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10/2/2016 Approachtoabnormaluterinebleedinginnonpregnantreproductiveagewomen

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Approachtoabnormaluterinebleedinginnonpregnantreproductiveagewomen

Author SectionEditors DeputyEditor


AndrewMKaunitz,MD RobertLBarbieri,MD SandyJFalk,MD,FACOG
DeborahLevine,MD

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Jan2016.|Thistopiclastupdated:Aug15,2014.
INTRODUCTIONAbnormaluterinebleeding(AUB)(atermwhichreferstomenstrualbleedingofabnormal
quantity,duration,orschedule)isacommongynecologiccomplaint,accountingforonethirdofoutpatientvisits
togynecologists[1].AUBcanbecausedbyawidevarietyoflocalandsystemicdiseasesorrelatedto
medications(figure1)[2].Themostcommonetiologiesinnonpregnantwomenarestructuraluterinepathology
(eg,fibroids,endometrialpolyps,adenomyosis),anovulation,disordersofhemostasis,orneoplasia.

TheinitialapproachtotheevaluationofnonpregnantreproductiveagewomenwithAUBwillbereviewedhere.
Anoverviewofgenitaltractbleedinginwomen,terminologyregardingAUB,bleedingduringpregnancy,and
postmenopausalbleedingarediscussedseparately.(See"Differentialdiagnosisofgenitaltractbleedingin
women"and"Postmenopausaluterinebleeding"and"Overviewoftheetiologyandevaluationofvaginal
bleedinginpregnantwomen".)

TERMINOLOGYArevisedterminologysystemforabnormaluterinebleeding(AUB)innongravid
reproductiveagewomenwasintroducedin2011bytheInternationalFederationofGynecologyandObstetrics
(FIGO)[3].Thiswastheresultofaninternationalconsensusprocesswiththegoalofavoidingpoorlydefined
orconfusingtermsusedpreviously(eg,menorrhagia,menometrorrhagia,oligomenorrhea).Theclassification
systemisreferredtobytheacronymPALMCOEIN(polyp,adenomyosis,leiomyoma,malignancyand
hyperplasia,coagulopathy,ovulatorydysfunction,endometrial,iatrogenic,andnotyetclassified)(figure1).

Inthistopic,thetermpremenopausalwomenreferstowomenofreproductiveageandthoseinthemenopausal
transition(figure2).

PREVALENCEANDETIOLOGYAbnormaluterinebleeding(AUB)iscommon.AUnitedStatespopulation
basedsurveyofwomenages18to50yearsreportedanannualprevalencerateof53per1000women[4].The
importanceofAUBrelatestoitsmajorimpactonwomensqualityoflife,productivity,andutilizationof
healthcareservices[5].

ThedifferentialdiagnosisofAUBinanonpregnantreproductiveagewomanislistedhere(table1andtable2)
anddiscussedinmoredetailseparately(see"Differentialdiagnosisofgenitaltractbleedinginwomen"):

StructuralabnormalitiesTheseabnormalitiesarecommonandalargeproportionofthemmaybe
asymptomatic.Evenwhenalesionisnoted,theclinicianmustdeterminewhetheritisthecauseofthe
patientssymptoms:

Uterineleiomyomas(See"Epidemiology,clinicalmanifestations,diagnosis,andnaturalhistoryof
uterineleiomyomas(fibroids)".)

Endometrialpolyps(See"Endometrialpolyps".)

Adenomyosis(See"Uterineadenomyosis".)

OtherlesionsCesareanscardefect,arteriovenousmalformation

Ovulatorydysfunction(AUBO)(See'Irregularbleeding(ovulatorydysfunction)'belowand"Differential
diagnosisofgenitaltractbleedinginwomen",sectionon'Ovulatorydysfunction'.)

Bleedingdisorders(See"Approachtotheadultpatientwithableedingdiathesis",sectionon
'Menorrhagia'.)

Iatrogenic(eg,anticoagulants,hormonalcontraceptives,intrauterinedevice[IUD])AUBiscommonin
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womenonprogestinonlycontraceptives,particularlyinitiallyandusersmayeventuallydevelop
amenorrhea.(See"Managementofunscheduledbleedinginwomenusingcontraception".)

Neoplastic(endometrialhyperplasiaorcarcinoma,oruterinesarcoma)(See"Endometrialcarcinoma:
Epidemiologyandriskfactors"and"Classificationanddiagnosisofendometrialhyperplasia"and"Uterine
sarcoma:Classification,clinicalmanifestations,anddiagnosis".)

InfectionandinflammationEndometritis,pelvicinflammatorydisease(See"Endometritisunrelatedto
pregnancy"and"Pelvicinflammatorydisease:Clinicalmanifestationsanddiagnosis".)

Disordersoflocalendometrialhemostasis(See"Differentialdiagnosisofgenitaltractbleedinginwomen",
sectionon'Localendometrialhemostasisdisorders'.)

INITIALEVALUATIONInapatientwithacomplaintofpossibleuterinebleeding,severalquestionsmust
beansweredinitiallytoconfirmpregnancystatus,reproductivestatus,andthesourceofthebleeding.This
guidesthefurtherevaluation,differentialdiagnosis,anddispositionofthepatient(ie,whetherimmediate
evaluationandinterventionareneeded).Thealgorithmincludesthebasiccomponentsoftheevaluation
(algorithm1).

Istheuterusthesourceofthebleeding?Womenwithabnormaluterinebleeding(AUB)typicallypresent
withacomplaintofvaginalbleeding.Therearemanypotentialsourcesofgenitaltractbleeding,andtheactual
sitemustbedetermined(table1).Sitesthatarecommonlymistakenforuterinebleedingincludethelower
genitaltract(vulva,vagina,orcervix),urinarytract,andgastrointestinaltract.Thefollowingelementsofthe
historyandphysicalexaminationhelptoexcludeextrauterinesourcesofbleeding:

Bleedingfromthevulva,vagina,orcervix

Mostgenitaltractbleedingisfromtheuterusorthelowergenitaltract(vulva,vagina,cervix).
Extrauterineuppergenitaltractbleedingislesscommon.Themostcommonetiologyofupper
genitaltractbleedingisectopicpregnancy,whichcanbeexcludedwithnegativepregnancytesting
(see'Pregnancytest'below).Uncommonextrauterineetiologiesofuppertractbleedingareovarian
orfallopiantubalcancer.

Thevolumeofbleedinggivessomesuggestionofthesourceforgenitaltractbleeding.Heavy
bleedingtypicallyderivesfromtheuterus,whilestaining,spotting,orlightbleedingmaybefromany
genitaltractsite.

Thecolorofthebloodprovidesalimitedamountofinformationregardingthesource.Brownstaining
mayrepresentoldbloodasaresultoflightbleedingorspottingfromtheuppervagina,cervix,or
uterus.Redbloodmayderivefromanygenitaltractsite.

Ifthebleedingisconsistentlypostcoital,thissuggestscervicalpathology,includingcervical
neoplasia.However,postcoitalbleedingmayoccurwithcontactduringintercourseofanysitealong
thelowergenitaltractthatisfriable(eg,duetocervicitisorvulvovaginalatrophy)orhasalesion
(eg,cervicalpolyporvulvarulcer).(See"Postcoitalbleedinginwomen".)

Pelvicexaminationshouldincludeevaluationofalllowergenitaltractsitestoassessforareasof
friabilityorlesions.Inaddition,afindingonbimanualexaminationofpelvictendernessorapelvic
masswarrantsfurtherevaluationforpelvicinflammatorydisease(PID)oruterineoradnexal
pathology.

Urinaryorgastrointestinaltractbleeding

Thefollowingmedicalhistoryquestionshelptodeterminewhetherthebleedingisfromanongenital
source:(1)Isthepatientcertainthatthebleedingisfromthevagina?(2)Doesthepatientseethe
bloodinthetoiletonlyduringoraftereitherurinationordefecation?(3)Doesthepatientseethe
bleedingonlywhenshewipeswithtoilettissue?Ifso,hastriedtoseparatelydabtheurethra,
vagina,andanuswithtoilettissuetocheckthesourceofthebleeding?(4)Doesshestillseethe
bleedingwhileshehasatamponinthevagina?

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Physicalexaminationhelpstoidentifysome,butnotall,urinaryorgastrointestinaltractbleeding
sources.Inspectionoftheurethramayrevealaurethralcaruncle(see"Urethralcaruncle").Afinding
onanorectalexaminationofalesion(eg,hemorrhoidorrectalmass)orpositivefecaloccultblood
testingprovidesevidenceofanongenitalsource.

Ingeneral,ifthebleedingoccurssolelywithurinationordefecationandthepatternofbleedingor
findingsonphysicalexaminationareconsistentwithaurinaryorgastrointestinaltractsource,this
shouldbethefocusoffurtherevaluation.Iftheseetiologiesareexcluded,evaluationofthegenital
tractshouldcontinue.Evaluationofhematuriaandrectalbleedingisdiscussedindetailseparately.
(See"Etiologyandevaluationofhematuriainadults"and"Approachtominimalbrightredbleeding
perrectuminadults".)

Isthepatientpremenarchalorpostmenopausal?ThedifferentialdiagnosisofAUBforreproductiveage
womendiffersfromthatofpremenarchalorpostmenopausalpatients.Thus,itisimportanttoestablishthe
reproductivestatusofthepatient.

Theaverageageofmenarcheis12years[6].Forpremenarchalgirls,thereisarangeofcausesofvaginal
bleeding,forexample,hormonalissues,infection,foreignbody,trauma,ormalignancy.(See"Evaluationof
vaginalbleedinginchildrenandadolescents",sectionon'Vaginalbleedingbeforenormalmenarche'.)

Theaverageageofmenopauseis51years[7].Menopauseisdefinedas12monthsofamenorrheainthe
absenceofotherbiologicalorphysiologicalcauses.Thisistypicallyprecededbyseveralyearsofirregular
uterinebleedingandmenopausalsymptoms(eg,hotflushes).Inhealthywomenage45yearsandolder,
laboratorytestingofserumfolliclestimulatinghormoneisnotrequiredtomakethediagnosis.(See"Clinical
manifestationsanddiagnosisofmenopause".)

WomenwithAUBwhohavenothadamenorrheafor12monthsshouldbeconsideredpremenopausalforthe
purposeofevaluation,butshouldhaveendometrialsamplingifriskfactorsforendometrialcancerarepresent
(table3andtable4).Allpostmenopausalbleedingisabnormal,andrequiresevaluationforendometrialcancer.
(See"Postmenopausaluterinebleeding"and'Endometrialsampling'below.)

