婦產(chǎn)課件 18-1子宮內(nèi)膜異位癥北醫(yī)教學(xué) 2016 5

子宮內(nèi)膜異位癥和子宮肌腺病endometriosis

DepartmentofObstetrics&GynecologyBeijingHospital

衛(wèi)生部北京醫(yī)院孟慶偉定義當(dāng)具有生長(zhǎng)功能的子宮內(nèi)膜出現(xiàn)在子宮腔被覆粘膜以及宮體肌層以外的其他部位時(shí)，稱(chēng)為子宮內(nèi)膜異位征。Endometriosisisdefinedhistologicallybythepresenceofendometrialtissueinanectopiclocation,exclusiveoftheeutopicendometrium.流行病學(xué)：Itaffectsasmanyas1in15womenofreproductiveage.Endometriosisisoneofthemostcommongynecologicdisordersandisfoundinapproximately70%ofpatientswithchronicpelvicpain.發(fā)病機(jī)制病理1發(fā)病部位：盆腔（骶韌帶、卵巢）子宮漿膜、輸卵管、乙狀結(jié)腸。盆腔：75%，雙卵巢50%，7-37%腸管，16%泌尿。盆腔：外見(jiàn)腹部傷口、會(huì)陰側(cè)切傷口。

2大體病理：紫藍(lán)色結(jié)節(jié)、血性濾泡、散在的燒灼樣灶、含鐵血黃素沉著、點(diǎn)狀出血瘀斑、漿膜下出血。

盆腔表現(xiàn)+遠(yuǎn)處病灶

卵巢型腹膜型3顯微鏡下檢查：1.子宮內(nèi)膜上皮、內(nèi)膜腺體、腺樣結(jié)構(gòu)、內(nèi)膜間質(zhì)及出血。2.少量子宮內(nèi)膜間質(zhì)細(xì)胞。3.囊腫中有紅細(xì)胞、含鐵血黃素或吞噬有含鐵血黃素的巨噬細(xì)胞等出血證據(jù)。4.異位內(nèi)膜可有增生及分泌改變但不一定與子宮內(nèi)膜同步。5.異位內(nèi)膜可癌變《1%。流行病學(xué)1.激素依賴(lài)疾?。荷龐D女、月經(jīng)周期短經(jīng)期長(zhǎng)2.絕經(jīng)后2%需要腹腔鏡治療發(fā)病機(jī)理學(xué)說(shuō)1種植學(xué)說(shuō)2體腔上皮化生學(xué)說(shuō)3誘導(dǎo)學(xué)說(shuō)能否發(fā)病取決于：遺傳、免疫、炎癥、在位內(nèi)膜的特性相關(guān)因素1遺傳2免疫3炎癥4在位內(nèi)膜特性病理巨檢：卵巢：微小、典型病灶型腹膜型：色素沉著、無(wú)色素沉著深部結(jié)節(jié)：》5MM

其他部位腹膜型1色素沉著型2無(wú)色素沉著型深部結(jié)節(jié)型病灶浸潤(rùn)深度結(jié)節(jié)：》5MM常見(jiàn)于子宮直腸窩鏡檢：4種成分，子宮內(nèi)膜腺體、間質(zhì)、纖維素、紅細(xì)胞(含鐵血黃素）

臨床表現(xiàn)一、癥狀1.疼痛：非經(jīng)期下腹痛陰道深部性交痛經(jīng)期肛門(mén)墜痛或抽搐急腹痛盆腔外痛及出血。

臨床表現(xiàn)一、癥狀2.月經(jīng)失調(diào)：15%經(jīng)量多、經(jīng)血淋漓不盡、臨床表現(xiàn)一、癥狀3不孕-40%

黃體功能未破裂卵泡黃素化綜合征（LUFS)

