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uk)

NICE

Amenorrhoea
LastrevisedinJuly2014

Changes
LastrevisedinJuly2014
July2014reviewed.AliteraturesearchwasconductedinJune2014toidentifyevidence
basedguidelines,UKpolicy,systematicreviews,andkeyRCTspublishedsincethelast
revisionofthistopic.Nomajorchangestorecommendationshavebeenmade.The
managementsectionhasbeenrestructuredtosimplifyuse.

Previouschanges
JulytoOctober2009convertedfromCKSguidancetoCKStopicstructure.Theevidence
basehasbeenreviewedindetail,andrecommendationsaremoreclearlyjustifiedand
transparentlylinkedtothesupportingevidence.Therearenomajorchangestothe
recommendations.
March2009minorupdatetoincludehypopituitarismfollowingtraumaticbraininjuryasa
causeofamenorrhoea.IssuedinApril2009.
JulySeptember2006reviewed.ValidatedinDecember2006andissuedinJanuary2007.
October2005minortechnicalupdate.IssuedinNovember2005.
February2005updatedtoincludeprescribingadvicefromtheCommitteeonSafetyof
Medicinesontheeffectofdepotmedroxyprogesteroneacetatecontraceptiononbones.Issued
inFebruary2005.
July2003reviewed.ValidatedinSeptember2003andissuedinOctober2003.
January2000written.ValidatedinMarch2000andissuedinMay2000.

Update
Newevidence
Evidencebasedguidelines
Nonewevidencebasedguidelinessince1June2014.
HTAs(HealthTechnologyAssessments)
NonewHTAssince1June2014.
Economicappraisals
NoneweconomicappraisalsrelevanttoEnglandsince1June2014.
Systematicreviewsandmetaanalyses
Nonewsystematicreviewormetaanalysissince1June2014.
Primaryevidence
Nonewrandomizedcontrolledtrialspublishedinthemajorjournalssince1June2014.

Newpolicies
Nonewnationalpoliciesorguidelinessince1June2014.

Newsafetyalerts
Nonewsafetyalertssince1June2014.

Changesinproductavailability
Nochangesinproductavailabilitysince1June2014.

Goals
Tomakeanappropriateassessment,includingtheappropriateuseofinvestigations,in

ordertoidentifythecauseofamenorrhoeaand/orrefertosecondarycare
Toofferadviceandtreatmentintheprimarycaresettingtowomenandgirlswith
hypothalamicamenorrhoea
Tomanageosteoporosisriskinwomenwithamenorrhoeaassociatedwithlowlevelsof
oestrogen

Definition
Whatisit?
Amenorrhoeaistheabsenceorcessationofmenses[Balen,2000
(/amenorrhoea#!references/A24721)PracticeCommitteeoftheAmericanSocietyfor
ReproductiveMedicine,2008(/amenorrhoea#!references/A51961)].
Itmaybephysiological(beforepubertyorduetopregnancy,lactation,ormenopause),
pathological,oriatrogenic(forexampleduetocontraceptivesorsurgery).
Primaryamenorrhoeaisgenerallydefinedasthefailuretoestablishmenstruationby
16yearsofageinwomenandgirlswithnormalsecondarysexualcharacteristics,orby
14yearsofageinwomenandgirlswithnosecondarysexualcharacteristics[Haydenand
Balen,2007(/amenorrhoea#!references/A52266)Edmonds,2012
(/amenorrhoea#!references/A78269)].
Secondaryamenorrhoeathereisnoconsensusinthepublishedliteratureonthe
definitionofsecondaryamenorrhoea:
Someauthorsandguidelinesdefinesecondaryamenorrhoeaastheabsenceof
menstruationforatleast6monthsinwomenwithpreviouslynormalandregularmenses,
orfor12monthsinwomenwithpreviousoligomenorrhoea[Kininghametal,1996
(/amenorrhoea#!references/A6531)McIveretal,1997
(/amenorrhoea#!references/A6569)LedgerandSkull,2004
(/amenorrhoea#!references/A52164)AlbertaMedicalAssociation,2008
(/amenorrhoea#!references/A51911)].
Othersdefinesecondaryamenorrhoeaastheabsenceofmensesfor3monthsinwomen
withpreviouslynormalmenstruation,orfor9monthsinwomenwithprevious
oligomenorrhoea[MasterHunterandHeiman,2006(/amenorrhoea#!references/A23046)
PracticeCommitteeoftheAmericanSocietyforReproductiveMedicine,2008
(/amenorrhoea#!references/A51961)Heiman,2009
(/amenorrhoea#!references/A52158)].
Oligomenorrhoea(notcoveredinthistopic)isdefinedasmensesoccurringlessfrequently
thanevery35days[Balen,2004(/amenorrhoea#!references/A23897)].

Prevalence
Howcommonisit?
Theprevalenceofamenorrhoeanotduetopregnancy,lactation,ormenopauseis

approximately34%inwomenofreproductiveage[PracticeCommitteeoftheAmerican
SocietyforReproductiveMedicine,2008(/amenorrhoea#!references/A51961)].

Causes
Whatcausesit?
Causesofprimaryamenorrhoea
Whatarethecausesofprimaryamenorrhoea?
Physiologicalcausesinclude[MasterHunterandHeiman,2006
(/amenorrhoea#!references/A23046)Edmonds,2012(/amenorrhoea#!references/A78269)
Clark,2013(/amenorrhoea#!references/A72229)]:
Pregnancy.
Constitutionaldelay(themostcommonphysiologicalcause).
Thereisnoanatomicalabnormality,andmaturationusuallyoccursspontaneouslyby
18yearsofage.Theconditionisfrequentlyfamilial.
Diagnosisisbyexclusionofpathologicalcauses.
Pathologicalcauses(seeTable1(/amenorrhoea#!backgroundsub:3/A397154:1))
Themostcommonpathologicalcausesassociatedwithnormalsecondarysexual
characteristicsaregenitourinarymalformations,includingimperforatehymen,transverse
vaginalseptum,absentvagina,orabsentuterus[Edmonds,2012
(/amenorrhoea#!references/A78269)].
Themostcommonpathologicalcausesassociatedwithnosecondarysexual
characteristicsareovarianfailure(forexampleinTurner'ssyndrome)andhypothalamic
pituitarydysfunction(forexamplecausedbychronicsystemicillness,weightloss,or
excessiveexercise)[Wilsonetal,2005(/amenorrhoea#!references/A52227)].
Mostofthecausesofsecondaryamenorrhoea(/amenorrhoea#!backgroundsub:4)can
alsocauseprimaryamenorrhoeaiftheyoccurbeforethemenarche.
Table1.Pathologicalcausesofprimaryamenorrhoea.
Secondarysexual
characteristics

Secondarysexualcharacteristics
usuallyabsent

Ambiguousexternal
genitalia

Genitourinary
malformations:
imperforatehymen,

Ovarianfailure:gonadaldysgenesis
(asinTurner'ssyndrome,46XO),
gonadalagenesis(46XXor46XY),

5alphareductase
deficiency.Theexternal
genitaliaarefemale,butthe

transversevaginal
septum,absentvagina,

prematureovarianfailure,
chemotherapy,pelvicirradiation.

internalgenitaliaaremale.
Characteristically,

absentuterus.
Androgeninsensitivity
syndrome(previously

Hypothalamicdysfunction:chronic
systemicillness(including
uncontrolleddiabetes,severerenal

virilizationbecomes
apparentatpuberty.
Androgensecretingtumour.

usuallypresent

knownas'testicular

andcardiacdisorders,coeliac

Thisisrareandresultsin

feminization'):46XY
female(breast
developmentpresent

disease,cancer,andinfectionssuch
astuberculosis),eatingdisorders,
weightloss,excessiveexercise,

extremevirilization
characterizedbytemporal
balding,clitoral

butreduced,and
pubic/axillaryhair
absent).Endocrine

stress,depression.Othercausesof
gonadotrophindeficiency:head
injury,infection,cranialirradiation,

enlargement,deepeningof
thevoice,andextreme
hirsutism.Congenital

disease:
hypothyroidism,

tumoursofthehypothalamusand
pituitary,hydrocephalus,Kallman's

adrenalhyperplasia.Asa
resultofanenzyme

hyperthyroidism,
syndrome(congenitalgonadotrophin
hyperprolactinaemia
deficiencycharacterizedbyanosmia
(forexamplecausedby andothercranialanomalies),empty

deficiency,theadrenal
glandproducestoomuch
androgen,resultingin

prolactinomaordrugs),
Cushing'ssyndrome.
Polycysticovary

femalebabiesdeveloping
malecharacteristics.The
degreeofvirilizationvaries

sellasyndrome,LaurenceMoon
Biedlsyndrome,PrderWilli
syndrome.

syndrome(ararecause
ofprimary

andcanbeoflateonset.

amenorrhoea).
Ingirlswithanorexianervosa,thegrowthspurtusuallyoccurs,butsecondarysexual
characteristicsareabsent.
Datafrom:[Khalaf,2003(/amenorrhoea#!references/A24238)GoldenandCarlson,
2008(/amenorrhoea#!references/A52222)PracticeCommitteeoftheAmericanSociety
forReproductiveMedicine,2008(/amenorrhoea#!references/A51961)Heiman,2009
(/amenorrhoea#!references/A52158)AbdelRahman,2012
(/amenorrhoea#!references/A72230)Edmonds,2012
(/amenorrhoea#!references/A78269)]

Causesofsecondaryamenorrhoea
Whatarethecausesofsecondaryamenorrhoea?
Physiologicalcausesincludepregnancy,lactationandmenopause[HorneandCritchley,
2012(/amenorrhoea#!references/A78271)].
Pathologicalandiatrogeniccauses(seeTable1(/amenorrhoea#!backgroundsub:4/A
397155:1))
Themostcommonpathologicalcausesarepolycysticovarysyndrome,hypothalamic
dysfunction(byweightloss,excessiveexercise,orchronicsystemicillness),premature
ovarianfailure,andhyperprolactinaemia[Balen,2012
(/amenorrhoea#!references/A78270)].

