Endometriosis is a common gynaecological condition affecting about 6–10% of women of reproductive age and can be a debilitating disease. It is the second most common reason for surgery in premenopausal patients. It is defined as the presence of endometrial-like tissue outside the uterine cavity, leading to a chronic inflammatory reaction. The exact aetiology is unknown, but the retrograde menstruation model is the most widely accepted theory explaining the development of pelvic endometriosis. According to this model, menstrual blood containing endometrial fragments passes through the fallopian tubes into the pelvic cavity, resulting in the formation of peritoneal endometrial deposits. There are three distinctive pathological types of pelvic endometriosis: superficial peritoneal implants, ovarian endometriomas, and deep infiltrating nodular lesions. The extent of the disease is very variable and often does not correlate with the severity of symptoms. Although it can sometimes be asymptomatic (in about 20% of cases), endometriosis is frequently associated with severe pain and infertility. Several management options exist for endometriosis and the choice depends on several factors such as age, fertility, severity of the symptoms, and extent of the disease. This review presents three different cases of endometriosis with different complexities and presentations. The diagnosis and various medical and surgical treatment options available to the clinician will be discussed.
Pathological Types of Endometriosis
Superficial peritoneal endometriosis: peritoneal implants consist of glandular and stromal tissue and respond to the hormonal changes associated with the menstrual cycle showing cyclical changes similar but not identical to the normal endometrium. These implants heal by fibrosis.
Deep infiltrating (adenomatous) endometriosis: this type of endometriosis is characterized by proliferative fibromuscular tissue with sparse endometrial glandular and stromal tissue (similar to adenomyosis), with no surface epithelium. Unlike the peritoneal endometriosis, deep endometriosis does not show significant changes during the menstrual cycle. These nodules are typically present in the recto-vaginal space and can involve the utero-sacral ligament, the posterior vaginal wall, and the anterior rectal wall. They can also extend laterally and affect the ureters.
Ovarian endometriomas: an endometrioma is an ovarian cyst lined by endometriotic tissue and containing dark brown or chocolate-coloured fluid, which results from recurrent chronic bleeding from the endometriotic implants. In long-standing endometriomas, the endometriotic tissue is gradually replaced by fibrotic tissue.
A 17-year-old patient presented to her general practitioner with a 6-month history of severe and excruciating dysmenorrhoea. Pelvic examination revealed no abnormality, and a diagnosis of primary physiological dysmenorrhoea was made. The general practitioner prescribed painkillers in the form of non-steroidal anti-inflammatory drugs, which provided some benefit. However, the dysmenorrhoea continued to disrupt the patient’s life, and she was eventually referred to the gynaecologist. Pelvic examination by the gynaecologist revealed tenderness over the utero-sacral ligaments and on cervical movement. A transvaginal ultrasound scan revealed no pelvic abnormality. The gynaecologist made a provisional diagnosis of endometriosis and prescribed combined oral contraceptive pill (COCP). Three months later, the patient reported a signifi-cant improvement of her pain, but continued to experience some degree of dysmenorrhoea. She was therefore advised to tricycle the pill.
What Are the Main Presenting Symptoms for Endometriosis?
The main presenting symptoms of endometriosis include chronic pelvic pain and infertility. Patterns of chronic pelvic pain caused by endometriosis include dysmenorrhoea, non-cyclical pelvic pain, and dyspareunia. The pain may also be associated with other cyclical symptoms, particularly related to the involvement of the urinary or gastrointestinal (GI) tract with endometriosis. The severity of these symptoms does not necessarily correlate with the extent of the disease when diagnosed at laparoscopy, as mild disease can cause severe symptoms. On the other hand, about 20% of women with advanced endometriosis have no symptoms.
Dysmenorrhoea: this is the most common presenting symptom, affecting up to 80% of women with endometriosis. It is often described as severe and debilitating and does not respond to simple analgesia. The pain classically starts 1–2 weeks before the onset of menstruation and gradually worsens, reaching a peak in severity during the first 2 days of the menstrual flow. The pain then gradually lessens until it disappears at the end of the period.
