AccessedJune4,2016.

21. DEA.ADangerousandIllegalWaytoSeekAthleticDominanceandBetter

35

Appearance-AGuideforUnderstandingtheDangersofAnabolicSteroids.March2004.https://www.deadiversion.usdoj.gov/pubs/brochures/steroids/public/.AccessedApril25,2017.

22. KanayamaG,BoynesM,HudsonJI,FieldAE,PopeHG.Anabolicsteroidabuseamongteenagegirls:anillusoryproblem?DrugAlcoholDepend.2007;88(2-3):156-162.doi:10.1016/j.drugalcdep.2006.10.013.

23. PopeHG,KanayamaG,AtheyA,RyanE,HudsonJI,BaggishA.Thelifetimeprevalenceofanabolic-androgenicsteroiduseanddependenceinAmericans:currentbestestimates.AmJAddictAmAcadPsychiatrAlcoholAddict.2014;23(4):371-377.doi:10.1111/j.1521-0391.2013.12118.x.

24. IrvingLM,WallM,Neumark-SztainerD,StoryM.Steroiduseamongadolescents:findingsfromProjectEAT.JAdolescHealthOffPublSocAdolescMed.2002;30(4):243-252.

25. PopeHG,KhalsaJH,BhasinS.BodyImageDisordersandAbuseofAnabolic-AndrogenicSteroidsAmongMen.JAMA.2017;317(1):23-24.doi:10.1001/jama.2016.17441.

26. IpEJ,BarnettMJ,TenerowiczMJ,PerryPJ.TheAnabolic500survey:characteristicsofmaleusersversusnonusersofanabolic-androgenicsteroidsforstrengthtraining.Pharmacotherapy.2011;31(8):757-766.doi:10.1592/phco.31.8.757.

27. GruberAJ,PopeHG.Compulsiveweightliftingandanabolicdrugabuseamongwomenrapevictims.ComprPsychiatry.1999;40(4):273-277.

28. WrightS,GroganS,HunterG.MotivationsforAnabolicSteroiduseAmongBodybuilders.JHealthPsychol.2000;5(4):566-571.doi:10.1177/135910530000500413.

29. AmericanAcademyofPediatrics.Adolescentsandanabolicsteroids:asubjectreview.AmericanAcademyofPediatrics.CommitteeonSportsMedicineandFitness.Pediatrics.1997;99(6):904-908.

30. BahrkeMS,WrightJE,StraussRH,CatlinDH.Psychologicalmoodsandsubjectivelyperceivedbehavioralandsomaticchangesaccompanyinganabolic-androgenicsteroiduse.AmJSportsMed.1992;20(6):717-724.

36

31. BeinerJM,JoklP,CholewickiJ,PanjabiMM.Theeffectofanabolicsteroidsandcorticosteroidsonhealingofmusclecontusioninjury.AmJSportsMed.1999;27(1):2-9.

32. FerryA,NoirezP,PageCL,SalahIB,DaegelenD,RieuM.Effectsofanabolic/androgenicsteroidsonregeneratingskeletalmusclesintherat.ActaPhysiolScand.1999;166(2):105-110.doi:10.1046/j.1365-201x.1999.00549.x.

33. FerryA,VignaudA,NoirezP,BertucciW.Respectiveeffectsofanabolic/androgenicsteroidsandphysicalexerciseonisometriccontractilepropertiesofregeneratingskeletalmusclesintherat.ArchPhysiolBiochem.2000;108(3):257-261.doi:10.1076/1381345520000710831ZFT257.

34. EklöfA-C,ThureliusA-M,GarleM,RaneA,SjöqvistF.Theanti-dopinghot-line,ameanstocapturetheabuseofdopingagentsintheSwedishsocietyandanewservicefunctioninclinicalpharmacology.EurJClinPharmacol.2003;59(8-9):571-577.doi:10.1007/s00228-003-0633-z.