Table1.Pathologicalandiatrogeniccausesofsecondaryamenorrhoea.
Nofeaturesofandrogenexcesspresent

Featuresofandrogenexcess
present

Iatrogenic/illicitdrugs:progestogenmethodsof
contraceptionduring,andforalimitedtimeaftertreatment,
thecombinedoralcontraceptivepillforalimitedtimeafter
treatment,radiotherapy,chemotherapy,andsurgery
(oophorectomy,hysterectomy,endometrialresection)

Tumour:androgensecreting
tumoursoftheovaryoradrenal
gland.Thesearerareand
resultsinextremevirilization
characterizedbytemporal

drugscausinghyperprolactinaemia(antipsychotics,
metoclopramide,methyldopa,cimetidine,opiates,
cocaine).

balding,clitoralenlargement,
deepeningofthevoice,and
extremehirsutism.

Uterinecauses:cervicalstenosis,Asherman'ssyndrome
(intrauterineadhesions).
Ovariancauses:prematureovarianfailure,resistant
ovarysyndrome*,chemotherapyorpelvicirradiation,
mosaicTurner'ssyndrome.
Hypothalamicdysfunction:weightloss,eatingdisorders,
excessiveexercise,stress,depression,chronicsystemic
illness(forexampleseverecardiac,renal,orliverdisease
inflammatoryboweldiseasecoeliacdiseaseAIDSor
cancer),idiopathic.
Otherhypothalamiccauses:centralnervoussystem
tumours(suchascraniopharyngiomasormetastases),
cranialirradiation.
Pituitarycauses:prolactinoma,otherhormonesecreting
pituitarytumours,headinjury,hypopituitarism(forexample
aftertraumaticbraininjury),Sheehan'ssyndrome(pituitary
infarctionaftermajorobstetrichaemorrhage),sarcoidosis,
tuberculosis,cranialirradiation.
Endocrinecauses:polycysticovarysyndrome,Cushing's
syndrome,lateonsetcongenitaladrenalhyperplasia.
Thyroiddisease:hypothyroidism,hyperthyroidism.
*Someconsiderresistantovarysyndrometobeavariantofprematureovarianfailure.
Datafrom:[Balen,2000(/amenorrhoea#!references/A24721)Balen,2004
(/amenorrhoea#!references/A23897)PracticeCommitteeoftheAmericanSocietyfor
ReproductiveMedicine,2008(/amenorrhoea#!references/A51961)Heiman,2009

(/amenorrhoea#!references/A52158)Balen,2012(/amenorrhoea#!references/A78270)]

Complications
Whatarethecomplications?
Womenwithamenorrhoeamayhavethefollowingcomplications,dependingonthe
underlyingcause.
Osteoporosis
Evidencefromobservationalstudiesindicatesthatwomenwithamenorrhoea
associatedwithoestrogendeficiency(inparticularprematureovarianfailure,weight
loss,anorexianervosa,andexcessiveexercise)areatincreasedriskofosteoporosis.
Thisincreasedriskpersistsevenifnormalmensesareresumed,especiallyin
adolescentsbecausetheymaynotattainadesirablepeakbonemass[Daviesetal,
1990(/amenorrhoea#!references/A53376)McGee,1997
(/amenorrhoea#!references/A52246)WarrenandStiehl,1999
(/amenorrhoea#!references/A6533)MasterHunterandHeiman,2006
(/amenorrhoea#!references/A23046)Csermelyetal,2007
(/amenorrhoea#!references/A52139)Golden,2007
(/amenorrhoea#!references/A52135)].
Cardiovasculardisease
Womenwithamenorrhoeaassociatedwithoestrogendeficiencymaybeatincreased
riskofcardiovasculardisease.Althoughthishasnotbeenstudiedspecifically,the
increasedriskassociatedwithalowoestrogenstateinpostmenopausalwomeniswell
documented[Kininghametal,1996(/amenorrhoea#!references/A6531)Fogel,1997
(/amenorrhoea#!references/A6539)McIveretal,1997
(/amenorrhoea#!references/A6569)Reesetal,2009
(/amenorrhoea#!references/A56417)].
Infertility
Womenwithamenorrhoeadonotusuallyovulate[Baird,1997
(/amenorrhoea#!references/A6572)McIveretal,1997
(/amenorrhoea#!references/A6569)].Ovulatorydisordersareoneofthemaincauses
ofinfertilityintheUK[NICE,2013(/amenorrhoea#!references/A72427)].Pregnancy
maybeachievedbysomewomeneitherbytreatmentoftheunderlyingdisorderorby
assistedreproduction[NICE,2013(/amenorrhoea#!references/A72427)].
Psychologicaldistress
Amenorrhoeaoftencausesconsiderableanxiety,alteredselfimage,andlossofself
esteem.Manywomenhaveconcernsaboutlossoffertility,lossoffemininity,or
unwantedpregnancy.ThediagnosisofTurner'ssyndrome,androgeninsensitivity
syndrome,ordevelopmentalanomalycanbetraumaticforbothgirlsandtheirparents
[Fogel,1997(/amenorrhoea#!references/A6539)Rees,2003

(/amenorrhoea#!references/A15334)].

Diagnosisprimaryamenorrhoea
Diagnosisofprimaryamenorrhoea
Agefrom10yearsonwards(Female)
20091019

Diagnosisofprimaryamenorrhoea
HowdoImakeadiagnosisofprimaryamenorrhoea?
Diagnoseprimaryamenorrhoeaingirlswho:
Havenotestablishedmenstruationbytheageof14yearsandhavenosecondarysexual
characteristics.
Havenotestablishedmenstruationbytheageof16yearsandhavenormalsecondary
sexualcharacteristics.

Basisforrecommendation
Evaluatingforsecondarysexualcharacteristics
Therecommendationtoevaluateforsecondarysexualcharacteristicsisbasedonexpert
opinionfromnarrativereviewsandspecialisttextbooks[CrouchandCreighton,2004
(/amenorrhoea#!references/A23907)LedgerandSkull,2004
(/amenorrhoea#!references/A52164)MasterHunterandHeiman,2006
(/amenorrhoea#!references/A23046)HaydenandBalen,2007
(/amenorrhoea#!references/A52266)Heiman,2009(/amenorrhoea#!references/A52158)
Edmonds,2012(/amenorrhoea#!references/A78269)].
Thepresenceorabsenceofsecondarysexualcharacteristicshelpstodeterminewhento
investigateorreferwomenandgirlswithprimaryamenorrhoea,andcanhelpidentifythe
underlyingcause.
Whentodiagnoseprimaryamenorrhoea
Theageatwhichtodiagnoseprimaryamenorrhoeaisbasedonexpertopinionpublishedin
narrativereviewsandspecialisttextbooks[MasterHunterandHeiman,2006
(/amenorrhoea#!references/A23046)HaydenandBalen,2007
(/amenorrhoea#!references/A52266)Heiman,2009(/amenorrhoea#!references/A52158)
Edmonds,2012(/amenorrhoea#!references/A78269)].

Assessmenttoidentifyunderlyingcause
HowdoIidentifytheunderlyingcauseofprimaryamenorrhoea?
Excludepregnancy.
Enquireabout:
Cyclicallowerabdominalpain(suggestinghaematocolposcausedbyagenitaltract
malformation).
Stress,depression,weightloss,disturbanceofperceptionofweightorshape,levelof
exercise,andchronicsystemicillness(suggestinghypothalamicdysfunction).
Headache,visualdisturbance,orgalactorrhoea(suggestingprolactinoma).
Sexualhistoryandcontraception(suggestingpregnancyoracontraceptivecauseof
amenorrhoea).
Ageatmenarcheofmotherandsisters(familyhistoryoflatemenarchesuggests
constitutionaldelay).
Familyhistoryofgeneticanomalies(forexampleandrogeninsensitivity[46XYfemale]).
Drugs(suchasantipsychotics),previouschemotherapyorradiotherapy,andillicitdrug
use(inparticularopiatesandcocaine).
Measureheightandbodyweight,andcalculatebodymassindex(BMI)(thatmight
suggestamenorrhoeasecondarytoalowBMI).
Examinefor:
FeaturesofTurner'ssyndrome(shortstature,webneck,shieldchestwithwidelyspaced
nipples,widecarryingangle,andscoliosis).
Hirsutism,acneandweightgain(suggestingpolycysticovarysyndrome).
Signsofthyroidandotherendocrinedisease.
Ifappropriateexaminefor:
Clitoromegaly(indicatingvirilizationduetopossibleandrogensecretingtumour)if
hirsutismispresent.
Galactorrhoea(suggestingraisedprolactin).
Haematocolpos(ifthereisahistoryofcyclicallowerabdominalpainseparationofthe
labiarevealsabulgingbluecolouredmembraneandapelvicmassmaybepalpable).
Featuresofandrogeninsensitivity(absenceofaxillaryandpubichairwithnormalbreast
developmenttestesmaybepalpableintheinguinalcanalorlabia).
Pelvicexamination:
Thisisinappropriateinyounggirlswhoarenotsexuallyactiveultrasonographycanbe
donetoassesspelvicanatomy.
Inolderwomenpresentingwithprimaryamenorrhoea,itmaybeappropriatetodoa
pelvicexamination,forexampletolookforanabsentuterus.
Investigations:althoughinvestigationsforprimaryamenorrhoeaareusuallydonebya
specialist,thefollowingpreliminaryinvestigationsmayhelpfacilitatediagnosis(seealso
Interpretationofinvestigationfindings(/amenorrhoea#!diagnosisadditional)):
Pelvicultrasonography(ifthepresenceofavaginaanduteruscannotbeconfirmedby

physicalexaminationorinyounggirlswhoarenotsexuallyactiveinplaceofapelvic
examination).
Serumprolactin.Donotexaminethebreastsbeforetakingbloodforprolactinlevels,as
thismaythenbefalselyelevated.Ifthebreastshavebeenexamined,delaythebloodtest
foratleast48hours.
Thyroidstimulatinghormone.
Folliclestimulatinghormoneandluteinizinghormone.
Totaltestosteroneiftherearefeaturesofandrogenexcess.
Ifchronicillnessissuspected,investigationsshouldbeguidedbyclinicalfindings.

