What is endometriosis?• Endometriosis is defined as the presence of endometrial-like tissue outside the uterus, which induces a chronic, inflammatory reaction. The condition is predominantly found in women of reproductive age, from all ethnic and social groups
Endometriosis - Symptoms• ● severe dysmenorrhoea• ● deep dyspareunia• ● chronic pelvic pain• ● ovulation pain• ● cyclical or perimenstrual symptoms, such as bowel or bladder, with or without abnormal bleeding or• pain• ● infertility• ● chronic fatigue• ● dyschezia (pain on defaecation).
Localisation and appearance of endometriosis• pelvic organs and peritoneum, although other parts of the body such as the bowel or lungs are occasionally affected.• ‘powder-burn’ or ‘gunshot’ lesions on the ovaries, serosal surfaces and peritoneum: black, dark-brown or bluish puckered lesions, nodules or small cysts containing old haemorrhage surrounded by a variable extent of fibrosis
• Atypical or ‘subtle’ lesions are also common,• including red implants (petechial, vesicular, polypoid, hemorrhagic, red flame-like) and serous or clear vesicles. Other appearances include white plaques or scarring and yellow-brown peritoneal discoloration of the peritoneum.
Surgically, endometriosis can be staged I–IV (Revised Classification of the American Society• Stage I (Minimal) Findings restricted to only superficial lesions and possibly a few filmy adhesion• Stage II (Mild) In addition, some deep lesions are present in the cul de sac
• Stage III (Moderate) As above, plus presence of endometriomas on the ovary and more adhesions.• Stage IV (Severe) As above, plus large endometriomas, extensive adhesions. Endometrioma on the ovary of any significant size (Approx. 2 cm +) must be removed surgically because hormonal treatment alone will not remove the full endometrioma cyst, which can progress to acute pain from the rupturing of the cyst and internal bleeding
Classification of Endometriosis Stage I (Minimal) Stage II (Mild)4* 9 Stage III (Moderate) Stage IV (Severe)29 114 * Revised AFS Score
Endometriosis – Physical Exam• Uterosacral nodularity• Adnexal mass (endometrioma)• Normal exam
Endometriosis - Incidence• 7-10% of general population• 20-50% of infertile women• 70-85% in women w/ CPP• No racial predisposition• +Familial association with almost 10x increased risk of endometriosis if affected 1 st degree relative
Endometriosis - Pathogenesis• Retrograde menstruation (Sampson’s theory) - Monkey experiments – sutured cervix closed to create outflow obstruction caused development of endometriosis - Clinical observation of retrograde menstrual flow during laparoscopy in humans - Increased risk of endometriosis in women with cervical/vaginal atresia, other outflow obstruction - Increased risk with early menarche, longer and heavier flow - Decreased risk with decreased estrogen levels e.g. exercise-induced menstrual disorders, decreased body fat, + tobacco use
Endometriosis - Pathogenesis• Hematogenous or lymphatic spread - Endometriosis found in remote sites – lung, nose, spinal cord, pelvic lymph nodes.
Endometriosis - Pathogenesis• Coelomic metaplasia - Mullerian ducts are derived from coelomic epithelium during fetal development - Hypothesize that coelomic epithelium retains ability for multipotential development - Endometriosis seen in prepubertal girls, women w/ congenital absence of the uterus, and RARELY in men
Endometriosis - Pathogenesis• Iatrogenic dissemination - Endometriosis has been found in cesarean section scar• Immunologic defects• Genetic predisposition - polygenic, multi-factorial
Endometriosis - Diagnosis• For a definitive diagnosis of endometriosis, visual inspection of the pelvis at laparoscopy is the gold standard investigation, unless disease is visible in the posterior vaginal fornix or elsewhere• Good surgical practice is to use an instrument such as a grasper, via a secondary port, to mobilise the pelvic organs and to palpate lesions, which can help determine their nodularity
Endometriosis - Diagnosis• Laparoscopy with biopsy proven histologic diagnosis – standard for dx of endometriosis - Extent of visible lesions do not correlate with severity of sx, but depth of infiltration of lesions seems to correlate best with pain severity
• Laparoscopy with biopsy proven histologic diagnosis – standard for dx of endometriosis• Positive histology confirms the diagnosis of endometriosis; negative histology does not exclude it• Empiric medical treatment with improvement in symptoms• CA 125 – NOT considered to be of clinical utility• Imaging – US, MRI, CT – only useful in the presence of pelvic or adnexal masses (endometriomas)
