18-1子宫内膜异位症北医教学 2016 5.ppt

1、子宫内膜异位症和子宫肌腺病 endometriosis,Department of Obstetrics&Gynecology Beijing Hospital 卫生部北京医院 孟庆伟,定义,当具有生长功能的子宫内膜出现在子宫腔被覆粘膜以及宫体肌层以外的其他部位时，称为子宫内膜异位征。 Endometriosis is defined histologically by the presence of endometrial tissue in an ectopic location , exclusive of the eutopic endometrium.,流行病学：It affects

2、 as many as 1 in 15 women of reproductive age.Endometriosis is one of the most common gynecologic disorders and is found in approximately 70% of patients with chronic pelvic pain. 发病机制 病理1 发病部位： 盆腔（骶韧带、卵巢） 子宫浆膜、输卵管、乙状结肠。 盆腔： 75%，双卵巢50%，7-37%肠管，16%泌尿。盆腔：外见腹部伤口、会阴侧切伤口。 2 大体病理：紫蓝色结节、血性滤泡、散在的烧灼样灶、含铁血黄素沉

3、着、点状出血瘀斑、 浆膜下出血。,盆腔表现+ 远处病灶,卵巢型 腹膜型,3 显微镜下检查：,1.子宫内膜上皮、内膜腺体、腺样结构、内膜间质及出血。 2.少量子宫内膜间质细胞。 3.囊肿中有红细胞、含铁血黄素或吞噬有含铁血黄素的巨噬细胞 等出血证据。 4.异位内膜可有增生及分泌改变但不一定与子宫内膜同步。 5.异位内膜可癌变1%。,流行病学,1.激素依赖疾病：生育妇女、月经周期短经期长 2.绝经后2%需要腹腔镜治疗,发病机理,学说 1种植学说 2体腔上皮化生学说 3诱导学说 能否发病取决于：遗传、免疫、炎症、在位内膜的特性,相关因素,1遗传 2免疫 3炎症 4在位内膜特性,病理,巨检：卵巢：微小

4、、典型病灶型 腹膜型：色素沉着、无色素沉着 深部结节：5MM 其他部位,腹膜型,1色素沉着型 2无色素沉着型,深部结节型,病灶浸润深度结节：5MM 常见于子宫直肠窝,镜检,：4种成分，子宫内膜腺体、间质、纤维 素、红细胞(含铁血黄素）,临床表现 一、症状,1.疼痛： 非经期下腹痛 阴道深部性交痛 经期肛门坠痛或抽搐 急腹痛 盆腔外痛及出血。,临床表现 一、症状,2.月经失调：15%经量多、经血淋漓不尽、,临床表现 一、症状,3不孕-40% 黄体功能 未破裂卵泡黄素化综合征（LUFS) 自身免疫 卵细胞质量下降,二 体征：,子宫 位置、子宫直肠窝、可触痛结节、宫骶韧带、附件包块。,辅助检查,超声

5、、核磁、 血清CA125 抗子宫 内膜抗体 其他,诊断及鉴别诊断,妇科检查 超声 血 CA125 腹腔镜 R-AFS评分 目的：统一衡量病情轻重的标准并制定出子宫内膜异位征导致不孕征的治疗规范。,鉴别诊断,1卵巢恶性肿瘤 2盆腔炎性包块 3子宫肌腺征,良性鉴别,脓肿,脓肿,脓肿,恶性鉴别,治疗 The treatment of endometriosis,1疼痛的处理 2内异症伴附件囊肿的处理 3内异症伴不孕的处理,个体化,1年龄 2要解决的问题 3对生育要求 4经济状态,治疗,期待治疗 药物治疗 手术治疗,期待治疗,轻型：3-6个月随诊 鼓励早妊娠,药物治疗,对症治疗 假孕疗法 假绝经治疗

6、其他治疗,对症药物治疗 假孕治疗 假绝经治疗,性激素药物治疗,1 口服避孕药 2 孕激素 3雄激素 4GNRH A,药物治疗Medical treatment of endometriosis,Medical treatment of endometriosis Danazol Gestrinone Combined Oral Contraceptives Progestogens GnRH Agonists Aromatase Inhibitors Selective Estrogen Receptor Modulators Selective Progesterone Receptor M