Non-cyclical pelvic pain: this affects up to a third of patients with endometriosis. It is often associated with adhesions, large ovarian endometriomas, peritoneal inflammation, and bladder or bowel endometriosis. Pain resulting from pelvic adhesions is usually provoked or worsened by certain body movements. Other pains may be triggered by ovulation, bowel movements (dyschezia), or urination. All types of non-cyclical pains often worsen around the time of menstruation.
Deep dyspareunia: this affects about a third of patients with endometriosis and is mainly seen in advanced disease with deep infiltrating nodules. It may be severe enough to force the patient to abstain from intercourse. The pain is usually described as a stabbing pain on deep penetration. It is triggered by pressure on the scarred utero-sacral ligaments, recto-vaginal nodules or adhesions obliterating the pouch of Douglas, or involving the ovaries. The symptoms are typically worse before menstruation.
How Would You Diagnose Endometriosis in Adolescents?
Symptoms: adolescents with endometriosis often present with acyclic and/or cyclic pelvic pain. Bowel and bladder symptoms are also common in this group of patients. Chronic pelvic pain severe enough to disrupt normal activities and school attendance in adolescents is suggestive of endometriosis. The presence of the classical patterns of pain described above has a sensitivity of 76% and a specificity of 58% in detecting endometriosis. Around 30% of adolescents with chronic pelvic pain have endometriosis. Adolescents with pelvic pain not responding to analgesia and/or the COCP have about a 70% prevalence of endometriosis.
Analysing the pattern of pelvic pain is crucial in establishing the diagnosis of endometriosis in adolescents. A pain diary documenting the frequency and character of the pain will help to determine whether the pain is cyclical and if it is related to bowel or bladder function. A family history of en-dometriosis is correlated with a higher likelihood of endometriosis in these patients.
Although, endometriosis is the commonest cause of chronic pelvic pain in adolescents, other causes such as sexual abuse, ovarian tumour or genital tract anomalies, eg, imperforate hymen should be considered.
Examination: pelvic examination, which may not be possible in adolescents, does not usually reveal specific signs in most patients with endometriosis. However, this examination is important mainly to rule out other causes of chronic pelvic pain such as ovarian tumour or genital tract anomalies. In adolescents who are not sexually active, bimanual rectal–abdominal examination may be considered as it is better tolerated than a bimanual vaginal–abdominal examination. A number of signs can be detected in some patients with endometriosis, including thickening, nodularity and tenderness over the uterosacral ligaments, fixation and retroversion of the uterus, and fullness or a mass in the pouch of Douglas.
Differential diagnosis: this includes all gynaecological and non-gynaecological conditions that cause chronic pelvic pain. Gynaecological disorders include primary dysmenorrhoea, sexual abuse, ovarian cysts/tumours, and genital tract anomalies. In sexually active adolescents, pelvic adhesions should also be considered (due to a previous pelvic inflammatory infection) in the differential diagnosis. Non-gynaecological diseases to be considered in the differential diagnosis include irritable bowel syndrome, inflammatory bowel disease, interstitial cystitis, and musculoskeletal pain.
Imaging: this is of limited value in the diagnosis of endometriosis. A transvaginal ultrasound scan is useful in detecting endometriomas; however, endometriomas are rarely seen in adolescents. Magnetic resonance imaging is of value in identifying the presence and the extent of deeply infiltrating lesions. It may also help in detecting bowel and ureteric involvement.
Laparoscopy: this is the ‘gold-standard’ for the diagnosis of endometriosis. However, in adolescents, this procedure should only be considered in patients with disabling pain not responding to analgesia and/or the COCP. Ideally, a laparoscopic surgeon competent in managing endometriosis surgically should perform the procedure. The surgeon should also be comfortable operating on adolescents and be familiar with all the various morphologies of endometriosis. Clear, red, white, and/or yellow-brown lesions are more frequently found in adolescents than black or blue lesions. The procedure carries a 3% risk of minor complications and a 0.6–1.8/1,000 risk of major complications such as bowel perforation and vascular damage (Box 1).
