Post-Menopausal Bleeding: Role of Imaging

a
Sandra Hurtado, (MD) and Mahesh K. Shetty, (MD, FRCR) b ]]
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Post-menopausal bleeding (PMB) accounts for 5% of gynecologic office visits and is the pre­
senting symptom in 90% of women with endometrial cancer, which requires prompt evaluation.
The most common etiology of PMB is vaginal or endometrial atrophy and endometrial polyps,
while endometrial hyperplasia and carcinoma account for less than 10% of PMB. Transvaginal
ultrasonography measurement of an endometrial thickness (EMT) less than or equal to 4 mm has
a 99% negative predictive value for endometrial carcinoma. Endometrial sampling is required if
EMT > 4 mm or persistent bleeding occurs. Further evaluation can be accomplished with saline
infusion sonography, magnetic resonance imaging, and hysteroscopy.
Semin Ultrasound CT MRI 44: 519–527 © 2023 Published by Elsevier Inc.

P ost-menopausal bleeding (PMB) is reported in about

10% of women after menopause. PMB is classically de­
fined as any amount of bleeding in a female who has gone
12 months without a cycle due to the depletion of the ovarian
follicles.1 Vaginal bleeding is presumed to originate from the
uterus but other nonuterine causes and lower genital tract
etiologies should be ruled out by performing a careful history
and physical examination, and appropriate testing such as ur­
inalysis, pap test, and hormone levels. Transvaginal ultra­
sonography and endometrial biopsy are essential tools in the
diagnosis of PMB. PMB occurs in 4%-11% of postmenopausal
women and accounts for 5% of gynecologic visits.2 The in­
cidence appears to be inversely related to time from menopause.
A prospective study of 417 Danish women showed a 10-fold
reduction in occurrence of PMB in women who were more than
3 years post-menopausal compared to only 1 year.3 Vaginal
bleeding is the presenting sign in 90% of postmenopausal
women with endometrial cancer, and any female presenting
with PMB needs to be evaluated for the possibility of uterine
carcinoma.4 Endometrial cancer is the most common type of
gynecologic cancer and accounts for 92% of uterine cancers.5
The American Cancer Society predicts in the US 66,200 new
cases of cancer of the uterine body in 2023 and of these 13,030
women will die from this cancer.6 The incidence of endometrial
cancer increases with age with a 1%-2% cumulative risk of
endometrial cancer in females age 50-70.
Etiology
Postmenopausal vaginal bleeding is usually caused by
atrophic changes of the vagina or endometrium secondary to
hypoestrogenemia.7 Hypoestrogenic changes of the vulva,
urethra, vagina, and cervix are usually diagnosed on in­
spection during physical exam, as well as other etiologies
such as vulvar dermatoses, vaginal infections, trauma, or
vulvar, vaginal, or cervical neoplasia. Additional testing with
cultures and vulvar, vaginal or cervical biopsies may be ne­
cessary to establish diagnosis and appropriate management.
Once lower genital causes are excluded then intrauterine
etiologies must be evaluated. Atrophic endometrium col­
lapsed surfaces have little fluid and friction creates micro­
erosions of the epithelium and subsequent chronic
inflammatory reaction that leads to light bleeding or spot­
ting.8 Atrophic endometrium can be detected by transvaginal
ultrasonography (TVUS) or hysteroscopy (Fig. 1).
A study of 454 postmenopausal women with uterine
bleeding found endometrial pathology as follows: en­
dometrial polyps (37.7%), endometrial atrophy (30.8%),
benign proliferative/secretory endometrium (14.5%), car­
cinoma (6.6%), fibroid (6.2%), hyperplasia (2%), and aty­
pical hyperplasia (0.2%).9 Table 1 adapted from Hsu et al
shows a lower incidence of endometrial polyps (2%-12%)
and includes hormone replacement therapy (HRT) as a
culprit for PMB in 15%-25% cases10 (Table 1).

