Endometriosis

Endometriosis is the presence of endometrial glands and stroma outside the normal location, excluding adenomyosis. It is a hormonally dependent disease, and therefore commonly presents as cyclical pelvic pain. Prevents chiefly in women of reproductive age. Should be considered as a differential in a pt presenting with ongoing pelvic pain and infertility/subfertility. Sx may overlap with adenomyosis. Tx depends on specific sx, severity, location, and desire for future fertility.

Prevalence of 2-10%. More common in East Asians > whites > blacks.

• Risk factors
  • Familial clustering (Increased incidence in first-degree relatives)
  • Genetic mutations/polymorphisms (some gene mutation candidates have been considered as risk factors – PTEN, EMX2)
  • Anatomic defects (increased incidence w/ outflow tract obstruction)
  • Nulliparity
  • Early menarche
  • Late menopause
  • Short menstrual cycle (< 27 days)
  • Menorrhagia (> 1 week)
  • Other environmental factors
    • TCDD/Dioxins (industrial pollutants)
    • Caffeine
    • Alcohol use
• Protective factors
  • Regular exercise
  • High parity
  • Longer duration of lactation
• Theories behind the cause of endometriosis
  • Retrograde menstruation: dissemination of endometrial fragments into the peritoneal cavity d/t uterine hyperperistalsis/dysperistalsis. Explains endometriosis in women with outflow obstruction.
  • Lymphatic/vascular spread: theory behind spread into weird tissues e.g. implants behind the eye
  • Coelomic metaplasia (Meyer’s theroy): suggests that the parietal peritoneum is pluripotent and can transform into endometrial tissue. Explains why some men can get endometriosis (chronic pelvic pain with Hx of hyperestrogenism)
  • Induction theory: exposure to estrogen induces tranformation of certain tissues into endometrial-like tissue. Ovarian surface epithelium can transform into endometrial like-tissue.
  • Immune dysfunction: very complex…
• Pathophysiology
  • Regardless of location of endometrial tissue it responds to the normal hormonal cycle resulting in:
    • Production of inflammatory and pain mediators
    • Infertility
    • Nerve dysfunction
  • There is increased prostaglandin and oestrogen formation leading to chronic inflammation (IL 1, IL6, IL 8, TNF alpha all play a role) = PAIN
  • Premenstruation – the tissue is stimulated to grow by progesterone and oestrogen. They enlarge and undergo secretory changes and bleeding.
  • However, surrounding tissues prevent expansion and enlargement of the hemorrhagic fluid causing an increase in pressure = PAIN
  • Severe pain is seen in cases where there are deeply infiltrating lesions.
• Signs and symptoms
  • Chronic Pelvic pain (severity correlated with depth of invasion)
    • Localized
    • Radiating to the upper back or leg
  • Pain Sx (chronic or cyclical, or cyclical superimposed on chronic)
    • Dysmenorrhoea (pain precedes menses by 24-48H, Less responsive to NSAIDs and COCs)
    • Dyspareunia (partly caused by implants in the uterosacral ligament)
    • Dysuria (associated with cyclical frequency and urgency)
    • Defecatory pain
  • Infertility/subfertility (d/t disruption of tubo-ovarian structure, or implants in ovaries)
  • Sx of intestinal obstruction
  • Sx of urethral obstruction
    • Urgency
    • Frequency
    • Can progress to post-renal failure
• Physical exam
  • Visual inspection
    • Normal
  • Speculum exam
    • Normal
    • Occasional blue or powder-burn red lesions which bleed easily
  • Bimanual exam (variable)
    • Uterosacral nodularity and tenderness
    • Fixed retroverted uterus
    • Enlarged cystic adnexal mass
    • Fixed, firm posterior cul-de-sac
• Gynaecologic differentials
  • Pelvic inflammatory disease (TOA, Sapingitis, Endometritis): Hx HOB and other infectious sx, Hx of untreated STDs
  • Hemorrhagic ovarian cyst
  • Ovarian torsion
  • Primary dysmenorrhea
  • Degenerating leiomyoma
  • Ectopic pregnancy
• Investigations
  • Labs
    • CBC
    • Urine hCG
    • Urinalysis + culture
    • Vaginal/Cervical culture
  • Imaging
    • Transvaginal ultrasound
      • Uterine is not enlarged (generally, unlike adenomyosis)
      • Chocolate cysts
      • Nodules
    • CT, MRI
  • Diagnostic laparoscopy: definitive dx
• Medical Treatment
  • NSAIDS (Ibruprofen, Naproxen): First-line Tx for primary dysmenorrhoea, pelvic pain prior to laparoscopy, or confirmed endometriosis w/mild sx
  • Combined oral contraceptives (COCs)
  • Progestins
    • DMPA (decreases BMD)
    • Norethindrone acetate (very effective with Leuprolide)
    • Levonorgestrel IUD (Mirena)
    • Ulipristal acetate(Ella)
    • Mifepristone (off-label)
    • Norethisterone
  • Androgens (Danazol, Gestrinone; have a significant adverse effect profile)
  • GnRH agonists (Leuprolide, Goserelin, Nafarelin)
  • Aromatase inhibitors (Anastrozole, Letrozole; second-line tx)
• Surgical Treatment
  • Lesion ablation w/ adhesiolysis
  • Endometrioma resection
  • Presacral neurectomy
  • Hysterectomy w/ BSO: most definitive surgical tx. Considered in women who are done bearing children.