Copyright© ABE&M todos os direitos reservados. review São Paulo, SP, Brazil FMUSP,e Metabologia, (SUS), SãoPaulo, SP, Brazil no SistemaÚnicodeSaúde Processo Transexualizadordo da SaúdeparaRegulamentação Comitê Técnico doMinistério de Transexualismo,HCFMUSP. Clínicas (HC),FMUSP. Ambulatório das Hospital e Metabologia, deEndocrinologia (FMUSP). Serviço Universidade deSãoPaulo Faculdade deMedicinada 188 the International tothe source: ently namedaccording I INTRODUCTION Accepted onNov/6/2013 Received onOct/23/2013 [email protected] –SãoPaulo,05403-900 SP, Brazil 155, 8ºandar, bloco3 Av. Dr. EnéasdeCarvalho Aguiar, Universidade deSãoPaulo Faculdade deMedicina, dasClínicas, Hospital Elaine MariaFrade Costa Correspondence to: 2 1 Disciplina deEndocrinologia Disciplina deEndocrinologia, to the one they identify themselves with are differ to theonetheyidentifythemselves withare iscontrary ndividuals whosegenderassigned atbirth http://dx.doi.org/10.1590/0004-2730000003091 transsexual subjects Clinical managementof Elaine Maria FradeElaine Maria Costa Manejo clínico desujeitos transexuais sem causarefeitoscolateraisimportantes. mos afirmarquedosesfisiológicasdesseshormôniossãocapazes deproduzirosefeitosdesejados secundários femininosnotransexualmasculino.Combasenaexperiência donossoserviço,pode nos transexuaisfemininoseoestrógenoéhormônioutilizado parainduziroscaracteressexuais hormônio utilizadoparainduzirodesenvolvimento doscaracteressexuaissecundáriosmasculinos como membrosdasociedadenogênerocomoqualelesseidentificam. Atestosteronaéoprincipal dereabilitá-los esegurocomoobjetivo devem sersubmetidosaumregimedetratamentoefetivo transexuaisbuscamdesenvolverindivíduos característicasfísicaspertencentes aosexo desejadoe ter realizadohormonioterapiaporpelomenosumanoepsicoterapiadoisanos.Os e urologistas).Para seremsubmetidosàcirurgia,ospacientesdevemterde21a75anos, por psicólogo,assistentesocial,psiquiatra,endocrinologistaecirurgiões(ginecologistas,plásticos Serviços ondeforemrealizadostaisprocedimentoscontemcomequipemultidisciplinarcomposta mento depacientestransexuaisestãoautorizadoseregulamentadosnonossopaís,desdequeos masculino. Há16 anososprocedimentosmédicosclínicosecirúrgicosnecessáriosparaotrata eseraceitocomomembrodosexo víduo 46,XXcomfenótipofemininonormalquedesejaviver eseraceitocomomembrodosexo feminino, jáotransexualismofemininorefere-seaoindi viver Transexualismo 46,XYcomfenótipomasculinonormalquedeseja masculinorefere-seaoindivíduo RESUMO patients, respectively. and estradioltreatmentinphysiological dosesareeffective andsafeinfemalemaletranssexual of experience, male we transsexual can patients. conclude Based that on our 15 years patients, andtheestrogenischosen hormoneusedtoinducethefemalesexualcharacteristics in 2 years. Testosterone istheprincipalagentusedtoinducemalecharacteristics infemaletranssexual Patients old and in psychological must be between 21 to 75 years andhormonaltreatmentfor at least a psychiatrist, anendocrinologistandsurgeons(gynecologists,plasticsurgeons,urologists). at MedicalServices thathaveamultidisciplinaryteamcomposedofpsychologist, asocialworker, signment proceduresnecessaryforthetreatmentoftranssexualpatientsareallowedinourcountry, asamemberofsocietyinthegenderheorsheidentifieswith. rehabilitate theindividual Sexreas gender, andshouldundergoaneffective andsafetreatmentregimen. The goaloftreatmentisto as possible with one’s preferred sex. They seek to develop the physical characteristics of the desired one’sanatomic sex,andawishtohavesurgeryhormonaltreatmentmake bodyascongruent opposite sex,usuallyaccompaniedbyasenseofdiscomfort with,orinappropriatenessof, one’s Transsexual andbeacceptedasamemberofthe whohaveadesiretolive subjectsareindividuals ABSTRACT Transexualismo; tratamentohormonal;manejo Descritores Transsexualism; hormonetreatment;management Keywords Arq BrasEndocrinolMetab. 2014;58(2):188-96 - 1 ,

