Abstract
Endometriosis is the most common gynecological condition leading to pelvic pain and often it is the only one recognized by gynecologists. In many cases it coexists with pelvic floor muscle spasm, interstitial cystitis/bladder pain syndrome and irritable bowel syndrome and often all four are called “evil quadruplets.” Endometriosis can be diagnosed only surgically, and pathology confirmed tissue biopsy is by far the most accurate way of diagnosis. Unfortunately, all medical treatments of endometriosis are quite inadequate because they all rely on causing a hypoestrogenic state that only provides temporary relief of pain, and soon after medication is discontinued, symptoms return. Development of drugs addressing the cause of the disease is currently not possible because the cause of the disease is known. Multiple existing theories fail to explain all the cases, leading to the possibility that different etiologies may lead to a presence of endometrial glands and stroma in the peritoneal cavity and outside. Surgical resection of endometriosis in skilled hands is effective but patients need to be warned that disease will most likely return within a few years of initial surgery. Deep infiltrating endometriosis requires a very knowledgeable surgeon and often specialized center for treatment. Additional procedures such as presacral neurectomy, although controversial and potentially risky, may alleviate dysmenorrhea symptoms in some patients. Meticulous removal of ovarian endometriomas is a must in all infertility patients and most pelvic pain patients as simple drainage will result in almost immediate return of endometrioma.
Editor’s Introduction
Endometriosis is the most common gynecological condition leading to pelvic pain and often it is the only one recognized by gynecologists. In many cases it coexists with pelvic floor muscle spasm, interstitial cystitis/bladder pain syndrome and irritable bowel syndrome and often all four are grouped as “evil quadruplets.” Endometriosis can be diagnosed only surgically; and pathology confirmed tissue biopsy is by far the most accurate way of diagnosis. Unfortunately, all medical treatments of endometriosis are quite inadequate because they all rely on causing a hypoestrogenic state that only provides temporary relief of pain, and soon after medication is discontinued, symptoms return. Development of drugs addressing the cause of the disease is currently not possible because the cause of the disease is unknown. Multiple existing theories fail to unify an explanation of all cases, leading to the possibility that different etiologies may lead to a presence of endometrial glands and stroma in the peritoneal cavity and outside. Surgical resection of endometriosis in skilled hands is effective but patients need to be informed that disease will most likely return within a few years of initial surgery. Deep infiltrating endometriosis requires a very knowledgeable surgeon and often a specialized center for treatment. Additional procedures such as presacral neurectomy, although controversial and potentially risky, may alleviate dysmenorrhea symptoms in some patients. Meticulous removal of ovarian endometriomas is a must in all infertility patients and most pelvic pain patients as simple drainage will result in almost immediate return of endometrioma. Pre and postsurgical treatment with hormonal suppression is still debatable, and there is research to support it and research showing it ineffective. In my practice I do not use pre- and postsurgical hormonal suppression.
Introduction
Endometriosis is a common cause of pelvic pain, affecting an estimated 10% to 15% of women of reproductive age [1]. The disease has been associated with 70% of women who present to chronic pelvic pain clinics [2] and about 50% of all infertility patients [3]. Despite its high prevalence, treatment methodologies for endometriosis remain controversial, even as the cannon of endometriosis literature continues to grow. Traditionally, surgical evaluation and treatment of endometriosis were the mainstays of treatment; however, pain symptomatology associated with endometriosis is increasingly recognized as a syndrome of painful conditions rather than a single pain etiology to be corrected surgically. This greater recognition of comorbid disease states as (secondary pain generators) is providing a much better understanding of the etiology of pain associated with endometriosis and guiding less invasive and more effective treatment options.
In this chapter we will address the link between endometriosis and pain symptomatology including the ways that different types of endometriosis lead to pain symptoms. Furthermore, we will evaluate surgical and nonsurgical techniques that have been shown useful in the treatment of endometriosis-related pain.
