Contents
Introduction
Endometriosis is a condition in which endometrial, or endometrial like tissue grows outside of the uterus. Although in the vast majority of cases the endometriosis is located within the pelvis (on the uterosacral ligaments, in the ovaries or on the pelvic wall) it can rarely been found in other locations such as the lungs, umbilicus and skin. The growth of these lesions is hormonally mediated, and as such, endometriosis is a disease of reproductive age women.
In severe cases, large cystic lesions may form, and other lesions can invade the bladder or bowels and cause extensive adhesions.
The main symptom of endometriosis is cyclical abdominal pain, which can make it difficult to differentiate form dysmenorrhoea. It typically begins in adolescence with dysmenorrhoea, which gradually increases in severity over time (typically over a period of years). There is often a family history of endometriosis and / or hysterectomy + oophorectomy. As the disease develops, the symptoms can become more constant and less cyclical.
Patients often have symptoms for many years before a diagnosis – the average time from symptom onset to diagnosis is about 7 years.
One theory of the pathophysiology suggests that with each menstrual cycle, there is a risk of “seeding” of endometrial tissue into the intra-abdominal cavity, due to retrograde flow of menses. This explains why many women’s symptoms progress over time, however it does not explain the extra-abdominal manifestations of some cases of endometriosis.
As such, many treatment aim to reduce the number of episodes of menses to prevent seeding of further tissue, and to prevent bleeding of the ectopic endometrial tissue that has already appears at extra-endometrial locations. It is thought that is it eh blood from the tissue that is responsible for a lot of the symptoms of endometriosis as it irritates the surrounding tissues.
In the past, diagnosis was almost exclusively done by laparoscopy. However, more recently, clinical diagnosis has become acceptable. Symptoms can be wide ranging, and the appearance of endometrial tissue on laparoscopy does not correlate with the severity of symptoms; some women have severe symptoms and only minimal laparoscopic findings, whilst other have relatively few symptoms and extensive laparoscopic disease.
Management can be divided into:
- Symptomatic treatments – such as those for menorrhagia and dysmenorrhoea, including NSAIDs or mefanamic acid
- Hormonal treatments – which suppress the normal cycle and prevent menses. The COCP is often used first line, but Mirena is also commonly used
- Surgical treatments – such as ablation of endometrial tissue on laparoscopy
Most patients can be managed in the community with a combination of symptomatic and hormonal treatments. The disease can be severely disabling for some patients, and can result in a lot sick days. Patients with severe disease may be advised to plan to have their family earlier in life and plan for a subsequent hysterectomy.
Epidemiology and Aetiology
- Affects 5-10% of reproductive age women
- About 1/3 of cases are asymptomatic
- About 20% of patients will improve spontaneously
- In the other 80% symptoms will be stable or gradually become more severe
- Associated with reduced fertility
- Risk factors include:
- A genetic link has been established for endometriosis. The origin of the lesions is mostly retrograde menstruation; however for some of the further afield lesions, such as lungs, spread is thought to be through blood or lymph.
- Some books mention Sampson’s theory, which ties in patient age, with their obstetric and gynaecological histories and predicts various things like the site of the lesions, and the likelihood they will recur after surgery. It’s quite complex, but likens the endometrial tissues to dandelion seeds spreading throuought the pelvis.
- There are also some autoimmune and environmental factors implicated.
Pathophysiology
It is believed that retrograde flow of uterine contents – up into the abdominal cavity rather than down into the vagina – is important in the formation of endometriosis. This might explain why symptoms often start off mild shortly after menarche, and gradually progress – typically over a period of years.
- It is thought that some anatomical variations – such as cervical stenosis, or other atypical variants of uterine anatomy can contribute to this process
It is also believed that there are genetic variations in cell apoptosis and adhesional qualities, which mean that the tissue which has flowed in a retrograde fashion into the abdominal cavity is more likely to adhere to other structures, and then live on – and continue to function as endometrial tissue.