Berenice Mendonca Bilharinho – version5. published,DSM in version4(DSM-4),orthe recently Diagnostic andStatisticalManual ofMentalDisorders Classification ofDiseases – version10(ICD-10),the Arq BrasEndocrinolMetab. 2014;58(2):188-96 Arq Bras Metab. Endocrinol 2014;58/2 2 - - - - Arq Bras Metab. Endocrinol 2014;58/2 (www.portal.cfm.org.br). writtenconsent form informed ter atleast2yearsofpsychotherapy andaftersigningan 21 years old orolder, at public or university hospitals, af inpatients diagnosedastranssexuals,whowere surgery Medicine (FCM), of Resolution nº 1482/97 15yearsagowith the publication xual patientsoccurred for transse ­ regulation of medical procedures The first BRAZIL REGULATION OFTHETRANSSEXUALPROCESS IN 1:200,000 forfemaletranssexualism(4). 1:45,000 formaletranssexualism,and1:30,400to 1:11,900to ratesfrom prevalence riety inreported toliveandbeacceptedasamale. with desire femalephenotype to all 46, XXindividualswithnormal accepted asafemale;2)Femaletranssexualism:refers malephenotypewhowishestoliveandbe with normal toall46, XY individuals Male transsexualism:refers used term. Transsexualism, because it has been the most widely (3). isnot,byitself,amentaldisorder nonconformity signed tothem.Thetextalsoemphasizesthatgender thegenderas from see themselvesandfeeldifferent tothose who clinicalcare ing stigmatizationandensure by GenderDysphoriawiththemainobjectiveofavoid wasreplaced GenderIdentityDisorder theterm where (DSM-5), and StatisticalManualofMentalDisorders tion havepublishedthefiftheditionofDiagnostic or surgicalposite sex through hormonal manipulation (2). opposite sexortoacquire thephysicalappearanceofop fested asanintensedesire toadoptthesocialroleof maybemani as amemberoftheoppositesex.Thisconcern marked uneasinesswiththedesire toliveandbeaccepted the (DSM-4),isattributedtoindividualswhomanifest possible withone’spreferred sex(1)”. treatment as hormonal tomakeone’sbodyascongruent and of, one’sanatomicsex,andawishtohavesurgery with, or inappropriateness panied by asenseofdiscomfort accepted asamemberoftheoppositesex,usuallyaccom sexualism (F64.0),definedas:“Adesire toliveandbe According toICD-10,thisconditioniscalledTransAccording Transsexualism is a va and there rare is extremely Didactically, Transsexualism is classified into:1) In thispaper, wewillusetheICD-10nomenclature, recently,More theAmericanPsychiatricAssocia Gender IdentityDisorder, denomination givenby which authorized sex reassignment which authorizedsexreassignment by the Federal Council of by the Federal Council of ------It removed the experimental nature ofthemaletofe theexperimentalnature It removed 1652/02, Hospital dasClínicasattheMedicalSchoolofUniversi –Rio de Janeiro/RJ, dade EstadualdoRiodeJaneiro atUniversi Ernesto RS, HospitalUniversitárioPedro Alegre/ versidade FederaldoRioGrandeSul–Porto Centers,HospitaldeClínicasatUni named Reference are earlier bytheFCM.Fourhospitalsincountry with the guidelines determined System, in accordance the Transsexual in the Brazilian Public Health Process nº457/2008,whichregulated SUS/MS Ordinance ing itsexperimentalcharacter(www.portal.cfm.org.br). touniversityhospitals, maintain isstillrestricted gery ­ reso criteriaoftheprevious required which fulfilledthe rizing itsexecutioninanypublicorprivatehospitals, (feminization),autho surgery male sexreassignment gist hasakey role. multi- andinterdisciplinary, inwhichtheendocrinolo vulnerable population(6). forthis programs andtreatment to developreception theneed Thisdataunderscore family/social support. attempted suicide,orsymptomsofimpulsivity, orno significantly higheramongthosewhohadpreviously (6,7). Suicide risk was or experience depression harm, riskof committing suicideandself- atincreased are Several studieshaveshownthattransgenderindivi­ TRANSSEXUAL PATIENT MANAGEMENT at least1year, andpsychotherapy foratleasttwoyears. therapyfor hormone 75 yearsold,beingincross-sex To undergo surgery, transsexualpatientsmustbe21- geons (gynecologists,plasticsurgeons, andurologists). social worker, apsychiatrist,anendocrinologistandsur teamcomposedofapsychologist, multidisciplinary thathavea lowed inourcountry, atMedicalServices al oftranssexualpatientsare forthetreatment essary (www.portal.cfm.org.br).requisites establishedpre that fullycontemplatedthepreviously only ininstitutions ing themulti-modalitytreatment authoriz resolutions, contained in