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ULTRASONOGRAPHIC ASSESSMENT OF ENDOMETRIAL

THICKNESS: A REVIEW
Richard J. Persadie, MD, FRCSC
Department of Obstetrics and Gynecology. McMaster University. Hamilton ON

Abstract: Measurement of endometrial thickness with ultra- INTRODUCTION


sonography is a modality commonly used today. Its clinical
importance and applications extend throughout the phases of
Sonographic assessment of endometrial thickness is frequently
the reproductive lives of women. In premenopausal women,
endometrial thickness is used to monitor infertility treat- used in the investigation of postmenopausal uterine bleeding, 1,2
ment, while in postmenopausal women with abnormal uterine monitoring during infertility treatment,3,4 and other clinicaJ sce-
bleeding it is useful as an initial investigation for endometrial narios. Since the introduction of ultrasound into gynaecologicaJ
hyperplasia or cancer. Moreover, endometrial thickness can practice by Donald et al in 1958,5 sonographic evaluation of the
vary with the menstrual cycle and with the use of hormone
endometrium has become an integral component of the inves-
replacement therapy or selective estrogen receptor modu-
lators. In this review, the use of ultrasound to measure both tigation of abnormal uterine bleeding. Endometrial cancer
the premenopausal and postmenopausal endometrium is remains the most common gynaecological cancer in North
discussed. America, affecting 18.5/100 000 women per year in Canada. 6
The lifetime risk of developing this disease is 2%. Investigation
Resume: La mesure de I'epaisseur de I'endometre par echogra- of the endometrium has often required endometrial sampling,
phie est une methode utilisee regulierement de nos jours. Son
either by a dilatation and curettage (D&C) or via an office
importance clinique et ses applications s'etendent sur toutes
les etapes de la reproduction chez la femme. Pendant la peri- endometrial biopsy? Transvaginal ultrasound is a useful modal-
ode de premenopause, la mesure de I'epaisseur de I'en- ity that can usually be completed without much discomfort as
dometre est utilisee pour surveiller Ie traitement contre an initial visual investigation for abnormal uterine bleeding. The
I'infecondite, alors que chez la femme menopausee souffrant purpose of this review is to discuss the use of transvaginal ultra-
d'un saignement uterin anormal, elle est utile comme
sound for measurement of endometrial thickness in pre-
recherche initiale pour deceler une hyperplasie ou un cancer
de I'endometre. De plus, I'epaisseur endometriale peut varier menopausal and postmenopausal patients in clinicaJ practice.
avec Ie cycle menstruel et I'usage d'une hormonotherapie sub-
stitutive ou de modulateurs selectifs des recepteurs METHODS
d'c:estrogene. Cette revue examine I'utilisation de I'echogra-
phie pour mesurer I'endometre durant la premenopause ainsi A Medline search of the English language literature was com-
qu'apres la menopause.
pleted using the search terms "endometrial thickness,"
"endometrium," and "ultrasound." Studies that were included
J Obstet Gynaecol Can 2002;24(2): I 3 1-6.
in the review were those that correlated ultrasound measure-
ments of endometrial thickness with endometrial histology, or
examined the effects of hormone replacement therapy (HRT),
tamoxifen, and raloxifene on endometrial thickness as measured
by ultrasound. The level of evidence has been determined using
the criteria described by the Canadian Task Force on the Peri-
odic Health Examination. 8

HISTOLOGY

KeyWords The endometrium consists of two basic layers: the stratum


Endometrial thickness, transvaginal ultrasound, basalis, which lies adjacent to the myometrium, and the stra-
postmenopausal bleeding tum functionalis. 9 The stratum functionalis is further divided
into the stratum compactum, which contains mostly stroma
Competing interests: none declared.
and necks of glands, and the stratum spongiosum, consisting
Received on September 17, 200 I
mostly of glands, small amounts of stroma, and interstitial tis-
Revised and accepted on November 5. 200 I sue. The stratum fuctionalis is important for implantation of