Interpretationofinvestigationfindings
Referraltoaspecialistislikelytobeneededregardlessoftheresultofinvestigations,butthe
followinginformationmayguidereferral,speedupdiagnosis,andaidexplanationtothegirlor
womanandherfamilyaboutthepossiblecauseofamenorrhoea(pendingspecialistopinion).
Pelvicultrasonography
Uteruspresent
Ingirlswithnormalsecondarysexualcharacteristics,causesincludeoutflow
obstruction(forexampleimperforatehymenortransversevaginalseptum)and
polycysticovarysyndrome.
Ingirlswithnosecondarysexualcharacteristics,causesincludeTurner'ssyndrome
(46XO'streak'ovariesonly),gonadalagenesis(46XXor46XY).
Absentorabnormaluteruscausedbyandrogeninsensitivity.
Prolactinlevel
Prolactinlevelsgreaterthan1000mIU/Lusuallywarrantfurtherinvestigationbyan
endocrinologist(usuallymagneticresonanceimagingofthepituitaryfossaisrequired).
Causesincludepituitaryadenoma,emptysellasyndrome,hypothyroidism,anddrugs(in
particularantipsychotics).
Prolactinlevelsof5001000mIU/L:
Repeatthemeasurementpersistentmoderateelevationsmaybeduetopituitary
adenomas.
Othercausesincludestress,recentbreastexamination,venepuncture,drugs
(antipsychotics,antidepressants,methyldopa,cimetidine,opiates,andcocaine),renal
orliverfailure,hypothyroidism,andpolycysticovarysyndrome.
ThyroidstimulatinghormoneseetheCKStopicsonHypothyroidism(/hypothyroidism)
andHyperthyroidism(/hyperthyroidism).
Folliclestimulatinghormone(FSH)andluteinizinghormone(LH).Ifsecondarysexual
characteristicsareabsent,karyotypinginsecondarycaremaybenecessary.
ShortstatureandhighFSHandLHlevelssuggestTurner'ssyndrome.
ShortstatureandlowFSHandLHlevelssuggestanintracraniallesionforexample

hydrocephalus.
NormalheightandhighFSHandLHlevelssuggestovarianfailure(normalkaryotype)or
46XY(abnormalkaryotype).
NormalheightandlowFSHandLHlevelssuggestconstitutionaldelay,weightloss,
anorexianervosa,orexcessiveexercise.
Totaltestosteronelevel
Highlevelsoftotaltestosterone(5.0nanomol/Lorgreater)warrantinvestigationto
excludeandrogeninsensitivity(46XYgenotype,femalephenotype),lateonsetcongenital
adrenalhyperplasia,Cushing'ssyndrome,oranandrogensecretingtumour.
Amoderatelyincreasedtestosteronelevel(2.55.0nanomol/L)maybeseeninpolycystic
ovarysyndrome.

Basisforrecommendation
Assessment
Theserecommendationsarebasedonexpertopinionfromnarrativereviewsandspecialist
textbooks[MasterHunterandHeiman,2006(/amenorrhoea#!references/A23046)Golden
andCarlson,2008(/amenorrhoea#!references/A52222)Heiman,2009
(/amenorrhoea#!references/A52158)Edmonds,2012(/amenorrhoea#!references/A78269)].
Choiceofinvestigations
Theserecommendationsarebasedonexpertopinioninnarrativereviewsandspecialist
textbooks[MasterHunterandHeiman,2006(/amenorrhoea#!references/A23046)Hayden
andBalen,2007(/amenorrhoea#!references/A52266)GoldenandCarlson,2008
(/amenorrhoea#!references/A52222)Heiman,2009(/amenorrhoea#!references/A52158)
Edmonds,2012(/amenorrhoea#!references/A78269)],althoughthereisnoconsensuson
thechoiceoffirstlineinvestigations.
Someauthorsrecommendastepwiseapproachtotheinvestigationofprimary
amenorrhoea,takingintoaccountclinicalfeatures(suchasthepresenceofsecondary
sexualcharacteristicsandheight)andtheresultsofpelvicultrasonograph.
Totaltestosteronemeasurementisnotrecommendedbyanyauthorsasafirstline
investigation,butitisgenerallyrecommendedeitherifitisclinicallyindicatedorasa
secondlineinvestigation.Itmaybeusefultodetectandrogeninsensitivity(46XY),late
onsetcongenitaladrenalhyperplasia,Cushing'ssyndrome,andpolycysticovary
syndrome(allrelativelyrarecausesofprimaryamenorrhoea)inwomenandgirlswith
hirsutism.
Interpretationofinvestigations

Pelvicultrasonography.
Theinformationoninterpretingpelvicultrasonographyisbasedonexpertopinionfrom
narrativereviewsandspecialisttextbooks[MasterHunterandHeiman,2006
(/amenorrhoea#!references/A23046)HaydenandBalen,2007
(/amenorrhoea#!references/A52266)GoldenandCarlson,2008
(/amenorrhoea#!references/A52222)Edmonds,2012
(/amenorrhoea#!references/A78269)].
Prolactinlevel.
Theinformationoninterpretingprolactinlevelsisbasedonexpertopinionfromnarrative
reviewsandspecialisttextbooks[MasterHunterandHeiman,2006
(/amenorrhoea#!references/A23046)HaydenandBalen,2007
(/amenorrhoea#!references/A52266)PracticeCommitteeoftheAmericanSocietyfor
ReproductiveMedicine,2008(/amenorrhoea#!references/A51961)Heiman,2009
(/amenorrhoea#!references/A52158)].
Folliclestimulatinghormoneandluteinizinghormonelevels
Theinformationoninterpretingfolliclestimulatinghormoneandluteinizinghormone
levelsisbasedonexpertopinionfromanarrativereview[McIveretal,1997
(/amenorrhoea#!references/A6569)]andaspecialisttextbook[Edmonds,2012
(/amenorrhoea#!references/A78269)].
Totaltestosteronelevel
Theinformationoninterpretingtotaltestosteronelevelsisbasedonaspecialisttextbook
[Balen,2012(/amenorrhoea#!references/A78270)]andaguidelinefromtheRoyal
CollegeofObstetriciansandGynaecologistsonthediagnosisofpolycysticovary
syndrome[RCOG,2007(/amenorrhoea#!references/A49207)].

Diagnosissecondaryamenorrhoea
Diagnosisofsecondaryamenorrhoea
Agefrom10yearsonwards(Female)
20091019

Diagnosisofsecondaryamenorrhoea
HowshouldIdiagnosesecondaryamenorrhoea?
Diagnoseandinvestigatesecondaryamenorrhoeainwomenwhohavehad:
Normalandregularmenses,after36consecutivemonthsofamenorrhoea.
Oligomenorrhoea,after912consecutivemonthsofamenorrhoea.
Thecombinedoralcontraceptive,6monthsafterstoppingthepill.
Aninjectableprogesterone,9monthsafterthelastinjection.

Basisforrecommendation
Thereisnoconsensusinthepublishedliteratureonthedefinitionofsecondary
amenorrhoea,orwhentoinvestigateforanunderlyingcause.Therecommendationto
evaluateafter36monthsisinclusiveofallopinions.
Someauthorsandguidelinesdefinesecondaryamenorrhoeaastheabsenceof
menstruationforatleast6monthsinwomenwithpreviouslynormalandregularmenses,
orfor12monthsinwomenwithpreviousoligomenorrhoea[Kininghametal,1996
(/amenorrhoea#!references/A6531)McIveretal,1997
(/amenorrhoea#!references/A6569)LedgerandSkull,2004
(/amenorrhoea#!references/A52164)AlbertaMedicalAssociation,2008
(/amenorrhoea#!references/A51911)].
Othersdefinesecondaryamenorrhoeaastheabsenceofmensesfor3monthsinwomen
withpreviouslynormalmenstruation,orfor9monthsinwomenwithprevious
oligomenorrhoea[MasterHunterandHeiman,2006(/amenorrhoea#!references/A23046)
PracticeCommitteeoftheAmericanSocietyforReproductiveMedicine,2008
(/amenorrhoea#!references/A51961)Heiman,2009
(/amenorrhoea#!references/A52158)].
Therecommendationsonwhentoevaluatewomenwithamenorrhoeaafterstoppingthe
combinedoralcontraceptiveordepotmedroxyprogesteronearebasedonexpertopinion
fromnarrativereviews[Rees,2003(/amenorrhoea#!references/A15334)Warrenand
Hagey,2004(/amenorrhoea#!references/A52229)]andCKSexpertreviewers.

