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http://dx.doi.org/10.1590/0004-2730000002923 Hirsutism; hypertricosis;hairgrowth;diagnosis;treatment Keywords Arq Bras Metab. Endocrinol 2014;58/2 fac factors, non-androgenic divided into androgenic feminine identity(1).The causes ofhirsutismmaybe self-image of the patient quality of life, andanimpaired lying diseases,andisoften associated withadecreased Itmaybelinkedtosignificantunder metic problem. thanacos andiscoarse.Hirsutismmore tion pattern H PATHOGENESIS OFHIRSUTISM se, fisiopatologia,diagnósticodiferencialeestratégiasdetratamento. periférico deandrógenosetratamentoscosméticos. A presenterevisãodiscutedefinição,patogêne do transtorno.Otratamentoincluialteraçõesnoestilodevida,supressãoandrógenos,bloqueio deexcesso decrescimentodospeloseafisiopatologia deveserbaseadononível do hirsutismo detumorovariano oudeadrenal.Otratamento ng/dLéaltamentesugestiva de testosterona>200 tismo possui a variedade idiopática, e o diagnóstico é feito por exclusão. Uma concentração sérica te importantes naavaliação doexcessodecrescimentopelos. A maioriadasmulherescomhirsu idiopático sãoascausasmaiscomunsdotranstorno.Ohistóricoeoexamefísicoparticularmen sensibilidade dofolículocapilaraosandrogênios. A síndromedosovários policísticoseohirsutismo teração entreasconcentraçõesdeandrógenoscirculantes,locaisea causa. refleteain A condiçãoestágeralmenteassociadacom aperdadeautoestima.Ohirsutismo éumproblemaclínicocomum emmulheres,eotratamentodependeda masculino. Ohirsutismo de andrógenos no corpo de mulheres, com crescimento em um padrão de distribuição tipicamente édefinidocomooexcessodecrescimentoterminalpelosemáreasdependentes O hirsutismo RESUMO fferential diagnosis,diagnostic strategies,andtreatment. and cosmetictreatments. The current reviewdiscussesdefinition,pathogenesis,physiopathology, di disorder. Treatment includeslifestyletherapies,androgensuppression,peripheralblockage, based onthedegreeofexcesshairgrowthpresentedbypatientandinpathophysiology ofthe ofadrenalorovarian tumor. ng/dLishighlysuggestive level >200 Treatment shouldbe ofhirsutism havetheidiopathicvariety,with hirsutism andthediagnosisismadebyexclusion.Serum examination areparticularly important inevaluating excesshairgrowth. The vastmajorityofwomen arethemostcommoncausesofcondition. idiopathic hirsutism A woman’s historyand,physical ofthehairfollicletoandrogens.Polycysticgen concentrations,andthesensitivity syndromeand reflectstheinteractionbetweencirculatingandrogenconcentrations,localandro -esteem. Hirsutism women, andthetreatmentdependsoncause. The conditionisoften associatedwithalossofself women, which growsinatypicalmaledistributionpattern. isacommonclinicalproblemin Hirsutism terminalhairgrowth inandrogen-dependent areas ofthebodyin is definedas excessive Hirsutism ABSTRACT Alexandre Hohl Hirsutismo: diagnósticoetratamento Hirsutism: diagnosisandtreatment body inwomen.Hairappearsamasculinedistribu Hirsutismo; hipertricose;crescimentodepelos;diagnóstico;tratamento Descritores Metab. 2014;58(2):97-107 growth in -dependent areas ofthe areas inandrogen-dependent growth irsutism isdefinedasexcessiveterminal 1 , Marcelo Fernando Ronsoni 1 , MônicadeOliveira Arq BrasEndocrinolMetab. 2014;58(2):97-107 - - - - ized or localized growth of vellus type (non-terminal) of vellustype(non-terminal) ized orlocalized growth Usually,of . general presents generalized nonsexual distribution and is independent in a hairgrowth sis, whichischaracterizedby increased hirsute women. about70-80%of (PCOS),whichaffects syndrome ry than 80%ofpatients,andincludepolycysticova more causesaccountfor whileandrogenic rare, relatively are factors tors, and idiophatic hirsutism. Non-androgenic Hirsutism must be distinguished from hypertricho Hirsutism mustbedistinguished from 2 Arq BrasEndocrinol ------Pernambuco, Recife, PE,Brazil Florianópolis, SC,Brazil (HU-UFSC), Catarina Santa Universidade Federal de 2 1 Accepted onNov/26/2013 Receivedon Aug/10/2013 [email protected] 88015-200 –Florianópolis,SC,Brazil Av. RioBranco,404/704,torre 1 Alexandre Hohl Correspondence to: Instituto deMedicinaIntegral Universitário, Hospital review 97 - - -

Copyright© ABE&M todos os direitos reservados. Copyright© ABE&M todos os direitos reservados. Hirsutism 98 oftime cle size,hairfiber diameter, andthe proportion hairfolli involved inkeratinization,increased They are hairfollicleorasebaceousgland. into eitheraterminal ofpilosebaceousunits ment, andcausedifferentiation hairandsebaceous glanddevelop forterminal essary nec modulation.Theyare associated withhairgrowth themostsignificanthormones are women. Androgens hairoccursinhirsutism ing ofvellushairtoterminal transition occur inpathologicalstates,andabnormal and folliclesmayalso ing betweenterminal hair. stimulatedtobecometerminal eas are Transition after . Duringpuberty, ar vellushairincertain cycle,mainly inthehairgrowth role plays animportant diameter, pigmentedandcoarseintexture. –longerhair,diameter; terminal atleast0.06mmin ally