18.06.2017 Abnormal(Dysfunctional)Uterine...

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Abnormal(Dysfunctional)Uterine
Bleeding
StephenD.CagleMD

MatthewJ.Snyder,DO

BASICS

DESCRIPTION

Abnormaluterinebleeding(AUB)isirregularmenstrualbleeding(usuallyheavy,prolonged,orfrequent)itisadiagnosisof
exclusionafterestablishmentofnormalanatomyandtheabsenceofothermedicalillnesses.

TheInternationalFederationofGynecologyandObstetrics(FIGO)revisedtheterminologysystemandnowusesAUBratherthan
dysfunctionaluterinebleeding(DUB).

Commonlyassociatedwithanovulation

EPIDEMIOLOGY

Adolescentandperimenopausalwomenareaffectedmostoften.

Incidence

5%ofreproductiveagewomenwillseeadoctorinanygivenyearforAUB.

Prevalence

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1030%ofreproductiveagewomenhaveAUB.

ETIOLOGYANDPATHOPHYSIOLOGY

Anovulationaccountsfor90%ofAUB.

Lossofcyclicendometrialstimulation

Elevatedestrogenlevelsstimulateendometrialgrowth.

Noorganizedprogesteronewithdrawalbleeding

Endometriumeventuallyoutgrowsbloodsupply,breaksdown,andsloughsfromuterus.

610%willhavepolycysticovariansyndrome(PCOS).

AdolescentAUBisusuallyduetoanimmaturehypothalamicpituitaryovarian(HPO)axisthatleadstoanovulatorycycles.

ThemnemonicPALMCOEINwasdevelopedasthenewnomenclaturetodescribeAUBinreproductiveagedwomen.

PALMdescribesstructuralcausesofabnormaluterinebleeding,andCOEINdescribesnonstructuralcausesofAUB.

PALM:polyp,adenomyosis,leiomyoma,andmalignancyand/orhyperplasia

COEIN:coagulopathy,ovulatorydisorders,endometrial,iatrogenic,andnotyetclassified.

Reproductivepathologyandstructuraldisorders

Uterus:leiomyomas,endometritis,hyperplasia,polyps,trauma

Adnexa:salpingitis,functionalovariancysts

Cervix:cervicitis,polyps,STIs,trauma

Vagina:trauma,foreignbody

Vulva:lichensclerosus,STIs

Malignancyofthevagina,cervix,uterus,andovaries

Systemicdiseases
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Hematologicdisorders(e.g.,vonWillebranddisease,thrombocytopenia)

Diseasescausinganovulation

Hyperthyroidism/hypothyroidism

Adrenaldisorders

Pituitarydisease(prolactinoma)

PCOS

Eatingdisorders

Medications(iatrogeniccauses)

Anticoagulants

Steroids

Tamoxifen

Hormonalmedications:intrauterinedevices(IUDs)

Selectiveserotoninreuptakeinhibitors(SSRIs)

Antipsychoticmedications

OthercausesofAUBnotdefinedinPALMCOEIN

Pregnancy:ectopicpregnancy,threatenedorincompleteabortion,orhydatidiformmole

Advancedorfulminantliverdisease

Chronicrenaldisease

Inflammatoryboweldisease

Excessiveweightgain

Increasedexercise

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Genetics

Unclearbutcanincludeinheriteddisordersofhemostasis

RISKFACTORS

Riskfactorsforendometrialcancer(whichcancauseAUB)

Age>40years

Obesity

PCOS

Diabetesmellitus

Nulliparity

Earlymenarcheorlatemenopause(>55yearsofage)

Hypertension

Chronicanovulationorinfertility

Unopposedestrogentherapy

Historyofbreastcancerorendometrialhyperplasia

Tamoxifenuse

Familyhistory:gynecologic,breast,orcoloncancer

DIAGNOSIS

HISTORY

Menstrualhistory

Onset,severity(quantifiedbypad/tamponuse,presenceandsizeofclots),timingofbleeding(unpredictableorepisodic)

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Menorrhagiawithonsetofmenarcheissuggestiveofacoagulationdisorder.

