Diagnosis of Endometriosis

Robert Z. Spaczynski, MD, PhD, Antoni J. Duleba, MD

Disclosures

Semin Reprod Med. 2003;21(2) 

In This Article

Clinical Assessment

Clinical presentations of endometriosis are highly diverse and none of the presenting symptoms or signs are pathognomonic for this disorder. However, a complete history and detailed physical examination assist in the identification of symptoms and signs highly suggestive of endometriosis. This is crucial because subsequently discussed diagnostic tests will have adequate positive and negative predictive value only when performed on an appropriately selected high-risk population.

History

Most risk factors for endometriosis relate to the concept of this condition being estrogen dependent and associated with reflux of menstrual effluent to the peritoneal cavity. Endometriosis is almost always detected in women of reproductive age; the mean age at diagnosis ranges from 25 to 29 years.[7,8] Endometriosis may be found in early adolescence, especially in patients with partial or complete obstructive müllerian anomalies, such as cervical atresia, or in patients with obstructed rudimentary uterine horns, whereby the disease is presumably induced by severe retrograde menstrual flow.[9,10,11,12] However, about 47 to 73% of teenagers with no outflow tract obstruction but with severe dysmenorrhea and pelvic pain not responding to analgesics are also diagnosed with endometriosis.[13,14,15] An association between early menarche (before age 11-13) and endometriosis was demonstrated in several, but not all, epidemiological studies.[4,16,17,18,19] Symptomatic endometriosis after menopause is rare and is usually related to hormone replacement therapy.[20,21] Nevertheless, de novo cases of endometriosis in postmenopausal women have been described.[22]

The risk of endometriosis seems to be directly related to the total amount of menstrual flow. Endometriosis is more common in women with a short menstrual cycle (≤27 days), longer menstrual flow (≥7 days), and spotting before onset of menses.[16,17,23]

Selected constitutional factors correlate with the risk for endometriosis. Tall women with low body mass appear to be at increased risk for endometriosis because, according to some reports, taller women tend to have shorter menstrual cycles, possibly due to reduced germ cell endowment, and/or higher chance for defective canalization of the cervix.[16,24] Endometriosis was also found more commonly in women of Asian origin than in Caucasian women.[3] Factors that may lower estrogen levels, such as smoking and regular exercise, were associated with a decreased risk for endometriosis; however, these observations were not confirmed in more recent studies.[4,16,19]

A decreased likelihood of endometriosis has also been observed in women who have been pregnant. This may be due to a protective effect of pregnancy, or it may reflect decreased fertility of patients with endometriosis. Risk of endometriosis is inversely related to the number of term pregnancies.[3,19] In a study of 817 women with infertility or pelvic pain, the odds ratio for endometriosis in multiparous women with two or more births, when compared with nulliparous women, was 0.4.[19] However, the protective effect of pregnancy appears to wane gradually and an increased risk of endometriosis has been observed with an increase in the number of years since the last childbirth.[4,25] In a case-controlled study, the odds ratio for endometriosis was 4.5 after 10 years without a birth, compared with the first 5 years after a delivery.[25]

A family history of endometriosis is relevant, especially in light of growing evidence suggesting a genetic component of the disease, probably involving a polygenic pattern of inheritance.[26,27,28] There is significant familial clustering, and first-degree relatives of a women with endometriosis have a sevenfold greater chance of developing the disease.[29,30] Moreover, endometriosis is more likely to develop in monozygotic than dizygotic twin sisters.[31,32] Associations between red hair, dysplastic nevi, and endometriosis have been demonstrated.[33,34] Further evidence for a hereditary component of endometriosis is provided by population genetic studies.[35,36,37]

From the clinical standpoint, the most important risk factors for endometriosis are infertility and chronic pelvic pain. In the population of infertile women undergoing surgical evaluation, the rate of endometriosis was higher than in fertile controls and ranged from 4.5 to 33% (mean 14%).[2,5,38,39] Interestingly, the prevalence of infertility among patients with endometriosis has not been precisely evaluated. The etiology of infertility appears clear in women with stage III or IV endometriosis, when periadnexal adhesions and endometriomas distort the anatomy of the fallopian tubes and ovaries. In minimal and mild endometriosis the cause of infertility is less clear, and it may be related to a higher incidence of abnormal oocytes, defective embryos, or failed implantation.[40]

