//fpnotebook.com/
Endometriosis
Aka: Endometriosis
- Epidemiology
- Age at diagnosis: 20-40 years (peak Incidence age 25 to 29)
- Prevalence: 10-15% of women
- Prevalence in women with Pelvic Pain: 82%
- Prevalence in women with Infertility: 21%
- Eskenazi (1997) Obstet Gynecol Clin North Am 24:235 [PubMed]
- Pathophysiology: Ectopic Endometrial Tissue implant Sites
- Ovary (50%)
- Uterosacral ligaments
- Rectovaginal septum
- Sigmoid colon
- Serosal surface of
- Uterus or fallopian Tubes
- Cervix, Vagina or vulva
- Bladder
- Distant intrapelvic or low Abdominal Sites
- Appendix or Ileum
- Abdominal scars
- Umbilicus
- Ureter
- Distant extrapelvic sites (rare)
- Diaphragm, Pleura, or Lungs
- Spleen
- Gallbladder
- Kidney
- Pathophysiology: Theories of etiology
- Implantation during Menstruation (Sampson)
- Most accepted theory
- Endometrial cells spread via tube to peritoneum
- Retrograde flow
- Retrograde flow likely occurs in most women but at higher volumes in those with Endometriosis
- Implantation more likely in the presence of the plasminogen activator inhibitor gene
- Vascular and lymphatic spread (Halban)
- Associated with abdominal surgery
- Would explain distant spread to organs such as lung
- Metaplasia (Meyer)
- Coelomic epithelium differentiates into endometrium
- Decreased Cellular Immunity (Dmowski)
- Risk Factors: More days of menstrual flow
- Early Menarche
- Late Menopause
- Nulliparity
- Mullerian abnormalities
- Low Body Mass Index
- Mother or sister with Endometriosis (Odds Ratio 7.2)
- Menstrual flow 6 or more days (Odds Ratio 2.5)
- Menstrual Cycle <28 days (Odds Ratio 2.1)
- References
- Mounsey (2006) Am Fam Physician 74:594-602 [PubMed]
- Symptoms
- Asymptomatic in 25-30% of women with Endometriosis
- Chronic Pelvic Pain (70%, Odds Ration 5.2)
- Dysmenorrhea (71%, Odds Ratio 8.1)
- Cyclic
- Progressively increasing in severity
- Affects bilateral lower Abdomen
- Associated with sense of rectal pressure
- Refractory to anti-prostaglandins
- Dyspareunia (44%, Odds Ration 6.8)
- Infertility (15-20%, Odds Ratio 8.2)
- Ovarian Cysts (Odds Ratio 7.3)
- Painful Defecation (Dyschezia)
- Premenstrual spotting
- Heavy Menstrual Bleeding
- Suprapubic Pain
- Dysuria
- Hematuria
- Constipation
- Signs: Pelvic exam
- Tender, nodular uterosacral ligaments (pathognomonic for Endometriosis)
- Fixed uterine retroversion
- Types: Presentations
- Endometrial implantation
- Ectopic tissue lies superficially on peritoneum
- Endometriomas (chocolate cysts)
- Edometrial lined Ovarian Cysts
- Endometriotic Nodules
- Solid, complex mix of endometrium with fibromuscular and fatty tissue
- Localized between vagina and Rectum
- Diagnosis
- Precaution
- Endometriosis is a histologic diagnosis
- Presentations are often non-specific and associated with >10 years on average delay in formal diagnosis from symptom onset
- Laparoscopy
- Red, Brown or blue-black nodular implants
- Powder-burn spots
- Multiple, tiny, puckered hemorrhagic foci
- Ectopic tissue findings predictive factors for Endometriosis
- Implants >10 mm wide or >5 mm deep
- Implants with mixed coloration
- Implants in cul-de-sac, ovarian fossa, or utero-sacral ligaments
- References
- Stegmann (2008) Fertil Steril 89: 1632 [PubMed]
- Histology (confirms visual diagnosis)
- Hemosiderin-laden Macrophages
- Endometrial tissue (epithelium, glands, stroma) found in ectopic tissue samples
- Tests not recommended for diagnosis
- CA 125
- CA 19-9
- MRI Abdomen
- Imaging
- Trasvaginal Ultrasound
- Identifies retroperitoneal and uterosacral lesions
- Identifies cystic endometriomas (89% sensitivity, 91% Specificity)
- Misses peritoneal lesions
- Differential Diagnosis
- See Dysmenorrhea
- See Dyspareunia
- See Dysuria
- See Infertility
- See Pelvic Pain
- See Chronic Pelvic Pain
- Management: First Line
- Precautions
- First-line management listed below are directed to primary care providers
