多囊卵巢綜合癥診治進展

PolycysticOvarySyndrome

(PCOS)

----ProgressinDiagnosisandTherapyOutlineDefinitionofPCOSPathogenesisofPCOSDiagnosiscriteriaofPCOSDifferentiationindiagnosisofPCOS

TherapyofPCOSDefinitionofPCOS-1AsyndromeofovariandysfunctionAlongwiththecardinalfeatureshyperandrogenism(HA)polycysticovary(PCO)morphology.Itsclinicalmanifestationsinclude:menstrualirregularities,signsofandrogenexcessandobesity.IRandelevatedserumLHlevelsarealsocommonfeatures.Associatedwithanincreasedriskoftype2diabetesandcardiovascularevents.The2003RotterdamconsensusworkshopDefinitionofPCOS-2AhyperandrogenicdisorderPCOshouldbeconsidered,althoughnotall;Ovulatorydysfunctionisaprominent,butnotauniversalfeature.Otherwell-defineddisordershadtobeexcluded.JCEM2006,TheAndrogenExcessSociety(AES)DefinitionofPCOS-3Theconditionthathaveamajoreffectthroughoutlifeonthereproductive,metabolic,andcardiovascularhealth.SimplifiedbyEhrmannDAinNEnglJMed2005;352:1223PathophysiologicFeaturesofPCOS-1AsyndromeofovariandysfunctionAlongwiththecardinalfeatures

hyperandrogenism

（HA）polycysticovary(PCO)morphology.Itsclinicalmanifestationsinclude:menstrualirregularities,signsofandrogenexcessandobesity.

IRandelevatedserumLHlevelsarealsocommonfeatures.Associatedwithanincreasedriskoftype2diabetesandcardiovascularevents.The2003RotterdamconsensusworkshopPathophysiologicFeaturesofPCOS-2Theconditionthathaveamajoreffectthroughoutlifeonthereproductive,metabolic,andcardiovascularhealth.SimplifiedbyEhrmannDAinNEnglJMed2005;352:1223OutlineDefinitionofPCOSPathogenesisofPCOSDiagnosiscriteriaofPCOSDifferentialdiagnosisofPCOS

TherapyofPCOSPathogenesisofPCOS—overviewNotclearGeneticbackground：genepolymorphismsusceptibility！Developmentalorigin：abnormalityinepigeneticmodification!Endocrinopathy：DysfunctioninH-P-O-axisGlucose&lipidmetabolismdisorderPathogenesisofPCOS-

GeneticbackgroundIntenselyfamilialorfamilialgeneticpredispositionRelatedgenesormorphorism>70,include:Genesrelatedtosteroidmetabolism:

SHBG、CYP11A、AR,FSH-R,etc.Genesrelatedtoinsulinsecretionandobesity:INS,INS-R,etc.11newrisklociforChinesePCOSthroughGWAS:relatedtoINSsignaling,sexualhormonefunction,T2DM,calciumsignalingandendocytosis.NatGenet2012,44:1020;NatGenet2011,43:55PathogenesisofPCOS–

developmentaloriginsPCOSDiabetesCVDInfertility……

？FetalphaseDeliveryAdultTheoryof‘Fetaloriginsofadultdisease’(Barker1996)Theoryof‘Developmentaloriginsofhealth&disease，DOHaD’(Gluckman2007)Hypothesisof‘Diseasesofembryo-fetalorigin’

(Motrenko2010)Gamete-embryonicphaseupto6wpost-fertilizationPathogenesisofPCOS–

DysfunctioninH-P-O-axisNewEnglJMed,2005PathogenesisofPCOS

----Summaryof

DysfunctioninH-P-O-axisIncreasedLH

secretionandabnormalhighratioofLH/FSHEnhancingandrogenproduction&secretionhyperandrogenemia(HA)Inhibitedfolliculogenesis(卵泡生成)&anovulation(無排卵)PCOHyperandrogenism,menstrualdysfunction,infertility&endometriopathyInsulinResistance

