2023 CNGOF临床实践指南：子宫异常出血的管理

J.LBrunetaL EuropeanJournalofObstetrics&GynecologyandReproductiveBiology288(2023)90-107

#

EuropeanJournalofObstetricsandGynecology288(2023)

#

-107

ELSEVIER

Keywords:

Guidelines

Abnormaluterinebleeding

Diagnosis

Treatment

ContentslistsavailableatScicnccDircct

EuropeanJournalofObstetrics&Gynecologyand

ReproductiveBiology

journalhomepage:

/european-journal-of-obstetrics-and-gynecology-and-

reproductive-biology

Reviewarticle

Managementofwomenwithabnormaluterinebleeding:ClinicalpracticeguidelinesoftheFrenchNationalCollegeofGynaecologistsandObstetricians(CNGOF)

J.L.Brun'•\G.Plu-BureauC.Huchonc,X.Ah-Kit;,,M.Barral'1,P.Chauvetl,F.Comelisd,M.Cortet,P.CrochetV.DelporteG.DubernardG.Giraudet11,A.GossetO.Graesslin1,J.Hugon-Rodinb,L.Lecointrek,G.Legendre1,L.Maitrot-Manteletb,L.Marcellinh,L.Miquel8,M.LeMitouardC.ProustA.Roquetteb,P.Rousset",E.Sangnier',M.SapovalT.Thubertp,A.Torreq,F.TremollieresH.Vernhet-Kovacsik',F.VidalH.Marretm

ServicedechirurgiegynecologiquefcentreAlienord，Aquitaine,hbpitalPellegrirtCHUBordeaux.PlaceAmelieRabaLeon,33076Bordeaux,France

卜Unitedegynecologiemedicale,hopitalPon-RoyalCochin,AP-HP,27rueduFaubourgSaint-Jacques,75014Paris,France

cServicedegynecologie-obsteDique,hopicalLariboisiere,AP-HP,2rueAmbroisePar^75010Paris,France

右Servicederadlologieiruervemionnelle,hbpiialTenon^4ruedelaChine.75020Parts.France

eServicedechirurgiegynecologique,CHUClermont-Ferrand,1PlaceLucieetRaymondAubrac,63000Clermont-Femm(LFrance

(Servicedegynecologie,hopitalCroixRoussyCHULyon,103granderuedelaCroix-Rousse,69004Lyon,France

8Servicedegynecologie-obstetrique^hopitaldelaConception.CHUMarseille,147boulevardBailie,13005Marseille.France

hServicedegynecologichopitalJeannedeFlandre,CHULilley49ruedeValmy,59000Lille,France

1Centredemenopauseermaladiesosseusesmetaboliques,hopitalPauledeViguier,CHU,330AvenuedeGrande-Bretagne,31059Toulouse,France

JServicedegynea>logie-ob$tetrique,instiaamereenfantAlixdeChampagne,CHUReims,45rueCognac-Jay,51092Reims,France

kServicedechirurgiegynicologique.CHUStrasbourg,1avenueMolierc,67200StraibourgtFrance

1Servicedegynecologie-obstetrique^CHUAngers,4rueLarrey,49933Angers,Fhmce

mServicedechirurgiepelviennegynecologiqueetoncologique,hopitalBrexonneau,CHRUTours,2boulevardTonnelle,37044TogFrance

nServicederadiotogie,hopitalSud,CHULyon,165cheminduGrandRevoyei.69495Pierre・Beniie,France

0Servicederadiologicinitrventionnelle,hopitaleuropeenGeorges-Pompidou.APHP,20rueLeblanc,75015Paris.France

pServicedegynecologie-obstetrique,HotelDieu,CHUNantes,38,boulevardJean-Monnet,44093Nantes,France

qCentredeprocreationmedicalemencassisiee,centrehospitalierSudFrandUen.40aveniteSergfiDassault,91106Corbeil・Essonnes,France

rService^imageriethoradqueetvasculaire,hopitalAmaud-de-Villeneuve,CHUMonq>eUier,371avenueduDoyen-Gaston-Girau(L34295Montpellier.France

ABSTRACT

ARTICLEINFO

14questions.Wechosetoabstainfromrecommendationsratherthanprovidingadvicebasedsolelyonexpertclinicalexperience.