Isthepatientpregnant?AllpatientswithAUBshouldhavepregnancytesting.Thehistoryofthelast
severalmenstrualperiodsshouldbeelicitedtogetsomesenseofwhethermensesaredelayed.However,
pregnancytestingshouldbeperformedeveninwomenwithrecentvaginalbleeding,sincethismayrepresent
bleedingduringpregnancyratherthanmenses.Itshouldalsobeperformedinwomenwhoreportnosexual
activityandinthosewhoreportuseofcontraception.

Womenwhoarepregnantareevaluatedprimarilyforpregnancyrelatedcausesofbleeding,buttheevaluation
shouldincludeassessmentforetiologiesnotrelatedtopregnancyifappropriate.(See"Overviewoftheetiology
andevaluationofvaginalbleedinginpregnantwomen".)

FURTHEREVALUATIONInnonpregnantreproductiveagewomenwithabnormaluterinebleeding(AUB),
thegoalsoftheevaluationaretodeterminethepattern,severity,andetiologyofthebleeding,andtherebyto
guidemanagement.Keyquestionsthathelptoguidetheclinicianinclude:

Whatisthebleedingpattern?

Shouldendometrialsamplingbeperformed?

Shouldacoagulationevaluationbeperformed?

Isbleedingrelatedtoacontraceptivemethod?

Astheevaluationproceeds,thepossibilityofconcurrentfactorsshouldbeconsidered.Asanexample,a
womanwithafibroiduterusmayalsohaveadefectofhemostasisthatistheprimaryreasonforherheavy
bleedingorshemaybebleedingfromanendometrialorendocervicalmalignancyunrelatedtothefibroiduterus.
Therefore,severalpotentialetiologiesoftenneedtobeinvestigatedand,ifacauseofAUBisdeterminedbut
bleedingpersistsdespitetreatment,thepatientshouldbeevaluatedforadditionaletiologies.

Thebasiccomponentsoftheevaluationareshowninthealgorithm(algorithm1).Thetableprovides

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informationabouthowtochooseadditionaltestingandusetheinformationfromtheevaluationtomakea
diagnosis(table5).

HISTORYTherelevantmedicalhistoryinnonpregnantreproductiveagewomenwithabnormaluterine
bleeding(AUB)includesthefollowing:

Generalhistory

Gynecologicandobstetrichistory,including:

Menstrualhistory.(See'Menstrualhistory'below.)

SexualhistoryThisinformationmayhelpdeterminethepatientsriskforpregnancyorsexually
transmittedinfections.

HistoryofobstetricorgynecologicsurgeryApriorcesareandelivery,particularlymultipleprior
abdominaldeliveries,raisesthepossibilitythatacesareanscardefectmayberesponsibleforAUB
[8].ApriormyomectomyraisesthepossibilitythatuterinefibroidsareresponsibleforAUB.

ContraceptivehistoryWomenusingestrogenprogestincontraceptivesmaydevelopunscheduled
bleeding,whileuseofprogestinonlycontraceptivesoftenresultsinirregularuterinebleedingor
amenorrhea.Useofthecopperintrauterinedevice(IUD)increasesmenstrualflow.Levonorgestrel
IUDstypicallycauseaninitialperiodofirregularspottingorbleeding,followedbyagradual
decreaseinmenstrualflowandpossibleamenorrhea.(See"Managementofunscheduledbleedingin
womenusingcontraception".)

Riskfactorsforendometrialcancer.Theindicationsforendometrialsamplingarediscussedbelow.
(See'Endometrialsampling'below.)

OthermedicalhistoryissuesthathelptodeterminetheetiologyofAUBinclude:

Symptoms,riskfactors(anticoagulanttherapy,liverorrenaldisease),orafamilyhistoryofa
bleedingdisorder.Theindicationsforcoagulationtestingarediscussedbelow.(See'Coagulation
tests'below.)

Symptomsorfamilyhistoryofthyroiddisease.(See'Endocrinetests'belowand"Pathogenesis,
epidemiology,andclinicalmanifestationsofceliacdiseaseinadults",sectionon
'Nongastrointestinalmanifestations'.)

Celiacdisease.(See"Pathogenesis,epidemiology,andclinicalmanifestationsofceliacdiseasein
adults",sectionon'Menstrualandreproductiveissues'.)

MedicationsMedicationscancauseAUBinavarietyofways:(1)anticoagulantsmayresultinheavyor
prolongeduterinebleeding(2)avarietyofmedicationscancausehyperprolactinemia(table6),resulting
inoligomenorrheaoramenorrhea.

Additionalquestionsthatmayhelptosuggestanetiologyinclude:

Werethereprecipitatingfactors,suchastrauma?Bleedingrelatedtotraumasuggestsavaginalor
cervical,ratherthanuterine,sourceofbleeding.

Arethereanyassociatedsymptoms?Lowerabdominalpain,fever,and/orvaginaldischargecould
indicateinfection(pelvicinflammatorydisease[PID],endometritis).Dysmenorrhea,dyspareuniaor
infertilitysuggestendometriosisandpossibleadenomyosis.Changesinbladderorbowelfunction
suggestextrauterineuterinebleedingoramasseffectfromaneoplasm.Galactorrhea,heatorcold
intolerance,hirsutism,orhotflashessuggestanendocrinologicissue.

Hastherebeenarecentillness,stress,excessiveexercise,orpossibleeatingdisorder?Thissuggests
hypothalamicdysfunction.

MenstrualhistoryAUBvariesfromnormalmensesintermsoffrequency,regularity,volume,orduration.
Thecharacteristicsofnormalmenstrualbleedingare(table7)[9,10]:

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Frequencyevery21to35days
Occursatfairlyregularintervals
Volumeofblood80mL
Durationis5days

Theclinicianshoulddeterminethebleedingpatternbyaskingthepatientthefollowingquestions:

Whatwasthefirstdayofthelastmenstrualperiodandseveralpreviousmenstrualperiods?

Forhowmanydaysdoesbleedingcontinue?Howmanydaysoffullbleedingandhowmanydaysoflight
bleedingorbrownstainingdoesthisinclude?

Doesbleedingoccurbetweenmenstrualperiods?

Howheavyisthebleeding?Thedefinitionofnormalmensesis<80mLofblood.Populationbased
studiesthatemployedpreciseassessmentofmenstrualbloodlossfoundthatwomenwithalossper
cycleof>80mLweremorelikelytobecomeanemic[11].However,volumeofbloodisdifficultto
measure.Inclinicalpractice,heavymensesaregenerallydefinedassoakingapadortamponmorethan
everytwohoursorasavolumeofbleedingthatinterfereswithdailyactivities(eg,wakespatientfrom
sleep,stainsclothingorsheets).Questionsthathelptocharacterizethevolumeofuterinebleedingare
showninthetable(table8).

Ifbleedingisirregular,howmanybleedingepisodeshavetherebeeninthepast6to12months?Whatis
theaveragetimefromthefirstdayofonebleedingepisodetothenext?

Awomanmayhavestrongconcernsoverchangesinmenstrualbloodloss,however,patientselfreportsare
inaccurateindicatorsofthequantityofbloodlostatmensesandpathologicexaminationoftheuterusoften
showsnoabnormality[1216].Thiswasillustratedbyapopulationbasedstudyinwhichonequarterofwomen
withnormalperiodsconsideredtheirbloodlossexcessive,whereas40percentofthosewithexcessive
bleeding(>80mL)describedtheirperiodsaslightormoderate[11].Inanotherstudy,onlyonethirdofwomen
whoconsideredtheirperiodsheavyhadbloodloss>80mL[17].

ThereareseveraltypicalbleedingpatternsthatcorrelatewithparticularetiologiesofAUB,including:

HeavymenstrualbleedingBaseduponcurrentterminology,regularbleedingthatisheavyorprolonged
(referredtoasheavymenstrualbleeding)refersonlytocyclic(ovulatory)menses.Thetermheavymenstrual
bleeding(HMB)wasintroducedaspartofthePALMCOEIN(polyp,adenomyosis,leiomyoma,malignancyand
hyperplasia,coagulopathy,ovulatorydysfunction,endometrial,iatrogenic,andnotyetclassified)classification
systemforAUB[3].Thisreplacesthetermmenorrhagia,whichwaspreviouslyusedtodescribeheavyor
prolongeduterinebleeding.Menorrhagiaisalessprecisewordbecauseitdoesnotdifferentiatebetween
volumeanddurationofbleedingorbetweencyclicandanovulatorybleeding.(See'Terminology'above.)

ThemostcommonetiologiesofHMBare:

UterineleiomyomasHMBassociatedwithuterineleiomyomasismostlikelytooccurwithsubmucosal
leiomyomas,butleiomyomasatothersitesmayalsocauseAUB.(See"Epidemiology,clinical
manifestations,diagnosis,andnaturalhistoryofuterineleiomyomas(fibroids)".)

AdenomyosisThisisoftenaccompaniedbydysmenorrheaorchronicpelvicpain.(See"Uterine
adenomyosis".)

CesareanscardefectSometwothirdsofwomenwhohavehadoneor(inparticular)multiplecesarean
birthsmayhaveacesareanscardefect,andapproximatelyonethirdofwomenwiththiscondition
experiencecyclical,postmenstrualbleeding[18].

Bleedingdisorder.(See'Coagulationtests'below.)

OtheretiologiesassociatedwithHMBinclude:

Endometrialhyperplasiaorcarcinomaor,rarely,uterinesarcomamaybeassociatedwithHMB,butthe
typicalbleedingpatternfortheseconditionsisirregularorpostmenopausalbleeding.(See"Endometrial
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carcinoma:Clinicalfeaturesanddiagnosis"and"Classificationanddiagnosisofendometrialhyperplasia"
and"Uterinesarcoma:Classification,clinicalmanifestations,anddiagnosis".)

IUDTheTcu380A(Paraguard)IUDisassociatedwithiatrogenicheavyorprolongedmensesin
contrast,thelevonorgestrelIUDsdecreasemenstrualbloodloss.(See"Intrauterinecontraception:
Devices,candidates,andselection".)

Endometrialpolyps,endometritis,orPIDTheseentitiesmaypresentwithheavyorprolongedmenses,
butintermenstrualbleedingisthemorecommonclinicalmanifestation.(See"Endometrialpolyps"and
"Postpartumendometritis"and"Endometritisunrelatedtopregnancy".)