Assessmenttoidentifyunderlyingcause
HowdoIidentifytheunderlyingcauseofsecondaryamenorrhoea?
Excludepregnancyandotherphysiologicalcauses,suchaslactationormenopause(in
women40yearsofageorolder).
Enquireabout:
Thedurationofamenorrhoea.
Contraceptiveuse(combinedoralcontraceptivemaycauseamenorrhoeaforupto6
monthsafterstoppingtreatmentandinjectableprogesteroneforupto9months).
Hotflushesandvaginaldryness(suggestingprematureovarianfailure).
Headaches,visualdisturbances,orgalactorrhoea(suggestingapituitarytumour).
Acne,hirsutismandweightgain(suggestingpolycysticovarydisease).
Weightloss(suggestinganeatingdisorder).
Stressordepression(suggestingstressrelatedhypothalamicamenorrhoea).
Exerciselevels(suggestingexerciseassociatedhypothalamicamenorrhoea).
Symptomsofthyroidandotherendocrinedisease.
Ahistoryofobstetricorsurgicalprocedures(suchasendometrialcurettage)thatmay

haveresultedinintrauterineadhesions).
Ahistoryofchemotherapypelvicradiotherapy(whichcancauseprematureovarian
failure)andcranialradiotherapy,headinjury,ormajorobstetrichaemorrhage(whichcan
causehypopituitarism).
Drugs(suchasantipsychoticswhichcancauseincreasedprolactinlevels)andillicitdrug
use(inparticularcocaineandopiateswhichcancausehypogonadism).
Afamilyhistoryofcessationofmensesbefore40yearsofage(forprematureovarian
failure).
Measureheightandbodyweight,andcalculatebodymassindex(forweightrelated
causesforamenorrhoea).
Examinefor:
Galactorrhoea,ifappropriate(suggestingraisedprolactinlevels).
Signsofexcessandrogens(hirsutism,acne)orvirilization(hirsutism,acne,deepvoice,
temporalbalding,increaseinmusclebulk,breastatrophy,andclitoromegaly).
Signsofthyroiddisease.
SignsofCushing'ssyndrome(striae,buffalohump,significantcentralobesity,easy
bruising,hypertension,andproximalmuscleweakness).
Assessvisualfieldsifapituitarytumourissuspected.
Considercarryingoutthefollowingpreliminaryinvestigationsinprimarycaretohelp
diagnosisorguidereferral(seealsoInterpretationofinvestigationfindings
(/amenorrhoea#!diagnosisadditional:1)):
Folliclestimulatinghormoneandluteinizinghormone.
Prolactinlevel.
Totaltestosterone.
Thyroidstimulatinghormone.
Pelvicultrasoundifpolycysticovarysyndromeissuspected.

Interpretationofinvestigationfindings
SeeTable1(/topicunderreview)forlaboratoryfindingsincommoncausesofsecondary
amenorrhoea.
Folliclestimulatinghormone(FSH)andluteinizinghormone(LH)
HighFSHandLHlevelsontwooccasionssuggestprematureovarianfailure(inwomen
youngerthan40yearsofage).
NormalorlowFSHlevelsandnormalorlowLHlevelssuggesthypothalamiccauses
(weightloss,excessiveexercise,stress,orrarely,ahypothalamicorpituitarytumour).
NormalFSHlevelsandnormalormoderatelyincreasedLHlevelsmaybefoundin
polycysticovarysyndrome.
Prolactinlevel
Prolactinlevelsgreaterthan1000mIU/Lwarrantfurtherinvestigationbyan

endocrinologist(usuallymagneticresonanceimagingofthepituitaryfossaisrequired).
Causesincludepituitaryadenomaandhypothyroidism.
Ifprolactinlevelsare5001000mIU/L:
Repeatthemeasurementiftheselevelspersist,pituitaryadenomamaybethecause.
Othercausesincludestress,recentbreastexamination,venepuncture,drugs,ectopic
production(forexampleteratomaorrenalcellcarcinoma),renalorliverfailure,
hypothyroidism,andpolycysticovarysyndrome.
Thyroidstimulatinghormone
SeetheCKStopicsonHypothyroidism(/hypothyroidism)andHyperthyroidism
(/hyperthyroidism).
Totaltestosterone
Highlevelsoftotaltestosterone(5.0nanomol/Lorgreater)warrantinvestigationto
excludeothercauses,suchasCushing'ssyndrome,lateonsetcongenitaladrenal
hyperplasia,oranandrogensecretingtumour.
Ultrasonography
Polycysticovariesonultrasonographyaredefinedbythepresenceof12ormorefollicles
inatleastoneovary,measuring29mmdiameter,orincreasedovarianvolume(greater
than10mL).
Table1.Laboratoryfindingsincommoncausesofsecondaryamenorrhoea.
State

FSH

LH

Hyperprolactinaemia

Normal/low Normal/low

Polycysticovary
syndrome

Normal

Prolactin

Testosterone

High

Normal

Normal/slightly Normal/slightly Normal/moderately


increasedin
increasedin
increasedFree
40%

530%

androgenindex
increased

High

Normal

Normal

Normal

Normal

Ovarianfailure

High

Hypothalamic(for

Low/normal Low/normal

exampleweightloss,
excessiveexercise,or
stress)
FSH,folliclestimulatinghormoneLH,luteinizinghormone.Datafrom:[Rees,2003
(/amenorrhoea#!references/A15334)WarrenandHagey,2004
(/amenorrhoea#!references/A52229)PracticeCommitteeoftheAmericanSocietyfor
ReproductiveMedicine,2008(/amenorrhoea#!references/A51961)]

Basisforrecommendation
Assessment
Theserecommendationsarebasedonexpertopinionfrompublishednarrativereviewsand
specialisttextbooks[Balen,2000(/amenorrhoea#!references/A24721)Rees,2003
(/amenorrhoea#!references/A15334)Balen,2004(/amenorrhoea#!references/A23897)
LedgerandSkull,2004(/amenorrhoea#!references/A52164)WarrenandHagey,2004
(/amenorrhoea#!references/A52229)Wilsonetal,2005
(/amenorrhoea#!references/A52227)MasterHunterandHeiman,2006
(/amenorrhoea#!references/A23046)Dickersonetal,2009
(/amenorrhoea#!references/A55252)Heiman,2009(/amenorrhoea#!references/A52158)].
Choiceofinvestigations
Theserecommendationsarebasedonreportsoftherelativefrequenciesofunderlying
causesofsecondaryamenorrhoea[Balen,2000(/amenorrhoea#!references/A24721)
Balen,2004(/amenorrhoea#!references/A23897)],recommendationsfromtheAmerican
SocietyforReproductiveMedicine[PracticeCommitteeoftheAmericanSocietyfor
ReproductiveMedicine,2008(/amenorrhoea#!references/A51961)],andexpertopinionfrom
narrativereviewsandspecialisttextbooks[Balen,2000
(/amenorrhoea#!references/A24721)LedgerandSkull,2004
(/amenorrhoea#!references/A52164)Wilsonetal,2005
(/amenorrhoea#!references/A52227)MasterHunterandHeiman,2006
(/amenorrhoea#!references/A23046)Dickersonetal,2009
(/amenorrhoea#!references/A55252)Heiman,2009(/amenorrhoea#!references/A52158)].
Excludingpregnancyiswidelyrecommendedinparticular,oneexpertnotesthat'itis
commontoseeoneortwopatientsayearwhoarepregnantdespitedenyingthepossibility'
[Balen,2000(/amenorrhoea#!references/A24721)].
Thereisnoconsensusinthepublishedliteratureonthemostappropriatefirstline
investigationsforsecondaryamenorrhoea.
Allofthecitedstudiesrecommendtestingforpregnancyandassessingserumprolactin.
MostalsorecommendFSH,LH,andthyroidstimulatinghormone(TSH)measurement,
althoughthyroiddiseaseappearstobearelativelyrarecauseofsecondaryamenorrhoea
andsomeexpertsrecommendTSHmeasurementonlyifthewomanhasfeaturesof
thyroiddisease.
Theroutinemeasurementoftotaltestosteroneisrecommendedonthebasisthat:
ThesetestsarerecommendedfortheinvestigationofPCOSinaRoyalCollegeof
ObstetriciansandGynaecologistsguideline[RCOG,2007
(/amenorrhoea#!references/A49207)].
Polycysticovarysyndrome(PCOS)isacommoncauseofsecondaryamenorrhoea

[Balen,2000(/amenorrhoea#!references/A24721)Balen,2004
(/amenorrhoea#!references/A23897)].
Thereissomeevidencethatwomenconcealhirsutism[Balenetal,2005
(/amenorrhoea#!references/A51682)].
TheUKbasedauthorsofareviewpaperrecommendthatprimarycarecliniciansperform
severalinitialinvestigationsbeforethewomanisseeninsecondarycare[Ledgerand
Skull,2004(/amenorrhoea#!references/A52164)].Theystatethat,althoughamenorrhoea
hastraditionallybeeninvestigatedusingastepwiseapproach,thisislikelytoleadtoan
increasednumberofvisitstocompleteeachstageofinvestigation,andthusincrease
expense.
PCOS,prematureovarianfailure,hyperprolactinaemia,andhypothalamicdysfunction(due
to,forexample,weightloss,stress,orexcessiveexercise)arethemostcommoncausesof
secondaryamenorrhoea[Balen,2000(/amenorrhoea#!references/A24721)Balen,2004
(/amenorrhoea#!references/A23897)].Totaltestosterone,folliclestimulatinghormone(FSH),
luteinizinghormone(LH),andprolactinmeasurementsareappropriatefirstlinetestsfor
theseconditions.
Interpretationofinvestigationfindings
FSHandLH
TheinformationoninterpretingFSHandLHlevelsisbasedonexpertopinionfrom
narrativereviewsandaspecialisttextbook[Balen,2000
(/amenorrhoea#!references/A24721)MasterHunterandHeiman,2006
(/amenorrhoea#!references/A23046)],andonaCanadianguidelineonendocrinetesting
inamenorrhoea[AlbertaMedicalAssociation,2008(/amenorrhoea#!references/A51911)].
Prolactinlevels
Theinformationoninterpretingprolactinlevelsisbasedonnarrativereviews[Wieckand
Haddad,2003(/amenorrhoea#!references/A54992)LedgerandSkull,2004
(/amenorrhoea#!references/A52164)MasterHunterandHeiman,2006
(/amenorrhoea#!references/A23046)PracticeCommitteeoftheAmericanSocietyfor
ReproductiveMedicine,2008(/amenorrhoea#!references/A51961)Heiman,2009
(/amenorrhoea#!references/A52158)],andaspecialisttextbook[Balen,2004
(/amenorrhoea#!references/A23897)].
Totaltestosteronelevels
Theinformationoninterpretingtotaltestosteronelevelsisbasedonguidelinesfromthe
RoyalCollegeofObstetriciansandGynaecologistsonthediagnosisofPCOS[RCOG,
2007(/amenorrhoea#!references/A49207)]andonexpertopinioninaspecialisttextbook
[Balen,2012(/amenorrhoea#!references/A78270)].
Ultrasonography
Thediagnosticappearanceofpolycysticovariesonultrasonographyarebasedonthe
widelyacceptedRotterdamdiagnosticcriteria[RotterdamESHRE/ASRMSponsored
PCOSConsensusWorkshopGroup,2004(/amenorrhoea#!references/A23214)

Ehrmann,2005(/amenorrhoea#!references/A23215)].

