Endometriosis 1

Endometriosis
INTRODUCTION
Background: Endometriosis, the presence of endometriumlike glands and stroma outside the uterus, is a common, poorly understood, and extremely debilitating benign gynecological condition. The psychological impact of the severe pain experienced by the patient is compounded by the negative impact of the disease on fertility. The etiology and pathophysiology of endometriosis is not well understood because of the lack of a suitable animal model on which to study the anatomic correlates and natural history of disease (ACOG Committee on Practice Bulletins, 1999). No cure exists for the disease, and treatment is directed toward medical suppression, surgical excision, and symptom alleviation.
Adenomyosis is the invasion of the myometrium by endometrial tissue.
Frequency:
In the US: Endometriosis occurs in 7-10% of women in the general population (Wheeler, 1989). It is an estrogen-dependent disease and, thus, usually affects reproductive-aged women. Endometriosis has a prevalence rate of 20-50% in infertile women (Rawson, 1991; Strathy, 1982; Verkauf, 1987) and as high as 80% in women with chronic pelvic pain (Carter, 1994). Evidence of endometriosis was found during laparoscopy in 20-50% of asymptomatic women (Williams, 1977). Approximately 4 per 1000 women are hospitalized with endometriosis each year. A familial association exists, with a 10-fold increased incidence in women with an affected first-degree relative (Cramer, 1987). Monozygotic twins are markedly concordant for endometriosis (Hadfield, 1997).
CLINICAL
History: A significant number of women with endometriosis remain asymptomatic.
Cyclic pain: Cyclic pain is pain that accompanies bleeding at the time of menstruation. This could involve the bladder (hematuria), bowel (hematochezia and painful defecation), or, rarely, bleeding at uncommon sites such as the umbilicus, abdominal wall, or perineum.
Chronic pain: The most important point to remember is that the degree of visible endometriosis has no correlation with the degree of pain or other symptomatic impairment (Demco, 1998). However, pain does correlate with the depth of tissue infiltration (Konickx, 1992; Konickx, 1994). Midline disease is generally believed to be more painful than lateral disease.
Acute exacerbations: These are believed to be caused by chemical peritonitis due to leakage of old blood from an endometriotic cyst. Recently, with conscious laparoscopic pain mapping, painful lesions were found to involve peripheral spinal nerves rather than autonomic nerves (Demco, 1998).
Dysmenorrhea: Secondary dysmenorrhea occurs twice as often in women with endometriosis as in controls (Williams, 1977). Pain frequently commences prior to menses. Endometriosis should be considered in a patient presenting with significant dysmenorrhea, and the patient should be started on empiric therapy.
Dyspareunia: Deep dyspareunia may be due to scarring of the uterosacral ligaments, nodularity of the rectovaginal septum, cul-de-sac obliteration, and/or uterine retroversion. All of these may also lead to chronic backache. These symptoms are exaggerated during menses.
Physical:
Pelvic examination: Tenderness upon examination is best detected at the time of menses. Nodularity of the uterosacral ligaments and the cul-de-sac may be found. The uterus may be fixed in retroversion, owing to adhesions. Occasionally, a bluish nodule may be seen in the vagina due to infiltration from the posterior vaginal wall.
Causes: Theories of causation include the following:
Retrograde menstruation
Sampson described this theory in his classic paper published in 1927. Retrograde flow of endometrial tissue through the fallopian tubes into the peritoneal cavity is believed to cause endometriosis.
Various animal experiments and clinical observations support this theory (Liu, 1986; Kruitwagen, 1991; Scott, 1953; D’Hooghe, 1996).
Lymphatic and vascular spread
These pathways may explain the occurrence of endometriosis at distant, noncontiguous sites.
Ovarian endometriosis is also believed to be caused by lymphatic spread (Ueki, 1991), although superficial ovarian endometriosis may also be due to implantation via retrograde menstruation.
Coelomic metaplasia
Transformation of coelomic epithelium into endometrial-type glands in response to as yet unknown stimuli could explain endometriosis in unusual sites (Suginami, 1991).
Coelomic metaplasia is also believed to explain the occurrence of endometriosis in women who have undergone total hysterectomy and are not taking estrogen replacement (Metzger, 1991).
Endometriosis may also occur in men on high-dose estrogen therapy (Schrodt, 1980).
Immunogenetic defects
These are believed to increase the susceptibility of a woman to endometriosis. Humoral antibodies to endometrial tissue have also been found in sera of women with endometriosis (Mathur, 1982).
Recent work has focused on studying the differences between eutopic endometrium and endometriosis. In endometriosis, an aberrantly expressed factor SF-1 activates the expression of the enzyme aromatase, which converts C19 steroids to estrogens. Consequently, estrogen increases the synthesis of prostaglandin E2, which exerts a positive feedback effect, resulting in increased aromatase activity. Additionally, endometriotic tissue is deficient in the enzyme 17-beta hydroxy steroid dehydrogenase type 2, which converts E2 in eutopic endometrium to the less potent E1 under the direction of progestins.