non-pigmentedandgenerallylessthan0.03mmin vellus –softhair, usu butlarger thanlanugo.Theyare life; disappears withinthefirstmonthsofpost-partum soft hair densely covering the skin of thefetus,which (4,5). the hairfollicletoandrogens concentrations,andthe sensitivityof local androgen concentrations, androgen teraction betweencirculating thein Hirsutismreflects androgens. tors, particularly fac to numerous type ofhaircanchangeinresponse ge overanindividual’slifetime,butthefolliclesizeand The numberofhairfolliclesdoesnotsignificantlychan A large numberofhairfolliclescoverthehumanbody. PHYSIOPATHOLOGY (3). andevenparaneoplasticsyndrome thyroidism, hypo tuberculosis, trition, juveniledermatomyositis, malnu nervosa, disease, includingporphyria,anorexia trichosis canalsooccurinpatientswithsomesystemic months after discontinuing themedications. Hyper within weeksor canusuallybetreated hypertrichosis acid,andheavymetals(2).Inthesecases, cin, valproic streptomy mine, phenothiazines,,reserpine, poisoning,,penicilla methyldopa, mercure metoclopramide, sporine, diazoxide,, cyclo clude acetazolamide,citalopram,corticotrophin, in Thesedrugs isassociatedwithhypertrichosis. drugs Alonglistof mayaggravatetheproblem. drogens Despitethis,an it isnotcausedbyexcessandrogen. mentioned, but,aspreviously non-endocrine disorders, factors,ormetabolic other hereditary use ofdrugs, hair overthebody. the from canresult Hypertrichosis Depending upon the body site, hormonal regulation regulation Depending uponthebodysite,hormonal Structurally, typesofhair:lanugo– three are there ------circulatory androgens, as well as other hormonal vari aswellotherhormonal androgens, circulatory andvariabilityinend-organ sensitivityto of androgens but alsoonlocalfactors,suchasperipheralmetabolism concentration, androgen depend solelyoncirculatory thefollicledoesnot from stimulation ofhairgrowth hairspendsintheanagen phase(4).However,terminal the isthmus, and the dermal papilla migrates from with papillamigratesfrom the isthmus,anddermal toward ofthehairfollicletractsupward deepest part ceases. The and hair production regresses, hair(5). maximumlengthofeyebrow short anagenphaseaccountsfor therelatively abbreviated months.The and hasananagenphaseoftwotothree onlyatarateof0.1mmper day hairgrows eyebrow twotosixyears.Incontrast, anagen phaserangesfrom 0.3mmperday,approximately andthedurationof hairis rateof terminal phase. Onthescalp,growth intheanagen ofhairfolliclesonthescalpare percent the longestanagenphaseandatanygiventime,90 with thetypeofhairandlocation.Scalpfollicleshave andtheduration of anagenvary rate ofhairgrowth years.The phaselaststwotothree period, thegrowth Usually intheanagen maximum lengthofhairgrowth. the anddetermines bodyregions hair cycleindifferent quiescence. orrelative gen –aperiodofrest telo involution, with a apoptosis-mediated regression; catagen –aperiodof gen –aperiodofrapidgrowth; periods:ana different which ischaracterizedbythree containingcellsofmultiplecelllineages(7). tory events. Thehairfolliclefunctionsasastemcellreposi andtissue-remodeling regression, growth, repetitive for haircycling.Thecycleconsistsofrhythmic mously withamolecularoscillatorsystemresponsible organ. Itisacomplexorgan thatfunctionsautono (6). ables, suchasinsulinresistance tween 50 and 150 telogen are shedperday.tween 50and 150telogenhairsare Hair inthetelogenphase.Typically,scalp folliclesare be months onthescalp.Normally, of upto10percent follows thecatagenphase and lastsfortwotofour follicles onthescalpisin catagenphase(5). of weeks.Lessthan1percent twotothree ally around the bulge.Thedurationofcatagenonscalpisusu tolienear papillaisrelocated catagen phase,thedermal ofthe epithelialcolumnduringthe lowing regression Fol dermis. in thesubcutaneousfatintoreticular During the catagen phase, the lower portion ofthe During thecatagenphase,lowerportion the Thedurationoftheanagenphasedetermines life,hairfolliclesundergo cycling, Throughout Hair originatesinthehairfollicle,ahighlydynamic The telogen phase, also known as the resting phase, The telogenphase,alsoknown astheresting Arq Bras Metab. Endocrinol 2014;58/2 ------Arq Bras Metab. Endocrinol 2014;58/2 Other causes must be excluded, such as , tumors(11). plasia (CAH),andandrogen-secreting hyper to patients with hirsutism: congenital adrenal intheapproach should beconsidered cess disorders and/or polycysticovarianmorphology. dysfunction togetherwithovulatory phology; classicPCOS–clinicaland/orbiochemical ovarianmor cycles, and normal ovulatory with normal –patientswithhyperandrogenism, hyperandrogenism ;idiopatic cycles,andnormal ovulatory normal androgens, circulating tients withhirsutism,butnormal manifestations suchas(9,10):idiopatichirsutism–pa phenotypesofwomenwithhirsutismby guish different todistin itisnecessary cases ofhirsutism.Therefore, tumors. drogen-secreting andneoplasms, suchasan tion, Cushingsyndrome, dysfunc hyperplasia,thyroid such asPCOS,adrenal evaluation is focused on testing for endocrinopathies, tomedicationuse, tients whose condition