Endometriosis

Endometriosis is a chronic condition characterised by growth of endometrial tissue in sites other than the uterine cavity, most commonly in the pelvic cavity, including the ovaries, the uterosacral ligaments, and pouch of Douglas.¹ Other sites are rarely involved but include the umbilicus, scar sites post caesarean section and laparoscopy, pleura, pericardium, and the central nervous system.² Adenomyosis is the invasion of the myometrium by endometrial tissue.

• Estimates of the prevalence of endometriosis vary from 1% to 15%.² The prevalence can only be estimated as diagnosis can only be confirmed by laparoscopy. Endometriosis is the underlying cause in 15% of cases of pelvic pain.³
• Endometriosis is found almost exclusively in women of reproductive age, with an average age at diagnosis of 25-29 years.²
• The use of oral contraceptives reduces the risk of developing endometriosis.

Risk Factors

• Risk factors include an early menarche and late menopause.²
• Genetic factors: risk for first-degree relatives of women with severe endometriosis is six times higher than that for relatives of unaffected women. Familial aggregation has been shown in clinical and population-based samples and in twin studies.⁴

Common symptoms include dysmenorrhoea, dyspareunia, non-cyclic pelvic pain, and subfertility. The clinical presentation is variable, with some women experiencing several severe symptoms and others having no symptoms at all. The severity of symptoms tend to increase with age.¹ The severity of symptoms is not necessarily indicative of the severity of endometriosis.

• Women with endometriosis may have no symptoms and be diagnosed incidentally or during investigations for infertility.
• Symptoms are most commonly cyclical or chronic pelvic pain, dysmenorrhoea, and deep dyspareunia. The appearance or worsening of symptoms at the time of menstruation suggests endometriosis.²
• Other symptoms include dysuria, painful defecation, abdominal pain, backache, menstrual irregularity, rectal bleeding and cyclical pain at extrapelvic sites.

Signs

• Examination is often normal.
• With pelvic examination, there may be tenderness in the posterior fornix or adnexa, nodules in the posterior fornix, cystic lesions on the ovaries ('chocolate cysts'), or adnexal masses may indicate endometriosis.
• Bluish haemorrhagic nodules may be visible in the posterior fornix or at other sites on speculum examination.²

• Pelvic inflammatory disease
• Ectopic pregnancy
• Torsion of an ovarian cyst
• Appendicitis
• Primary dysmenorrhoea
• Adenomyosis
• Irritable bowel disease
• Uterine fibroids

A definitive diagnosis of most forms of endometriosis requires visual inspection of the pelvis at laparoscopy as the 'gold standard' investigation. However, pain symptoms suggestive of the disease can be treated without a definitive diagnosis using a therapeutic trial of a hormonal drug to reduce menstrual flow.⁵

• Laparoscopy is the gold standard diagnostic test but is invasive, with a small risk of major complications, e.g. bowel perforation.⁴ Symptoms and laparoscopic appearance do not always correlate.¹
• Transvaginal ultrasound scanning appears to be a useful test both to make and to exclude the diagnosis of an ovarian endometrioma.⁴
• MRI scan may be a useful non-invasive tool in diagnosis, especially for subperitoneal deposits.¹
• CA-125 measurement: limited value as a screening test or diagnostic test.⁴

The general principle of management is to create a pseudo-pregnancy or pseudo-menopause.

• For laparoscopically confirmed disease, suppression of ovarian function for 6-months reduces endometriosis-associated pain.
• All hormonal drugs are equally effective. The combined oral contraceptive pill, danazol, oral or depot medroxyprogesterone acetate, and the levonorgestrel intrauterine system are as effective as the gonadotrophin releasing hormone (GnRH) analogues and can be used long term.¹
• Ablation of endometriotic lesions reduces endometriosis-associated pain. The smallest effect is seen in patients with minimal disease.
• There is no evidence that laparoscopic uterine nerve ablation (LUNA) is beneficial.

Drugs

• Non-steroidal anti-inflammatory drugs may be effective in reducing the pain associated with endometriosis. Paracetamol with or without added codeine are an alternative.
• If there is no evidence of a pelvic mass on examination, there may be a role for a therapeutic trial of a combined oral contraceptive (monthly or tricycling) or a progestogen to treat pain symptoms suggestive of endometriosis without performing a diagnostic laparoscopy first.⁴
• There is no role for medical therapy with hormonal drugs in the treatment of endometriosis associated infertility.⁴
• There is currently no evidence for any benefit of preoperative or postoperative hormonal treatment.
• GnRH agonist therapy given for three months may be as effective as treatment given for six months in relieving endometriosis-associated pain. If longer treatment is required, GnRH agonist use can be extended safely with 'add-back' therapy (progestogen, with or without oestrogen, can be used to relieve menopausal side-effects, to prevent bone loss and allow therapy to continue beyond six months).⁴

Surgical

• Laparoscopic excision or ablation at the time of diagnostic laparoscopy. The main conservative surgical techniques performed by laparoscopy are thermal or laser ablation, excision, ovarian cystectomy and denervation procedures.²
• Endometriomata (large cysts of endometriosis) are best stripped out instead of drainage and ablation.¹
• Hysterectomy with salpingo-oophorectomy is reserved for women as a last resort.
• Laparoscopic ablation of minimal-moderate endometriosis appears to relieve pain, although it is unclear whether uterine nerve ablation is required as well.

Fertility⁵

• Medical treatment for endometriosis should be avoided for women who are trying to conceive.
• In minimal-mild endometriosis, suppression of ovarian function to improve fertility is not effective, but ablation of endometriotic lesions plus adhesiolysis is effective compared to diagnostic laparoscopy alone.
• There is insufficient evidence available to determine whether surgical excision of moderate-severe endometriosis enhances pregnancy rates.
• IVF is appropriate treatment especially if there are coexisting causes of infertility and/or other treatments have failed, but IVF pregnancy rates are lower in women with endometriosis than in those with tubal infertility.

• Women with endometriosis are at higher risk developing ovarian cancer, and they also may be at increased risk of breast and other cancers, autoimmune and atopic disorders.⁶
• Infertility: moderate to severe endometriosis can cause tubal damage leading to infertility.
  Lesser degrees of endometriosis, even in the absence of any obvious tubal damage, are also associated with sub-fertility² and increased risk of ectopic pregnancy.
• Adhesion formation may occur due to the endometriosis or following surgery.

• The natural course of the disease is variable and may or may not be progressive. In 2 studies following the natural history of endometriosis over 6-12 months, endometrial deposits resolved spontaneously in a third of women, deteriorated in nearly half, and were unchanged in the remainder.¹
• In the five years after surgery or medical treatment 20-50% of women will have a recurrence. Long term medical treatment (with or without surgery) has the potential to reduce recurrence but there is no clear evidence for this.¹
• Relapse following surgical treatment may occur in about 20% of women.² Surgical treatment: surgical cohort studies report 20% recurrence at 5 years after surgery.²