is a senior resident and
is Associate Professor of Radiology and Obstetrics &
Gynecology and Director of Ultrasound at Dartmouth Medical School
and Dartmouth-Hitchcock Medical Center, Lebanon, NH.
Endometriosis is a common, sometimes debilitating, and often
elusive gynecologic condition characterized by the presence of
ectopic foci of endometrial tissue outside the uterus, as a result
of retrograde menstruation and subsequent abnormal implantation.
Endo-metriosis has an estimated prevalence of 10% in women of
reproductive age: the mean age of onset is 25 to 29 years.
It is the third leading cause of gynecologic hospitalizations in
the United States and a leading cause of hysterectomy.
This article will review current epidemiological and pathological
concepts of endometriosis and present the typical imaging findings
with discussion of the accuracy and role of currently available
noninvasive imaging techniques.
Risk factors for endometriosis largely relate to the concept of
endometriosis as an estrogen-dependent disease associated with
reflux of menstrual effluent into the peritoneal cavity.
Endometriosis, defined according to pathologic criteria, is ectopic
endometrial stroma and glands beyond the myometrium. Ectopic
endometrial mucosa located within the uterus is defined as
adenomyosis, a subject beyond the scope of this treatise. True
endometriosis is located outside the uterus and is also known as
Because endometriosis can only be definitively diagnosed
surgically, usually during laparoscopy or laparotomy, most
prevalence estimates are highly selective. Furthermore, there is a
high percentage of mild endometriosis in asymptomatic women
undergoing tubal ligation.
Prevalence estimates vary depending upon 1) the definition and
criteria used for diagnosis; and 2) the limitation that the lack of
disease cannot be confirmed in those who have not been examined,
undergone lapa-roscopy, or reported symptomatology. Nonetheless, it
is thought to be a relatively common. Endometriosis has been
detected in 4.5% to 32% (mean 18.8%) of women undergoing
laparoscopic evaluation of chronic pelvic pain and in 4.5% to 33%
(mean 14%) of women with infertility.
Clinical definitions require the additional criteria of
symptomatology and/or infertility as a direct result of
endometriotic lesions. This description, however, does not explain
the frequent detection of endometrial glands and stroma in
asymptomatic and fertile women, nor does it recognize the broad
histologic spectrum of endometriotic lesions and their natural
evolution to fibrotic, hemosiderin-stained lesions.
It has been estimated that the prevalence of asymptomatic, but
pathologically confirmed, endo-metriosis in healthy women
undergoing tubal ligation ranges from 6% to 43%.
Furthermore, microscopic foci have been found in normal-appearing
peritoneum in women with no gross evidence of endometriosis
It has been speculated that meticulous sampling may detect lesions
in most, if not all women; however these microscopic foci can
hardly be considered disease, especially in the absence of
Because of controversies in defining the disease, the diagnosis
cannot be made by history and physical examination findings alone.
Nonsurgical diagnostic techniques include hysterosalpingography,
abdominal ultrasound (US), transvaginal pelvic US, and MRI.
Conclusive diagnosis, however, currently requires invasive
techniques such as laparoscopy or laparotomy with histologic
confirmation of the surgical specimen. Therefore, clinicians should
attempt to identify women at high risk for endometriosis and select
those who warrant further testing. Because transvaginal sonography
is well tolerated and widely available, it remains the primary
screening modality for imaging the female pelvis. High-resolution
MRI techniques have some limitations, but offer the potential to
identify early pathological changes when interventions may be more
effective. It also provides evaluation of areas unapproachable
Epidemiologically, endometriosis has been clearly linked to both
pain and infertility, but the mechanism by which these symptoms
result from the disease remains elusive.
Endometriosis in early adolescence is usually associated with
partial or complete obstructive Mullerian abnormalities, such as
cervical atresia or obstructed rudimentary uterine horns, which
presumably induce severe retrograde menstrual flow. In
postmenopausal women, symptomatic endometriosis is very rare and is
typically associated with hormone replacement therapy.
Other risk factors include women with short menstrual cycles
(<27 days), longer menstrual flow (>7 days), and premenstrual
spotting. Smoking, exercise, and prior pregnancy are associated
with decreased risk, the latter may reflect a protective effect of
pregnancy. It may also reflect a decreased fertility of patients
with endometriosis, because the pregnancy protective effect appears
to wane with increased years since last pregnancy.