Conclusions:The36recommendationsmakeitpossibletospecifythediagnosticandtherapeuticstrategiesforvariousclinicalsituationspractitionersencounter,fromthesimplesttothemostcomplex.

Introduction

Abnormaluterinebleeding(AUB)istheleadingcauseofmedicalconsultationsforwomenaged30to50years.ThelastFrenchguidelinesissuedbytheCollegeNationaldesGynecologuesetObstetriciensFran^cus(CNGOF)onAUBmanagementdatebackto2008⑴.In2018,theUnitedKingdomNICE(NationalInstituteforClinicalExcellence)issuednewnationalguidelinesforheavymenstrualbleedinginadults;ACOG(AmericanCollegeofObstetriciansandGynecologists)alsoreleasedguidelinesonthistopicintheUSA,butfocusedonadolescents[2,31-Sincethen,theavailabilityofhormonetherapyinFrancehastendedtodecrease,andtheliteratureontherapiesthatarealternativestohysterectomyhasgrown.

TheobjectivesofthesenewguidelinesaretodefinetheclinicalandotherdiagnosticstrategiesforAUBandtodiscusstreatmentstrategiesaccordingtothepresumedaetiologicaldiagnosisandthepatient'sage.TheseguidelinesestablishedaccordingtotheGRADEmethodologyarebasedonevidenceobtainedfromtheinternationalliterature[4,5].Theyhavebeenproducedbyexpertsusingamultidisciplinaryapproachtoprovideanup-to-dateandvalidatedtooltohelpcliniciansmanagepatientswithAUB.

Materialsandmethods

TheCNGOFnamedanorganizingcommitteethatinturnsetupagroupofexperts,mainlygynaecologistsbutalsoradiologistsbelongingtootherprofessionalsocieties(e.g.,theFrenchSocietyofRadiology).Thegroupincludedtwopatients,bothrepresentativesofpatientorganizations.

Theorganizingcommitteeandexpertcoordinatorsinitiallydeterminedthequestionstobeaddressedandappointedexpertsresponsibleforeachquestion.ThesewereformulatedusingaPICO(Patients,Intervention,Comparison,Outcome)format.PubMedandCochranedatabaseswereusedtoperformanextensivesearchoftheliteraturesince2000.TheanalysisonlyincludedpublicationsinEnglishorFrenchissuedthroughSeptember2020,orthoseconsideredessentialbytheexperts.

Wechosetoaddress37questionsdividedintosevendomains.ThesedomainsreflectthePALM-COEIN(polyp;adenomyosis;leiomyoma;malignancyandhyperplasia;coagulopathy;ovulatorydysfunction;endometrial;iatrogenic;andnotyetclassified)classificationdevelopedbytheInternationalFederationofGynaecologyandObstetrics(FIGO).Itdescribesbleedingaccordingtoitsfunctionalororganicorigin(AUB-X)andtheFIGOclassificationoffibroidsaccordingtotheirsituationintheuterus(types0to7)[6-8J.Thequestionswerechosenforthreedifferentreasons:theirimportance,theexistenceofsignificantadvancessincethepreviousguidelines,orthelackofconsensusaboutthem.Thefollowingdomainsandquestionswereusedforthecollectionandanalysisoftheliterature:Domain1:DiagnosisofAUB(8questions);Domain2:AUBinadolescents(4questions);Domain3:TreatmentofidiopathicAUB(AUB-N)(4questions);Domain4:Treatmentofhyperplasiaandendometrialpolyps:AUB-PandAUB-M(3questions);Domain5:Treatmentoftype0-2fibroids(AUB-L)(5questions);Domain6:Treatmentoftype2or3(orhigher)fibroids(AUB-L)(6questions);Domain7:Treatmentofadenomyosis(AUB-A)(7questions).

Theevidencewaspresentedanddiscussedandrecommendationsdraftedinmeetings,bothinpersonandonline.Proposedrecommendationsbytheexpertswerethendiscusseduntilaconsensuswasreached.Eachrecommendationwaslabelledasstrongorweakandagradewasassignedbasedonthestrengthofthesupportingevidence(high,moderate,low,andverylow).Strongrecommendations(framedas“werecommend,'or"'cliniciansshould")shouldbeappliedtomostpatients,whileweakrecommendations(proposedassuggestions)requirediscussionandshareddecision-making.Overall,36recommendationsweredrafted,19ratedstrongand17weak.Theliteratureprovidednoconclusiveresponseto14questions,andwepreferrednottorenderadecisionratherthantoofferanexpertclinicalopinionbasedonlyonexperience,ratherthanevidence.