previous procedures surgical nº 1955/2010,expandedsexreassignment at UniversidadeFederaldeGoiás–Goiânia/GO(5). dade deSãoPaulo–Paulo/SP, HospitaldasClínicas Five yearslater, theFCMpublishedResolutionnº In 2008, the Brazilian Ministry of Health published ofHealthpublished In 2008,theBrazilianMinistry The process of gender reassignment shouldbe ofgenderreassignment The process In summary, nec procedures thesex reassignment Finally in2010,theFCM,bymeansofResolution lution. The female to male sex reassignment sur lution. Thefemaletomalesexreassignment which revoked andextendedtheearlierone. which revoked Management oftransexuals duals 189 ------

Copyright© ABE&M todos os direitos reservados. Copyright© ABE&M todos os direitos reservados. 190 psy and patterned interviews, structured such as:freely dual bymeansofpsychological assessmentinstruments, population, contemplating the evolutionofindivi­ intendedforanyother logical assessmentprocedures thepsycho from patients doesnotsignificantly differ Generally speaking, PREPARATORY PSYCHOTERAPY FORSURGERY PSYCHOLOGICAL EVALUATION AND of societyinthegenderthathe/sheidentifieswith. theindividualasamember istorehabilitate treatment Thegoalof regimen. andsafetreatment to aneffective gender physicalcharacteristicsandshouldbesubmitted year, andfollowedupindefinitelybytheendocrinologist. is maintainedinpostoperativepsychotherapyforatleast1 surgeries; 5)Finally,for thesexreassignment thepatient tosurgeons use,thepatientisreferred hormone cross-sex therapy; 4)Afteratleasttwoyearsofpsychotherapyand hormone toanendocrinologistforcross-sex is referred ated; 3)Aftersixmonthsofpsychotherapy, thepatient of transsexualismisestablished,psychotherapyiniti andduringtheevaluation);2)Once thediagnosis fore foratleast1monthbe hormones stop takingcross-sex thatpatients the DSM-4andICD-10(werecommend thediagnosticcriteriaestablishedby thataddress naires andquestion and apsychiatristbymeansofinterviews is submitted to diagnostic evaluation by a psychologist patients obeythefollowingflow:1)Initiallypatient team. developed bythemultidisciplinary the EvaluationandTreatment ofTransgender Patients” for to the “Protocol evaluated according patients are Universidade deSãoPaulo,theself-calledtransgender Unit ofHospitaldasClínicasattheMedicalSchool (9). tocompletethetranssexualprocess ies required surger forsexreassignment surgeon mustberesponsible surgery.the indicationofsexreassignment Finally, the andcollaboratein treatment hormonal tor thecross-sex would initiateandmoni docrinologist, inhisorherturn, theen treatment; hormonal sexualism andrecommend and thepsychiatristshouldmakediagnosisoftrans of transsexuals (8). The psychologist process treatment allthestepsof integrated andconsistentwayacross inan crinologist, andasurgeon whoshouldparticipate should consistofapsychologist,psychiatrist,anendo team sociation ofGenderDysphoria,theinterdisciplinary Management oftransexuals As proposed by the Harry Benjamin International As BenjaminInternational bytheHarry As proposed Transgender individualsseektodevelopdesired oftranssexual process The evaluationandtreatment In theoutpatientDevelopmentalEndocrinology psychological evaluationfor these ------CROSS-SEX HORMONETHERAPY offered. the treatment forelaborationandguidanceregarding for interviews ofsurgery.results invited Relativesand/orspousesare to the idealization ofesthetic and functional relation in andlimitations,particularly deal withfrustrations ability to lution, quality of interpersonal relationships, reso health ofthepatient,abilityandstyleconflict takenintoaccount,suchasgeneralstateofmental are genderidentity,and issuesregarding severalvariables a psychotherapeuticspaceforelaborationofconflicts ship betweenpatientandtherapist.Besidesoffering basedontherelation the psycotherapeuticprocess veloped ofourpsychologists. aspects ofchildhood,adolescenceandadulthood,de thatcovers iew weuseaspecificquestionnaire interv Forthestructured chological assessmentinstruments. the genderidentity. fering causedbytheinadequacy ofthephenotypewith s. associated withundesirable side effect frequently and are effects, toachievethedesired