35. MedlinePlus.TestosteroneTopical.June2016.https://www.nlm.nih.gov/medlineplus/druginfo/meds/a605020.html#why.

36. TrentonAJ,CurrierGW.Behaviouralmanifestationsofanabolicsteroiduse.CNSDrugs.2005;19(7):571-595.

37. EvansNA.Gymandtonic:aprofileof100malesteroidusers.BrJSportsMed.1997;31(1):54-58.

38. WilsonJD.Androgenabusebyathletes.EndocrRev.1988;9(2):181-199.doi:10.1210/edrv-9-2-181.

39. FratiP,BusardòFP,CipolloniL,DominicisED,FineschiV.AnabolicAndrogenicSteroid(AAS)relateddeaths:autoptic,histopathologicalandtoxicologicalfindings.CurrNeuropharmacol.2015;13(1):146-159.doi:10.2174/1570159X13666141210225414.

40. BronsonFH,MatherneCM.Exposuretoanabolic-androgenicsteroidsshortenslifespanofmalemice.MedSciSportsExerc.1997;29(5):615-619.

41. UrhausenA,AlbersT,KindermannW.Arethecardiaceffectsofanabolicsteroidabuseinstrengthathletesreversible?HeartBrCardSoc.2004;90(5):496-501.

37

42. KaskutasLA.Alcoholicsanonymouseffectiveness:faithmeetsscience.JAddictDis.2009;28(2):145-157.doi:10.1080/10550880902772464.

43. VanbergP,AtarD.Androgenicanabolicsteroidabuseandthecardiovascularsystem.HandbExpPharmacol.2010;(195):411-457.doi:10.1007/978-3-540-79088-4_18.

44. BaggishAL,WeinerRB,KanayamaG,etal.CardiovascularToxicityofIllicitAnabolic-AndrogenicSteroidUse.Circulation.2017;135(21):1991-2002.doi:10.1161/CIRCULATIONAHA.116.026945.

45. ElScheichT,WeberA-A,KleeD,SchweigerD,MayatepekE,KarenfortM.Adolescentischemicstrokeassociatedwithanabolicsteroidandcannabisabuse.JPediatrEndocrinolMetabJPEM.2013;26(1-2):161-165.doi:10.1515/jpem-2012-0057.

46. SantamarinaRD,BesockeAG,RomanoLM,IoliPL,GonorazkySE.Ischemicstrokerelatedtoanabolicabuse.ClinNeuropharmacol.2008;31(2):80-85.doi:10.1097/WNF.0b013e3180ed4485.

47. PalatiniP,GiadaF,GaravelliG,etal.Cardiovasculareffectsofanabolicsteroidsinweight-trainedsubjects.JClinPharmacol.1996;36(12):1132-1140.

48. BhasinS,WoodhouseL,CasaburiR,etal.Testosteronedose-responserelationshipsinhealthyyoungmen.AmJPhysiolEndocrinolMetab.2001;281(6):E1172-1181.

49. LintonMF,YanceyPG,DaviesSS,JeromeWG(Jay),LintonEF,VickersKC.TheRoleofLipidsandLipoproteinsinAtherosclerosis.In:DeGrootLJ,ChrousosG,DunganK,etal.,eds.Endotext.SouthDartmouth(MA):MDText.com,Inc.;2000.http://www.ncbi.nlm.nih.gov/books/NBK343489/.AccessedApril21,2017.

50. Robles-DiazM,Gonzalez-JimenezA,Medina-CalizI,etal.Distinctphenotypeofhepatotoxicityassociatedwithillicituseofanabolicandrogenicsteroids.AlimentPharmacolTher.2015;41(1):116-125.doi:10.1111/apt.13023.

51. SchwingelPA,CotrimHP,SantosCRdos,etal.RecreationalAnabolic-AndrogenicSteroidUseAssociatedWithLiverInjuriesAmongBrazilianYoungMen.SubstUseMisuse.2015;50(11):1490-1498.

38

doi:10.3109/10826084.2015.1018550.

52. KosakaA,TakahashiH,YajimaY,etal.Hepatocellularcarcinomaassociatedwithanabolicsteroidtherapy:reportofacaseandreviewoftheJapaneseliterature.JGastroenterol.1996;31(3):450-454.

53. SocasL,ZumbadoM,Pérez-LuzardoO,etal.Hepatocellularadenomasassociatedwithanabolicandrogenicsteroidabuseinbodybuilders:areportoftwocasesandareviewoftheliterature.BrJSportsMed.2005;39(5):e27.doi:10.1136/bjsm.2004.013599.