Thedraftguidelinesweresenttoreviewers(listedbelow)fromvariousspecialties(gynaecologists,radiologists,paediatricians,endocrinologists,haematologists,andgeneralpractitioners).Theirextensivecommentsresultedinmodificationorcorrectioninthetextofthisdraft.

Theseguidelinesreplacethosefrom2008,previouslyissuedbytheCNGOFonthistopic.Nonetheless,inapplyingtheseguidelines,alldoctorsmustexercisetheirownjudgment,takingintoaccounttheirownexpertiseandthespecificitiesoftheirpracticeorestablishment,todeterminethemethodofdiagnosisortreatmentbestsuitedtothespecificpatient.

Results

Background

AUBgenerallyinvolvesheavymenstrualbleeding,definedbyfrequentmenstruation(morefrequentthanevery24days),prolongedmenstruation(longerthan8days),andheavyflowvolume(morethan80mLofbloodlosseachperiod).Thetotalvolumeofbloodlosscanbeassessedbythepictorialbloodassessmentchart(PBAC)[9].

Theseguidelinesdonotcoverlowergenitalhaemorrhages(vulvar,vaginal,orexocervical)orvaginalbleedingassociatedwithpregnancy,menopause,orotherdiseases(endocrinopathiesandchronicdiseases).

Detailedquestioningenablingtheestablishmentofableedingscorebasedonfamilyandindividualhistoryofheavybleedinghelpstoidentifywomenrequiringanexplorationofhaemostasis.Agynaecologicalexaminationwithaspeculumisrecommendedtoruleoutlowergenitalbleeding[1J.

ThefirstlaboratorytesttoprescribeforawomanconsultingforAUBisacompletebloodcounttosearchforanaemiaandthrombocytopoe-nia.AplasmahCGassaymustbeperformedifpregnancyissuspectedtobeassociatedwithuppergenitaltractbleeding.Ahormonalwork-upisunnecessaryforAUB,exceptforTSHforwomenwithsignsorriskfactorsofhypothyroidismfl].

ThefirstimagingexaminationtoperformforwomenconsultingforAUBisapelvicultrasound.Ideally,thisexaminationshouldbeperformedbyanexpertconsultantexperiencedinpelvicimagingofwoman,withappropriateequipmentusedinoptimalconditions.Magneticresonanceimaging(MRI)ishabituallyasecond-lineexamination.

Whenanendometrialbiopsyisnecessary,thesampleisusuallytakenwithaCornierpipelie.

Anycurrentuseofhormonaltreatmentthatinfluencesthemenstrualcycleislikelytomodifydiagnosticandtreatmentstrategies.Mostofthesetreatmentshaveanantigonadotropiceffect:combinedoralcontraceptives(COC)),progestogens,GnRHanalogues(GnRHa),danazol,anti-aromatases,selectiveprogesteronereceptormodulators(SPRMs)includingulipristalacetate(UPA),levonorgestrel-releasingintrauterinesystems(52mg)(LNG-IUS),etc.

Theinterventionalradiologytechniquesstudiedfordiagnosisandtreatmentoffibroidsandadenomyosisareuterinearteryembolization(UAE)andhigh-intensityfocusedultrasound(HIFU).

Conservativesurgicaltreatmentreferstothetechniquesofendometrialresectionandendometrialablation,andmyomectomyforfibroids.Thefirst-generationtechniquesareperformedunderhysteroscopy:endometrialresectionbyloopdiathermyorablationbyroller-ball.Thesecond-generationtechniquesallowthermocoagulationoftheendometriumbythermalballoonendometrialablation,withtheintrauterineballoonheatedtoaround80°Corasystememittingradiofrequencywaves(radiofrequencyablation,RFA).Myomectomiescanbeperformedbyhysteroscopy(type0-2fibroids)orbylaparoscopyandlaparotomy(type3orhigher).