CongenitaloracquireduterinearteriovenousmalformationThisisararecauseofHMB[1921].This
lesionshouldbesuspectedwhenaninvasiveprocedureforunexplainedbleedingseemstoaggravatethe
problem.Acquireduterinearteriovenousmalformationstypicallyoccurafteranintrauterineprocedure.
(See"Differentialdiagnosisofgenitaltractbleedinginwomen",sectionon'Arteriovenousmalformation'.)

DisordersoflocalendometrialhemostasisAlterationsinprostaglandinsmayresultinHMB.(See
"Differentialdiagnosisofgenitaltractbleedinginwomen",sectionon'Localendometrialhemostasis
disorders'.)

ThyroiddiseasehastraditionallybeenthoughttobeacommoncauseofHMB.However,theavailabledata
suggestthatitisanuncommonetiologyofthisbleedingpattern.Asanexample,onestudyreportedthatthe
prevalenceofmenstrualdisturbanceswassimilaramong586womenwithhyperthyroidismand111women
withhypothyroidismcomparedwith105healthycontrols[22].Ratesofhypermenorrheawerecomparablein
womenwiththyroiddiseasecomparedwithcontrols,buttherewerefewwomenwiththisbleedingpattern
(hyperthyroidism:2of586womenhypothyroidism:0of111and1of105controls).Anotherstudyfoundthat
menorrhagiawasmorecommonin171womenwithhypothyroidismthanin214healthycontrols(7versus1
percent),buttheproportionofwomenwiththissymptomwaslow[23].(See"Clinicalmanifestationsof
hypothyroidism",sectionon'Reproductiveabnormalities'and'Endocrinetests'below.).

AdditionalcausesofHMBarelistedinthetable(table9).

IntermenstrualbleedingIntermenstrualuterinebleedingmayberelatedtoavarietyofetiologies(table
10),including:

Endometrialpolyps.(See"Endometrialpolyps".)

Unscheduledbleedingduetoacontraceptivemethod.(See"Managementofunscheduledbleedingin
womenusingcontraception".)

Endometrialhyperplasiaorcarcinomaor,rarely,uterinesarcoma.(See"Endometrialcarcinoma:Clinical
featuresanddiagnosis"and"Classificationanddiagnosisofendometrialhyperplasia"and"Uterine
sarcoma:Classification,clinicalmanifestations,anddiagnosis".)

EndometritisorPIDAUBinwomenwithsymptomaticchronicendometritismaypresentas
intermenstrualbleedingorspotting,postcoitalbleeding,orheavymenstrualbleeding(HMB).Inwomen
withAUB,thepresenceofpelvicpain,cervicitis,orvaginalleukorrheashouldalertthecliniciantothe
possibilityofendometritis.Endometritisismostlikelytooccurinwomenwitharecenthistoryofchildbirth
oranintrauterineprocedure(eg,pregnancytermination,IUDinsertion).RegardingPID,forexample,in
oneseries,15percentofwomenwithpossibleuppergenitaltractinfectionpresentedwithAUB[24].(See
"Endometritisunrelatedtopregnancy"and"Postpartumendometritis"and"Pelvicinflammatorydisease:
Clinicalmanifestationsanddiagnosis".)

Endometrialabnormalitiesrelatedtopreviousendometrialtrauma(eg,ahysterotomyscarorniche
followingcesareandelivery)(See"Differentialdiagnosisofgenitaltractbleedinginwomen",sectionon
'Cesareanscardefect'.)Amongwomenwithregularmenses,intermenstrualspottingoccursinlessthan
3percentofcyclesandmayrepresentphysiologicintermenstrualbleedingassociatedwithovulation[25].

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Intermenstrualbleedingisoftenduetoconditionsofthecervix,includingcervicalcancer,cervicalpolyps,
cervicitis,orectropion.Theseconditionsarediscussedseparately.(See"Invasivecervicalcancer:
Epidemiology,riskfactors,clinicalmanifestations,anddiagnosis",sectionon'Clinicalmanifestations'and
"Congenitalcervicalanomaliesandbenigncervicallesions",sectionon'Polyps'and"Congenitalcervical
anomaliesandbenigncervicallesions",sectionon'Cervicitis'and"Congenitalcervicalanomaliesandbenign
cervicallesions",sectionon'Ectropion'.)

Irregularbleeding(ovulatorydysfunction)Irregularuterinebleedingismostcommonlyassociated
withovulatorydysfunction(AUBO).Womenmayeitherhaveanovulation,whichreferstotheabsenceof
ovulatorycycles,oroligoovulation,inwhichtheyshiftbetweenovulatorycyclesandanovulation.(See
"Differentialdiagnosisofgenitaltractbleedinginwomen",sectionon'Ovulatorydysfunction'.)

IrregularbleedingassociatedwithAUBOistypicallycharacterizedbyphasesofnobleedingthatmaylastfor
twoormoremonthsandotherphaseswitheitherspottingorepisodesofheavybleeding.Moliminaaretypically
absent.

AUBOshouldbesuspectedinwomenwithanirregularbleedingpattern,particularlythoseattheextremesof
reproductiveage(postmenarchalandinthemenopausaltransition).Inaddition,polycysticovariansyndrome
andotherendocrinedisorderscancauseAUBO(thyroiddisease,hyperprolactinemia).Causesofovulatory
dysfunctionareshowninthetable(table11).

Thediagnosisofanovulatorybleedingismadeprimarilybythebleedingpattern,providedthatetiologiesof
intermenstrualbleedinghavebeenexcluded(see'Intermenstrualbleeding'above).Laboratoryevaluationisnot
generallyrequiredtoconfirmanovulation,butishelpfulinexcludingthyroiddiseaseorhyperprolactinemia.(See
'Endocrinetests'belowand"Evaluationoffemaleinfertility",sectionon'Assessmentofovulatoryfunction'.)

IfapatienthasableedingpatternconsistentwithAUBO,subsequentevaluationisdirectedtowardidentifying
thecause.Inaddition,womenwithprolongedamenorrheaduetoanovulationareexposedtounopposed
estrogenandareatriskofendometrialhyperplasiaorcancer,andendometrialsamplingmayberequired(table
4).Ideally,thecauseofanovulationcanbeidentifiedandtreatedsothatnormalcyclicmensescanbere
established.(See'Endometrialsampling'below.)

OtherbleedingpatternsOthertypesofbleedingpatternsinclude:

AmenorrheaAmenorrheareferstoabsenceofbleedingforatleastthreeusualcyclelengths.
Amenorrheamaybeprimary(ie,menarcheisabsent)orsecondary(mensesceaseaftermenarche).The
evaluationofamenorrheaisdiscussedseparately.(See"Evaluationandmanagementofprimary
amenorrhea"and"Evaluationandmanagementofsecondaryamenorrhea".)

DecreasedvolumeWomensometimesreportthatperiodsthatareregular,buthavebecomeunusually
lightorofshortduration.Thismayoccurwithuseofhormonalcontraception.Othercausesincludepartial
cervicalstenosisorAshermansyndrome.However,thebleedingpatternshouldbereviewedtodetermine
whetherthelightbleedingrepresentsirregularbleedingorintermenstrualbleeding.(See"Congenital
cervicalanomaliesandbenigncervicallesions",sectionon'Cervicalstenosis'and"Intrauterine
adhesions".)

RegularmenseswithincreasedfrequencyDuringthemenopausaltransition(figure2),womenmay
experienceadecreaseintheintervalbetweenmenses(figure3).Cyclelengththathasshortened,butnot
tolessthanevery21days,maybenormalduringthisphase.Ifthebleedingisalsoirregularoroccurs
lessoftenthanevery21days,otheretiologiesshouldbeinvestigated.(See'Irregularbleeding(ovulatory
dysfunction)'aboveand'Intermenstrualbleeding'above.)

PHYSICALEXAMINATIONVitalsignsshouldbeassessedandacompletepelvicexaminationshouldbe
performed,withaparticularfocuson:

Potentialsitesofbleedingonthevulva,vagina,cervix,urethra,anus,orperineum

Anyabnormalfindingsalongthegenitaltract(eg,mass,laceration,ulceration,friablearea,vaginalor
cervicaldischarge,foreignbody)

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SizeandcontouroftheuterusAnenlargeduterusmaybeduetopregnancy,uterineleiomyomas,
adenomyosis,oruterinemalignancy.Limiteduterinemobilityshouldbenoted,ifpresentthisfinding
suggeststhatpelvicadhesionsorapelvicmassispresent.Pelvicadhesionsmaybeduetoprior
infection,surgery,orendometriosis,andalsomayimpactsurgicalplanningifsurgicaltreatmentis
indicated.Aboggy,globular,tenderuterusistypicalofadenomyosis.Uterinetendernessispresentin
womenwithpelvicinflammatorydisease(PID),butisnotconsistentlyfoundinthosewithchronic
endometritis.

CurrentuterinebleedingThepresenceandvolumeofbleedingfromthecervicalosshouldbenoted.
Bloodorbloodclotsinthevaginalvaultshouldbenoted.Patientswhopresentwithacomplaintofheavy
vaginalbleedingshouldbeassessedforacutebleeding.Patientswhoarehemodynamicallyunstableor
whohavecopious,ongoingbloodflowfromtheuterusorothergenitaltractsiteshouldbeevaluatedand
managedinanurgentcarefacility.(See"Managinganepisodeofsevereorprolongeduterinebleeding",
sectionon'Hemodynamicallyunstablewomen'and"Approachtovaginalbleedingintheemergency
department".)

Presenceofanadnexalmassortenderness

Ageneralexaminationshouldbeperformedtolookforsignsofsystemicillness,suchasfever,ecchymoses,
anenlargedthyroidgland,orevidenceofhyperandrogenism(hirsutism,acne,clitoromegaly,ormalepattern
balding).Acanthosisnigricansmaybeseeninwomenwithpolycysticovariansyndrome(PCOS).Galactorrhea
(bilateralmilkynippledischarge)suggeststhepresenceofhyperprolactinemia.

LABORATORYEVALUATION

InitialtestsMostreproductiveagewomenwithabnormaluterinebleeding(AUB)shouldbeevaluated
initiallywiththefollowingtests:

Humanchorionicgonadotropin(hCG)toexcludepregnancy

Completebloodcount,hemoglobinand/orhematocrittoassessforanemiatheexceptiontothisare
patientswhodonothaveheavyorfrequentbleeding

PregnancytestPregnancyshouldbeexcludedinallreproductiveagewomenwithAUB.

