Endometriosis is a chronic oestrogen-dependent condition characterised by the growth of endometrial tissue in sites other than the uterine cavity, most commonly the pelvic cavity (including the ovaries), the uterosacral ligaments, the pouch of Douglas, the rectosigmoid colon, and the bladder and distal ureter.
Other sites are rarely involved but include the umbilicus, scar sites (eg, following caesarean sectionand laparoscopy), the pleura and pericardium, and the central nervous system.
Adenomyosis is the invasion of the myometrium by endometrial tissue. Extrauterine endometrial tissue causes inflammation, pain and the formation of adhesions. Clinically its significance is as a cause of chronic pelvic pain, dyspareunia and female infertility.
- Endometriosis is estimated to affect 10-15% of women of reproductive age.However, it is difficult to determine the prevalence because of the diversity of symptoms and their severity and because endometriosis may be asymptomatic.
- Endometriosis has a much higher prevalence in infertile women, estimated as between 25% and 40%.
- Endometriosis is found almost exclusively in women of reproductive age, with diagnosis usually during a woman's 30s. It is uncommon in the under-20s.
- Traditionally, the diagnosis has not been commonly applied in adolescence but should be considered, as early recognition and treatment may be beneficial.
- Risk factors include: an early menarche, late menopause, delayed childbearing, short menstrual cycles or long duration of menstrual flow.
- Obstruction to vaginal outflow eg, hydrocolpos, female genital mutilation or defects in the uterus or Fallopian tubes.
- 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.
- There is evidence of linkage to chromosomes 7 and 10 but no relevant genes have yet been identified.
- Multiparity and the use of oral contraceptives are protective.
The histological origin of endometriosis remains controversial. Historically, suggested theories have included retrograde menstruation, lymphatic or haematogenous spread, and metaplasia.
However, currently the consensus is that endometriosis has a multifactorial aetiology, involving possible genetic, immunological and endocrinological factors.
The ovarian steroids oestrogen and progesterone are intimately involved in the development of endometriosis, as evidenced by the relationship of disease activity to uninterrupted menstrual cycles, onset following menarche and remittance of disease at menopause and the benefit of medical therapy which suppresses ovulation. Increasingly, the interactions of these sex steroids with the inflammatory cascades are being understood at a molecular level.
Common symptoms include:
Other symptoms may include bloating, lethargy, constipation and low back pain. Less common symptoms include cyclical rectal bleeding, menorrhagia, diarrhoea and haematuria.
The clinical presentation is variable, with some women experiencing several severe symptoms and others having no symptoms at all. The severity of symptoms tends to increase with age.
- Women with endometriosis may have no symptoms and be diagnosed incidentally or during investigations for infertility.
- The appearance or worsening of symptoms at the time of menstruation, or just prior to it, suggests endometriosis.
- Other symptoms include lower urinary tract symptoms (eg, dysuria), painful defecation, abdominal pain, backache, menstrual irregularity, and cyclical pain or bleeding (eg, epistaxis, haemoptysis) at extrapelvic sites.
- Examination is often normal.
- However, there may be:
- Posterior fornix or adnexal tenderness.
- Palpable nodules in the posterior fornix or adnexal masses (endometriosis can cause cystic lesions on the ovaries, known as 'chocolate cysts').
- Bluish haemorrhagic nodules visible in the posterior fornix.
- Pelvic inflammatory disease.
- Ectopic pregnancy.
- Torsion of an ovarian cyst.
- Primary dysmenorrhoea.
- Irritable bowel syndrome.
- Uterine fibroids.
- Urinary tract infection.
Clinical Editor's comments (September 2017)
Dr Hayley Willacy would like to draw your attention to the recently released NICE guidelines dealing with endometriosis. They advise on recognition of symptoms and diagnosis. Transvaginal ultrasound can be used to investigate suspected endometriosis even if the pelvic and/or abdominal examination is normal and also to identify endometriomas and deep endometriosis involving the bowel, bladder or ureter. Pelvic MRI should not be used as the primary investigation to diagnose endometriosis in women with symptoms or signs suggestive of endometriosis. However, it might be used to assess the extent of deep endometriosis involving the bowel, bladder or ureter. When pelvic MRI scans are used in assessment of pelvic pain symptoms, they should be interpreted by a healthcare professional with specialist expertise in gynaecological imaging. They also cover use of treatments for symptom control and when a couple are trying to conceive.
