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ENDOMETRIOSIS

ENDOMETRIOSIS. Ozgul Muneyyirci-Delale. Endometriosis. The presence of functional endometrial tissue outside the uterine cavity. Prevalence of Endometriosis. Affects 10% menstruating women Found in 25% - 50% of all infertile women 71-87% of women with chronic pelvic pain

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ENDOMETRIOSIS

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  1. ENDOMETRIOSIS Ozgul Muneyyirci-Delale

  2. Endometriosis • The presence of functional endometrial tissue outside the uterine cavity.

  3. Prevalence of Endometriosis • Affects 10% menstruating women • Found in 25% - 50% of all infertile women • 71-87% of women with chronic pelvic pain • Often begins in adolescence

  4. Endometriosis in Adolescents • A 65% incidence of endometriosis was found among 43 laparoscopies in symptomatic teenagers. DL Chatman & AB Ward, 1982 • Endometriosis was encountered in 66 of 140 patients (47%) who underwent laparoscopy for chronic pelvic pain. DP Goldstein et al., 1980

  5. Theories on the Pathogenesis of Endometriosis • Retrograde menstruation/transplantation • Coeleomic metaplasia • Altered cellular immunity • Metastasis • Genetic basis • Environmental basis • Multifactorial mode of inheritance with interactions between specific genes and the environment

  6. Genetic Factors • Simpson and coworkers reported 6.9% of first-degree relatives of patients with endometriosis had the disease, compared with 1.0% in control group. • The proposed inheritance is characterized of polygenic-multifactorial mechanism.

  7. Candidate Genes and Susceptibility to Endometriosis • Cytochrome P450 1A1 • N-actyl transferase 2 • Glutathione-S-transferase M1, T1 • Galactose-1-phosphate uridyl transferase • Oestrogen receptor • Progesterone receptor • Androgen receptor • PTEN • p53 • Peroxisome proliferator-activated receptor y2 Pro-12-Ala allele

  8. Genes and Gene Products • Aromatase • Endometrial bleeding factor • Hepatocyle growth factor • 17-B-hydroxysteroid dehydrogenase • HOX A10 • HOX A11 • Leukaemia inhibitory factor • Matrix metalloproteinases 3,7, and 11 • Tissue inhibitors of metalloproteinases • Progsterone-receptor isoforms • Complement 3

  9. Glutathione peroxidase • Catalase • Thrombospondin 1 • Vascular endothelial growth factor • Integrin

  10. Immune System • The immune system is believed to be involved in the pathogenesis of endometriosis and a lack of adequate immune surveillance in the peritoneum is thought to be a cause of the disorder.

  11. The major immune alterations include: • Increased presence of circulating autoantibodies • Increased numbers and activation of peritoneal macrophages • Decreased T-lymphocytes reactivity and natural killing activity.

  12. IMMUNOLOGIC ABNORMALITIES IN ENDOMETRIOSIS • Systemic Increased immunoglobulin production Increased presence of helper (CD4) cells Deficient lymphocyte-mediated cytotoxicity against endometrium Embryotoxic serum Serum that suppresses natural killer cell activity Deficient cellular immunity Defective natural killer activity Abnormal autoimmune function Decrease in suppressor cell activity

  13. Peritoneal Endometrial stromal cell proliferation Increased cytotoxicity of peritoneal macrophages Decreased sperm binding to zona pellucida Proliferation of lymphocytes Increased sperm phagocytosis by peritoneal macrophages Increased cytokine levels Increased sperm phagocytosis by peritoneal macrophages

  14. Environmental Factors • Rhesus monkeys exposed to whole-body proton irradiation have a higher frequency of endometriosis than controls (53% vs. 26%). • Rhesus monkeys exposed to 5-25 ppm dioxin per day for 4 years developed endometriosis that dose-dependent in staging.

  15. Increase Risk Factors for Endometriosis • Heavy menstrual flow • Prolonged menstrual flow • Outflow obstruction • Early menarche without pregnancy

  16. Decrease Risk Factors for Endometriosis • Exercise-induced menstrual disorders • Decrease in body-fat content • Tobacco smoking

  17. Delay in Diagnosing Endometriosis • Times to diagnosis can be very long (mean 11.7 years in the USA and 8.0 years in the UK) because of variability in symptoms and signs and confusion with other disorders.