sary notneces ever, are hormones highdosesofcross-sex How offacialhairgrowth. andcontrol ment ofbreasts by maletranssexualswhowishtoobtainrapiddevelop mainly hormones, dosesofcross-sex pharmacological placement therapyforhypogonadicpatients. gender,desired re adoptingtheprinciplesofhormone levels compatible withthe patient’s serum cal hormone thatallowsphysiologi hormones age ofthecross-sex tics of biological sex; and 3) to establish the ideal dos sexualcharacteris thesecondary levels and,therefore, reduce endogenoushormone der identification;2)to pearance ofsexualcharacteristicscompatiblewithgen 1)to induce theap ment fortranssexualpatientsare: manner(9). inaresponsible hormones to consolidategenderidentityand3)belikelytake bythepsychotherapist therapy foraperioddetermined months,orpsycho genderforatleastthree desired lifeexperienceinthe use;2)completeareal hormone of cross-sex derstanding of the expected and side effects The patientmust:1)demonstrateknowledgeandun therapymustfollowwell-definedcriteria. of hormone ment guidelines of transsexual patients, the beginning toAmericanSocietyofEndocrinologytreat According The proper time for surgery is determined during isdetermined timeforsurgery The proper provides a strong relief from suf from relief astrong therapyprovides Hormone We inour medical practice,theuseof oftenobserve, treat hormone The mainobjectivesofthecross-sex Arq Bras Metab. Endocrinol 2014;58/2 ------Arq Bras Metab. Endocrinol 2014;58/2 Adapted from: CostaandMendonça(30). Table 1. Available androgensforclinicaluse With this cal levelsduringthefirstdaysafterinjection. supraphysiologi and promote release, of testosterone rhythm they donotmimictheendogenouscircadian cular because of their low cost. However, estersforintramus testosterone theshort-acting are therapy. notindicatedforandrogen theyare fore, hepatotoxicity. to them important conferring There thefasthepaticmetabolism, modifiedtodecrease are suchasfluoximetazonaandmethyltestosterone, form, undecanoate.Theoral17α-alkylated of testosterone subcutaneous systems,buccaladhesiveandtheoralform adhesives and gels, tramuscular injection, testosterone undecanoateforin esters, thelong-actingtestosterone intramuscularinjectionsoftestosterone short-acting available,includingthe are formulations testosterone duce malecharacteristicsinthesepatients.Several world. Testosterone istheprincipalagentusedtoin the around main Centersfortranssexualmedicalcare havebeenusedinthe oftestosterone ceutical forms pharma withdifferent therapeuticregimens Different Female transsexual subjects Oral system Oral testosteroneundecanoate Subcutaneous implants Transdermal gel Transdermal patch Injectable testosteroneundecanoate Testosterone cypionateinjection injectable testosteronedecanoate Propionates +isocaproate Composition The most widely preparations used in our country used in our country The most widely preparations 30 mg/12h 80-160 mg/d months 600 mg/4-6 5 g/d 5 mg/d 1,000 mg/12week 200 mg/2-3week 250 mg/2-3week Dose injection site Does notseemtocausemucosalirritation atthe Leads tophysiologicallevelsoftestosterone Mimics thecircadianrhythm Does notcausehepatotoxicity The onlyeffectiveandsafeoraltestosteroneester 6months One implantevery Leads tostableandphysiologicaltestosteronelevels Does notcauseskinirritationattheapplicationsite levelsoftestosterone Maintains satisfactory Quick andefficientabsorption Leads tophysiologicallevelsoftestosterone Moderate cost Mimics thecircadianrhythmoftestosteronerelease testosterone Does notprovidessupra-physiologicallevelsof 4 injections/year 2-3weeks One doseevery Low cost 2-3weeks One doseevery Low cost ------Advantages days isindicated. 