Sangrado Uterino Anormal

10/2/2016
Approachtoabnormaluterinebleedinginnonpregnantreproductiveagewomen
OfficialreprintfromUpToDate
www.uptodate.com2016UpToDate
Author
AndrewMKaunitz,MD
SectionEditors
RobertLBarbieri,MD
DeborahLevine,MD
DeputyEditor
SandyJFalk,MD,FACOG
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
http://www.uptodate.com/contents/approachtoabnormaluterinebleedinginnonpregnantreproductiveagewomen?topicKey=OBGYN%2F3263&elapse
1/42
10/2/2016
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?
2/42
10/2/2016
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
3/42
10/2/2016
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]:
4/42
10/2/2016
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
5/42
10/2/2016
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].
6/42
10/2/2016
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)
7/42
10/2/2016
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".)
8/42
10/2/2016
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'.)
9/42
10/2/2016
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
http://www.uptodate.com/contents/approachtoabnormaluterinebleedinginnonpregnantreproductiveagewomen?topicKey=OBGYN%2F3263&elaps
10/42
10/2/2016
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.
11/42
10/2/2016
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.)
12/42
10/2/2016
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.
REFERENCES
1.SpencerCP,WhiteheadMI.Endometrialassessmentrevisited.BrJObstetGynaecol1999106:623.
2.CommitteeonPracticeBulletinsGynecology.Practicebulletinno.128:diagnosisofabnormaluterine
bleedinginreproductiveagedwomen.ObstetGynecol2012120:197.
3.MunroMG,CritchleyHO,BroderMS,etal.FIGOclassificationsystem(PALMCOEIN)forcausesof
abnormaluterinebleedinginnongravidwomenofreproductiveage.IntJGynaecolObstet2011113:3.
4.KjerulffKH,EricksonBA,LangenbergPW.ChronicgynecologicalconditionsreportedbyUSwomen:
findingsfromtheNationalHealthInterviewSurvey,1984to1992.AmJPublicHealth199686:195.
5.MattesonKA,BoardmanLA,MunroMG,ClarkMA.Abnormaluterinebleeding:areviewofpatientbased
outcomemeasures.FertilSteril200992:205.
6.AndersonSE,MustA.Interpretingthecontinueddeclineintheaverageageatmenarche:resultsfrom
twonationallyrepresentativesurveysofU.S.girlsstudied10yearsapart.JPediatr2005147:753.
7.McKinlaySM.Thenormalmenopausetransition:anoverview.Maturitas199623:137.
8.TowerAM,FrishmanGN.Cesareanscardefects:anunderrecognizedcauseofabnormaluterine
bleedingandothergynecologiccomplications.JMinimInvasiveGynecol201320:562.
13/42
10/2/2016
9.CommitteeonPracticeBulletinsGynecology.Practicebulletinno.128:diagnosisofabnormaluterine
bleedinginreproductiveagedwomen.ObstetGynecol2012120:197.
10.TreloarAE,BoyntonRE,BehnBG,BrownBW.Variationofthehumanmenstrualcyclethrough
reproductivelife.IntJFertil196712:77.
11.HallbergL,HgdahlAM,NilssonL,RyboG.Menstrualbloodlossapopulationstudy.Variationat
differentagesandattemptstodefinenormality.ActaObstetGynecolScand196645:320.
12.GreenbergM.Themeaningofmenorrhagia:aninvestigationintotheassociationbetweenthecomplaint