MEDICAL TREATMENT OF ENDOMETRIOSIS IN ADOLESCENTS
What Are the Available Medical Treatment Options That You Would Like to Discuss With This Young Patient?
Non-hormonal medical therapy (analgesia): empirical treatment with analgesics for chronic pelvic pain with a pattern suggestive of endome-triosis (without a definitive diagnosis) should be considered as a first-line treatment option in ado-lescents. Non-steroidal anti-inflammatory drugs (eg, mefenamic acid or diclofenac) can be effective. The administration of these medications should be limited to episodes of pains lasting for a few days, eg, dysmenorrhoea.
1. The COCP is a good choice for adolescents with possible endometriosis and can be used as an alter-nate first-line therapy. It improves dysmenorrhoea and offers a reliable method of contraception. COCP is generally well tolerated, safe, and inexpensive. Another advantage of the pill is that it can be used as long-term therapy. Tricycling the pill reduces the number of bleeds and the associated pain. Possible side effects include weight gain, headaches, nausea, breast enlargement, and depression. Patients should be warned about the increased risk of thromboembolism during COCP administration.
2. Gonadotrophin-releasing hormone (GnRH) agonists: the empirical use of GnRH agonists in adolescents without a definitive diagnosis of endometriosis is controversial. Although, it may help to avoid laparoscopic surgery, GnRH agonists could adversely affect the final bone density formation, particularly in patients younger than 17 years. Furthermore, a definitive diagnosis and staging with laparoscopy may be necessary to plan long-term management of endometriosis, which is potentially a progressive disease with no cure (Boxes 2 and 3).
A 38-year-old woman presented to the gynaecology outpatient clinic with a 12-month history of worsening intermittent lower abdominal and pelvic pain, and severe dyspareunia. The pains were severe enough to disrupt her life and sexual relationship. A recent severe episode of the pain led to an emergency admission to the hospital. She had no previous surgery and had completed her family, having had one child delivered vaginally in the past.
Pelvic examination revealed tenderness affecting the right adnexa and the pouch of Douglas. She underwent a laparoscopy, which revealed widely spread deposits of active peritoneal endometriosis affecting both ovarian fossae, the utero-sacral ligaments, the pouch of Douglas, and the utero-vesical peritoneal fold. Extensive adhesions were also present between the bowel and anterior abdominal wall. All endometriotic deposits were ablated with electro-diathermy, and the adhesions were divided with scissors. At post-operative follow-up, her pain and dyspareunia were much improved. However, 6 months later she experienced a recurrence of her symptoms. She was then counselled regarding further management options and decided to take a 6-month course of GnRH agonist. This improved her pain dramatically, and she found the side effects manageable. However, a few months after the completion of GnRH agonist therapy, the symptoms started to recur. The patient returned to clinic requesting a hysterectomy as a more definitive treatment for her pain.
What Is the Current Role of GnRH Agonists in Endometriosis?
How Do GnRH Agonists Work and What Should You Warn the Patient About?
How Can You Treat Potential Side Effects and How Long Would You Prescribe the Treatment for?
GnRH agonists are usually offered as a second-line medical therapy for endometriosis in patients with severe symptoms not responding to analgesics or COCP. They are also a good option for women experiencing persistence or recurrence of severe symptoms after conservative surgery as is in our case. GnRH agonists cause an initial stimulation of the GnRH receptors on the gonadotrophs of the anterior pituitary gland, followed by inhibition due to loss of these receptors (known as receptor down-regulation). The resulting fall in follicle-stimulating hormone leads to a pseudo-menopausal status with oestrogen deficiency due to ovarian suppression. Prolonged oestrogen deficiency eventually causes atrophy of the ectopic endometrial tissue with sub-sequent relief of pain. The initial stimulation often causes worsening of the symptoms during the first 2 weeks of treatment. Patients may also experience irregular bleeding during the first 2 months of GnRH agonist therapy, but amenorrhoea then usually ensues. About 80% of patients start to experi-ence improvement or complete relief of pain about 4 weeks after the initiation of treatment. This im-provement will continue throughout the 6-month course of GnRH analogue therapy. However, the majority of patients will experience a recurrence of symptoms few months after discontinuation of treatment. GnRH agonists are given as injections either on a monthly or 3-monthly basis. Side effects include menopausal symptoms of hot flushes, night sweats, mood changes, and vaginal dryness. The most worrying potential side effect is a 5–6% loss of bone mineral density. This limits the safe use of GnRH agonists to 6 months. The bone loss usually recovers partially after 6–12 months of discontinu-ation of GnRH agonists. The hypo-oestrogenic side effects and bone mineral loss can be significantly reduced by the daily administration of tibolone 2.5 mg as an add-back therapy. In some patients, it may be necessary to continue the GnRH agonist therapy beyond 6 months (unlicensed use). It is rec-ommended in these cases to monitor bone density on a yearly base.
