Endometriosis: Symptoms, Diagnosis and Treatment

Definition and overview

Endometriosis is define as the presence of endometrial tissue (glands and stroma) outside of the uterine cavity.

Endometriosis is a hormonally dependent disease. Estrogen has been definitively established as having a causative role in the development of endometriosis.

It classically presents in nulliparous infertile women in their 30s. However, it may occur at earlier ages (childhood and adolescents) and in such cases its associated with obstructive genital anomalies.

• Following menopause, it regresses unless estrogen is prescribed. 5% of new cases develop in that age group.

Its estimated that 5-15% of women have some degree of the disease. Its been noted in 5-15% of women undergoing gynaecological laparotomies (an unexpected finding in 50% of these cases).

Site

Endometriosis can occur anywhere in body including abdominal wall, lung, pleura, brain, and arm. Most commonly found in the dependant portions of the pelvis

• M/C sites is Ovaries (2 out of 3 women with endometriosis)
• 2nd M/C sites is Pouch of Douglas
• Laparotomy scars especially after C section or myomectomy or after the uterine cavity, also has been entered.

Risk Factors 

1. Family history (7–10 fold increased risk if affected 1st degree relative)
2. Obstructive anomalies of genital tract (earlier onset)
3. Nulliparity 
4. Regular menstrual cycle <27 days. 
5. Prolonged menses of 8 or more days.
6. High socioeconomic status due to late marriage and late childbirth
7. In utero exposure to DES 
8. Hormone – estrogen dependant condition

Protective Factors: Regular exercise, Smoking, Pregnancy

Pathogenesis of disease

Pathogenesis is not fully understood. However; several hypotheses have been used to explain the various manifestations of the disease and its various locations

1. The retrograde menstruation theory of Sampson: Endometriosis occurs as a result of reflux of menstrual endometrium through the fallopian tubes and its subsequent implantation and growth on pelvic peritoneum and surrounding structures
2. The mullarian metaplasia theory of Meyer: Endometriosis arises as a result of metaplastic changes in embryonal cell rests of embryonic mesothelium, which are capable of responding to hormone stimulation
3. The lymphatic spread theory of Halban: Explains occurrence of endometriosis at less accessible sites like umblicus, pelvic nodes, ureter, etc. The theory suggests embolization of menstrual fragments occurs through vascular or lymphatic channels. This leads to launching of endometriosis at distant sites
4. The hematogenous spread theory: The theory proposes that an endogenous (undefined) biochemical factor can induce undifferentiated peritoneal cells to develop into endometrial tissue

Clinical Features & Classification of endometriosis

Endometriosis is classified according to a scoring system standardized by the American Society for Reproductive Medicine

1. Minimal: Isolated superficial disease on peritoneal surface. 
2. Mild: Superficial multiple implants < 5 cms with no significant adhesions.
3. Moderate: Multifocal disease, both superficial and invasive and associated with adhesions in tube and/or ovaries.
4. Severe: Multifocal disease like in moderate cases along with large ovarian endometriomas and adhesions in tube, ovaries, and cul de sac

Peritoneum 

• Earliest lesion is red petechial lesion later becoming cystic, dark brown or blue black in appearance called as powder-burn appearance/ gunshot appearance
• Presence of defects in peritoneum (usually scarring overlying implants) is called as Allen-Masters syndrome

Peritoneal cavity: Contains yellowish brown fluid which has prostaglandin responsible for pain of endometriosis

Ovary 

• Characteristic chocolate cyst (True cyst with columnar lining epithelium. This characteristic fluid represents aged, haemolysed blood and desquamated epithelium.
• The glands and stroma lining the cyst’s wall may be destroyed due to an increase in pressure. This leaves behind a fibrotic wall with infiltrating haemosiderin layden macrophages.