14 this period,theusualdoseofoneinjectionevery clitoral size, facialhairandmusclemass.After increase cypionate each 1-2weeksfor6monthsto tosterone we use a 200 mgoftes observed, are if no side effects plication. Aftertheinductionofvirilizationperiod, peakinthefirst daysafterap hightestosterone a very esters isthatitdoesnotdetermine testosterone three thatcombines form advantage overthepharmaceutical 15-21days.Itsmain tion inadosageof200mgevery cypionate for intramuscularinjec acting testosterone School ofUniversidadedeSãoPaulo,weusetheshort- nology UnitofHospitaldasClínicasattheMedical summarizedintable1. vantages are therapywiththeiradvantagesanddisad replacement per-sweating (10). andhy ,aggressiveness suchasincreased effects, ofside ofthefrequency isanincrease there regimen, the worldisshownintable2. ment offemaletranssexualsintheprincipalcenters Primary therapeutic schemes proposed forthetreat therapeuticschemesproposed Primary In theoutpatientsofDevelopmentalEndocri forandrogen forms The availablepharmaceutical Short experienceofclinicaluse High cost 2 dailydoses Not availableinBrazil 2 to4dailydoses Daily use Possibility ofextrusionandlocalinfection Not availableinBrazil High cost Daily use Not availableinBrazil High cost Often causesskinirritationattheapplicationsite Daily use Not availableinBrazil High cost within thefirstdaysafterapplication Leads tosupra-physiologicallevelsoftestosterone release Does notmimicthecircadianrhythmoftestosterone within thefirstdaysafterapplication Provides supra-physiologicallevelsoftestosterone release Does notmimicthecircadianrhythmoftestosterone Disadvantages Management oftransexuals 191 ------

Copyright© ABE&M todos os direitos reservados. Copyright© ABE&M todos os direitos reservados. 192 administration infemaletransse ­ oftestosterone effect doses formales. atphysiological ly inhibitedbyexogenoustestosterone ovarian axis is not complete the hypothalamic pituitary levelsformalesex,showingthat testosterone normal 9.4 U/Land12.17±15.2respectively, despite rangeforwomeninthefollicularphase,6.13± normal abovethe 200-950 ng/dL). LH and FSH levels were rangeforadultmen(normal: levels withinthenormal onate biweeklywasalsoabletomaintaintestosterone cypi theuseof200mgtestosterone our cohort, rangeforyoungadultmen(11).In within thenormal levels testosterone two weeks is able to maintain serum the patients. in91%of in 77%,andfatredistribution mass occurred inmuscle Atclinicalexaminationanincrease terone. testos ses occursinthefirst2-3dosesofshort-acting ofmen tohighlightthattheinterruption important libido.Itis andincreased atrophy (3.5-5.0 cm),breast bodyhair,ing, increased enlargement oftheclitoris showed voice deepen at leastoneyearoftreatment our 40patients,demonstratedthatallpatientsinto therapy.by femaletranssexualsundertestosterone expected theeffects musclemass,are fat andincreased ofbody redistribution largement, libidoimprovement, phy, bodyhair, voicedeepening,increased clitorisen Adapted from: CostaandMendonça(30). Table 2. Proposedregimensforthetreatmentoffemaletranssexualsubjects Management oftransexuals Personal experience Erlangen, Germany Department ofObstetricsandGynecology, ErlangenUniversityHospital, Singapore Department ofObstetricsandGynecology, NationalUniversitofSingapore Texas, USA Gender Clinic, Universityof Texas Munich, Germany Max-Planck-Institute EndocrinologyClinic New York,USA Division ofEndocrinology, MountSinai Liége, Belgium Psychoneuroendocrinology Unit, UniversityofLiége Amsterdam, Netherlands Academic Hospital Vrije Univesiteit Treatment center The interruption of menstrual cycles, breast atro cycles,breast ofmenstrual The interruption Despite the few number of studies that evaluated the Despite thefewnumberofstudies thatevaluatedthe enanthateevery The administrationoftestosterone 10years)of follow-up(around The long-term Not reported Not reported Number of ------patients 293 50 37 70 30 93 the schemes proposed in the literature (12,13). intheliterature with theschemesproposed achieved described above are xuals, most of the effects tients; however, polycythemiclevels. It nonereached inhematocritallpa wasanincrease them. There in 25% of in 20% and hypertension and aggressiveness in 70%ofcases,weightgain in25%,hyper-sexuality therapywasacnewhichoccurred ofandrogen effects side that themostfrequent in ourclinic,weobserved (15). sistent results variedandhaveincon are regimens dition, treatment follow-upperiod.Inad numbers ofpatientsandshort withsmall nature, andhaveanobservational trolled notcon low levelofevidencethestudies.Theyare tion in these patients is limited