Scenario:Primaryamenorrhoea
Scenario:Managementofprimaryamenorrhoea
Agefrom10yearsonwards(Female)

Management
HowshouldImanageawomanorgirlwithprimaryamenorrhoea?
Ingeneral,referforspecialistinvestigationand,whereappropriate,managementof
thecause:
Girlswhohavenosecondarysexualcharacteristicswhohavenotstartedmenstruatingby
14yearsofage.
Girlswithnormalsecondarysexualcharacteristicswhohavenotstartedmenstruatingby
16yearsofage.
Referatanearlierageifthegirl,orherparentsareconcernedorifanabnormalityis
suspectedforexample,ingirlsandwomenwith:
Growthretardation.
Symptomsandsignsofandrogenexcess(suchashirsutism)orthyroiddisease.
Galactorrhoea.
Suspectedgenitaltractmalformation,intracranialtumour(forexampleprolactinoma),
chromosomalanomaly(forexampleTurner'ssyndromeorandrogeninsensitivity),or
anorexianervosa.
Pubertylasting5yearswithoutmenarche(forexamplepresentingat15yearsofage
whenpubichairandbreastdevelopmentstartedat10yearsofage).
Referraltoagynaecologist(preferablywithaspecialinterestinadolescentgynaecology)
isappropriateformostgirlsandwomen.
Refertoanendocrinologistthosegirlsandwomenwithhyperprolactinaemia,thyroid
disease,orsignsofandrogenexcess.
Manageamenorrhoeacausedbyweightloss,excessiveexercise,stress,orchronic
illnessafteranendocrinologisthasassessedandexcludedahypothalamicor
pituitarytumour.For:
Weightrelatedamenorrhoeaencourageweightgainandrefertoadieticianif
necessary.Ifaneatingdisorderissuspected,considerreferraltoapsychiatrist.For
furtherinformationseetheCKStopiconEatingdisorders(/eatingdisorders).
Exerciserelatedamenorrhoeaadvisereducingexercise,increasingcalorieintake,and
weightgain.Considerreferralto,orliaisonwithasportsphysician,ifavailable.
Stressrelatedamenorrhoeaconsidermeasurestomanagestressandimprovecoping
strategies,suchascognitivebehaviouraltherapy.ForfurtherinformationseetheCKS
topicsonGeneralizedanxietydisorder(/generalizedanxietydisorder),Depression

(/depression),andDepressioninchildren(/depressioninchildren).
Ifamenorrhoeapersistsformorethan12months,considerwhetherosteoporosis
prophylaxisisrequired.ForfurtherinformationseeManagingosteoporoticrisk
(/amenorrhoea#!scenariorecommendation:1).

Basisforrecommendation
Referraltoaspecialist
Thecriteriaforreferralbasedonageandthepresenceorabsenceofsecondarysexual
characteristicsareextrapolatedfromexpertopinioninpublishednarrativereviewsand
specialisttextbooksonwhentoinvestigateawomanorgirlwithprimaryamenorrhoea
[Garden,1998(/amenorrhoea#!references/A6609)MasterHunterandHeiman,2006
(/amenorrhoea#!references/A23046)HaydenandBalen,2007
(/amenorrhoea#!references/A52266)Heiman,2009(/amenorrhoea#!references/A52158)
Edmonds,2012(/amenorrhoea#!references/A78269)].
Earlierreferral
Expertsrecommendreferralforspecialistassessmentatanyagewhentheparentorthegirl
areconcernedaboutadelayedonsetofsecondarysexualcharacteristicsormenstruation
becauseitistheexperienceofexpertsthattheseconcernsoftenarewellfounded
[Edmonds,2012(/amenorrhoea#!references/A78269)].
Expertsrecommendearlierreferralforgirlswithasuspectedabnormalitycausing
amenorrhoeatoenableearlyconfirmationandmanagementoftheunderlyingcause[Balen,
2004(/amenorrhoea#!references/A23897)CrouchandCreighton,2004
(/amenorrhoea#!references/A23907)LedgerandSkull,2004
(/amenorrhoea#!references/A52164)MasterHunterandHeiman,2006
(/amenorrhoea#!references/A23046)Edmonds,2012
(/amenorrhoea#!references/A78269)].
Whentorefertoagynaecologistorendocrinologist
Onenarrativereviewrecommendsreferraltoanendocrinologistifthegirlis14yearsofage
andshowingnosecondarysexualcharacteristics,andreferraltoagynaecologistifthegirl
hassecondarysexualcharacteristicsbuthasnotstartedmenstruationby16yearsofage
[CrouchandCreighton,2004(/amenorrhoea#!references/A23907)].
HoweverCKSrecommendsreferringmostgirlstoagynaecologist,exceptforthosewitha
suspectedendocrinologicalcondition,becausethemostcommonpathologicalcauseof
primaryamenorrhoeainwomenandgirlswithoutsecondarysexualcharacteristicsisovarian
failure(oftencausedbyachromosomalanomaly)andthisconditionismoreappropriately
investigatedandmanagedbyagynaecologist[ReindollarandMcDonough,1981

(/amenorrhoea#!references/A53157)Garden,1998(/amenorrhoea#!references/A6609)
Wilsonetal,2005(/amenorrhoea#!references/A52227)].
Treatmentoftheunderlyingcause
Specialistsrecommendreferralforassessmentforallgirlswithprimaryamenorrhoeato
confirm,andwherenecessarymanage,theunderlyingcause[MasterHunterandHeiman,
2006(/amenorrhoea#!references/A23046)HaydenandBalen,2007
(/amenorrhoea#!references/A52266)Heiman,2009(/amenorrhoea#!references/A52158)
Edmonds,2012(/amenorrhoea#!references/A78269)].Primarycareclinicianscommonly
haveexperienceinmanagingsomeoftheunderlyingcausesofamenorrhoeasuchas
chronicillness,eatingdisorders,exerciseorstressassociatedamenorrhoea,andtherefore
CKSrecommendthattheseconditionscanbesafelymanagedinprimarycareonceother
causeshavebeenexcluded.
Consideringosteoporosisprophylaxis
Evidencefromobservationalstudiesindicatesthatwomenwithamenorrhoeaassociated
withlowoestrogenlevelsareatincreasedriskofosteoporosis[Daviesetal,1990
(/amenorrhoea#!references/A53376)McGee,1997(/amenorrhoea#!references/A52246)
WarrenandStiehl,1999(/amenorrhoea#!references/A6533)MasterHunterandHeiman,
2006(/amenorrhoea#!references/A23046)Csermelyetal,2007
(/amenorrhoea#!references/A52139)Golden,2007(/amenorrhoea#!references/A52135)].
Opinionsinthepublishedliteraturedifferontheperiodofamenorrhoeaafterwhich
oestrogenreplacementisrecommended,varyingfrom612months[Balen,2000
(/amenorrhoea#!references/A24721)Balen,2004(/amenorrhoea#!references/A23897)
LedgerandSkull,2004(/amenorrhoea#!references/A52164)PracticeCommitteeofthe
AmericanSocietyforReproductiveMedicine,2008(/amenorrhoea#!references/A51961)].
CKSrecommends12months,toallowtimefortreatmentoftheunderlyingcausetobe
effective.

Managingosteoporoticrisk
HowshouldImanagetheriskofosteoporosis?
Forgirlsandwomenwithhypothalamicamenorrhoea,orhyperprolactinaemia(women
withamenorrhoeaassociatedwithlowoestrogenlevelswhoareatincreasedriskof
developingosteoporosis):
Treattheunderlyingcause,ifpossible.
Assesstheirfragilityfracturerisk,correctvitaminDdeficiencyandensurean
adequatecalciumintake.ForfurtherinformationseetheCKStopiconOsteoporosis
preventionoffragilityfractures(/osteoporosispreventionoffragilityfractures).

Considerofferinghormonereplacementtherapyorthecombinedoral
contraceptivepill(bothofflabeluse)ifamenorrhoeapersistsformorethan12months.
Offercyclicalcombinedhormonereplacementtherapy(atthedosesusedfor
menopause)or,ifcontraceptionisneeded,acombinedoralcontraceptive.Seethe
CKStopicsonMenopause(/menopause)andContraceptioncombinedhormonal
methods(/contraceptioncombinedhormonalmethods)forprescribinginformation.
Reviewtreatmentatleastannually.Forwomenwithamenorrhoeaduetoreversible
causes(suchasweightlossorexcessiveexercise),oestrogenreplacementshouldbe
periodicallystopped(forexampleafter12monthsoftreatment,for6months)tosee
whethermensesresumeofftreatment.