is not related variables,suchasinsulinresistance. by otherhormonal and by thesensitivityoftarget tissuestoandrogens, influenced bytheperipheralmetabolismofandrogens, levels, butitisalso androgen circulating only reflects mentioned, because hirsutism not ppens, as previously excess (8). It ha poorly with the severity ofandrogen pilosebaceus unit, the severity of hirsutism correlates action at the quivocal markerofexcessive androgen seriouscondition.Althoughhirsutism isanune more etiology, mainlybecauseitmaybethefirstsignofa the exact However, todetermine process. itiscrucial Most commonly, ofabenign hirsutismistheresult CAUSES cycle. growth in justifying the perpetual rhythm of the important are (4,5).Theseandotherfactors wingless-type proteins factor,cyte growth and bonemorphogenicproteins, factor, growth factorβ,fibroblast growth keratino factor-I, suchasinsulingrowth growth, transforming alotofmolecularmechanismsinvolvedinhair are there Furthermore, bythesamehormones. affected that are ofthebody areas indifferent inhairgrowth erogeneity telogen phase,andthenextcycleistheninitiated(5). thehairshaftandshedatendof from is released Experts also suggest that two more androgen-ex alsosuggestthattwomore Experts As mentioned,functionalcausesaccountformost Many medicationscanalsocausehirsutism.Inpa het for important Gene transcription is responsible ------idiopatic hirsutism).Itisoftenduetoanethnicorfa of8-15have score all womenwithaFerriman-Gallwey common inmild hirsutism cases(one-halfof is more levels. It androgen ovulationandnormal with regular dysfunction. andthyroid hyperprolactinemia, Cushing syndrome, ovulation, b)clinicalandorbiochemicalsignsofhyper criteria: a)oligo-an at leasttwoofthefollowingthree encompassing seenasasyndrome PCOS iscurrently women. ofreproductive-age fecting 4to12percent ofallcases(12)andaf counting for72to82percent function. receptor the androgen and/orachangein by5-α-reductase drotestosterone to dihy peripheral conversion of testosterone increased toexplainidiopatichirsutismbyan Some authorstry cases. Itmustalwaysbeadiagnosisofexclusion(12). ofhirsutism milial trait,andaccountsfor4to7percent with PCOS. However, CAH is diagnosed at birth by with PCOS.However, by CAHisdiagnosed atbirth those en with non-classical congenital hyperplasia from no clinicalsymptomsthatconsistently distinguishwom are of phenotypes. There in a spectrum defect, resulting biosynthesis totheseverityofandrogen according manifestations ofthisdisease different are mones. There hor steroid synthesis andaccumulationofandrogen bio ofcortisol leadingtoimpairment 21-hidroxylase, gland.Themostcommonisadefectin in theadrenal synthesis matic deficiencies involved in steroid “lossoffunction”enzy todifferent sified according synthesis pathway. clas isfurther disorder Thisbroad intotheandrogen precursors synthesisdiverts cortisol stimulationtest,becauseadefectinadrenal cotrophin andafteracorti levelbefore 17-hydroxyprogesterone and Slavicpeople.Itischaracterizedbyanelevated suchasAshkenaziJews, Hispanics, risk ethnicgroups, high- common in certain and it is more sive pattern, Itisinheritedinanautosomal reces perandrogenism. causeofhy hirsutism. Itisthemostcommonadrenal hirsutism cases(12). of explainable causes.Itaccountsfor6to15percent nography, levels without other and elevated androgen ovaries onultraso menses,normal woman hasnormal central , andacanthosisnigricans. also includesdysfunctionaluterinebleeding,infertility, in women with this condition of findings observed tern andc)polycysticovaries.A commonpat androgenism, Idiopatic hirsutismisdefinedasinpatients PCOS isthemostcommoncauseofhirsutism,ac CAH accounts for 2 to 4 percent of the cases of ofthecases CAH accountsfor2to4percent occurs when the Idiopatic hyperandrogenemia Hirsutism 99 ------

Copyright© ABE&M todos os direitos reservados. Copyright© ABE&M todos os direitos reservados. Hirsutism per centofhirsutismcases.Itmust,however, bere 100 alter management oroutcome.Testing ofandrogen thatwould likelihood ofidentifyingamedical disorder tests,andbecauseofthelow conventional laboratory 50%ofthesecasesusing undetectable inapproximately is 8-15), since hyperandrogenemia sutism (FG score levels amongwomenwithmildhir androgen creased againsttestingforin Endocrine Societyrecommends tour, shouldalsobenoted (14). of thehaironscalp),andlossfemalebodycon thinning andvertex alopecia(fronto-temporal pattern tion, includingclitoromegaly, deepeningvoice,male- ominoussignsofviriliza More pecia, andseborrhea. alo ,female-pattern excess, includingrecalcitrant forotherassociatedmanifestationsofandrogen search and diagnosisismadebyexclusion(14). of womenwithhirsutismhavetheidiopathicvariety, physiologic andpathologichirsutism.Thevastmajority isnoabsoluteclinicaldistinction between because there inwomen, inevaluatingexcesshairgrowth important justifyingit. disorder isanendocrinologic ifthere sessment istodetermine ofhirsutism, clinicalas inconvenience ofthepresence Although mostwomenseekmedicalattentionforthe DIAGNOSIS