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4% in asymptomatic women having sterilization. 5-20% in women with pelvic pain ... low estrogen and anovulation no retrograde menstruation ... – PowerPoint PPT presentation

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Title: Endometriosis

  • Hsin-Yang Li, M.D., Ph.D.
  • OB/GYN Dept.,
  • Taipei Veterans General Hospital

Endometriosis presence of endometrial glands
and stroma outside of the normal location
Ovarian endometrioma
Ovarian chocolate cyst
Ovarian endometriosis histology
Peritoneal endometrioma
Lung endometriosis
(BMJ, 2003 Med. Inform., 2006 BMJ, 2001
Respirology, 2006)
  • Prevalence
  • 4 in asymptomatic women having sterilization
  • 5-20 in women with pelvic pain
  • 20-40 among infertile women,
  • 3-10 of the general female population
  • Most commonly diagnosed in women of reproductive
    age. Mean age at time of diagnosis 25-30 years
  • Risk factors early menarche, short menstrual
    cycle, alcohol, caffeine
  • Protection factors term pregnancy, regular
    exercise, smoking
  • Asians gt Whites gt Blacks

Clinical features
  • Symptoms and signs dysmenorrhea, intermenstrual
    pain, dyspareunia, and infertility
  • There is no relationship between stage, site, or
    morphological characteristics and the degree of
  • Pelvic pain diffuse, dull, and deep, may radiate
    to the back, may be associated with nausea,
    diarrhea and rectal pressure
  • Dysmenorrhea begins before menses and persists
    throughout menses
  • Intermenstrual pain 1/2 to 2/3 of patients
  • Dyspareunia disease involving the cul-de-sac and
    rectovaginal septum

Diagnosis of endometriosis
  • Clinical diagnosis history and physical
    examination (rectovaginal septum lesion, fixed
    adnexal mass, tenderness/nodularity of U-S lig.)
    ? poor predictive value
  • CA125 elevated in endometriosis (also elevated
    in menstruation, early pregnancy, PID, and
    myomas) low sensitivity predicts the success of
    surgical but not medical treatment
  • Transvaginal ultrasound/ MRI ovarian
    endometrioma/chocolate cyst
  • Surgical diagnosis laparoscopy with histologic
    examination ? gold standard

Transvaginal ultrasound Chocolate cysts
Laparoscopy Endometriomas and adhesions
Theories on the pathogenesis of endometriosis
  • Retrograde menstruation/transplantation
  • Coelomic metaplasia
  • Metastasis
  • Genetic basis
  • Immunologic basis

Retrograde menstruation/transplantation as the
primary mechanism involved in the pathogenesis
of endometriosis
First described by John Sampson in 1927
Lines of evidence supporting Sampsons theory of
retrograde menstruation
  • Laparoscopy during menses peritoneal blood can
    be found in 75-90 of women with patent tubes
  • Peritoneal endometrial cells recovered during
    menses can attach to and penetrate the peritoneum
  • Incidence of endometriosis is increased in women
    with early menarche, short cycle, menorrhagia or
    obstructing Mullerian anomalies
  • Commonly found in dependent sites ovaries,
    cul-de-sac, U-S lig., post. uterus, post. broad
  • Endometriosis can be induced in baboons by
    ligation of the cervix

Coelomic metaplasia theory
  • Metaplastic change in the coelomic epithelium
    (peritoneum and pleura) spontaneous or induced
  • Supporting evidences
  • Endometriosis has been found in premenarcheal
  • Pleural and pulmonary endometriosis
  • Endometriosis in men treated with high doses of
  • In vitro, ovarian surface epithelium can be
    induced by estradiol to form endometrial glands

Metastasis theory
  • Hematogenous or lymphatic spread
  • Unusual sites of endometriosis brain, colon

A 35 year-old female complained of severe
abdominal pain and constipation as well as bloody
stool during menses. Colonoscopy showed a
fungating mass, which turned out to be a
endometriotic lesion.
The genetic basis
  • Genetic predisposition 6-7 times more prevalent
    among first-degree relatives of affected women
    than in the general population
  • Oxford endometriosis gene study
  • Resistance to apoptosis Bcl-2/bax family
  • Attachment to peritoneum integrins
  • Invasion of peritoneum MMP
  • High estrogen environment that stimulates growth
    of endometriosis aromatase, 17?HSD type 1/type 2

Immunobiology of endometriosis
The immunologic basis
  • A wide range of immunologic abnormalities have
    been described in women of endometriosis
  • The peritoneal fluid of affected women contains
    increased numbers of immune cells. However,
    instead of acting to efficiently remove refluxed
    endometrial cells, these immune cells appear to
    promote the disease by secreting a variety of
    cytokines and growth factors that stimulate
    endometriotic attachment, invasion,
    proliferation, and neovascularization.