ofmenorrhagiaanddepression.JPsychosomRes198327:209.
13.HurskainenR,AaltoAM,TeperiJ,etal.Psychosocialandothercharacteristicsofwomencomplaining
ofmenorrhagia,withandwithoutactualincreasedmenstrualbloodloss.BJOG2001108:281.
14.WrightB,GannonMJ,GreenbergM,etal.Psychiatricmorbidityfollowingendometrialablationandits
associationwithgenuinemenorrhagia.BJOG2003110:358.
15.GrantC,GallierL,FaheyT,etal.Managementofmenorrhagiainprimarycareimpactonreferraland
hysterectomy:datafromtheSomersetMorbidityProject.JEpidemiolCommunityHealth200054:709.
16.ClarkeA,BlackN,RoweP,etal.Indicationsforandoutcomeoftotalabdominalhysterectomyfor
benigndisease:aprospectivecohortstudy.BrJObstetGynaecol1995102:611.
17.WarnerPE,CritchleyHO,LumsdenMA,etal.MenorrhagiaI:measuredbloodloss,clinicalfeatures,and
outcomeinwomenwithheavyperiods:asurveywithfollowupdata.AmJObstetGynecol2004
190:1216.
18.vanderVoetLF,BijdeVaateAM,VeersemaS,etal.Longtermcomplicationsofcaesareansection.
Thenicheinthescar:aprospectivecohortstudyonnicheprevalenceanditsrelationtoabnormaluterine
bleeding.BJOG2014121:236.
19.HoffmanMK,MeilstrupJW,ShackelfordDP,KaminskiPF.Arteriovenousmalformationsoftheuterus:
anuncommoncauseofvaginalbleeding.ObstetGynecolSurv199752:736.
20.HalperinR,SchneiderD,MaymonR,etal.Arteriovenousmalformationafteruterinecurettage:areport
of3cases.JReprodMed200752:445.
21.NicholsonAA,TurnbullLW,CoadyAM,GuthrieK.Diagnosisandmanagementofuterinearteriovenous
malformations.ClinRadiol199954:265.
22.KakunoY,AminoN,KanohM,etal.Menstrualdisturbancesinvariousthyroiddiseases.EndocrJ2010
57:1017.
23.KrassasGE,PontikidesN,KaltsasT,etal.Disturbancesofmenstruationinhypothyroidism.Clin
Endocrinol(Oxf)199950:655.
24.PeipertJF,BoardmanLA,SungCJ.Performanceofclinicalandlaparoscopiccriteriaforthediagnosisof
uppergenitaltractinfection.InfectDisObstetGynecol19975:291.
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
14/42
10/2/2016
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.
Topic3263Version15.0
15/42
10/2/2016
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.
Graphic90483Version1.0
16/42
10/2/2016
TheStagesofReproductiveAgingWorkshop+10stagingsystemfor
reproductiveaginginwomen
Arrow:elevatedFMP:finalmenstrualperiodFSH:folliclestimulatinghormoneAMH:antimllerian
hormone.
*Blooddrawoncycledays2to5.
Approximateexpectedlevelbasedonassaysusingcurrentinternationalpituitarystandard.
Reproducedwithpermissionfrom:HarlowSD,GassM,HallJE,etal.ExecutiveSummaryoftheStagesof
ReproductiveAgingWorkshop+10:AddressingtheUnfinishedAgendaofStagingReproductiveAging.JClin
EndocrinolMetab2012.Copyright2012TheEndocrineSociety.
17/42
10/2/2016
Causesofabnormalgenitaltractbleedinginwomen
Genitaltractdisorders
Uterus
Benigngrowths:
Trauma
Sexualintercourse
Sexualabuse
Endometrialpolyps
Foreignbodies(includingintrauterine
Endometrialhyperplasia
device)
Adenomyosis
Pelvictrauma(eg,motorvehicleaccident)
Leiomyomas(fibroids)
Straddleinjuries
Cancer:
Endometrialadenocarcinoma
Sarcoma
Infection:
Pelvicinflammatorydisease
Endometritis
Ovulatorydysfunction
Cervix
Benigngrowths:
Cervicalpolyps
Ectropion
Endometriosis
Cancer:
Invasivecarcinoma
Metastatic(uterus,choriocarcinoma)
Infection:
Cervicitis
Vulva
Benigngrowths:
Skintags
Sebaceouscysts
Condylomata
Angiokerataoma
Cancer
Vagina
Benigngrowths:
Gartnerductcysts
Polyps
Adenosis(aberrantglandulartissue)
Cancer
Vaginitis/infection:
Drugs
Contraception:
Hormonalcontraceptives
Intrauterinedevices
Postmenopausalhormonetherapy
Anticoagulants
Tamoxifen
Corticosteroids
Chemotherapy
Phenytoin
Antipsychoticdrugs
Antibiotics(eg,duetotoxicepidermal
necrolysisorStevensJohnsonsyndrome)
Systemicdisease
Diseasesinvolvingthevulva:
Crohn'sdisease
Behcet'ssyndrome
Pemphigoid
Pemphigus
Erosivelichenplanus
Lymphoma
Bleedingdisorders:
vonWillebranddisease
Thrombocytopeniaorplateletdysfunction
Acuteleukemia
Somecoagulationfactordeficiencies
Advancedliverdisease
Thyroiddisease
Polycysticovarysyndrome
Chronicliverdisease
Cushing'ssyndrome
18/42
10/2/2016
Bacterialvaginosis
Sexuallytransmitteddiseases
Atrophicvaginitis
Uppergenitaltractdisease
Fallopiantubecancer
Ovariancancer
Pelvicinflammatorydisease
Pregnancycomplications
Hormonesecretingadrenalandovarian
tumors
Renaldisease
Emotionalorphysicalstress
Smoking
Excessiveexercise
Diseasesnotaffectingthe
genitaltract
Urethritis
Bladdercancer
Urinarytractinfection
Inflammatoryboweldisease
Hemorrhoids
Other
Endometriosis
Vasculartumorsandanomaliesinthe
genitaltract
19/42
10/2/2016
Usualcausesofabnormalgenitalbleedinginwomenbyagegroup
Neonates
Estrogenwithdrawal
Premenarchal
Foreignbody
Trauma,includingsexualabuse
Infection
Urethralprolapse
Sarcomabotryoides
Ovariantumor
Precociouspuberty
Earlypostmenarche
Ovulatorydysfunction(hypothalamic
immaturity)
Bleedingdiathesis
Stress(psychogenic,exerciseinduced)
Pregnancy
Infection
Reproductiveage
Ovulatorydysfunction
Pregnancy
Cancer
Polyps,leiomyomas,adenomyosis
Infection
Endocrinedysfunction(polycysticovary
syndrome,thyroid,hyperprolactinemia)
Bleedingdiathesis
Medicationrelated(eg,hormonal
contraception)
Menopausaltransition
Anovulation
Polyps,fibroids,adenomyosis
Cancer
Menopause
Endometrialatrophy
Cancer
Postmenopausalhormonetherapy
Adaptedfrom:APGOeducationalseriesonwomen'shealthissues.Clinicalmanagementofabnormal
uterinebleeding.AssociationofProfessorsofGynecologyandObstetrics,May2002.
20/42
10/2/2016
Evaluationofabnormaluterinebleedinginnonpregnant
reproductiveagewomen
21/42
10/2/2016
Riskfactorsforendometrialcancer
Relativerisk(RR)
Riskfactor
(otherstatisticsarenotedwhen
used)
Increasingage
Women50to70yearsoldhavea1.4
percentriskofendometrialcancer
Unopposedestrogentherapy
2to10
Tamoxifentherapy
Earlymenarche
NA
Latemenopause(afterage55)
Nulliparity
Polycysticovarysyndrome(chronic
anovulation)
Obesity
2to4
Diabetesmellitus
Estrogensecretingtumor
NA
Lynchsyndrome(hereditarynonpolyposis
colorectalcancer)
22to50percentlifetimerisk
Cowdensyndrome
13to19percentlifetimerisk
Familyhistoryofendometrial,ovarian,breast,
orcoloncancer
NA
NA:RRnotavailable.
AdaptedfromdatainSmithRA,vonEschenbachAC,WenderR,etal.AmericanCancerSociety
GuidelinesforEarlyEndometrialCancerDetection:Update2001.
