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Endometriosis - Symptoms, Diagnosis and Treatments

 

Introduction to Endometriosis

Endometriosis is defined as the presence of endometrial-type tissue outside the uterus. It is most commonly located within the pouch of Douglas and causes a chronic inflammatory reaction around nearby tissues. Endometriosis symptoms include pelvic pain and can also have a significant detrimental effect on a woman's quality of life. It is also associated with infertility and when severe can be the direct primary cause. Where possible it is essential to diagnose and treat endometriosis at any early stage.

Prevalence of Endometriosis

The prevalence of endometriosis is not accurately known although estimates vary greatly, it is believed to affect around 10% of women of reproductive age. It is also associated with infertility in up to 40% of women dependent upon the age of diagnosis. A more recent in-depth study in women over the age of 16 years, however, showed a prevalence closer to 1.44%. The peak incidence is 40 years of age and endometriosis symptoms usually resolve with the onset of the menopause. There are racial and ethnic variations with the highest prevalence amongst Asian women, followed by Caucasian with African women the least frequently affected.

In a large survey of over 70,000 adolescent women, dysmenorrhoea (painful periods) was a common cause of reported school absence. In the United States chronic pelvic pain affects approximately 1:7 women with very high associated annual health costs. A Norwegian study demonstrated that 2% of women had been treated for this condition by the age of forty. Endometriosis associated pain may be found in up to 60% of women with dysmenorrhoea and 40-50% of women with pelvic pain and dyspareunia (pain during sexual intercourse). Despite the identification of endometriosis symptoms there is often delay in establishing a diagnosis of endometriosis and hence a delay in ensuring effective treatment. This delay is up to 7 years and a consistent feature of most female populations.

Endometriosis Symptoms & Diagnosis

A detailed gynaecological history is essential when diagnosing endometriosis. It typically presents with dysmenorrhoea, menorrhagia (heavy regular menstrual periods), as well as deep dyspareunia, ovulatory pain and chronic pelvic pain in advanced cases. Urinary and bowel symptoms are more common in cases of severe endometriosis. A detailed examination is important and this should include a pelvic examination in women who are or have been sexually active. A pelvic ultrasound is an important screening tool for the markers of endometriosis such as endometriomas (ovarian cysts containing endometriosis.

Other endometriosis symptoms include the presence of free fluid within the pouch of Douglas, hydrosalpinges and pelvic tenderness. Magnetic resonance imaging (MRI) is a very useful tool in delineating cases of severe endometriosis with involvement of the bowel, bladder, ovaries, uterus and fallopian tubes. It can also identify adenomyosis, endometriosis within the myometrium of the uterus, which is a cause of severe dysmenorrhoea and pelvic pain. Where uretric involvement is suspected then an intravenous urogram (IVU) is of assistance in identifying the level of extrinsic ureteic constriction.

Two important markers for severe pelvic endometriosis are the presence of hydrosalpinges and endometriomas. Both should result in carefully planned treatment with the use of bowel preparation prior to surgery. They are both highly associated with infertility as well as pelvic pain.

Genetics of Endometriosis

Endometriosis has been seen to cluster within families and studies have identified a significant increase in women with an affected first-degree relative. This trend is also evident not only in daughters and sisters with the disease but also cousins. Studies of monozygotic and dizygotic twins have reported the disease to be expressed frequently in both types of twin, as well as exhibiting a similar age of onset compared to non twins sisters. These findings highly suggested a genetic basis for endometriosis with inheritance transmitted as a complex genetic trait.

Histology of Endometriosis

Endometriosis includes the presence of endometrial glands and stroma outside of the uterine cavity, most commonly within the pelvis. There is peritoneal invasion from the endometriotic foci within the ovaries, peritoneal covering of the uterorectal space (pouch of Douglas) and uterosacral ligaments. This results in a pro-inflammatory response leading to adhesion formation.

Consequences of pro-inflammatory response of endometriosis

Infertility and pelvic pain are two direct effects of endometriotic implant invasion. Abnormal proteolytic activity causes an altered activity of plasminogen activators and fibrinolytic activity. Endometrial implants present within the peritoneal fluid leading to adhesion formation and damage to surrounding, adjacent viscera such as the ovaries, fallopian tubes, uterus and large bowel. There appears to be altered apoptosis within ectopic endometrium leading to prolonged cell survival, increased cell proliferation and adhesion formation.