7、odulators,药物治疗,假孕疗法1口服避孕药Oral contraceptives (OCs),连续口服类似妊娠的长期闭经。高效孕激素和炔雌醇复合片。 副作用,假孕疗法,孕激素 机制：抑制垂体促性腺激素释放并直接作用于子宫内膜，子宫内膜开始蜕膜化，最终导致内膜萎缩和闭经。 醋酸甲孕酮30毫克，甲地孕酮40毫克，炔诺酮5毫克，连续用6个月。,孕激素,妇康片 妇宁片 安宫黄体酮,假绝经疗法,GNRH-A 达那唑danazol 200毫克TID,其他治疗,孕三烯酮：雄激素、抗孕激素和抗雌激素作用。 米非司酮：孕激素受体调节，抗孕酮和抗糖皮质作用。,Medical treatment of en

8、dometriosis,Mechanisms: As with oral contraceptives, their proposed mechanism of action involves decidualization and subsequent atrophy of endometrial tissue. Another, more recently proposed, mechanism involves a progestogen-induced suppression of matrix metalloproteinases, a class of enzymes import

9、ant in the growth and implantation of ectopic endometrium.,Medical treatment of endometriosis,Combined Oral Contraceptives Mechanism: Decidualization, followed by atrophy of the endometrial tissue is the proposed mechanism of action. Effect: Hormonal contraceptives have been used in both a cyclic an

10、d a continuous fashion in the treatment of symptoms associated with endometriosis.,Medical treatment of endometriosis,The efficacy has been poorly assessed, with about 80% improvement in symtoms and an 12% recurrence rate after 6 months of follow-up. A prospective observational trial demonstrated th

11、at continuous low-dose OCs were more effective than cyclic OCs in controlling endometriosis symptoms in patients after surgical treatment for endometriosis.,Medical treatment of endometriosis,Side-effect: A common side effect is transient breakthrough bleeding, which occurs in 38% to 47%. Other side

12、 effects include nausea, breast tenderness, and fluid retention, all resolved after discontinuation.,Medical treatment of endometriosis,Combined Oral Contraceptives Side effects: including androgenic, estrogenic and progestogenic effects. These have been largely lessened with the advent of the low-d

13、ose oral contraceptive pill.,Medical treatment of endometriosis,Danazol: a derivative of 17a-ethinyltestosterone Mechanisms: Danazol does not alter basal levels of gonadotropins, but diminishes the midcycle LH and FSH surge. Thus, the drug creates a chronic anovulatory state to inhibit the growth an

14、d development of endometriosis.,Medical treatment of endometriosis,Danazol Effect: It was also found that 60% of those treated with danazol experienced partial or complete recurrence of the endometriosis 12 months after completion of drug therapy.,Medical treatment of endometriosis,In addition, dana

15、zol displaces testosterone and estradiol from SHBG as well as progesterone and cortisol from corticosteroid-binding globulin, this action increases the free hormone levels in the circulation, especially testosterone. Finally, danazol inhibits multiple enzymes of the steroidogenic pathway.,Medical tr

16、eatment of endometriosis,Danazol Effect: 400mg, tid or bid, 6 months Pain relief has been evaluated, with improvement in symptoms noted in 84% to 92%, and this effect could be continued up to 6 months after discontinuation of the medication.,Medical treatment of endometriosis,Danazol Side-effects: C

17、ommon side effects relate to hyperandrogenism, such as weight gain, muscle cramps, decreased breast size, flushing, mood change, oily skin, depression, sweating, edema, change in appetite, acne, fatigue, hirsutism, decreased or increase libido, nausea, headache, dizziness, rash, deepening of voice e

18、t al. Alternate routes of danazol administration are under investigation. Cobellis L, et al. Fertil Steril 2004;82:23940,Medical treatment of endometriosis,Progestogens The levonorgestrel-releasing intrauterine system (Lng-IUS) represents another novel approach to the medical treatment of endometrio

19、sis. The mechanism of action is unknown. The response rate of pelvic pain was about 70% with very limited side-effect.,Medical treatment of endometriosis,Progestogens Effect: High-dose MPA was administered for 6 moths and the pain relief rate was roughly 70%-90%. A meta-analysis of four randomized,