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the blastocyst. Endometrial proliferation, secretion, and degen- secretory under the influence of progesterone. In addition, there
eration occur in the stratum fuctionalis. The stratum basalis is vascularization of the stroma. With ultrasound imaging, one
regenerates the endometrium following shedding of the func- observes hyperechogenicity of the endometrium after ovulation.
tionalis with menses. There are many benign causes of endometrial thickening
Ultrasound measurements of endometrial thickness were in premenopausal women. These include endometrial polyps
originally carried out by measuring the distance from anterior (Figure 2), submucosal leiomyomas, decidualization,
stratum basalis to the posterior stratum basalis, and dividing endometritis, and retained products of conception. Sonohys-
by 2 to give a single-layer measurement. 10 The current method terography by saline infusion is a useful procedure that can be
of choice is to include the measurement of both layers from used to further investigate cases in which a thickened
anterior basalis to posterior basalis. With transvaginal ultra- endometrium is suspected to be secondary to endometrial
sound, the transducer is physically closer to the endometrium polyps or submucous leiomyomas as seen on plain ultrasound
and uses a higher frequency (5-7 MHz) than transabdominal without contrast (Figure 3).12-21 Sonohysterograms are not
transducers. The closer proximity to the target organ and the used to measure double-layer endometrial thickness.
higher frequency result in better sonographic resolution and Collections of fluid such as blood, pus, or secretions with-
thus better visualization of the endometrium. in the endometrial cavity can produce distention of the cavity,
thereby giving the appearance of an abnormally thickened
THE PREMENOPAUSAL ENDOMETRIUM
FIGURE 2
The detection of an abnormal endometrial thickness in pre-
TRANSVAGINAL SONOGRAM DEMONSTRATING
menopausal women is usually not a cause for alarm. The AN ENDOMETRIAL POLYP
endometrial thickness in premenopausal patients varies with
the menstrual cycle. In one small series of patients, 10 a range of
6-12 mm was considered to be normal. Similar findings were
reported in another study by Bakos et aL ~ I A mean maximal
endometrial thickness of 10-,-12 mm during the menstrual
cycle was observed. In this study the sonographic appearance
of the endometrium throughout the menstrual cycle was
described. In the preovulatory phase, proliferation of endome-
trial glands and stroma occurs under the influence of estrogen,
and sonographically appears as two hypoechogenic layers
(Figure 1). Three hyperechogenic lines delineate these layers.
They represent the myoendometrial borders (two outer lines) and
apposition of the anterior and posterior endometrial surfaces
(one central line). Following ovulation, the endometrium becomes

FIGURE I FIGURE 3
TRANSVAGINAL SONOGRAM VIEW OF SONOHYSTEROGRAM OF TWO SUBMUCOUS
NORMAL ENDOMETRIUM ON DAY II OF UTERINE LEIOMYOMAS
THE MENSTRUAL CYCLE