22/42
10/2/2016
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).
23/42
10/2/2016
Evaluationanddifferentialdiagnosisofabnormaluterinebleeding
(AUB)innonpregnantreproductiveagewomen
Other
associated
clinical
features
Bleeding
pattern
Regularmenses
thatareheavy
orprolonged
Differentialdiagnosis
Less
common
etiologies
Common
etiologies
Evaluation
Enlargeduterus
onexamination,
discretemasses
maybenoted
Uterineleiomyoma
Pelvicultrasound
Dysmenorrhea
Adenomyosis
Pelvicultrasound
Bleedingdisorder
Testingfor
bleedingdisorder
Riskfactorsfor
uterine
malignancy
Endometrial
carcinomaor
uterine
sarcoma
Endometrial
sampling
Endometrialpolyp
Pelvicultrasound
Salineinfusion
sonographyor
hysteroscopy(if
intracavitary
pathologyis
suspected)
Enlarged,
boggyuteruson
examination
Familyhistory
ofbleeding
disorder
Symptomsof
bleeding
diathesis
Anticoagulant
therapy
Regularmenses
with
intermenstrual
bleeding
Salineinfusion
sonographyor
hysteroscopy(if
available)
Riskfactorsfor
uterine
malignancy
Recenthistory
ofuterineor
cervical
procedureor
childbirth,
particularlyif
Endometrial
Seeendometrial
carcinomaor
uterine
sarcoma
carcinomaabove
Chronic
endometritis
Endometrial
sampling
infectionwas
present
24/42
10/2/2016
Irregular
bleeding,may
bemoreorless
frequentthan
normalmenses
andvolumeand
durationmay
vary
Ovulatory
dysfunction:
Hirsutism,acne,
and/orobesity
PCOS
Totaltestosterone
and/orother
androgens(may
notbeincreasedin
allwomenwith
PCOS)
Galactorrhea
Hyperprolactinemia
Prolactin
Recentweight
gainorloss
Thyroiddisease
Thyroidfunction
tests
Endometrial
Heatorcold
intolerance
Familyhistory
ofthyroid
dysfunction
Riskfactorsfor
uterine
malignancy
Secondary
amenorrhea
Poornutritionor
intenseexercise
carcinomaor
uterine
sarcoma
Hypothalamic
amenorrhea
Follicle
stimulating
hormone
Luteinizing
hormone
Estrogen/progestin
withdrawaltest
Hotflushes
Prematureovarian
insufficiency
Folliclestimulating
hormone
Recenthistory
ofuterineor
cervical
procedureor
childbirth,
particularlyif
infectionwas
present
(mensesmay
present,but
abnormallylight
Cervical
stenosis
Onpelvic
examination,
instrumentcannot
bepassedthrough
internalcervicalos
Intrauterine
Hysteroscopy
adhesions
(Asherman
syndrome)
orbrief)
Irregularor
heavybleeding
inapatienton
IatrogenicAUB
hormonal
contraceptives
orwithan
intrauterine
25/42
10/2/2016
device
OtheruncommonetiologiesofAUBincludeauterinearteriovenousmalformationor
endometriosis.
PCOS:polycysticovariansyndrome.
26/42
10/2/2016
Medicationsthatcausehyperprolactinemia
Medicationclass
Frequencyof
prolactinelevation*
Mechanism
Antipsychotics,firstgeneration
Chlorpromazine
Moderate
Fluphenazine
High
Haloperidol
High
Loxapine
Moderate
Perphenazine
Moderate
Pimozide
Moderate
Thiothixene
Moderate
Trifluoperazine
Moderate
DopamineD 2 receptor
blockadewithinhypothalamic
tuberoinfundibularsystem
Antipsychotics,secondgeneration
Aripiprazole
Noneorlow
Asenapine
Moderate
Clozapine
Noneorlow
Iloperidone
Noneorlow
Lurasidone
Noneorlow
Olanzapine
Low
Paliperidone
High
Quetiapine
Noneorlow
Risperidone
High
Ziprasidone
Low
blockade