自身免疫卵細(xì)胞質(zhì)量下降二體征：

子宮位置、子宮直腸窩、可觸痛結(jié)節(jié)、宮骶韌帶、附件包塊。輔助檢查超聲、核磁、血清CA125抗子宮內(nèi)膜抗體其他

診斷及鑒別診斷婦科檢查超聲血 CA125腹腔鏡R-AFS評(píng)分目的：統(tǒng)一衡量病情輕重的標(biāo)準(zhǔn)并制定出子宮內(nèi)膜異位征導(dǎo)致不孕征的治療規(guī)范。鑒別診斷1卵巢惡性腫瘤2盆腔炎性包塊3子宮肌腺征良性鑒別膿腫膿腫膿腫惡性鑒別治療Thetreatmentofendometriosis1疼痛的處理2內(nèi)異癥伴附件囊腫的處理3內(nèi)異癥伴不孕的處理個(gè)體化1年齡2要解決的問(wèn)題3對(duì)生育要求4經(jīng)濟(jì)狀態(tài)治療期待治療藥物治療手術(shù)治療期待治療輕型：3-6個(gè)月隨診鼓勵(lì)早妊娠藥物治療對(duì)癥治療假孕療法假絕經(jīng)治療其他治療對(duì)癥藥物治療假孕治療假絕經(jīng)治療性激素藥物治療1口服避孕藥2孕激素3雄激素4GNRHA藥物治療MedicaltreatmentofendometriosisMedicaltreatmentofendometriosisDanazolGestrinoneCombinedOralContraceptivesProgestogensGnRHAgonistsAromataseInhibitorsSelectiveEstrogenReceptorModulatorsSelectiveProgesteroneReceptorModulators藥物治療假孕療法1口服避孕藥Oralcontraceptives(OCs),連續(xù)口服類(lèi)似妊娠的長(zhǎng)期閉經(jīng)。高效孕激素和炔雌醇復(fù)合片。副作用假孕療法孕激素機(jī)制：抑制垂體促性腺激素釋放并直接作用于子宮內(nèi)膜，子宮內(nèi)膜開(kāi)始蛻膜化，最終導(dǎo)致內(nèi)膜萎縮和閉經(jīng)。醋酸甲孕酮30毫克，甲地孕酮40毫克，炔諾酮5毫克，連續(xù)用6個(gè)月。孕激素婦康片婦寧片安宮黃體酮假絕經(jīng)療法GNRH-A達(dá)那唑danazol200毫克TID其他治療孕三烯酮：雄激素、抗孕激素和抗雌激素作用。米非司酮：孕激素受體調(diào)節(jié)，抗孕酮和抗糖皮質(zhì)作用。MedicaltreatmentofendometriosisMechanisms:Aswithoralcontraceptives,theirproposedmechanismofactioninvolvesdecidualizationandsubsequentatrophyofendometrialtissue.Another,morerecentlyproposed,mechanisminvolvesaprogestogen-inducedsuppressionofmatrixmetalloproteinases,aclassofenzymesimportantinthegrowthandimplantationofectopicendometrium.MedicaltreatmentofendometriosisCombinedOralContraceptivesMechanism:Decidualization,followedbyatrophyoftheendometrialtissueistheproposedmechanismofaction.Effect:Hormonalcontraceptiveshavebeenusedinbothacyclicandacontinuousfashioninthetreatmentofsymptomsassociatedwithendometriosis.

MedicaltreatmentofendometriosisTheefficacyhasbeenpoorlyassessed,withabout80%improvementinsymtomsandan12%recurrencerateafter6monthsoffollow-up.Aprospectiveobservationaltrialdemonstratedthatcontinuouslow-doseOCsweremoreeffectivethancyclicOCsincontrollingendometriosissymptomsinpatientsaftersurgicaltreatmentforendometriosis.MedicaltreatmentofendometriosisSide-effect:Acommonsideeffectistransientbreakthroughbleeding,whichoccursin38%to47%.Othersideeffectsincludenausea,breasttenderness,andfluidretention,allresolvedafterdiscontinuation.MedicaltreatmentofendometriosisCombinedOralContraceptivesSideeffects:includingandrogenic,estrogenicandprogestogeniceffects.Thesehavebeenlargelylessenedwiththeadventofthelow-doseoralcontraceptivepill.MedicaltreatmentofendometriosisDanazol:aderivativeof17a-ethinyltestosteroneMechanisms:Danazoldoesnotalterbasallevelsofgonadotropins,butdiminishesthemidcycleLHandFSHsurge.Thus,thedrugcreatesachronicanovulatorystatetoinhibitthegrowthanddevelopmentofendometriosis.MedicaltreatmentofendometriosisDanazolEffect:Itwasalsofoundthat60%ofthosetreatedwithdanazolexperiencedpartialorcompleterecurrenceoftheendometriosis12monthsaftercompletionofdrugtherapy.MedicaltreatmentofendometriosisInaddition,danazoldisplacestestosteroneandestradiolfromSHBGaswellasprogesteroneandcortisolfromcorticosteroid-bindingglobulin,thisactionincreasesthefreehormonelevelsinthecirculation,especiallytestosterone.Finally,danazolinhibitsmultipleenzymesofthesteroidogenicpathway.MedicaltreatmentofendometriosisDanazolEffect:400mg,tidorbid,6monthsPainreliefhasbeenevaluated,withimprovementinsymptomsnotedin84%to92%,andthiseffectcouldbecontinuedupto6monthsafterdiscontinuationofthemedication.MedicaltreatmentofendometriosisDanazolSide-effects:Commonsideeffectsrelatetohyperandrogenism,suchasweightgain,musclecramps,decreasedbreastsize,flushing,moodchange,oilyskin,depression,sweating,edema,changeinappetite,acne,fatigue,hirsutism,decreasedorincreaselibido,nausea,headache,dizziness,rash,deepeningofvoiceetal.Alternateroutesofdanazoladministrationareunderinvestigation.