Medical Treatment Progestin Ovary Estrogen EndometriosisOral contraceptives TissueDanazolGnRH agonists
COCP• COCPs act by ovarian suppression and continuous progestin administration. Initially, a trial of continuous or cyclic• Continuous noncyclical administration of COCPs, omitting the placebo menstrual tablets, for 3-4 months helps avoid any menstruation and associated pain.• Women with endometriosis are at increased risk of epithelial ovarian cancer, and COCPs are believed to protect against this.• Eg: MARVELON
Progestational agents• All progestational agents act by decidualization and atrophy of the endometrium.• Medroxyprogesterone acetate has proven efficacy in pain suppression in both the oral and injectable depot preparations. Oral doses of 10-20 mg/d can be administered continuously. The time to resumption of ovulation is longer and variable with depot preparations. Adverse effects include weight gain, fluid retention, depression, and breakthrough bleeding.• The levonorgestrel intrauterine system (LNG-IUS) has been shown to reduce endometriosis-associated pain. It has been found to reduce the recurrence of dysmenorrhea by 35%
Danazol• Danazol acts by inhibiting the midcycle follicle-stimulating hormone (FSH) and luteinizing hormone (LH) surges and preventing steroidogenesis in the corpus luteum. It is the most extensively studied agent for endometriosis.• The recommended dose is 600-800 mg/d. However, smaller doses have been used with success.
GnRH Analogs• GnRH analogues produce a hypogonadotrophic- hypogonadic state by downregulation of the pituitary gland. Ie Leucrin ( 3.75mg monthy or 11.25mg 3 monthly)• GnRH therapy may lead to improvement in pain associated with endometriosis in 85-100% of women. Furthermore, the pain relief is believed to persist for 6-12 months after cessation of treatment.Treatment is usually restricted to monthly injections for 6 months. Loss of trabecular bone density caused by GnRH is restored by 2 years after cessation of therapy .Other prominent adverse effects include hot flashes and vaginal dryness
• Add-back therapy GnRH agonist treatment with GnRH agonist plus ‘add- back’ therapy (i.e. tibolone) for at least 6 months, bone mineral density was significantly• How long a GnRH agonist plus ‘add-back’ may safely be continued is unclear, but treatment for• up to 12 months with ‘add-back’ appears to be effective• and safe in terms of pain relief and bone mineral density protection.• consideration should be given to the use of GnRH agonists in women who may not have reached their maximum bone density.
Endometriosis – Treatment Considerations in Adolescents• If no improvement in symptoms after 3 months of empiric treatment with NSAIDs and OCPs, diagnostic laparoscopy should be offered
Endometriosis - SURGERY• Surgical care can be broadly classified as 1)conservative- preserve reproductive ability• 2)semiconservative- when reproductive ability is eliminated but ovarian function is retained• 3) Radical- when the uterus and ovaries are removed
Conservative surgery Aim- destroy visible endometriotic implants and lyse peritubal and periovarian adhesions that are a source of pain and may interfere with ovum transport.-laparoscopic drainage-laparoscopic cystectomy-laparoscopic ablation-LUNA-presacral neurectomy
Semiconservative Surgery• The indication for this semiconservative surgery is mainly in women who have completed their childbearing, are too young to undergo surgical menopause, and are debilitated by the symptoms.• Such surgery involves hysterectomy and cytoreduction of pelvic endometriosis
Radical Surgery• Radical surgery involves total hysterectomy with bilateral oophorectomy (TAH-BSO) and cytoreduction of visible endometriosis. Adhesiolysis is performed to restore mobility and normal intrapelvic organ relationships
Endometriosis - Treatment• Medications vs. Surgery - Lack of data to support surgery vs. medical treatment for tx of pain symptoms due to endometriosis - Starting with empiric medical therapy is appropriate - Offer GnRH agonist therapy if initial medical treatment with OCPs and NSAIDs not helping - Cost of comparing empiric medical management with definitive surgical diagnosis is difficult to assess, but 3 months of empiric treatment is less than a laparoscopic procedure
Endometriosis - Treatment• Medications vs. Surgery - Surgery is associated with significant decrease in pain sx during the 1st 6 months following surgery - Approximately 40% experience recurrent symptoms within 1 yr post-op - Cumulative 5-yr recurrence rate of pain sx after d/c GnRH tx is ~50%