Antidepressants,cyclic
Amitriptyline
Low
Desipramine
Low
Clomipramine
High
Nortriptyline
None
Notwellunderstood.Possibly
byGABAstimulationand
indirectmodulationof
prolactinreleasebyserotonin.
Antidepressants,SSRI
Citalopram,fluoxetine,
fluvoxamine,paroxetine,
sertraline
Noneorlow(rarereports)
Sameasforcyclic
antidepressants
None
Notapplicable
Antidepressants,other
Bupropion,venlafaxine,
mirtazapine,nefazodone,
trazodone
Antiemeticandgastrointestinal
Metoclopramide
High
Domperidone(notavailable
High
blockade
27/42
10/2/2016
inUnitedStates)
Prochlorperazine
Low
Antihypertensives
Verapamil
Low
Notwellunderstood.Specific
toverapamil.Mayinvolve
calciuminfluxinhibition
withintuberoinfundibular
dopaminergicneurons.
Methyldopa
Moderate
DecreasedconversionofL
dopatodopamine
suppressionofdopamine
synthesis
Mostother
antihypertensives
(includingothercalcium
channelblockers)
None
Notapplicable
Transientincreaseforseveral
hoursfollowingdose
Potentiallyanindirecteffectof
muopiatereceptoractivation
Opioidanalgesics
Methadone,morphine,
others
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.
28/42
10/2/2016
Characteristicsofnormalmensesversusabnormaluterine
bleeding
Normal
menses
Characteristic
Abnormaluterinebleeding
Frequency
Every21to35
days
<21daysor>35days
Regularity
Cyclesoccur
withafairly
consistent
frequency
Variationfromonecycletothenextofmorethan20
daysisconsideredirregular
Volume
5 [1]to80mL
ofblood
Volumeofbloodisdifficulttomeasure.Inclinical
practice,heavymensesaregenerallydefinedas
soakingapadortamponmorethaneverytwohours
orasavolumeofbleedingthatinterfereswithdaily
activities(eg,wakespatientfromsleep,stainsclothing
orsheets).
Duration
Bleedingfor5
days
Bleedingfor>5days
Reference:
1.FraserIS,CritchleyHO,MunroMG,BroderM.Canweachieveinternationalagreementon
terminologiesanddefinitionsusedtodescribeabnormalitiesofmenstrualbleeding?Hum
Reprod200722:635.
Datafrom:CommitteeonPracticeBulletinsGynecology.Diagnosisofabnormaluterinebleedingin
reproductiveagedwomen.PracticeBulletinNo.128.ObstetGynecol2012120:197.
29/42
10/2/2016
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.
30/42
10/2/2016
Causesofheavyorprolongedmenses
Coagulopathy
Structurallesion
vonWillebranddisease
Uterineleiomyomas(fibroids)
Thrombocytopenia(duetoidiopathic
thrombocytopenicpurpura,hypersplenism,
chronicrenalfailure)
Adenomyosis
Acuteleukemia
Endometrialpolyps
Other
Anticoagulants
Endometritis
Advancedliverdisease
Hypothyroidism
Neoplasm
Endometrialhyperplasiaorcarcinoma
Uterinesarcoma
Intrauterinedevice
Hyperestrogenism
Endometriosis
31/42
10/2/2016
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.
32/42
10/2/2016
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
33/42
10/2/2016
Agerelatedintervalbetweenmenses
Selectedpercentilesforthedistributionofmenstrualintervalbyage
basedondatafromover200,000cycles.Longerintermenstrual
intervalsoccurinwomenjustaftermenarcheandintheyears
precedingmenopause.
Datafrom:TreloarAE,BoyntonRE,BehnBG,BrownBW.Variationofthe
humanmenstrualcyclethroughreproductivelife.IntJFertil196712:77.
34/42
