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Endometriosis

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1International Journal of Gynecology&Obstetrics 74 S1 (2001) S25-30. 2International Journal of Gynecology&Obstetrics 74 S1 (2001) S15-20. Theories on Pathogenesis ... – PowerPoint PPT presentation

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Title: Endometriosis


1
Endometriosis
  • Presence of endometrial glands and stroma
    outside the uterus
  • Ovaries, pelvic peritoneum, tubal serosa,
  • gastrointestinal tract, urinary tract.
  • Surgical scars
  • Extra-abdominal sites.

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Prevalence
  • 5 to 15 of women of childbearing age1
  • 50 to 70 of women with chronic pelvic pain
  • 20 to 40 of infertile women2
  • 6 million women in North America3

1National Institute of Health, 91-2413 2 Mayo
Foundation for Medical Education and
Research 3American Family Physician, 1999, vol
60, p. 1753
11
Epidemiology
  • 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

12
Prevalence
  • 30,000 new cases diagnosed each year in Canada
    (300,000 in the U.S.)
  • A 6 to 9 year period between the onset of
    symptoms and diagnosis of endometriosis1
  • 40 recurrence within 2 to 5 years following
    laparoscopic procedure2

1International Journal of GynecologyObstetrics
74 S1 (2001) S25-30 2International Journal of
GynecologyObstetrics 74 S1 (2001) S15-20
13
Theories on Pathogenesis
  • Transplant of endometrial tissue via retrograde
    menstruation
  • Coelemic metaplasia
  • Lymphatic or vascular transport
  • Altered cellular immunity/ autoimmune mechansisms

14
Pathogenesis
  • Retrograde flow supported by
  • Endometrial cells in menstrual fluid are capable
    of implanting on peritoneal surfaces
  • Endometriosis is most commonly seen in dependent
    portions of pelvis
  • Endometriosis occurs in patients with uterine
    outlet obstruction

15
Pathogenesis
  • Coelemic metaplasia transformation of embryonic
    tissue
  • Peritoneal mesothelium, mullerian epithelium, and
    germinal epithelium may be derived from a common
    embryonic tissue
  • Endometriosis reported in
  • Prepubertal girls
  • Women who have never menstruated
  • Men
  • Unusual sites such as knee, thumb, eye

16
Pathogenesis
  • Lymphatic vascular metastasis
  • May explain endometriosis in distant sites
    outside pelvis

17
Pathogenesis
  • Immune mechanisms supported by
  • Not all women with seeding of menstrual debris
    into pelvis develop endometriosis
  • Evidence for decreased cellular immunity
  • Increased prevalence of humoral antibodies
    against endodmetrial tissue

18
ENDOMETRIOSIS (Hypothesis)
  • In patients affected, there is an intrinsic
    difference in the endometrium
  • Remains viable (apoptosis)
  • Adheres to mesothelial cells (integrins)
  • Erodes extracellular matrix (MMPs)
  • Prompts vascularization (VEGF)
  • Circumvents immune system mechanisms (i. e.
    leucocytes)

19
Endometriosis
  • Many evidences that endometrium of
  • patients with endometriosis is different
  • Aromatase P450 expression
  • ? Expression of MCP-1
  • ? FGF
  • ? Apoptosis in endometrium of patients with
  • endometriosis
  • Ref From the VIII World Congress on
    Endometriosis, San Diego, Ca. February 2002

20
ENDOMETRIOSIS (Hypothesis)
  • In patients affected, feedback control mechanisms
    alter the endometrium

21
Signs Symptoms
  • Chronic pelvic pain
  • Dysmenorrhea
  • Dyspareunia
  • Infertility
  • Abnormal uterine bleeding

22
Presenting symptoms
  • Dysmenorrhea (25-80 of patients with pelvic pain
    or dysmenorrhea have endometriosis)
  • Dyspareunia
  • Dyschezia
  • History of infertility (30-40 of patients with
    endometriosis)
  • Abnormal uterine bleeding
  • Other GI complaints (50 of pts with severe
    endometriosis have GI involvement)
  • Diarrhea, constipation, perimenstrual changes in
    bowel habits, rectal bleeding
  • Urinary tract complaints hematuria, dysuria,
    urgency, frequency
  • Low back pain