Non-conservative—thatis,radical—surgicaltreatmentisahysterectomy,preferentiallybyalaparoscopicorvaginalapproach.Nonetheless,iftechnicaloranatomicalconditionsdonotallowasafeminimally-invasiveapproach,alaparotomycanbeenvisioned.

Domain1:Diagnosis

PICO1:ForwomenwithAUB,isaPBACmoreeffectivethanothertechniques(chemicalmethodorself-report)forassessingmenstrualvolumeandreachingaspecificAUBdiagnosis?

Rl.l-IncasesofdiagnosticdoubtforadultswithAUB,wcsuggestaPBACwithathresholdof100(fortheHighamscore)todefinethetypesofAUB.Weakrecommendation.Moderatequalityofevidence.

R1.2-InadolescentswithAUB,werecommendaPBACwithathresholdof100(fortheHighamscore)todefinetypesofAUB.

Strongrecommendation.Moderatequalityofevidence.

Rationale

TheperformanceofthePBACforassessingAUB,asvalidatedbythealkalinehaematintechnique,issatisfactorywithitssensitivityrangingfrom58%to97%anditsspecificityfrom8%to96%[10].NodatacomparethePBACandself-reportfbradultwomencomplainingofAUB.ThereisnoevidencesupportingthesystematicperformanceofPBACinallwomentoestablishadiagnosisofAUB,exceptwhendiagnosticdoubtexists.OnestudyhascomparedthePBACandself-reportinadolescents:morethan60%ofadolescentswhoconsideredtheirperiodsnormalhadaPBAC>100[11J.TheseresultsthusfavourPBACuseinthisagegroup.

PICO2:ForwomenwithAUB,isahaematologicalwork-upincludingacompletebloodcountandferritinaemiamoreeffectivethanacompletebloodcountaloneforassessingtheextentandconsequencesofthisbleeding?

NoRecommendation

Rationale

Theprevalenceofirondeficiencyamongwomenisestimatedat10%andthatofanaemiaat2%to5%[12],Theprevalenceofsymptomsassociatedwithisolatedirondeficiencyisnotknown,buttheyaregenerallyminor,non-specific,andnotsevere.WecannotissuearecommendationabouttheutilityofprescribingaferritinaemiameasurementtogetherwithacompletebloodcountinwomenreportingAUBgiventheabsenceofanystudycomparingthiscombinationwiththecompletebloodcountalone.

PICO3:InwomenwithAUBnotusinghormonaltreatment(contraceptiveorother),areimagingexaminationsmoreeffectivethanlaboratoryhaemostasistestingasafirst-linemethodforestablishinganaetiologicaldiagnosis?

R1.3-ThefollowingtestsarcrecommendedforadultswithAUBnotusinganyhormonaltreatmentandwithnormalultrasoundfindings:acompletebloodcount,acoagulationwork-up(prothrombintime,activatedclottingtime,andfibrinogen),(continuedonnextcolumn)

(continued)

andtestingforvonWillebranddisease(vonWillebrandfactor(vWFJ,FactorVIII,vWFactivity,andvWFantigen).

Strongrecommendation,Lowqualityofevidence.

Rationale

Therearenoavailabledatacomparingtheperformanceofimagingandlaboratorytesting.OnlyonethirdofadultswithAUBhaveultrasoundabnormalities(PALM)[13,14].Inotherwomenwithoutanaetiologyfoundonpelvicultrasound,acompletebloodcount,acoagulationwork-up,andasearchforvonWillebranddiseasemustbeperformed.

PICO4:InwomenwithAUBnotusinghormonetreatment(contraceptiveorother),withouthaemostasisdisorders,andwithnormalpelvicultrasoundfindings,isapelvicMRInecessarytoestablishanaetiologies]diagnosis?

R1.4-InawomanwithAUBnotusinghormonetreatmentandwithoutanyhaemostasisdisorders,wesuggestthatapelvicMRInotbeperformedunlessthepelvicultrasoundperformedbyanexpertshowsabnormalities.

Weakrecommendation,Verylowqualityofevidence.

