婦產(chǎn)科-子宮內(nèi)膜異位癥

子宮內(nèi)膜異位癥EndometriosisEMTDefinition“Presenceofendometrialtissueoutsidetheliningoftheuterinecavity”or

“Proliferationofendometriuminanysiteotherthantheuterinemucosa”定義子宮內(nèi)膜異位癥——具有生長(zhǎng)功能的子宮內(nèi)膜組織（腺體和間質(zhì)）出現(xiàn)在子宮腔被覆粘膜及宮體肌層以外的身體其他部位時(shí)。Age:commoninreproductiveperiodTrueIncidenceUnknown:?10-15%&30–50%infertility.DoesNOTDiscriminatebyRace.Histology:EndometrialGlandswithStroma+/-InflammatoryReaction.Herdietary(↑↑amongsisters).EpidemiologyAgeatDiagnosis<196%19–2524%26–3552%36–4515%>453%發(fā)病率年齡25—45歲婦女居多；明顯上升趨勢(shì)，育齡婦女多見(jiàn)；80%有明顯痛經(jīng)，

50%合倂不孕；妊娠可暫時(shí)阻止此病發(fā)展；與遺傳有關(guān)；可出現(xiàn)身體的各個(gè)部位，卵巢多見(jiàn)。-Pelvic-ExtrapelvicUmbilicus.Scars(Lap.).Lungs&plura.Others.SitesUterine=Adenomyosis(50%).Extraut:-Ovary30%-Pelvicperitoneum10%.-F.tube.-Vagina.-Bladder&rectum.-Pelviccolon.-Ligaments.PelvicEndometriosisIntroductionWhydoesendometriosishappen?

EndometrialimplantationtheoryRetrogradeVascularandlymphaticMechanicalImmunologicalandgenetictheoryCompositetheoryTheoriesofhistiogenesisPathogenesisEctopictransplantationtheory(異位種植學(xué)說(shuō)）

(DirectImplantation)

70-90%womenhaveretrogrademenstruation(經(jīng)血逆流).Viableendometrialcellsexistintheperitonealfluidinmorethan50%womanduringmenstruation.Implantationofmenstrualtissuehasbeendemonstratedexperimentally(inthemonkeys)andiatrogenic(醫(yī)源性的)implantationoccurs(e.g.endometriosisinthescarofabdominalwallafteranabdominalcesareansection).Oftenpelvicdepositsofendometriosisoccurclosetotheendsofthefallopiantubes.MetaplasiaofCoelomicEpithelium(體腔上皮化生學(xué)說(shuō))Serosa(漿膜)andperitoneum(腹膜)originatefrommultipotentcoelomicepitheliumPredisposingfactorsGeneticinfluencesIncidenceis6.9%infirst-graderelativesofpatientswithendometriosiscomparedwith1%inacontrolgroup.Incidenceis75%ifoneofthetwinsistershasendometriosis.ImmunedeficiencyMonkeyswithspontaneousendometriosiswerefoundtohaveloweredcell-mediatedresponsetoautologous(自體的)endometrialtissue.Pathogenesis發(fā)病機(jī)制

1

子宮內(nèi)膜種植學(xué)說(shuō)：異位內(nèi)膜來(lái)源于在位的子宮內(nèi)膜。

經(jīng)血逆流醫(yī)源性種植

淋巴及靜脈播散學(xué)說(shuō)：遠(yuǎn)離盆腔的EM

2體腔上皮化生學(xué)說(shuō)：異位內(nèi)膜來(lái)源于盆腔腹膜的體腔上皮化生臨床依據(jù)?