- For a definitive diagnosis of most forms of endometriosis, laparoscopy is the gold standard investigation but it is invasive with a small risk of major complications - eg, bowel perforation.
- Symptoms and laparoscopic appearance do not always correlate.
- Transvaginal ultrasound scanning appears to be a useful test, both to make and to exclude the diagnosis of an ovarian endometrioma.
- MRI scan may be a useful non-invasive tool in diagnosis, especially for subperitoneal deposits.
- CA 125 measurement has limited value as a screening test or diagnostic test.
In an acute setting, blood tests (eg, FBC), urinalysis and MC&S, cervical swabs (MC&S, chlamydia testing) and beta human chorionic gonadotrophin (beta-hCG) may be helpful in excluding some important differentials.
- The treatment of endometriosis is usually individually based, depending on the nature and severity of symptoms and the need for future fertility.
- Medical treatment may reduce symptoms in 80-90% of patients but none of the treatment options has been shown to reduce recurrence of symptoms once treatment has stopped.
- Suppression of ovarian function for at least six months is the basis for most medical treatment, and the options include the combined oral contraceptive pill (COCP), medroxyprogesterone acetate and gonadotrophin-releasing hormone (GnRH) agonist.
- The levonorgestrel intrauterine system has been shown to be effective even after three years of use.
- Surgical options include removing severe and deeply infiltrating lesions (which may reduce pain related to endometriosis), ovarian cystectomy (for endometriomas), adhesiolysis and bilateral oophorectomy (often with a hysterectomy).
- The National Institute for Health and Care Excellence (NICE) recommends that the evidence for uterine artery embolisation for treating adenomyosis shows that the procedure is effective for symptom relief in the short and medium term and there are no major safety concerns.
- Management may also include pain management specialists and clinical psychologists.
For pain, the general principle is to create a pseudo-pregnancy or pseudo-menopause, whilst the treatment of infertility requires a different approach.
- For laparoscopically confirmed disease, suppression of ovarian function for six months reduces endometriosis-associated pain.
- All hormonal drugs are equally effective: the COCP, danazol, oral or depot medroxyprogesterone acetate and the levonorgestrel intrauterine system are as effective as the GnRH analogues and can be used long-term.Approximately 80-85% of patients improve with treatment.
- Ablation of endometrioid lesions reduces endometriosis-associated pain. The smallest effect is seen in patients with minimal disease.
- Non-steroidal anti-inflammatory drugs (eg, naproxen) may be effective in reducing the pain associated with endometriosis, although the evidence to date is inconclusive.Paracetamol, with or without added codeine, is an alternative.
- If there is no evidence of a pelvic mass on examination, there may be a role for a therapeutic trial of a COCP (monthly or tricycling) or a progestogen to treat pain symptoms suggestive of endometriosis, without a diagnostic laparoscopy first.
- Danazol is effective in treating endometriosis but its use is limited by androgenic side-effects.
- GnRH analogues (GnRH agonists) appear to be effective at relieving pain associated with endometriosis.
- GnRH agonist therapy given for three months may be as effective as treatment given for six months in relieving endometriosis-associated pain. If longer or repeated treatment is required, GnRH agonist use can be extended with 'add-back' therapy (a low-dose oestrogen, progestogen or tibolone to relieve menopausal side-effects and prevent bone loss).
- 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.
- Endometriomata (large cysts of endometriosis) are best stripped out instead of drainage and ablation.
- Hysterectomy with salpingo-oophorectomy is reserved for women as a last resort.
- Laparoscopic surgery has been shown to reduce pelvic pain when compared to diagnostic laparoscopy alone.
- 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 endometrioid lesions plus adhesiolysis is effective compared to diagnostic laparoscopy alone.
- The use of laparoscopic surgery in the treatment of subfertility related to minimal and mild endometriosis may improve future fertility.
- There is insufficient evidence available to determine whether surgical excision of moderate-to-severe endometriosis enhances pregnancy rates.
- In vitro fertilisation (IVF) is appropriate treatment, especially if there are co-existing causes of infertility and/or other treatments have failed.
- A recent review found an association between endometriosis and some histological subtypes of ovarian cancer:
- Endometriosis was associated with a significantly increased risk of clear-cell, low-grade serous and endometrioid invasive ovarian cancers.
- No association was noted between endometriosis and risk of mucinous or high-grade serous invasive ovarian cancer, or borderline tumours of either subtype.
- Endometriosis may also be associated with an increased risk of breast and other cancers, and autoimmune and atopic disorders.
- 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 subfertility and increased risk of ectopic pregnancy.