Compared with medical therapy, surgery offers a more definitive treatment of endometriosis and tends to achieve longer lasting improvement of symptoms. The principles of surgical treatment of endometriosis include ablation, vaporization or excision of peritoneal implants, excision or ablation of endometriomas, excision of deep infiltrating nodular endometriosis, and restoration of pelvic anatomy by adhesiolysis. The reported incidence of disease recurrence at 5-year follow-up is about 20% for surgery compared with about 50% for medical treatment. However, about 30% of patients will not experience any improvement in symptoms after surgery. Also of note is that surgery is more effective in reducing pain in patients with more advanced endometriosis.
A laparoscopic approach for endometriosis surgery is superior to laparotomy as it allows a more thorough inspection of the pelvis with higher magnification, allowing the detection of subtle en-dometriotic lesions. In addition, laparoscopic surgery minimizes trauma to tissues, resulting in less post-operative adhesion formation. Laparoscopy is also associated with less blood loss, and with its magnification it allows good detection and control of small bleeders. From the patient’s perspective, laparoscopic surgery shortens hospital stay and allows quicker return to normal activities.
The stage and severity of endometriosis should be assessed and documented at laparoscopy by describing the findings and using the revised American Fertility Society classification system (stages I–IV). Systematic inspection of the whole pelvis and abdominal cavity is essential. The laparoscopic sur-geon should be familiar with the different typical and atypical forms of pelvic endometriosis. Typical peritoneal implants are pigmented lesions including dark powder-burn, black puckered, brown, blue-black, and yellow deposits. Atypical non-pigmented lesions include clear, white or red polypoid or flame-like lesions. Other lesions include defects (windows) in the peritoneum. Ovarian endome-triomas are thick-walled unilocular or multilocular cysts of varying sizes (usually < 12 cm in diameter) containing chocolate-coloured fluid due to repeated bleeding from the endometriotic tissue. They are typically associated with advanced endometriosis and extensive adhesions between the affected ovary and pelvic sidewall, back of the uterus, and broad ligament. However, about 12% of endometri-omas are not associated with adhesions or severe disease. Deep infiltrating endometriosis (> 5 mm depth of infiltration) usually affects the recto-vagi nal septum and uterosacral ligaments. Utero-sacral ligament endometriosis is usually characterized by thickening and firmness of the ligament with visible scarring. It is therefore necessary to palpate the utero-sacral ligament either with the end of a blunt laparoscopic probe or by vaginal examination. Obliteration of the pouch of Douglas occurs when the affected rectum is pulled upwards and becomes fixed to the back of the uterus, causing partial or complete obliteration of the pouch of Douglas.
Minimal-to-mild peritoneal endometriosis can either be excised or ablated with electro-coagula-tion or laser vaporization. Care should be taken to avoid thermal damage to the ureters when treating the pelvic sidewall. Both ablation and excision of mild endometriotic implants have been shown to be equally effective in improving post-operative pain.
Deep infiltrating endometriosis affecting the utero-sacral ligaments and/or recto-vaginal septum should be completely excised.