AurinehCGtestmaybeperformedasaninitialtestinaclinicorurgentcaresetting,sincetheseresultsare
availablequickly.Regardlessoftheresult,aquantitativeserumhCGshouldalsobeperformed:

Iftheurinetestisnegative,butthecliniciancontinuestosuspectearlypregnancymaybepresent,serum
hCGshouldbemeasured.AserumhCGassaycandetectapregnancybyoneweekafterconception,
whileaurinehCGtestisabletodetectmostpregnancieswithintwoweeksafterconception(table12)
[26,27].

Iftheurinetestispositive,serialquantitativeserumhCGtestingisappropriateifectopicpregnancyor
spontaneousabortionissuspected.(See"Spontaneousabortion:Riskfactors,etiology,clinical
manifestations,anddiagnosticevaluation"and"Ectopicpregnancy:Clinicalmanifestationsand
diagnosis".)

IftheserumhCGisnegative,thetestshouldberepeatedinoneweekifanearlypregnancyis
suspected.

Diagnosisofpregnancyisdiscussedindetailseparately.(See"Clinicalmanifestationsanddiagnosisofearly
pregnancy".)

Gestationaltrophoblasticdisease,whichinsomecasespresentsweekstoyearsafterapregnancy,isalso
associatedwithuterinebleedingandapositivepregnancytest.(See"Hydatidiformmole:Epidemiology,clinical
features,anddiagnosis".)

CompletebloodcountWomenwithheavyorprolongedbleedingshouldbeevaluatedwitha
hemoglobinand/orhematocritforanemia.(See"Approachtotheadultpatientwithanemia".)

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Inaddition,aplateletcountishelpfulifableedingdisorderissuspected.Awhitebloodcellcountishelpfulif
aninfectionissuspected.Pelvicinflammatorydisease(PID)withendometritisisapotentialetiologyofAUB.
Acuteendometritisfollowingchildbirthoranintrauterineproceduremaybeassociatedwithleukocytosis,but
thewhitebloodcellcountistypicallynormalinchronicendometritis.(See"Endometritisunrelatedto
pregnancy"and"Pelvicinflammatorydisease:Clinicalmanifestationsanddiagnosis",sectionon'Pointofcare
andlaboratorytests'.)

AdditionaltestsAdditionaltestingisselectiveanddependsuponinformationobtainedonhistoryand
physicalexamination.

EndocrinetestsTestsofendocrinefunctionareperformedbaseduponthehistoryandphysical
examinationfindings:

ThyroidfunctiontestsItisnotnecessarytoassessforthyroiddiseaseinallwomenwithAUB.
Thyroiddiseaseappearstobeassociatedmainlywitholigomenorrheaoramenorrhea.Ifthemenstrual
historysuggestsovulatorydysfunction,checkingathyroidstimulatinghormone(TSH)isappropriate.
Somedatasuggestthatheavymenstrualbleeding(HMB)isassociatedwithhypothyroidisminasmall
proportionofwomen.ForwomenwithHMB,aTSHshouldbeperformedifnootheretiologyhasbeen
identified.(See'Irregularbleeding(ovulatorydysfunction)'aboveand'Heavymenstrualbleeding'above.)

ProlactinlevelAprolactinlevelshouldbemeasuredinwomenwhocomplainofanovulatorybleeding,
amenorrhea,orgalactorrhea,oraretakingmedicationsthatcancausehyperprolactinemia(table6).(See
"Clinicalmanifestationsandevaluationofhyperprolactinemia".)

AndrogenlevelsSerumandrogensshouldbemeasuredinwomenwithAUBandsignsofandrogen
excess.Hirsutism(excessivemalepatternfacialandbodyhair)isfarmorecommonthanvirilization
(deepeningofthevoice,temporalbalding,breastatrophy,changestowardamalebodyhabitus,and/or
clitoromegaly)[28].Polycysticovariansyndrome(PCOS)isthemostcommoncauseofhirsutismand
amenorrheaoranovulatorybleeding.However,clinicalmanifestationsofhyperandrogenismmayalsobe
seeninwomenwithcongenitaladrenalhyperplasia.Ifvirilizationispresent,amoresevereandrogen
excessshouldbesuspectedandthepatientshouldbeevaluatedforanandrogensecretingtumorofthe
adrenalglandorovary(table13).(See"Diagnosisofpolycysticovarysyndromeinadults",sectionon
'Serumandrogens'and"Pathogenesisandcausesofhirsutism".)

FolliclestimulatinghormoneorluteinizinghormoneFolliclestimulatinghormone(FSH)and
luteinizinghormone(LH)arereleasedbythepituitarygland.Ifprematureovarianinsufficiencyis
suspected,aserumFSHshouldbeperformed.Forwomenwithsuspectedhypothalamicdysfunction(due
topoornutritionorintenseexercise),aFSHandLHshouldbeperformed,aswellasan
estrogen/progestinwithdrawaltest.(See"Clinicalmanifestationsandevaluationofspontaneousprimary
ovarianinsufficiency(prematureovarianfailure)",sectionon'Diagnosis'and"Evaluationandmanagement
ofsecondaryamenorrhea",sectionon'Followuptestingbaseduponinitialresults'.)

EstrogenlevelsEstrogenexcessduetoanestrogensecretingovariantumorisarareetiologyofAUB,
butshouldbeconsideredifanadnexalmassispresentandifotheretiologieshavebeenexcluded(table
13).(See"Sexcordstromaltumorsoftheovary:Granulosastromalcelltumors".)

AssessmentofovulatoryfunctionAnovulationistypicallydiagnosedbaseduponthecharacteristic
bleedingpatternlaboratoryevaluationisnottypicallyrequired.Laboratoryconfirmationofanovulation
maybeusefulinwomenwithinfertility.(See"Evaluationoffemaleinfertility",sectionon'Assessmentof
ovulatoryfunction'.)

CoagulationtestsBleedingdisordersarecommoninreproductiveagewomen.Upto15to24percentof
womenpresentingwithmenorrhagiamayhavesometypeofbleedingdiathesis(eg,vonWillebranddisease,
immunethrombocytopenia,orplateletfunctiondefect)[2931].Inaddition,excessivebleedingmaybecaused
byleukemia,liverorrenaldisease,anticoagulants,prescriptionandnonprescriptiondrugsthatimpact
coagulationorplateletfunction,andchemotherapeuticagents.(See"Approachtotheadultpatientwitha
bleedingdiathesis",sectionon'Menorrhagia'and"Differentialdiagnosisofgenitaltractbleedinginwomen",
sectionon'Bleedingdisorders'.)

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Coagulationdisorderstypicallypresentasheavybleedingatmenarcheorinwomenintheirlaterreproductive
years.ForvonWillebranddisease,decreasingestrogenlevelsduringthemenopausaltransitionimpactvon
Willebrandfactorsynthesis.Excessivebleedingrelatedtomedicationsorsystemicillnessmaypresentatany
age.(See"ClinicalpresentationanddiagnosisofvonWillebranddisease",sectionon'VariationsinVWFlevels
inhealthanddisease'.)

Ableedingdisordershouldbesuspectedifheavyorprolongedmensesbeganatmenarche,isassociatedwith
afamilyhistoryofcoagulopathy,thepatienthassignsofableedingdiathesis(eg,easybruisingorprolonged
bleedingfrommucosalsurfaces),oristakingmedicationsassociatedwithanincreasedbleedingtendency
(table14)[3234].

Womenwhoaretakingwarfarinshouldhavecoagulationparametersassessedtoseeiftheeffectiswithinthe
therapeuticwindow.Inaddition,patientsshouldbeaskedaboutotherprescriptionornonprescription
medicationsthatmayimpactcoagulationorplateletfunction.(See"Approachtotheadultpatientwitha
bleedingdiathesis",sectionon'Medicationuse'.)

Theevaluationforpatientswithasuspectedbleedingdisorderisdiscussedseparately.(See"Approachtothe
adultpatientwithableedingdiathesis",sectionon'Laboratorytesting'.)

TeststoexcludecervicalbleedingItisoftendifficulttodifferentiatecervicalanduterinebleeding
baseduponhistoryandphysicalexamination.Ifthereisuncertaintyaboutthesourceofthebleeding,abasic
evaluationforetiologiesofcervicalbleedingshouldbeperformed.(See'Istheuterusthesourceofthe
bleeding?'above.)

CervicalcancerscreeningCervicalneoplasiacancausecervicalbleeding,whichisoftenmistakenfor
uterinebleeding.AllwomenwithAUBshouldbeappropriatelyscreenedforcervicalcancer,accordingto
currentguidelines.(See"Screeningforcervicalcancer".)

TestsforcervicitisGenitaltractinfectionwithNeisseriagonorrhoeaeorChlamydiatrachomatismay
causecervicitisandpresentwithcervicalbleeding.Inaddition,thesearecommonpathogensinPID,
whichisanetiologyofAUB.AlthoughlesscommonthanN.gonorrhoeaeandC.trachomatisasacause
ofcervicitis,trichomonasandherpessimplexvirusinfectionscancausecervicitisandresultincervical
bleeding.Testingfortheseinfectionsshouldbeperformedinwomenathighriskandinthosewitha
findingonexaminationofafriablecervix,purulentvaginalorcervicaldischarge,orpelvictenderness[2].
(See"ClinicalmanifestationsanddiagnosisofNeisseriagonorrhoeaeinfectioninadultsandadolescents"
and"Acutecervicitis"and"ClinicalmanifestationsanddiagnosisofChlamydiatrachomatisinfections".)

ENDOMETRIALSAMPLINGAfterpregnancyhasbeenexcluded,endometrialsamplingshouldbe
performedinwomenwithAUBandanincreasedriskofendometrialhyperplasiaorcancer(table3andtable4).

IndicationsforendometrialsamplinginwomenofreproductiveagewithAUBvarybyagegroup(table3):

Age45yearstomenopauseInwomenwhoareovulatory,anyAUB,includingintermenstrualbleeding.
Inanywoman,bleedingthatisfrequent(intervalbetweentheonsetofbleedingepisodesis<21days),
heavy,orprolonged(>5days)(table7).

Youngerthan45yearsInreproductiveagewomen,themajorityofcasesofendometrialneoplasia
occurinthesettingofovulatorydysfunctionduetoestrogenicproliferationwithabsentorinadequate
progestationalprotection[35].EndometrialsamplingisindicatedifAUBispersistent,occursinthe
settingofahistoryofunopposedestrogenexposure(obesity,chronicanovulation)orfailedmedical
managementofthebleeding,orinwomenathighriskofendometrialcancer(eg,tamoxifentherapy,
LynchorCowdensyndrome).