10/2/2016
Pregnancytesting
MinimumhCG
levelfora
positivetest
Causesofa
falsenegative
test
Urinepregnancytest
Qualitativetest:20to50int.
units/L,dependingontest
Serumpregnancytest
Qualitativetest:5to10int.units/L,
dependingontest
Quantitativetest:1to2int.units/L
foranultrasensitivetest
1.PerformedtoosoonafterconceptionhCGconcentrationisbelow
thresholdforapositivetest
2.ThehCGisoformmeasuredisdifferentfromthehCGisoforminthe
sample(pertainsmostlytourinetests)
3.HookeffectduetoextremelyhighhCGconcentration(>500,000int.
units/L,theselevelsaremostcommonlyseeningestational
trophoblasticneoplasia)
Causesofa
falsepositive
test
1.Pregnancylossverysoonafterimplantation("biochemical
pregnancy")
2.hCGsecretionfromatumor
3.PituitaryhCGsecretion
4.Interferencefromhumanantibodiesagainstanimalantibodiesor
heterophilicantibodies(serumtestpositivebuturinehCGwillbe
negative)
5.PatienthasreceivedamedicationcontaininghCGorcertainantibodies
hCG:humanchorionicgonadotropin.
35/42
10/2/2016
Markerssecretedbygermcellandsexcordstromaltumorsofthe
ovary
AFP
hCG
LDH
E2
Inhibin
Testost
Andro
DHEA
Dysgerminoma
Embryonal
Immature
teratoma
Choriocarcinoma
Endodermalsinus
Gonadoblastoma
Polyembryona
Mixedgermcell
AMH
Germcelltumors
Sexcordstromaltumors
Thecomafibroma
Granulosacell
SertoliLeydig
AFP:alphafetoproteinhCG:humanchorionicgonadotrophinLDH:lactatedehydrogenaseE2:
estradioltestost:testosteroneandro:androstenedioneDHEA:dihydroepiandrostenedioneAMH:
antiMullerianhormone.
*Borderlineelevationsincasereports(<16ng/ml).
Lowlevelseenindysgerminomaswitheithernondysgerminomatouselementsof
syncytiotrophobalsticcells.
Typeofgermcellsexcordstromaltumorconsistingofneoplasticgermcellsandsexcordstromal
derivatives.
36/42
10/2/2016
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.
37/42
10/2/2016
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.
38/42
10/2/2016
Salineinfusionsonohysterogramofasubmucous
myoma
Aposteriormidsegmentsubmucousmyomameasuring1.6x1.9cm
isidentifiedafterinfusionofsaline.Thedistancefromthebackofthe
myomatotheserosalsurfacemeasures1.2cm(calipers).The
endometriumsurroundingthefluidisthin,compatiblewithearly
proliferativephase.
CourtesyofStevenGoldstein,MD.
39/42
10/2/2016
Fibroidlocationsintheuterus
Thesefiguresdepictthevarioustypesandlocationsoffibroids.Awomanmayhave
oneormoretypesoffibroids.
40/42
10/2/2016
Salineinfusionsonographyofapatientwith
uterinebleeding
Salineinfusionsonographyofapatientwithuterinebleedingreveals
fluffyendometrialtissueoccupyingtherightlateralhalfofthe
endometrialcavitywhiletheleftsideisthin.
CourtesyofStevenGoldstein,MD.
41/42
10/2/2016
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
42/42

Sangrado Uterino Anormal

Transféré par

Informations du document

Copyright

Formats disponibles

Partager ce document

Partager ou intégrer le document

Options de partage

Avez-vous trouvé ce document utile ?

Ce contenu est-il inapproprié ?

Droits d'auteur :

Formats disponibles

Sangrado Uterino Anormal

Transféré par

Droits d'auteur :

Formats disponibles

10/2/2016

Vous aimerez peut-être aussi