ENDOMETRIOSIS

I. Pathophysiology/epidemiology

  1. Growth of endometrial tissue outside uterine cavity; the tissue is functional and responds to hormonal stimuli and, as the endometrium, sloughs with the menstrual cycle
  2. Prevalence: 7-10% of women
  3. Etiology:
  1. "Metaplasia" theory: dormant celomic epith. cells differentiate into ectopic endomet.
  2. "Retrograde tubal transmission" theory: Menstrual fluid escaping out tubes; prob. not direct seeding of endomet. cells but of an irritating substance (compatible with #1)
  3. Hereditary component evident (RR 10 with 1st-degree relative)
  1. Risk factors
    1. Family history
    2. Early menarche
    3. Long/heavy periods
    4. Obesity (possibly due to increased estrogen levels)
  1. Pathology
  1. Gross: Depends on stage/duration; if occurs in myometrium, called "adenomyosis"; diff. clin. picture
  1. Early--blue-red spots: big ones are endometriomas
  2. Late--may coalesce & obliterate cul-de-sac, form adhesions between adnexae & post. peritoneum, rectorigmoid & uterus; peritoneum forms dense scars in resp. to cyclic bleeding
  1. In ovaries, simple or loculated cysts
  1. Other, rarer involvement: rectosig. serosa, ur. tract, cervix, vag., lungs, extrem's
  2. Histol.: Like nl endometrium, occ. with trapped blood

II. Classification:

  1. Several systems, no one universally accepted
  2. American Society for Reproductive Medicine scheme
  1. Stages I-IV, point scale of 1-40
  2. Requires laparoscopy/-tomy
  3. Classifies on basis of depth & extent; adhesions, & cul-de-sac obliteration
  4. Does not correlate well ith pain, dyspareunia, or likelihood of pregnancy following treatment

III. Clinical features & Natural history--Highly variable!

  1. Usual presentation 25-35yo; rarely symptomatic before menarche/after menopause
  2. Low abdominal/pelvic pain, usually ass'd with menses
    1. Usually severe, noncrampy, radiating to back & legs (indicates involv. of uterosacral ligaments & cul-de-sac)
    2. Ovarian involvement is usually painless; can even have stage IV without pain
    3. Tenesmus
    4. Dyspareunia
    5. Pain usually relieved during pregnancy.
  3. Abnormal bleeding, usually due to advanced ovarian involvemena
  4. Infertility, probably from mechanical distortion of adnexae, although sometimes occurs with scanty lesions (unclear pathogenesis in that case, poss. immune or biochemical)
  5. Ruptured ovarian endometrioma (from blood buildup)
    1. Sudden, debilitating pain due to hemoperitoneum; requires immediate surgery with poss. oophorectomy
  6. Malignant transformation: rare; us. adenocarcinoma, more common with ovaian. involvement
  7. Pulmonary lesions: can get cyclic hemoptysis from bronchial endo.
  8. Urinary tract lesions (for women with UT endometriosis): cause cyclic hematuria, can cause ureteral obstr.
  9. Bowel lesions: bowel endo.--can get cyclic hematochezia
  10. Px:
  1. Fixed, retroflexed uterine corpus
  2. Tenderness & nodularity of uterosacral lig.
  3. Bilat. fixed, tender adnexal masses
  4. Tender thickening of recto-vag. septum

IV. Diagnosis

  1. Usually made by direct inspection & histologic examination
    1. Histologic evidence sometimes seen with normal gross appearance to the peritoneum
  2. Serum CA-125 levels have been proposed but sensitivity/specificity only around 85%/20-50%
  3. Imaging studies, e..g ultrasound or MRI--not hightly sensitive
  4. Presumptive tx w/o visual/histologic dx OK per ACOG

V. Treatment

  1. Medical therapy (to eliminate cyclic changes in estrogen/progesterone)
  1. Reduces pain c/w placebo
  2. No data as of 2000 to suggest that eradicates lesions or affects future fertility
  3. Specific meds
    1. Low-dose cyclic combined Oral Contraceptives--Usually first-line in mild-moderate disease
      1. Can skip the placebo pills at the end of the cycle to avoid menses altogether
    2. Long-acting progestins, e.g. depo-Medroxyprogesterone--anovulation/amenorrhea can persist months after stopping tx.
      1. Comparisons of tx: 80 women with laparoscopically confirmed endometriosis and mod-severe pelvic pain randomized (open-label) to DMPA 150mg IM Q3mos OR ethinyl estradiol 20ug + desogestrel 0.15mg + danazol 50mg for 21d of each 28d cycle. Followed for 1y. Similar reductions in dyspareunia and nonmenstrual pain; greater reduction of menstrual pain in DMPA group (because of higher degree of amenorrhea!). At 1y, 72.5% of DMPA women satisfied with tx. vs 57.5% in danazol/OCP group.
    3. Danazol
      1. A synthetic steroid that inhibits midcycle FSH and LH surge by an unclear mechanism, causing low estrogen and progesterone levels and endometrial atrophy, creating pseudomenopausal state
      2. Patients may conceive on this medication and as it is potentially teratogenic, other contraception is important (can use along with OC's)
      3. Causes estrogen withdrawal sx: hot flashes, vasomotor sx, st gain, acne
      4. Start at 800mg Qd; can lower to 400-600 to limit side f/x
    4. GnRH agonist
      1. Prevent ovarian estrogen production
      2. Often used for no more than 6mos at a time in order to limit effects of hypoestrogenemia, e.g. loss of bone mineral density
      3. If used > 6mos, many experts recommend "adding back" low dose progestin, estrogen/progestin, or calcitonin; the former do not seem to limit efficacy of the GnRH agonist
    5. Anastrazole
      1. In an uncontrolled study in 18 women with surgically-documented endometriosis and pain despite medical treatment, anastrozole 1mg/d plus a continuous monophasic combined oral contraceptive to prevent bone loss, over 6mos, was associated with sig. reductions in pelvic pain  (Fertil. Steril. 84:300, 2005--JW)
  1. Surgical therapy
    1. Surgical tx ass'd with sig. reduction of sx during the first 6mos, but about 50% experience recurrence of sx by 1y
    2. No data as of 2000 on effect of surgical tx on long-term fertility
    3. No data as of 2000 on whether adjunctive medical tx increases effectiveness of surgical tx, EXCEPT for GnRH agonists, which reduced need for medical tx at 18mos f/u in one randomized study.
    4. Relative effectiveness of cautery or vaporization vs. excision of lesions is unknown
    5. If further pregnancy not desired, may include TAH-BSO (ovarian conservation ass'd with higher risk of recurrence of sx)
      1. Sx may recur even after TAH-BSO
      2. Traditionally, many have avoided or delayed Hormone Replacement Therapy after TAH-BSO for endometriosis in fear or stimulating recurrent disease; no data available on this issue as of 12/99; also no data on whether estrogen-only HRT is OK in pts with h/o endometriosis.
  1. Surgical vs. medical tx--No good data as of 2000 re: which is better for pain or maintenance of fertility
  2. Approach in the pt desiring pregnancy
  1. If infertile, tx with conserv. surg; chance of getting preg. depends on stage; in one series, 73% of mild, 56% of mod, 40% of severe cases got preg. <15mos post-surg.
  2. Consider having kids close together because endo. will grow between prenancies & lower chance of future conception
  1. Approach in asymptomatic pt dx'd incidentally--per ACOG, there is no evidene that tx of asymptomatic pts preserves fertility as of 12/99

(Source: ACOG Practice Bulletin #11, 12/99, and others)