Laparoscopy and the diagnosis of endometriosis

The diagnosis of endometriosis is made primarily at the time of laparoscopy and the correlation between operative findings and pre-operative pain symptoms is not always uniform. Treatment should therefore, be targeted at the women's symptoms and assessed in terms of improvement in pain scores and quality of life. Both medical and surgical treatments have a significant role to play in the management of pain caused by endometriosis. It is important to assess outcome measures using validated pain scores and quality of life questionnaires. Careful examination of the pelvis can identify and treat early stage disease leading to effective treatment. Peritubal and periovarian disease is a direct cause of tubal infertility and can be better managed at a less advanced stage.

Medical management of endometriosis associated pain

Medical treatment of endometriosis symptoms is often the first line management treatment of pelvic pain. Precise documentation of the past surgical and medical history, including previous treatments, should be made before starting medication. The choice of treatment depends predominantly on the severity of pain and side-effects and to a certain extent costs.

Non-steroidal anti-inflammatory agents (NSAIDs)

NSAIDs do not treat endometriotic lesions but are effective in the treatment of pelvic pain. In particular the pain associated with dysmenorrhoea is mediated by prostaglandin symphysis. NSAIDs such as ibuprofen and mefenamic acid, inhibit cyclo-oxygenase enzyme activity therefore reducing prostaglandin production with a resultant improvement in pelvic pain. The main side effect of NSAIDs include gastric irritation.

Oral contraceptive pills

The oral contraceptive pill is often used as a first line treatment of endometriosis-associated pain. It works by creating a pseudo-pregnancy hormonal environment avoiding fluctuations in oestrogen and progesterone levels. It is effective in controlling and regulating menstrual blood loss and improving dysmenorrhoea. When taken on a continuous basis every 21-days for three pill packets amenorrhoea is likely to be induced and this regime is well tolerated. Its main use is a holding phase to keep endometriosis quiescent whilst a more effective treatment is planned such as laparoscopic surgery of fertility treatment.

Progestins

The commonest medication is oral Medroxyprogesterone acetate (Provera) taken daily in doses between 30-50mg. Progestins exert their effect by causing pseudo-decidualisation and atrophy of both the endometrium and endometriosis. Amenorrhoea results in a concomitant improvement in dysmenorrhoea and pelvic pain. Side effects of treatment include breakthrough bleeding, bloatedness, breast tenderness and weight gain, all of which reduce compliance.

The Levonorgestrel-releasing intrauterine coil device (Mirena IUCD) has shown benefits by significantly reducing menstrual blood flow and is some cases inducing amenorrhoea endometriosis-associated pelvic can be improved. It is often fitted at the time of laparoscopy and can be changed every five years.

Gonadotrophin-releasing hormone agonists

Gonadotrophin-releasing hormone agonists (GnRH agonists) induce stimulate and bind to the gonadotrophin receptors on the anterior pituitary resulting in down-regulation and a hypo-oestrogen state. Following an initial stimulation of the anterior pituitary and a flare of gonadotrophin release, gonadotrophin levels are suppressed and the ovarian becomes unstimulated with amenorrhoea resulting. There are three modes of administration for the different types of GnRH agonist dependent upon their half-life profile. Goserilin acetate (Zoladex) and Prostap are subcutaneous monthly injections, Naferelin (Synarel) is a nasal spray used every 12 hours and Leuprolide (Lupron) is a monthly depot intramuscular injection. There is a significant improvement in pelvic pain but there is a high incidence of vasomotor side effects. They can be used on short term basis for three months prior to or after laparoscopic excisional surgery for advanced endometriosis.

Surgical management of endometriosis

Laparoscopy allows a diagnosis of endometriosis to be made along with an assessment of the extent of disease. With the advent of improved laparoscopic equipment and enhanced surgical techniques complex conservative surgery can now be performed safely. In severe cases where bowel, bladder and ureter are involved, laparotomy may be required sometimes with the assistance of surgical colleagues. The aim of surgery is to remove or destroy visible and or palpable endometriosis with the specific aim of improving pelvic pain and enhancing fertility.