Rationale

NorecentstudyhasevaluatedtheutilityofMRIamongwomenwithAUBandnormalpelvicultrasoundfindings.Thenegativepredictivevalue(NPV)was82%fortwo-dimensional(2D)pelvicultrasoundinthetwooldstudiesthatconsideredthequestion[15,16].TheestimatedNPVof3Dultrasoundis92%(16).MRIhasanNPVof86%forthediagnosisofuterinecavityabnormalities(17).Thedataintheliteratureshowthatapelvicultrasound,whenperformedbyaspecialistukrasonographerandwithnormalfindings,enablesuterinepathologytoberuledout[15,16].

PICO5:InwomenwithAUBnotusinghormonaltreatment(contraceptiveorother),withouthaemostasisdisorders,andwithabnormalpelvicultrasoundfindings,isapelvicMRInecessarytosupportanaetiologicaldiagnosis?

Rl.S-InwomenwithAUBnotusinghormonaltreatmentwhosepelvicultrasoundrevealsoneormoretype2(orhigher)uterinefibroids,apelvicMRIisrecommendedtomapthesefibroidsbeforemyomectomy(iftheultrasoundisconsideredinsuflicient)orinterventionalradiology.

Strongrecommendation,Lowqualityofevidence.

Rl-6-WesuggestthatanadditionalpelvicMRInotbeperformedinwomenwithAUBnotusinghormonaltreatmentwhosepelvicultrasoundfindingsshowpolypsoradenomyosis,unlessthereisdoubtaboutthediagnosisofadenomyosis.Weakrecommendation.Lowqualityofevidence.

Rationale

Threeprincipaluterinedisordersareconsideredwhentheultrasoundfindingsareabnormal:polyps,fibroids,andadenomyosis.Forthediagnosisofpolyps,MRIisnomorevaluablethan2Dultrasound[18].HysterosonographyperformsbetterthanMRI[17,19].Forthediagnosisoffibroids,MRIperformsnobetterthanultrasoundwhenthefibroidhasatypicalappearance.MRIisbetterthanultrasoundforspecifyingfibroidsize,site,andmorphologyandthereforefordeterminingthetreatmentstrategy.Forsubmucosalfibroids,hysterosonographyperformsbetterthanbothMRIandultrasound117,18,20].Foradenomyosis,metaanalysesestimatingthepooleddiagnosticpropertiesofMRIandofultrasoundhavereportednosignificantdifferencebetweenthem,withthereferencediagnosisbasedonthepathologyexaminationofthehysterectomyspecimen[21].ArecentstudywithMRIresultsasthereferencesuggeststhatultrasoundsensitivityforadiagnosisofadenomyosisislow[22].

PICO6:InwomenwithAUBnotusinghormonaltreatment(contraceptivesorother)withnormallaboratoryresultsandapelvicultrasoundsuggestiveofanintracavitarypathology,doeshysteroscopyperformbetterthantheotherimagingexaminations(hysterosonography,pelvicMRI)forestablishinganaetiologicaldiagnosis?

R1.7-Wcsuggestthatcomplementaryexaminations(diagnostichysteroscopy,hysterosonographyorpelvicMRI)notberoutinelyorderedforwomenwithAUBwhoarenotusinghormonaltreatment,whohavenonnallaboratoryresults,andwhosepelvicultrasoundenableddiagnosisofanintracavitarypathology.Weakrecommendation,Lowqualityofevidence

R1.8-Incasesofdoubtabouttheultrasounddiagnosisofanintracavitarypathology,werecommendthatahysteroscopyorahysterosonographybeperformedtoestablishadiagnosisofoneormorepolypsortype0-2fibroids,oranMRIifthedevelopmentofasubmucosalfibroid(types1and2)issuspectedandtheprecedingexaminationscannotbecarriedout.

Strongrecommendation,Lowqualityofevidence

Rationale

Ultrasound,hysteroscopy,andhysterosonographyallhavegood-andsimilar-diagnosticperformanceforaffirmingthediagnosisofanintracavitarypathology[17,19,23].

MRIperformslesswellthanhysterosonographyforthediagnosisofpolyps,butbetterthanhysteroscopyforthediagnosisofasubmucosalfibroid[17,19].Noevidencesupportspreferringtorecommendoneortheotherofthesemethodstocharacterizeintracavitaryuterineabnormalities.Thechoicecanbebasedonthefeasibilityandacceptabilityofhysterosonographyatthesametimeasultrasound(incasesofdiagnosticdoubt),ofoutpatienthysteroscopyifthefacilityallowsit,andthepossibilityofanMRI(incasesofdiagnosticdoubt),takingintoaccounttheavailabilityofthedeviceandthecostoftheprocedure.