3誘導(dǎo)學(xué)說(shuō)：異位內(nèi)膜釋放某種物質(zhì)，如生長(zhǎng)因子、巨噬細(xì)胞等4相關(guān)因素：遺傳因素、免疫因素、炎癥因素在位內(nèi)膜的特性：在位內(nèi)膜決定論determinantofuterineeutopicendometrium在位內(nèi)膜的特點(diǎn)：功能活躍，血管增生及侵襲力強(qiáng)，易于種植

發(fā)病機(jī)制EM是個(gè)遺傳性疾?。籈M是個(gè)免疫性疾??；EM是個(gè)炎癥性疾?。籈M是個(gè)由于出血性疾?。籈M是個(gè)器官依賴(lài)性疾?。籈M是個(gè)激素依賴(lài)性疾?。籋istology:Endometriosisoftheovary:-Theovaryisenlargedandcystic.-Surfaceburntmatchheadappearance.-Tunicaalbuginea--->thickened.Chocolateortarrycysts.EndometrialGlandswithStroma+/-InflammatoryReaction病理特點(diǎn)：廣泛性和多形（多樣）性。主要變化：異位內(nèi)膜隨卵巢激素的變化發(fā)生周期性出血，伴纖維組織增生和粘連形成。

紫褐色斑點(diǎn)

小泡

紫藍(lán)色結(jié)節(jié)

囊腫病理卵巢子宮內(nèi)膜異位癥腹膜子宮內(nèi)膜異位癥深部侵潤(rùn)型內(nèi)異癥其他部位的內(nèi)異癥PathologyGrossappearancePathologyGrossappearanceEndometrioma(子宮內(nèi)膜異位囊腫）Chocolatecyst(巧克力囊腫）PathologyGrossappearance病理——鏡下檢查病灶中子宮內(nèi)膜腺體，子宮內(nèi)膜間質(zhì)，纖維素和紅細(xì)胞/含鐵血紅素。反復(fù)出血，結(jié)構(gòu)破壞，僅有少量?jī)?nèi)膜間質(zhì)細(xì)胞，即可確診斷；手術(shù)及肉眼典型，僅在卵巢壁中發(fā)現(xiàn)紅細(xì)胞或含鐵血黃素巨噬細(xì)胞，應(yīng)視內(nèi)異癥。MicroscopicappearancePathologyMicroscopicappearanceSiderocyte(含鐵血黃素細(xì)胞)Clinical

FeaturesSymptomsandsignsvaryaccordingtositeoflesions.25%asymptomatic.MenstrualpainorlowerabdominalpainDyspareunia(性交痛)InfertilityAbnormaluterinebleedingPaincausedbyruptureofendometriomaSymptomsandsignsinothersystemscausedbyendometriosis

InfertilityInpatientswithinfertility,incidenceofendometriosisis25%-35%.Inpatientswithendometriosis,infertilityrateis40%.Causes:1)Mechanicalreason2)EnvironmentalchangeintheperitonealcavityActivitychangesofmacrophageAutoimmuneinjuryIncreaseinprostaglandinsClinical

FeaturesCauses(Continued):3)AbnormalovarianfunctionOvulationdefects:17-27%Inadequatedevelopmentofcorporalutea(黃體)Luteinizedunrupturedfolliclesyndrome,LUFS(未破裂卵泡黃素化綜合征):18-79%4)Increaseinspontaneousabortion:40%(vs.normal15%)ClinicalFeaturesInfertility

Menstrualdisorders

15-30%Heavymenses,prolongedmenstruationorpremenstrualspotting.Causes:Damageofovariancortexandadhesionresultsinovariandysfunction,anovulationanddysfunctionofcorporalutea.ClinicalFeaturesSigns