CobellisL,etal.FertilSteril2004;82:239–40MedicaltreatmentofendometriosisProgestogensThelevonorgestrel-releasingintrauterinesystem(Lng-IUS)representsanothernovelapproachtothemedicaltreatmentofendometriosis.Themechanismofactionisunknown.Theresponserateofpelvicpainwasabout70%withverylimitedside-effect.MedicaltreatmentofendometriosisProgestogensEffect:High-doseMPAwasadministeredfor6mothsandthepainreliefratewasroughly70%-90%.Ameta-analysisoffourrandomized,controlledtrialscomparingMPAtodanazolalone,danazolandOCs,oraGnRHagonist(goserelinacetate)concludedthatMPAwasaseffectiveastheothertreatments(OR1.1;95%CI,0.4to3.1).MedicaltreatmentofendometriosisArandomized,controlledtrialcomparingtheLng-IUStoexpectantmanagementafterlaparoscopicsurgicaltreatmentforsymptomaticendometriosisfoundthattheLng-IUSwasmoreeffectivethannotreatmentinreducingsymptomsofdysmenorrhea.Moderateorseveredysmenorrhearecurredin2of20(10%)subjectsinthepostoperativeLng-IUDgroupand9/20(45%)inthesurgery-onlygroup.Otherstudieshavedemonstratedimprovedsymptomsassociatedwithrecto-vaginalendometriosis.抗孕激素內(nèi)美通MedicaltreatmentofendometriosisGestrinone:aderivativeofnorgestrel,R2323

Mechanisms:Includeandrogenic,anti-progestogenicandantiestrogenicactions.MedicaltreatmentofendometriosisGestrinone:Effect:2.5—5mg,biw,6monthsThereliefofpelvicpainwasnotedinmorethan80%ofsubjects.However,within1yearfollowingdiscontinuationofthedrug,recurrenceofpainwasobservedin15%to30%.MedicaltreatmentofendometriosisGestrinoneSide-effects:LikeDanazol,butless.Althoughthemostofsideeffectsaremildandtransient,somearepotentiallyirreversible,suchasvoicechanges,hirsutism,andclitoralhypertrophy,asseenintheDanazoltherapy.

