Endometriosis Women’s Hospital, School of Medicine Zhejiang University Wu Ruijin

1. EndometriosisWomen’s Hospital, School of Medicine Zhejiang UniversityWu Ruijin

2. Definition Endometriosis (EMs)is usually defined as the presence of functioning endometrial glands and stroma outside their usual location within the uterine cavity and myometrium. ---Primarily a pelvic disease ---Generally benign disease ---Incidence: 10%-15%. 20% with chronic pelvic pain 30%-40% in infertile patients.

3. Common sites of endometriosis The most common sites： • uterosacral ligament（宫骶韧带) • rectouterine pouch （子宫直肠陷凹） • ovary Others： • uterine serosa (子宫浆膜) • fallopian tube • sigmoid colon (乙状结肠) outside of the pelvis: • Umbilicus (脐) • , bladder, kidney

4. Pathogenesis Theories of sources of ectopic endometrium • Implantation theory (种植学说)——Sampson 1921 endometrium transfer → implant →grow ⒈ retrograde menstruation (经血逆流) theory ⒉ iatrogenic (医源性的) implantation ⒊ transport by lymph and vein

5. Metaplasia of the coelomic epithelium (化生学说) Multipotential cells undergo metaplastic transformation into functional endometrial tissues--Meyer theory • Genetic and immunologic influences

6. Pathology ectopic endometrium—disrupting normal tissues ↓ hemorrhage ↓ proliferation of fibrous tissue ＆ adhesions ↓ dark blue or dark brown spots ↓ scarring nodules or cysts

7. Gross appearance : ovarian endometriosis • red, blue, or brown spots • endometriomas —— chocolate cysts ovary develops large cystic collections of EMs filled with thick, dark, old blood

9. Gross appearance : peritoneal endometriosis (腹膜型) common sites： uterosacral ligament、rectouterine pouch • purple spots • dark brown spots • red lesions • white lesions • peritoneum lack

10. peritoneal endometriosis purple spots, dark brown spots on uterosacral ligament or rectouterine pouch

11. peritoneal endometriosis On uterosacral ligament or rectouterine pouch peritoneum lack

12. cervix umbilicus

13. The microscopic findings： • endometrial glands • endometrial stroma • fibrin • red blood cells and hemosiderin（含铁血黄素） ≥2 findings to be diagnosed

14. Clinical Findings symptoms： • Cyclic dysmenorrhoea（痛经）and chronic pelvic pain: the most typical symptom：secondary dysmenorrhea that worsens over time, pelvic pain at its worst 1 to 2 days before menses, subsides at the onset of flow or shortly thereafter • Dyspareunia（性交痛） associated with deep penetration and aggravated the lesions in cul-de-sac or uterosacral lgs • abnormal uterine bleeding （月经异常） heavy menses, prolonged menstruation or premenstrual spotting • infertility：40% of patients • The severity of above symptoms may not correlate with extent of disease.

15. Clinical Findings symptoms： others： Vary depending on the area involved. acute abdomen: inter-cyst hemorrhage or rupture diarrhoea（腹泻） constipation（便秘） bloody stool painful urination bloody urine backache

16. Causes of infertility • Mechanical reason Dense adhesions, distort the pelvic architecture, interfere tubal mobility and cause its obstruction 2) Environmental change in the peritoneal cavity 3) Abnormal immune function 4) Abnormal ovarian function (anovulation, LPD, Lufs) 5) Increase in spontaneous abortion

17. Clinical Findings Pelvic Examination： • Early EMs may subtle or nonexistent. • When more disseminated disease present--- fixed retroverted uterine • tender nodules on uterosacral ligaments or rectouterine pouch • Palpable of tender and fixed adnexal masses—ovary involved bimanual or vagino-recto-abdominal examination

18. Diagnosis • History Cyclic/secondary dysmenorrhoea, dyspareunia, abnormal uterine bleeding, infertility, ect. • pelvic examination fixed retroverted uterine or adnexal masses, tender nodules, ect. • serum CA125 ↑ but usually ＜100 IU/ml • Pelvic imaging: ultrasound, (CT and MRI) ---”ground glass” appearance

19. Laparoscopy or laparotomy ——the only way (golden diagnosis standard) direct visualized,definitivelydiagnosis, classification ＆treatment • anti-endometrium antibody

20. Diagnosis Clinical classification Revised American Fertility Society (r-AFS), 1985 Useful for: • A point system to stage EMs based on the location, depth, diameter of lesions and density of adhesions • Assessment of severity • Selection of therapeutic regimen • Comparison • Prognosis

22. Differential Diagnosis • Ovarian tumor ascites（腹水）, solid or mixed, U/S image, CA-125 >100 IU/ml • Abdominal inflammatory mass such as pelvic inflammatory disease, recurrent acute salpingitis, adhesions, hemorrhagic corpus luteum cysts, ectopic pregnancy ----history of infection, fever, not cyclic, treatment with antibiotics effectively • Adenomyosis medial, severe pain, uterus slightly enlarged • Fifbroids

23. Treatment Principles of treatment： Treatment should be individualized according to the age, severity of the condition, the extent and location of disease and desire for childbearing. • With minimal or mild symptom:expectant therapy • With childbearing desire: mild-condition: medication severe-condition: fertility preservation surgery • No childbearing desire : Surgical treatment: ovary preservation or radical (definitive) surgery

24. Treatment Expectant Therapy（期待疗法） ----minimal or nonexistent symptoms and in patients actively attempting to conceive. • Follow-up • symptoms management： analgesics,NSAIDs（非甾体类抗炎药）(such asBrufen, Fenbid, ect)

25. Treatment Medical therapy • Hormonal suppression of menses as the basis of medical therapy for EMs. • Aimed at suppression and atrophy of the endometrial tissue. • Temporizing measures: often recur following cessation of treatment.

