Endometriosis is increasingly being recognised as a disease which commonly affects women through the reproductive years.
It is the commonest cause of chronic pelvic pain in developed countries, and frequently begins in adolescence.
Endometriosis is a highly variable condition, and diagnosis can be difficult. Confirmation of diagnosis still requires laparoscopy in most situations, but successful therapy of many, especially milder, cases can be based on a presumptive diagnosis. A careful history needs to be taken to try and exclude other common causes of pelvic pain.
Medical management requires treatment of pain with analgesics, and suppression of disease activity mainly with hormonal preparations. This needs to be integrated with the potential need for surgery.
Patients with persistent pain unresponsive to hormonal treatments and analgesics should be referred for specialist care.
Early recognition of endometriosis
Assessing women with suspected endometriosis
The initial assessment involves taking a detailed history of the duration and nature of pelvic pain. Ask about its relationship to the menstrual cycle, the presence of bowel and bladder symptoms and the impact of posture and movement on pain.
There may be overlap between the symptoms of irritable bowel syndrome, pelvic inflammatory disease and endometriosis and it can sometimes be difficult to distinguish clinically between these conditions.5 There are also a number of co-existing pain conditions in women with endometriosis, such as interstitial cystitis, which should be considered in the assessment of a woman with pelvic pain. Women with irritable bowel syndrome will usually experience relief following a bowel motion, whereas this relief does not usually occur with endometriosis.
Initial investigations may include urinalysis, screening for sexually transmitted infections and a transvaginal ultrasound scan. Transvaginal ultrasound scanning by a specialist in pelvic sonography has a reasonably high sensitivity and specificity for diagnosing ovarian endometriotic cysts and deep infiltrating bowel endometriosis.6,7 but is of little use in identifying the commoner types of peritoneal disease. Diagnostic laparoscopy by an experienced gynaecological endoscopist remains the best way of confirming or excluding most types of endometriosis as there is no consistently reliable non-invasive test.8
Box 1 - Variable factors leading to a heterogeneous clinical picture of endometriosis
Box 2 - Symptoms suspicious of endometriosis
Box 3 - When to refer women for specialist opinion
Table 1 - Treatment options for endometriosis (in addition to necessary analgesia)
When no diagnosis is evident
When examination and investigations reveal no definitive diagnosis, women should be offered simple analgesia to control their pain, beginning with non-steroidal anti-inflammatory drugs (NSAIDs) or paracetamol in effective doses. Patients with persistent pain unresponsive to these analgesics should be referred for specialist care, including a gynaecologist for diagnostic laparoscopy.
Management of women with confirmed endometriosis – factors to consider
The management of endometriosis may be influenced by the woman’s presenting complaint, for example pain or infertility.
Endometriosis is a chronic condition that may require lifelong management. Medical treatment is usually based on suppressing ovulation and inducing a steady hormonal environment. Commonly used drugs and their mechanisms of action are listed in Table 1 . Both oral progestogens and combined oral contraceptives may be effective in relieving pain. They are generally well tolerated and are initially preferable to danazol, gonadotrophin releasing hormone agonists and aromatase inhibitors.10 In our clinical experience, in most women progestogen-only methods that induce decidualisation of the endometrial lesions are more effective than combined oral contraceptives. There is a trend towards use of the delivery systems like the levonorgestrel intrauterine system, which has evidence of efficacy,11, 12 and the subdermal etonogestrel implant, where the benefit has been documented so far mainly in case reports. It is not logical to give an oestrogen-containing preparation (combined oral contraceptive) to a woman with an oestrogen-sensitive disease, but all modern combined oral contraceptives have a strong progestogenic balance and many women do well with this treatment. There is no evidence that one combined oral contraceptive is superior to another.