This includes total abdominal hysterectomy with or without bilateral oophorectomy. This treatment option should only be considered in patients who have completed their family and have had failed medical or conservative surgical treatments. A pre-operative trial of GnRH analogues may be helpful in determining whether this treatment will be successful and whether oophorectomy should also be performed. All deep-seated endometriosis should be removed during the hysterectomy to prevent remaining disease from causing persistent pain. Bilateral salpingo-oophorectomy may result in a better pain relief with reduced chances of further surgery in the future. However, this benefit has to be balanced against the disadvantage of inducing menopause with the need of hormone replacement therapy (HRT), especially in patients under 40 (Box 4).
A 26-year-old lady presented with a long-standing history of severe dysmenorrhoea and dyspareunia. The pattern of dysmenorrhoea was typical of endometriosis (as described above). She had been trying to conceive for the previous 15 months without success. She had also been troubled with indigestion and constipation. Her GI symptoms gradually worsened until she became unable to have solid food and survived on fluids only. As a result, her weight dropped dramatically from 58 to 38 kg over a period of 6 months.
Pelvic examination revealed a fixed and retroverted uterus, but no recto-vaginal nodules were found.
A transvaginal ultrasound scan showed a thick-walled, 7-cm, right ovarian cyst with internal echoes, suggestive of an endometrioma. A diagnostic laparoscopy was performed and showed grade IV endometriosis with extensive adhesions involving the bowel and completely covering the pelvic organs. Only the superficial part of a right-sided ovarian cyst was seen firmly adherent to the bowel, uterus, and abdominal wall. The tubes and ovaries could not be visualized. In view of the extent and severity of the endometriosis and the involvement of the bowel, no treatment was performed on that occasion.
Post-operatively, a magnetic resonance imaging scan was performed showing an 8-cm multi locular cyst on the right ovary with several pelvic deposits of endometriosis involving the bowel. In view of the bowel involvement with endometriosis and the severe GI symptoms, the patient was reviewed by a colorectal surgeon who discussed various surgical options for bowel endometriosis. The patient was also counselled about the possible need of a colostomy.
The patient was offered conservative surgery through laparotomy for her extensive endometrio-sis. The procedure was carried out jointly with the colorectal surgeon.
At laparotomy, extensive adhesiolysis was carried out freeing the bowel, uterus, tubes, and ova-ries. The right ovarian endometrioma was opened and drained. The cyst wall was then stripped off and sent for histology. A large segment of the colon was found to be affected by the disease. A hemi-colectomy was therefore performed. Interestingly, the histological examination of the resected colon revealed coexisting Crohn’s disease in addition to the endometriosis.
Two months after surgery, the patient recovered very well, and all her pain and GI symptoms have completely resolved. She was able to eat normally and gradually gained weight. At this stage, she was referred to have in vitro fertilization (IVF) treatment.
SURGERY FOR EXTENSIVE DISEASE
What Is the Importance of Pre-operative Assessment?
Pre-operative assessment helps to achieve an accurate diagnosis of the stage of the disease and to assess patient’s fitness for the surgery. This will help to choose the best surgical approach and to anticipate possible difficulties. In patients with suspected deep infiltrating endometriosis, it is important to exclude ureteric, bladder or bowel involvement. A magnetic resonance imaging scan is of value in determining the extent of deeply infiltrating lesions and the involvement of bowel and bladder. Other investigations of value may be a contrast enema and intravenous urogram. The management of deeply infiltrating lesions is very complex. Patients should be referred to centres with the necessary expertise and a multidisciplinary team should be involved in the treatment. Pre-operative bowel preparation should be considered.
What Is the Association Between Endometriosis and Infertility and What Treatment Option Should You Offer These Patients?
Infertility: 30–40% of women with endometriosis suffer from infertility. The mechanism of infertil-ity in mild endometriosis is not fully understood. In moderate-to-severe endometriosis, infertility results from anatomical distortion of the fallopian tubes and the tubo-ovarian relationship due to ad-hesions.