PICO7:InanadultwomanwithAUBandathickenedendometriumonpelvicultrasound,isanendometrialbiopsynecessarytoenableadiagnosisofendometrialhyperplasia?

R1.9-InadultswithAUB,werecommendanendometrialbiopsyiftheendometrialthicknessexceeds15mm.

Strongrecommendation,Lowqualityofevidence

R1.10-InadultswithAUB,werecommendanendometrialbiopsyinthepresenceofriskfactorsforendometrialcancer(pcrimcnopausc,highbodymassindex,diabetes,nulliparity,genetics).

Strongrecommendation,Lowqualityofevidence

Rationale

AUBisassociatedwithariskofcomplexoratypicalhyperplasiaorcancerin1.7%to4.9%ofcases[2426J.Athickenedendometriumonpelvicultrasoundisassociatedwithariskofendometrialhyperplasiain7.6%ofcases[26].Nonethelesstheultrasoundthresholdforabnormalendometrialthickeningamongwomenduringaperiodofnormalmenstruationhasnotbeenclearlyestablished:12to15mmdependingontheseries[27,28].Moreoverthemaximumvaluesofendometrialthicknessobservedduringthesecretoryphaseofanormalmenstrualcycle(12to14mm)mustalsobetakenintoaccount.

Studieshaveevaluatedthediagnosisofabnormalhistology,definedbycomplexand/oratypicalhyperplasiaorcarcinomaincasesofmenometrorrhagia,regardlessofendometrialthickness.InpremenopausalwomenwithAUB,abnormalendometrialhistologyissignificantlycorrelatedwithage,bodymassindex,diabetes,nulliparity,andendometrialtliicknessgreaterthan12mm[26].Anendometrialbiopsymustthereforebeperformedamongwomenwithriskfactorsforendometrialcancer.

PICO8:InwomenwithAUBandusinghormonalcontraception,aremodificationsofthetreatmentregimenpreferabletodiagnosticexploration(imagingorbiopsy)asafirst-linetreatment?

NoRecommendation

Rationale

Unexpectedvaginalbleedingand/orspottinginusersofhormonalcontraceptionarefrequentevents:COC(30%to50%),oralpro-gestogens(30%),andcontraceptiveimplant(34%)[29-321.Nonetheless,thecasesofAUBdefinedbyaPBACbleedingscore>100occurringduringtheuseofhormonalcontraceptionarerarereventsthataredifficulttoquantify.

TherearenodataintheliteraturethatdefineadiagnosticstrategyortreatmentorientationfbrwomenwithAUBwhoareusinghormonalcontraception.Professionalsocietieshaveformulatedexpertopinionssuggestingtheperformanceofawork-uptosearchforacausethatcouldexplaintheonsetofthebleedingaccordingtotheclinicalcontextbeforeproposingtomodifythetreatmentregimen[33,34].Thedifferentialdiagnosestoruleoutarepregnancy,infection,druginteraction,oranorganicuterinepathology.Numeroustreatmentoptionshavebeentestedfbrshort-termcontrolofunexpectedbleedinginusersofcontraception,especiallyofpureprogestogens.Theseoptionsincludecombinedoestrogens,tranexamicacid,non-steroidalanti-inflammatorydrugs(NSAIDs),andmifepristone.Theresultshavebeendisparateandthelowpowerofthestudiesmeansthatnomanagementcanyetbeproposed|35].

InadultswithAUBusinghormonalcontraception,thereisnoevidencefbrpreferringeitheradiagnosticexploration(imagingorbiopsy)ormodificationsofthetreatmentregimen.

Domain2:Adolescents

PICO9:InadolescentswithAUB,ishaemostasistestingamoreeffectivefirst-lineexaminationthanimagingforestablishinganaetiologicaldiagnosis?

R2.1-InadolescentswithAUB,werecommendhaemostasistestingasalirst-linework-up.

Strongrecommendation,lx)wqualityofevidence

Rationale

TheprevalenceofhaemostasisdisordersinadolescentswithAUBisontheorderof10%to65%accordingtoseriestliatcomemainlyfromspecialisedcentres136-44J.Theirdiagnosisinvolvescomplementarytesting(especiallyhaematological,forexample,forvonWillebranddisease)thatwillbenecessarythroughouttheirlives.TheothercausesofAUBthatcanbediagnosedbypelvicultrasoundarerelativelyrareinadolescents(1.3%)[45J.