26. Medication ⒈ oral contraceptive pills (OCPs)：first-line therapy. Mode of action; Dosage; Prognosis. ⒉ progestins：medroxyprogesterone, megestrol Side effects: irritability, depression, breakthrough bleeding, bloating ----suppress both ovulation and menstruation and by decidualizing the endometrial implants ----Pseudopregnancy therapy(假孕治疗)

27. Medication 3. Danazol A derivative of 17-α-ethinyltestosterone Mechanism: • Directly suppressing ovarian steroidogenesis • Direct inhibiting the growth of endometrium Dosage: 400-600 mg/d for 6 months Side effects: androgen related, anabolic acne, deepening of the voice, oily skin, headache, hot flashes, loss of libido, hirsutism, weight gain

28. Medication 4. GnRH-a (gonadotropin releasing hormone agonist,促性腺激素释放激素激动剂) Mechanism:Medical hypophysectomy(药物性垂体切除) , Medical oophorectomy(药物性卵巢切除) then ovaries do not produce estrogen ---existing endometrial implants atrophy ---new implants are prevented Side effects: estrogen deficiency (1) Menopausal symptoms : hot flashes, dryness in vagina, loss of libido(性欲) (2) Osteoporosis (骨质疏松) -----Pseudomenopause therapy Leuprorelin（亮丙瑞林，抑那通） Goserelin （戈舍瑞林，诺雷德） Tryptorelin （曲普瑞林，达菲林）

29. Medication others： • Gestrinone (孕三烯酮) • Mifepristone • All the medical treatment are to reduce pain, but are used mainly as temporizing agents. • Limited to 6 months: costly and side effects • Add-back therapy: add a small amount of E to GnRHa to minimize the E deficiency symptoms (hot flashes and bone density loss).

30. Surgical therapy Moderate to severe-condition or no childbearing desire. Purposes： ⑴ diagnosis and classification ⑵ excise or destroy all endometriotic tissue ⑶ remove all adhesions, restore pelvic anatomy ⑷ enhance fecundity ⑸ relieve pain

31. Surgical therapy Modes of surgical operation: (1) Fertility preservation (2) Ovarian function preservation (3) Radical (definitive) surgery (4) Surgery for pain relief

32. Conservative surgical therapy Endometriomas: • Best treated using laparoscopic cystectomy with removal of as much of the cyst wall as possible. • The uterus and ovaries are left in situ to allow for future fertility. • Pregnant rate depends on disease extent. • Pain but not desire pregnant immediate can be treated by medicine immediately after surgical treatment.

33. Definitive surgical therapy • Total abdominal hysterectomy and bilateral salpingo-oophorectomy • Lysis of adhesions • Removal of endometriosis lesions

34. Treatment Combination of medication and surgery • surgery + medication • medication + surgery + medication Treatment for patients with infertility

35. Prevention • Prevent retrograde flow of menses • Contraception with medicine • Avoid iatrogenic implantation of the ectopic endometrium

36. Adenomyosis

37. Definition • Adenomyosis is defined by the presence of endometrial glands and stroma within the myometrium, making the uterus diffusely enlarged, boggy, and globular.

38. Pathogenesis • It occurs in 15% of women, most of whom are parous in their 30s or early 40s. • It is associated with myometrial hypertrophy and proliferation. • High level E stimulate hyperplasia of the basalis layer of the endometrium. • Barrier between endometrium and myometrium broken and the endometrial cells invade the myometrium. • Most extensive in the fundus and posterior uterine wall.

39. Endometriosis ＆ Adenomyosis • Pathogenesis ＆ histological confirmation • Sites of lesions • Clinical findings Adenomyosis is thought to be unrelated to endometriosis.

40. Clinical findings Symptoms： • Symptoms occurs most often in parous women between age 35-50. • Typically present with increasing secondary dysmenorrhea and/or menorrhagia. Prolonged and heavy menses Dysmenorrhea that worsens over time • 30% of patients are asymptomatic. Pelvic examination ： • Reveal a diffusely enlarged globular uterus. 2 to 3 times normal size. • Tenderness

41. Diagnosis • Typical symptoms and signs • Be suggested on pelvic U/S. • MRI is the most accurate imaging tool, can best distinguish between adenomyosis and fibroids. • Hysterectomy is the only definitive means of diagnosing and treating adenomyosis. • Patients age 35 and older with irregular menses should also have an endometrial biopsy to rule out hyperplasia and cancer.

42. Treatment • Minimal symptoms may be treated with analgesics, NSAIDs, OCPs, or progestins although it is less responsive to hormone management than EMs. • Sometimes using GnRH-a. • Not generally responsive to regulation with OCPs or other hormonal treatments. • Surgical treatment :total hysterectomy is the only definitive means of treating adenomyosis.

43. Thank You