Endometriosis

Introduction

Endometriosis is the presence of endometrial glands or stroma outside of the endometrial cavity. It affects 1–7% of the general population [1]. Endometriosis encompasses a wide spectrum of presentations ranging from disease found incidentally during laparoscopy to extensive, seemingly malignant disease that can spread outside of the pelvis and into the upper abdomen. The severity of symptoms also varies greatly and does not always correlate with the amount of endometriosis.

Classically, endometriosis presents with one or more of the following: an adnexal mass, infertility, or pelvic pain. Up to 70% of women with endometriosis have some type of pain symptoms, most commonly dysmenorrhea, non-cyclic pelvic pain, or deep dyspareunia [2, 3]. A total of 60–79% of patients undergoing surgery for endometriosis have been affected by deep dyspareunia, resulting in a negative attitude toward sexuality, anxiety toward and avoidance of intercourse, lower levels of desire and arousal, and fewer orgasms [4, 5]. Women with uterosacral ligament endometriosis in particular have the most severe impairment of sexual function, higher intensity of pain, and less satisfying orgasms [6].

Etiology

The two etiological aspects of endometriosis of clinical importance are the cause of the disease and the cause of symptoms of endometriosis (pelvic pain and infertility). Neither is completely understood.

The etiology of endometriosis is complex. Both genetic and environmental factors are important. There are several general theories regarding the etiology of endometriosis (Table 19.1). None of these theories is sufficient to explain the protean manifestations and locations of endometriosis, or the predilection of some women, but not others, to develop endometriosis. The theory of retrograde menstruation leading to the implantation of endometrial cells in the peritoneal cavity (also known as Sampson’s theory) is supported by observational data [7, 8].

Adolescents with obstructive reproductive tract malformations [9, 10] and adult women with cervical stenosis both have high rates of endometriosis [11]. However, most, if not all, women experience some form of retrograde menstruation, so retrograde menstruation is not the sole source of endometriosis [12]. There must be other factors that allow implantation, invasion, and proliferation of ectopic endometrium in some, but not all, women. Other theories include immune system defects [13–15], genetic predisposition [16], metaplasia of coelomic epithelium into endometrial cells [17], and lymphatic spread of disease [18].

Recently, research has focused on environmental factors and on the unique attributes of the endometrial cells of endometriosis. Environmental pollutants such as poly-chlorinated biphenyls (PCBs) and dioxin have been associated with an increased risk of confirmed endometriosis among women undergoing laparoscopy [19–21]. This effect has also been shown experimentally in primates [22]. Endometriotic cells have the ability to produce enzymes such as aromatase, an enzyme that is not present in normal endometrium and is integral to the conversion of androstenedione and testosterone to estrogen, a conversion usually done only in the ovary [23]. The ability to produce estrogen locally may lead to auto-stimulation of endometriotic lesions. Not only do endometriotic lesions show high levels of estradiol biosynthesis, they also show low estradiol inactivation compared to normal en-dometrium. Additionally, there is some evidence that alterations in progesterone receptors in endometriosis may play a role in the development or progression of en-dometriotic lesions.

Table 19.1 Theories of etiology of endometriosis.

Retrograde menstruation (Sampson’s theory)

Metaplasia

Lymphatic and vascular metastases

Immunologic defect

Genetic predisposition

Abnormal endometrium in endometriosis

The etiology of pain symptoms with endometriosis is less well understood, although there is ample epidemio-logical evidence of the relationship of endometriosis and pelvic pain symptoms. Because endometriosis is most commonly a disease of the pelvic viscera and visceral peritoneum, endometriosis pain is usually visceral in origin. Visceral pain has a number of characteristics that are important to any understanding of endometriosis-associated pain: (1) not all viscera are sources of visceral pain, possibly due to lack of sensory receptors or the lack of an appropriate nociceptive stimulus; (2) visceral pain is not always linked to injury and thus may be functional; (3) visceral pain frequently results in somatic referral of pain, possibly due to central convergence of visceral and somatic afferents; and (4) visceral pain tends to be diffuse or poorly localized, probably due to the low concentration of nociceptive afferents within viscera [24]. Visceral noci-ception and pain are generated in response to distention, ischemia, inflammation, and traction on mesentery. In the case of endometriosis, inflammation may be the primary nociceptive stimulus. A number of studies have shown that endometriotic lesions produce and release inflammatory mediators, particularly prostaglandins F_2α and E₂, potent mediators of the inflammatory response [25–27].