Menopausalstatus

Associationwithotherfactors(e.g.,coitus,contraception,weightloss/gain)

Gynecologichistory:gravidityandparity,STIhistory,previousPapsmearresults

Reviewofsystems(excludesymptomsofpregnancyandofbleedingdisorders,bleedingfromotherorifices,stress,exercise,recent
weightchange,visualchanges,headaches,galactorrhea)

Medicationhistory:Evaluateforuseofaspirin,anticoagulants,hormones,andherbalsupplements(1,2).

ALERT

Postmenopausalbleedingisanybleedingthatoccurs>1yearafterthelastmenstrualperiodcancermustalwaysberuledout(2)[C].

PHYSICALEXAM

DiscoveranatomicororganiccausesofAUB.

Evaluatefor

Bodymassindex(obesity)

Pallor,vitalsigns(anemia)

Visualfielddefects(pituitarylesion)

Hirsutismoracne(hyperandrogenism)

Goiter(thyroiddysfunction)

Galactorrhea(hyperprolactinemia)

Purpura,ecchymosis(bleedingdisorders)

Pelvicexam

EvaluateforuterineirregularitiesandTannerstage.

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Checkforforeignbodies.

Ruleoutrectalorurinarytractbleeding.

IncludePapsmearandtestsforSTIs(2)[C].

PediatricConsiderations

Premenarchalchildrenwithvaginalbleedingshouldbeevaluatedforforeignbodies,physical/sexualabuse,possibleinfections,and
signsofprecociouspuberty.

DIFFERENTIALDIAGNOSIS

SeeEtiology.

DIAGNOSTICTESTS&INTERPRETATION

InitialTests(lab,imaging)

Everyone:urinehumanchorionicgonadotropin(hCGruleoutpregnancyand/orhydatidiformmole)andcompletebloodcount
(CBC)(1)

Foracutebleeding,atypeandcrossshouldbeobtained(3)[C].

Ifdisorderofhemostasisissuspected,apartialthromboplastintime(PTT),prothrombintime(PT),activatedpartial
thromboplastintime(aPTT),andfibrinogenlevelisappropriate(3)[C].

Ifanovulationissuspected:thyroidstimulatinghormone(TSH)level,prolactinlevel(1)

Considerothertestsbasedondifferentialdiagnosis.

Folliclestimulatinghormone(FSH)leveltoevaluateforhypoorhypergonadotropism

Coagulationstudiesandfactorsifcoagulopathyissuspected(1)

17Hydroxyprogestroneifcongenitaladrenalhyperplasiaissuspected

Testosteroneand/ordehydroepiandrosteronesulfate(DHEAS)ifPCOS

ScreeningforSTI
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Endometrialbiopsy(EMB)shouldbeperformedaspartoftheinitialevaluationforpostmenopausaluterinebleedingandin
premenopausalwomenwithriskfactorsforendometrialcarcinoma.Medicalmanagementcanbeinitiatedinpremenopausal
womenwithnormalTVUSandlowriskformalignancy(1)[A].

TVUS,sonohysterography,andhysteroscopymaybesimilarlyeffectiveindetectionofintrauterinepathologyinpremenopausal
womenwithAUB(1)[A].

Ifnormalfindingsfollowingimaginginpatientswithoutknownriskfactorsforendometrialcarcinoma,abiopsyshouldbe
performedifnotdonesopreviously(2)[C].

DiagnosticProcedures/Other

Papsmeartoscreenforcervicalcancerifage>21years(2)[C]

EMBshouldbeperformedin

Womenage>35yearswithAUBtoruleoutcancerorpremalignancy

Postmenopausalwomenwithendometrialthickness>5mm

Womenaged18to35yearswithAUBandriskfactorsforendometrialcancer(seeRiskFactors)

Performonorafterday18ofcycle,ifknownsecretoryendometriumconfirmsovulationoccurred.

Dilationandcurettage(D&C)

Performifbleedingisheavy,uncontrolled,orifemergentmedicalmanagementhasfailed.

PerformifunabletoperformEMBinoffice(2)[C].

Hysteroscopyifanotherintrauterinelesionissuspected

TestInterpretation

Papsmearcouldrevealcarcinomaorinflammationindicativeofcervicitis.MostEMBsshowproliferativeordyssynchronous
endometrium(suggestinganovulation)butcanshowsimpleorcomplexhyperplasiawithoutatypia,hyperplasiawithatypia,or
endometrialadenocarcinoma.

TREATMENT

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Attempttoruleoutothercausesofbleedingpriortoinstitutingtherapy.