In a woman wishing to conceive, medical treatment will relieve symptoms but there is strong evidence that it does not improve fecundity. The recommended approaches are surgical excision of macroscopically recognisable lesions on the peritoneal surface, deep lesions or ovarian cyst linings by a specialist, or referral for assisted fertilisation techniques.13
Management by a gynaecologist
In women with minimal to mild endometriosis-associated infertility, there is evidence that surgery that excises visible deposits, divides adhesions, and normalises pelvic anatomy may enhance fertility.14 Although there are no randomised controlled trials or meta-analyses available to answer the question of whether surgical excision of deep invasive endometriosis enhances pregnancy rates, observational studies provide some support.15 Laparoscopic cystectomy for ovarian endometriomas greater than four centimetres in diameter improves fertility, compared to drainage and coagulation of the cysts, but the presence of a small asymptomatic endometrioma may not require surgical intervention before in vitro fertilisation.
There is usually amelioration of symptoms during pregnancy and there may sometimes be long-term improvement in pain after pregnancy. However, many women with endometriosis will experience recurrence of symptoms as soon as pregnancy and breastfeeding have been completed.
It is important to recognise that the extent of endometriosis may not correlate with the presenting symptoms, and some women with mild peritoneal endometriosis may have severe debilitating pain while others with severe disease and gross distortion of pelvic anatomy may experience minimal or no symptoms. Further, if endometriosis is found at laparoscopy it may not always be the major cause of pain in an individual, and pain symptoms attributed to endometriosis occur in some women without obvious laparoscopic evidence of endometriosis.
Recurrence after surgery
Endometriosis has a propensity to recur with time after conservative surgery (excision of visible lesions, rather than removal of the ovaries and uterus). At least 10–20% of treated patients developed signs and symptoms of persistent or recurrent endometriosis within one year.16
There is good evidence that hormonal treatments after surgery reduce symptoms and disease recurrence. The combined pill and oral progestogens have been found to reduce the frequency and severity of recurrent endometriosis-related dysmenorrhoea17 and endometriomas after surgery.18 Local pelvic release of levonorgestrel via an intrauterine system is an effective way of delivering progestogen therapy and has been found to be as effective at relieving dysmenorrhoea as gonadotropin releasing hormone agonists19 or injectable progestogens, without the same degree of systemic symptoms.20 The role of the subdermal etonogestrel implant in this situation has not yet been clarified.
If recurrence occurs, initial treatment should be appropriate analgesics and hormonal treatment. Repeat surgery has the same limitations as primary surgery in terms of disease recurrence. In the most severe and troublesome symptomatic endometriosis, combined off-label use of the two progestogen delivery systems (levonorgestrel intrauterine system and etonogestrel subdermal implant used simultaneously) may have a major beneficial impact on quality of life, but there is only one case report to support this line of management.21 It also needs to be recognised that a minority of severe endometriosis sufferers experience persistent pelvic pain, which has a major impact on quality of life. Ongoing management may require involvement of a specialised pain management clinic.
Dr Black is a consultant for Bayer HealthCare on an international advisory board (Bayer is the maker of Mirena). Professor Fraser has undertaken consultancies, lectures and research projects for Bayer Pharmaceuticals, Merck/MSD, Daiichi Sankyo and Vifor Pharma and has received honoraria, lecture fees and expenses. These honoraria and lecture fees are directed to his research program.
- Fraser IS. Mysteries of endometriosis pain: Chien-Tien Hsu Memorial Lecture 2009. J Obstet Gynaecol Res 2010;36:1-10.
- Latthe P, Latthe M, Say L, Gülmezoglu M, Khan KS. WHO systematic review of prevalence of chronic pelvic pain: a neglected reproductive health morbidity. BMC Public Health 2006;6:177.
- Arruda MS, Petta CA, Abrao MS, Benetti-Pinto CL. Time elapsed from onset of symptoms to diagnosis of endometriosis in a cohort study of Brazilian women. Hum Reprod 2003;18:756-9.
- Husby GK, Haugen RS, Moen MH. Diagnostic delay in women with pain and endometriosis. Acta Obstet Gynecol Scand 2003;82:649-53.