Basisforrecommendation
Theserecommendationsarebasedonexpertopinionfromnarrativereviewsandspecialist
textbooks[Balen,2000(/amenorrhoea#!references/A24721)Balen,2004
(/amenorrhoea#!references/A23897)LedgerandSkull,2004
(/amenorrhoea#!references/A52164)PracticeCommitteeoftheAmericanSocietyfor
ReproductiveMedicine,2008(/amenorrhoea#!references/A51961)].
Identifyingwomenatrisk
Evidencefromobservationalstudiesindicatesthatwomenwithamenorrhoeaassociated
withlowoestrogenlevelsareatincreasedriskofosteoporosis[MasterHunterandHeiman,
2006(/amenorrhoea#!references/A23046)Csermelyetal,2007
(/amenorrhoea#!references/A52139)Golden,2007(/amenorrhoea#!references/A52135)
Balen,2012(/amenorrhoea#!references/A78270)].
Treatingtheunderlyingcause
Thisisapragmaticrecommendationbasedonestablishedprinciplesofgoodmedical
practice.
Hormonereplacementtherapyandcombinedoralcontraceptives
Thereisaconsensusofexpertopinioninthepublishedliteraturethatoestrogen
replacementshouldbeinitiatedtopreventexcessivebonelossinwomenwithhypothalamic
amenorrhoea[Balen,2000(/amenorrhoea#!references/A24721)Balen,2004
(/amenorrhoea#!references/A23897)LedgerandSkull,2004
(/amenorrhoea#!references/A52164)PracticeCommitteeoftheAmericanSocietyfor
ReproductiveMedicine,2008(/amenorrhoea#!references/A51961)Marjoribanksetal,
2012(/amenorrhoea#!references/A71649)].
Thereisnoconsensusonwhich(HRTorCOCs)ispreferable.Oneexpertrecommends

HRT(unlesscontraceptionisrequired)becauseoftheloweroestrogendose[Balen,2004
(/amenorrhoea#!references/A23897)],whereasanotherstatesthatthedosesofoestrogenin
HRTareinsufficienttoimprovebonemineraldensityinteenagersandyoungadults
[Hergenroeder,1995(/amenorrhoea#!references/A52251)].
Therecommendationtoperiodicallystoptreatmentispragmaticandisbasedonastudyof
93womenwithhypothalamicamenorrhoeaduetostress,exercise,orweightloss,inwhich
morethan70%recoveredsomeovarianfunctionover8years[Falsettietal,2002
(/amenorrhoea#!references/A53538)].
Opinionsinthepublishedliteraturedifferontheperiodofamenorrhoeaafterwhich
oestrogenreplacementisrecommended,varyingfrom612months[Balen,2000
(/amenorrhoea#!references/A24721)Balen,2004(/amenorrhoea#!references/A23897)
LedgerandSkull,2004(/amenorrhoea#!references/A52164)PracticeCommitteeofthe
AmericanSocietyforReproductiveMedicine,2008(/amenorrhoea#!references/A51961)].
CKSrecommends12months,toallowtimefortreatmentoftheunderlyingcausetobe
effective.

Scenario:Secondaryamenorrhoea
Scenario:Managementofsecondaryamenorrhoea
Agefrom10yearsonwards(Female)

Management
HowshouldImanagesecondaryamenorrhoea?
Managegirlsandwomenwiththefollowingcausesforsecondaryamenorrhoeain
primarycare:
PolycysticovarysyndromewhenappropriateforfurtherinformationseetheCKS
topiconPolycysticovarysyndrome(/polycysticovarysyndrome).
Hypothyroidismmensesmaytakeseveralmonthstoresumewithtreatment(seethe
CKStopiconHypothyroidism(/hypothyroidism)).
Menopause(women40yearsofageorolder,seetheCKStopiconMenopause
(/menopause)).
PregnancyforfurtherinformationseetheCKStopiconAntenatalcare
uncomplicatedpregnancy(/antenatalcareuncomplicatedpregnancy).
Referallothergirlsandwomenforspecialistinvestigationand,whereappropriate,
managementofthecause:
Refertoagynaecologistifshehasanyofthefollowing:
Persistentlyelevatedfolliclestimulatinghormone(FSH)andluteinizinghormone(LH)
levelswhichsuggestsprematureovarianfailureinwomenyoungerthan40yearsof
age.
Recenthistoryofuterineorcervicalsurgery(suchasendometrialcurettage,

Caesareansection,ormyomectomy)orseverepelvicinfection(endometritis)which
suggestsAsherman'ssyndromeorcervicalstenosis.
InfertilityseetheCKStopiconInfertility(/infertility).
Suspectedpolycysticovarysyndrome,ifdiagnosisandmanagementarenotfeasible
inprimarycareseetheCKStopiconPolycysticovarysyndrome(/polycysticovary
syndrome).
Refertoanendocrinologistifshehasanyofthefollowing:
Hyperprolactinaemia:serumprolactinlevelgreaterthan1000mIU/L,or500
1000mIU/Lontwooccasions.Thisincludesgirlsandwomenondrugsthatareknown
toincreaseprolactinlevels(/amenorrhoea#!backgroundsub:4).
LowFSHandLHlevels(toexcludehypopituitarismorapituitarytumour,although
stress,excessiveexercise,orweightlossaremorelikelycauses).
Anincreasedtestosteronelevelthatisnotexplainedbypolycysticovarysyndrome
(suggestinganandrogensecretingtumour,lateonsetcongenitaladrenalhyperplasia,
orCushing'ssyndrome).
OtherfeaturesofCushing'ssyndromeorlateonsetcongenitaladrenalhyperplasia
(besidesanincreasedtestosteronelevel).
Manageamenorrhoeacausedbyweightloss,excessiveexercise,stress,orchronic
illnessafteranendocrinologisthasassessedandexcludedahypothalamicor
pituitarytumour.For:
Weightrelatedamenorrhoeaencourageweightgainandrefertoadieticianif
necessary.Ifaneatingdisorderissuspected,considerreferraltoapsychiatrist.For
furtherinformationseetheCKStopiconEatingdisorders(/eatingdisorders).
Exerciserelatedamenorrhoeaadvisereducingexercise,increasingcalorieintake,and
weightgain.Considerreferralto,orliaisonwithasportsphysician,ifavailable.
Stressrelatedamenorrhoeaconsidermeasurestomanagestressandimprovecoping
strategies,suchascognitivebehaviouraltherapy.ForfurtherinformationseetheCKS
topicsonGeneralizedanxietydisorder(/generalizedanxietydisorder),Depressionin
children(/depressioninchildren),andDepression(/depression).
Offercontraceptiveadvicetowomenwhodonotwishtobecomepregnant,asasmall
numberofwomenwithsecondaryamenorrhoeawillbecomepregnantseetheCKStopic
onContraceptionassessment(/contraceptionassessment).
Ifamenorrhoeapersistsformorethan12months,considerwhetherosteoporosis
prophylaxisisrequired.ForfurtherinformationseeManagingosteoporosisrisk
(/amenorrhoea#!scenariorecommendation:3).

Basisforrecommendation
Primarycaremanagementofgirlsandwomenwithpolycysticovarysyndrome,
hypothyroidism,menopauseandpregnancy

CKSrecommendsprimarycaremanagementofwomenwithpolycysticovarysyndrome,
hypothyroidism,menopause,orpregnancybecauseitisnormalclinicalpracticetomanage
theseconditionsinprimarycare.
Referralforspecialistinvestigationtoidentifyandtreattheunderlyingcause
Theserecommendationsarebasedonwhetherfurtherinvestigationortreatmentisneeded
insecondarycaretoidentifyandmanagelikelyunderlyingcausesofsecondary
amenorrhoea.Explicitrecommendationsonwhentoreferarelackinginthepublished
literature.Oftheauthorsthatdocomment,mostrecommendreferraliftheunderlyingcause
cannotbeidentifiedortreatmentcanonlybegiveninsecondarycare[Wilsonetal,2005
(/amenorrhoea#!references/A52227)].
Referraltoagynaecologist
Expertsrecommendreferringgirlsandwomenwithsuspectedprematureovarianfailure
forspecialistassessmentandmanagementtoenable[Balen,2000
(/amenorrhoea#!references/A24721)Balen,2004(/amenorrhoea#!references/A23897)
LedgerandSkull,2004(/amenorrhoea#!references/A52164)MasterHunterandHeiman,
2006(/amenorrhoea#!references/A23046)PracticeCommitteeoftheAmericanSociety
forReproductiveMedicine,2008(/amenorrhoea#!references/A51961)]:
Confirmationofthediagnosis,whichmayincludekaryotypinginwomenyoungerthan
30yearsofage.
Screeningforotherautoimmunedisease(presentinupto40%ofwomen)themost
commonisthyroiditis.
Monitoringandprophylaxisortreatmentofosteoporosis.
Treatmentforinfertility,ifdesired[NICE,2013(/amenorrhoea#!references/A72427)].
WomenwithsuspectedAsherman'ssyndromerequirehysteroscopytoconfirmthe
diagnosis[Balen,2000(/amenorrhoea#!references/A24721)PracticeCommitteeofthe
AmericanSocietyforReproductiveMedicine,2008(/amenorrhoea#!references/A51961)].
Referraltoanendocrinologist
Therecommendationtoreferthewomaniftheserumprolactinlevelisgreaterthan
1000mIU/L,or5001000mIU/Lontwooccasions,isbasedonexpertopinionfrom
narrativereviewsandspecialisttextbooksthatsuchfindingscanbecausedbyapituitary
adenoma,whichrequiresimagingofthepituitaryfossaandsecondarycaremedicalor
surgicaltreatment[Balen,2004(/amenorrhoea#!references/A23897)MasterHunterand
Heiman,2006(/amenorrhoea#!references/A23046)PracticeCommitteeoftheAmerican
SocietyforReproductiveMedicine,2008(/amenorrhoea#!references/A51961)Heiman,
2009(/amenorrhoea#!references/A52158)].
Evidenceinnarrativereviewsfoundapoorcorrelationbetweenprolactinlevelsandthe
presenceofatumourandthereforeitisrecommendedthatgirlsandwomenwithraised
prolactinlevels,whoaretakingdrugsthatareknowntoraisedprolactinlevels,shouldstill
bereferredtoexcludeatumour[MasterHunterandHeiman,2006
(/amenorrhoea#!references/A23046)PracticeCommitteeoftheAmericanSocietyfor