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endometrium. 22 Often, with the presence of a fluid collection Patients with infertility comprise another subpopulation
in the endometrial cavity there will be a hypoechoic or sonolu- of premenopausal women for whom sonographic measurement
cent area between the two basalis layers. The presence of blood of endometrial thickness is useful. It has been shown that preg-
within the endometrial cavity (hematometra) can arise from nancy rates in patients receiving ovarian stimulation are
outflow obstruction of the lower genital tract, such as an imper- improved when a trilaminar pattern (as described above) of the
forate hymen, a transverse vaginal septum, or cervical stenosis endometrium is seen, as compared to a homogeneous pattern.3,4
(Figure 4). Although hematometra and pyometra are often Ijland et al. 4 have studied endometrial activity, thickness, and
associated with benign conditions, they can also be indicators ultrasound texture in a series of 19 women with unexplained
of endometrial or cervical cancer.23 Tissue sampling is indicat- infertility who underwent controlled ovarian hyperstimulation
ed when there is a high index of suspicion for these diseases cycles (total of 35 cycles). The endometrial thickness was
(Ill-C). Anovulation is a frequent cause of endometrial hyper- 4.9 ± 2.2 mm at the start of the cycles and reached a maximum
plasia and endometrial thickening or transvaginal ultrasound. of 11.8 ± 3.5 mm on day nine following administration of
Although the prevalence of endometrial cancer is very low in human chorionic gonadotropin (hCG). In addition, the
premenopausal women,24 abnormal uterine bleeding warrants endometrial texture changed throughout the cycles. At the start
investigation. Atypical endometrial hyperplasia may be a cause of the cycles, 83% of the endometrial patterns were hyper-
of endometrial thickening and requires treatment because of echogenic and homogeneous. On the day of hCG adminis-
the risk of progression to carcinoma.25 tration a triple line pattern developed in 73% of patients, while
on day nine following hCG, the endometrium demonstrated
USE OF TRANSVAGINAL SONOGRAPHY a homogeneous pattern again (93%). An endometrium that
IN PREMENOPAUSAL WOMEN displays a triple line pattern on ultrasound appears to be the
most favourable type of endometrium for nidation of the
In premenopausal women with abnormal uterine bleeding, embryo.4
transvaginal sonography is a useful investigation to examine the
endometrium. 26 When the endometrium is thickened, abnor- THE POSTMENOPAUSAL ENDOMETRIUM
malities including neoplasia, polyps, leiomyomas, and retained
products of conception must be considered. In a recent small Vaginal ultrasonography is an important tool for the investiga-
observational study of 74 women? 7 the endometrium was exam- tion of postmenopausal bleeding, but does not replace the need
ined by ultrasound in women who had undergone first trimester for endometrial sampling by an office endometrial biopsy or a
aborrion (termination of pregnancy, incomplete spontaneous D&C to rule out neoplasia? Measurement of endometrial
abortion, and missed abortion). In 77% of the cases, the ultra- thickness (Figure 5) has been extensively studied to suggest
sound exams demonstrated intrauterine material of varying which women are at higher risk for precancerous or cancerous
echogenic patterns. The endometrial thickness varied from 7 to changes.!
61 mm. These measurements suggest that the endometrial cav- A meta-analysis performed by Smith-Bindman et al. I
ity is seldom completely empty after a first trimester abortion. included 35 studies in which measurements of endometrial

FIGURE 4 FIGURE 5
HEMATOMETRA IN A PATIENT WITH TRANSVAGINAL SONOGRAM OF A NORMAL
CERVICAL STENOSIS POSTMENOPAUSAL ENDOMETRIUM

