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A clinical update on endometriosis

Key learning points:

- Endometriosis is a common gynaecological condition affecting one-in-10 women of reproductive age

- Endometriosis is classified as lesions or cysts found around the pelvic organs that histologically resemble the normal endometrium. The presence of these lesions can cause severe and debilitating pain symptoms

- Although medical treatment can reduce the symptoms of endometriosis in some cases, surgical excision of the lesions gives the best outcomes

Endometriosis is a chronic gynaecological condition affecting approximately one-in-10 women of reproductive age1 and is the third most common gynaecological condition after polycystic ovarian syndrome and fibroids. The condition is defined as the presence of tissue resembling the normal endometrium being found outside the uterus forming endometriotic lesions or cysts. Due to the histological similarity between the normal (eutopic) endometrium and endometriotic (ectopic) endometrium, it is thought that endometriosis responds to cyclical hormonal changes by growing and bleeding synchronously with the menstrual cycle. However, depth analysis of endometriosis has shown multiple and distinct differences between eutopic and ectopic endometrium. Although there are several theories regarding the origin of endometriosis, at present the true cause of the disease remains debated.


While a small percentage of women with endometriosis can be asymptomatic, pain is the most common symptom, other common symptoms are:

·      Excessive menstrual pain (dysmenorrhoea) that can begin around the time of ovulation and continue into menses. It should be noted that debilitating menstrual pain resulting in time being taken off from work or school requires further investigation.

·      Pain during or after sex (dyspareunia), particularly pain on deep penetration, this also applies during an internal examination.

·      Non-cyclic pain in the pelvic area for six months or more (chronic pelvic pain).

One of the other major symptoms of endometriosis is subfertility, a factor that affects around 50% of women with endometriosis.2 Women who wish to conceive may therefore undergo assisted reproductive therapies (ART). A review of ART for women with endometriosis compared to those without found that minimal endometriosis does not affect in vitro fertilisation outcomes. However, more severe forms decrease live birth rate, clinical pregnancy rate and the number of oocytes retrieved.

 In terms of pregnancy outcomes, women with endometriosis may be at an increased risk of pre-term birth, pre-eclampsia, placenta praevia and postpartum haemorrhage. Several studies have investigated the risk of miscarriage in women with endometriosis, so far no definite conclusion has been drawn.

Given the association with adverse pregnancy outcomes, women with endometriosis should be carefully monitored throughout pregnancy.

Surgical excision of endometriotic lesions has been found to improve conception rates up to 12 months post-surgery, as well as live birth rates. The evidence available does not show an improvement in conception rates for women with endometriosis undergoing medical treatment alone.4 It is also a commonly held belief that pregnancy is curative for endometriosis; this is however incorrect. During pregnancy pain symptoms may temporarily abate, however recurrence of symptoms is common post-partum.  

Other symptoms

Endometriosis can present with a multitude of symptoms, often making appropriate referrals difficult. Other symptoms include:

·      Pain with or after urination (dysuria).

·      Pain with or after bowel movements or bleeding from the bowel (dyschezia).

·      Irritable bowel like symptoms (diarrhoea, constipation, bloating).

·      Back pain.

·      Leg pain.

·      Chronic fatigue.

Symptoms can often be overlooked or dismissed in general practice due to a lack of awareness and normalisation of menstrual pain in women and young girls. It is therefore important to carefully assess young women presenting with menstrual symptoms in order to reduce diagnostic delay.

In addition to the physiological symptoms, the debilitating and chronic nature contributes to an increased risk of depression and anxiety.

Types and staging of endometriosis

Endometriosis can present with a multitude of different macroscopic appearances. These are broadly categorised into classes outlined in Table 1.

Endometriosis is classified according to the American Society for Reproductive Medicine point based system that divides endometriosis into four stages: minimal, mild, moderate and severe. Table 2 gives an overview of how the scoring system works.

It is very important to note the stage of endometriosis does not necessarily correlate with the severity of symptoms experienced. A woman with minimal disease may experience severe symptoms and conversely a woman with extensive disease may have minimal symptoms.

In rare instances endometriosis can be found away from the reproductive organs in sites such as, the diaphragm, bowel and bladder. Symptoms involving these organs (such as pain when breathing or shortness of breath for diaphragmatic endometriosis) that occur or worsen during menstruation can be an indication of endometriosis involving that area. However, a thorough assessment is recommended to eliminate more serious causes of symptoms involving the chest, bowel and bladder.


Because of the non-specific nature of some symptoms there is a lack of awareness and a high rate of misdiagnosis, the delay between onset of symptoms and receiving a diagnosis is seven to nine years.5 The gold standard for diagnosing is laparoscopic investigation of the pelvic organs.

Currently there are no non-invasive tests with a clinically relevant degree of sensitivity. A pelvic examination is usually only useful for assessing the presence of large endometriotic ovarian cysts (endometrioma), palpable nodules on the uterosacral ligaments or nodules visible on the cervix or posterior vaginal fornix.