Medical treatment of endometriosis does not improve fertility. Surgery, on the other hand can improve fertility in women with moderate-to-severe endometriosis. Subfertile women with severe endometriosis who have minimal or no symptoms are better treated with IVF, which gives them a higher pregnancy rate than surgery. On the other hand, subfertile women with severe symptoms or who have large endometriomas should be offered surgery. Post-operative hormonal treatment has no beneficial effect on pregnancy rates after surgery. However, down-regulation with GnRH analogues after debulking surgery for stage III–IV disease may be required prior to IVF. If satisfactory anatomical restoration has been achieved with surgery, the patient could be advised to try to conceive naturally for 6–12 months before resorting to IVF. If the anatomical outcome of surgery is suboptimal, IVF should be considered shortly after surgery.
How Would You Treat an Endometrioma Seen on Scan?
The management of endometriomas in patients receiving fertility treatment is controversial. Whilst some reproductive specialists believe that endometriomas (> 3 cm) should be treated surgically before assisted reproductive treatment, others argue that surgery could significantly damage ovarian reserve, which could consequently compromise success of treatment. On the other hand, advocates of surgery claim that untreated endometriomas could adversely affect ovarian response to follicle-stimulating hormone stimulation and could make egg retrieval difficult. In addition, inadvertent insertion of the egg retrieval needle into an endometrioma could cause severe pelvic infection with abscess formation. However, most fertility specialists would surgically treat very large endometriomas (> 8 cm). The optimal type of surgery for endometriomas remains controversial. There are two main surgical approaches to endometriomas, including excision or ablation of the cyst wall after drainage and irrigation. Most surgeons would excise the cyst wall as this has been shown to be superior to ablation with fewer recurrences. Excision of the cyst is achieved by stripping the cyst wall off from the underlying ovarian tissue. Bleeding points are then secured with diathermy. Ablation of the cyst could be achieved by laser vaporization or electrocoagulation of the inner cyst wall. Simple aspiration of the endometrioma is not sufficient as it is associated with a high recurrence rate. A biopsy of the cyst wall should always be sent for histology to exclude rare cases of malignancy.
How Should Dyspareunia Caused by Severe Recto-vaginal Endometriosis Be Treated?
Surgery is usually the only effective treatment for women with severe debilitating symptoms due to recto-vaginal endometriosis, which do not usually respond to medical therapy. Surgery for recto vaginal septum endometriosis is very difficult and requires considerable skill and experience. Tradi-tionally, this surgery has been performed through laparotomy. However, more recently, a laparoscopic approach has been developed in a few centres. Whilst laparoscopy offers several advantages over open surgery, it takes a considerably longer time, which increases the risk of compartment syndrome (an acute calf muscle ischaemia due to prolonged pressure within the confined fascial compartment leading to muscle necrosis). In addition to reducing the operating time, open surgery allows careful palpation for nodular disease, which is necessary for accurate determination of the extent of the disease. This type of surgery is usually carried out jointly with a colorectal surgeon (and sometimes an urologist) who may not be comfortable performing this complicated surgery laparoscopically.
The recto-vaginal space is accessed by mobilizing the rectum and the nodules removed until nor-mal tissue is identified. Depending on the extent of rectal involvement, removal of endometriotic tissue from the rectum can be achieved by shaving the anterior wall, disc resection, anterior wall resection, or segment resection. Occasionally, a temporary colostomy may be necessary in severe cases.
Endometriosis can be a very complex condition to treat, and it is important to tailor the treatment to the individual patient. As we have seen, medical treatment may be a very good option for an ado-lescent like Case 1 but would not be appropriate in someone seeking to get pregnant like Case 3. More invasive treatment is necessary if the initial conservative therapy is not effective or if the disease is more advanced. Again, in these cases, patient’s wishes must be kept into consideration. A hysterec-tomy, although a good option for Case 2, would not be appropriate for Case 1 or 3.
© 2011 Elsevier Ltd. Initially published in Obstetrics, Gynaecology & Reproductive Medicine 2011; 21(4):112–117.
About the Authors
Francesca Raffi is a Clinical Research Fellow at Royal Derby Hospital, Derby, UK. Saad Amer is Associate Professor of Obstetrics and Gynaecology at Royal Derby Hospital, Derby, UK.