Useof45yearsoldasthethresholdforincreasedconcernregardingendometrialneoplasiaissupportedby
evidencethattheriskofendometrialhyperplasiaandcarcinomaisfairlylowpriortoage45yearsand
increaseswithadvancingage19percentofcasesoccurinwomenaged45to54yearscomparedwith6
percentinthoseaged35to44years[3638].ThisagethresholdisalsoconsistentwithAmericanCollegeof
ObstetriciansandGynecologists(ACOG)guidelines[9,35].(See"Classificationanddiagnosisofendometrial
hyperplasia",sectionon'Epidemiology'and"Endometrialcarcinoma:Epidemiologyandriskfactors",section
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on'Epidemiology'.)

Amongwomen<45yearsold,thereisnostandarddefinitionofpersistentAUB.Forwomenwithovulatory
dysfunction,giventhatsixmonthsofunopposedestrogentherapysubstantiallyincreasestheriskof
endometrialhyperplasiainmenopausalwomen,itisreasonabletoconsidersixmonthsormoreofAUBOas
persistent[39].ForothertypesofAUB,theclinicianmustusetheirjudgementregardingwhenabnormal
bleedingispersistent.

Endometrialneoplasiaisrareinadolescentsages13to18years(0.05percentofcasesofendometrialcancer
occurinpatientsages15to19years[40]),butitmaydevelopinthesettingofobesitywithanovulation
(polycysticovariansyndrome[PCOS])[41].Inthisagegroup,aswithotherreproductiveagewomen,thelevel
ofsuspicionishigherinpatientswhoareobeseorwhofailmedicaltherapy.

Transvaginalultrasoundmeasurementofendometrialthicknesstoevaluateforendometrialneoplasiaisan
alternativetoendometrialsamplinginwomenwithpostmenopausalbleeding,butNOTinpremenopausal
women.Inpremenopausalwomen,measurementofendometrialthicknessisnotausefultest,sincemajor
variationofthethicknessoccursduringthenormalmenstrualcycle.Inthispatientpopulation,transvaginal
ultrasounddoesprovideusefulinformationregardingstructuralcausesofAUBandcanidentifyaheterogenous
endometriumduetohyperplasiaorcancer.(See"Evaluationoftheendometriumformalignantorpremalignant
disease",sectionon'Premenopausalwomen'.)

Suspicionofendometritisisanotherindicationforendometrialsampling.ForwomenwithAUBduringthe
postpartumorpostabortalperiod,endometrialsamplingmayrevealretainedproductsofconception.(See
"Postpartumendometritis"and"Endometritisunrelatedtopregnancy"and"Retainedproductsofconception".)

Endometrialsamplingistypicallyperformedasanofficebiopsy,butdilationandcurettageorhysteroscopically
directedbiopsymaybeperformedifbleedingpersistsafteranormalendometrialbiopsyorifthereareother
indicationsforanoperativeprocedure.(See"Endometrialsamplingprocedures"and"Evaluationofthe
endometriumformalignantorpremalignantdisease".)

IMAGINGANDHYSTEROSCOPYThedecisiontoproceedwithpelvicimagingshouldbebaseduponthe
cliniciansjudgement,dependingonpatientage,historyandsymptoms.

Thechoicetodoimagingisguidedbyseveralfactors:

Iftheabdominaland/orbimanualpelvicexaminationfindingsincludeanenlargedorglobularuterusor
adnexalmass,imagingisappropriatetoevaluateforleiomyomas,adenomyosis,andadnexalpathology.

Imagingmaybeomitted,atleastintheinitialevaluation,ifthebleedingisthoughttobeduetoalesion
observedonphysicalexamination(endocervicalpolyp),anovulation,orinfection[42].

Ifthepelvicexaminationisnormal,imagingisalsoappropriateifsymptomspersistdespitetreatment.

ChoiceofmodalityPelvicultrasoundisthefirstlineimagingstudyinwomenwithAUB.Transvaginal
examinationshouldbeperformed,unlessthereisareasontonotperformthevaginalstudy(eg,virginal
patient).Transabdominalsonographyshouldalsobeperformediftransvaginalimagingdoesnotallowadequate
assessmentoftheuterusoradnexaorifalargepelvicmassispresent.

Ultrasoundiseffectiveatcharacterizinguterineandadnexallesions.Asnotedabove,assessmentof
endometrialthicknessisnotausefultestinpremenopausalwomen.Ultrasoundislessexpensivethan
magneticresonanceimaging(MRI),whichshouldbeusedforpelvicassessmentonlyasafollowupimaging
testandonlywhenitwillgiveinformationthatisnotavailableonultrasound.Computedtomographyisusedto
evaluatethepelvisformetastaticdiseaseinsomemalignancies,buthasnoroleinroutinepelvicassessment.
(See"Evaluationoftheendometriumformalignantorpremalignantdisease",sectionon'Premenopausal
women'.)

Ifintracavitarypathology(lesionsthatprotrudeintotheuterinecavity,ie,endometrialpolyps,submucosal
myomas,intramuralmyomaswithanintracavitarycomponent)issuspectedbasedupontheinitialultrasound,
thepatientmaybeevaluatedwitheithersalineinfusionsonohysterographyorhysteroscopy.

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Salineinfusionsonography(SIS)Salineinfusionsonography(alsocalledsonohysterography)isa
techniqueinwhichsterilesalineisinstilledintotheendometrialcavityandatransvaginalultrasound
examinationisperformed[43].Thisprocedureallowsforanarchitecturalevaluationoftheuterinecavity
todetectlesions(eg,polypsorsmallsubmucousfibroids)thatmaybemissedorpoorlydefinedby
transvaginalsonographyalone(image1).SISisalsousefulinevaluatingAUBassociatedwithcesarean
scardefects[8].(See"Salineinfusionsonohysterography".)

HysteroscopyHysteroscopyprovidesdirectvisualizationoftheendometrialcavity.Diagnostic
hysteroscopycanbeperformedinanofficesetting.Inanoperativesetting,hysteroscopyallowstargeted
biopsyorexcisionoflesionsidentifiedduringtheprocedure[44,45].(See"Overviewofhysteroscopy".)

WesuggestSISformostwomenforintracavitaryevaluation.BothSISandhysteroscopyareeffectivetests
fordiagnosingendometrialpolypsandsubmucosalleiomyoma[46],whileultrasoundalonehaslimited
sensitivityandspecificityforthecharacterizationoftheselesions[47,48].Comparedwithhysteroscopy,the
majoradvantageofSISisthatitcanassessthedepthofextensionofleiomyomasintothemyometriumor
serosalsurface(image2).Somefibroidsappeartobesubmucosalathysteroscopy,butareactuallyintramural
withacomponentthatprotrudesintotheuterinecavity.Thisinformationandtheabilitytoidentifyfibroidsat
othersites(figure4)canhelpsurgicalplanning.SomedataalsosuggestthatSISislesspainfulthanoffice
hysteroscopy[47,49].SISalsoisabletoidentifyasymmetricorfocalendometrialthickening,apotentially
importantmarkerofendometrialneoplasia(image3)[46].

Advantagesofhysteroscopyarethatofficehysteroscopymayofferpatientsgreaterconvenience,particularlyif
itcanbeperformedatthesamevisitastheinitialevaluation.Operativehysteroscopyisnottypicallyavailable
inanofficesettingandthereforeisnotpartoftheinitialevaluationofAUB.

Factorssuchasconvenience,availabilityofequipmentandtrainedpersonnel,andcostofSISand
hysteroscopyvaryindifferentclinicalsettings,andthesefactorsofteninfluencethechoiceofstudy.

INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,TheBasics
andBeyondtheBasics.TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6th
gradereadinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagiven
condition.Thesearticlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoread
materials.BeyondtheBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.
Thesearticlesarewrittenatthe10thto12thgradereadinglevelandarebestforpatientswhowantindepth
informationandarecomfortablewithsomemedicaljargon.

Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthese
topicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon
patientinfoandthekeyword(s)ofinterest.)

Basicstopics(see"Patientinformation:Heavyperiods(TheBasics)")

BeyondtheBasicstopics(See"Patientinformation:Abnormaluterinebleeding(BeyondtheBasics)"and
"Patientinformation:Heavyorprolongedmenstrualbleeding(menorrhagia)(BeyondtheBasics)"and
"Patientinformation:Absentorirregularperiods(BeyondtheBasics)".)

SUMMARYANDRECOMMENDATIONS

Abnormaluterinebleeding(AUB)isacommongynecologiccomplaint.AUBcanbecausedbyawide
varietyoflocalandsystemicdiseasesorrelatedtomedications(table1)[2].Themostcommon
etiologiesareconditionsassociatedwithpregnancy,structuraluterinepathology(eg,fibroids,endometrial
polyps,adenomyosis),anovulation,bleedingdisorders,orneoplasia.(See'Introduction'aboveand
'Prevalenceandetiology'above.)

TheinitialapproachtoevaluationofnonpregnantreproductiveagewomenwithAUBistoconfirmthatthe
sourceofbleedingistheuterus,excludepregnancy,andconfirmthatthepatientispremenopausal.In
addition,womenwithacutebleedingshouldbeevaluatedinanurgentcarefacility.(See'Initialevaluation'
above.)

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Thegoalsoffurtherevaluationaretodeterminethepattern,severity,andetiologyofthebleedingtoguide
management.Aprimaryfocusistoidentifywomenwhorequireevaluationforendometrialcarcinomaor
otheruterinemalignancies.(See'Furtherevaluation'above.)

AUBvariesfromnormalmensesintermsoffrequency,regularity,volume,orduration(table7).Typical
abnormalbleedingpatternsinclude:regularmensesthatareheavyorprolonged,intermenstrualbleeding,
irregularbleeding(typicallyassociatedwithovulatorydysfunction),andamenorrhea.(See'Menstrual
history'above.)

EndometrialsamplingshouldbeperformedinnonpregnantwomenwithAUBandanincreasedriskof
endometrialhyperplasiaorcancer.Indicationsforendometrialsamplingvarybyagegroup(table3and
table4).(See'Endometrialsampling'above.)

Bleedingdisorders,particularlyvonWillebranddisease(VWD),arecommoninreproductiveagewomen.
Adisordershouldbesuspectedifheavyorprolongedmensesbeganatmenarcheorisassociatedwitha
familyhistoryofcoagulopathyorothersignsofableedingdiathesis(eg,easybruisingorprolonged
bleedingfrommucosalsurfaces).Inaddition,anticoagulantsmaycauseheavyorprolongeduterine
bleeding.(See'Coagulationtests'above.)