Therearenoexistingstudiescomparingthediagnosticperformanceofahaemostasiswork-upwiththatofapelvicultrasoundinadolescentswithAUB.Nonetheless,inviewofthehighprevalenceofhaemostasisdisordersandthelowprevalenceofultrasoundabnormalitiesinthispopulation,haemostasistestingisindicatedfirst.

PICO10:InadolescentswithAUBandnormalhaemostasisresults,ispelvicMRImoreeffectivethanpelvicultrasoundforestablishinganaetiologicaldiagnosis?

R2.2-InadolescentswithAUBandnormalhaemostasisresults,wesuggestperformingapelvicultrasoundratherthananMRIasthefirst-lineimagingwork-up.Weakrecommendation,Lowqualityofevidence

Rationale

OrganicaetiologiesofAUBarerareinadolescents(1.3%)(45].Apelvicultrasoundcanbeperformedbythesuprapubicortransvaginalroute,byexpertultrasonographers,andthisequipmentisoftensimplertoaccessthanMRI.Nonetheless,theperformanceofthesuprapubicroutecanbelimitedbyparietalechogenicity,andthetransvaginalroutemaynotbepossibleforteenswithnoprevioussexualactivity.

NostudyhascomparedthediagnosticperformanceofMRIand

pelvicultrasoundinadolescentswithAUBandnormalhaemostasisfindings.PelvicMRIhasnotbeenevaluatedinadolescentswithAUB.PelvicMRIdoesnotappeartoperformbetterthanpelvicultrasoundforapelvicevaluationofadolescentswithAUB[46].

PICO11:InadolescentswithAUB,normalhaemostasisfindings,andnormalpelvicimaging,ishormonaltreatment(contraceptiveorother)moreeffectiveandbettertoleratedthannon-hormonaltherapiesfortreatingAUB?

NoRecommendationtherapiesmoreeffectiveandbettertoleratedthannon-hormonaltherapiesfortreatingAUB?

R3.1-InwomenwithidiopathicAUBandwantingtobecomepregnantsoon,wesuggestanon-hormonalHrst-linetreatment,withapreferenceforanti-librinolyticagents.

Weakrecommendation.Lowqualityofevidence.

R3.2-InwomenwithidiopathicAUBandnodesireforpregnancyintheshort-term,werecommendasafirst-linetreatmentanLNG-IUS(52mg)(intheabsenceofanycontraindication).

Strongrecommendation,Moderatequalityofevidence

Rationale

Althoughitisfrequentanddisabling,fewstudieshaveexaminedtreatmentoptionsforidiopathicAUBinadolescents.Moreover,thevarioustreatmenttrialsforadultsincludenoadolescent'subgroup".

Theobjectiveofhormonaltherapyistoobtainlong-termoligome-norrhoeaoramenorrhoea,whileanti-inflammatoryoranti-fibrinolytictreatmentsareadministeredonanadhocbasis.OnerandomizedtrialcomparingtenoxicamtoaCOCprovidedevidencesupportingtheuseofthisNSAIDattheacutephaseofidiopathicAUB:shorterhospitalizations(6.9+/-2.9dvs8.5+/-2.6d,P=0.001);significantimprovementinhaemoglobinconcentration(11.5+/-1.8g/dLvs10.4+/-1.5g/dL,P=0.05)[47].

Otherstudies,comparativeornot,haveshownthattheeffectivenessoftranexamicacidinreducingthemenstrualflowissimilartothatofCOC(44).Theeffectivenessandtolerabilityofhormonaltreatmentsvaryaccordingtotheirroutesofadministration(intrauterineversusoral)butalsobetweenpatients.Onestudyshowedanimprovementofsymptomsin93%ofadolescentstreatedbytheplacementofanLNG-IUS[48].Finally,forwomenwantingcontraception,among193womenaged18to25years,continuationoftreatmenttotheendofoneyearwassimilarforEPC(73%)andLNG-IUS(80%),P=0.28[49].

InadolescentswithidiopathicAUB,alltre