- Lea R, Bancroft K, Whorwell PJ. Irritable bowel syndrome, chronic pelvic inflammatory disease and endometriosis: a comparison of symptomatology. Eur J Gastroenterol Hepatol 2004;16:1269-72.
- Hudelist G, English J, Thomas AE, Tinelli A, Singer CF, Keckstein J. Diagnostic accuracy of transvaginal ultrasound for non-invasive diagnosis of bowel endometriosis: systematic review and meta-analysis. Ultrasound Obstet Gynecol 2011;37:257-63.
- Moore J, Copley S, Morris J, Lindsell D, Golding S, Kennedy S. A systematic review of the accuracy of ultrasound in the diagnosis of endometriosis. Ultrasound Obstet Gynecol 2002;20:630-4.
- Kennedy S, Bergqvist A, Chapron C, D’Hooghe T, Dunselman G, Greb R, et al. ESHRE guideline for the diagnosis and treatment of endometriosis. Hum Reprod 2005;20:2698-704.
- Family Planning New South Wales. Reproductive and Sexual Health: An Australian Clinical Practice Handbook. 2nd ed. Sydney: FPNSW; 2011.
- Vercellini P, Crosignani P, Somigliana E, Viganò P, Frattaruolo MP, Fedele L. ‘Waiting for Godot’: a commonsense approach to the medical treatment of endometriosis. Hum Reprod 2011;26:3-13.
- Vercellini P, Aimi G, Panazza S, De Giorgi O, Pesole A, Crosignani PG. A levonorgestrel releasing intrauterine system for the treatment of dysmenorrhea associated with endometriosis: a pilot study. Fertil Steril 1999;72:505-8.
- Vercellini P, Frontino G, De Giorgi O, Aimi G, Zaina B, Crosignani PG. Comparison of a levonorgestrel-releasing intrauterine device versus expectant management after conservative surgery for symptomatic endometriosis: a pilot study. Fertil Steril 2003;80:305-9.
- Bulletti C, Coccia ME, Battistoni S, Borini A. Endometriosis and infertility. J Assist Reprod Genet 2010;27:441-7.
- Adamson GD, Baker VL. Subfertility: causes, treatment and outcome. Best Pract Res Clin Obstet Gynaecol 2003;17:169-85.
- Vercellini P, Somigliana E, Viganò P, Abbiati A, Barbara G, Crosignani PG. Surgery for endometriosis-associated infertility: a pragmatic approach. Hum Reprod 2009;24:254-69.
- Evers JL, Dunselman GA, Land JA, Bouckaert PX. Is there a solution for recurrent endometriosis? Br J Clin Pract Suppl 1991;72:45-50.
- Seracchioli R, Mabrouk M, Frascà C, Manuzzi L, Savelli L, Venturoli S. Long-term oral contraceptive pills and postoperative pain management after laparoscopic excision of ovarian endometrioma: a randomized controlled trial. Fertil Steril 2010;94:464-71.
- Takamura M, Koga K, Osuga Y, Takemura Y, Hamasaki K, Hirota Y, et al. Post-operative oral contraceptive use reduces the risk of ovarian endometrioma recurrence after laparoscopic excision. Hum Reprod 2009;24:3042-8.
- Bayoglu Tekin Y, Dilbaz B, Altinbas SK, Dilbaz S. Postoperative medical treatment of chronic pelvic pain related to severe endometriosis: levonorgestrel-releasing intrauterine system versus gonadotropin-releasing hormone analogue. Fertil Steril 2011;95:492-6.
- Wong AY, Tang LC, Chin RK. Levonorgestrel releasing intrauterine system (Mirena) and depot medroxyprogesterone acetate (Depoprovera) as long-term maintenance therapy for patients with moderate and severe endometriosis: a randomised controlled trial. Aust N Z J Obstet Gynaecol 2010;50:273-9.
- Al-Jefout M, Palmer J, Fraser IS. Simultaneous use of a levonorgestrel intrauterine system and an etonogestrel subdermal implant for debilitating adolescent endometriosis. Aust N Z J Obstet Gynaecol 2007;47:247-9.