Endometriosis

Question 1

Definition of endometriosis

Answer 1

Characterised by the growth of endometrium-like tissue outside the uterus. Endometriosis is hormone mediated and is associated with menstruation. The hormonal changes in the menstrual cycle induce bleeding, chronic inflammation and scar tissue formation.

Question 2

Where are endometriotic deposits most common

Answer 2

In the ovaries, uterosacral ligaments, pouch of Douglas, rectum and sigmoid colon, bladder.
Extrapelvic deposits are rare

Question 3

Prevalence of endometriosis

Answer 3

• One of the most common gynaecological disorders in women of reproductive age (second most common gynaecological condition after fibroids)
• Estimated prevalence of 1 in 10 women of reproductive age (prevalence is difficult to determine due to variability of presentation)

Question 4

Complications of endometriosis

Answer 4

• Endometriomas (ovarian cysts containing blood and endometriosis-like tissue)- if the ovaries are affected, endometriomas may develop (may rupture and affect fertility due to distortion of pelvic anatomy)
• Infertility, likely due to tubal adhesions
• Adhesion formation- may occur due to endometriosis itself or secondary to surgery or infection, may cause chronic pelvic pain
• Bowel obstruction- partial or complete bowel obstruction can occur due to adhesion formation
• Chronic pain and reduced QOL

There is a possible small increased risk of ovarian cancer in women with endometriosis

Question 5

Cause of endometriosis

Answer 5

The exact cause of endometriosis is unknown. May be a combination of factors:
* Retrograde menstruation- Endometrial cells flow backwards through the uterine cavity, through the fallopian tubes and implant on pelvic organ (but endometriosis can occur in women after hysterectomy or in men following oestrogen exposure)
* Lymphatic or circulatory dissemination
* Genetic predisposition
* Metaplasia- a process by which cells in the pelvic and abdominal area change into endometrial-type cells of the germinal epithelium
* Immune function- many women with endometriosis appear to have reduced immunity to other conditions
* Environmental factors- certain environmental toxins have been implicated (dioxin)

Question 6

Risk factors for endometriosis

Answer 6

Early menarche, late menopause, delayed childbearing, nulliparity, vaginal outflow obstruction, white, low BMI, AI disorders, late first coitus, smoking (factors increasing oestrogen exposure)

Question 7

Pathophysiology of endometriosis

Answer 7

• The endometrial tissue has oestrogen receptors so undergoes some proliferation, secretion and menstruation as normal cells. However, implanted cells contain high levels of aromatase, allowing them to produce their own oestrogen. They also release pro-inflammatory factors causing inflammation and scarring.
• The scar tissue can lead to adhesion formation.
• Additionally inflammation and oestrogen promote neovascularisation, whilst changes in hormone levels cause the implant to bleed, especially during menstruation.
• If the implant is on an ovary, it could form an endometrioma which contains the old, dark blood and shed tissue- rupture can cause pain and further inflammation
• Endometriomas also may develop mutations such as PTEN and ARIDIA which increases the risk of developing ovarian cancer.

Question 8

Presentation of endometriosis

Answer 8

Suspect endometriosis in women (including young women aged 17 years or younger) presenting with 1 or more of the following:
* Chronic pelvic pain (minimum of 6 months of cyclical or continuous pain)
* Period-related pain (dysmenorrhoea) affecting daily activities and quality of life
* Deep dyspareunia
* Period-related or cyclical GI symptoms, in particular painful bowel movements
* Period-related or cyclical urinary symptoms, in particular blood in the urine or pain passing urine
* Infertility in associated with one of these symptoms

Endometriosis may be asymptomatic (do not exclude endometriosis if abdominal or pelvic examination is normal)

O/E: Reduced organ mobility and enlargement, tender nodularity in the posterior vaginal fornix, visible vaginal endometriotic lesions, visible vaginal lesions may be seen.