In women with chronic pelvic pain, endometriosis was detected at the time of surgery in 4.5 to 32% (mean 19%).[38,41,42] Typically, pelvic pain consists of dysmenorrhea, intermenstrual pain, and dyspareunia. Dysmenorrhea is the most commonly reported symptom and its severe form, although not entirely predictive, is highly suggestive of endometriosis.[43] Dyspareunia was found less frequently in ovarian endometriosis (77%) compared with peritoneal (88%) and rectovaginal (100%) forms of the disease.[44] Dysmenorrhea is usually progressive, with onset of pain often preceding the onset of menstrual flow. It usually continues throughout the menses and occasionally persists for several days afterward. The pain is most often localized in the low abdomen and deep pelvis; it is bilateral, often radiating to the back and thighs. It is often described as dull and aching and may be associated with rectal pressure, nausea, and episodes of diarrhea.[45] Intermenstrual pain may represent an extension of dysmenorrhea; in severe cases, patients may suffer from pain throughout the menstrual cycle. Intermenstrual pain has been reported in 57 to 68% of women with endometriosis and pain.[44] In the absence of a cyclic component, this pain may be due to conditions other than endometriosis.[46]

Endometriosis-related dyspareunia is usually positional and most intense upon deep penetration. It is most intense prior to menstruation, but in severe cases it may preclude vaginal intercourse throughout the month. Dyspareunia is usually associated with endometriosis of the cul-de-sac and rectovaginal septum.[47] Interestingly, dysmenorrhea and dyspareunia are more suggestive of endometriosis if the symptoms begin after years of relatively pain-free menses and coitus.[48]

The relationship between pain and the stage and site of endometriosis is controversial. Subjects with advanced disease may have little discomfort, whereas women with minimal or mild endometriosis may present with incapacitating pain. Some reports show a correlation between the severity of dysmenorrhea and the stage of endometriosis.[48,49] Yet, observations to the contrary, revealing no association between the stage of endometriosis and the severity of dysmenorrhea as well as nonmenstrual pelvic pain, have also been published.[44,47,50] Perper et al[51] observed that the intensity of dysmenorrhea was related to the number of endometrial implants but not to the stage of the disease. However, this finding was contradicted by Muzii et al,[49] who reported a lack of correlation between pain severity and the number as well as the type (typical "black" and atypical "fresh/clear") of endometriotic lesions. Evidence regarding the association between the intensity of pain and morphologic features of the endometriotic implants is inconclusive and contradictory.[44,49,52,53,54] Some data indicate that endometriosis-associated pain persists throughout the reproductive years and that endometriosis stage is directly related to the persistence of pain.[55] Furthermore, deeply infiltrating endometriosis is strongly correlated with pelvic pain and the degree of pain is related to the depth and the volume of infiltration.[47,56,57] In a multicenter cross-sectional observational study of 469 women with surgically diagnosed endometriosis and pain symptoms (>6 months), rectovaginal septum endometriosis was associated with more frequent dyspareunia; however, the statistical significance of this finding was borderline.[44] The same study found no significant correlation between stage and site of endometriosis and severity of dysmenorrhea, nonmenstrual pain, and dyspareunia.

Rarely, endometriosis may present as acute pelvic pain, typically perimenstrual, and usually in the context of hemoperitoneum and rupture or torsion of endometrioma.[58] Endometriosis has also been found in extrapelvic locations, giving rise to atypical symptoms. Nongynecologic organs most often affected by endometriosis include: the intestinal tract, the urinary tract, surgical scars, the lungs and thorax, peripheral nerves, and the central nervous system. Consequently, patients may present with a wide range of cyclic, menses-aggravated symptoms presumably reflecting cyclic bleeding and inflammation. About 0.1% of women who have undergone cesarean section may present with cyclic superficial pain, worsening when coughing and tensing the abdominal wall, that may resemble symptoms of a postoperative hernia.[59,60,61] Abdominal wall endometriomas are also found in abdominal scars following gynecologic surgeries and in the perineum after episiotomy. Surprisingly, cases of abdominal wall endometriosis have also been described in patients without previous surgical history.[62]