A case report has been published describing treatment with the aromatase inhibitor anastrozole in a women with severe postmenopausal endometriosis, resulting in dramatic symptom resolution (Zeitoun, 1999). Additional data are needed before recommending this as treatment.
Anatomic spread
The ovary is the most common site for endometriosis. Spread to the ovary is believed to be lymphatic (Ueki, 1991), although superficial implants may be due to retrograde menstrual flow because the ovaries are in a dependent part of the pelvis. Lesions can vary in size from spots to large endometriomas. The classic lesion is a chocolate cyst of the ovary that contains old blood that has undergone hemolysis. Once intracystic pressure rises, the cyst perforates, spilling its contents within the peritoneal cavity. This can cause the severe abdominal pain typically associated with endometriosis exacerbations. The inflammatory response causes adhesions that further increase the morbidity of the disease.
Uterine serosa can be affected. Vesicular lesions may provoke an inflammatory response and scarring that cause the bladder to adhere anteriorly. Posteriorly, the disease may cause obliteration of the cul-de-sac and form dense adhesions between the posterior vaginal wall or cervix and the anterior rectum. Severe dyspareunia, dyschezia, and alteration of bowel habits are the clinical sequelae of this common spread.
Deep peritoneal disease is caused by infiltration of the uterosacral ligaments and rectovaginal septum by endometriotic nodules. Tethering of the uterus can lead to fixed retroversion. Dyspareunia is an important feature.
Through contiguous spreading, endometriosis may invade the rectovaginal septum and the anterior rectal wall. It may also involve the upper rectum and sigmoid colon, infiltrating the muscularis. Cyclical rectal bleeding (hematochezia) is pathognomonic of endometriosis. However, transmural bowel involvement by endometriosis remains a rarity. The ileum, appendix, and cecum may also be involved, leading to intestinal obstruction. Cicatrization as a consequence of endometriosis may lead to symptoms of obstruction even in postmenopausal women.
Although uncommon, interference in the genitourinary tract by endometriosis can affect the bladder, ureters, and kidneys by invasion, compression, or scarring. Medical therapy has less than satisfactory results, and surgical intervention is often required.
Uncommon sites include incisional scars, the umbilicus, and the thoracic cavity. Catamenial or cyclic pneumothorax can cause hemoptysis. Remember that ectopic endometrial tissue theoretically can undergo malignant transformation; histologic evaluation may be necessary.
Postmenopausal endometriosis may be encountered in women who are on estrogen replacement therapy (ERT). Occasionally, if ERT is administered after total abdominal hysterectomy, endometriosis can be stimulated in an ovarian remnant. Extrapelvic endometriosis is believed to be hormone-resistant when it occurs after surgical castration (Metzger, 1991). Transplantation of endometrial implants during the original surgery is believed to explain this occurrence. Another possible explanation is coelomic metaplasia.
DIFFERENTIALS
Pelvic Inflammatory Disease
WORKUP
Lab Studies:
Serum cancer antigen 125 test: Serial measurements have a low sensitivity in detecting endometriosis (Barbati, 1994), but the results are useful as prognosticators of treatment outcome (Chen, 1998). However, normal posttreatment values do not mean that endometriosis is absent.
Imaging Studies:
Ultrasonography: Transvaginal sonography is a useful method of identifying the classic chocolate cyst of the ovary. The typical appearance is that of a cyst containing low-level homogenous internal echoes consistent with old blood.
MRI: MRI has a low sensitivity in detecting rectal involvement (Kinkel, 1999) but may help detect deeply infiltrating endometriosis that involves the uterosacral ligaments and cul-de-sac. The cost-effectiveness of this imaging modality for endometriosis has yet to be justified in view of the low diagnostic yield.
Other Tests:
Laparoscopy: Laparoscopy is considered the primary diagnostic modality for endometriosis. Endometriosis has been described as protean in appearance. The classic lesions are blue-black or have a powder-burned appearance. However, the lesions can be red, white, or nonpigmented. Peritoneal defects and adhesions are also indicative. Bear in mind that microscopic evidence of endometriosis may be found in normal-appearing peritoneum.
Conscious pain mapping: Recently, conscious pain mapping (ie, with the patient awake) has been used to locate the specific areas that cause pain (Demco, 1998). Subsequently, the patient is placed under anesthesia and the deposits are ablated.
Staging: The American Society for Reproductive Medicine classification is currently the most widely used staging system (American Society for Reproductive Medicine, 1997). Point scores are assigned based on the number of lesions and their bilaterality. Lesion size is also a scoring factor. This classification is a fairly accurate method of recording laparoscopic findings. However, high intraobserver and interobserver variability precludes its use in comparing the outcomes of therapeutic studies (Hornstein, 1993). Further, this staging system does not correlate well with pain and dyspareunia (Konickx, 1991) and fecundity rates cannot be predicted accurately.