医学知识一HOMONEREPLACEMENTTHERAPY(HRT)：激素替代疗法(HRT)

MENOPAUSEWHAT?MenopauseisadeviationoftheancientGreekwordsmenos(month)andpauses

(ending).Themenopauseissometimesknownasthe'changeoflife'andismarkedbytheendingofmenstruation.

WHAT?Itbedefinedwithcertaintyaftertwelvemonths'spontaneousamenorrhoea.Endofreproductivelife.Age(years)Pre-menopausePost-menopauseMENOPAUSE1YEARPeri-menopause“Climacteric”RELATEDTERMINOLOGYWHEN?Menopausalage:45-55years(mean:50.7years)Ifthemenopauseoccursinawomanwhoisunder45yearsofage,itisknownasprematuremenopause.Latemenopause:>55yearsoldWHEN?Otherfactorsthatcanaffecttheageatwhichwomenhavetheirfinalperiodincludeageatmenarche,parity,previousoralcontraceptivehistoryethnicityandfamilyhistory.WHY?RELATIVEACTIVITYOFESTROGENWHY?Themenopauseistheendofeggproduction(ovulation).Thisoccursasaresultoffallinglevelsofthefemalesexhormoneoestrogen,whichregulatesawoman'speriods.WHY?Themenopauseresultsfromafallinthelevelofthefemalehormoneoestrogenintheblood.WHY?Atahormonallevel-asovarianfollicularactivitybeginstofail,oestrogenandprogesteronelevelsfallandthereducednegativefeedbacktothepituitarycausesariseinluteinisinghormone(LH)andfolliclestimulatinghormone(FSH).HOW?Oestrogenreductioneventuallyresultsinmenstrualcycledisruptionandothermenopausalsymptoms.

HOW?Oestrogenreductioneventuallyresultsinmenstrualcycledisruptionandothermenopausalsymptoms.

*FSH high

(30–170mU/ml) *LH high

(20–80mU/ml) *Estradiol low

(<110pmol/L)

VasomotorSymptomsSleepDisordersMenstrualDisordersMoodChangesVaginalAtrophyDyspareuniaSkinAtrophyOsteoporosisAtherosclerosisCoronaryHeartDiseaseCerebrovascularDisease40yrs50yrsMenopause60yrsSYMPTOMS!ONSETOFSYMPTOMSINRELATIONTOAGEOFMENOPAUSESYMPTOMS!Changesinyourperiod—timebetweenperiodsorflowmaybedifferent.Hotflashes(“hotflushes”)—gettingwarmintheface,neckandchest.Nightsweatsandsleepingproblemsthatmayleadtofeelingtired,stressedortense.Vaginalchanges—thevaginamaybecomedryandthin,andsexmaybepainful.Thinningofyourbones,whichmayleadtolossofheightandbonebreaks(osteoporosis).

SYMPTOMS!Itisestimatedthat8outof10womenintheUKexperiencesymptomsleadinguptothemenopause.Ofthese,45%findtheirsymptomsdifficulttodealwith.

SYMPTOMS!Withouttreatment,mostmenopausalsymptomsgraduallystopnaturally.Thisusuallyhappenstwotofiveyearsafterthesymptomsstart.Althoughsomewomenexperiencesymptomsformanymoreyears.

SYMPTOMS!SYMPTOMS!

NORMALTRABECULARBONEOSTEROPEROTICBONETREATMENTOnly1in10womenseekmedicaladvicewhentheygothroughthemenopauseandmanydonotneedanytreatment.Ifmenopausalsymptomsaresevereenoughtointerferewithdailylife,therearetreatmentsthatcanhelp.

TREATMENTThekindoftreatmentyoucantakedependsontheseverityofthesymptoms,medicalhistoryandpatient’sownpreferences.

TREATMENTHRTNON-HRT

HOMONEREPLACEMENTTHERAPY(HRT)Asthenamesuggests,HRTworksbyreplacingoestrogen.Hormonereplacementtherapy(HRT)canbeaneffectivetreatmentforthetypicalmenopause-relatedsymptoms.

HOMONEREPLACEMENTTHERAPY(HRT)HRTmayalsohaveaninfluenceonthelongtermhealthproblems(osteoporosis,cardiovasculardiseaseandstroke),thoughitshouldbenotedthatitdoesnotnecessarilyreducetheirriskforallwomen.

HOMONEREPLACEMENTTHERAPY(HRT)BENEFITSRISKSHOMONEREPLACEMENTTHERAPY(HRT)Forthetreatmentofmenopausalsymptomswheretherisk-benefitratio*isfavorable,infullyinformedwomen,inthelowestpossibledosetocontrolsymptomsandfortheshortestdurationpossible.

HOMONEREPLACEMENTTHERAPY(HRT)BENEFITSRelievemenopausalsymptomsMaintenanceofqualityoflifePreventionofosteoporosisNote:HRTshouldnotbeusedasafirst-linetreatmentinosteoparosisexceptinwomenwhohaveprematuremenopause

HOMONEREPLACEMENTTHERAPY(HRT)RISKSOFVTE

HRT(combinedoroestrogen-alone)increasestheriskofadeepveinthrombosisorpulmonaryembolism,especiallyinthefirstyearoftreatment.Theriskismorepronouncedinwomenwithpre-existingriskfactors. Arecentmeta-analysissuggeststhattransdermaloestrogensmaybeasaferoptionthanoraloestrogensforHRT.