Question 9

Endometriosis symptoms by site of implantation

Answer 9

Question 10

Investigations for endometriosis

Answer 10

• Pain and symptom diary
• Abdominal and pelvic examination + speculum
• TVUSS- May reveal large endometriosis and chocolate cysts. USS is unreliable in patients with endometriosis-but may reveal ovarian and rectal disease. Negative scans do not exclude diagnosis. May reveal ‘kissing ovaries’- where bilateral endometrioma are adherent together
• MRI pelvis- assessment of the extent of disease
• Laparoscopy is the gold standard to diagnose abdominal and pelvic endometriosis. A definitive diagnosis can be established with a biopsy and histology of the lesions during laparoscopy (is also therapeutic)
• Lesions may be: Red, puckered, black ‘match-stick’, white fibrous, chocolate cysts
• Should not use measurement of biomarkers in endometrial tissue, blood, menstrual or uterine fluids to diagnose endometriosis (e.g CA-125)

Question 11

Differentials for endometriosis

Answer 11

• Uterine conditions, such as adenomyosis or uterine fibroids (lower abdominal pain and HMB), primary dysmenorrhoea, uterine myoma (usually asymptomatic, but may present with heavy and/or irregular bleeding- enlarged nodular mass)
• Urological conditions- Interstitial cystitis (primarily bladder related symptoms), recurrent UTI
• Gynaecological conditions- PID (not associated with menstruation), benign ovarian cyst, ovarian cancer, pregnancy
• GI conditions- IBS, IBD, chronic constipation, appendicitis, gastroeneteritis, coeliac disease

Question 12

How can endometriosis be staged, what are its limitations

Answer 12

Use the American Society of Reproductive Medicine (ASRM)
o Stage 1- small superficial lesions
o Stage 2- mild, but deeper lesions than stage 1
o Stage 3- deeper lesions, with lesions on the ovaries and mild adhesions
o Stage 4- deep and large adhesions affecting the ovaries with extensive adhesions

NOT used in the NICE guidelines since it does not correlate well with symptom severity

Question 13

When should a woman with endometriosis be referred to gynae

Answer 13

• Consider the need for referral to gynaecology for USS if the woman has severe, persistent or recurrent symptoms of endometriosis, or pelvic signs
• Refer to a specialist endometriosis service (endometriosis centre) if the woman has suspected deep endometriosis involving the bowel, bladder, or ureter
• Refer young women (17 years or longer) to paediatric or adolescent gynaecology service

Question 14

What treatment options are tehre for endometriosis in primary care

Answer 14

Management of endometriosis-related pain:
* Consider a short trial (e.g 3 months) of paracetamol and/or an NSAID for first-line management of pain
* Offer hormonal treatment, for example with a COCP (tricycled) or Nexplanon, LNG-IUS, Depot-Provera
* Hormonal treatment can reduce endometriosis-related pain and has no permanent negative effect on subsequent fertility
* Do not offer hormonal treatment to women trying to conceive
* 2nd line- GnRH agonists (e.g Leuprorelin) or antagonists:
* Effective at relieving the severity and symptoms of endometriosis- usually administered as slow-release depot formulas (lasting 1 month or more)
* Should not be used for >6 months due to the risk of osteoperosis
* Can use neuromodulators (gabapentin, pregabalin, duloxetine)

Offer fertility treatment: IVF, intrauterine insemination if required

Assess the impact of the disease on the woman’s QOL including anxiety and depression and offer treatment if required

Review the woman after 3-6 months, or earlier if the symptoms are troublesome (refer if needed)

Question 15

How can endometriosis be treated in secondary care

Answer 15

Fertility sparing surgery: laparoscopy is used to both diagnose and treat endometriosis (treatment via excision rather than ablation). This is the preferred management choice if fertility is a priority.
* 3 months of GnRH agonists should be given prior to surgery
* Hormonal treatment may be considered post-surgery to manage symptoms
* Risk of recurrence following surgery is as high as 30%- long-term medical therapy is often necessary
* Specialist surgery may be needed if the endometriosis has caused extensive adhesions or involved other organs

Hysterectomy and oophorectomy- Should be considered in women who have completed their family and failed to respond to conservative treatment (will NOT necessarily cure the symptoms or the disease