- There may also be important immunological factors relating to how the immune system deals with this tissue that allow it to survive in some individuals and go on to cause endometriosis
Symptoms typically settle during pregnancy and breastfeeding, but return again with the return of menstruation. Symptoms almost always settle with menopause.
The tissue outside of the uterus typically responds in exactly the same way as the uterine tissue – in response to hormonal changes with each menstrual cycle.
- Endometriosis is a relapsing/remitting condition.
- The endometrial tissue acts just like it would in the uterus, responding to cyclical hormone levels, growing and bleeding at certain times of the cycle.
- If the tissue is in the ovaries, then chocolate cysts may form into which the lesions bleed
- Due to inflammation that happens at the site of the endometrial tissue, fibrosis occurs and in the abdomen and pelvis this leads to adhesions forming. These can lead to a frozen pelvis, and often affect fertility.
- Very rarely these can be malignant
Some specialists divide endometriosis lesions into three types
- Superficial endometrial implantation into the peritoneum
- Endometrial lined ovarian cysts – which may go on to form ‘chocolate cysts’
- Endometriotic nodules – large collections of endometrial, fat and connective tissue, found between the vagina and rectum
Signs and Symptoms
Many patients with endometriosis are asymptomatic. However endometriosis is a common cause of chronic pelvic pain, and can also cause deep dyspareunia, dysmenorrhoea and subfertility.
The cyclical nature of the symptoms can help to rule out other causes. It might be useful to ask patients to keep a symptom diary to work out if the symptoms are truly cyclical.
A typical presentation might include:
- Dysmenorrhoea / cyclical abdominal pain.
- Often from an early age
- Generally progressive over time
- Pain both pre-menstrual and menstrual – often beings a few days before menstruation and settles a few days afterwards
- May be difficult to differentiate from primary dysmenorrhoea in teenage women
- Primary dysmenorrhoea typically begins within 2 years of menarche, but usually does not worsen with time
- Dyspareunia
- Pain on vaginal examination / vaginal USS
- Strong FHx of endometriosis and / or early hysterectomy
- The rare but obvious sign is bleeding from odd places, and indeed depending on the site of the lesion patients may experience haematuria, rectal bleeding, bleeding from the skin, or even in the eyes!
- Bleeding from these other sites (if present) will usually be cyclical
- If a chocolate cyst ruptures, then you get signs of an acute abdomen, acute pain, tenderness, fever etc.
- All of the symptoms tend to be cyclical in response to circulating hormones; however some may persist for periods.
- Abdominal tenderness, without rebound or guarding
- Usually no palpable masses
- Often the examination will be normal
Pelvic examination (PV examination)
- NOT appropriate in an adolescent whom has never been sexually active
- Indicated only if:
- Not responding to conventional treatment, OR
- Organic pathology is suspected
- If indicated:
- Speculum examination
- Bimanual examination
- Often painful
- Consider STI testing if indicated
Differential Diagnosis
- Primary dysmenorrhoea
- Adenomyosis
- Mittelschmirtz
- PID / STI
- IBS
- Diverticulitis
- Interstitial cystitis
Investigations
The definitive “investigation” is the discovery of patches of endometriosis on laparoscopy – and in practice, in patients with severe and recurrent pain, this is often performed as the diagnostic test. However, endometriosis can be a clinical diagnosis. Many of the investigations are performed to rule out other differentials, and will typically be normal in endometriosis.
- Therapeutic ablation can often be performed at the same time as a diagnostic laparoscopy
Often, imaging such as USS is not able to detect areas of endometriosis within the abdomen, however it is frequently performed to assess for other causes – such as fibroids or ovarian cysts. USS is often normal in endometriosis. A transvaginal scan is preferred over transabdominal scan as it provides better quality images, but may not be appropriate in some (particularly younger) patients.
Other investigations are often performed and may be supportive of the diagnosis, or of a differential.