ReproductiveMedicine,2008(/amenorrhoea#!references/A51961)].
Therecommendationtoreferwomenwithanincreasedtestosteronelevelthatisnot
explainedbypolycysticovarysyndromeisbasedonaguidelinefromtheRoyalCollegeof
ObstetriciansandGynaecologistsonthediagnosisofpolycysticovarysyndrome[RCOG,
2007(/amenorrhoea#!references/A49207)],andonexperttextbookopinion[Balen,2012
(/amenorrhoea#!references/A78270)],whichrecommendthatanandrogensecreting
tumour,lateonsetcongenitaladrenalhyperplasia,andCushing'ssyndromeshouldbe
excluded.Thisislikelytorequiresecondarycareexpertise.
Therecommendationtoreferwomenwithlowfolliclestimulatinghormoneandluteinizing
hormonelevelstoexcludehypopituitarismorapituitarytumourisbasedonopinionsof
severalCKSexpertreviewers.
Managingamenorrhoeacausedbyweightloss,excessiveexercise,stress,orchronic
illnessafterassessmentbyanendocrinologist
Therecommendationtomanagehypothalamicamenorrhoeacausedbyweightloss,
excessiveexercise,stress,orchronicillnessafterassessmentbyanendocrinologistis
basedonexpertopinionfromnarrativereviewsandaspecialisttextbookthata
hypothalamicorpituitarytumourshouldbeexcludedbeforetreatingtheseconditions[Balen,
2000(/amenorrhoea#!references/A24721)Rees,2003
(/amenorrhoea#!references/A15334)MasterHunterandHeiman,2006
(/amenorrhoea#!references/A23046)PracticeCommitteeoftheAmericanSocietyfor
ReproductiveMedicine,2008(/amenorrhoea#!references/A51961)Heiman,2009
(/amenorrhoea#!references/A52158)Balen,2012(/amenorrhoea#!references/A78270)].
Referraltoadietitian
Therecommendationtoconsiderreferringwomenwhoareunderweighttoadietitianis
basedonexpertopinion[McIveretal,1997(/amenorrhoea#!references/A6569)].The
definitionofunderweightisbasedonexpertopinionthatamenorrhoeacanoccurwhen
bodymassindexislessthan19kg/m2[LedgerandSkull,2004
(/amenorrhoea#!references/A52164)].
Contraceptiveadvice
Therecommendationtooffercontraceptiontowomenwhodonotwishtobecomepregnant,
isbasedonevidencethatwomenwithprematureovarianfailurehavea510%chanceof
naturalconception,owingtointermittentovarianfunction[Balen,2000
(/amenorrhoea#!references/A24721)MasterHunterandHeiman,2006
(/amenorrhoea#!references/A23046)PracticeCommitteeoftheAmericanSocietyfor
ReproductiveMedicine,2008(/amenorrhoea#!references/A51961)Heiman,2009
(/amenorrhoea#!references/A52158)].
Managingosteoporosisrisk

Evidencefromobservationalstudiesindicatesthatwomenwithamenorrhoeaassociated
withlowoestrogenlevelsareatincreasedriskofosteoporosis[MasterHunterandHeiman,
2006(/amenorrhoea#!references/A23046)Csermelyetal,2007
(/amenorrhoea#!references/A52139)Golden,2007(/amenorrhoea#!references/A52135)
Balen,2012(/amenorrhoea#!references/A78270)].

Managingosteoporosisrisk
HowshouldImanagetheriskofosteoporosis?
Forwomenwithprematureovarianfailure(youngerthan40yearsofage),
hypothalamicamenorrhoea,orhyperprolactinaemia(womenwithamenorrhoea
associatedwithlowoestrogenlevelswhoareatincreasedriskofdevelopingosteoporosis):
Treattheunderlyingcause,ifpossible.
Assesstheirfragilityfracturerisk,correctvitaminDdeficiencyandensurean
adequatecalciumintake.ForfurtherinformationseetheCKStopiconOsteoporosis
preventionoffragilityfractures(/osteoporosispreventionoffragilityfractures).
Considerofferinghormonereplacementtherapyorthecombinedoral
contraceptivepill(bothofflabeluse)ifamenorrhoeapersistsformorethan12months.
Offercyclicalcombinedhormonereplacementtherapy(atthedosesusedfor
menopause)or,ifcontraceptionisneeded,acombinedoralcontraceptive.Seethe
CKStopicsonMenopause(/menopause)andContraceptioncombinedhormonal
methods(/contraceptioncombinedhormonalmethods)forprescribinginformation.
Reviewtreatmentatleastannually.Forwomenwithamenorrhoeaduetoreversible
causes(suchasweightlossorexcessiveexercise),oestrogenreplacementshouldbe
periodicallystopped(forexampleafter12monthsoftreatment,for6months)tosee
whethermensesresumeofftreatment.

Basisforrecommendation
Theserecommendationsarebasedonexpertopinionfromnarrativereviewsandspecialist
textbooks[Balen,2000(/amenorrhoea#!references/A24721)Balen,2004
(/amenorrhoea#!references/A23897)LedgerandSkull,2004
(/amenorrhoea#!references/A52164)PracticeCommitteeoftheAmericanSocietyfor
ReproductiveMedicine,2008(/amenorrhoea#!references/A51961)].
Identifyingwomenatrisk
Evidencefromobservationalstudiesindicatesthatwomenwithamenorrhoeaassociated
withlowoestrogenlevelsareatincreasedriskofosteoporosis[MasterHunterandHeiman,

2006(/amenorrhoea#!references/A23046)Csermelyetal,2007
(/amenorrhoea#!references/A52139)Golden,2007(/amenorrhoea#!references/A52135)
Balen,2012(/amenorrhoea#!references/A78270)].
Treatingtheunderlyingcause
Thisisapragmaticrecommendationbasedonestablishedprinciplesofgoodmedical
practice.
Hormonereplacementtherapyandcombinedoralcontraceptives
Thereisaconsensusofexpertopinioninthepublishedliteraturethatoestrogen
replacementshouldbeinitiatedtopreventexcessivebonelossinwomenwithhypothalamic
amenorrhoeaorprematureovarianfailure[Balen,2000
(/amenorrhoea#!references/A24721)Balen,2004(/amenorrhoea#!references/A23897)
LedgerandSkull,2004(/amenorrhoea#!references/A52164)PracticeCommitteeofthe
AmericanSocietyforReproductiveMedicine,2008(/amenorrhoea#!references/A51961)
Marjoribanksetal,2012(/amenorrhoea#!references/A71649)].
Thereisnoconsensusonwhich(HRTorCOCs)ispreferable.Oneexpertrecommends
HRT(unlesscontraceptionisrequired)becauseoftheloweroestrogendose[Balen,2004
(/amenorrhoea#!references/A23897)],whereasanotherstatesthatthedosesofoestrogenin
HRTareinsufficienttoimprovebonemineraldensityinteenagersandyoungadults
[Hergenroeder,1995(/amenorrhoea#!references/A52251)].
Therecommendationtoperiodicallystoptreatmentispragmaticandisbasedonastudyof
93womenwithhypothalamicamenorrhoeaduetostress,exercise,orweightloss,inwhich
morethan70%recoveredsomeovarianfunctionover8years[Falsettietal,2002
(/amenorrhoea#!references/A53538)].
Opinionsinthepublishedliteraturedifferontheperiodofamenorrhoeaafterwhich
oestrogenreplacementisrecommended,varyingfrom612months[Balen,2000
(/amenorrhoea#!references/A24721)Balen,2004(/amenorrhoea#!references/A23897)
LedgerandSkull,2004(/amenorrhoea#!references/A52164)PracticeCommitteeofthe
AmericanSocietyforReproductiveMedicine,2008(/amenorrhoea#!references/A51961)].
CKSrecommends12months,toallowtimefortreatmentoftheunderlyingcausetobe
effective.

Supportingevidence
Thereisalackofgoodqualityevidencetosupportmanagementrecommendations.The
managementofamenorrhoeaisthereforelargelybasedonexpertopinion.

Searchstrategy

Scopeofsearch
Aliteraturesearchwasconductedforguidelinesandbackgroundreviewsontheprimarycare
managementofamenorrhoea,withadditionalsearchesinthefollowingareas:
Managementofosteoporosisrisk,cardiovascularrisk,andriskofendometrialhyperplasiain
womenwithchronicamenorrhoea(2006)
Etiologyofprimaryandsecondaryamenorrhoea(1950)
Searchdates
Guidelines/backgroundreviews:June2009June2014
Keysearchterms
Variouscombinationsofsearcheswerecarriedout.Thetermslistedbelowarethecoresearch
termsthatwereusedforMedline.
expamenorrhea/,amenorrhoea.tw,amenorrhea.tw
exposteoporosis/,expcardiovasculardiseases/,expendometrialhyperplasia/,exprisk
factors/,exprisk/
Table1.Keytosearchterms.
Search

Explanation

commands
/

indicatesaMeSHsubjectheadingwithallsubheadingsselected

.tw

indicatesasearchforaterminthetitleorabstract

exp

indicatesthattheMeSHsubjectheadingwasexplodedtoincludethenarrower,
morespecifictermsbeneathitintheMeSHtree

indicatesthatthesearchtermwastruncated(e.g.wart$searchesforwartand
warts)

Topicspecificliteraturesearchsources
AmericanSocietyforReproductiveMedicine(http://www.asrm.org)
RoyalCollegeofObstetriciansandGynaecologists(http://www.rcog.org.uk)
Sourcesofguidelines
NationalInstituteforHealthandCareExcellence(NICE)(http://www.nice.org.uk)
ScottishIntercollegiateGuidelinesNetwork(SIGN)(http://www.sign.ac.uk)
RoyalCollegeofPhysicians(http://www.rcplondon.ac.uk/)
RoyalCollegeofGeneralPractitioners(http://www.rcgp.org.uk/)
RoyalCollegeofNursing(http://www.rcn.org.uk/development/practice/clinicalguidelines)
NICEEvidence(https://www.evidence.nhs.uk/topics/)