Endometriosis is broadly defined as the presence of endometrioid glands and stroma ectopic to the uterus. This definition, though histologically accurate, does not fully describe the link between endometriosis and associated painful symptoms. Furthermore, endometriosis does not present as a singular phenotype; rather it presents in varied tissue architectures. There are superficial peritoneal blebs (superficial endometriosis), cystic lesions (endometriomas), and large fibrous nodules (deep infiltrating endometriotic nodules). The architecture of each endometriosis subtype dictates its own unique pain signature. Endometriosis subtypes can present in isolation or in combination with one another. As such, each patient’s endometriosis disease must be evaluated and treated as a unique constellation of lesion subtypes. Further complicating pain resolution is the myriad of associated, downstream pain sequelae. These secondary pain generators are further described in this book and are commonly a reaction to the pain in the pelvis created by endometriosis. Frequently encountered secondary pain generators are pelvic floor tension myalgia, abdominal myofascial pain, vulvodynia, and centralized pain syndromes (irritable bowel syndrome, interstitial cystitis/bladder pain syndrome). Downstream sequelae of unchecked painful symptomatology can further lead to depression, anxiety, catastrophizing, and chronic widespread pain syndromes.
Recognizing the link between endometriosis subtypes and their accompanying pain syndromes is of vital importance in developing a plan to adequately address the complex milieu that defines pelvic pain arising from endometriosis. It is no longer acceptable to measure endometriosis cure rates solely by the absence of lesions in the pelvis at the time of surgery. True successful treatment of endometriosis should be measured by control of the disease itself as well as correction of its downstream sequelae.
Subtypes of Endometriosis
Superficial Endometriosis
Superficial endometriosis is the most common subtype of endometriosis and is most commonly found in the pelvis (Figure 8.1). It can present as dark purple-blue blebs, deep red splinter hemorrhages, gunpowder marks, and blister-like pustules. Though the varied appearance of each of these lesions is not completely understood in terms of etiology and clinical significance, the difference of appearance is likely due to the age and activity of the individual lesions [4]. Technically speaking, a lesion is considered to be superficial endometriosis when it histologically contains endometrioid glands and stroma and does not invade >5 mm into the surface on which it is attached. It is not possible to know for sure the depth of an endometriosis lesion by mere appearance, as studies have shown that up to 15% of lesions thought to be superficial invade >5 mm, making them technically deep infiltrating endometriotic lesions [5].
The etiology of superficial endometriosis is not beyond debate. Sampson’s theory on endometriosis is the most widely accepted and appears to best describe superficial endometriosis. It states that reflux menstruation causes products of the menstrual cycle to spill into the peritoneal cavity. This ectopic tissue, aided by the natural counterclockwise flow of peritoneal fluid, travels and attaches to peritoneal surfaces within the abdomen and pelvis. Evidence of this reflux menstruation has been described in women with and without endometriosis, indicating reflux menstruation is a common occurrence. The reason some women develop endometriosis and others do not is believed to be related to a complex interplay of the intraperitoneal immune system, hormonal milieu, and the endometrial cells themselves.
Cystic Endometriosis
Cystic endometriosis, commonly known as endometrioma, is most commonly associated with the ovarian cortex. It occurs in 17%–44% of women who carry the diagnosis of endometriosis [6]. These cysts can range from subcentimeter intraovarian cystic structures to large cysts that completely encompass the ovary. They are typically filled with a thick brown semiviscous fluid that resembles liquid milk chocolate, hence the nickname “chocolate cysts.” The cysts themselves are frequently thin walled and are easily ruptured surgically, though they rarely grossly rupture spontaneously. Quite often, endometriomas are associated with pelvic adhesive disease, scarring to the pelvic sidewall, loops of bowel, or posterior cul-de-sac. Because of their tendency to form as bilateral ovarian cystic structures (28%)[7], they commonly scar together in the midline, posterior to the uterus, forming “kissing ovaries.” These adjoined ovaries are frequently imbedded deep in the pelvis, scarred to the uterus, bilateral fallopian tubes, or the colon or rectum or both. Their presence can portend deep infiltrating nodules along the uterosacral ligaments, posterior cul-de-sac, or rectovaginal septum.