- GnRH are the best studied and most effective agents for Endometriosis
- GnRH (with add-back therapy) should be considered first-line therapy for specialist initiation
- Laparoscopy recommended initially
- Confirmation of diagnosis
- Especially if fertility desired
- Analgesics
- NSAIDs
- Oral Contraceptives
- Use for at least 3-4 months
- Norethindrone Acetate containing OCP may be preferred for Osteoporosis Management
- Desogestrel OCPs (moderate Progestin, low Estrogen)
- Desogen (monophasic, 30 mcg Ethinyl Estradiol)
- Ortho-Cept (monophasic, 30 mcg Ethinyl Estradiol)
- Mircette (monophasic with 20 mcg Ethinyl Estradiol)
- Cyclessa (triphasic with 25 mcg Ethinyl Estradiol)
- Progesterone
- Provera 20-30 mg daily for 2 months
- Depo Provera every 3 months
- Higher Incidence of adverse effects including Osteoporosis and weight gain risk
- Levonorgestrel IUD (Mirena IUD)
- High Dose Progesterone (not recommended)
- Unclear efficacy and safety
- Recent study suggests no benefit over standard dose
- Protocol
- Start: Depo Provera 150 mg IM q2 weeks for 4 doses
- Next: Depo Provera 150 mg IM monthly for 4 months
- Last Provera 30-50 mg for 4-6 months
- Management: Second Line
- Gonadotropin-releasing Hormone Agonist (GnRH agonist)
- Efficacy
- GnRH are the best studied and most effective agents for Endometriosis
- Up to 100% improvement for 6-12 months post-therapy
- Mechanism
- Initially stimulates LH and FSH release
- After 7 days, LH and FSH are depleted
- Ultimately results in pituitary GnRH receptor down-regulation
- Agents: Used for 6 months as initial course
- Leuprolide (Lupron)
- Dose: 3.75 mg injected every 4 weeks
- Goserelin (Zoladex)
- Implanted 3.6 mg SubQ for 6 months or
- Nafarelin (Synarel)
- Dose: 200 mcg intranasal twice daily for 6 month
- Buserelin
- Decapeptyl
- Adverse effects (most women are Hypoestrogenic at 8 weeks)
- Risk of Osteoporosis
- Initial Endometriosis symptom flare
- Use add-back therapy for most patients
- Maintains BMD and decreases hot flash symptoms
- Norethindrone Acetate (Aygestin) 5 mg orally daily
- Gonadotropin-Releasing Hormone antagonist (GnRH antagonist)
- Elagolix (Orilissa)
- Oral tablet taken 150 mg once daily, or if Dyspareunia, 200 mg twice daily ($870/month in 2019)
- Adverse effects include Menopause effects (Osteoporosis, Hot Flashes), Headaches, Insomnia
- Not associated with Endometriosis symptom flare (unlike GnRH agonists)
- Decreases efficacy of hormonal contraceptives (non-Hormonal Contraception is recommended)
- (2018) Presc Lett 25(10): 58 [PubMed]
- Ford (2019) Am Fam Physician 100(8): 503-4 [PubMed]
- Other hormonal agents
- Danazol (androgenic agent)
- Dose: 200-800 mg PO qd for 6 months
- Efficacy: Improvement in 55-93% of patients
- Adverse effects in up to 85% of patients
- Older, but effective agent
- Gestrinone (anti-Progestin agent)
- Dose: 2.5 mg PO bid for 6 months
- Norethindrone 2.5 mg PO and Premarin 0.625 mg PO qd
- Management: Surgical
- Laparoscopy for diagnosis and treatment
- Laser or electrocautery of implanted endometrium
- Ablate as much extopic endometrial tissue as possible for maximal pain relief
- Pain Management (unclear efficacy)
- Presacral neurectomy (midline pain)
- Laparoscopic uterosacral nerve ablation (LUNA)
- Refractory cases
- Hysterectomy with oophorectomy and lesion ablation
- Endometriosis may still recur in up to 10% of cases
- Complications
- Infertility (50-60%)
- Catamenial Pneumothorax
- Minimal to no risk of malignancy
- However has been associated with clear cell and endometrioid Ovarian Cancer
- Resources
- Endometriosis Association
- http://www.endometriosisassn.org
- References
- Jensen (2012) Mayo POIM Conferences, Rochester
- Bulun (2009) N Engl J Med 360(3): 268-79 [PubMed]
- Mounsey (2006) Am Fam Physician 74:594-601 [PubMed]
- Schrager (2012) Am Fam Physician 87(2): 107-13 [PubMed]
- Vercellini (2003) Fertil Steril 80:560-3 [PubMed]
- Winkel (2003) Obstet Gynecol 102:397-408 [PubMed]