Hormonalcontraceptionoranintrauterinedevice(IUD)maycauseAUB.(See'Generalhistory'above.)

AllwomenwithAUBshouldhaveacompletehistoryandphysicalexamination.Informationshouldbe
obtainedonthefrequency,duration,andvolumeofAUB,aswellasthepresenceofassociated
symptomsandprecipitatingfactors.(See'History'aboveand'Physicalexamination'above.)

MostreproductiveagewomenwithAUBshouldbeevaluatedinitiallywiththefollowingtests:human
chorionicgonadotropin(hCG),completebloodcount,hemoglobinand/orhematocrit.Additionaltestsmay
beperformedtoassessforparticularetiologies.(See'Initialtests'aboveand'Additionaltests'above.)

Pelvicimagingisusefulifastructurallesion(endometrialpolyps,leiomyomas,adenomyosis,oran
adnexalmass)issuspectedbaseduponthehistoryandphysicalexaminationitisnotrequiredinevery
womanwithAUB.Pelvicultrasoundisthefirstlinestudyandisoftenusedalone,ormaybecombined
witheithersalineinfusionsonographyorhysteroscopytoprovideinformationaboutlesionsthatprotrude
intotheendometrialcavity(submucosalleiomyomas,myometrialleiomyomasthatprotrudeintothe
cavity,andendometrialpolyps).(See'Imagingandhysteroscopy'above.)

ACKNOWLEDGMENTTheauthorandUpToDatewouldliketoacknowledgeDr.AnnekathrynGoodman,
whocontributedtoearlierversionsofthistopicreview.

UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.

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25.DasharathySS,MumfordSL,PollackAZ,etal.Menstrualbleedingpatternsamongregularly
menstruatingwomen.AmJEpidemiol2012175:536.
26.O'ConnorRE,BibroCM,PeggPJ,BouzoukisJK.Thecomparativesensitivityandspecificityofserum
andurineHCGdeterminationsintheED.AmJEmergMed199311:434.
27.NormanRJ,MenabaweyM,LowingsC,etal.Relationshipbetweenbloodandurineconcentrationsof
intacthumanchorionicgonadotropinanditsfreesubunitsinearlypregnancy.ObstetGynecol1987
69:590.
28.FritzMA,SperoffL.Hirsutism.In:ClinicalGynecologicEndocrinologyandInfertility,8thed.,Lippincott
Williams&Wilkins,Philadelphia2011.p.533.
29.KadirRA,EconomidesDL,SabinCA,etal.Frequencyofinheritedbleedingdisordersinwomenwith
menorrhagia.Lancet1998351:485.
30.KouidesPA,ByamsVR,PhilippCS,etal.Multisitemanagementstudyofmenorrhagiawithabnormal
laboratoryhaemostasis:aprospectivecrossoverstudyofintranasaldesmopressinandoraltranexamic
acid.BrJHaematol2009145:212.
31.CommitteeonAdolescentHealthCare,CommitteeonGynecologicPractice.CommitteeOpinion
No.580:vonWillebranddiseaseinwomen.ObstetGynecol2013122:1368.
32.DilleyA,DrewsC,MillerC,etal.vonWillebranddiseaseandotherinheritedbleedingdisordersin
womenwithdiagnosedmenorrhagia.ObstetGynecol200197:630.
33.PhilippCS,FaizA,DowlingN,etal.Ageandtheprevalenceofbleedingdisordersinwomenwith
menorrhagia.ObstetGynecol2005105:61.
34.LukesAS,KadirRA,PeyvandiF,KouidesPA.Disordersofhemostasisandexcessivemenstrual
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bleeding:prevalenceandclinicalimpact.FertilSteril200584:1338.
35.CommitteeonPracticeBulletinsGynecology.Practicebulletinno.136:managementofabnormal
uterinebleedingassociatedwithovulatorydysfunction.ObstetGynecol2013122:176.
36.http://seer.cancer.gov/statfacts/html/corp.html(AccessedonAugust13,2012).
37.ReedSD,NewtonKM,ClintonWL,etal.Incidenceofendometrialhyperplasia.AmJObstetGynecol
2009200:678.e1.
38.http://seer.cancer.gov/statfacts/html/corp.html(AccessedonDecember20,2011).
39.LethabyA,SucklingJ,BarlowD,etal.Hormonereplacementtherapyinpostmenopausalwomen:
endometrialhyperplasiaandirregularbleeding.CochraneDatabaseSystRev2004:CD000402.
40.http://seer.cancer.gov/statfacts/html/corp.html(AccessedonSeptember11,2013).
41.BrownAJ,WestinSN,BroaddusRR,SchmelerK.Progestinintrauterinedeviceinanadolescentwith
grade2endometrialcancer.ObstetGynecol2012119:423.
42.DoubiletPM.Diagnosisofabnormaluterinebleedingwithimaging.Menopause201118:421.
43.KhanF,JamaatS,AlJaroudiD.Salineinfusionsonohysterographyversushysteroscopyforuterine
cavityevaluation.AnnSaudiMed201131:387.
44.APGOeducationalseriesonwomen'shealthissues.Clinicalmanagementofabnormaluterinebleeding.
AssociationofProfessorsofGynecologyandObstetrics,2006.
45.BradleyLD.Diagnosisofabnormaluterinebleedingwithbiopsyorhysteroscopy.Menopause2011
18:425.
46.LaSalaGB,BlasiI,GallinelliA,etal.Diagnosticaccuracyofsonohysterographyandtransvaginal
sonographyascomparedwithhysteroscopyandendometrialbiopsy:aprospectivestudy.Minerva
Ginecol201163:421.
47.KelekciS,KayaE,AlanM,etal.Comparisonoftransvaginalsonography,salineinfusionsonography,
andofficehysteroscopyinreproductiveagedwomenwithorwithoutabnormaluterinebleeding.Fertil
Steril200584:682.
48.FarquharC,EkeromaA,FurnessS,ArrollB.Asystematicreviewoftransvaginalultrasonography,
sonohysterographyandhysteroscopyfortheinvestigationofabnormaluterinebleedinginpremenopausal
women.ActaObstetGynecolScand200382:493.
49.VandenBoschT,VergutsJ,DaemenA,etal.Painexperiencedduringtransvaginalultrasound,saline
contrastsonohysterography,hysteroscopyandofficesampling:acomparativestudy.UltrasoundObstet
Gynecol200831:346.

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GRAPHICS

PALMCOEINclassificationsystemforabnormaluterine
bleedinginnongravidreproductiveagewomen

Basicclassificationsystem.Thebasicsystemcomprisesfourcategoriesthat
aredefinedbyvisuallyobjectivestructuralcriteria(PALM:polyp
adenomyosisleiomyomaandmalignancyandhyperplasia),fourthatare
unrelatedtostructuralanomalies(COEI:coagulopathyovulatory
dysfunctionendometrialiatrogenic),andonereservedforentitiesthatare
notyetclassified(N).Theleiomyomacategory(L)issubdividedintopatients
withatleastonesubmucosalmyoma(LSM)andthosewithmyomasthatdo
notimpacttheendometrialcavity(LO).

Reproducedfrom:MunroMG,CritchleyHO,BroderMS,FraserIS,FIGOWorkingGroup
onMenstrualDisorders.FIGOclassificationsystem(PALMCOEIN)forcausesof
abnormaluterinebleedinginnongravidwomenofreproductiveage.IntJGynaecol
Obstet2011113:3.IllustrationusedwiththepermissionofElsevierInc.Allrights
reserved.

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TheStagesofReproductiveAgingWorkshop+10stagingsystemfor
reproductiveaginginwomen

Arrow:elevatedFMP:finalmenstrualperiodFSH:folliclestimulatinghormoneAMH:antimllerian
hormone.
*Blooddrawoncycledays2to5.
Approximateexpectedlevelbasedonassaysusingcurrentinternationalpituitarystandard.

Reproducedwithpermissionfrom:HarlowSD,GassM,HallJE,etal.ExecutiveSummaryoftheStagesof
ReproductiveAgingWorkshop+10:AddressingtheUnfinishedAgendaofStagingReproductiveAging.JClin
EndocrinolMetab2012.Copyright2012TheEndocrineSociety.

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Causesofabnormalgenitaltractbleedinginwomen

Genitaltractdisorders Trauma
Uterus Sexualintercourse

Benigngrowths: Sexualabuse

Endometrialpolyps Foreignbodies(includingintrauterine
Endometrialhyperplasia device)

Adenomyosis Pelvictrauma(eg,motorvehicleaccident)

Leiomyomas(fibroids) Straddleinjuries

Cancer: Drugs
Endometrialadenocarcinoma
Contraception:
Sarcoma
Hormonalcontraceptives
Infection:
Intrauterinedevices
Pelvicinflammatorydisease
Postmenopausalhormonetherapy
Endometritis
Anticoagulants
Ovulatorydysfunction
Tamoxifen
Cervix
Corticosteroids
Benigngrowths:
Chemotherapy
Cervicalpolyps
Phenytoin
Ectropion
Antipsychoticdrugs
Endometriosis
Antibiotics(eg,duetotoxicepidermal
Cancer:
necrolysisorStevensJohnsonsyndrome)
Invasivecarcinoma
Systemicdisease
Metastatic(uterus,choriocarcinoma)
Diseasesinvolvingthevulva:
Infection:
Crohn'sdisease
Cervicitis
Behcet'ssyndrome
Vulva
Pemphigoid
Benigngrowths:
Pemphigus
Skintags
Erosivelichenplanus
Sebaceouscysts
Lymphoma
Condylomata
Bleedingdisorders:
Angiokerataoma
vonWillebranddisease
Cancer
Thrombocytopeniaorplateletdysfunction
Vagina
Acuteleukemia
Benigngrowths:
Somecoagulationfactordeficiencies
Gartnerductcysts
Advancedliverdisease
Polyps
Thyroiddisease
Adenosis(aberrantglandulartissue)
Polycysticovarysyndrome
Cancer
Chronicliverdisease
Vaginitis/infection:
Cushing'ssyndrome

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Bacterialvaginosis
Hormonesecretingadrenalandovarian
Sexuallytransmitteddiseases
tumors
Atrophicvaginitis
Renaldisease
Uppergenitaltractdisease
Emotionalorphysicalstress
Fallopiantubecancer
Smoking
Ovariancancer
Excessiveexercise
Pelvicinflammatorydisease
Diseasesnotaffectingthe
Pregnancycomplications genitaltract
Urethritis

Bladdercancer

Urinarytractinfection

Inflammatoryboweldisease

Hemorrhoids

Other
Endometriosis

Vasculartumorsandanomaliesinthe
genitaltract

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Usualcausesofabnormalgenitalbleedinginwomenbyagegroup

Neonates Reproductiveage
Estrogenwithdrawal Ovulatorydysfunction

Premenarchal Pregnancy

Foreignbody Cancer

Polyps,leiomyomas,adenomyosis
Trauma,includingsexualabuse

Infection Infection

Endocrinedysfunction(polycysticovary
Urethralprolapse
syndrome,thyroid,hyperprolactinemia)
Sarcomabotryoides
Bleedingdiathesis
Ovariantumor
Medicationrelated(eg,hormonal
Precociouspuberty contraception)

Earlypostmenarche Menopausaltransition
Ovulatorydysfunction(hypothalamic Anovulation
immaturity)
Polyps,fibroids,adenomyosis
Bleedingdiathesis
Cancer
Stress(psychogenic,exerciseinduced)
Menopause
Pregnancy
Endometrialatrophy
Infection
Cancer

Postmenopausalhormonetherapy

Adaptedfrom:APGOeducationalseriesonwomen'shealthissues.Clinicalmanagementofabnormal
uterinebleeding.AssociationofProfessorsofGynecologyandObstetrics,May2002.