- Bloods for anaemia and consider hormone levels
- CA-125 is often raised, but non-specific and should not be used as a diagnosis test
- Urine dipstick to confirm haematuria
- Laparoscopy, as diagnosis is made by actually seeing the lesions (plus or minus biopsy)
- Transvaginal ultrasound to exclude other causes (endometrial cancers, ovarian cysts, adenomyosis)
- Endometrotic lesions can sometimes be seen on USS
- MRI scan may be able to detects endometriosis lesions, but its role in diagnosis is uncertain and not standard practice
Many cases may be diagnosed clinically on the basis of significant cyclical abdominal pain.
Management
The earlier that treatment is started, the better the long-term outcome, particularly in regards to subfertility and pain.
- If the endometriosis is asymptomatic then often no treatment is needed
- Analgesia may help, but is not particularly effective
- Suppression of ovarian function is effective at controlling pain. This can be achieved through hormonal means, or surgically
- Start with non-surgical treatment options. If patients do not respond in 3-6 months – consider referral to gynaecology for consideration for surgical management
Medical management
- Analgesia for the pelvic pain
- Paracetamol 1g QID
- NSAIDs – e.g. naproxen 750mg daily
- More effective if you use a large dose right at the start of the cyclical symptoms
- Evidence for their effectiveness in endometriosis is por, but they are proven effective in other causes of dysmenorrhoea
- Hormonal treatments
- Almost all type of hormonal contraception will have some benefit in endometriosis, including the progesterone only options
- Consider the patients short and medium term fertility options – hormonal options are not suitable in patients who wish to become pregnant
- These aim to reduce or stop bleeding from endometrial tissue
- The goal is to prevent ovulation, and subsequently to prevent build-up and breakdown of endometrial tissue
- COCP is typically the first-line treatment
- Make sure to ensure there are no contraindications (use UKMEC)
- Suggest concurrent packet usage – without withdrawal bleed – for up to 12 months between each withdrawal bleed
- Mirena / IUD also often considered as a first or second line option
- Is effective and preventing retrograde uterine flow, but less effective at treating established endometriosis
- The latest NICE guidelines even suggest this as a first line agent and advise that Mirena has the best evidence
- Progesterone only pill – e.g. cerezette (desogestrel)
- MPA – medroxyprogesterone acetate orally may also be considered
- Induces amenorrhoea
- Side effects are common and can include:
- Weight gain
- Acne
- Loss of libido
- Moodiness
- Not effective as a contraception – additional barrier contraception is recommended
- Depot injection of MPA (Depo-provera)
- Causes amenorrhoea in 50-70% of patients
- Gonadotropin releasing hormone (GnRH) may occasionally be used
Management in patients who are trying to conceive can be very difficult. These patients can only really take analgesia if they wish to continue trying to conceive. These patients should be referred to obs & gynae early.
Surgical management
Many patients can be managed in primary care. Consider specialist referral for patients whose symptoms do not respond to medical management or who have very severe symptoms. Significant disease can lead to adhesions. Surgical treatment can involve several procedures.
- Incision or ablation of the pelvic adhesions
- Typically should be performed by a gynaecologist with a special interest in this area
- Is effective for pain relief, but 10-50% of patients have recurrence within1 2 months
- Use of IUD or COCP for 18-24 months after surgery may prolong the effectiveness of surgery
- Last resort – Total hysterectomy and bilateral salpingo-oophorectomy. (Can be done vaginally, abdominally or laprascopically)
- Patients with severe disease maybe advised early in the course of their illness to consider early family planning and subsequent hysterectomy and salpingo-oophorectomy
- Fertility help for if the woman wishes to conceive
Prognosis
- 30-50% of women with endometriosis have infertility
- Early referral to gynaecology is the best way to maximise treatment effectiveness and fertility
Useful Resources
Flashcard
References
- Murtagh’s General Practice. 6th Ed. (2015) John Murtagh, Jill Rosenblatt
- Oxford Handbook of General Practice. 3rd Ed. (2010) Simon, C., Everitt, H., van Drop, F.
- Beers, MH., Porter RS., Jones, TV., Kaplan JL., Berkwits, M. The Merck Manual of Diagnosis and Therapy