23
Specifics on pain
  • Pain related to endometrial implants enlarging in
    response to hormonal stimulation
  • History of years of pain-free menses, gradual
    onset and progressively worsening dysmennorhea
  • Severity does not predict degree of pain
  • Diffuse or localized
  • Constant or vary throughout menstrual cycle
  • Relief from oral contraceptives or GnRH agonists

24
Physical findings
  • Perform good bimanual exam
  • Diffuse abdominal or pelvic pain
  • Uterosacral ligament tenderness and nodularity is
    very specific to endometriosis
  • Pain/nodularity in cul-de-sac
  • Obliteration of the cul-de-sac occurs with fixed
    uterine retroversion implying severe disease
  • Adnexal tenderness and palpable enlargement of
    endometriomas (chocolate cysts)

25
Laboratory Findings CA-125 Assay
  • CA-125 is a glycoprotein expressed on the cell
    surface of some coelomic epithelium (including
    endometrial tissue)
  • Elevated levels found in women with endometriosis
  • Shouldnt be used for screening but may correlate
    with patients response to treatment
  • Elevated in other benign conditions - early
    pregnancy, acute pelvic inflammatory disease,
    uterine fibroids, and menstruation

26
Sites of endometriosis
  • Can occur in almost every organ
  • Most common Ovaries, anterior and posterior
    cul-de-sac, uterosacral ligaments, posterior
    uterus, posterior broad ligaments
  • Less common GI tract rectosigmoidgtappendixgtsmal
    l bowel Urinary tract
  • Uncommon lungs, CNS, extremities, skin, eye,
    nasal mucosa, episiotomy scars

27
Diagnosis
  • Rule out other causes of pelvic pain first (PID,
    fibroids, malignancy)
  • Trial of OCPs or GnRH agonists to help delineate
    etiology of pain
  • Ultrasound to evaluate for chocolate cysts
  • Colonoscopy if suspect GI involvement
  • IVP/Cystoscopy if suspect urinary tract
    involvement

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Diagnosis
  • Medical history, pelvic exam
  • Diagnostic laparoscopy
  • 40 inconclusive1
  • 15 false negatives

1International Journal of GynecologyObstetrics
74 S1(2001) S15-20
30
Diagnosis
  • Laparotomy or laparoscopy for definitive dx and
    staging
  • Classic powder-burn appearance but may be red,
    black, brown, white or hypopigmented
  • Biopsy needed to make dx must reveal
    endometrial stroma and glands
  • Staging American Society of Reproducitve
    Medicine Staging System based on depth,
    location, size of implants, presence or absence
    of cul-de-sac obliteration and extent and quality
    of adhesions

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Treatment
  • Medical management NSAIDs, hormonal agents
  • All treatment options are suppressive rather than
    curative
  • Very helpful for dysmenorrhea, chronic pelvic
    pain, but not very effective for infertility
  • Pain relief, recurrence rates, pregnancy rates
    similar for all
  • Surgery

34
Laparoscopy
  • BENEFITS
  • Precision
  • Surgical treatment
  • Sole standard available
  • DISADVANTAGES
  • Risks
  • Costs
  • Delays
  • False negatives (15)
  • Invasive

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Course of the Disease
  • Spontaneous Recovery
  • Natural Healing
  • Pregnancy
  • Menopause
  • Infiltration
  • Local
  • Remote
  • Blood
  • Lymphatic

37
Treatment
  • NSAIDs
  • Inhibit prostaglandins produced by endometrial
    implants
  • Fenamate class meclofenamate, mefenamic acid
    and indomethacin work best
  • Begin 1 to 2 days before the onset menses and
    continue for the duration of menstrual cycle

