Department of Obstetrics and Gynecology Endometriosis Disease Xiaoli Chen Department of Obstetrics and Gynecology 2009.5.5

Endometriosis Adenomyosis

What is...? Endometriosis A condition in which the tissue that normally lines the uterus grows in other areas of the body, causing pain, irregular bleeding, and frequently infertility.

Characteristics Common in reproductive-age women Estrogen dependence Genetic disease Immunologic disease Inflammatory disease Benign diseases, malignant behavior 5-10% of reproductive-age women 25-35% of patients with infertility Usually regresses following menopause and not usually found prior to menarche No differences among ethnic groups or socioeconomic status Genetic predisposition - 6-7% increased risk with history of first degree relative

Pathogenesis

Pathogenesis Not clear. 4 theories proposed: - Retrograde menstruation theory - Coelomic metaplasia theory - Lymphatic or vascular dissemination theory - Immunology theory No single theory can account for the location of endometriosis in all cases.

Pathology

Pathology: Classification of Common Pelvic Endometriosis Ovarian endometriosis Minimal: superficial minimal Classic: cyst Peritoneal endometriosis Pigmentation: classic indigo or brown ectopic tubercles。 Non-pigmentation ：early focus

Pathology: Microscopic Examination Endometrial tissue (glands and stroma) Fibrin and red cell Hemosiderin

Clinical presentation Symptoms Dysmenorrhea (progressive) Chronic pelvic pain Dyspareunia Pain caused by rupture of endometrioma Infertility Menstrual disturbance Painful defecation

Clinical presentation Signs Fixed,retroverted uterus Enlargement of the ovaries Tender nodular uterosacral ligament

Diagnosis

Diagnosis Medical history Gynecological examination Auxiliary examination laparoscopy Imaging laboratory

Diagnosis: Medical History Menstruation Reproduction Family history Operation history Relationship of dysmenorrhea and gynecological operation

Diagnosis: Gynecological Examination Bimanual or trimanual examination Uterus Mass Tenderness nodes

Diagnosis: Laparoscopy The best method for diagnosis Diagnosis by direct inspect Pathological confirmation needed Treatment at the same time

Diagnosis: Imaging B-mode sonography Sensitivity 97％, specificity 96％. Mass: location, size, content, blood supply, etc.

Diagnosis: Imaging CT or MRI Provide additional and confirmatory information More costly

Diagnosis: Laboratory CA125 Slightly elevated in moderate or severe patients. Limited on sensitivity and specificity. No single use for diagnosis.

Diagnosis: Laboratory Anti-endometrium antibody Negative in most of normal women. Positive rate over 60％ in endometriosis patients. Positive means active ectopic endometrium. Not popular used in clinic.

Differential Diagnosis

Differential Diagnosis Diseases Malignant tumor of ovary Pelvic inflammatory mass Adenomyosis Aspects History Gyn Examintion B-mode ultrasonography Lab research

Treatment Expectant therapy Medical treatment Surgical treatment - Pseudomenopause therapy - Danazol - GnRH agonists - Pseudopregnancy therapy Surgical treatment All treatment options are suppressive rather than curative Very helpful for dysmenorrhea, chronic pelvic pain, but not very effective for infertility

Medical Oophorectomy - GnRH agonists Mechanism: - Desensitization of the pituitary - Medical hypophysectomy →medical oophrectomy Drugs used: - Leuprorelin 3.75mg/28 Days D5 - Goserelin/Zoladex 3.6mg/28 Days D5 - Triptorelin/Decapreptyl 3.75mg/28 Days D5 Side dffects: - (1)Menopausal symptoms: hot flashes, dryness in vagina, loss of libido - (2)Osteoporosis Add-Back Therapy

Pseudomenopause therapy- Danazol Synthetic steroid - 17α-ethinyltestosterone Derivative Mechanism: - Directly suppressing ovarian steroidogenesis - Direct inhibiting endometrial growth Doses: - 400-800 mg/day for 6 months Side effects: - Hypoestrogenic environment: decreased breast size, atrophic vaginitis, hot flashes, emotional swings - Virilism