In addition to directly causing visceral pain, inflammation induced by endometriosis may also enhance pain sensitivity. The presence of inflammation tends to significantly enhance both the sensitivity and the severity of visceral pain. This characteristic of visceral pain may be relevant in patients with endometriosis, because in the presence of local inflammation, visceral afferents may develop peripheral hypersensitization and start to respond to previously innocuous physiological stimuli.

In addition to nociceptive pain, neuropathic pain may also be a significant factor in endometriosis-associated pelvic pain. For example, there are significant differences in the uterine innervation of women with endometriosis and chronic pelvic pain compared to those without pelvic pain. Women with endometriosis and chronic pelvic pain have an increase in nerve fibers, microneuroma formation, and perivascular nerve proliferation in their uteri [28]. These neural changes may be a cause of both dys-menorrhea and chronic pelvic pain.

Finally, referred visceral pain with hyperalgesia may be an important mechanism in endometriosis-associated pain. Referral of pain with hyperalgesia of somatic tissue is a well-known characteristic of visceral pain. In the case of endometriosis, there are both animal experimental and human clinical evidence of hyperalgesia of the vagina, abdominal wall, and lumbosacral back. Referred pain with hyperalgesia may be an important mechanism in the generation of dyspareunia in women with endometriosis [29–32].

Epidemiology

Endometriosis is estimated to be present in 1–7% of the general population, although the true prevalence is unknown. In women undergoing laparoscopy for pelvic pain and infertility, endometriosis lesions are present 33% and 40% of the time, respectively [33].

Seventy percent of women with endometriosis diagnosed by laparoscopy experience pelvic pain of some type [34]. There is not a direct relationship between severity of pelvic pain and the extent of disease: A patient with large, bilateral endometriomas and stage IV endometriosis obliterating the posterior cul-de-sac can experience little or no pain, whereas a woman with only a few lesions identified laparoscopically can have debilitating pain symptoms. This is not inconsistent with modern theories of pain, especially chronic pain, but can make clinical management perplexing. There is, however, a relationship between pain relief with surgical treatment and extent of disease [35].

Diagnosis

History

Endometriosis occurs in women of reproductive age, so it is rarely a cause of pelvic pain or dyspareunia in post-menopausal women. About 60% of women with endometriosis have the onset of their symptoms before 20 years of age [2]. Ninety percent or more of women with pelvic pain and endometriosis classically present with a history of dysmenorrhea [2, 36]. A common complaint, dyspareunia occurs with deep penetration and not with initial entry. Dyspareunia occurs in up to 60% of patients with pain symptoms [2]. Rarely is dyspareunia an isolated pain symptom of endometriosis. Deep dyspareunia is often associated with uterosacral and/or rectovaginal endometriosis lesions; 60–78% of women with deep dyspareunia had positive uterosacral ligament pathology during laparoscopy [37].

Physical Examination

Physical examination findings in women with endometriosis are often negative. Many women only have tenderness during menses, and sometimes repeating the exam at this time can be useful [38]. Other women with endometriosis have persistent areas of tenderness that coincide with areas of endometriosis, whether or not they are menstruating [39]. In particular, a fixed retroverted uterus with posterior tenderness and tender nodularity of the uterosacral ligaments or cul-de-sac are suggestive of endometriosis. Narrowing of the posterior vaginal fornix may rarely be present. There may be lateral displacement or deviation of the cervix [40]. Asymmetrically enlarged, tender ovaries that are fixed to the broad ligaments or pelvic sidewalls are sometimes found. In patients with endometriomas, a tender adnexal mass may be noted. In women whose primary complaint is deep dyspareunia, localized tenderness of the cervix, cul-de-sac, or a fixed, retroverted uterus may be found at the time of examination.

Imaging Studies

Radiologic studies can be useful in the preoperative evaluation and surgical planning in a patient with suspected endometriosis, but are not sensitive or specific for diagnostic purposes. Pelvic ultrasound findings of a hypo-echoic adnexal mass with diffuse low-level internal echoes consistent with an endometrioma can guide the operative plan, particularly when ovarian endometriomas are small and do not result in an enlarged ovary visible laparoscopically. Magnetic resonance imaging has also been described to identify endometriosis lesions, particularly in unusual locations, such as with rectal, nervous system, or thoracic involvement.

Laparoscopy

Only gold members can continue reading. Log In or Register to continue