GENERALMEASURES

NSAIDs(naproxensodium500mgBID,mefenamicacid500mgTID,ibuprofen600to1,200mg/day)(1)[B]

Decreasesamountofbloodlossandpaincomparedwithplacebo,withnooneNSAIDclearlysuperior

MEDICATION

FirstLine

Acute,emergent,nonovulatorybleeding

Conjugatedequineestrogen(Premarin):25mgIVq4h(max6doses)or2.5mgPOq6hshouldcontrolbleedingin12to24
hours(4)[A].

D&CifnoresponseaftertwotofourdosesofPremarinorsoonerifbleeding>1pad/hr(2)[C]

Thenchangetooralcontraceptivepill(OCP)orprogestinforcycleregulation,thatis,IUD(5)[A]

Acute,nonemergent,nonovulatorybleeding

CombinationOCPwith30gestrogengivenasataper.Anexampleofatapereddose:4pills/dayfor4days3pills/dayfor
3days2pills/dayfor2days,dailyfor3weeksthen1weekoff,thencycleonOCPforatleast3months.

Nonacute,nonovulatorybleeding(rankedinorderbasedondecisionanalysisasbestoptionbasedonefficacy,cost,sideeffects,
andconsumeracceptability)(5)[A]

LevonorgestrelIUD(Mirena)isthemosteffectiveformofprogesteronedeliveryandisnotinferiortosurgicalmanagement.

Progestins:medroxyprogesteroneacetate(Provera)10mg/dayfor5to10dayseachmonth.Dailyprogesteronefor21days
percycleresultsinsignificantlylessbloodloss.

OCPs:20to35gestrogenplusprogesterone

Donotuseestrogenifcontraindications,suchassuspicionforendometrialhyperplasiaorcarcinoma,historyofdeepvein
thrombosis(DVT),orthepresenceofsmokinginwomen>35yearsofage(relativecontraindication),arepresent.

Precautions
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Failedmedicaltreatmentrequiresfurtherworkup.

ConsiderDVTprophylaxiswhentreatingwithhighdoseestrogens(2)[C].

SecondLine

Leuprolide(varyingdosesanddurationofaction)gonadotropinreleasinghormone(GnRH)agonist

Danazol(200to400mg/dayforamaximumof9months)ismoreeffectivethanNSAIDsbutislimitedbyandrogenicsideeffects
andcost.IthasbeenessentiallyreplacedbyGnRHagonists.

Antifibrinolyticssuchastranexamicacid(Lysteda)650mg,2tabletsTID(max5daysduringmenstruation)(1)[A]

MetforminorClomidaloneorincombinationinwomenwithPCOSwhodesireovulationandpregnancy

ISSUESFORREFERRAL

Ifanobviouscauseforvaginalbleedingisnotfoundinapediatricpatient,refertoapediatricendocrinologistorgynecologist.

Patientswithpersistentbleedingdespitemedicaltreatmentrequirereevaluationandpossiblereferral.

ADDITIONALTHERAPIES

Antiemeticsiftreatingwithhighdoseestrogenorprogesterone(2)[C]

Ironsupplementationifanemia(usuallyirondeficiency)isidentified

SURGERY/OTHERPROCEDURES

Hysterectomyincasesofendometrialcancerorifmedicaltherapyfailsorifotheruterinepathologyisfound

Endometrialablationislessexpensivethanhysterectomyandisassociatedwithhighpatientsatisfactionfailureofprimary
medicaltreatmentisnotnecessary(1,4)[A].

Thisisapermanentprocedureandshouldbeavoidedinpatientswhodesirecontinuedfertility.

ADMISSION,INPATIENT,ANDNURSINGCONSIDERATIONS

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Significanthemorrhagecausingacuteanemiawithsignsofhemodynamicinstabilitywithacutebleeding,replacevolumewith
crystalloidandblood,asnecessary(1)[A].

Padcountsandclotsizecanbehelpfultodetermineandmonitoramountofbleeding.

Dischargecriteria

Hemodynamicstability

Controlofvaginalbleeding(2)[C]

ONGOINGCARE

FOLLOWUPRECOMMENDATIONS

Oncestablefromacutemanagement,recommendfollowupevaluationin4to6monthsforfurtherevaluation(5).