Endometriomas are thought to have a pathogenesis similar to that of superficial endometriosis. Consistent with Sampson’s theory, Hughesdon suggested that endometrial cells are refluxed into the peritoneal cavity. These cells travel to the surface of an ovary that has just undergone ovulation. The endometrial cells implant and as the ovarian cortex heals over, thus trapping the endometriotic tissue within a superficial cystic structure on the surface of the ovary. These cells are bathed in the ovarian hormonal milieu and begin to cycle as typical endometrium. As this tissue is trapped, endometrial debris and blood products are contained within a cystic structure that continues to expand into an endometrioma [8].
Deep Infiltrating Endometriosis
Deep infiltrating endometriosis (DIE) is the most complex form of endometriosis in the way it interacts with tissues and pelvic organs. While numbers may be underreported given the difficulty of diagnosis, as many as 20% of patient with endometriosis have been reported to have DIE [9]. DIE typically presents as a thick fibrous nodule that contains smooth muscle tissues, fibroblasts, a fibrous matrix, and characteristic endometrial gland and stroma [10]. Because of the ability of endometriosis to secrete neural and epithelial growth factors, the lesions are rich in blood supply and neural tissue. The technical definition of deep infiltrating endometriosis is a lesion of endometrioid glands and stroma that invades >5 mm into its place of attachment; however, this definition is somewhat antiquated, as the histologic makeup of DIE more closely resembles adenomyosis than just a deeper invading form of superficial endometriosis lesion [11]. Interestingly, when DIE was primarily described by Karl von Rokitansky in 1860, it was termed “adenomyosis externa” because it contained endometrial tissue associated with extensive fibromuscular and loose connective tissue elements [12], resembling our current understanding of adenomyosis. This indicates that our increased understanding of endometriosis today may be leading back to the origins of its diagnosis.
The most common place to find deep infiltrating endometriosis is at the junction of the uterus and uterosacral ligament [13]. Because of its proximity to the gastrointestinal tract, this type often invades the colorectum (Figure 8.2). Other abdomino-pelvic sites of endometriosis include sites along the ureter, urinary bladder, appendix, and diaphragm. Endometriosis has also been discovered in remote locations including the lungs, heart, brain, and even the ear lobe. Theories suggest that these may be from stem cell rests that formed during embryonic development. Still other theories suggest a hematogenous or lymphatic spread of endometriosis is possible. The basic science of endometriosis is evolving at a rapid rate, and further discoveries continue to elucidate the etiology of the complex pathogenesis of this disease and its many subtypes.
Diagnosis of Endometriosis
In the setting of chronic pelvic pain, establishing a diagnosis of endometriosis may be important; however, establishing a definitive diagnosis often requires surgical intervention, which confers certain risks to the patient. Given a physician’s duty to “first do no harm,” it is important that one weighs the risks and benefits of performing a diagnostic procedure, especially if diagnosis will not alter management. There are certain situations in which surgical intervention will be superior to nonsurgical interventions and thus may justify an initial surgical approach. These situations will be highlighted later in the chapter. Surgery should not be the primary therapeutic approach when a patient has a high pretest probability of disease and conservative therapies are likely to be of therapeutic success. It is, however, important to recognize histology from directed biopsy is the gold standard in the diagnosis of endometriosis. Other diagnostics tests including imaging and serum blood tests have proven disappointing in the definitive diagnosis of endometriosis; however, some subtypes of endometriosis are more easily discernible with certain methods than others.