Family history is relevant, as some studies have suggested a
polygenic pattern of genetic inheritance.
Various other risk factors have been examined such as age, race,
socioeconomic and marital status, reproductive history, menstrual
cycle characteristics, pregnancy-related factors (such as parity,
gravidity, length of preceding infertility, spontaneous or induced
abortions, age at first pregnancy or birth), contraceptive use,
personal habits (such as smoking, alcohol, caffeine intake,
exercise, illicit drug use, number of sexual partners), and body
characteristics (such as height, weight, and body mass). A
prospective study even found that women with red hair are at
Epidemiologic findings reported across studies have been
contradictory and inconsistent. This is probably because most of
the studies were not formal epidemiologic studies and different
diagnostic and inclusion criteria were used. Different populations
(those referred for infertility, pain, etc.) have been studied and
often no controls were studied for confounding factors. Zreik and
reviewed almost 100 studies and identified those risk factors for
which there has been some consistency of findings based on
well-designed, well-controlled analytic studies. The most
significant risk factors for endometriosis were heavy menstrual
flow and increased peripheral body fat, i.e., fat distributed in
the subcutaneous tissues versus intra-abdominal fat. It is
theorized that greater peripheral body
fat may be related to higher estrogen levels and hence increased
risk for endometriosis.
Pathogenesis and pathophysiology
Most theories of the pathogenesis of endometriosis suggest
either development as a consequence of: 1) dissemination of
endometrium by vascular, lymphatic, uterotubal, or direct invasion;
or 2) in situ metaplasia of coelom, Wolffian or Mullerian duct
Oral and Arici
point out that the second mechanism is problematic for several
reasons. If peritoneal epithelium has the potential to undergo
metaplasia, endometriosis would be expected to develop in men, and
in women with congenital absence of the uterus there should be
increasing frequency with advanced age. Cultured tissue fragments
from antegrade menstruation have shown the presence of adhering,
proliferating fibroblastic or epitheloid cells.
This agrees with the concept that these cells are seeded during
retrograde menstruation. Transtubal dissemination appears to be the
most common route; vascular, lymphatic and iatrogenic (mechanical)
deposition have also been observed.
Data supporting this theory include demonstration of viable
endometrial cells in peritoneal fluid and an association between
menstrual outflow obstruction and endometriosis.
There is strong evidence suggesting that endometriosis is
estrogen dependent. It does not occur before menarche and is rare
in women with anovulatory cycles.
Its occurrence in postmenopausal women is associated with obesity
or estrogen therapy and, though very rare, can occur in the
prostatic utricle of men on high-dose estrogen treatment.
Interestingly, the connection be-tween estrogen-containing oral
contraceptive pills (OCP) and the risk of endometriosis is
controversial, because some authors report a lowered risk in this
group of patients, while others do not confirm this finding.
There is no unifying explanation for infertility in women with
endometriosis, but there is general agreement that women with
adhesions, scarring, and distortion of the normal pelvic anatomy
from endometriotic lesions have a clear cause for decreased
fertility. Endometriosis can produce massive, dense adhesions among
reproductive structures resulting in tubal obstruction,
inaccessibility of the ovary to the fallopian tube, or even
destruction of ovarian stroma. Mechanisms theorized to be
responsible include inflammation, pressure, adhesions, neuronal
involvement, increased prostaglandin production, and even
Because the fallopian tubes and ovaries are constantly bathed in
peritoneal fluid, components of this fluid have been extensively
studied for a causal linkage. Studies in women with endometriosis,
regardless of the presence of pelvic pain, show significantly
elevated levels of specific prostaglandins in peritoneal fluid.
Others suggest that only a specific subtype of prostaglandin is
elevated during days 8 to 12 of the menstrual cycle.
Another study demonstrated no differences between prostaglandin
levels in women with endometriosis when compared with normal women,
women with pelvic inflammatory disease, and other women with
chronic pelvic pain.
Although the data is conflicting, it does appear that at least a
subgroup of patients with endometriosis may suffer from
prostaglandin exposure, either as a result of lesion activity or a
degree of inflammatory response.
Other theories suggest immunologic abnormalities in women with
endometriosis, but there has been no direct link to fertility
status. Immunologic factors such as the increased circulation of
autoantibodies, activation of peritoneal macrophages, and/or
decreased T-lymphocyte reactivity and natural killer cell activity
may predate, coincide with, or result from endometriosis. The
disease does appear to be systemic in some cases, accounting for
the presence of endometriosis in distant sites such as lung, nose,
pelvic lymph nodes, and extremities, with immunologic mediation.