38
Treatment
  • Oral contraceptives
  • Causes decidualization of endometrial tissue
  • Low dose monophasic combination
    estrogen-progestin pills
  • Use continuously for 6 to 12 months

39
Treatment
  • Danazol
  • 17 alpha-ethinyl testosterone derivative
  • Eliminates midcycle surge of LH and FSH,
    decreasing estrogen and progesterone creates
    high androgen low estrogen state
  • Up to 90 of of patients with minimal to moderate
    disease have improvement
  • 400mg bid
  • Side effects weight gain, fluid retention,
    acne, decreased breast size, hot flashes, muscle
    cramps, emotional lability, deepened voice
  • Contraindicated in women with liver disease

40
Treatment
  • Progestins
  • Suppress ovarian function and cause atrophy of
    endometrial implants
  • Provera 10 to 30 mg/day
  • Megace 40mg qd
  • Depo-Provera 150mg IM q3 months
  • Side effects Breakthrough bleeding, depression,
    nausea, bloating, breast tenderness

41
Treatment
  • GnRH agonists (Leuprolide, Goserelin)
  • Suppress ovarian function and produce
    hypoestrogenic state
  • Equal efficacy compared with Danazol but less
    androgenic side effects
  • Given monthly (Leuprolide IM, Goserelin SC)
  • Monitor estradiol levels (20-40pg/nl)
  • Side effects decreases bone density (can add
    low dose estrogen/progesterone or bisphosphonate)

42
Surgical Treatment
  • Laparoscopy
  • Laparotomy
  • Conservative vs Radical Treatment

43
Treatment
  • Surgery
  • Try expectant management for mild disease first
  • Minimal to mild disease can be removed by laser
    or electrocautery
  • Surgery indicated for severe adhesive disease or
    endometriomas gt 2cm
  • Severe disease removal of implants/adhesions
    if fertility not desired consider
    hysterectomy/oopherectomy
  • Pre-sacral neurectomy has been used to treat
    severe dysmenorrhea

44
Treatment (of associated infertility)
  • Minimal disease - Pregnancy rate without
    treatment after 5 years is 90
  • If severe disease is suspected proceed to
    laparoscopy
  • If time is a factor (woman over 35 yrs old) -
    proceed with treatment
  • Medical therapy is of limited value

45
Endometriosis (Pelvic Pain)Medical Treatment
  • BENEFITS
  • Avoid Trauma and adhesion formation
  • Treat microscopic endometriosis
  • May improve surgical outcomes
  • RISKS
  • Side effects
  • High recurrence rates
  • Not effective for treatment of endometriomas or
    adhesions (infertility)

46
Endometriosis (Pelvic Pain)Efficiency of medical
treatment
Canadian Consesus on Endometriosis SOGC Journal
0599
47
Endometriosis (Infertility)Stages 1 - 2
  • Monthly Fertility without treatment 3
  • Pregnancy rate after 3 years 30-70
  • Treatment efficiency ?(Relative Risks)
  • Laparoscopy monthly fertility ?4.7 vs 2.4 1
  • C.Clomiphere ?1.9 2
  • C.C. I.U.I. ?3 3
  • F.S.H. I.U.I. ?5 4
  • I.V.F. ?10 5

1 Marcoux 1997 2 Samson 1993 3 Deaton 1990 4
Fedele 1992 5 Barbieri 2001
48
Endometriosis (Infertility)Stages 3 - 4
  • LSC Surgery Laparotomy
  • Pregnancy rate after 3 years 40 70
  • Vs ? 5 if expectative
  • Repeat Surgery no increase of fertility vs
    I.V.F.
  • In vitro Fertilization
  • Implantation rate similar to non-endometriosis
    patients
  • Pre-IVF surgical treatment of endometriomas ?
    outcome

Canadian Consensus Journal SOGC 1999
49
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
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