Superficial Endometriosis
Currently, neither serum blood testing nor imaging can successfully diagnose superficial endometriosis. Ultrasound, CT, and MRI do not have the fidelity to identify small, subcentimeter peritoneal lesions of superficial endometriosis. These modalities can occasionally identify coexisting intraabdominal adhesive disease that can suggest the diagnosis, but since extensive scarring seems to occur with less frequency among isolated superficial endometriosis, these noninvasive imaging techniques are nonspecific. Blood tests to date have been shown to be ineffective in the diagnosis of superficial endometriosis, though CA-125 a nonspecific marker of intraperitoneal inflammation, will often be elevated when endometriosis is present.
Apart from a surgical diagnosis, the most effective tool for diagnosis of endometriosis comes from the history and physical exam. The most common symptoms in women with endometriosis are dysmenorrhea and dyspareunia. Dysmenorrhea is typically present from the first few menstrual periods in a woman’s reproductive lifecycle or sometime later in the teenage years. Differentiating pathologically painful periods from the typical period cramping can be difficult. It is important to ask patients about painful menses, as many women think the pain they experience is normal and may not report concerns without prompting. A typical differentiating factor is whether periods are painful enough to cause a patient to stay home from work or school. Additionally, young women with endometriosis may have more abnormal bleeding cycles than age-matched controls [14]. Dyspareunia is a common complaint in women with superficial endometriosis as well. This is sometimes linked to endometriosis at the junction of the uterus and the cervix, resulting in an area of tenderness that may be struck on deep insertion during intercourse. This pain is termed deep thrust dyspareunia and should be differentiated from entry dyspareunia. Alternatively, entry and deep thrust dyspareunia can develop as part of the sequelae of endometriosis-related pain, for example, in cases of vulvodynia or pelvic floor tension myalgia.
From a physical exam standpoint, superficial endometriosis in isolation can be difficult to diagnose. There are no palpable lesions to confirm diagnosis; however, one can infer the presence of superficial endometriosis when retrocervical tenderness is present on bimanual exam. Similarly, DIE can also lead to this finding.
As previously mentioned, the gold standard in diagnosis of endometriosis is histological, which means a sample needs to be surgically collected. For diagnosis, it is important that endometriosis lesions be both directly visualized and biopsied, as visual identification of lesions alone can lead to a false-positive diagnosis [4]. Furthermore, it is important that a full survey of the abdomen and pelvis be completed and fully documented in the operative report. This level of detail ensures that future practitioners will have the confidence that a full evaluation of the abdomen and pelvis was completed to rule out endometriosis. The areas of the pelvis that should be separately visualized and commented on are in Table 8.1.
Table 8.1 Important anatomy to evaluate during diagnostic laparoscopy for endometriosis
| Anterior cul de sac |
| Posterior cul de sac |
| Left ovarian fossa |
| Right ovarian fossa |
| Bilateral fallopian tubes and ovaries |
| Uterus |
| Uterosacral ligaments |
| Appendix |
| Colon and rectum |
| Diaphragm (both left and right sides) |
Endometrioma
The diagnosis of endometrioma is typically less enigmatic than superficial endometriosis because it typically presents as a cystic structure with characteristics findings on various imaging modalities. Pelvic ultrasound and MRI can both be employed to discern the etiology of an endometriotic cyst to a limited degree of efficacy. While an endometrioma has specific features on each of these modalities, it can appear similar to the hemorrhagic corpus luteal cyst, a common, nonpathological, self-limited finding. Persistence of a mass and clinical correlation to tenderness on bimanual exam are important adjunct findings to aid in the diagnosis of endometriomas. Malignancy must also be considered when a complex cystic structure is present and should be included in the differential diagnosis.