Classification of endometriosis
Endometriosis has widely variable appearances that evolve over
time and the natural history of the disease is still poorly
Current classification systems are unable to predict pregnancy
outcome or aid in management of pelvic pain. The American Fertility
Society (Revised) staging is based on a presumed natural history of
progression and assigns points based on the number of implants or
adhesions and their relationship to pregnancy.
Because the cause of infertility may be different than the
mechanism by which endometriosis causes pain, there has been very
poor correlation between the presence and severity of symptoms and
disease stage. Further revisions of the current staging system are
anticipated that will allow for recording of variables such as
depth of invasion, histology, data from adjunct investigations, and
preoperative physical findings.
Clinical presentation and diagnostic approach
The most important clinical factors suggestive of endometriosis
are chronic pelvic pain (including dysmenorrhea, intermenstrual
pain, or dyspareunia) and infertility. Physical examination
generally reveals nonspecific diffuse or focal abdominal tenderness
or, rarely, a tender mass (e.g., in a post-cesarean section scar).
The uterus may be retroverted or fixed with decreased mobility and
increased tenderness. The adnexa can be enlarged, tender, and with
limited mobility or fixed in the pelvis. Nodularity or focal
tenderness may also be found in the cul-de-sac, rectovaginal
septum, or over the uterosacral ligaments.
Three classes of techniques have been used to diagnose and
observe women with endometriosis: 1) serum immunology, 2)
radiologic imaging, and 3) laparoscopic examination. The current
laboratory tests lack the necessary sensitivity and specificity to
serve as reliable screening tests. There is some evidence that
Ca-125 may be useful in following the course of the disease and
response to therapy.
The most useful imaging techniques in identifying patients with
endo-metriosis have been US and MRI. Standard radiography,
hysterosalpingography, and computed tomography (CT) are
infrequently helpful in localizing and describing lesions, and the
findings are most often nonspecific and rarely useful in the
diagnosis of endometriosis. CT or barium enema may help visualize
endometriosis within the bowel, pleura, or other rare locations,
but the nonspecific findings may represent other inflammatory or
neoplastic processes. Laparoscopy is invasive and has several
limitations, including its ability to detect atypical, nonpigmented
lesions, and areas ob-scured by pelvic adhesions.
Though there are a broad range of US and MR appearances, it is
possible to achieve a high degree of accuracy in diagnosis and
differentiation of endometriosis from other adnexal masses or
lesions with similar imaging characteristics, such as ovarian
abscesses, neoplasm, metastasis, and ectopic pregnancy.
Because of its widespread availability, US is typically the
first modality used for the evaluation of pelvic disease, but it
may not differentiate two common pelvic masses from endometriomas:
hemorrhagic cysts and dermoids. Ultrasound is also insensitive in
the detection of peritoneal implants. The reliability of sonography
depends on operator skill and experience, as well as on the nature
of the endometriotic lesion, and may be enhanced with Doppler flow
analysis. Three entities may be distinguished: the peritoneal
implant, the endometrial cyst, and the deep nodular lesion. The
sensitivity for detection of focal implants with US has been
reported as low as 11%, compared with a sensitivity of 83% and a
specificity of 98% for detection of endometriomas.
Pelvic MRI is probably more accurate for the detection and
identification of small endometrial implants (<3 mm) than other
non-invasive imaging tests.
Ultrasonographic examination in patients with clinical suspicion
of endometriosis is best performed using a transvaginal (TV)
approach and a high frequency probe (5 to 10 MHz). Peritoneal
implants are small (usually 2 to 3 mm) and are not seen with
transvaginal US (TVUS). Typically, endometriomas are visualized on
US as predominantly cystic masses with thick (and generally
regular) walls, increased acoustic enhancement, and homogeneous,
low-level internal echoes (figure 1). Blood flow, if present, is
usually pericystic with a resistive index above 0.45.
Not uncommonly, septations or fluid-fluid levels are seen (figures
2 and 3). Multilocular cysts (7% of endometriomas in one series)
and solid-cystic masses (10%) are seen less commonly.
Endometriomas are usually multiple and occur bilaterally.