The extent of surgery is dependent on the preoperative endometriosis symptoms and the severity of disease. Most clinicians use the revised American Fertility Society (AFS) scoring system for endometriosis, comprising 4 groups, minimal (stage I), mild (stage II), moderate (stage III) and severe (stage IV) according to the operative findings. Various treatment modalities are available for use at laparoscopic surgery. These include; laser, scissors with monopolar electrocautery and bipolar coagulation, harmonic scalpel, all of which allow resection, cauterisation and vaporisation of endometriosis. It is clear that the severity of disease has a direct effect on fallopian tube function as well as pelvic pain and infertility.

Early Stage Disease - Minimal and Mild Endometriosis

These two groups of endometriosis more often involve the superficial peritoneal covering of the pelvic organs. They are usually treated with coagulation or laser vaporisation of the endometriotic implants. Ablation or laser destruction of early stage disease endometriosis has been shown to increase fertility and should be routinely planned and performed at the time of laparoscopy.

Advanced Disease - Moderate and Severe Endometriosis

These two groups relate to the extensive presence of endometriosis within the pelvis but this does not always correlate to the severity of pelvic pain especially dysmenorrhoea. Deep infiltrating endometriosis is present when endometriosis penetrates greater than 5mm under the peritoneal surface. It can involve the uterosacral ligaments, the posterior vaginal wall and anterior rectal wall. The presence of severe endometriosis requires careful pelvic examination to identify the lesions and does not always correlate with a high revised AFS score. A recent study demonstrated that the severity of pelvic pain in particular dysmenorrhoea correlated to the depth of involvement of endometriosis. To reduce pelvic pain and prevent recurrence of symptoms, surgery would require excision of the endometriotic lesion as well as coagulation or laser vaporisation of more superficial endometriotic implants.

Endometrioma management

Endometriomas are endometriotic ovarian cysts and often associated with moderate to severe endometriosis. There treatment objectives are best achieved by therapeutic laparoscopic surgery and should reduce pelvic pain, prevent recurrence and enhance fertility. Small endometriomas, less than 5mm, are normally drained and coagulated but can be vaporised or excised. An alternate method is to perform laparoscopic cyst fenestration, ablation of the cyst capsule and ablation of coexisting endometriosis. This significantly improves pelvic pain with a very high patient satisfaction rating.

Laparoscopic Uterine Nerve Ablation (LUNA)

This procedure involves transection of both uterosacral ligaments with the specific aim of disrupting the efferent nerve fibres supplying the uterus. The technique remains controversial as there is no good evidence to demonstrate it is effective. The use LUNA laparoscopic laser vaporisation of endometriosis has not been found to improve pelvic pain. Only in the presence of deep infiltrating endometriotic lesions on the uterosacral ligaments is excision advised.

Laparoscopic fallopian tube surgery

Laparoscopy is an effective treatment for terminal fallopian tube disease. Peritubal adhesions can be dissected and lysed and the pelvic anatomy restored. Opening of the terminal end of the fallopian tubes when closed, neosalpingostomies can allow for drainage of terminal hydrosalpinges and enhanced fertility. For permanently damaged fallopian tubes it may be necessary to perform salpingectomy to increase the chances of implantation following in vitro fertilisation (IVF) treatment.

Endometriosis and its effect on the fallopian tubes

Endometriosis has an extrinsic effect on the fallopian tubes by altering the peritoneal pelvic environment with the expression of pro-inflammatory cytokines leading to adhesion formation and terminal fimbrial damage. There is evidence that the altered fallopian tube configuration can lead to infertility.

Expectant management of endometriosis

It is unclear what the natural history of endometriosis is as in some situations endometriosis can improve without any treatment. Expectant management may be reasonable especially if the finding of endometriosis is incidental and the woman is in her forties and completed her family. The prevalence of endometriosis in women identified at the time of laparoscopic sterilisation was 14% and the majority had no symptoms of pelvic pain.

Conclusions

Endometriosis is common disease and is a direct cause of infertility and pelvic pain. It causes adhesion formation within the pelvis and terminal damage to the fallopian tubes. Even in early stage disease there is a direct effect on fallopian tube function. Treatment by laparoscopic ablative surgery is most likely to reduce pain and enhance fertility. It is essential at all times to plan treatment and monitor response to ensure an improvement in pelvic pain, fertility and quality of life.

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From the first consulation with Mr. Davis | immediately felt confident in his abilities and expertise. He explained everything | needed to know about endometriois and PCOS so that we could make decisions to fix the problems and avoid fertillty issues...