a
b
University of Texas Health Science Center, Houston, TX. Endometrial Polyp
Baylor College of Medicine, Houston, TX.
Endometrial polyps are typically benign epithelial growths of
Address reprint requests to Sandra Hurtado, MD, University of Texas
Health Science Center Obstetrics and Gynecology Houston, Texas. the endometrial glands and stroma around a vascular core
Email: Sandra.M.Hurtado@uth.tmc.edu that project from the surface and growth is stimulated by

https://doi.org/10.1053/j.sult.2023.10.003 519
0887-2171/© 2023 Published by Elsevier Inc.
520 S. Hurtado and M.K. Shetty

pooled sensitivity of 93% [95% Confidence Interval (CI) 86%-

96%] and specificity of 81% [95% CI 76%-86%] for detecting
endometrial polyps.12 The prevalence of polyps increases in
postmenopausal females to 12%13 and are seen more often in
women who are obese (Odds Ratio (OR) 4.6), have elevated
glucose (OR 2.83), dyslipidemia (OR 7.0) or use HRT (OR
2.7).14,15 The incidence of malignant polyps in systematic
review and meta-analysis of over 10,000 patients was about
3.5% and the risk is higher in postmenopausal women with
Figure 1 Hysteroscopic image demonstrates an atrophic en­ bleeding, women who use of tamoxifen, or have Lynch or
dometrium. Cowden syndrome.16,17 Endometrial polyps are usually
missed when performing an endometrial biopsy or dilatation
and curettage (D&C) but can be detected on TVUS or hys­
Table 1 Post-Menopausal Bleeding Etiologies10 teroscopy. On TVUS, an endometrial polyp is a well-defined
Estimated homogeneous isoechoic polypoid lesion with preservation of
Causes Percentages (%) the endometrial-myometrial interface (Fig. 2).
Color flow Doppler is used to enhance the diagnosis of a
Atrophic endometrium/atrophic 60-80
polyp by identifying the central feeding vessel with a positive
vagina
predictive value of 83%.18 SIS demonstrated a pooled sensi­
Endometrial cancer 7-10
Endometrial hyperplasia 5-10 tivity of 93% [95% CI 86%-96%] and specificity of 81% [95%
Endometrial / cervical polyps 2-12 CI 76%-86%] in a meta-analysis of 5 studies19 (Fig. 3). In
HRT 15-5 women on Tamoxifen, there is a 30%-60% prevalence of
Other < 10 endometrial polyps. Risk factors for development of en­
Uterine leiomyoma dometrial polyps include obesity and hypertension, increased
Cervicitis levels of circulating estrogen are the likely cause of polyp
Tamoxifen therapy development and growth in obese women. Symptoms from
Trauma polyps do not relate to the size, number, or location of en­
Anticoagulation dometrial polyps. Co-existing endometrial and cervical polyps
are seen in 24%-27% of women at presentation.8 A meta-
analysis study showed that the risk of malignancy in a polyp is
highest in post-menopausal women with vaginal bleeding and
unopposed estrogen and use of tamoxifen. An endometrial is 2.3%. In asymptomatic women, the risk of malignancy was
polyp is a well-defined homogeneous, polypoid lesion iso­ extremely low at 0.3%.20 The gold standard management is
echoic to hyperechoic to the endometrium with preservation hysteroscopy with guided biopsy with a sensitivity of 100%
of the endometrial-myometrial interface. Atypical features are and a specificity of 91% for diagnosing endometrial polyps.
defined as including cystic components, multiple polyps, This approach has an advantage of being able to remove a
broad-based hypoechoic or heterogenous. The diagnosis of polyp which is recommended in all women with bleeding.
polyp can be enhanced during TVUS by the use of color flow Endometrial polyps are typically hyperechoic with well-de­
Doppler for identifying the central feeding vessel, with a fined margins and surrounded by a thin hyperechoic halo,
positive predictive value of 83%.11 A meta-analysis of 5 cystic spaces represent dilated glands with proteinaceous fluid.
studies showed that saline infusion sonography (SIS) had a Identification of a single feeding vessel to a suspected polyp

Figure 2 (A) Endovaginal midline sagittal image of the endometrium demonstrates an echogenic mass (arrowhead) in
the endometrium suggestive of an endometrial polyp. (B) Hysteroscopic image demonstrates a smooth margin
endometrial mass proven to be an endometrial polyp.
Post-Menopausal Bleeding 521

Figure 3 (A) Endovaginal ultrasound with color Doppler midline sagittal image of the uterus demonstrates an en­
dometrial mass with feeding vessels (arrowhead) consistent with an endometrial polyp. (B-C) Sonohysterogram. (B)
Endovaginal midline sagittal image shows a normal saline distended endometrial cavity. (C) Endovaginal midline
sagittal image shows an endometrial polyp (arrowhead).

