II. Epidemiology

  1. Age at diagnosis: 20-40 years (peak Incidence age 25 to 29)
  2. Prevalence: 10-15% of women
    1. Prevalence in women with Pelvic Pain: 82%
    2. Prevalence in women with Infertility: 21%
    3. Eskenazi (1997) Obstet Gynecol Clin North Am 24:235 [PubMed]

III. Pathophysiology: Ectopic Endometrial Tissue implant Sites

  1. Ovary (50%)
  2. Uterosacral ligaments
  3. Rectovaginal septum
  4. Sigmoid colon
  5. Serosal surface of
    1. Uterus or fallopian Tubes
    2. Cervix, Vagina or vulva
    3. Bladder
  6. Distant intrapelvic or low Abdominal Sites
    1. Appendix or Ileum
    2. Abdominal scars
    3. Umbilicus
    4. Ureter
  7. Distant extrapelvic sites (rare)
    1. Diaphragm, Pleura, or Lungs
    2. Spleen
    3. Gallbladder
    4. Kidney

IV. Pathophysiology: Theories of etiology

  1. Implantation during Menstruation (Sampson)
    1. Most accepted theory
    2. Endometrial cells spread via tube to peritoneum
    3. Retrograde flow
      1. Retrograde flow likely occurs in most women but at higher volumes in those with Endometriosis
      2. Implantation more likely in the presence of the plasminogen activator inhibitor gene
  2. Vascular and lymphatic spread (Halban)
    1. Associated with abdominal surgery
    2. Would explain distant spread to organs such as lung
  3. Metaplasia (Meyer)
    1. Coelomic epithelium differentiates into endometrium
  4. Decreased Cellular Immunity (Dmowski)

V. Risk Factors: More days of menstrual flow

  1. Early Menarche
  2. Late Menopause
  3. Nulliparity
  4. Mullerian abnormalities
  5. Low Body Mass Index
  6. Mother or sister with Endometriosis (Odds Ratio 7.2)
  7. Menstrual flow 6 or more days (Odds Ratio 2.5)
  8. Menstrual Cycle <28 days (Odds Ratio 2.1)
  9. References
    1. Mounsey (2006) Am Fam Physician 74:594-602 [PubMed]

VI. Symptoms

  1. Asymptomatic in 25-30% of women with Endometriosis
  2. Chronic Pelvic Pain (70%, Odds Ration 5.2)
  3. Dysmenorrhea (71%, Odds Ratio 8.1)
    1. Cyclic
    2. Progressively increasing in severity
    3. Affects bilateral lower Abdomen
    4. Associated with sense of rectal pressure
    5. Refractory to anti-Prostaglandins
  4. Dyspareunia (44%, Odds Ration 6.8)
  5. Infertility (15-20%, Odds Ratio 8.2)
  6. Ovarian Cysts (Odds Ratio 7.3)
  7. Painful Defecation (Dyschezia)
  8. Premenstrual spotting
  9. Heavy Menstrual Bleeding
  10. Suprapubic Pain
  11. Dysuria
  12. Hematuria
  13. Constipation

VII. Signs: Pelvic exam

  1. Tender, nodular uterosacral ligaments (pathognomonic for Endometriosis)
  2. Fixed uterine retroversion

VIII. Types: Presentations

  1. Endometrial implantation
    1. Ectopic tissue lies superficially on peritoneum
  2. Endometriomas (chocolate cysts)
    1. Edometrial lined Ovarian Cysts
  3. Endometriotic Nodules
    1. Solid, complex mix of endometrium with fibromuscular and fatty tissue
    2. Localized between vagina and Rectum

IX. Diagnosis

  1. Precaution
    1. Endometriosis is a histologic diagnosis
    2. Presentations are often non-specific and associated with >10 years on average delay in formal diagnosis from symptom onset
  2. Laparoscopy
    1. Red, Brown or blue-black nodular implants
    2. Powder-burn spots
      1. Multiple, tiny, puckered hemorrhagic foci
    3. Ectopic tissue findings predictive factors for Endometriosis
      1. Implants >10 mm wide or >5 mm deep
      2. Implants with mixed coloration
      3. Implants in cul-de-sac, ovarian fossa, or utero-sacral ligaments
    4. References
      1. Stegmann (2008) Fertil Steril 89: 1632 [PubMed]
  3. Histology (confirms visual diagnosis)
    1. Hemosiderin-laden Macrophages
    2. Endometrial tissue (epithelium, glands, stroma) found in ectopic tissue samples
  4. Tests not recommended for diagnosis
    1. CA 125
    2. CA 19-9
    3. MRI Abdomen