HOMONEREPLACEMENTTHERAPY(HRT)RISKSOFBREASTCANCERTheincreasedbreastcancerriskisproportionaltothedurationofHRT.HRTincreasesthisriskbyabout1.6

timesafter5yearsofuseand2.3

timesafter10

yearsofuse.RiskdecreaseswithinafewyearsofstoppingHRT.WomenconsideringHRTshouldbecounselledthattheabsoluteriskforbreastcancerforanyindividualremainsrelativelylow*Heractualriskincreases0.08%(ACOG)

HOMONEREPLACEMENTTHERAPY(HRT)RISKSOFENDOMETRIALCANCER

Endometrialcancer:increasedriskonlywithunopposedoestrogen.Thereisnoincreasedriskwithcombined(oestrogenandprogestogen)HRT.RISKSOFOVARIANCANCER

long-termuseofoestrogen-onlyHRTandcombinedHRTmayslightlyincreasetherisk.RiskdecreasesafterstoppingHRT.

HOMONEREPLACEMENTTHERAPY(HRT)RISKSOFCARDIOVASCULARDISEASEThereisnotthesameevidenceofcardioprotectionfromHRTaswasoriginallythought.Assessallwomen'sriskofCHDpriortostartingHRT.

HOMONEREPLACEMENTTHERAPY(HRT)HOMONEREPLACEMENTTHERAPY(HRT)sSequentiallycombinedHRT

E(continuouslyD1-D21)P(sequentiallyD11-D21)ContinuouscombinedHRT

E&P(continuous:D1-D28)HOMONEREPLACEMENTTHERAPY(HRT)WomenwithanintactuterusVasomotorsymptomsPerimenopausal:systemiccyclicalcombinedHRT.Postmenopausal:systemiccontinuouscombinedHRTortibolone.UrogenitalsymptomsPerimenopausal:low-dosevaginaloestrogenorsystemiccyclicalcombinedHRT.Postmenopausal:low-dosevaginaloestrogenorsystemiccontinuouscombinedHRT.

HOMONEREPLACEMENTTHERAPY(HRT)WomenwhohavehadahysterectomyVasomotorsymptoms:systemicoestrogen-onlyHRT.Urogenitalsymptoms:low-dosevaginaloestrogenorsystemicoestrogen-onlyHRT.

HOMONEREPLACEMENTTHERAPY(HRT)

HOMONEREPLACEMENTTHERAPY(HRT)

CONTRAINDICATIONSOFHRT!Pregnancyandbreast-feedingUndiagnosedabnormalvaginalbleedingVenousthromboembolicdiseaseActiveorrecentanginaormyocardialinfarctionSuspected,currentorpastbreastcancerEndometrialcancerorotheroestrogen-dependentcancerActiveliverdiseasewithabnormalliverfunctiontests

START-UPSYMPTOMSOFHRT!BreasttendernessNipplesensitivityBloatingNausea,headachesAppetiteWeightgainLegcramps

INVESTIGATIONSBEFOREHRT!InvestigationsarenotusuallynecessarybeforestartingHRTunlessthereis:suddenchangeinmenstrualpattern(IMB/PCB)HighriskofbreastcancerPersonal/familyhistoryofVTEWomanhasarterialriskfactors

ALTERNATIVETOHRT!“Tibolone”isasynthetichormonethatactsinthesamewayasHRT(SERM)Usefulforpost-menopausalwomenwhowanttoendtheirperiods.Whichhasoestrogenic,progestogenicandandrogenicproperties.(estrogenicactivityinbone,CNSvasomotorsuppressionofhotflushesandhelpfulinimprovingsexualfunction.

STARTINGHRT!

“Afullphysicalexaminationismandatory”FullbloodcountRenalProfile -BaselineLiverFunctionTestLipidprofileFOLLOWUPOFTAKINGHRT!Reviewthewoman3monthsafterstartingHRTandonceeachyearthereafter.At3-months:Enquireaboutbleedingpatterns,checkbloodpressure,andbodyweight.Assesstheeffectivenessoftreatmentandadjusttoachievesymptomcontrol.Enquireaboutadverseeffectsandmanageappropriately.

FOLLOWUPOFTAKINGHRT!Onceeachyear:Checkbloodpressure,effectivenessoftreatmentandadjusttoachievesymptomcontrol.Enquireaboutadverseeffectsandmanageappropriately.ConsiderswitchingfromcyclicalHRTtocontinuouscombinedHRT,ifappropriate.

FOLLOWUPOFTAKINGHRT!DiscusstherisksandbenefitsofHRT.Performabreastexaminationifindicatedbypersonalorfamilyhistory.Encouragebreastawarenessandparticipationinthenationalbreastscreeningprogrammeasappropriatefortheirage.Pelvicexaminationisrequiredonlyifclinicallyindicated

NON-HRTLifestylemodificationStopsmokingHealthydietWeightcontrolRegularmoderate-intensityexerciseControlbloodpressureandcholesterolNON-HRTForvasomotorsymptomsAtrial(2weeks)ofparoxetine,fluoxetinecitalopramorven