54. WakabayashiT,OndaH,TadaT,IijimaM,ItohY.Highincidenceofpeliosishepatisinautopsycasesofaplasticanemiawithspecialreferencetoanabolicsteroidtherapy.ActaPatholJpn.1984;34(5):1079-1086.

55. HansmaP,DiazFJ,NjiwajiC.FatalLiverCystRuptureDuetoAnabolicSteroidUse:ACasePresentation.AmJForensicMedPathol.2016;37(1):21-22.doi:10.1097/PAF.0000000000000218.

56. BonettiA,TirelliF,CatapanoA,etal.Sideeffectsofanabolicandrogenicsteroidsabuse.IntJSportsMed.2008;29(8):679-687.doi:10.1055/s-2007-965808.

57. LiuPY,SwerdloffRS,ChristensonPD,HandelsmanDJ,WangC,HormonalMaleContraceptionSummitGroup.Rate,extent,andmodifiersofspermatogenicrecoveryafterhormonalmalecontraception:anintegratedanalysis.LancetLondEngl.2006;367(9520):1412-1420.doi:10.1016/S0140-6736(06)68614-5.

58. Torres-CallejaJ,González-UnzagaM,DeCelis-CarrilloR,Calzada-SánchezL,PedrónN.Effectofandrogenicanabolicsteroidsonspermqualityandserumhormonelevelsinadultmalebodybuilders.LifeSci.2001;68(15):1769-1774.

59. CalzadaL,Torres-CallejaJ,MartinezJM,PedrónN.Measurementofandrogenandestrogenreceptorsinbreasttissuefromsubjectswithanabolicsteroid-dependentgynecomastia.LifeSci.2001;69(13):1465-1469.

60. ChristouMA,ChristouPA,MarkozannesG,TsatsoulisA,MastorakosG,TigasS.EffectsofAnabolicAndrogenicSteroidsontheReproductiveSystemofAthletesandRecreationalUsers:ASystematicReviewandMeta-

39

Analysis.SportsMedAucklNZ.March2017.doi:10.1007/s40279-017-0709-z.

61. SchürmeyerT,KnuthUA,BelkienL,NieschlagE.Reversibleazoospermiainducedbytheanabolicsteroid19-nortestosterone.LancetLondEngl.1984;1(8374):417-420.

62. OrlandiMA,VenegoniE,PaganiC.Gynecomastiaintwoyoungmenwithhistoriesofprolongeduseofanabolicandrogenicsteroids.JUltrasound.2010;13(2):46-48.doi:10.1016/j.jus.2010.07.006.

63. ChimentoA,SirianniR,ZoleaF,etal.NandroloneandstanozololinduceLeydigcelltumorproliferationthroughanestrogen-dependentmechanisminvolvingIGF-Isystem.JCellPhysiol.2012;227(5):2079-2088.doi:10.1002/jcp.22936.

64. BakerJ.Areportonalterationstothespeakingandsingingvoicesoffourwomenfollowinghormonaltherapywithvirilizingagents.JVoiceOffJVoiceFound.1999;13(4):496-507.

65. ScottMJ,ScottAM.Effectsofanabolic-androgenicsteroidsonthepilosebaceousunit.Cutis.1992;50(2):113-116.

66. NieschlagE,VoronaE.MECHANISMSINENDOCRINOLOGY:Medicalconsequencesofdopingwithanabolicandrogenicsteroids:effectsonreproductivefunctions.EurJEndocrinolEurFedEndocrSoc.2015;173(2):R47-58.doi:10.1530/EJE-15-0080.

67. ZemelBS,KatzSH.Thecontributionofadrenalandgonadalandrogenstothegrowthinheightofadolescentmales.AmJPhysAnthropol.1986;71(4):459-466.doi:10.1002/ajpa.1330710409.

68. BierichJR.Effectsandsideeffectsofanabolicsteroidsinchildren.ActaEndocrinolSuppl(Copenh).1961;39(Suppl63):89-110.

69. SeynnesOR,KamandulisS,KairaitisR,etal.Effectofandrogenic-anabolicsteroidsandheavystrengthtrainingonpatellartendonmorphologicalandmechanicalproperties.JApplPhysiolBethesdaMd1985.2013;115(1):84-89.doi:10.1152/japplphysiol.01417.2012.