- Adhesion formation may occur due to the endometriosis or following surgery.
- Women with endometriosis have an increased risk of inflammatory bowel disease.
- The natural course of the disease is variable and may or may not be progressive. In two 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.
- 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.
- Relapse following surgical treatment is common.Surgical cohort studies report a 20% recurrence rate at two years and 40-50% at five years. Few risk factors for recurrence have been consistently identified. The use of biomarkers to identify recurrence is under investigation.
Further reading and references
Gajjar KB, Mahendru AA, Khaled MA; Caesarean scar endometriosis presenting as an acute abdomen: a case report and review of literature. Arch Gynecol Obstet. 2008 Feb277(2):167-9. Epub 2007 Aug 14.
Engemise S, Gordon C, Konje JC; Endometriosis. BMJ. 2010 Jun 23340:c2168. doi: 10.1136/bmj.c2168.
Mehedintu C, Plotogea MN, Ionescu S, et al; Endometriosis still a challenge. J Med Life. 2014 Sep 157(3):349-57. Epub 2014 Sep 25.
Ozkan S, Murk W, Arici A; Endometriosis and infertility: epidemiology and evidence-based treatments. Ann N Y Acad Sci. 2008 Apr1127:92-100.
Endometriosis; NICE CKS, May 2014 (UK access only)
Sanfilippo JS, Lara-Torre E; Adolescent gynecology. Obstet Gynecol. 2009 Apr113(4):935-47.
Management of women with endometriosis; European Society of Human Reproduction and Embryology (Sept 2013)
Bulun SE; Endometriosis. N Engl J Med. 2009 Jan 15360(3):268-79.
Endometriosis: diagnosis and management; NICE Guidelines (Sept 2017)
Farquhar C; Endometriosis. BMJ. 2007 Feb 3334(7587):249-53.
Brown J, Farquhar C; Endometriosis: an overview of Cochrane Reviews. Cochrane Database Syst Rev. 2014 Mar 103:CD009590. doi: 10.1002/14651858.CD009590.pub2.
Uterine artery embolisation for treating adenomyosis; NICE Interventional Procedure Guidance, Dec 2013
Zito G, Luppi S, Giolo E, et al; Medical treatments for endometriosis-associated pelvic pain. Biomed Res Int. 20142014:191967. doi: 10.1155/2014/191967. Epub 2014 Aug 7.
Allen C, Hopewell S, Prentice A, et al; Nonsteroidal anti-inflammatory drugs for pain in women with endometriosis. Cochrane Database Syst Rev. 2009 Apr 15(2):CD004753.
Ferrero S, Remorgida V, Venturini PL; Endometriosis. Clin Evid (Online). 2010 Aug 132010. pii: 0802.
Brown J, Pan A, Hart RJ; Gonadotrophin-releasing hormone analogues for pain associated with endometriosis. Cochrane Database Syst Rev. 2010 Dec 8(12):CD008475. doi: 10.1002/14651858.CD008475.pub2.
Jacobson TZ, Duffy JM, Barlow D, et al; Laparoscopic surgery for pelvic pain associated with endometriosis. Cochrane Database Syst Rev. 2009 Oct 7(4):CD001300. doi: 10.1002/14651858.CD001300.pub2.
Jacobson TZ, Duffy JM, Barlow D, et al; Laparoscopic surgery for subfertility associated with endometriosis. Cochrane Database Syst Rev. 2010 Jan 20(1):CD001398. doi: 10.1002/14651858.CD001398.pub2.
Surrey ES; Endometriosis-Related Infertility: The Role of the Assisted Reproductive Technologies. Biomed Res Int. 20152015:482959. doi: 10.1155/2015/482959. Epub 2015 Jul 9.
Pearce CL, Templeman C, Rossing MA, et al; Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies. Lancet Oncol. 2012 Apr13(4):385-94. doi: 10.1016/S1470-2045(11)70404-1. Epub 2012 Feb 22.
Giudice LC, Kao LC; Endometriosis. Lancet. 2004 Nov 13-19364(9447):1789-99.
Jess T, Frisch M, Jorgensen KT, et al; Increased risk of inflammatory bowel disease in women with endometriosis: a nationwide Danish cohort study. Gut. 2012 Sep61(9):1279-83. doi: 10.1136/gutjnl-2011-301095. Epub 2011 Dec 19.
Guo SW; Recurrence of endometriosis and its control. Hum Reprod Update. 2009 Mar 11.
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