X. Imaging

  1. Trasvaginal Ultrasound
    1. Identifies retroperitoneal and uterosacral lesions
    2. Identifies cystic endometriomas (89% sensitivity, 91% Specificity)
    3. Misses peritoneal lesions

XI. Differential Diagnosis

XII. Management: First Line

  1. Precautions
    1. First-line management listed below are directed to primary care providers
      1. GnRH are the best studied and most effective agents for Endometriosis
      2. GnRH (with add-back therapy) should be considered first-line therapy for specialist initiation
    2. Laparoscopy recommended initially
      1. Confirmation of diagnosis
      2. Especially if fertility desired
  2. Analgesics
    1. NSAIDs
  3. Oral Contraceptives
    1. Use for at least 3-4 months
    2. Norethindrone Acetate containing OCP may be preferred for Osteoporosis Management
    3. Desogestrel OCPs (moderate Progestin, low Estrogen)
      1. Desogen (monophasic, 30 mcg Ethinyl Estradiol)
      2. Ortho-Cept (monophasic, 30 mcg Ethinyl Estradiol)
      3. Mircette (monophasic with 20 mcg Ethinyl Estradiol)
      4. Cyclessa (triphasic with 25 mcg Ethinyl Estradiol)
  4. Progesterone
    1. Provera 20-30 mg daily for 2 months
    2. Depo Provera every 3 months
      1. Higher Incidence of adverse effects including Osteoporosis and weight gain risk
    3. Levonorgestrel IUD (Mirena IUD)
  5. High Dose Progesterone (not recommended)
    1. Unclear efficacy and safety
    2. Recent study suggests no benefit over standard dose
    3. Protocol
      1. Start: Depo Provera 150 mg IM q2 weeks for 4 doses
      2. Next: Depo Provera 150 mg IM monthly for 4 months
      3. Last Provera 30-50 mg for 4-6 months

XIII. Management: Second Line

  1. Gonadotropin-releasing Hormone Agonist (GnRH agonist)
    1. Efficacy
      1. GnRH are the best studied and most effective agents for Endometriosis
      2. Up to 100% improvement for 6-12 months post-therapy
    2. Mechanism
      1. Initially stimulates LH and FSH release
      2. After 7 days, LH and FSH are depleted
      3. Ultimately results in pituitary GnRH receptor down-regulation
    3. Agents: Used for 6 months as initial course
      1. Leuprolide (Lupron)
        1. Dose: 3.75 mg injected every 4 weeks
      2. Goserelin (Zoladex)
        1. Implanted 3.6 mg SubQ for 6 months or
      3. Nafarelin (Synarel)
        1. Dose: 200 mcg intranasal twice daily for 6 month
      4. Buserelin
      5. Decapeptyl
    4. Adverse effects (most women are Hypoestrogenic at 8 weeks)
      1. Risk of Osteoporosis
      2. Initial Endometriosis symptom flare
      3. Use add-back therapy for most patients
        1. Maintains BMD and decreases hot flash symptoms
        2. Norethindrone Acetate (Aygestin) 5 mg orally daily
  2. Gonadotropin-Releasing Hormone antagonist (GnRH antagonist)
    1. Elagolix (Orilissa)
      1. Oral tablet taken 150 mg once daily, or if Dyspareunia, 200 mg twice daily ($870/month in 2019)
      2. Adverse effects include Menopause effects (Osteoporosis, Hot Flashes), Headaches, Insomnia
      3. Not associated with Endometriosis symptom flare (unlike GnRH agonists)
      4. Decreases efficacy of hormonal contraceptives (non-Hormonal Contraception is recommended)
      5. (2018) Presc Lett 25(10): 58 [PubMed]
      6. Ford (2019) Am Fam Physician 100(8): 503-4 [PubMed]
  3. Other hormonal agents
    1. Danazol (androgenic agent)
      1. Dose: 200-800 mg PO qd for 6 months
      2. Efficacy: Improvement in 55-93% of patients
      3. Adverse effects in up to 85% of patients
      4. Older, but effective agent
    2. Gestrinone (anti-Progestin agent)
      1. Dose: 2.5 mg PO bid for 6 months
    3. Norethindrone 2.5 mg PO and Premarin 0.625 mg PO qd