20、controlled trials comparing MPA to danazol alone, danazol and OCs, or a GnRH agonist (goserelin acetate) concluded that MPA was as effective as the other treatments (OR 1.1; 95% CI, 0.4 to 3.1).,Medical treatment of endometriosis,A randomized, controlled trial comparing the Lng-IUS to expectant mana

21、gement after laparoscopic surgical treatment for symptomatic endometriosis found that the Lng-IUS was more effective than no treatment in reducing symptoms of dysmenorrhea. Moderate or severe dysmenorrhea recurred in 2 of 20 (10%) subjects in the postoperative Lng-IUD group and 9/20 (45%) in the sur

22、gery-only group. Other studies have demonstrated improved symptoms associated with recto-vaginal endometriosis.,抗孕激素,内美通,Medical treatment of endometriosis,Gestrinone: a derivative of norgestrel, R2323 Mechanisms: Include androgenic, anti-progestogenic and antiestrogenic actions.,Medical treatment o

23、f endometriosis,Gestrinone: Effect: 2.55mg, biw, 6months The relief of pelvic pain was noted in more than 80% of subjects. However, within 1 year following discontinuation of the drug, recurrence of pain was observed in 15% to 30%.,Medical treatment of endometriosis,Gestrinone Side-effects: Like Dan

24、azol, but less. Although the most of side effects are mild and transient, some are potentially irreversible, such as voice changes, hirsutism, and clitoral hypertrophy , as seen in the Danazol therapy. Dawood MY, et al. Am J Obstet Gynecol 1997;176:387-394,GNRH-A,Medical treatment of endometriosis,G

25、nRH Agonists: GnRH agonists are modified forms of GnRH that bind to receptors in the pituitary, but have a longer half life than native GnRH and thereby result in down-regulation of the pituitaryovarian axis and hypoestrogenism. Mechanism: The likely mechanism of action involves the induction of ame

26、norrhea and progressive endometrial atrophy.,Effect: Response can be seen in 80% or more during treatment. A long-term follow-up study of patients treated with a GnRH agonist alone for six months revealed a 53% recurrence of disease/symptoms two years after treatment. Another report indicated that t

27、he cumulative 5-year recurrence rate was 53% for all stages, 37% for minimal disease and 75% for severe disease.,In a single study that compared treatments with GnRH agonist and gestrinone, the gestrinone was more effective in relieving symptoms of dysmenorrhea six months after cessation of therapy.

28、,治疗,术后给予诺雷德治疗， 第二个月反向添加治疗两个月。,Medical treatment of endometriosis,GnRH Agonists: Side effects: The side-effect relate primarily to the induced hypoestrogenic state and include hot flushes, vaginal dryness, decreased libido, mood swings, headache, and bone mineral depletion. Add-back therapy with a pr

29、ogestogen or a combination of estrogen and progestogen has been advocated for reducing the severity of hypoestrogenic side effects associated with GnRH agonist treatment. Numerous studies have compared the effectiveness of treatment with a GnRH agonist with and without add-back therapy. Add-back the

30、rapies did not alter the efficacy of GnRH agonist treatment, but did result in fewer side effects.,Medical treatment of endometriosis,Other Treatments under Investigation Aromatase Inhibitors Mechanism: Endometriotic tissue, unlike disease-free endometrium, exhibits a high level of aromatase activit

31、y that may result in increased local concentrations of estrogen that may favor growth of endometriosis. Effect: In pilot studies involving very small numbers of patients, aromatase inhibitors have been shown effective for the reatment of endometriosis and pelvic pain. However, such treatment still i

32、s considered investigational.,Medical treatment of endometriosis,Selective Estrogen Receptor Modulators: (Tamoxifen et al) Selective Progesterone Receptor Modulators (RU486,mefipristone, et al) In their series of studies, Kettel et al suggest that with RU486 50mg/daily for 6 months, the lesions were