withisolatedhirsutism. rare also are levels.Hypo/hyperthyroidism evated infertility, amenorrhea, galactorrhea, presents andel oftenfound.Hyperprolactinemia are bolic impairment purple skinstriae,muscularweakness,acneandmeta cases,centralobesity,In Cushingsyndrome moonface, present. anddeepenedvoiceare ment, , handandfootsize,mandibularenlarge ing, increased sutism. Usually, boss suchasfrontal clinical features, occurs with isolated hir rarely hirsutism. Acromegaly levels(12). ten causesignificantelevationinandrogen orovarianinorigin,andof Neoplasms maybeadrenal ism, virilizationorapalpableabdominalpelvicmass. isarapidonsetofhirsut wheneverthere membered symptoms when womendevelophyperandrogenic asymptomaticuntilafterpuberty,cal casescanremain ambiguous genitaliaandsalt-wasting,whilenon-classi Androgen-secreting tumorsaccountforonly0.2 Androgen-secreting A recent clinicalpracticeguidelinepublishedbythe A recent to Once hirsutismhasbeenidentified,itisprudent particularly andphysicalexamare Family history lesscommoncausesof Other endocrinophatiesare (13). ------levels is recommended inwomen with moderatetose levels is recommended Table 1. relatedtohirsutism(16) Focusedhistory (15,16). or clitoromegaly irregularity,strual centralobesity, acanthosisnigricans, when itisassociatedwithanyofthefollowing:men or ism whenitissuddeninonset,rapidlyprogressive, ofhirsut hirsutismandinwomenwithanydegree vere A: ogntl dea hprlsa HI-N hprnrgns, nui rssac, and resistance, acanthosis nigricans;PCOS: polycysticovariansyndrome. hyperandrogenism, HAIR-AN: hyperplasia; adrenal congenital CAH: Medications Family history • • • • • • • • Menstrual history Associations illness onset ofpresenting History History Cushing’s syndrome Thyroid dysfunction tumor Adrenal orovarian tumor Pituitary Hyperprolactinemia hyperplasia congenital adrenal Late-onset HAIR-AN PCOS – – – Glucocorticoids – – – – – – – – – – – – – – – – – – – – Progression – – Onset Valproic acid–raisesplasmatestosterone Androgen therapy(testosterone) Anabolic steroids() (, , norethindrone) Oral contraceptiveswithandrogenicprogestins before 30yearsofage disease, lateonsetCAH, male-patternbalding alopecia, typeIIdiabetes, cardiovascular Hirsutism, PCOS, androgenetic(patterned) susceptibility toinfections fatigue, excessivethirst, increased weakness inrisingfromsittingorcombinghair, bruising, thin/fragileskin, weightgain, Mood orsleepdisturbance, striae, easy , weightchange, texturalskinchanges Hot orcoldintolerance, tremors, diffusescalp deepened voice, clitoromegaly Symptoms ofvirilization: increasedlibido, Visual disturbance, headache expressible) ofgalactorrhea(spontaneousor History menstrual irregularities, amenorrhea primary Onset pre-puberty, prematurepubarche, ofhypertensionorhyperlipidemia History intolerance Polydypsia/polyuria relatedtoglucose Weight gain, acanthosisnigricans ofhypertensionorhyperlipidemia History intolerance Polydypsia/polyuria relatedtoglucose Weight gain, acanthosisnigricans reproductive history ofoligomenorrhea,History amenorrhea, Acne, androgeneticalopecia, seborrhea Treatments todate/management Psychosocial impact Sites involved Arq Bras Metab. Endocrinol 2014;58/2 Clinical data - - - Arq Bras Metab. Endocrinol 2014;58/2 Figure 1. Modified Ferriman-Gallwey (F-G)hirsutismscoringsystem (18) © isaqualita score tism. ThemodifiedFerriman-Gallwey toexcludepathologiccausesofhirsu gh information enou andphysicalexamoftenprovide Detailed history Physical exam weight gain,hypertension. acne, associated withhirsutism,suchasgalactorrhea, ofothersymptoms of ;Medication;presence orabsence ity andcourseofbodyweight);presence livinghabits(diet,physicalactiv of hypercortisolism; ofhirsutismorotherfindings ethnicity); familyhistory ethnicity(distributionbynaturalduetotheir history; andmenstrual of symptoms(diseasecourse);menarche thefollowingtopics:timeofonset mainly addressing gain orafterdiscontinuingoralcontraceptives(17). berty, afterweight secretion androgen withincreasing ration. Non-neoplastichirsutismisusuallyseenatpu history, andmedication,shouldbetakenintoconside factors,suchasapatient’sage,ethnicity,History family Clinical history Ricardo Azziz, 1997. The history shouldbeascompletepossible, The history ------because of the somewhat subjective nature oftheas because ofthesomewhatsubjectivenature (14).Thisscoringsystemhaslimitations by Ferriman include acanthosisnigricans(suggestiveofinsulinre shouldalsobetaken (16). Skinfindingscan reading and body mass index (BMI) calculated. Blood pressure (17). logic examinationismandatory orlocalizedlossofhair, adermato ordiffuse secretion, suchasacne,excessive sebum pilosebaceous responses, theirhair(17). have cosmeticallyremoved ofevaluatingwomenwho sessments andthedifficulty defined bythe95 of≥8typicallyindicateshirsutism,as ble, butascore of 36 is possi evaluated. A maximum score body part visible)foreach visible) tofour(extensivehairgrowth hairgrowth (noexcessiveterminal zero ranging from and thigh), with scores abdomen, lower abdomen, arm, (upper lip,chin,chest,upperback,lower bodyparts This scoringsystemevaluatesninedifferent 1). inwomen(Figure areas nine androgen-dependent in tive toolforevaluatingandquantifyinghairgrowth The patients’ height and weight should be recorded, The patients’heightandweightshouldberecorded, levelsmayalsoleadto androgen Because increased th percentile ofdatainitiallycollected percentile Hirsutism 101 - - - -