An ulltrasound is a technique commonly employed to assess the presence, but serves little use in diagnosing other forms of the disease. Magnetic resonance imaging (MRI) can be a useful adjuvant to other diagnostic methods, particularly in cases where extensive adhesions limit surgical exploration of the pelvis, or determining the extent of deeply infiltrating endometriosis. However, as with an ultrasound, the resolution of MRI can be inadequate for identifying all endometriotic lesions. MRI is also useful for diagnosing comorbid conditions frequently associated with endometriosis such as adenomyosis (endometrial-like tissue inside the uterine muscle), which is found in around a fifth of women with endometriosis.6

Risk factors

There are several known risk factors for endometriosis, however there are also many stories in the press and online regarding endometriosis risks, with little supporting evidence, which have also become synonymous with the disease.

It is therefore important to provide patients with accurate information on which factors influence endometriosis risk. Table 3 gives an overview of risk factors commonly associated with endometriosis.


In accordance with the National Institute for Health and Care Excellence (NICE) guidelines,10 analgesics such as paracetamol, NSAIDs, ibuprofen, naproxen or mefenamic acid are often offered, unless contraindicated, to patients for pain management.

As endometriosis is an oestrogen dependant disease, many of the first line treatment options involve regulating or suppressing endogenous oestrogen production.

As hormonal manipulation frequently results in side effects, patients should be made fully aware of the advantages and disadvantages before starting a new treatment regimen.

Finding an optimal treatment approach that manages symptoms with minimal side effects can be a trial and error process; the most commonly used treatments include:

·      If the patient does not wish to conceive, a regimen of combined oral contraceptives (COCs) can be considered. Initially a monophasic three-month trial of a COC comprising 30-35mg ethinylestradiol and either norethistrone, norgestimate or levonorgestrel can be used. If this does not result in acceptable symptom control, a tricyclic or continuous regimen can be used. If symptoms still persist, COCs containing estradiol valerate and dienogest may be useful, if available.

·      Progestogen only contraceptives, such as oral desogestrel or levonorgestrel, medroxyprogesterone acetate, a subdermal implant and an intra-uterine system can also be used.

·      If the patient does not wish to take hormonal contraceptives, oral progestogens such as medroxyprogesterone or norethisterone can be offered.

·      Gonadotrophin-releasing hormone (GnRH) agonists such as goserelin and leuprolide depo injections, or nafarelin nasal spray may be offered if other hormone therapies do not give adequate symptomatic relief. Because of adverse effects on bone density, these treatments are restricted to six months of use. Patients taking GnRH medications frequently report adverse side effects from these treatments, therefore add-back therapy may be given to reduce side effects. It is important to note that medical therapy can only treat the symptoms of endometriosis and is not curative. Symptoms can quickly relapse after treatment cessation, therefore surgical intervention is required for long-term relief.

·      Laparoscopic excision of any identifiable endometriotic lesions/cysts is considered the best option for symptomatic relief and restoration of fertility.

·      Hysterectomy alone is not considered an effective treatment for endometriosis. It has been reported that conservation of ovaries carries a six fold risk of recurrent pain and an eight fold risk of reoperation where endometriosis was the primary cause of symptoms. This effect is particularly pronounced in patients with severe disease. It is therefore important to correctly distinguish endometriosis from other conditions, such as adenomyosis, and select appropriate surgical intervention. Patients undergoing hysterectomy with oophorectomy who require hormone replacement therapy should seek specialist medical advice if their symptoms recur. 


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2. Fadhlaoui A, Bouquet de la Jolinière J, Feki A. Endometriosis and infertility: how and when to treat? Frontiers in Surgery 2014;1:24

3. Hamdan M, Omar SZ, Dunselman G, Cheong Y. Influence of endometriosis on assisted reproductive technology outcomes: a systematic review and meta-analysis. Obstetrics and Gynecology 2015 125(1):79-88.

4. Brown J, Farquhar C. Endometriosis: an overview of Cochrane Reviews. Cochrane Database of Systematic Reviews. 2014;10;3:CD009590.

5. Moradi M1, Parker M, Sneddon A, Lopez V, Ellwood D. Impact of endometriosis on women's lives: a qualitative study. BMC Womens Health. 2014;14:123.

6. Di Donato N, Montanari G, Benfenati A, et al.  Prevalence of adenomyosis in women undergoing surgery for endometriosis. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2014;181:289-93.

7. Kennedy, S. and Koninckx, P. (2012) Endometriosis. In: Edmonds, D.K. (Ed.) Dewhurst's textbook of obstetrics & gynaecology. 8th edn. Chichester: Wiley-Blackwell. 615-624.

8. Nnoaham KE, Webster P, Kumbang J, et al. Is early age at menarche a risk factor for endometriosis? A systematic       review and meta-analysis of case-control studies. Fertility and Sterility. 2012;98(3):702-712.e6.

9. Vitonis AF, Baer HJ, Hankinson SE, Laufer MR, Missmer SA. A prospective study of body size during childhood and early adulthood and the incidence of endometriosis. Human Reproduction. 2010;25(5):1325-34.

10. National Institute for Health and Care Excellence (NICE). Endometriosis - Revised May 2014. (accessed 20 May 2015)