70. KrausSL,EmmertS,SchönMP,HaenssleHA.Thedarksideofbeauty:acnefulminansinducedbyanabolicsteroidsinamalebodybuilder.Arch

40

Dermatol.2012;148(10):1210-1212.doi:10.1001/archdermatol.2012.855.

71. MelnikB,JansenT,GrabbeS.Abuseofanabolic-androgenicsteroidsandbodybuildingacne:anunderestimatedhealthproblem.JDtschDermatolGesJGerSocDermatolJDDG.2007;5(2):110-117.doi:10.1111/j.1610-0387.2007.06176.x.

72. VoelckerV,SticherlingM,BauerschmitzJ.Severeulcerated“bodybuildingacne”causedbyanabolicsteroiduseandexacerbatedbyisotretinoin.IntWoundJ.2010;7(3):199-201.doi:10.1111/j.1742-481X.2010.00676.x.

73. RichJD,DickinsonBP,FlaniganTP,ValoneSE.Abscessrelatedtoanabolic-androgenicsteroidinjection.MedSciSportsExerc.1999;31(2):207-209.

74. CabbE,BaltarS,PowersDW,MohanK,MartinezA,PittsE.TheDiagnosisandManifestationsofLiverInjurySecondarytoOff-LabelAndrogenicAnabolicSteroidUse.CaseRepGastroenterol.2016;10(2):499-505.doi:10.1159/000448883.

75. YoshidaEM,ErbSR,ScudamoreCH,OwenDA.Severecholestasisandjaundicesecondarytoanesterifiedtestosterone,anon-C17alkylatedanabolicsteroid.JClinGastroenterol.1994;18(3):268-270.

76. IpEJ,YadaoMA,ShahBM,LauB.Infectiousdisease,injectionpractices,andriskysexualbehavioramonganabolicsteroidusers.AIDSCare.2016;28(3):294-299.doi:10.1080/09540121.2015.1090539.

77. HughesTK,FulepE,JuelichT,SmithEM,StantonGJ.Modulationofimmuneresponsesbyanabolicandrogenicsteroids.IntJImmunopharmacol.1995;17(11):857-863.

78. PerryPJ,KutscherEC,LundBC,YatesWR,HolmanTL,DemersL.Measuresofaggressionandmoodchangesinmaleweightlifterswithandwithoutandrogenicanabolicsteroiduse.JForensicSci.2003;48(3):646-651.

79. LundholmL,FrisellT,LichtensteinP,LångströmN.Anabolicandrogenicsteroidsandviolentoffending:confoundingbypolysubstanceabuseamong10,365generalpopulationmen.AddictAbingdonEngl.2015;110(1):100-108.doi:10.1111/add.12715.

41

80. BurnettKF,KleimanME.Psychologicalcharacteristicsofadolescentsteroidusers.Adolescence.1994;29(113):81-89.

81. ChoiPY,PopeHG.Violencetowardwomenandillicitandrogenic-anabolicsteroiduse.AnnClinPsychiatryOffJAmAcadClinPsychiatr.1994;6(1):21-25.

82. DalyRC,SuT-P,SchmidtPJ,PagliaroM,PickarD,RubinowDR.Neuroendocrineandbehavioraleffectsofhigh-doseanabolicsteroidadministrationinmalenormalvolunteers.Psychoneuroendocrinology.2003;28(3):317-331.

83. KouriEM,LukasSE,PopeHG,OlivaPS.Increasedaggressiverespondinginmalevolunteersfollowingtheadministrationofgraduallyincreasingdosesoftestosteronecypionate.DrugAlcoholDepend.1995;40(1):73-79.

84. BahrkeMS,YesalisCE,WrightJE.Psychologicalandbehaviouraleffectsofendogenoustestosteroneandanabolic-androgenicsteroids.Anupdate.SportsMedAucklNZ.1996;22(6):367-390.

85. TrickerR,CasaburiR,StorerTW,etal.Theeffectsofsupraphysiologicaldosesoftestosteroneonangrybehaviorinhealthyeugonadalmen--aclinicalresearchcenterstudy.JClinEndocrinolMetab.1996;81(10):3754-3758.doi:10.1210/jcem.81.10.8855834.

86. IpEJ,LuDH,BarnettMJ,TenerowiczMJ,VoJC,PerryPJ.Psychologicalandphysicalimpactofanabolic-androgenicsteroiddependence.Pharmacotherapy.2012;32(10):910-919.doi:10.1002/j.1875-9114.2012.01123.