Pseudopregnancy therapy- Progestogen Mechanism: Inhibition of uterine contraction Inhibition on growth of the endometrium Doses: Medroxyprogesterone 20-50mg/day 6 months Side effects : weight, fluid retention, breakthrough bleeding, depression

Surgery Diagnostic surgery Very conservative surgery no attempt to treat any of the endometriosis Very conservative surgery treatment of a very large, obvious, or treatable area of endometriosis Aggressive surgery removes all the endo while preserving the organs maintains fertility Radical surgery removal of the reproductive organs hysterectomy

Treatment -- infertility Minimal disease - pregnancy rate without treatment after 5 years is 90% severe disease - proceed to laparoscopy woman over 35 yrs old - proceed with treatment Medical therapy is of limited value Assisted reproduction

Lifestyle Exercise Eating well and getting enough rest Practicing relaxation techniques such as yoga and meditation Exercise often helps to relieve or lessen pelvic pain and menstrual cramps. Eating well and getting enough rest also helps the body to manage pain. Practicing relaxation techniques such as yoga and meditation help to ease pain too.

Recurrences May recur with medical therapy or surgical therapy GnRH agonists or Danazol - Minimal disease – 37%, - severe disease – 74% Surgery – 40% after 5 years 56% of all patients after 7 years

Adenomyosis

Basic Concepts Definition of Adenomyosis: Presence of functioning endometrial glands and stroma in the myometrium. Myometrial cells around become hypertrophy and hyperplasia compensatively

Pathogenesis

Pathogenesis The pathogenesis is not known. Propose by Cullen in 1908, the theory of direct growth of the basal layer of endometrium into the myometrium is widely accepted.

Pathogenesis Estrogen has been implicated as a stimulus to the development of adenomyosis. The symptomatic improvement that occurs with the onset of menopause supports this concept.

Pathogenesis Induction Factors Inheritance Trauma (curettage / cesarean section ) Hyperestrogenemia Virus infection 经血逆流：背景：70％-90％的妇女有经血返流。

Pathology

Pathology Macroanatomy Uterus enlarges uniformly, like a ball. Usually not bigger than 12 weeks of gestation. Thick muscle fiber and micro vesicle seen in myomerium. Some grew like myoma, called adenomyoma.

Pathology Microscopic examination Endometrial glands and stroma in the myometrium, scattered like islands. Ectopic glands usually in proliferate phase. Local secretory changes seen occasionally.

Symptoms and Signs Hypermenorrhea 50% Dysmenorrhea 30% Symmetrically enlarged uterus - Improved ultrasound: preoperative diagnosis - MRI: negative/equivocal sonogram presence of leiomyomas

Diagnosis Primary diagnosis Classic symptoms and signs. B-mode ultrasonography and CT is helpful in diagnosis. Confirmative diagnosis Pathological examination.

Diagnosis Differ from Pregnancy: pregnancy test, ultrasound Submucous leiomyomas: hysteroscopy Endometrial cancer: endometrial biopsy Myoma: ultrasound Endometriosis:ultrasound premenstrual and intramenstrual dysmenorrhea, adherent adnexal masses, and “shotty” cul-de-sac/uterosacral ligament nodulations

Complications and Prevention Chronic severe anemia Primary adenocarcinoma ★Adenomyosis can’t be prevented.

Treatment

Treatment: Medication No medication is radical Mild symptoms NSAID Oral contraceptive pills Young, pregnancy-desiring, close to menopause Try GnRHa

Treatment: Surgery Suitable for patients with： Severe symptoms Relatively old age No desire for pregnancy No effect by medication

Treatment: Surgery Methods Total hysterectomy Adenomyoma resection Young with pregnancy desiring Prone to recurrence Laparoscopic uterosacral nerve ablation / Presacral neurectomy Pain relief rate: 80％

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