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Evaluationofabnormaluterinebleedinginnonpregnant
reproductiveagewomen

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Riskfactorsforendometrialcancer

Relativerisk(RR)
Riskfactor (otherstatisticsarenotedwhen
used)
Increasingage Women50to70yearsoldhavea1.4
percentriskofendometrialcancer

Unopposedestrogentherapy 2to10

Tamoxifentherapy 2

Earlymenarche NA

Latemenopause(afterage55) 2

Nulliparity 2

Polycysticovarysyndrome(chronic 3
anovulation)

Obesity 2to4

Diabetesmellitus 2

Estrogensecretingtumor NA

Lynchsyndrome(hereditarynonpolyposis 22to50percentlifetimerisk
colorectalcancer)

Cowdensyndrome 13to19percentlifetimerisk

Familyhistoryofendometrial,ovarian,breast, NA
orcoloncancer

NA:RRnotavailable.

AdaptedfromdatainSmithRA,vonEschenbachAC,WenderR,etal.AmericanCancerSociety
GuidelinesforEarlyEndometrialCancerDetection:Update2001.

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Womenwhoshouldundergoevaluationforendometrial
hyperplasiaorendometrialcancer

Abnormaluterinebleeding

PostmenopausalwomenAnyuterinebleeding,regardlessofvolume(includingspotting
orstaining).Furtherevaluationofasonographicfindingofanendometrialthickness>4
mm(evenifthepatienthasnouterinebleeding).

Age45yearstomenopauseAnyabnormaluterinebleeding,includingintermenstrual
bleedinginwomenwhoareovulatory.Abnormaluterinebleedinginanywomanthatis
frequent(intervalbetweentheonsetofbleedingepisodesislessthan21days),heavy
(totalvolumeof>80mL),orprolonged(longerthansevendays).

Youngerthan45yearsAbnormaluterinebleedingthatispersistent,occursinthe
settingofahistoryofunopposedestrogenexposure(obesity,chronicanovulation)or
failedmedicalmanagementofthebleeding,orinwomenathighriskofendometrial
cancer(eg,tamoxifentherapy,Lynchsyndrome,Cowdensyndrome).

Inaddition,endometrialneoplasiashouldbesuspectedinpremenopausalwomenwhoare
anovulatoryandhaveprolongedperiodsofamenorrhea(sixormoremonths).

Cervicalcytologyresults

Presenceofatypicalglandularcells(AGC)endometrial.

PresenceofAGCallsubcategoriesotherthanendometrialIf35yearsoldORatriskfor
endometrialcancer(riskfactorsorsymptoms).

Presenceofbenignappearingendometrialcellsinwomen40yearsofagewhoalsohave
abnormaluterinebleedingorriskfactorsforendometrialcancer.

Otherindications

Monitoringofwomenwithendometrialpathology(eg,endometrialhyperplasia).

Screeninginwomenathighriskofendometrialcancer(eg,Lynchsyndrome).

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Evaluationanddifferentialdiagnosisofabnormaluterinebleeding
(AUB)innonpregnantreproductiveagewomen

Other Differentialdiagnosis
Bleeding associated
Less Evaluation
pattern clinical Common
common
etiologies
features etiologies

Regularmenses Enlargeduterus Uterineleiomyoma Pelvicultrasound


thatareheavy onexamination,
Salineinfusion
orprolonged discretemasses
sonographyor
maybenoted
hysteroscopy(if
intracavitary
pathologyis
suspected)

Dysmenorrhea Adenomyosis Pelvicultrasound

Enlarged,
boggyuteruson
examination

Familyhistory Bleedingdisorder Testingfor


ofbleeding bleedingdisorder
disorder

Symptomsof
bleeding
diathesis
Anticoagulant
therapy

Riskfactorsfor Endometrial Endometrial


uterine carcinomaor sampling
malignancy uterine
sarcoma

Regularmenses Endometrialpolyp Pelvicultrasound


with Salineinfusion
intermenstrual sonographyor
bleeding
hysteroscopy(if
available)
Riskfactorsfor Endometrial Seeendometrial
uterine carcinomaor carcinomaabove
malignancy uterine
sarcoma

Recenthistory Chronic Endometrial


ofuterineor endometritis sampling
cervical
procedureor
childbirth,
particularlyif
infectionwas
present

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Irregular Ovulatory
bleeding,may dysfunction:
bemoreorless
Hirsutism,acne, PCOS Totaltestosterone
frequentthan
and/orobesity and/orother
normalmenses
androgens(may
andvolumeand
notbeincreasedin
durationmay
allwomenwith
vary
PCOS)

Galactorrhea Hyperprolactinemia Prolactin

Recentweight Thyroiddisease Thyroidfunction


gainorloss tests

Heatorcold
intolerance
Familyhistory
ofthyroid
dysfunction

Riskfactorsfor Endometrial
uterine carcinomaor
malignancy uterine
sarcoma

Secondary Poornutritionor Hypothalamic Follicle


amenorrhea intenseexercise amenorrhea stimulating
hormone
Luteinizing
hormone

Estrogen/progestin
withdrawaltest

Hotflushes Prematureovarian Folliclestimulating


insufficiency hormone

Recenthistory Cervical Onpelvic


ofuterineor stenosis examination,
cervical instrumentcannot
procedureor bepassedthrough
childbirth, internalcervicalos
particularlyif
infectionwas
present Intrauterine Hysteroscopy
(mensesmay adhesions
present,but (Asherman
abnormallylight syndrome)
orbrief)

Irregularor IatrogenicAUB
heavybleeding
inapatienton
hormonal
contraceptives
orwithan
intrauterine

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device

OtheruncommonetiologiesofAUBincludeauterinearteriovenousmalformationor
endometriosis.

PCOS:polycysticovariansyndrome.

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Medicationsthatcausehyperprolactinemia

Frequencyof
Medicationclass Mechanism
prolactinelevation*

Antipsychotics,firstgeneration

Chlorpromazine Moderate DopamineD 2 receptor


blockadewithinhypothalamic
Fluphenazine High
tuberoinfundibularsystem
Haloperidol High

Loxapine Moderate

Perphenazine Moderate

Pimozide Moderate

Thiothixene Moderate

Trifluoperazine Moderate

Antipsychotics,secondgeneration

Aripiprazole Noneorlow DopamineD 2 receptor


blockade
Asenapine Moderate

Clozapine Noneorlow

Iloperidone Noneorlow

Lurasidone Noneorlow

Olanzapine Low

Paliperidone High

Quetiapine Noneorlow

Risperidone High

Ziprasidone Low

Antidepressants,cyclic

Amitriptyline Low Notwellunderstood.Possibly


byGABAstimulationand
Desipramine Low
indirectmodulationof
Clomipramine High prolactinreleasebyserotonin.
Nortriptyline None

Antidepressants,SSRI

Citalopram,fluoxetine, Noneorlow(rarereports) Sameasforcyclic


fluvoxamine,paroxetine, antidepressants
sertraline

Antidepressants,other

Bupropion,venlafaxine, None Notapplicable


mirtazapine,nefazodone,
trazodone

Antiemeticandgastrointestinal

Metoclopramide High DopamineD 2 receptor


blockade
Domperidone(notavailable High
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inUnitedStates)

Prochlorperazine Low

Antihypertensives

Verapamil Low Notwellunderstood.Specific


toverapamil.Mayinvolve
calciuminfluxinhibition
withintuberoinfundibular
dopaminergicneurons.

Methyldopa Moderate DecreasedconversionofL


dopatodopamine
suppressionofdopamine
synthesis

Mostother None Notapplicable


antihypertensives
(includingothercalcium
channelblockers)

Opioidanalgesics

Methadone,morphine, Transientincreaseforseveral Potentiallyanindirecteffectof


others hoursfollowingdose muopiatereceptoractivation

Medicationinducedhyperprolactinemiacancausedecreasedlibidoanderectiledysfunction
inmenandgalactorrheaandamenorrheainwomen.

GABA:gammaaminobutyricacidSSRI:selectiveserotoninreuptakeinhibitor.
*Frequencyofincreasetoabnormalprolactinlevelswithchronicuse:high>50percentmoderate:
25to50percentlow:<25percentnoneorlow:casereports.Effectmaybedosedependent.

Datafrom:
1.MolitchME.Drugsandprolactin.Pituitary200811:209.
2.MolitchME.Medicationinducedhyperprolactinemia.MayoClinProc200580:1050.
3.CokerF,TaylorD.Antidepressantinducedhyperprolactinemia.CNSDrugs201024:563.
4.Drugsforpsychiatricdisorders.TreatGuidelMedLett201311:53.

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Characteristicsofnormalmensesversusabnormaluterine
bleeding

Normal
Characteristic Abnormaluterinebleeding
menses
Frequency Every21to35 <21daysor>35days
days

Regularity Cyclesoccur Variationfromonecycletothenextofmorethan20


withafairly daysisconsideredirregular
consistent
frequency

Volume 5 [1]to80mL Volumeofbloodisdifficulttomeasure.Inclinical


ofblood practice,heavymensesaregenerallydefinedas
soakingapadortamponmorethaneverytwohours
orasavolumeofbleedingthatinterfereswithdaily
activities(eg,wakespatientfromsleep,stainsclothing
orsheets).