Endometriosis of ovary is called as endometrioma

Clinical Features

Classic triad of endometriosis: Dysmenorrhea, Infertility, Dyspareunia
There is little correlation, between the extent of disease & symptomatology; pain coincides with the depth of the lesion

Female reproductive tract:

1. May be asymptomatic.
2. M/C symptom is secondary dysmenorrhea commencing after 30 years and gradually increasing
3. Dyspareunia occurs when pouch of douglas and rectovaginal septum are involved
4. Deep-seated pelvic pain 
5. low sacral backpain (especially premenstually).
6. Ovulatory pain and mid-cycle vaginal bleeding.
7. Premenstrual and postmenstrual spotting
8. Infertility: 30–40% of patients with endometriosis will be infertile. 15–30% of those who are infertile will have endometriosis

Other 

1. If the Bladder is involved: Cyclic hematuria/ dysuria, ureteric obstruction.
2. If the rectosigmoid colon is involved: premenstrual tensmus or diarrhea, obstruction.
3. Lung: Cyclical haemoptysis، Haemopneumothorax
4. Surgical scars/umbilicus: Cyclical pain and bleeding

Examination Findings 

1. Fixed retroversion of uterus 
2. Firm fixed adnexal mass (endometrioma) 
3. Tender nodularity of uterine ligaments and cul-de-sac felt on rectovaginal examination
4. Episiotomy or cesarean section scars.

Diagnosis & Management

Suspected in afebrile patient with the characteristic triad:

1. Pelvic pain 
2. Firm, fixed tender adnexal mass
3. Tender nodularity in cul-de-sac and uterosacral ligament

Investigation of choice in endometriosis—Laparoscopy

Gold standard: Histo pathological examination 

• Macroscopical appearance: ‘’Classic’’ are red, dark brown, dark blue or black peritoneal implants
• Newer implants: red, blood filled active lesions
• Older lesions: scarred with a puckered appearance.

Others 

• CA-125-CA-125 levels are raised in endometriosis. Sensitivity only 20% to 30%. Not used to diagnose endometriosis
• Monocyte chemotatic protein (MCP–1) levels are rised in peritoneal fluid of women with endometriosis

Unfortunately, even the most experienced surgoen may fail to identify endometriosis implants because:

• The older implants may have a very subtle apperance
• The deeper infiltration lesions may not be visible at the surface

Biopsy of suspecious lesions improves diagnosis accuracy - Microscopically: 2 out of 4 must be present in the biopsied specimen to confirm Dx 

1. Endometrial epithelium 
2. Endometrial glands 
3. Endometrial stroma 
4. Hemosiderin laden macrophages

Treatment

Treatment is justified in all patients regardless of clinical profile as endometriosis progresses in 30–60% patient’s within an year of diagnosis. 

No treatment: If small symptom less lesions 

• Patient observed & examined every 6 months

Non-hormonal treatment: If small lesions with mild symptoms

• Analgesics are given for pain: NSAIDs (if only pain) 
• Prostaglandin inhibitors (naproxen, ibuprofen) are given for pain and menorrhagia

Hormonal treatment: 

Pseudo pregnancy: Ovulation and menstruation are inhibited for 9 months (6-18 months) using a combined OCP or a progestogen alone to avoid the oestrogenic side effects

• Oral medroxyprogesterone acetate (provera tablets) is givin in a dose of 1030 mg daily

Pseudo menopause

1. Danazol: Weak synthetic androgen. given orally 400-800 mg/day for 6-9 months. 
2. GnRH (agonist): Nafarelin (synarel), Goserelin (zoladex), Triptorelin (decapeptyl)
3. Mifepristone 50 mg/day for 6 months

Indications for Hormonal treatment

1. Severe symptoms with small pelvis lesions
2. Recurrence of symptoms after conservative surgery
3. May be given for a short time (6-12 weeks) before surgery to make dissection easier
4. After conservative surgery to allow any residual lesion to regress
5. When operation is contraindicated or refused by the patient

Surgical treatment

Surgery-Done only if medical management fails. Endometriosis of ovary, i.e. endometrioma, bladder and bowel cannot be managed medically & should be managed surgically

Conservative surgery

• If young patients below 40 years 
• Pre-sacral neurectomy has been used to treat severe dysmenorrhea
• Minimal to mild disease – can be removed by laser or electrocautery

Radical surgery

• Patient above 40 years 
• Treatment is total hysterectomy & bilateral salpingo-oophorectomy

Radiological treatment

• Induction of artificial menopause by external pelvic radiation cures the condition by causing atrophy of endometrial tissue
• It is applied only in patients above 40 in whom operation can’t be done as in case of wide spread pelvic endometriosis (frozen pelvis) or endometriosis of the rectovaginal septum which is difficult to excise surgically