Copyright© ABE&M todos os direitos reservados. Copyright© ABE&M todos os direitos reservados. Hirsutism 102 demonstrated thatthe diagnosis of hyperandrogenism infemales(21).Somestudieshave testosterone free totaland available methods of measuring serum rently technical limitationsforthecur are level (16). There oral contraceptives will have a falsely lower testosterone tumors (14). Patients taking most androgen-producing levelscandetect ofthesetwohormone measurement cycle)andDHEAS,becausethe ten ofthemenstrual (ondaysfourto testosterone disease includeserum teststoexcludeaseriousunderlying Initial laboratory evaluation Laboratory diagnosedwiththeseconditions(19,20). are womenwho andtoadequatelytreat anxiety disorders, allwomenwithPCOSformoodand need toscreen the These data underscore the healthburden. creasing coexist,in number ofpatients,somethesedisorders andpanicdisorder.sessive-compulsive disorders, Ina suchassocialphobia,ob of otheranxietydisorders, disorder. dataexaminingtherisk isinsufficient There also at risk forsymptomsofgeneralizedanxiety are Women anddepression. ism orinfertility withPCOS tween variables, suchas biochemical hyperandrogen Similarly, islimiteddataon the associationbe there unclear. iscurrently acne, bodyimage,anddepression lated qualityoflife,theassociationbetweenhirsutism, thehealth-re affect ofhyperandrogenism cal features independentofBMI. Although clini risk ofdepression andahigher scores with PCOShavehigherdepression inwomenwithPCOS.Womenders hasbeenreported (17). considered sary, additionalcounseling orpsychotherapyshouldbe should also be evaluated. If neces morphic disorder life behavior, and life-events, and signs of body dys drive). Feelingsofdisgust,changesinsexualactivity, lossofenergy,sion (suchassleepingdifficulties, and life changesandexaminedforsymptomsofdepres uation ofvisualfielddefectisimportant. tumor mass (16). Eval to exclude an ovarian oradrenal muscle mass.Theabdomenandpelviscanbepalpated ened voice,clitoromegaly, atrophy, breast andincreased for signsandsymptomsofvirilizationincludingdeep alopecia (16). (patterned) andandrogenetic on theskin),seborrhea, cystsandnodules oftherapy-resistant formation strual ispremen ifthere sistance), acnevulgaris(particularly Recently, ahigherriskofmoodandanxietydisor Patients shouldalsobeaskedaboutquality-of- Clinical examinationshouldalsoincludeevaluation ------of testosterone alone. These studies recommended in alone.Thesestudiesrecommended of testosterone usedinstead (CFT)were testosterone calculated free index(FAI)or androgen was mostobviouswhenfree hormone (LH) and decreased follicle-stimulatinghor (LH)anddecreased hormone (>50ng/dL),withelevated luteinizing testosterone free CAH. PatientswithFOHgenerallyhaveincreased [50-300 nmol/L])isseeninwomenwithlate-onset (5,000-10,000ng/dL vated 17-hydroxyprogesterone of hirsutism. An ele­ these functional sources differentiate (CAH). Asecondstageofdiagnostictestingcanhelp hyperplasia (FOH) and late-onset congenital adrenal in functional ovarian hyperandrogenism often present cause ofhirsutism(14). shouldbesuspectedasthe source one level,anadrenal testoster serum despiteanormal 700 μg/dLispresent likely. ismore an ovariansource IfaDHEASlevel> DHEASlevel, is elevateddespiteanormal tosterone orovariantumor.suggestive ofanadrenal tes Ifserum (21). randrogenism toclinicalorbiochemicalhype related with disorders investigationandassessmentofwomen in theroutine cluding thesecalculatedparameters(CFTand/orFAI) pectations toward treatment should be addressed. She shouldbeaddressed. treatment pectations toward the pathophysiologyof disorder. Thepatient’s ex bythepatientandin presented of excesshairgrowth Treatment ofhirsutismshouldbebasedonthedegree TREATMENT disorder. of pituitary issuspicion ifthere systemmaybeperformed nervous or signsofvirilization(17).Animagethecentral and/ amenorrhea ifapatientpresents exam isnecessary (14).Apelvic oplasm ishelpfulinguidingtreatment thelocationof ne diagnostic imaging to confirm or ovarian neoplasm is suspected, When an adrenal Imaging (17). treatment initiatingany outbefore shouldberuled menstruation, (17). Inwomenwithabsentorirregular to exclude Cushing syndrome test should be performed (14).Ifsuspected,24-hour urinecortisol thyroidism andhypo hyperprolactinemia obtained todifferentiate functiontestsshouldbe levelsandthyroid prolactin mone (FSH)(FSH:LH=1:2or1:3)(14). Mildly elevated serum testosterone and DHEAS are andDHEASare testosterone Mildly elevatedserum level>200ng/dLishighly testosterone A serum In the presence of both amenorrhea andhirsutism, ofbothamenorrhea In thepresence Arq Bras Metab. Endocrinol 