DawoodMY,etal.AmJObstetGynecol1997;176:387-394

GNRH-AMedicaltreatmentofendometriosisGnRHAgonists:GnRHagonistsaremodifiedformsofGnRHthatbindtoreceptorsinthepituitary,buthavealongerhalflifethannativeGnRHandtherebyresultindown-regulationofthepituitaryovarianaxisandhypoestrogenism.Mechanism:Thelikelymechanismofactioninvolvestheinductionofamenorrheaandprogressiveendometrialatrophy.Effect:Responsecanbeseenin80%ormoreduringtreatment.Along-termfollow-upstudyofpatientstreatedwithaGnRHagonistaloneforsixmonthsrevealeda53%recurrenceofdisease/symptomstwoyearsaftertreatment.Anotherreportindicatedthatthecumulative5-yearrecurrenceratewas53%forallstages,37%forminimaldiseaseand75%forseveredisease.InasinglestudythatcomparedtreatmentswithGnRHagonistandgestrinone,thegestrinonewasmoreeffectiveinrelievingsymptomsofdysmenorrheasixmonthsaftercessationoftherapy.治療術(shù)后給予諾雷德治療，第二個(gè)月反向添加治療兩個(gè)月。MedicaltreatmentofendometriosisGnRHAgonists:Sideeffects:Theside-effectrelateprimarilytotheinducedhypoestrogenicstateandincludehotflushes,vaginaldryness,decreasedlibido,moodswings,headache,andbonemineraldepletion.‘‘Add-back’’therapywithaprogestogenoracombinationofestrogenandprogestogenhasbeenadvocatedforreducingtheseverityofhypoestrogenicsideeffectsassociatedwithGnRHagonisttreatment.NumerousstudieshavecomparedtheeffectivenessoftreatmentwithaGnRHagonistwithandwithoutadd-backtherapy.Add-backtherapiesdidnotaltertheefficacyofGnRHagonisttreatment,butdidresultinfewersideeffects.MedicaltreatmentofendometriosisOtherTreatmentsunderInvestigationAromataseInhibitorsMechanism:Endometriotictissue,unlikedisease-freeendometrium,exhibitsahighlevelofaromataseactivitythatmayresultinincreasedlocalconcentrationsofestrogenthatmayfavorgrowthofendometriosis.Effect:Inpilotstudiesinvolvingverysmallnumbersofpatients,aromataseinhibitorshavebeenshowneffectiveforthereatmentofendometriosisandpelvicpain.However,suchtreatmentstillisconsideredinvestigational.MedicaltreatmentofendometriosisSelectiveEstrogenReceptorModulators:(Tamoxifenetal)SelectiveProgesteroneReceptorModulators(RU486,mefipristone,etal)Intheirseriesofstudies,KetteletalsuggestthatwithRU48650mg/dailyfor6months,thelesionswereregressedby55%,pelvicpainimprovedinallpatientswithouthypoestrogenismorchangeofserumlipidandbonemineraldensity.手術(shù)治療1手術(shù)原則：腹腔鏡微創(chuàng)開(kāi)腹：巨大囊腫、有粘連、需行腸切除或判斷為復(fù)雜的手術(shù)。生殖系統(tǒng)外的病灶。術(shù)式：保留生殖器的病灶切除術(shù)1.分離粘連、電燒及電切術(shù)。2.子宮內(nèi)膜異位囊腫穿刺術(shù)、囊腫切開(kāi)、囊壁燒灼或激光照射術(shù)。囊腫穿刺抽液酒精硬化。3腹膜病灶激光照射或電燒術(shù)。4患側(cè)附件切除術(shù)。5合并肌瘤及肌腺瘤術(shù)式術(shù)式：保留生殖器的病灶切除術(shù)6.后位子宮懸吊7.不孕美蘭通液術(shù)輸卵管整形術(shù)術(shù)式：保留卵巢功能的子宮全切除術(shù)適用無(wú)生育要求的。術(shù)式：根治性手術(shù)卵巢去世手書(shū)全子宮+雙附件緩解疼痛的手術(shù)宮骶神經(jīng)的切除術(shù)（LUNA)骶前神經(jīng)離斷術(shù)手術(shù)+藥物+手術(shù)+藥物聯(lián)合術(shù)前、術(shù)后用藥不孕的治療個(gè)體化術(shù)中評(píng)分：輸卵管粘連、功能評(píng)分助孕療預(yù)防1減少醫(yī)院性子宮內(nèi)膜種植的機(jī)會(huì)。積極治療高危人群其他：口服避孕藥SurgicaltreatmentforendometriosisPelvicPainOvarianEndometriomasInfertilityHysterectomyLaparoscopicUterosacralNerveAblationPresacralNeurectomySurgicaltreatmentforendometriosisIndication:pelvicpain,ovarianendometriomas,infertilityIndication--PelvicPain:Reliefofpainfollowingsurgicaltreatmentofendometriosisatone-yearfollow-uprangesbetween50%and95%.ConservativeSurgicaltreatmentforendometriosisConservativesurgicaloptionsincludeexcisionofthecystwall,drainageandcoagulation/ablationofthecyst,andsimpledrainageofthecyst.Cystexcisionismoreeffectivethanfenestrationandablationofthecystwall.Surgicaltreatmentforendometriosis--HysterectomyHysterectomywithbilateralsalpingo-oophorectomy(TAHBSO)generallyisreservedforwomenwithendometriosiswhohavecompletedchildbearingandinwhomothertherapieshavefailed.Therecurrencerateofthisapproachisminimalattributingtodebulkingofthediseaseandtheresultingsurgicalmenopausecausingatrophyofendometrialtissue.Hysterectomywithoutbilateralsalpingooophorectomyislesseffective,asdiseaserecurrenceandsubsequentre-operationratesarehigher.

Surgicaltreatmentforendometriosis--LaparoscopicUterosacralNerveAblationLaparoscopi