RetrovertedandfixeduterusTendernodulesinrectouterinepouch,uterosacralligament,posteriorwall(lowersegment)andrectovaginalseptumFixedmassalongthesideofuterusClinicalFeatures臨床表現(xiàn)1癥狀（25%患者無(wú)癥狀）疼痛：痛經(jīng)和持續(xù)性下腹痛；繼發(fā)性、非正比；月經(jīng)失調(diào)：15—30%經(jīng)量經(jīng)期點(diǎn)滴出血；不孕：50%其他；囊腫破裂，腸道，膀胱，腹壁……。2體征DiagnosisLaparoscopy(“GoldStandard)LaparotomyInconclusive:CA-125,PelvicExam,History,ImagingStudiesBiopsyPreferableOverVisualInspectionClinicalclassificationRevisedAmericanFertilitySociety(R-AFS),1985Usefulfor:AssessmentofseveritySelectionoftherapeuticregimenComparisonPrognosisDiagnosis診斷——輔助檢查病史婦科檢查輔助檢查：B型超聲盆腔核磁+強(qiáng)化CA125測(cè)定：<100U/ml；監(jiān)測(cè)指標(biāo)；抗子宮內(nèi)膜抗體：60%以上呈陽(yáng)性。腹腔鏡檢查：金標(biāo)準(zhǔn)，確診，分期。DiagnosisBultrasound臨床分期1973年Acosta輕、中、重；1985年美國(guó)生育協(xié)會(huì)RAFS分期標(biāo)準(zhǔn)：病灶大小、粘連程度、直腸窩封閉情況。臨床意義：病變類(lèi)型（腹膜、卵巢、深部）病變活動(dòng)狀態(tài)（紅色、白色）

RAFS分期

1.Ovariancysts.2.Pelvicinflammatorydisease.3.OthercausesofnodularityinDouglaspouchastuberculousperitoni-tisandmetastasesofovariancancer.4.Causesofhaematuria,bleedingperrectumandacuteabdominalpainifthepatientispresentedbyoneofthesesymptoms.5.Asymmetricalenlargeduterus.Differentialdiagnosis鑒別診斷卵巢惡性腫瘤：診斷不明，盡快手術(shù)；盆腔炎性包塊：抗炎有效；子宮腺肌癥：可同時(shí)存在；治療——目標(biāo)任何卵巢腫物均應(yīng)除外惡性縮小和去除病灶減輕和控制疼痛減少卵巢損傷，保護(hù)卵泡治療和促進(jìn)生育預(yù)防和減少?gòu)?fù)發(fā)子宮內(nèi)膜異位癥的藥物治療短效避孕藥:高效孕激素:丹那唑:17?—乙炔睪丸酮衍生物(假絕經(jīng)療法)孕三烯酮:19—去甲睪酮甾類(lèi)藥物,抗雌,抗孕,GnRH?:合成的十肽類(lèi)化合物.PainManagement:MedicalTherapyNSAIDsOCPs(Continuous)ProgestinsDanazolGnRH-aGnRH-a+Add-BackTherapyMisc:Opoids,TCAs,SSRIs卵巢抑制是最好的治療GnRHa

降調(diào)節(jié)

垂體FSHLH

卵巢E(低雌激素狀態(tài))

“反向添加”治療

什么是“反向添加”治療在用GnRHa的同時(shí)補(bǔ)充雌激素

2—3個(gè)月后補(bǔ)多少?

抑制血管神經(jīng)癥狀30pg/ml抑制骨丟失20—40pg/mlEM生長(zhǎng)>40pg/ml窗口劑量Treatment

PrinciplesoftreatmentTreatmentshouldbeindividualizedaccordingtothepatient’sage,severityoftheconditionanddesireforchildbearing.Forthosewithmildsymptom:expectanttherapyForthosewhodesirechildbearing:ifconditionismild:medicaltreatmentifconditionissevere:fertilitypreservationsurgeryForthosewhodonotdesirechildbearing:Surgicaltreatment:ovarypreservationorradical

ExpectantTherapyEndometriosistendstoimproveduringpregnancyandmenopause.Follow-upandsymptomsmanagementwithprostaglandinsynthetaseinhibitors(前列腺素合成酶抑制劑)suchas:a)Indomethacin(吲哚美辛)/Indocin(消炎痛)25mgtidp.o.b)Naproxen(萘普生)c)Ibuprofen(布洛芬)300mgtipp.o.d)Diclofenacpotassium(雙氯芬酸鉀片)/Kaflan(凱扶蘭)25-50mgtidp.o.TreatmentTreatment