due tothe extremely administra cluded thattheassessmentriskofandrogen (9).However,recomended meta-analysiscon arecent diovascular functioninfemaletransexualspatientsis theevaluationofcar replacement, testosterone from andovariancancer(14). riskofbreast as increased insulin sensitivity, factors,aswell growth andincreased decreased sion, polycythemia,worseninglipidprofile, hyper-sexuality,of sleepapnea,aggressiveness, hyperten weightgain,onsetorworsening bolism, atherosclerosis, suchasacne,venousthromboem with adverseeffects, forfemaletranssexualpatientsmay beassociated terone toacceptthatthe useoftestos It isquitereasonable Side effectsofandrogenreplacement In the group oftransgenderwomenfollowedup In thegroup risksderived Based onthecombinedcardiovascular Optional: progesterone500mgIM2doses3-4daysaftertestosterone 4weeks desired effecttoonedoseevery Testosterone 2weeks, esters250mgIMevery reducein9-12mafter Testosterone 2-4weeks esters250mgIMevery Testosterone 240mg/d3doses Testosterone 2-3weeks cypionate200mgIMevery Testosterone 12weeks undecanoate1,000mgIMevery Testosterone cyclopentilpropianate100mgIMaweek Testosterone 3-4weeks esters250mgIMevery Testosterone 2weeks cypionate200mgIMevery 2-3 weeks Testosterone esters(cypionateorenanthate)250-400mgIMevery Testosterone undecanoate160mgaday Testosterone 2weeks esters250mgIMevery Arq Bras Metab. Endocrinol 2014;58/2 Regimens ------Arq Bras Metab. Endocrinol 2014;58/2 Table 3.Mostfrequentlyusedestrogensinhormonereplacement levels to fe testosterone 50-100 mg/day can reduce bindingtoitsreceptor,testosterone andinadoseof acetateblocks tible withthefemalesex. tolevelscompa­ oftestosterone and thesuppression ofmalesexual characteristics especially inthereduction shownintable3. placement therapyare dissatisfaction andabuseofdosagebypatients(17). sexualcharacteristicsislonger, leading to of secondary muscular injections,theperiodfordevelopment forintra thepreparations embolic events(16).With withthrombo 17β-estradiolreplacement transdermal duetothelowerassociationof isrecommended route male transsexualsover40yearsofage,thetransdermal However, route. the highercostoftransdermal for ). or synthetic(estradiolvalerate,estradiolbenzoate,and , and 17α 17β-estradiol), be natural (, can usedinthesepreparations Theestrogens terone. associatedornotwithproges and intravaginalforms includingoral,injectable, transdermal, preparations, sexualcharacteristicsinthesepatients. ondary toinducefemalesec isthechosenhormone Male transsexual subjects safe forfemaletranssexualstreatment. and anthate inadoseof200 mg biweeklywas effective en testosterone of intramuscularinjectionshort-acting another haddyslipidemia. and treatment; foundinone patient before ovaries were one patient had endometrial hyperplasia; polycystic unchanged; enzymesandbonemassremained (10). with supra-physiological levels of testosterone has been demonstrated that polycythemia is associated Ethinyl estradiol Conjugated Estradiol valerate Micronized estradiol Estradiol cypionate 17β estradiol 17β estradiol Estrogen type Anti- are used as adjuvants to estrogen, usedasadjuvantstoestrogen, are Anti-androgens re usedforhormone currently The mainestrogens themostwidelyused,dueto are Oral preparations estrogen isa large numberofpharmaceutical There wecanconcludethattheuse Based onourresults, Administration route Patch Oral Oral Oral Oral Gel IM Replacement dose 1.25-2.5 mg/d 100-200 μg/d 1.5-2 mg/d 2-4 mg/d 2-4 mg/d 3 mg/m 20 μg/d ------suppressed testosterone levelsand inadequate mam testosterone suppressed periodoftimeinspecialsituations,suchasnot short may beusedfor Doses higherthanthoserecommended intheworld (Tablecenters oftranssexualtreatment 4). that potentiate its action have been used in major drugs aloneorcombinedwith ofestrogens maceutical forms (15). rare very population are outcomes in this concluded that cardiovascular review literature comparison.Furthermore, being anindirect used,withthis women, aswellthetypeofestrogen thoseofmenopausal from different transsexuals are tomentionthatthecharacteristicsof it isimportant in postmenopausal women (20). On the other hand, cancer