2014;58/2 ------Arq Bras Metab. Endocrinol 2014;58/2 iftheyare particularly syndrome, with polycystic ovary inwomen first-linetreatments Lifestyle therapiesare therapies Lifestyle Non-pharmacological methods therapyissuggested. tion ofpharmacologic methods,theaddi genemia whochooseshairremoval hair. foranywoman withknownhyperandro Therefore, oftheexcess metic solutionsforeliminationorreduction due to the condition. They seek cos lower values suffer isaboveeight,manypatientswith the sethirsutismscore However, score. modified Ferriman-Gallwey although basedon ofhirsutismscore takes intoaccountthedegree tween cosmeticmethods(,plucking,). be ming less intense, and demanding longer intervals butitcanbemitigated,beco treatment, with thedrug thatcompleteeliminationisunlikely should beaware hormone; T4:thyroxine. thyroid-stimulating TSH:imaging; resonance magnetic MRI: tomography; CT:ratio.computed * Table 2. Laboratory testing for androgen excess in women with hirsutism (16)

Absolute luteinizing hormone (LH) and follicle-stimulating hormone (FSH) values and LH/FSH and values (FSH) hormone follicle-stimulating and (LH) hormone luteinizing Absolute – – – – – tests Ancillary – – – Imaging – – – – – – – – – – – Extensive evaluation – – – – – Simple screeningtests TSH, T4, antimicrosomalantibodies Potassium levels(Cushing’s syndrome) Lipid panel Oral glucosetolerancetest Fasting bloodglucose Transvaginal ultrasound Cranial MRI CT/MRI abdomenorpelvis Serum B-humanchorionicgonadotropin hormone analogue Combined stimulationtest: corticotrophinandgonadotropin-releasing Serum adrenocorticotropichormonelevel Dexamethasone suppressiontesting cortisol 24-hour urinary-free Serum prolactin Serum estradiol Luteinizing hormonelevel* Follicle-stimulating hormonelevel* level Sex hormone-bindingglobulinlevel 17-OH-progesterone level Dehydroepiandrosterone sulfatelevel Testosterone-sex hormone-bindingglobulinratio(freetestosterone) Testosterone level(totalandfree) Most of the literature on the treatment of hirsutism ofhirsutism onthetreatment Most oftheliterature - - - - - therapy may be needed to prevent recurrence. Thetre recurrence. therapy maybeneededtoprevent follicles have a half-life of up to six months and lifelong to sixmonthsaftertherapyhasbegun,becausehair foratleastthree not toexpectimprovement warned Women scores. in theirFerriman-Gallway shouldbe globulin,and animprovement sex hormone-binding in anincrease oftestosterone, including areduction intheirbiochemicalprofile, a significantimprovement oftheirinitialbodyweighthave thanfivepercent more whomanage tolose syndrome with polycysticovary (22).Ithasbeenshownthatobesewomen overweight supplement to drug therapy(17). supplement todrug either alone orasa andtheiruseisreasonable effective, visible (shaving, plucking, waxing, bleaching) can be hairormaking it less Physical methodsof removing methods Cosmetic not required. testingis andfollow-uphormonal hirsutism scores, in canbeassessedbyimprovement atment response sutism (15). therapyforhir tobeaneffective notconsidered are after sixmonthsoftherapy. Insulinloweringagents issuboptimal isadded iftheclinicalresponse drogen for themanagementofhirsutism;ananti-an of drugs tobethefirstline considered Oral contraceptivesare Pharmacologic management therapy(17). withpharmacologic drogens endogenousan bysuppressing This canbeprevented stimulation ofhairfolliclesbyendogenousandrogens. becauseofthecontinued to experiencehairregrowth likely are women withunderlyinghyperandrogenemia canbeachievedeachsession.However,to 40percent isusuallyfinerandlighter,growth reduction of10 anda notsuitableforlaser. andwhitehairsare red, Hairre blond, optimal target isdarkhaironfairskin,whereas number ofsessions, fluence, and haircolorintensity. The wth temporarily, dependonthe results butpermanent hairgro Alloftheseinterrupt and pulsedlightsources. ser, 800-nmdiodelaser, and1064-nmNd: YAG laser the755-nmalexandritela techniques. Mostlyusedare hairreduction toas“permanent” alsoreferred light), are andphotoepilation(laser intensepulsed electrolysis including ormechanicalmethodsofhairremoval, Direct reduction hair Permanent Hirsutism 103 ------

Copyright© ABE&M todos os direitos reservados. Copyright© ABE&M todos os direitos reservados. Hirsutism 104 with treated of childbearing agewhoare Women spironolactone. hyperkalemia shouldnotreceive sion andhyperkalemia(23). Women or failure withrenal and,rarely, effect clude amilddiuretic postural hypoten in ofspironolactone Sideeffects cycle regulation. strual andmen prevention pregnancy actions, andOCensures anti-androgenic gether, havecomplementary thesedrugs hirsutismwhencombinedwithOC,because,to treating in effective ismore above 100mg(17).Spironolactone atdoses thesetendtoincrease ated, withfewsideeffects; 50-200 mg daily (14). It is usually well toler are istered typicallyadmin biosynthesis.Dosesthatare in androgen receptor, to theandrogen andinhibitsenzymesinvolved (DHT) for binding competes with dihydrotestosterone It similar to