MedicaltreatmentObjective:causeatrophicchangesintheectopicendometriumProgestins(孕激素)Mechanism:InhibitionofuterinecontractionInhibitionongrowthoftheendometrium1.Pseudopregnancy(假孕)withoralcontraceptives

Atabletoncedailyfor6-12days

2.PseudopregnancywithProgestins(孕激素)

Medicaltreatment

Drugs(Progestins)usedDerivatives(衍生物)fromhydroxyprogesterone(羥孕酮)：(1)Medroxyprogesteroneacetate/provera(醋酸甲羥孕酮/醋酸甲孕酮/安宮黃體酮）30mgdaily(2)Megestrol(甲地孕酮/婦寧片)40mgdaily(3)Longactingdrugsa)Depo-provera(醋酸甲羥孕酮避孕針)150mgmonthlyb)Hydroxyprogesterone(羥孕酮)250mgoncefor2weeksTreatment

Medicaltreatment

Drugs(Progestins)usedDerivativesfrom19-demethyltestosterone(1)Norethindrone(炔諾酮)5mgdaily(2)Gestrinone(孕三烯酮/內(nèi)美通)2.5mgtwiceaweekTreatmentwithprogestinsusuallylast6months.Sideeffects:Intermittentbreakthroughbleeding,nausea,breasttenderness,fluidretention,weightgainTreatment

Medicaltreatment

Danazol（達(dá)/丹那唑）AveryfrequentlyuseddrugforendometriosisAweakandrogenAderivativeof17-α-ethinyltestosterone(17-α乙炔睪酮）Mechanism:AnantigonadotrophicagentDirectlysuppressingovariansteroidogenesis(甾體激素生成）

DirectinhibitingendometrialgrowthTreatment

MedicaltreatmentDoses:400-800mg/dayfor6monthsSideeffects:Hypoestrogenicenvironment:deceasedbreastsize,atrophicvaginitis,hotflashes,emotionalswings.Virilism(男性化):weightgain,growthoffacialhair,acne,oilyskin,etc.Treatment

Medicaltreatment

GnRHa(促性腺激素釋放激素激動(dòng)劑)Mechanism:DesensitizationofthepituitaryMedicalhypophysectomy(藥物性垂體切除)→Medicaloophorectomy(藥物性卵巢切除)Drugsused:Leuprorelin(亮丙瑞林/抑那通）3.75mg,Triptorelin/Decapreptyl(曲譜瑞林/達(dá)必佳/達(dá)菲林)3.75mg,Goserelin/Zoladex（戈舍瑞林/諾雷德）3.6mg,injection,oncepermonthTreatment

Treatment

MedicaltreatmentSideeffects:(1)Menopausalsymptoms(絕經(jīng)期癥狀):hotflashes,drynessinvagina,lossoflibido(2)Osteoporosis(骨質(zhì)疏松)Expensive子宮內(nèi)膜異位癥的手術(shù)治療

術(shù)式范圍適應(yīng)征有效率復(fù)發(fā)率保守性手術(shù)剝除“巧囊”、切或燒病灶年輕（保留生育功能）分離粘連，卵管整型渴望生育80—90%50%輕、中度40%半根治手術(shù)切除子宮、卵巢病變，保較年輕（保留卵巢功能）留一側(cè)卵巢。無(wú)生育要求80%20%中、重度5%根治性手術(shù)切除子宮、雙側(cè)附件年齡較大可見(jiàn)病變無(wú)生育要求95%0-1%重度

SurgicaltreatmentIndications:(1)Failedmedicaltreatment(2)Largeendmetrioma(largerthan5-6cm)Modesofsurgicaloperation(1)Fertili