87. PopeHG,KatzDL.Psychiatricandmedicaleffectsofanabolic-androgenicsteroiduse.Acontrolledstudyof160athletes.ArchGenPsychiatry.1994;51(5):375-382.

88. KanayamaG,PopeHG.Illicituseofandrogensandotherhormones:recentadvances.CurrOpinEndocrinolDiabetesObes.2012;19(3):211-219.doi:10.1097/MED.0b013e3283524008.

89. KanayamaG,CohaneGH,WeissRD,PopeHG.Pastanabolic-androgenicsteroiduseamongmenadmittedforsubstanceabusetreatment:anunderrecognizedproblem?JClinPsychiatry.2003;64(2):156-160.

42

90. WinesJD,GruberAJ,PopeHG,LukasSE.Nalbuphinehydrochloridedependenceinanabolicsteroidusers.AmJAddict.1999;8(2):161-164.

91. ArvaryD,PopeHG.Anabolic-androgenicsteroidsasagatewaytoopioiddependence.NEnglJMed.2000;342(20):1532.doi:10.1056/NEJM200005183422018.

92. KeenanBS,RichardsGE,PonderSW,DallasJS,NagamaniM,SmithER.Androgen-stimulatedpubertalgrowth:theeffectsoftestosteroneanddihydrotestosteroneongrowthhormoneandinsulin-likegrowthfactor-Iinthetreatmentofshortstatureanddelayedpuberty.JClinEndocrinolMetab.1993;76(4):996-1001.doi:10.1210/jcem.76.4.8473416.

93. MorrisJA,JordanCL,BreedloveSM.Sexualdifferentiationofthevertebratenervoussystem.NatNeurosci.2004;7(10):1034-1039.doi:10.1038/nn1325.

94. RomeoRD,RichardsonHN,SiskCL.Pubertyandthematurationofthemalebrainandsexualbehavior:recastingabehavioralpotential.NeurosciBiobehavRev.2002;26(3):381-391.

95. SchulzKM,Molenda-FigueiraHA,SiskCL.Backtothefuture:Theorganizational-activationalhypothesisadaptedtopubertyandadolescence.HormBehav.2009;55(5):597-604.doi:10.1016/j.yhbeh.2009.03.010.

96. ZehrJL,NicholsLR,SchulzKM,SiskCL.AdolescentdevelopmentofneuronstructureindentategyrusgranulecellsofmaleSyrianhamsters.DevNeurobiol.2008;68(14):1517-1526.doi:10.1002/dneu.20675.

97. CunninghamRL,ClaiborneBJ,McGinnisMY.Pubertalexposuretoanabolicandrogenicsteroidsincreasesspinedensitiesonneuronsinthelimbicsystemofmalerats.Neuroscience.2007;150(3):609-615.doi:10.1016/j.neuroscience.2007.09.038.

98. HildebrandtT,LangenbucherJW,FloresA,HartyS,BerlinHA,BerlinH.Theinfluenceofageofonsetandacuteanabolicsteroidexposureoncognitiveperformance,impulsivity,andaggressioninmen.PsycholAddictBehavJSocPsycholAddictBehav.2014;28(4):1096-1104.doi:10.1037/a0036482.

99. OlivaresEL,SilveiraALB,FonsecaFV,etal.Administrationofananabolicsteroidduringtheadolescentphasechangesthebehavior,cardiac

43

autonomicbalanceandfluidintakeinmaleadultrats.PhysiolBehav.2014;126:15-24.doi:10.1016/j.physbeh.2013.12.006.

100. GrimesJM,MelloniRH.Prolongedalterationsintheserotoninneuralsystemfollowingthecessationofadolescentanabolic-androgenicsteroidexposureinhamsters(Mesocricetusauratus).BehavNeurosci.2006;120(6):1242-1251.doi:10.1037/0735-7044.120.6.1242.

101. RicciLA,RasakhamK,GrimesJM,MelloniRH.Serotonin-1Areceptoractivityandexpressionmodulateadolescentanabolic/androgenicsteroid-inducedaggressioninhamsters.PharmacolBiochemBehav.2006;85(1):1-11.doi:10.1016/j.pbb.2006.06.022.