Duration Bleedingfor5 Bleedingfor>5days


days

Reference:
1.FraserIS,CritchleyHO,MunroMG,BroderM.Canweachieveinternationalagreementon
terminologiesanddefinitionsusedtodescribeabnormalitiesofmenstrualbleeding?Hum
Reprod200722:635.
Datafrom:CommitteeonPracticeBulletinsGynecology.Diagnosisofabnormaluterinebleedingin
reproductiveagedwomen.PracticeBulletinNo.128.ObstetGynecol2012120:197.

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Questionstoasktohelpquantifybloodlossduringmenses
Howoftendoyouchangeyoursanitarypad/tamponduringpeakflowdays?

Howmanypads/tamponsdoyouuseoverasinglemenstrualperiod?

Doyouneedtochangethepad/tamponduringthenight?

Howlargeareanyclotsthatarepassed?

Hasamedicalprovidertoldyouthatyouareanemic?

Womenwithanormalvolumeofmenstrualbloodlosstendto:

changepads/tamponsat3hourintervals,

usefewerthan21pads/tamponspercycle,

seldomneedtochangethepad/tamponduringthenight,

haveclotslessthan1inchindiameter,

notbeanemic

Adaptedfrom:WarnerPE,CritchleyHD,LumsdenMA,etal.MenorrhagiaI:measuredbloodloss,
clinicalfeatures,andoutcomeinwomenwithheavyperiods:asurveywithfollowupdata.AmJ
ObstetGynecol2004190:1216.

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Causesofheavyorprolongedmenses

Coagulopathy Structurallesion
vonWillebranddisease Uterineleiomyomas(fibroids)

Thrombocytopenia(duetoidiopathic Adenomyosis
thrombocytopenicpurpura,hypersplenism,
Endometrialpolyps
chronicrenalfailure)

Acuteleukemia
Other

Anticoagulants Endometritis

Advancedliverdisease Hypothyroidism

Intrauterinedevice
Neoplasm
Hyperestrogenism
Endometrialhyperplasiaorcarcinoma
Endometriosis
Uterinesarcoma

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Causesofintermenstrualbleeding

Drugs
Oralcontraceptives

Infection
Cervicitis*

Endometritis

Sexuallytransmittedulcerations*

Vaginitis

Benigngrowths
Cervicalpolyps*

Endometrialpolyps

Ectropion*

Uterinefibroids

Vulvarskintags,sebaceouscysts,condylomata

VaginalGartner'sductcysts,polyps,adenosis

Cancer
Uterine

Cervical*

Vaginal

Vulvar

Rarelyovarianorfallopiantube

Trauma
Previouscesareandeliveryincision

*Oftencausepostcoitalbleeding.

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Causesofovulatorydysfunction

Primaryhypothalamicpituitarydysfunction
Kallman'ssyndrome

Idiopathichypogonadotropichypogonadism

Tumors,trauma,orradiationofthehypothalamicorpituitaryarea

Sheehan'ssyndrome

Emptysellasyndrome

Pituitaryadenomaorotherpituitarytumors

Lymphocytichypophysitis(autoimmunediseases)

Lactationalamenorrhea

Stress

Eatingdisorders

Intenseexercise

Immaturityatonsetofmenarcheorperimenopausaldecline

Otherdisorders
Polycysticovarysyndrome

Hyperthyroidismorhypothyroidism

Hormoneproducingtumors(adrenal,ovarian)

Chronicliverorrenaldisease

Cushing'sdisease

Congenitaladrenalhyperplasia

Prematureovarianfailure,whichmaybeautoimmune,genetic,surgicalidiopathic,orrelated
todrugsorradiation

Turnersyndrome

Androgeninsensitivitysyndrome

Medications
Estrogenprogestincontraceptives

Progestins

Antidepressantandantipsychoticdrugs

Corticosteroids

Chemotherapeuticagents

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Agerelatedintervalbetweenmenses

Selectedpercentilesforthedistributionofmenstrualintervalbyage
basedondatafromover200,000cycles.Longerintermenstrual
intervalsoccurinwomenjustaftermenarcheandintheyears
precedingmenopause.

Datafrom:TreloarAE,BoyntonRE,BehnBG,BrownBW.Variationofthe
humanmenstrualcyclethroughreproductivelife.IntJFertil196712:77.

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Pregnancytesting

Urinepregnancytest Serumpregnancytest
MinimumhCG Qualitativetest:20to50int. Qualitativetest:5to10int.units/L,
levelfora units/L,dependingontest dependingontest
positivetest
Quantitativetest:1to2int.units/L
foranultrasensitivetest

Causesofa 1.PerformedtoosoonafterconceptionhCGconcentrationisbelow
falsenegative thresholdforapositivetest
test 2.ThehCGisoformmeasuredisdifferentfromthehCGisoforminthe
sample(pertainsmostlytourinetests)
3.HookeffectduetoextremelyhighhCGconcentration(>500,000int.
units/L,theselevelsaremostcommonlyseeningestational
trophoblasticneoplasia)

Causesofa 1.Pregnancylossverysoonafterimplantation("biochemical
falsepositive pregnancy")
test 2.hCGsecretionfromatumor
3.PituitaryhCGsecretion
4.Interferencefromhumanantibodiesagainstanimalantibodiesor
heterophilicantibodies(serumtestpositivebuturinehCGwillbe
negative)
5.PatienthasreceivedamedicationcontaininghCGorcertainantibodies

hCG:humanchorionicgonadotropin.

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Markerssecretedbygermcellandsexcordstromaltumorsofthe
ovary

AFP hCG LDH E2 Inhibin Testost Andro DHEA AMH

Germcelltumors

Dysgerminoma * +

Embryonal +

Immature
teratoma

Choriocarcinoma +

Endodermalsinus + +

Gonadoblastoma

Polyembryona +

Mixedgermcell

Sexcordstromaltumors

Thecomafibroma

Granulosacell +

SertoliLeydig

AFP:alphafetoproteinhCG:humanchorionicgonadotrophinLDH:lactatedehydrogenaseE2:
estradioltestost:testosteroneandro:androstenedioneDHEA:dihydroepiandrostenedioneAMH:
antiMullerianhormone.
*Borderlineelevationsincasereports(<16ng/ml).
Lowlevelseenindysgerminomaswitheithernondysgerminomatouselementsof
syncytiotrophobalsticcells.
Typeofgermcellsexcordstromaltumorconsistingofneoplasticgermcellsandsexcordstromal
derivatives.

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Screeningforbleedingdisordersinwomenwithheavymenstrual
bleeding

Initialscreeningforanunderlyingdisorderofhemostasisinpatients
withexcessivemenstrualbleedingshouldbestructuredbymedical
history(positivescreencomprisesanyofthefollowing):*
Heavymenstrualbleedingsincemenarche

Oneofthefollowing:
Postpartumhemorrhage

Surgeryrelatedbleeding

Bleedingassociatedwithdentalwork

Twoormoreofthefollowingsymptoms:

Bruisingonetotwotimespermonth

Epistaxisonetotwotimespermonth

Frequentgumbleeding

Familyhistoryofbleedingsymptoms

*Patientswithapositivescreenshouldbeconsideredforfurtherevaluation,includingconsultation
withahematologistandtestingofvonWillebrandfactorandristocetincofactor.

Originalfiguremodifiedforthispublication.KouidesPA,ConardJ,PeyvandiF,etal.Hemostasisand
menstruation:appropriateinvestigationforunderlyingdisordersofhemostasisinwomenwith
excessivemenstrualbleeding.FertilSteril200584:1345.TableusedwiththepermissionofElsevier
Inc.Allrightsreserved.

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Singleendometrialpolypin44yearoldwomanwho
presentedwithexcessivebleeding

(A)Sagittaltransvaginalsonogramshowsendometrialpolyp(arrows)infundus.
Endometriumappearsthickandisdifficulttomeasure.(B)Sagittal
sonohysterogramshowssingleround1.9cmechogenicpolyp(arrow).Note
otherwisethinendometrium(2mm).

ReproducedwithpermissionfromJoizzo,JR,Chen,MY,Riccio,GJ,EndometrialPolyps:
SonohysterographicEvaluation.AJRAmJRoentgenol2001176:617.Copyright2001
AmericanJournalofRoentgenology.

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Salineinfusionsonohysterogramofasubmucous
myoma

Aposteriormidsegmentsubmucousmyomameasuring1.6x1.9cm
isidentifiedafterinfusionofsaline.Thedistancefromthebackofthe
myomatotheserosalsurfacemeasures1.2cm(calipers).The
endometriumsurroundingthefluidisthin,compatiblewithearly
proliferativephase.

CourtesyofStevenGoldstein,MD.

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Fibroidlocationsintheuterus

Thesefiguresdepictthevarioustypesandlocationsoffibroids.Awomanmayhave
oneormoretypesoffibroids.

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Salineinfusionsonographyofapatientwith
uterinebleeding

Salineinfusionsonographyofapatientwithuterinebleedingreveals
fluffyendometrialtissueoccupyingtherightlateralhalfofthe
endometrialcavitywhiletheleftsideisthin.

CourtesyofStevenGoldstein,MD.

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Disclosures
Disclosures:AndrewMKaunitz,MDGrant/Research/ClinicalTrialSupport:Agile[Contraception(Investigationalcontraceptive
patch)]Bayer[Uterinefibroids(IUDs,implants,oralcontraceptives,menopausaltherapies)]TherapeuticsMD[Menopausal
symptoms(Investigationalmenopausaltherapies)]Merck[Contraception(Contraceptivevaginalring,contraceptiveimplant)]Teva
[Contraception(CopperIUD,oralcontraceptives)].Consultant/AdvisoryBoards:Actavis[Contraception(Vaginalestrogen,IUD,oral
contraceptives)]Bayer[Contraception(IUDs,implants,oralcontraceptives,menopausaltherapies)]Merk[Contraception
(Contraceptivevaginalring,contraceptiveimplant)]Teva[Contraception(CopperIUD,oralcontraceptives)].RobertLBarbieri,MD
Nothingtodisclose.DeborahLevine,MDNothingtodisclose.SandyJFalk,MD,FACOGNothingtodisclose.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseareaddressedbyvetting
throughamultilevelreviewprocess,andthroughrequirementsforreferencestobeprovidedtosupportthecontent.Appropriately
referencedcontentisrequiredofallauthorsandmustconformtoUpToDatestandardsofevidence.
Conflictofinterestpolicy

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