RoutinefollowupwithaprimarycareorOB/GYNprovider

PatientMonitoring

WomentreatedwithestrogenorOCPsshouldkeepamenstrualdiarytodocumentbleedingpatternsandtheirrelationtotherapy.

DIET

Norestrictions,althougha5%reductioninweightcaninduceovulationinanovulationcausedbyPCOS.

PATIENTEDUCATION

Explainpossible/likelyetiologies.

Answerallquestions,especiallythoserelatedtocancerandfertility.

http://www.acog.org/Patients

PROGNOSIS

Varieswithpathophysiologicprocess

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Mostanovulatorycyclescanbetreatedwithmedicaltherapyanddonotrequiresurgicalintervention.

COMPLICATIONS

Irondeficiencyanemia

Uterinecancerincasesofprolongedunopposedestrogenstimulation

REFERENCES

SweetMG,SchmidtDaltonTA,WeissPM,etal.Evaluationandmanagementofabnormaluterinebleedinginpremenopausal
women.AmFamPhysician.201285(1):3543.
BibliographicLinks
CommitteeonPracticeBulletinsGynecology.Practicebulletinno.128:diagnosisofabnormaluterinebleedinginreproductive
agedwoman.ObstetGynecol.2012120(1):197206.
OvidFullText|BibliographicLinks
AmericanCollegeofObstetriciansandGynecologists.ACOGCommitteeOpinionNo.557:managementofacuteabnormaluterine
bleedinginnonpregnantreproductiveagedwomen.ObstetGynecol.2013121(4):891896.
OvidFullText|BibliographicLinks
DeVoreGR,OwensO,KaseN.UseofintravenousPremarininthetreatmentofdysfunctionaluterinebleedingadoubleblind
randomizedcontrolstudy.ObstetGynecol.198259(3):285291.
BuyNow|BibliographicLinks
MarjoribanksJ,LethabyA,FarquharC.Surgeryversusmedicaltherapyforheavymenstrualbleeding.CochraneDatabaseSyst
Rev.2006(2):CD003855.
BibliographicLinks

AdditionalReading

FarquharC,EkeromaA,FurnessS,etal.Asystematicreviewoftransvaginalultrasonography,sonohysterographyand
hysteroscopyfortheinvestigationofabnormaluterinebleedinginpremenopausalwomen.ActaObstetGynecolScand.
200382(6):493504.

KouidesPA,ConardJ,PeyvandiF,etal.Hemostasisandmenstruation:appropriateinvestigationforunderlyingdisordersof
hemostasisinwomenwithexcessivemenstrualbleeding.FertilSteril.200584(5):13451351.

LethabyAE,CookeI,ReesM.Progesteroneorprogestogenreleasingintrauterinesystemsforheavymenstrualbleeding.Cochrane
DatabaseSystRev.2005(4):CD002126.

http://ovidmd.ovid.com.am.enformation.ro/Chapter?ovidid=ovid:/fts/bookdb/02008467/26th_Edition/2/OVIDBOOK[1]/TXTBKBD[1]/CHAPTER[2]&q=mullerian+duct 11/12
18.06.2017 Abnormal(Dysfunctional)Uterine...:OvidMD

LethabyA,FarquharC,CookeI.Antifibrinolyticsforheavymenstrualbleeding.CochraneDatabaseSystRev.2000
(4):CD000249.

LethabyA,IrvineG,CameronI.Cyclicalprogestogensforheavymenstrualbleeding.CochraneDatabaseSystRev.2008
(1):CD001016.

SeeAlso

DysmenorrheaMenorrhagia(HeavyMenstrualBleeding)

Algorithm:Menorrhagia

Codes

ICD10

N93.9Abnormaluterineandvaginalbleeding,unspecified

N93.8Otherspecifiedabnormaluterineandvaginalbleeding

N91.2Amenorrhea,unspecified

ClinicalPearls

AUBisirregularbleedingthatoccursintheabsenceofpathology,makingitadiagnosisofexclusion.

Anovulationaccountsfor90%ofAUB.

AnEMBshouldbeperformedinallwomen>35yearsofagewithAUBtoruleoutcancerorpremalignancy,anditshouldbe
consideredinwomenaged18to35yearswithAUBandriskfactorsforendometrialcancer.

Itisappropriatetoinitiatemedicaltherapyinfemales<35yearsofagewithnoapparentriskofendometrialcancerpriorto
performinganEMB.
Copyright20112017

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