102. MenardCS,HarlanRE.Up-regulationofandrogenreceptorimmunoreactivityintheratbrainbyandrogenic-anabolicsteroids.BrainRes.1993;622(1-2):226-236.

103. MatsumotoT,SakariM,OkadaM,etal.Theandrogenreceptorinhealthanddisease.AnnuRevPhysiol.2013;75:201-224.doi:10.1146/annurev-physiol-030212-183656.

104. VicencioJM,EstradaM,GalvisD,etal.Anabolicandrogenicsteroidsandintracellularcalciumsignaling:aminireviewonmechanismsandphysiologicalimplications.MiniRevMedChem.2011;11(5):390-398.

105. YangP,JonesBL,HendersonLP.Mechanismsofanabolicandrogenicsteroidmodulationofalpha(1)beta(3)gamma(2L)GABA(A)receptors.Neuropharmacology.2002;43(4):619-633.

106. YangP,JonesBL,HendersonLP.RoleofthealphasubunitinthemodulationofGABA(A)receptorsbyanabolicandrogenicsteroids.Neuropharmacology.2005;49(3):300-316.doi:10.1016/j.neuropharm.2005.03.017.

107. KindlundhAM,LindblomJ,BergströmL,WikbergJE,NybergF.Theanabolic-androgenicsteroidnandrolonedecanoateaffectsthedensityofdopaminereceptorsinthemaleratbrain.EurJNeurosci.2001;13(2):291-296.

108. ThiblinI,FinnA,RossSB,StenforsC.Increaseddopaminergicand5-hydroxytryptaminergicactivitiesinmaleratbrainfollowinglong-termtreatmentwithanabolicandrogenicsteroids.BrJPharmacol.

44

1999;126(6):1301-1306.doi:10.1038/sj.bjp.0702412.

109. ZottiM,TucciP,ColaiannaM,etal.Chronicnandroloneadministrationinducesdysfunctionoftherewardpathwayinrats.Steroids.2014;79:7-13.

110. KanayamaG,BrowerKJ,WoodRI,HudsonJI,PopeHG.IssuesforDSM-V:clarifyingthediagnosticcriteriaforanabolic-androgenicsteroiddependence.AmJPsychiatry.2009;166(6):642-645.doi:10.1176/appi.ajp.2009.08111699.

111. BrowerKJ,BlowFC,YoungJP,HillEM.Symptomsandcorrelatesofanabolic-androgenicsteroiddependence.BrJAddict.1991;86(6):759-768.

112. MaloneDA,DimeffRJ,LombardoJA,SampleRH.Psychiatriceffectsandpsychoactivesubstanceuseinanabolic-androgenicsteroidusers.ClinJSportMedOffJCanAcadSportMed.1995;5(1):25-31.

113. WADA.2015Anti-DopingRuleViolations(ADRVs)Report.;2017.https://www.wada-ama.org/sites/default/files/resources/files/2015_adrvs_report_web_release_0.pdf.

114. WADA.ComplianceMonitoring.https://www.wada-ama.org/en/questions-answers/compliance-monitoring.Published2017.AccessedMay18,2017.

115. GeyerH,SchänzerW,ThevisM.Anabolicagents:recentstrategiesfortheirdetectionandprotectionfrominadvertentdoping.BrJSportsMed.2014;48(10):820-826.doi:10.1136/bjsports-2014-093526.

116. CatlinDH,SekeraMH,AhrensBD,StarcevicB,ChangY-C,HattonCK.Tetrahydrogestrinone:discovery,synthesis,anddetectioninurine.RapidCommunMassSpectromRCM.2004;18(12):1245-1049.doi:10.1002/rcm.1495.

117. CatlinDH,AhrensBD,KucherovaY.Detectionofnorbolethone,ananabolicsteroidnevermarketed,inathletes’urine.RapidCommunMassSpectromRCM.2002;16(13):1273-1275.doi:10.1002/rcm.722.

118. SekeraMH,AhrensBD,ChangY-C,StarcevicB,GeorgakopoulosC,CatlinDH.Anotherdesignersteroid:discovery,synthesis,anddetectionof“madol”inurine.RapidCommunMassSpectromRCM.2005;19(6):781-784.doi:10.1002/rcm.1858.