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thickness were obtained by endovaginal ultrasound prior to endometrial sampling. The most common findings were
endometrial sampling, with a total study population of 5892 endometrial atrophy (23 patients), endometrial polyps (13
women. Using a 5-mm threshold as the criteria for increased patients), benign endometrial hyperplasia (5 patients), tubal
endometrial thickness, it was determined that endovaginal ultra- metaplasia (3 patients), and endometrial carcinoma (2 patients).
sound has a sensitivity of 96% (95% CI, 94-98%) and a speci- One woman had metastatic breast carcinoma in the endome-
ficity of 61 % (95% CI, 59-63%) for detecting endometrial trial specimen. The endometrium was considered to be thick-
cancer, and a sensitivity of 92% (95% CI, 90-93%) and speci- ened on ultrasound if the thickness was greater than 2.5 mm
ficity of81 % (95% CI, 79-85%) for identifYing endometrial for a single layer. Transabdominal and transvaginal views were
disease. This meta-analysis suggested that receiver-operator used. From these findings, it can be concluded that women
characteristic curves were developed to examine the effect of using tamoxifen require ultrasound monitoring and should have
using various thresholds for a normal endometrial thickness on endometrial sampling if the endometrium is thickened or if
ultrasound,1 an approach which one day may permit women there is uterine bleeding (II-2B).
who have a low probability of endometrial hyperplasia or can- Raloxifene, another SERM, is used primarily for prevention
cer to avoid the discomfort of endometrial sampling. and treatment of osteoporosis. Cohen et aL 43 reviewed data from
two prospective, randomized, double-blind, placebo-controlled
HORMONE REPLACEMENT THERAPY trials to investigate the effect of raloxifene on the endometrium.
There were 969 patients who were randomized to one of three
Hormone replacement therapy (HRT) is known to increase doses of raloxifene or placebo for a period of three years. This
endometrial thickness through estrogenic stimulation. 2 A study study confirmed that raloxifene does not increase the endome-
by Omodei et aL 28 investigated the endometrial thickness of trial thickness as measured by transvaginal ultrasound when a
women on either sequential or combined HRT, in cyclic or con- cut-off of5 mm is used. In a smaller study, Fugere etaL44 com-
tinuous regimens. The authors determined that there was no sta- pared the use of 150 mg of raloxifene to continuous combined
tistically significant difference in the mean endometrial thickness HRT in 136 postmenopausal patients over 24 months and
between women on cyclic (3.6 ± 1.5 mm) and combined also found that raloxifene did not increase the endometrial thick-
(3.2 ± 1.8 mm) regimens. The authors concluded that patients ness. Of the biopsies taken, 94.4% demonstrated normal,
on HRT with an endometrial thickness greater than 4 mm benign, postmenopausal endometrial tissue. In-the group of
should undergo endometrial sampling to rule out pathology. 28 women on continuous combined HRT, 78.7% of biopsy spec-
In Smith-Bindman's meta-analysis, the sensitivity for detection imens showed normal benign endometrium; 19.1 %, benign
of endometrial disease did not change with use ofHRT, 1 but the stimulatory endometrium; and 2.1 %, benign abnormal post-
specificity declined as the percentage of women with normal menopausal endometrium.
endometrial histology who had an endometrial thickness greater
than 5 mm increased (8% vs 23%). In addition to post- SALINE INFUSION SONOHYSTEROGRAPHY
menopausal bleeding, endometrial sampling should be consid- IN POSTMENOPAUSAL PATIENTS
ered for postmenopausal women with a thickened endometrium
greater than 5 mm who do not experience abnormal uterine Sonohysterography has been investigated in a cross-sectional
bleeding (III-C). 1There is currently no evidence-based recom- study of 148 asymptomatic early postmenopausal women. 45
mendation to guide the use of endometrial sampling for women The results suggest that saline infusion sonohysterography is
who have postmenopausal uterine bleeding with an endometrial more accurate than transvaginal ultrasound in detecting focal
thickness of 5 mm or less. When deciding whether or not to sam- endometrial thickening and endometrial polyps.
ple the endometrium of patients in the latrer group, one should Epstein et aL46 in a prospective study compared saline infu-
consider the false-negative rates of transvaginal ultrasound (8%), 1 sion sonohysterography, transvaginal sonography, and hys-
endometrial biopsy (5-15%),29-35 and D&C (2-6%).34,36-39 teroscopy for the investigation of postmenopausal bleeding
in women with an endometrial thickness greater than 5 mm.
SELECTIVE ESTROGEN RECEPTOR The authors concluded that saline infusion sonohysterography
MODULATORS AND THE ENDOMETRIUM is as good as hysteroscopy (96% agreement) for the detection
of focally growing lesions, but no modality was able to reliably
Tamoxifen is a selective estrogen receptor modulator (SERM) discriminate between benign and malignant focal lesions.
that is used as adjuvant treatment for patients with breast can-
cer. 40 It is known to have stimulatory estrogenic effects on the ENDOMETRIAL SCREENING
endometrium. 41 ,42 Tesoro et aL42 evaluated the endometrium
of 80 women who used tamoxifen by correlating ultrasound There have been three large studies completed to determine
findings with histology. Fifty-five of these women underwent whether screening asymptomatic postmenopausal women with

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