33、 regressed by 55%, pelvic pain improved in all patients without hypoestrogenism or change of serum lipid and bone mineral density.,手术治疗,1手术原则 ： 腹腔镜微创 开腹：巨大囊肿、有粘连、需行肠切除或判断为复杂的手术。 生殖系统外的病灶。,术式：保留生殖器的病灶切除术,1.分离粘连、电烧及电切术。 2.子宫内膜异位囊肿穿刺术、囊肿切开、囊壁烧灼或激光照射术。囊肿穿刺抽液酒精硬化。 3腹膜病灶激光照射或电烧术。 4患侧附件切除术。 5合并肌瘤及肌腺瘤术式,术式：

34、保留生殖器的病灶切除术,6.后位子宫悬吊 7.不孕美兰通液术输卵管整形术,术式：保留卵巢功能的子宫全切除术,适用无生育要求的。,术式：根治性手术,卵巢去世手书 全子宫+双附件,缓解疼痛的手术,宫骶神经的切除术（LUNA) 骶前神经离断术,手术+药物+手术+药物联合,术前、术后用药,不孕的治疗,个体化 术中评分：输卵管粘连、功能评分,助孕疗,预防,1减少医院性子宫内膜种植的机会。 积极治疗高危人群 其他：口服避孕药,Surgical treatment for endometriosis Pelvic Pain Ovarian Endometriomas Infertility Hysterec

35、tomy Laparoscopic Uterosacral Nerve Ablation Presacral Neurectomy,Surgical treatment for endometriosis,Indication: pelvic pain, ovarian endometriomas, infertility Indication-Pelvic Pain: Relief of pain following surgical treatment of endometriosis at one-year follow-up ranges between 50% and 95%.,Co

36、nservative Surgical treatment for endometriosis,Conservative surgical options include excision of the cyst wall, drainage and coagulation/ablation of the cyst, and simple drainage of the cyst. Cyst excision is more effective than fenestration and ablationof the cyst wall.,Surgical treatment for endo

37、metriosis-Hysterectomy,Hysterectomy with bilateral salpingo-oophorectomy (TAHBSO) generally is reserved for women with endometriosis who have completed childbearing and in whom other therapies have failed. The recurrence rate of this approach is minimal attributing to debulking of the disease and th

38、e resulting surgical menopause causing atrophy of endometrial tissue. Hysterectomy without bilateral salpingooophorectomy is less effective, as disease recurrence and subsequent re-operation rates are higher.,Surgical treatment for endometriosis-Laparoscopic Uterosacral Nerve Ablation,Laparoscopic u

39、terosacral nerve ablation (LUNA) is a technique designed to disrupt the efferent nerve fibers in the uterosacral ligaments to decrease uterine pain for women with intractable dysmenorrhea.,Surgical treatment for endometriosis-Presacral Neurectomy,Presacral neurectomy involves interrupting the sympat

40、hetic innervation to the uterus at the level of the superior hypogastric plexus. Presacral neurectomy has been proposed for treatment of midline pain associated with menses, because its effects on other components of pelvic pain have been inconsistent.,内膜异位征疼痛治疗,疼痛是子宫内膜异位症的主要症状， 约有80%的内异症病人受到各种疼痛的困扰

41、。,宫内膜异位症的治疗目的之一： 缓解并解除疼痛，减灭和消除病灶,Summary,Endometriosis is viewed best primarily as a medical disease with surgical back-up. Individuals with chronic superficial or presumed disease should be treated medically, reserving surgery for those having large endometriomas or palpable disease that fails to r

42、espond to treatment.,总结,1.内膜异位症的定义 2机理 3临床常见类型 4表现 5治疗,谢谢！,子宫肌腺症,定义；子宫内膜腺体和间质存在于子宫肌层中，伴随周围肌层细胞的代偿性肥大和增生。-内在性 病因：1与遗传有关，2损伤，刮宫，剖宫产。 3高雄激素 4病毒感染,病理,1巨检：均匀增大，12周，弥漫型；局限型。 2镜检：肌层见内膜腺体及间质,病例3,临床表现,月经：量多，经期长，经间出血 痛经，性交痛 妇查:子宫均匀增大,有压痛,结节.,诊断,症状 体征 辅助检查,治疗,1药物 2手术治疗:症状重,年龄大，无生育要求。,小结,经量多、经期长、逐年加重痛经。 病因：子宫内膜基底细胞侵入到肌层间质的结果。 病灶：弥漫、局灶型 治疗：无特效。对症、避孕药+手术治疗,