1. Ozgul Muneyyirci-Delale
ENDOMETRIOSIS
Ozgul Muneyyirci-Delale

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

4. 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

5. 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

6. 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

7. 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.

8. 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

9. 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

10. Glutathione peroxidase
Catalase
Thrombospondin 1
Vascular endothelial growth factor
Integrin

11. 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.

12. 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.

13. 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

14. 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

15. 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.

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

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

18. 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.

19. Research Shows Risk for Autoimmune 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.

20. 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.

22. Frequency of Commoner Symptoms of Endometriosis
Symptom Likely Frequency (%)
Dysmenorrhea
Pelvic pain
Infertility
Dyspareunia
Menstrual irregularities
Cyclical dysuria/hematuria 1-2
Dyschesia (cyclic) 1-2
Rectal Bleeding (cyclic) <1

25. Implants and Adhesions in 182 Patients with Endometriosis According to Anatomical Location
Location Implants Adhesions
# 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 (1.6)
Right round ligament 1 (0.5) 2 (1.1)
Left round ligament 1 (0.5) (1.1)
Right fallopian tube 8 (1.6) (11.0)

26. 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 (11.5) 6 (3.3)
Sigmoid (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)

27. Small bowel (2.2)
Anterior abdominal wall (1.6)
Omentum (2.2)

28. Detection
History
Clinical exam
Operative visualization
Operative palpation

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

30. >6mm infiltration 15% 21% 42%
APPEARANCE AND AGE
Appearance
Red lesions 27% % %
“Typical” lesions % % %
>6mm infiltration 15% % %
Konincky PR, et al.: Fertil Steril 55:763, 1991

31. APPEARANCE AND AGE
Appearance Age Range
Any clear papuls
Any red lesions
Any white lesions
Any black lesions
Redwine DB: Fertil Steril 106, 1987

48. 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)

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

50. Conservative Surgery for Pelvic Pain Associated with Endometriosis
Author Therapy Symptom Outcome
Relief
Puolakka CSEL % 17% CSEL + PN %
CSEL+PN % Req. reop.
Candiani Repeat CSEL % % req. reop
Polan CSEL + PN % % req. reop
Lee CSEL = PN % % req. reop

51. Operative Laparoscopy in the Treatment of Endometriosis-Associated Pain
Author Therapy Symptom Outcome
Relief
Hasson Unipolar 63% 14% (30m
electrocoag.
Sulewski Unipolar 67% 14% (16.5m)
Daniell KTP/532 laser % No (30m)
Keye Argon laser ab. 92% 33% (9m)
Davis CO2 laser vap % Rec. (?)

52. Operative Laparoscopy in the Treatment of Endometriosis-Associated Pain
Author Therapy Symptom Outcome
Relief
Shirk Nd:YAG laser % Rec. (?)
abl % Rec. (?) % Rec. (?)
Sutton & Hill CO2 or Nd:YAG % % (12m)
Perez CO2 or Nd:YAG % % (req.reop)
laser abl. & pre-
sacral neur.

53. Author Therapy Symptom Outcome
Relief
Nezhat & Co2 laser vap % Rec. (?)
Nezhat & presac. neure %
Redwine Laparoscopic Not spec % reop.
exc % (rec.?m)

54. Medical Treatment Pseudopregnancy (estrogen and progestin) Progestin
Medroxyprogesterone acetate
Lynestrenol
Norethynodiel
Megestrol acetate
Cyroterone acetate
Dydrogesterone
Dienogest
Norethindrone acetate

55. Danazol
GnRH agonist
Nafarelin
Goserelin
Leuprolide
Buserelin
Histrelin
Deslorelin
Tryptorelin
Gestrinone
Antiprogesterones

58. Effect of Norethindrone Acetate in the Treatment of Symptomatic Endometriosis
Dysmenorrhea was relieved in 48/52 (92.5%)
Noncyclic pelvic pain relief 25/28 (89.2)
Overall pain relief 49/52 (94.2%)

59. Long-Term Treatment of Symptomatic Endometriosis with Norethindrone Acetate
Long-term Norethindrone acetate (LTNA)
Other medications (OM)
LTNA patients were treated with Norethindrone acetate for at least 2 years (maximal treatment 15 years)
OM patients matched with LTNA patients with year of diagnosis and duration of follow-up

60. The duration of treatment for the LTNA group
was years. The duration of treatment for the OM group varied based on treatment type.
Patients on Depot and Danazol remained on
medication for a maximal of 6 months.

61. Summary of Demographic Findings Before Treatment

63. Summary of Treatment Effects

64. Summary of Treatment Effects (Continued)

65. Weight Change by Treatment Group

66. Conclusion
LTNA seems to be a cost-effective alternative, with relatively mild side effects, for continuous treatment of symptomatic endometriosis.