Approach To Abnormal Uterine Bleeding in Nonpregnant Reproductive-Age Women PDF

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
http://www.uptodate.com/contents/approachtoabnormaluterinebleedinginnonpregnantreproductiveagewomen?topicKey=OBGYN%2F3263&elapse 1/42
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?
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
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]:
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
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].

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)
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".)
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'.)
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
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.
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.)
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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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
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
TheStagesofReproductiveAgingWorkshop+10stagingsystemfor
reproductiveaginginwomen
Arrow:elevatedFMP:finalmenstrualperiodFSH:folliclestimulatinghormoneAMH:antimllerian
hormone.
*Blooddrawoncycledays2to5.
Approximateexpectedlevelbasedonassaysusingcurrentinternationalpituitarystandard.
Reproducedwithpermissionfrom:HarlowSD,GassM,HallJE,etal.ExecutiveSummaryoftheStagesof
ReproductiveAgingWorkshop+10:AddressingtheUnfinishedAgendaofStagingReproductiveAging.JClin
EndocrinolMetab2012.Copyright2012TheEndocrineSociety.
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
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
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.
Evaluationofabnormaluterinebleedinginnonpregnant
reproductiveagewomen
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.
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).
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
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
device
OtheruncommonetiologiesofAUBincludeauterinearteriovenousmalformationor
endometriosis.
PCOS:polycysticovariansyndrome.
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
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.
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.
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.
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
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.
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
Agerelatedintervalbetweenmenses
Selectedpercentilesforthedistributionofmenstrualintervalbyage
basedondatafromover200,000cycles.Longerintermenstrual
intervalsoccurinwomenjustaftermenarcheandintheyears
precedingmenopause.
Datafrom:TreloarAE,BoyntonRE,BehnBG,BrownBW.Variationofthe
humanmenstrualcyclethroughreproductivelife.IntJFertil196712:77.
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.
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.
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.
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.
Salineinfusionsonohysterogramofasubmucous
myoma
Aposteriormidsegmentsubmucousmyomameasuring1.6x1.9cm
isidentifiedafterinfusionofsaline.Thedistancefromthebackofthe
myomatotheserosalsurfacemeasures1.2cm(calipers).The
endometriumsurroundingthefluidisthin,compatiblewithearly
proliferativephase.
CourtesyofStevenGoldstein,MD.
Fibroidlocationsintheuterus
Thesefiguresdepictthevarioustypesandlocationsoffibroids.Awomanmayhave
oneormoretypesoffibroids.
Salineinfusionsonographyofapatientwith
uterinebleeding
Salineinfusionsonographyofapatientwithuterinebleedingreveals
fluffyendometrialtissueoccupyingtherightlateralhalfofthe
endometrialcavitywhiletheleftsideisthin.
CourtesyofStevenGoldstein,MD.
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.
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Author SectionEditors DeputyEditor

Regularmenses Enlargeduterus Uterineleiomyoma Pelvicultrasound

Dysmenorrhea Adenomyosis Pelvicultrasound

Familyhistory Bleedingdisorder Testingfor

Riskfactorsfor Endometrial Endometrial

Regularmenses Endometrialpolyp Pelvicultrasound

Recenthistory Chronic Endometrial

Galactorrhea Hyperprolactinemia Prolactin

Recentweight Thyroiddisease Thyroidfunction

Secondary Poornutritionor Hypothalamic Follicle

Hotflushes Prematureovarian Folliclestimulating

Recenthistory Cervical Onpelvic

Chlorpromazine Moderate DopamineD 2 receptor

Aripiprazole Noneorlow DopamineD 2 receptor

Amitriptyline Low Notwellunderstood.Possibly

Citalopram,fluoxetine, Noneorlow(rarereports) Sameasforcyclic

Bupropion,venlafaxine, None Notapplicable

Metoclopramide High DopamineD 2 receptor

Verapamil Low Notwellunderstood.Specific

Methyldopa Moderate DecreasedconversionofL

Mostother None Notapplicable

Methadone,morphine, Transientincreaseforseveral Potentiallyanindirecteffectof

Regularity Cyclesoccur Variationfromonecycletothenextofmorethan20

Volume 5 [1]to80mL Volumeofbloodisdifficulttomeasure.Inclinical

Duration Bleedingfor5 Bleedingfor>5days

AFP hCG LDH E2 Inhibin Testost Andro DHEA AMH

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