progestins. tor antagonist that is structurally ponse issuboptimalaftersixmonths. in womentakingoral contraceptives asacosmeticres therapy. theadditionofananti-androgen Furthermore, formono maybeconsidered method, anti-androgens contraceptive usingareliable not conceive,orwhoare However,male fetusintheuterus. inwomenwhocan onadeveloping because ofthepotentialadverseeffects hirsutism, theiruseisnotsuggestedasmonotherapy therapyfor aneffective are Although anti-androgens therapy Anti-androgen thatitmightworsenhirsutism. because ofconcerns shouldbeavoided progestin, themostandrogenic estrel, Intheory,tate ordrospirenone. OCscontaining levonorg ace suchascyproterone orananti-androgen, drogenicity continuously. withlowan Oneshouldchooseaprogestin unlessadministered toasomewhatlesserdegree, drogens an serum suppress 20 mcgethinylestradiolformulations contains 30to35mcgofethinylestradiol.Thelowerdose pment ofendometrialhyperplasia(15). thedevelo theadditionalbenefitofpreventing provide contraceptives women withPCOS,-progestin nefits suchascontraceptionandcyclemanagement.For additional non-hirsutism be also provide preparations These to be effective. also considered are preparations contraceptive andvaginalestrogen-progestin dermal oralcontraceptivestudies,buttrans primarily from tin contraceptivesasinitialtherapy. datacomes Efficacy therapy,pharmacological wesuggestestrogen-proges For themajorityofwomenwithhirsutismwhochoose (OC) contraceptives Oral Spironolactone that OC therapy is usually begun with a formulation is an aldosterone and androgen recep andandrogen is analdosterone ------risk offeminizationamalefetus(14). tive contraceptionbecauseofthepossible should useeffec and 7.5 mg/d. There are no reported serious complica no reported are and 7.5 mg/d. There dosesrangebetween5 and type2enzymes.Standard activityinhirsutisminvolvesboth thetype1 reductase becausetheenhanced 5-alpha- for excesshairgrowth, occurswhenused effect inhibitory one. Onlyapartial todihydrotestoster testosterone enzyme thatconverts (17). in women who have a uterus bined with activity,ties. Becauseofitsprogestin itneedstobecom irregulari inliverfunctionandmenstrual abnormalities andcancause CPAestrogen. sideeffects hassteroidal a higherdose(50to100mg)asmonotherapyorwith componentofOC,orin dose (2mg)astheprogestin concentrations.Itisusedinalow and ovarianandrogen LH serum andreducing receptor ing totheandrogen derivative,anditcompeteswithDHTforbind terone dence of androgen secretion inanygiven case(23). secretion dence ofandrogen dependence orindepen in documentinggonadotropin hirsutism.Theycanbeuseful ovarian androgen-related usedalonetotreat rarely ason, GnRHsuperagonistsare re beneficial. Forthis are of estrogen sutism, theeffects hir not thecasewithhirsutism. Infact,whentreating ofendometriosisorleiomyomata.Thisis the treatment such as in the cause of the problem, are and progestin ofestrogen atment isespeciallyusefulwhentheeffects ted withalong-actingGnRHsuperagonist.Thistre elimina canbeeffectively secretion Ovarian hormone agonist GnRH 1 mgofCPA. aloneisnotavailable(17). or 25 mg of spironolactone equivalent to approximately with ethinylestradiolinoralcontraceptives(3mg)is Thedoseused weakanti-androgen. ceptives. Itisavery nausea,andvomiting(17). skin,diarrhea, include dry frequently. thathavebeenreported Othersideeffects transaminasesshouldbemeasured serum albeit rare, (23). Becauselivertoxicityisapotentialsideeffect, 250-750 mg/d hirsutism. Theusualdoserangesfrom formanaging tate cancer, buthasbeenusedoff-label tagonist. It is used primarily in the management of pros asfeminizationofthemalefetuscan occur(14). sures, mea control this medicationwithoutadequatebirth (23). Women of childbearing potential should not use of hirsutism tions withthismedicationinthe treatment acetate(CPA)Cyproterone inhibits type 2 5-alpha-reductase, the Finasteride inhibitstype25-alpha-reductase, Drospirenone is a progestin used in some oral contra is a progestin Drospirenone Flutamine is a nonsteroidal androgen receptor an receptor androgen is anonsteroidal Arq Bras Metab. Endocrinol 2014;58/2 is a 17-hydroxyproges ------Arq Bras Metab. Endocrinol 2014;58/2 hormone. Adapted from: Bode and cols. (2) and Alonso and Fuchs (4). GI: gastrointestinal; NSAIDs: non-steroidal anti-inflammatory drugs; ACE: angiotensin-converting enzyme; Gn-RH: gonadotropin-releasing Table 3. Medicationsusedinthetreatmentofhirsutism(18) ens (17). biologically activeandrog and free circulating ducing insulin levels and, therefore, hirsutism by re Insulin-sensitizing agents may improve drugs Insulin-lowering contraceptives Oral Anti-androgens Class ofDrug Glucocorticoids GnRH agonist agents Insulin-lowering drospirenone Ethinyl estradiolwith diacetate norethindron,ethynodiol , norgestimate, Ethinyl estradiolwith Spironolac-tone Finasteride Prednisone Dexametha-sone Leuprolide acetate Drug Generalized hirsutism hirsutism Moderate orsevere hirsutism Moderate orsevere Severe hirsutism Hirsutism severe hirsutism Gn-RH agonistsfor contracep-tives