  18. Research Shows Risk forAutoimmune Diseases in Endo • Hypothyroidism was seven times more common. • Fibromyalgia was twice as common. • The autoimmune inflammatory diseases, systemic lupus erythematosus, Sjogren’s syndrome, rheumatoid arthritis, and multiple sclerosis occurred more frequently.

  19. Allergies and allergic conditions such as asthma and eczema were higher: 61 percent of the endo sufferers had allergies, compared with 18 percent of the U.S. general population, and 12 percent had asthma, compared with 5 percent. If a woman had endo plus an endocrine disease (such as hypothyroidism), the figure for allergies rose to 72 percent, and to 88 percent is she had endo plus fibromyalgia or chronic fatigue syndrome. • Two-thirds reported they had family members with diagnosed or suspected endo, confirming research that suggested there is a familial tendency.

  20. Frequency of Commoner Symptoms ofEndometriosis SymptomLikely Frequency (%) Dysmenorrhea 60-80 Pelvic pain 30-50 Infertility 30-40 Dyspareunia 25-40 Menstrual irregularities 10-20 Cyclical dysuria/hematuria 1-2 Dyschesia (cyclic) 1-2 Rectal Bleeding (cyclic) <1

  21. Implants and Adhesions in 182 Patients with Endometriosis According to Anatomical Location LocationImplantsAdhesions # of patients (%) Anterior cul-de-sac 63 (34.6) 4 (2.2) Posterior cul-de-sac 62 (34.0) 20 (11.0) Right ovary 57 (31.3) 26 (14.3) Left ovary 81 (44.0) 45 (24.7) Right anterior broad ligament 2 (1.1) 2 (1.1) Left anterior broad ligament 0 3 (1.6) Right round ligament 1 (0.5) 2 (1.1) Left round ligament 1 (0.5) 2 (1.1) Right fallopian tube 8 (1.6) 20 (11.0)

  22. Left fallopian tube 8 (4.4) 28 (15.4) R. posterior broad ligament 39 (21.4) 30 (16.5) Left posterior broad ligament 46 (25.3) 50 (27.5) Right uterosacral ligament 28 (15.4) 5 (2.7) Left uterosacral ligament 38 (20.9) 8 (4.4) Uterus 21 (11.5) 6 (3.3) Sigmoid 7 (3.8) 22 (12.1) Right ureter 3 (1.6) 0 Left ureter 2 (1.1) 3 (1.6) Anterior bladder flap 1 (0.5) 1 (0.5)

  23. Small bowel 1 4 (2.2) Anterior abdominal wall 0 3 (1.6) Omentum 0 4 (2.2)

  24. Detection • History • Clinical exam • Operative visualization • Operative palpation

  25. Clinical Manifestations • Nodularity of the utero-sacral ligaments and/or pelvic floor • Adnexal mass • Lateral displacement of cervix and uterus

  26. APPEARANCE AND AGE Appearance20-25 31-3541-45 Red lesions 27% 19% 0% “Typical” lesions 57% 61% 75% >6mm infiltration 15% 21% 42% Konincky PR, et al.: Fertil Steril 55:763, 1991

  27. APPEARANCE AND AGE Appearance Age Range Any clear papuls 17 - 31 Any red lesions 16 - 43 Any white lesions 17 - 43 Any black lesions 17 - 52 Redwine DB: Fertil Steril 106, 1987

  28. Management Decision-making factors • Reproductive status - a. Desire of future pregnancy b. Childbearing complete or undesired • Severity of symptoms • Extension of lesions • Failure of conservative treatment • Additional factors (age, economic aspects)

  29. Treatment of Endometriosis • Surgical extirpation or excision • Medical therapy • Combination of both

  30. Conservative Surgery for Pelvic Pain Associated with Endometriosis AuthorTherapy Symptom Outcome Relief Puolakka CSEL 80% 17% CSEL + PN 90% CSEL+PN 83% Req. reop. Candiani Repeat CSEL 75% 9% req. reop Polan CSEL + PN 80% 25% req. reop Lee CSEL = PN 61% 9% req. reop

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