婦產(chǎn)課件 18-1子宮內膜異位癥北醫(yī)教學 2016 5

子宮內膜異位癥和子宮肌腺病endometriosis

DepartmentofObstetrics&GynecologyBeijingHospital

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

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

盆腔表現(xiàn)+遠處病灶

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

其他部位腹膜型1色素沉著型2無色素沉著型深部結節(jié)型病灶浸潤深度結節(jié)：》5MM常見于子宮直腸窩鏡檢：4種成分，子宮內膜腺體、間質、纖維素、紅細胞(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：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)

自身免疫卵細胞質量下降二體征：

子宮位置、子宮直腸窩、可觸痛結節(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評分目的：統(tǒng)一衡量病情輕重的標準并制定出子宮內膜異位征導致不孕征的治療規(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內異癥伴附件囊腫的處理3內異癥伴不孕的處理個體化1年齡2要解決的問題3對生育要求4經(jīng)濟狀態(tài)治療期待治療藥物治療手術治療期待治療輕型：3-6個月隨診鼓勵早妊娠藥物治療對癥治療假孕療法假絕經(jīng)治療其他治療對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)口服類似妊娠的長期閉經(jīng)。高效孕激素和炔雌醇復合片。副作用假孕療法孕激素機制：抑制垂體促性腺激素釋放并直接作用于子宮內膜，子宮內膜開始蛻膜化，最終導致內膜萎縮和閉經(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個月。孕激素婦康片婦寧片安宮黃體酮假絕經(jīng)療法GNRH-A達那唑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：孕激素受體調節(jié)，抗孕酮和抗糖皮質作用。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.治療術后給予諾雷德治療，第二個月反向添加治療兩個月。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.手術治療1手術原則：腹腔鏡微創(chuàng)開腹：巨大囊腫、有粘連、需行腸切除或判斷為復雜的手術。生殖系統(tǒng)外的病灶。術式：保留生殖器的病灶切除術1.分離粘連、電燒及電切術。2.子宮內膜異位囊腫穿刺術、囊腫切開、囊壁燒灼或激光照射術。囊腫穿刺抽液酒精硬化。3腹膜病灶激光照射或電燒術。4患側附件切除術。5合并肌瘤及肌腺瘤術式術式：保留生殖器的病灶切除術6.后位子宮懸吊7.不孕美蘭通液術輸卵管整形術術式：保留卵巢功能的子宮全切除術適用無生育要求的。術式：根治性手術卵巢去世手書全子宮+雙附件緩解疼痛的手術宮骶神經(jīng)的切除術（LUNA)骶前神經(jīng)離斷術手術+藥物+手術+藥物聯(lián)合術前、術后用藥不孕的治療個體化術中評分：輸卵管粘連、功能評分助孕療預防1減少醫(yī)院性子宮內膜種植的機會。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