or combined withoral hyperplasia, maybe Congenital adrenal contracep-tive Alternative tooral ovary syndrome ovary Hirsutism, polycystic Indication pill-free interval days, followedby7-day One tabletperdayfor21 50-200 mg/day 5-15 mouth atbedtime, days: Maintenance: 50mgby 5-15 mouth atbedtime, days: Induction: 50-100mgby times daily 125-250 mg, twotothree 5 mgdaily mg bymouthatbedtime nightly, prednisone 5-7.5 Dexamethasone 0.5mg oestradiol 25-50 mcgtransdermal intramus-cularly, with 7/5 mgmonthly day) (maximal dose2.0-2.5g/ 500 mgthreetimesdaily 850 mgtwiceadayor - polyamine synthesis necessary for hair growth. Itdoes forhairgrowth. polyamine synthesisnecessary inhibitor. Itcatalyzestheratelimitingstepinfollicular decarboxylase ornithine isanirreversible hydrochloride Efornithine Dosage insufficiency, adrenaldisease dysfunction, renal Contraindicated withhepatic Hyperkalemia mayoccur. intolerance tocontactlenses gain, emotionallability, tenderness, headache, weight GI distress, breast hypotension, liverdysfunction irregular menstrualbleeding, gastrointestinal discomfort, decreased libido, fetus, gynecomastia, pseudoherma-phroditism in Hyperkalemia (rare), male changes andweightgain depression, fatigue, mood decreased libido, nausea, menstrual bleeding, phroditism infetus, irregular Male pseudoherma- phroditism infetus, Male pseudoherma- skin anddecreasedlibido disturbances, headaches, dry Minimal gastrointestinal typical ofCushing’s syndrome immune suppression, changes decreased bonedensity, adrenal suppression, impaired glucosetolerance, Weight gain, hypokalemia, vaginitis mineral density, atrophic Hot flashes, decreasedbone interactions 50%), numerousdrug (rare withmortalitynearly GI distress, lacticacidosis Side Effects sparing diuretics supplements, potassium- heparin, potassium II receptorblockers, ACE inhibitors, angiotensin- concurrent useofNSAIDs, during firstcyclewith Monitor serumpotassium component preferred Least androgenic progestin X.Pregnancy category monitor electrolytes D,Pregnancy category long-term use checked regularlyduring function shouldbe is discontinued. Liver 3 monthsaftertreatment recommended foratleast cyproterone acetate, andis whentaking mandatory Contraception is Monitor liverfunction D.Pregnancy category method ofcontraception. Combine withother Monitor liverfunction X.Pregnancy category Pregnancy category C Pregnancy category hypoestrogenic effect periods becauseof with cautionforshort X.Pregnancy category Use starting, andmonitor renal functionbefore function, confirmnormal may occur. Monitorliver Resumption ofovulation B.Pregnancy category Comments Hirsutism 105

Copyright© ABE&M todos os direitos reservados. Copyright© ABE&M todos os direitos reservados. Hirsutism 106 hirsutism iscombination therapy. Weight loss should for treatment teem ofthepatients.Themost effective theself-es toimprove isimportant benign, treatment Althoughmostcauses of hirsutismare hair growth. isthekeytriggerforexcess and hyperandrogenemia inwomen, Hirsutism isacommonclinical problem CONCLUSION on malesexualdevelopment(15,24). toconceivebecauseofpotentialadverseeffects trying contraindicatedinwomen inparticular, are androgens, forhirsutismmustbediscontinued.Anti- treatments ortheadditionofasecondagent. dose ordrug, suboptimal, optionstoconsiderincludeachangein has been months, if the patient feels that the response half-lifeofahairfollicle.Aftersix the approximate maynotoccurforuptosixmonths, tion inhairgrowth (15,24). therapy, biochemicalevaluationiswarranted repeated However, ofhirsutismduring isprogression ifthere duringtherapy. androgens dication tomonitorserum isnoin racteristics thathindertheirevaluation.There ormayhavespecificethniccha procedures, removal since thepatientsmaybeinvolvedinongoingcosmetic several questionsabouttheaccuracyofthisassessment, values. However, with previous and compared are there Objectively, canberated score theFerriman-Gallwey thehair.or lessneedtouseothermethodsremove ofhair inthegrowth wasadecrease ring whetherthere ses should be evaluated by thepatient herself, by decla dical follow-up.Theassessmentoftherapeuticrespon theme outthroughout Monitoring shouldbecarried MONITORING (14). tinuous usetomaintaineffects disadvantages includetwice-daily applications and con of any color,its ability to inhibit hair growth but the include skin(17).Benefitsofthecream itching anddry inclinicaluseinclude rimental conditions.Sideeffects inexpe onlywithoveruse of skinhasbeenreported in women.Systemicabsorptionislow, andirritation unwantedfacialhair ved inmanycountriesfortreating (13.9%)isappro cream hydrochloride cal eflornithine hair,not remove speed.Atopi itsgrowth butreduces When pregnancy is desired, all pharmacological all pharmacological is desired, When pregnancy reduc therapyhasbegun,asignificant After drug ------be encouraged in overweight andobesehirsutewo be encouragedinoverweight 20. 19. 18. 17. 16. 15. 14. 13. 12. 11. 10. 9. 8. 7. 6. 5. 4. 3. 2. 1. 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