events,andbreast thromboembolic ease, stroke, dis heart theriskofcoronary combination increases However, parenchyma. sensitivity ofthebreast this the enlargement anddecrease TM toenhancebreast of inthetreatment fend theassociationofprogestins (19). Some authors de tors limit the dose of estrogen suggested especiallyinthosepatientswhomriskfac hasbeen effects of GnRHasanenhancerestrogenic male levelsintranssexualsubjects(18).Theuse there was a change in skin texture, decrease ofsponta decrease wasachangeinskin texture, there inmostpatients, development wassatisfactory Breast for a variableperiodoftime. out medicalsupervision with formulations prioruseofothersestrogen reported one acetateforanaverageperiod of11years.Allpatients 0.625 mg/dayassociatedwith50ofcyproter atadoseof our clinicuseconjugatedequineestrogens adverse sideeffects. toprevent lowest possibledoseofmedications,inorder shouldbeachievedwiththe also occurs.Theseeffects of testicular volume and decrease tion of aggressiveness, ofbodyfat,reduc ment. Skinsoftness,redistribution replace clinical signsofestrogen themostdesired are bodyhair anddecreased spontaneouserections creased implants. indicate breast and totheinitialdoseofestrogen this period,wereturn after growth isnobreast μg/d for6months.Ifthere suchasethinylestradiol35 potentestrogens, by more doseis doubled (1.25mg/day) or replaced estrogen of 50mg/day. growth, breast Incasesofinsufficient acetateatadose mg/day associatedwithcyproterone ata dose of0.625 use conjugatedequineestrogens development. mary Different therapeutic schemes using different phar therapeuticschemesusingdifferent Different Currently, the vast majority of patients followed in de nipplesandareola, Enlargement ofbreasts, The 150 male transsexuals followed in ourclinic Management oftransexuals 193 ------

Copyright© ABE&M todos os direitos reservados. Copyright© ABE&M todos os direitos reservados. 194 in thesecond year. This incidenceissignificant when when theincidenceofthisevent is2-6%fallingto0.4% duringthefirstyearoftreatment, bolism, particularly therapy inmaletranssexuals isvenousthromboem axisinmale transsexuals. tuitary-testicular thehypothalamic-pi insuppressing acetate iseffective atlowdosesinassociationwithcyproterone estrogens dailyuseoforalconjugated in 40%ofcases.Therefore, (<1.0U/L) suppressed cases, andtheFSHlevelswere (< 0.6-0.7U/L)in72%ofthe pre-pubertal levels were tal femalerange(<14-99ng/dL)inallpatients;LH 50%. Testicular inallcases. volumewasreduced andnipplein 97% ofcasesandenlargement oftheareola in ofbodyfathasbeenclinically observed redistribution The aggression. acetate) and decreased with cyproterone (especiallyafterassociation aswellitstexture growth, andinthespeedoffacial andbodyhair neous erections Adapted from: CostaandMendonça(30). Table 4. Proposedregimensforthetreatmentoffemaletranssexualsubjects Management oftransexuals Personal experience Texas, USA Gender Clinic, Universityof Texas Erlangen, Germany Department ofObstetricsandGynecology, ErlangenUniversityHospital, Munich, Germany Max-Planck-Institute EndocrinologyClinic Department ofEndocrinology, UniversityofBritishColumbia, Vancouver, New York,USA Division ofEndocrinology, MountSinai Liége, Belgium University ofLiége Psychoneuroendocrinology Unit Amsterdam, Netherlands Academic Hospital Vrije Univesiteit Treatment center The most disturbing side effect related to estrogen toestrogen related The mostdisturbingsideeffect Testosterone orintra-puber atpre- levelsremained Not reported Not reported Not reported Number of - - - patients 150 816 60 37 50 compared withtheincidenceofthiseventinover compared sexuals patients who developed prolactinomas (26). sexuals patients whodevelopedprolactinomas casesof male trans reported are There prolactinomas. levelssimilartothose found in andprolactin lactorrhea However, ofthesepatientshavega asmallpercentage lactin levels. Typically, is mild. increase the prolactin especially in patients over 40 years of age (25). trogens, shouldbegiven tonaturalorconjugatedes preference that theuseofethinylestradiolshouldbeavoided,and is recommendation (24).Thecurrent anti-thrombin thefactorVand