Symptomatology
Women with endometriomas tend to develop more noncyclic pelvic pain than those with superficial endometriosis alone. Frequently pain develops semiacutely and persists as the tender cyst grows and leads to increased mass effect. This pattern of slowly increasing pelvic pain not directly associated with menses may be easily confused with the development of pelvic floor tension myalgia, which also tends to lead to increased noncyclic point tenderness on contact such as is present with intercourse. Fortunately, these etiologies can be differentiated with physical exam and imaging. A pelvic exam that demonstrates a painful mass or adnexal tenderness that reproduces painful symptoms suggests the presence of endometrioma, which is not seen in hemorrhagic corpus luteal cysts. It is also important to examine the pelvic floor musculature in these cases. Isolated tenderness of the pelvic floor (especially that reproduces the patient’s pain) may indicate that the pain is due solely to pelvic floor tension myalgia or dysfunction. When this test is equivocal ultrasound or MRI diagnosis can be helpful. We find that the information obtained from an exam for adnexal tenderness is most helpful when trying to decide whether to repeat imaging to establish persistence of a mass or whether to move to surgery more expeditiously.
Ultrasound and MRI
MRI sensitivity and specificity are just slightly better than ultrasound in the diagnosis of endometrioma [15]. Given the ability to further characterize cysts, MRI should be considered when transvaginal ultrasound (TVUS) is inconclusive or with concern for malignant transformation. MRI imaging with contrast enhancement should be utilized if question regarding potential neoplasm remains.
Deep Infiltrating Endometriosis
Diagnosis of DIE is more complex than the diagnosis of superficial endometriosis or endometrioma. No one methodology can definitively establish a diagnosis of DIE, though specificity can be high with certain findings on physical exam, ultrasound, and MRI. As with other subtypes of endometriosis, sensitivity of detection techniques is lacking in many cases. Colonoscopy has long been suggested to be an effective tool in the diagnosis of deep endometriosis, but studies have shown it to be of very little utility in detecting DIE of the bowel.
Because of the high cost of advanced imaging in endometriosis, the history and physical exam are very important in aiding diagnosis. A thorough history and physical examination can modify the pretest probability of finding DIE on imaging, allowing the practitioner to be judicious with testing. Patients with DIE frequently display organ-specific dysfunction. DIE that involves the bowel can cause increased pain with defecation, increasingly intense dysmenorrhea, and deep thrust dyspareunia [16] as well as constipation and rarely narrow-caliber stools. Similarly, DIE of the bladder often presents with higher rates of urinary urgency, frequency, and hematuria. Patients with DIE often complain of point tenderness at the sites of endometriotic nodules. For example, uterosacral ligament endometriosis commonly presents as deep thrust dyspareunia, specific to certain positioning during intercourse. Pain is frequently reproducible on physical exam with palpation of the nodule [17].
Physical exam findings with DIE can be quite impressive; often thick rubbery tissue is palpated on physical exam. Retrocervical nodules can be discovered along the uterosacral ligaments or along the bowel and are often described as uterosacral ligament nodularity. More rarely, an examiner may find tender nodularity in the inguinal fold or along the abdominal wall [17].
Ultrasound and MRI
Proper characterization of DIE is important, especially preoperatively. It is important to be able to properly counsel patients about steps that may need to be taken to partially or completely remove endometriotic lesions found intraoperatively. Abrao et al. demonstrated a sensitivity and specificity of 98% and 100% in TVUS for deep infiltrating endometriosis [13]. Given this accuracy, low cost, and ease of test, TVUS is the recommended initial test for those patients with suspected endometriosis, however, with the important caveat that the ultrasonographer is well versed in the identification of endometriosis. Unfortunately, this level of expertise currently exists in only a few centers around the world. Additional methods, such as tender-point guided ultrasound, where attention is focused on areas previously found to be tender on physical exam, can increase diagnosis of endometriosis with TVUS [18].
MRI is also well studied as an imaging modality for the diagnosis of endometriosis (Figure 8.3). It has been shown that the sensitivity and specificity of MRI is 83% and 98% respectively for those patients with DIE[13]. MRI should be considered as a follow-up form of imaging in cases in which TVUS is equivocal. This is also true in patients who are symptomatic with negative ultrasound findings. MRI has also been found to improve diagnosis of endometriosis in areas difficult to visualize with TVUS including the rectovaginal septum.