119. MareckU,GeyerH,OpfermannG,ThevisM,SchänzerW.Factors

45

influencingthesteroidprofileindopingcontrolanalysis.JMassSpectromJMS.2008;43(7):877-891.doi:10.1002/jms.1457.

120. YonamineM,GarciaPR,deMoraesMoreauRL.Non-intentionaldopinginsports.SportsMedAucklNZ.2004;34(11):697-704.

121. JungJ,Hermanns-ClausenM,WeinmannW.AnorecticsibutraminedetectedinaChineseherbaldrugforweightloss.ForensicSciInt.2006;161(2-3):221-222.doi:10.1016/j.forsciint.2006.02.052.

122. ParrMK,KoehlerK,GeyerH,GuddatS,SchänzerW.Clenbuterolmarketedasdietarysupplement.BiomedChromatogrBMC.2008;22(3):298-300.doi:10.1002/bmc.928.

123. GeyerH,BraunH,BurkeLM,StearSJ,CastellLM.A-Zofnutritionalsupplements:dietarysupplements,sportsnutritionfoodsandergogenicaidsforhealthandperformance--Part22.BrJSportsMed.2011;45(9):752-754.doi:10.1136/bjsports-2011-090180.

124. DeCockKJ,DelbekeFT,VanEenooP,DesmetN,RoelsK,DeBackerP.Detectionanddeterminationofanabolicsteroidsinnutritionalsupplements.JPharmBiomedAnal.2001;25(5-6):843-852.

125. FDA.TaintedProductsMarketedasDietarySupplements.https://www.accessdata.fda.gov/scripts/sda/sdNavigation.cfm?sd=tainted_supplements_cder.AccessedJanuary9,2018.

126. WADA.WorldAnti-DopingCode.2009.https://www.wada-ama.org/sites/default/files/resources/files/wada_anti-doping_code_2009_en_0.pdf.AccessedMay23,2017.

127. ElliotD,GoldbergL.Interventionandpreventionofsteroiduseinadolescents.AmJSportsMed.1996;24(6Suppl):S46-47.

128. GoldbergL,BentsR,BosworthE,TrevisanL,ElliotDL.Anabolicsteroideducationandadolescents:doscaretacticswork?Pediatrics.1991;87(3):283-286.

129. MiddlemanAB,FaulknerAH,WoodsER,EmansSJ,DuRantRH.High-riskbehaviorsamonghighschoolstudentsinMassachusettswhouseanabolicsteroids.Pediatrics.1995;96(2Pt1):268-272.

130. GoldbergL,MacKinnonDP,ElliotDL,MoeEL,ClarkeG,CheongJ.The

46

adolescentstrainingandlearningtoavoidsteroidsprogram:preventingdruguseandpromotinghealthbehaviors.ArchPediatrAdolescMed.2000;154(4):332-338.

131. ElliotDL,GoldbergL,MoeEL,DefrancescoCA,DurhamMB,Hix-SmallH.Preventingsubstanceuseanddisorderedeating:initialoutcomesoftheATHENA(athletestargetinghealthyexerciseandnutritionalternatives)program.ArchPediatrAdolescMed.2004;158(11):1043-1049.doi:10.1001/archpedi.158.11.1043.

132. ElliotDL,GoldbergL,MoeEL,etal.Long-termOutcomesoftheATHENA(AthletesTargetingHealthyExercise&NutritionAlternatives)ProgramforFemaleHighSchoolAthletes.JAlcoholDrugEduc.2008;52(2):73-92.

133. PopeHG,KanayamaG,Ionescu-PioggiaM,HudsonJI.Anabolicsteroidusers’attitudestowardsphysicians.AddictAbingdonEngl.2004;99(9):1189-1194.doi:10.1111/j.1360-0443.2004.00781.x.

134. BrennanBP,KanayamaG,PopeHG.Performance-enhancingdrugsontheweb:agrowingpublic-healthissue.AmJAddictAmAcadPsychiatrAlcoholAddict.2013;22(2):158-161.doi:10.1111/j.1521-0391.2013.00311.x.

135. KanayamaG,BrowerKJ,WoodRI,HudsonJI,PopeHG.Treatmentofanabolic-androgenicsteroiddependence:Emergingevidenceanditsimplications.DrugAlcoholDepend.2010;109(1-3):6-13.doi:10.1016/j.drugalcdep.2010.01.011