Endometriosis

Endometriosis is a common gynaecological condition characterised by the growth of endometrial tissue outside of the uterus. It affects around one in ten Australian women and is associated with the formation of adhesions, ovarian cysts, infertility, subfertility, and pain. 1 There is no cure for endometriosis. Medical and surgical interventions aim to reduce extrauterine endometrial tissue growth, minimise pain, and enhance fertility. While effective treatments are available, endometriosis remains a severe and debilitating condition with a significant impact on quality of life for many affected women. 2

Endometriosis is a chronic, oestrogen dependent, inflammatory condition. It occurs when endometrial tissue proliferates and forms lesions in extrauterine areas including the ovaries, anterior/posterior cul-de-sac, ovarian ligaments, uterus, fallopian tubes, sigmoid colon, and appendix. 3 Endometrial tissue growth is dependent on oestrogen, and therefore primarily affects women of childbearing age (see Illustration 1).

There are several theories to describe the pathogenesis of endometriosis. They can be broadly categorised into two groups; those that argue extra-uterine tissue originates in the uterus and those that purport that extrauterine tissue has arisen from another organ or area of the body. 2 No single theory can explain all presentations. At present, the strongest theory is known as the retrograde menstruation hypothesis. 4 It suggests that fragments of endometrial tissue from the uterine cavity travel up the fallopian tubes to the peritoneal cavity during menstruation. The tissue then implants itself into the peritoneum and abdominal organs and begins to grow. These growths induce chronic inflammation and the formation of adhesions. 4

Retrograde menstruation occurs in the majority of women, not just those with endometriosis. Therefore, other factors are thought to be required for the onset of disease such as genetic predisposition and hereditary or acquired changes to the endometrium, peritoneal epithelium, and/or immune clearance. 2

The two key symptoms of endometriosis are pain and subfertility. Types of pain include dysmenorrhoea (pain on menstruation), dyspareunia (pain on sexual intercourse), dysuria (painful urination), dyschezia (straining with stools), and generalised pelvic and abdominal pain. 1 Other symptoms include bowel and bladder complications, nausea, fatigue, and premenstrual syndrome. 5

Box 1. Endometriosis and infertility 3,6

Endometriosis is associated with subfertility and infertility. Up to 50% of women with infertility have endometriosis and vice versa (up to 50% of women with endometriosis have infertility). The exact relationship between endometriosis and infertility is not clearly understood. It is known that women with advanced endometriosis have altered pelvic anatomy, poor ovarian reserve, low oocyte quality, and poor implantation. Women with mild to moderate cases may be able to conceive without intervention. In severe cases, pregnancy rates are significantly lower. There is no evidence to support the use of medical therapies for endometriosis-associated infertility. Instead, treatment options include watchful waiting, surgery to remove ectopic implants and restore normal anatomy, ovulation induction and in vitro fertilisation. Selection of interventions is based on age, severity of the condition, and individual preference.

Preliminary diagnosis of endometriosis involves past medical history, signs and symptoms, physical examination, and medical imaging. Physical examination may include a vaginal and/or rectal exam. Transvaginal ultrasound may also be useful for viewing ovarian endometrioma (cysts) and rectal endometriosis, when performed by a highly experienced clinician. Further imaging of the ureters, bladder and/or bowel may also be indicated in some cases. The confirmed presence of endometrial tissue in the abdominal cavity is often considered gold standard for the diagnosis of endometriosis. This is obtained through laparoscopic surgery and histological verification of an implant sample collected during surgery. 5

There is no cure for endometriosis. Treatment is targeted at minimising pain and treating infertility associated with the disorder. Options include surgical interventions and medical therapies. Surgical interventions are used to reduce or remove external endometrial tissue, for the division of adhesions and to interrupt nerve pathways, while medical therapies are used for pain relief, prevention of disease progression, and to support for subfertility. 5,6

Surgery has been demonstrated to be effective for relieving pain associated with endometriosis and is an option for the treatment of endometriosis-associated infertility. 3 Laparotomy (open surgery) and laparoscopy (minimally invasive surgery) are equally effective. However, laparoscopy is typically preferred as it is associated with fewer complications and improved outcomes. 5

Surgical procedures that may be performed during laparoscopy include: 5

- Removal/destruction of endometrial implants or ovarian endometriomas (cysts) - Division of adhesions - Cystectomy • Surgical removal of all or part of the bladder

• May be recommended for women with ovarian endometrioma (cysts) as it reduces pain and has a lower recurrence rate than other treatment options

- Hysterectomy, with or without oophorectomy • Removal of the uterus and all visible endometriosis lesions, with or without one or both ovaries

• Women should be aware that symptoms may persist even after a complete hysterectomy

- Uterine nerve ablation (LUNA) or presacral neurectomy (PSN) Ectopic tissue may be removed via excision or ablation. Excision is the surgical removal of endometrial implants. Ablation destroys the tissue through melting or evaporation, for

example, using a laser or diathermy. 5 Excision is required for histological verification and may be preferred for more advanced conditions. It has also been associated with improved rates of spontaneous pregnancy at nine to 12 months, when compared with ablation. 6

The recommended type of surgery depends on the patient characteristics, location of the ectopic endometrial tissue, and associated symptoms. For example, hysterectomy is recommended for all women who have completed their family and have not adequately responded to alternative treatments. 5

The primary medical therapies for the relief of endometriosis-related pain include analgesics, such as non-steroidal anti-inflammatories (NSAIDs), and combined hormonal contraceptives or prostagens (for example, medroxyprogesterone acetate, DepoProvera). 5 Guidelines recommend empirical treatment for symptomatic women, once other potential causes of chronic pelvic pain have been excluded. 5 Other agents including anti-progestogens, levonorgestrel-releasing intrauterine devices, gonadotrophin-releasing hormone (GnRH) agonists, and aromatase inhibitors may also be considered. 6 No single agent is preferred in all cases. The appropriate treatment should be based on a woman’s symptoms, her preferences, medication efficacy and side effects, costs, and availability of treatment. 2

1. Hayes P (ed.). Endometriosis timely management [Internet]. Melbourne: The Royal Australian College of General Practitioners; 2015 Mar. Available from: http://www.racgp.org.au/ publications/goodpractice/archive/201503/ endometriosis-timely-management/ Accessed July 2017.

2. Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012 Sep;98(3):10.1016/j.fertnstert.2012.06.029 3. Macer LM, Taylor HS. Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosis-associated infertility. Obstet Gynecol Clin North Am. 2012 Dec; 39(4): 535–549. 4. Vercellini P, Vigano P, Somigliana E, Fedele L.

Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol. 2014 May;10(5):261-75.

5. Dunselman GA, Vermeulen N, Becker C, CalhazJorge C, D’Hooghe T, De Bie B, Heikinheimo O, Horne AW, Kiesel L, Nap A, Prentice A, Saridogan E, Soriano D, Nelen W. ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014 Mar;29(3):400-12. doi: 10.1093/humrep/det457.

6. Brown J, Farquhar C. Endometriosis: an overview of Cochrane Reviews. Cochrane Database of Systematic Reviews 2014, Issue 3. Art. No.: CD009590. DOI: 10.1002/14651858. CD009590.pub2.