factors,particularly thromboembolic disease,deficiencyof ence ofsmoking,cardiovascular significantlyinthepres increases taking estrogen (23). estrogens diol thannaturaloralortransdermal associatedwith ethinylestra transsexuals seemsmore eventsinmale This highincidenceofthromboembolic all youngpopulation(0.005to0.01%/year)(21,22). All patients on estrogen therapyhave elevatedpro All patientsonestrogen inpatients The riskofvenousthromboembolism Conjugated equineestrogens: 7.5-10mg/d Ethinyl estradiol: 100ug/d Goserelin acetate: 3-8mg/4week. +6mgestradiolvalerate necessary Medroxy-progesterone: 10mg/d2week/monthorcontinuous, if suppression : 100-200mg/dgradualincreaseuntiltestosterone : 0.625mg/dincreaseto5for34weeks Conjugated estrogens: 0,625-1,25mg/d testosterone : 100mg/dfor6-12muntillowerlevelof 17β-estradiol: 2-8mg/dafter1year Estradiol: 2weeks 80-100mgIMevery Cyproterone acetate Optional: spironolactone100-200mg/d 6 months Medroxy-progesterone acetate: 10mg/dford/monthduringthefirst Conjugated equineestrogens: 1.25-2.5mg/d Ethinyl estradiol: 100ug/d Cyproterone acetate: 50-100mg/d Optional: spironolactone: 100-200mg/d Estradiol benzoate: 25mg/week Conjugated estrogens: 1.25-2.5mg/d Ethinyl estradiol: 50-100ug/d Cyproterone acetate: 100mg/d 17b transdermalestradiol: 100ug2x/week Ethinyl estradiol: 100ug/d Arq Bras Metab. Endocrinol 2014;58/2 Regimens ------of estrogen caused a decrease inlevelsoftotalcholes causedadecrease of estrogen Arq Bras Metab. Endocrinol 2014;58/2 allowing the nextapplication ofinjectabletestosterone, shouldbeheldthedaybefore dosage oftestosterone evaluation ofthepelviswith endometrialecho.The andultrasound complete bloodcount,lipid profile, estradiol,liverenzymes, age ofLH,FSH,testosterone, largement oftheclitoris. atrophy, breast mass, bodyfatredistribution, anden body hair, muscle deepeningofthevoice,increasing months withevaluationofweight,bloodpressure, six every Clinical examinationshouldberealized Female transsexual subjects therapy. hormone monitoring oftranssexualsintocross-sex thefollowing ofthesepatients,wepropose treatment Based on15yearsofclinicalpracticeinthehormonal CROSS-SEX HORMONETHERAPY TRANSGENDER PATIENT MONITORINGDURING inourcohort. observed not cancerwere boneloss,andbreast in lipidprofile, dopamine . Elevated liver enzymes, alteration with with treatment lactinoma, which totally regressed inone case and two patients had macropro occurred also arrhythmia cardiac infarction, acute myocardial inonecase,patienthadan occurred thrombosis in10%ofcases,upperlimbvenous patients, observed inour wasthemostcommonsideeffect Depression acetate). conjugated+50mgcyproterone estrogen used(0.625mgequine withthetreatment side effects alowincidenceof follow-up of11years,weobserved our clinicwithanaverageageof34years,andamean therapy in150maletranssexualpatientsfollowedupat (29). intheliterature lated casesreported (28). tosterone bonelossinducedbydeprivationoftes and prevents bonemetabolism, transsexuals doesnotseemtoaffect cular outcomesinthesepatients(15). thecardiovas inconsistent andinconclusiveregarding ever, meta-analysisconcludedthattheworkis arecent B(27).How andapoprotein LDLcholesterol, terol, on estrogen therapy is extremely low, therapyisextremely on estrogen onlyiso are there Sosa and cols. observed that chronic administration thatchronic Sosa andcols.observed Laboratory evaluationshouldincludebiannualdos Laboratory hormone The evaluationoftheriskscross-sex cancerinmaletransse­ The incidenceofbreast inmale administrationofestrogens The chronic xuals ------for bonemassevaluation. between injections. intheinterval the analysisoflowestvaluereached age ofPSAshouldbeconductedannually. annually.performed blood count,coagulationfactors,andlipidprofile. liver enzymes, complete estradiol, prolactin, tosterone, ofLH,FSH,tes sixmonthswithmeasurement every andtesticularatrophy.redistribution, enlargement, involution ofbodyhair,breast bodyfat months withevaluationofweight,bloodpressure, six every Clinical examinationshouldbeperformed Male transsexual subjects 10. 9. 8. 7. 6. 5. 4. 3. 2. 1. 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