HealthProtectionAgency(http://www.hpa.org.uk)
NationalGuidelinesClearinghouse(http://www.guideline.gov)
GuidelinesInternationalNetwork(http://www.gin.net)
TRIPdatabase(http://www.tripdatabase.com)
GAIN(http://www.gainni.org/index.php/audits/guidelines)
InstituteforClinicalSystemsImprovement(http://www.icsi.org)
NationalHealthandMedicalResearchCouncil(Australia)
(http://www.nhmrc.gov.au/publications/index.htm)
RoyalAustralianCollegeofGeneralPractitioners(http://www.racgp.org.au/your
practice/guidelines/)
BritishColumbiaMedicalAssociation(http://www.health.gov.bc.ca/gpac/index.html)
CanadianMedicalAssociation(http://www.cma.ca/index.php/ci_id/54316/la_id/1.htm)
TowardsOptimalPractice(http://www.topalbertadoctors.org/cpgs/)
UniversityofMichiganMedicalSchool(http://ocpd.med.umich.edu/cme/selfstudy/)
MichiganQualityImprovementConsortium(http://www.mqic.org/guidelines.htm)
PatientUKGuidelinelinks(http://www.patient.co.uk/guidelines.asp)
DriverandVehicleLicensingAgency(https://www.gov.uk/government/organisations/driver
andvehiclelicensingagency)
Medline(withguidelinefilter)
Sourcesofsystematicreviewsandmetaanalyses
TheCochraneLibrary(http://www.thecochranelibrary.com):
Systematicreviews
Protocols
DatabaseofAbstractsofReviewsofEffects
Medline(withsystematicreviewfilter)
EMBASE(withsystematicreviewfilter)
Sourcesofhealthtechnologyassessmentsandeconomicappraisals
TheCochraneLibrary(http://www.thecochranelibrary.com):
NHSEconomicEvaluations
HealthTechnologyAssessments
CanadianAgencyforDrugsandTechnologiesinHealth(http://www.cadth.ca)
InternationalNetworkofAgenciesforHealthTechnologyAssessment
(http://www.inahta.org)
NIHRHealthTechnologyAssessmentprogramme(http://www.hta.ac.uk/)
Sourcesofrandomizedcontrolledtrials
TheCochraneLibrary(http://www.thecochranelibrary.com):
CentralRegisterofControlledTrials
Medline(withrandomizedcontrolledtrialfilter)
EMBASE(withrandomizedcontrolledtrialfilter)
Sourcesofevidencebasedreviewsandevidencesummaries

CentralServicesAgencyCOMPASSTherapeuticNotes
(http://www.medicinesni.com/courses/type.asp?ID=CN)
Sourcesofnationalpolicy
DepartmentofHealth(https://www.gov.uk/government/organisations/departmentofhealth)
HealthManagementInformationConsortium(HMIC)
Patientexperiences
Healthtalkonline(http://www.healthtalkonline.org/)
BMJPatientJourneys(http://www.bmj.com/bmjseries/patientjourneys)
Patient.co.ukPatientSupportGroups(http://www.patient.co.uk/selfhelp.asp)
Sourcesofmedicinesinformation
ThefollowingsourcesareusedbyCKSpharmacistsandarenotnecessarilysearchedbyCKS
informationspecialistsforalltopics.Someoftheseresourcesarenotfreelyavailableand
requiresubscriptionstoaccesscontent.
BritishNationalFormulary(http://bnf.org/bnf/)(BNF)
electronicMedicinesCompendium(http://www.medicines.org.uk)(eMC)
EuropeanMedicinesAgency(http://www.ema.europa.eu/ema/)(EMEA)
LactMed(http://toxnet.nlm.nih.gov/cgibin/sis/htmlgen?LACT)
MedicinesandHealthcareproductsRegulatoryAgency(http://www.mhra.gov.uk/index.htm)
(MHRA)
REPROTOX(http://www.reprotox.org/Default.aspx)
ScottishMedicinesConsortium(http://www.scottishmedicines.org.uk/Home)
Stockley'sDrugInteractions
(https://www.medicinescomplete.com/mc/stockley/current/login.htm)
TERIS(http://depts.washington.edu/terisweb/teris/)
TOXBASE(http://www.toxbase.org/)
Micromedex(http://www.micromedex.com/products/hcs/)
UKMedicinesInformation(http://www.ukmi.nhs.uk/)

AmenorrhoeaSummary
Amenorrhoeaistheabsenceorcessationofmenses.Itmaybephysiological,pathological,
oriatrogenic.
Primaryamenorrhoeaisgenerallydefinedasthefailuretoestablishmenstruationby16
yearsofageingirlswithnormalsecondarysexualcharacteristics,orby14yearsofage
ingirlswithnosecondarysexualcharacteristics.
Secondaryamenorrhoeathereisnoconsensusinthepublishedliteratureonthe
definitionofsecondaryamenorrhoea.Someauthorsandguidelinesdefinesecondary
amenorrhoeaastheabsenceofmenstruationforatleast6monthsinwomenwith
previouslynormalmenses,orfor12monthsinwomenwithpreviousoligomenorrhoea.

Othersdefineitastheabsenceofmensesfor3monthsinwomenwithpreviouslynormal
menstruation,orfor9monthsinwomenwithpreviousoligomenorrhoea.
Causesofprimaryamenorrhoeainclude:
Physiologicalcauses:pregnancyandconstitutional.
Pathologicalcausesassociatedwithnormalsecondarysexualcharacteristics.Themost
commonaregenitourinarymalformations,includingimperforatehymen,transverse
septum,absentvagina,orabsentuterus.
Pathologicalcausesassociatedwithnosecondarysexualcharacteristics.Themost
commonareovarianfailure(forexampleinTurner'ssyndrome)andhypothalamic
pituitarydysfunction(forexamplecausedbyweightloss,orexcessiveexercise).
Causesofsecondaryamenorrhoeainclude:
Physiologicalcauses:pregnancy,lactation,menopause.
Iatrogenic/illicitdrugs:progestogenmethodsofcontraception,radiotherapy,cocaine.
Uterinecauses:cervicalstenosis,Asherman'ssyndrome.
Ovariancauses:prematureovarianfailure,chemotherapy.
Hypothalamicdysfunction:weightloss,eatingdisorders,excessiveexercise,stress,
depression,chronicsystemicillness.
Pituitarycauses:prolactinoma,hypopituitarism,Sheehan's,sarcoidosis,cranial
irradiation.
Thyroiddisease:hypothyroidism,hyperthyroidism.
Endocrinecauses:polycysticovarysyndrome,Cushing'ssyndrome,lateonsetcongenital
adrenalhyperplasia.
Androgensecretingtumoursoftheovaryoradrenalgland.
Referralforinvestigationofprimaryamenorrhoeaisrecommendedforgirls:
Whohavenotstartedmenstruatingby14yearsofageandhavenosecondarysexual
characteristics.
Withnormalsecondarysexualcharacteristicswhohavenotstartedmenstruatingby16
yearsofage.
Diagnosisofamenorrhoeaandfurtherinvestigationisrecommendedforgirlsandwomen
whohavehad:
Normalandregularmenses,after36consecutivemonthsofamenorrhoea.
Oligomenorrhoea,after912consecutivemonthsofamenorrhoea.
Thecombinedoralcontraceptive,6monthsafterstoppingthepill.
Aninjectableprogesterone,9monthsafterthelastinjection.
Womenwithsecondaryamenorrhoeaduetopolycysticovarysyndrome,hypothyroidism,
menopause,orpregnancyshouldbemanagedinprimarycare,whereappropriate.
Referraltoagynaecologistshouldbearrangedifthewomanhasanyofthefollowing:
elevatedFSHandLHlevels(andyoungerthan40yearsofage)recenthistoryofuterineor
cervicalsurgeryorseverepelvicinfectioninfertilitysuspectedpolycysticovarysyndrome(if
diagnosisisnotfeasibleinprimarycare).
Referraltoanendocrinologistshouldbearrangedifthewomanhasanyofthefollowing:
hyperprolactinaemialowFSHandLHanincreasedtestosteronelevelnotexplainedby

polycysticovarysyndromefeaturesofCushing'ssyndromeorlateonsetcongenitaladrenal
hyperplasia.
Amenorrhoeacausedbyweightloss,excessiveexercise,stress,orchronicillnessshouldbe
managedafteranendocrinologisthasassessedandexcludedahypothalamiccauseor
pituitarytumour.

HaveIgottherighttopic?
Agefrom10yearsonwards(Female)
ThisCKStopiccoversthecauses,initialassessment,investigation,andinitialmanagementof
primaryandsecondaryamenorrhoea.Italsocoversthemanagementofosteoporosisriskin
womenwithamenorrhoeaassociatedwithlowoestrogenlevels.
ThisCKStopicdoesnotcoverindetailthemanagementofthespecificcausesof
amenorrhoea.Italsodoesnotspecificallycoveroligomenorrhoea,althoughmanyofthe
causes,andtheinitialassessmentandmanagement,ofoligomenorrhoeaarethesameas
amenorrhoea.
ThereareseparateCKStopicsonInfertility(/infertility),Menopause(/menopause),and
Polycysticovarysyndrome(/polycysticovarysyndrome).
ThetargetaudienceforthisCKStopicishealthcareprofessionalsworkingwithintheNHSin
theUK,andprovidingfirstcontactorprimaryhealthcare.

Howuptodateisthistopic?
Changes
Update

Goalsandoutcomemeasures
Goals

Backgroundinformation
Definition
Prevalence
Causes

Complications

Diagnosis
Diagnosisprimaryamenorrhoea
Diagnosissecondaryamenorrhoea

Management
Scenario:Primaryamenorrhoea(/amenorrhoea#!scenario):coversthetreatmentand
referralofwomenandgirlswithprimaryamenorrhoea.
Scenario:Secondaryamenorrhoea(/amenorrhoea#!scenario:1):coversthetreatment
andreferralofwomenandgirlswithsecondaryamenorrhoea.

Evidence
Supportingevidence
Searchstrategy

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