Mechanisms of pain
  • (1) Actions of inflammatory cytokines in the
    peritoneal cavity mild (early stage) disease or
    severe (advanced stage) disease
  • (2) Direct and indirect effects of focal bleeding
    from endometriotic implants mild disease or
    severe disease
  • (3) Irritation and direct infiltration of nerves
    in the pelvic floor severe disease
  • There is no relationship between stage, site, or
    morphological characteristics and the degree of
  • Hormonal modulation pain threshold and tolerance
    are lowest just prior to and during menses

Mechanisms of infertility
  • (1) Distorted adnexal anatomy that inhibit ovum
    capture and transport severe disease
  • (2) Interference with oocyte/sperm survival,
    fertilization, and embryogenesis mild or severe
  • (3) Reduced endometrial receptivity mild or
    severe disease
  • Endometriosis decreases fertility to an extent
    that roughly correlates with the severity of
  • IVF success rates lower in endometriosis lower
    in severe disease than in mild disease

  • Medical effective for pain, which tends to recur
    after cessation of treatment. Equal
    effectiveness among different approved
    medications. Not beneficial for improving
  • Surgical equally effective as medical treatment
    for pain, which also tends to recur. Surgical
    treatment improves fertility to some extent.
    Higher pregnancy rates are observed in the first
    year after conservative surgery.

  • Danazol
  • The first drug ever approved for the treatment
  • of endometriosis in th U.S.
  • 2. Orally administered isoxazol derivative of
    17?-ethinyl testosterone
  • 3. Mechanisms inhibit steroidogenic enzymes and
    LH surge ?
  • low estrogen and anovulation ? no retrograde
  • free testosterone ? low estrogen ? inhibit
    endometriotic growth
  • 4. Doses 600-800 mg daily
  • 5. Side effects weight gain, fluid retention,
    decreased breast size,
  • acne, atrophic vaginitis, irreversible deepening
    voice, poor lipid
  • profile

(Clin. Gynecol. Endocrinol. Infertil., 2005)

  • Gestrinone
  • A 19-nortestosterone derivative
  • Has androgenic, antiprogestinic and
    antiestrogenic actions
  • Doses 2.5-10 mg biw
  • Side effects similar to danazol, but less

(Clin. Gynecol. Endocrinol. Infertil., 2005)
  • Medroxyprogesterone acetate (provera) 20-100 mg
    daily or norethindrone acetate (primolut-nor) 40
    mg daily
  • Mechanisms atrophy of endometrial tissue and
    inhibition of ovulation (higher doses)
  • Side effects breakthrough bleeding (may be
    treated by conjugated estrogen 1.25 mg qd or
    estradiol 2 mg qd for a week), weight gain, fluid
    retention, breast tenderness, depression, and
    poor lipid profile

Oral contraceptives
  • Continuous treatment is preferred to induce an
    amenorrhea state
  • Mechanisms atrophy of endometrial tissue,
    absence of retrograde menstruation (high estrogen
    and high progesterone state ? pseudopregnancy)

Gonadotropin-releasing hormone agonists (GnRH-a)
  • Modifications
  • Position 6 ? enzymatic degradation
  • Position 10 ? potency
  • Position 6 and 10 ? receptor affinity

(Textbook of ART, 2004)
Pituitary desensitization by continuous GnRH-a
  • Adequate pituitary suppression is achieved after
    7-10 days of GnRH-a administration
  • Clinical application prevention of premature LH
    surge in COH, endometriosis,
  • uterine myoma, breast cancer, prostate cancer

(Coccia ME., et. al., 2004)
GnRH-a in the treatment of endometriosis
  • Mechanisms hypogonadotropic hypogonadism ?
    deprives endometriosis of estrogen support
    absence of retrograde menstruation
  • Administration im, sc, or nasal spray (depot
    form may be administered once per month)
  • Side effects hot flush, vaginal dryness,
    decreased libido, mood swings, skin dryness,
    decreased bone density (significant after 6
    months of treatment, 1 per month)
  • Add back conjugated estrogen 0.625 mg qd and
    medroxyprogesterone acetate 2.5 mg qd

Surgical treatment
  • Objectives restore normal anatomy, excise or
    destroy all visible lesions as possible, prevent
    or delay recurrence
  • Operate in the follicular phase instead of in the
    luteal phase
  • Excision of peritoneal implants and ovarian
  • Excision of adhesion bands
  • Dissection and excision of nodular lesion in the
    rectovaginal septum
  • Women with advanced disease who have completed
    childbearing hysterectomy BSO ? low-dose
    estrogen-progestin is recommended postoperatively
    (estrogen only will induce adenocarcinoma from
    residual endometriosis)

Ovarian endometrioma excision is better
than drainage and ablation as regards to
recurrence and pregnancy rates. (Hum. Reprod.,
(Surgical management of endometriosis, 2004)
Excision of adhesion bands
(Surgical management of endometriosis, 2004)
Perioperative treatments
  • Preoperative medical treatment no evidence
    showing that it improves pain control or
    infertility, except in cases with deep
    rectovaginal endometriosis
  • Postoperative medical treatment not indicated
    for those who wish immediate pregnancy. May have
    value for those who do not wish to be pregnant in
    the near future, since it will decrease
    recurrence rates.
  • Postoperative suggestions for infertile couples
  • mild disease ? observe for 6 months, then IUI or
  • severe disease with tubal obstruction ? IVF
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