Women with gastrointestinal involvement may suffer from disturbed bowel function, dyschezia, cyclical hematochezia, or even bowel obstruction.[63,64,65,66,67] Hepatic endometriosis may present with cyclic right-sided subcostal pain.[68] Endometriosis of the urinary tract can cause hematuria, dysuria, urgency, and frequency. Bladder detrusor endometriosis presents with symptoms similar to those of interstitial cystitis, whereas renal involvement, although very rare, presents predominantly with abdominal pain and hematuria.[22,69,70,71] Involvement of the ureter may cause flank and iliac fossa pain due to partial or complete ureteric stenosis. Interestingly, ureteral endometriosis was found in 4.4% of patients with rectovaginal endometriosis.[72] Pulmonary and pleural endometriosis may be manifested by hemoptysis, chest pain, and shortness of breath resembling pulmonary embolism.[73,74,75,76] Women with diaphragmatic endometriosis may present with a wide spectrum of symptoms including chronic, cyclical shoulder tip pain.[77,78] Invasion of peripheral nerves can mimic common musculoskeletal problems and may result in cyclic pain such as sciatica, and cerebral endometriosis can lead to perimenstrual headaches or even seizures.[79,80,81,82,83]

Physical Examination

Physical examination may provide a broad range of findings. In some cases, especially of mild endometriosis, the gynecologic examination may be entirely unremarkable. Ideally, the examination should be performed while the patient experiences at least some symptoms, preferably during menstruation, when it may be easiest to detect and localize areas suspected of harboring endometriosis.[84] A general physical examination is rarely rewarding unless the patient presents with focal cyclic symptoms suggestive of endometriosis in nongynecological organs. Abdominal examination often reveals tenderness, usually ill localized and deep. In rare instances of scar endometriomas, painful swelling and focal tenderness may mimic other lesions, such as hematomas, granulomas, or abscesses.

On pelvic examination, external genitalia and the vaginal surface are usually unremarkable. Speculum inspection may reveal bluish implants typical of endometriosis or red, hypertrophic lesions bleeding on contact, usually in the posterior fornix. In a recent retrospective analysis of 160 cases of histologically documented deeply infiltrative endometriosis, lesions were visible during speculum examination in only 14.4% and palpable during manual examination in 43.1% of patients.[85] Propst et al[86] described a new physical finding of lateral cervical displacement due to scarring of the ipsilateral uterosacral ligament that may be associated with endometriosis. The same group also reported an association between cervical stenosis (<4.5mm) and endometriosis in women with chronic pelvic pain.[87] Most commonly, positive physical signs are found on bimanual and rectovaginal examination of pelvic structures. Palpation of the uterus may reveal retroversion, decreased or absent mobility, and tenderness. Endometriomas may be detected as tender or nontender adnexal masses, often fixed to the uterus or to the pelvic sidewall. Tender masses, nodules, and fibrosis may be appreciated on palpation of the upper vagina, cul-de-sac, uterosacral ligaments, or rectovaginal septum. In a case-controlled study, the only signs of endometriosis in infertile patients were uterosacral nodularity and uterosacral tenderness.[88] Focal tenderness has been shown to correlate with the presence of endometriosis as well as the depth and volume of endometrial implants.[89] Koninckx and his associates[84] found that careful palpation during menstruation increases the detection rate of deep endometriosis, endometriomas, and cul-de-sac adhesions by over fivefold compared with a routine examination not timed to the menstruation.

However, a normal clinical examination does not rule out the diagnosis of endometriosis. When compared with surgical evaluation, pelvic examination showed poor sensitivity, specificity, and predictive values ( Table 1 ). A prospective study validating nonsurgical approaches to diagnosis of endometriosis found that pelvic examination was a reliable predictor of ovarian endometriomas but was not helpful in prediction of nonovarian lesions.[90]

It is essential to bear in mind that the physical signs listed here are not specific and none of the findings is diagnostic in and of itself of endometriosis. Caution should be exercised, and in the absence of conclusive evidence to the contrary, a differential diagnosis should include other conditions such as neoplasms or infections.

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