XIV. Management: Surgical

  1. Laparoscopy for diagnosis and treatment
    1. Laser or electrocautery of implanted endometrium
    2. Ablate as much extopic endometrial tissue as possible for maximal pain relief
  2. Pain Management (unclear efficacy)
    1. Presacral neurectomy (midline pain)
    2. Laparoscopic uterosacral nerve ablation (LUNA)
  3. Refractory cases
    1. Hysterectomy with oophorectomy and lesion ablation
      1. Endometriosis may still recur in up to 10% of cases

XV. Complications

  1. Infertility (50-60%)
  2. Catamenial Pneumothorax
  3. Minimal to no risk of malignancy
    1. However has been associated with clear cell and endometrioid Ovarian Cancer

XVI. Resources

  1. Endometriosis Association
    1. http://www.endometriosisassn.org

Images: Related links to external sites (from Bing)

Related Studies

Ontology: Endometriosis (C0014175)

Definition (CHV) a condition where uterine tissues are found outside the uterus
Definition (CHV) a condition where uterine tissues are found outside the uterus
Definition (CHV) a condition where uterine tissues are found outside the uterus
Definition (MEDLINEPLUS)

Endometriosis is a problem affecting a woman's uterus - the place where a baby grows when she's pregnant. Endometriosis is when the kind of tissue that normally lines the uterus grows somewhere else. It can grow on the ovaries, behind the uterus or on the bowels or bladder. Rarely, it grows in other parts of the body.

This "misplaced" tissue can cause pain, infertility, and very heavy periods. The pain is usually in the abdomen, lower back or pelvic areas. Some women have no symptoms at all. Having trouble getting pregnant may be the first sign.

The cause of endometriosis is not known. Pain medicines and hormones often help. Severe cases may need surgery. There are also treatments to improve fertility in women with endometriosis.

Definition (NCI_NCI-GLOSS) A benign condition in which tissue that looks like endometrial tissue grows in abnormal places in the abdomen.
Definition (NCI) The growth of functional endometrial tissue in anatomic sites outside the uterine body. It most often occurs in the pelvic organs.
Definition (MSH) A condition in which functional endometrial tissue is present outside the UTERUS. It is often confined to the PELVIS involving the OVARY, the ligaments, cul-de-sac, and the uterovesical peritoneum.
Definition (CSP) condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity.
Concepts Disease or Syndrome (T047)
MSH D004715
ICD9 617.9, 617
ICD10 N80 , N80.9
SnomedCT 11871002, 266588002, 198246007, 155988000, 198259004, 103677003, 396224008, 129103003
English Endometrioses, ENDOMETRIOSIS, Endometriosis, site unspecified, Endometriosis, unspecified, endometriosis (diagnosis), endometriosis, Endometriosis NOS, Endometriosis [Disease/Finding], displacement of the endometrial tissue, endometrioses, Endo, Endometriosis, Endometriosis NOS (disorder), Endometriosis (clinical), Endometriosis (disorder), Endometriosis (morphologic abnormality), Endometriosis, NOS, Endometriosis -RETIRED-
French ENDOMETRIOSE, Endométriose, site non précisé, Endométriose
Portuguese ENDOMETRIOSE, Endometriose de local NE, Endometriose
Spanish ENDOMETRIOSIS, Endometriosis, localización no especificada, endometriosis (clínica), endometriosis (trastorno clínico), endometriosis - RETIRADO - (concepto no activo), endometriosis, SAI, endometriosis - RETIRADO -, endometriosis, SAI (trastorno), endometriosis (anomalía morfológica), endometriosis (trastorno), endometriosis, Endometriosis
German ENDOMETRIOSE, Endometriose, Stelle unspezifisch, Endometriose, nicht naeher bezeichnet, Endometriose
Dutch endometriose, plaats niet-gespecificeerd, Endometriose, niet gespecificeerd, endometriose, Endometriose
Italian Endometriosi, sede non specificata, Endometriosi
Japanese 子宮内膜症, 子宮内膜症、部位不明, シキュウナイマクショウブイフメイ, シキュウナイマクショウ
Swedish Endometrios
Czech endometrióza, Endometrióza, Endometrióza, blíže neurčená lokalizace
Finnish Endometrioosi
Korean 자궁내막증, 상세불명의 자궁내막증
Polish Endometrioza, Gruczolistość macicy
Hungarian Endometriosis, Endometriosis nem meghatározott helyen
Norwegian Endometriose