(IR)andhyperinsulinemia

(HI)Enhancingandrogenproduction&secretionHADecreasedSHBG

productionHAHigherrisksofObesity,T2DM,CVDPathogenesisofPCOS–

startinginchildhoodFertilSteril,2013IR&Hyperinsulinemia(HI)IR(InsulinResistance)Low-sensitivityandlow-reactivityoftargettissuetoINSWithhighserumFFA,enhancedgluconeogenesis,hyperglycemiaAndcompensatoryHIatearlystageEtiologyofIRINSdefects:genemutation,auto-Ab,enhanceddegeneration,etc.INS-Rdefects:allelemutation,auto-Ab,etc.PostINS-Rdefects:abnormalityininsulinsignallingpathways,etc.IR&HIarethemainpathophysiologyandtraitsHyperandrogenemia&IR/HIHAisnottheetiologyofIR&HIIR&HImaycauseHAIR&HIarepreferredtoconsiderintherapyOutlineDefinitionofPCOSPathogenesisofPCOSDiagnosiscriteriaofPCOSDifferentialdiagnosisofPCOS

TherapyofPCOSDiagnosiscriteriaofPCOS-1AndrogenExcessandPolycysticOvarySyndromeSociety（AE-PCOS）2006DiagnosiscriteriaofPCOS-2AndrogenExcessandPolycysticOvarySyndromeSociety（AE-PCOS）2006DiagnosiscriteriaofPCOS-China2011(CMA-sponsoredGynecologicalendocrinologyConsensusWorkshopGroup，2011)ThesuspectedPCOSMusthave:oligomenorrhea,amenorrhea,irregularuterinehemorrhageTheattached：AnyoneoftwoHyperandrogenismorHAPCOExcludeotherdisordersClassificationofPCOSCentralobesity:ornotIGT,T2DM,metabolicsyndrome:ornotClassictype:abnormalmenses,HA&seriousmetabolicimpediment,+/-PCOPCOSwithoutHA:abnormalmenses&PCOwithmildmetabolicimpedimentDiagnosiscriteriaofPCOS-note1AstoOligo-oranovulationOligo-ovulationoligo-menorrheaFewerthanninemenses

peryearOrmenstrualcycle>35daysAnovulationamenorrheaLeadtodysfunctionaluterinebleedingandsubfertilityDiagnosiscriteriaofPCOS-note2AstoHyperandrogenism/HyperandrogenemiaHyperandrogenismClinicalsignsofandrogenexcessHirsutism,acne,andandrogenicalopeciaHyperandrogenemiaBiochemicalsignsofandrogenexcessElevatedlevelsofcirculatingandrogensDiagnosiscriteriaofPCOS-note3AstoPCOSignsunderultrasonographyFollicleNo.≥10-12and2~8mm

indiameterinaUSpictureWith/withoutenhancedUSfeedbackofovarianstromaNotnecessaryandmightnotaPCOS!JClinEndocrinolMetab93:196–199,2008DiagnosiscriteriaofPCOS-note4TherelatedpathophysiologyofPCOSInsulinresistance(IR),hyperinsulinism

andglucoseintoleranceHyperglycemia,HIorIGTHyperlipidemia

andobesityHighlevelofTG,TC,LDLPandBMIOthers：Endometrialcarcinoma:endometriumbiopsyObstructivesleepapnea：Polysomnography(多道睡眠描記術)RiskassessmentofCVDinPCOS

JClinEndocrinolMetab95:2038，2010Feriman-GallweyScoreforHirsutismAssessment

（modified）1-4scores/partUpperlipLowerjawChestUpperabdomenArmsLegsBackNormal＜7;

Hirsutism＞9DiagnosiscriteriaofPCOS-note5AstoExclusionofotheretiologiesCongenitaladrenalhyperplasiaAndrogen-secretingtumorsCushing’ssyndromeAndrogenic/anabolicdruguseorabuseInsulinresistanceThyroiddysfunctionHyperprolactinemiaetc.OutlineDefinitionofPCOSPathogenesisofPCOSDiagnosiscriteriaofPCOSDifferentialdiagnosisofPCOS

TherapyofPCOSDifferentialdiagnosisofPCOS

OutlineDefinitionofPCOSPathogenesisofPCOSDiagnosiscriteriaofPCOSDifferentialdiagnosisofPCOS

TherapyofPCOSTherapyofPCOSAproblemandachallengeLackofetiologicaltreatmentsComprehensive,cooperated&symptomaticLifestyleOperationsWestern/ChinesetraditionaltreatmentsClassificationsofPCOS

therapyLife-stylemodificationsSpecialforoligomenorrheaoramenorrheaSpecialforHA/masculinizationSpecialforIR,HI/IGTSpecialforhyperlipemia/obesitySpecialforinfertilityOthersLifestylemanagementofPCOS節食--LDLreduction減肥--Weightreduction鍛煉--Exercise戒煙酒--Avoidsmoking戒煙酒--AvoidalcoholHalfanddone!FertilSteril2007,ESHRE/ASRM-SponsoredPCOSConsensusWorkshopGroupJClinEndocrinolMetab2010,theAE-PCOSSocietyBoardSpecialforoligomenorrheaoramenorrheaIndications:MC>35dwithbirthplanorMC>60dwithbirthplanInducemenseswithP-test&,ifnecessary,E-testP-test:

Dydrogesterone10-mg,bidx10-daysE-test:

EstradiolValerate1.0-mg,bidx21-dayswithP-testonDay12TherapywithE&Pfor3-6artificialcyclesE&Pinasequentialway,likeFemoston(芬嗎通，雌二醇地屈孕酮片復合片)E&Pinasimultaneousway,likeDiane-35(達因-35，炔雌醇環丙孕酮片)Continuedwithovulationinduction&ARTor

monitoringnaturalmensesandovulationIfMC>60d,repeatthetherapiesaboveSpecialforHA-AcneIndicationsforacneWithmenstrualdysfunction,ovulationabnormalityorinfertilityWithconsiderationinpsychologyorbeautyTherapiesGnRHa:

DownregulationonpituitaryfunctiontodecreaseTproductionSpironolactone:inhibit5α-reductase&competethereceptorstomakeTineffectiveDiane-35:inhibitTproductiontomakeTinalowlevelOthers:DXM(地塞米松),Finasteride(非那雄胺),etc.NotesIfhyperinsulinemia,dealwithHIfirst.Therapiesshouldbelastedfor3-6months.Drugsunitedarepreferred.Sideeffectsshouldbemonitoredifalongtherapy.IndicationsoftreatmentModerateorseverehirsutismHirsutismsuddeninonset,rapidlyprogressiveHirsutismassociatedwithotherabnormalities：Menstrualdysfunction,obesity,orclitoromegaly.TreatmentsPatient-importanthirsutismdespitecosmeticmeasures：EitherpharmacologicaltherapyordirecthairremovalmethodsPharmacologicaltherapy,Oralcontraceptives,likeDiane-35Addingananti-androgensafter6monthsifsuboptimal.Hairremovaltherapy--Laser/photoepilationAgainstanti-Tmono-therapyorusinginsulin-loweringdrugs.JClinEndocrinolMetab,2008,AnEndocrineSocietyClinicalPracticeGuidelineSpecialforHA-HirsutismMetformin（二甲雙胍）:250-mg，bidx8-weeksPioglitazone（鹽酸吡格列酮):15mgqdx8-weeksSimilaritiesIncreasethetissuesensitivitytoINSStrenthentheconductionofINSinformationsystemStrenthentheglucosetransformationofperiferaltissuesFavorthefunctionofinletcellsinfatcellsEliminateIRandmaketheserumGSlevelinalowlevel

UnsimilaritiesMetformin:moreeffectiveinBWloss,cheapbutmoresideeffects.Pioglitazone:

moreeffectiveinabnormalitiesofglucolipidmetabolismSpecialforIR,HI&IGTAims：PreventCVDandDMThebasicintherapiesTherapeutic

life-stylechangeDecreasetheintakeofsaturatedFF&

CBodyweightdeductionExercise,avoidsmoking&saltinhibitionDrugtherapiesFenofibrate(非諾貝特TG);Simvastatin(辛伐他汀TC&CVD)SpecialforHyperlipemia&ObesityLifestylestrategies&effectsforLDLreductionJClinEndocrinolMetab95:2038，2010Preconceptionalcounseling&lifestyledirectionsEliminate:otherabnormalitiesinhealthEmphasize:healthylifestyleAttention:BWreduction,exercise,avoidsmoking&alcohol,etc.EspeciallyweightreductionandexerciseinoverweightwomenOvulationinductionCitrateClomiphene(CC)CC+Metformin(二甲雙胍)

orLOSGn-OI

remedyCC:thefirst-linetherapyinovulationinductionCC+Metformin:preferredinpatientswithIRLOS(laparoscopicovariansurgery腹腔鏡下卵巢手術):preferredinpatientswithinconvenienceinOIGn-OI:MoremultiplepregnancyrisksandmoremonitoringneededAromataseinhibitors(e.g.metformin):notroutinelyrecommendedinOIMetformin:preferredusedformetabolic/glucolipidabnormalitiesandformenstrualirregularitiesART:

IUI,IVF-ET,etcTherelatedrisks&hintsRiskofPOF/OHSSIndividualtherapySingleton/multiplepregnancyhigh-riskintensemonitoringFertilSteril2007,ESHRE/ASRM-SponsoredPCOSCon