Several studies have described particular features that have
great relevance in discriminating endometriomas from other adnexal
These features include a clearly demarcated adnexal mass with
diffuse, homogeneously dispersed, low-level internal echoes; and
the absence of neoplastic features, such as wall nodularity or
regional bright echoes. The latter are more closely associated with
cystic ovarian neoplasms and dermoids. Though hemorrhagic ovarian
cysts can also demonstrate diffuse low-level echoes with or without
mural wall thickening, they are almost exclusively non-neoplastic
(thinner walls and no mural nodules) and resolve spontaneously over
several months. As a result, the usual diagnostic strategy for
hemorrhagic cysts is a follow-up US exam (in 3 to 4 months) to
confirm resolution and avoid unnecessary surgery. Extraperitoneal
implants in the bladder or bowel may appear as nodular or polypoid
soft-tissue foci with active color or power Doppler flow
representing viable endometrial tissue (figure 3).
MRI has become increasingly accepted with a reported sensitivity
and specificity of 90% for detecting endometriosis before surgery.
Its main limitation is the detection of <3 mm peritoneal
implants, although the addition of fat-saturated T1-weighted
imaging (T1WI) has helped improve lesion conspicuity and
differentiation between fat-containing dermoids and those lesions
On MR imaging, the findings highly suggestive of endometrial
lesions are related to their underlying proteinaceous, hemorrhagic,
or fibrous content (figure 5). Additional findings include
tethering of the rectum or bowel due to adhesions and loss of a
clear uterine margin. The vast majority of endometriomas appear
hyperintense on T1WI and may be solid or cystic with hemorrhage in
differential stages of organization-producing fluid-fluid levels
(figure 4). On T2-weighted images (T2WI), large lesions appear
hypointense with areas of high signal due to the presence of
deoxyhemoglobin and methemoglobin. Acute hemorrhage is
characterized by hypointensity on T1WI and T2WI, while older
hemorrhage may be hyperintense on both T1WI and T2WI. It has been
reported that multiplicity of lesions characterized by hyperintense
cysts on T1WI, regardless of T2 characteristics, are particularly
characteristic of endometriosis (figure 5).
A small endometrioma may be suspected when a pelvic mass <1 cm
in diameter is hyperintense on T1WI, irrespective of its appearance
on T2WI, as lesions <1 cm have variable T2WI signal.
Diagnostic MRI accuracy is en-hanced with fat suppressed images.
In a prospective study, suspected endometriosis was evaluated with
conventional T1- and T2-weighted conventional spin-echo (CSE) MRI
alone and in combination with T1-weighted fat suppression (T1FS)
and gadolinium-enhanced T1FS (Gd-T1FS) spin-echo techniques. The
sensitivity for the detection of endometriosis was greatest for
CSE/T1FS at 86% compared with 76% for CSE and 81% for
CSE/T1FS/Gd-T1FS. Specificity was greatest for CSE alone (60%).
Large endometrial lesions were characterized by diameter >1 cm
and hyperintensity on T1WI and T2WI. Small lesions were well
demarcated, <1 cm, and hyperintense on T1WI or T1FS sequences.
Fat saturation accurately demonstrated 30 of 33 large and 9 of 19
small endometriomas compared with 27 of 33 and 2 of 19 using CSE
Dermoids are hyperintense on T1WI, but suppress with chemical shift
fat saturation. Because normal peritoneal contrast enhancement
occurs next to peritoneal implants, gadolinium does not appear to
provide further diagnostic information as there are numerous false
The single most important differential factor in identifying
endometriosis by MRI is the detection of pigmented hemorrhagic
lesions. A high-signal central lesion with low-signal rim (due to
hemosiderin-rich macrophages or a fibrous wall) and internal lower
signal shading (probably related to hemorrhage evolution) is almost
pathognomic (figure 6). MRI may be particularly helpful in
evaluating changes in size and number of endometriotic lesions
following treatment, detecting nerve invasion (as in sciatic
endometriosis), and in identification of incisional or abdominal
wall lesions. Other clues pointing toward endometriosis are
multiplicity of hemorrhagic cysts (often involving the cul-de-sac
and areas noncontiguous with the ovary) with associated free fluid.
Mimickers of endometriosis on MRI are normal peritoneal enhancement
with gadolinium, magnetic susceptibility artifacts from air-tissue
interfaces or metallic foreign bodies, and increased signal on T1WI
from mucous or proteinaceous bowel contents.
Analysis of multiple pulse sequences and imaging planes may help to
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