confirms presence of a polyp with a specificity and Negative

Predictive Value of 95% and 94%, respectively.21

Leiomyomas
Uterine fibroids will decrease in size after menopause and
their prevalence decreases by 90%.22 Generally, PMB in the
presence of fibroids should be considered to be from the
endometrium except for women on hormone replacement
which can induce fibroid growth and withdrawal
bleeding.23 TVUS depict submucosal fibroid as a well-de­
fined broad-based solid mass with shadowing and over­
Figure 4 Endovaginal sagittal ultrasound image of the uterus shows
laying layer of endometrium is echogenic and distorts the
a posterior submucosal fibroid (arrowhead) in a post-menopausal
endometrial-myometrial interface. Leiomyomas are a po­ patient with bleeding.
tential cause of postmenopausal bleeding especially if sub­
mucosal and the incidence of sarcomatous degeneration is
higher after menopause. (Fig. 4). infiltrating the myometrium, and it presents clinically in
Sonohysterogram can assist in determining the projection of premenopausal woman with heavy painful menstrual
the fibroid into the endometrial cavity and in visualizing the bleeding. It can be suspected on a pelvic sonogram or MRI,
rest of the endometrium. A meta-analysis found SIS to have a but a definitive histopathologic diagnosis is made with a
sensitivity of 94% [95% CI 89%-97%] and specificity of 81% surgical sample. Ultrasound findings include a heterogeneous
[95% CI 76%-86%] in detection of submucous myomas.21 myometrium, myometrial cysts, asymmetric myometrial
thickness, and subendometrial echogenic linear striations24
(Fig. 5). Adenomyosis is best visualized with MRI using T2-
Adenomyosis weighted images, and it is a superior modality in cases of
Adenomyosis is a benign histologic diagnostic finding at the large uterus or coexisting myomas.25 Adenomyosis may be
time of hysterectomy where the endometrial glands are found in menopausal women who are on HRT.
522 S. Hurtado and M.K. Shetty

Figure 5 67F with post menopausal bleeding showing adenomyosis with indistinct endometrial myometrial interface
and myometrial cysts.

Endometrial Hyperplasia endometrial hyperplasia is suspected, an endometrial

PMB is the hallmark presentation for endometrial hyper­
plasia which is classified as benign or atypical, also known
as endometrial intraepithelial neoplasia (EIN).26 Ten to
20% of PMB will be either hyperplasia or uterine cancer.27
Benign hyperplasia carries an up to 4-fold increase risk of
endometrial cancer and atypical hyperplasia will lead to a
diagnosis of carcinoma within a year in a third of pa­
tients.28,29 On TVUS endometrial hyperplasia can appear as
a diffuse echogenic endometrial thickness (EMT) (Fig. 6). If
sample can be obtained by endometrial biopsy or D&C.
Hysteroscopy or SIS enhances detection of focal lesions that
maybe missed on TVUS or endometrial sampling (Fig. 7).
Endometrial Cancer
Endometrial cancer needs to be excluded for any woman
with PMB, since more than 90% of women with endometrial
cancer present with vaginal bleeding. In a meta-analysis of
over 31,000 women with PMB, the pooled risk of

Figure 6 (A) Endovaginal ultrasound sagittal image of the uterus in a patient with post-menopausal bleeding de­
monstrates thickened endometrium proven to be endometrial hyperplasia. (B) Color Doppler images in the same
patient demonstrate increased endometrial vascularity (arrowhead).

Figure 7 Endometrial hyperplasia. (A) Hysteroscopic image of a patient with post-menopausal bleeding with en­
dometrial hyperplasia. (B) Midline sagittal endovaginal ultrasound image in another patient demonstrates a thick­
ened abnormal endometrium (arrowhead) in a patient on Tamoxifen.
Post-Menopausal Bleeding
Figure 8 (A and B) Endovaginal sagittal image of the uterus shows an irregularly thickened endometrium with
increased vascularity in a post-menopausal patient with bleeding proven to be an endometrial cancer.
Figure 9 (A and B) Hysteroscopic images of 2 patients with postmenopausal bleeding showing endometrial mass
proven to be endometrial carcinoma.
endometrial cancer was 9%.30 Women in the USA have a 1
in 32 lifetime risk of uterine cancer and internationally the
rate have increased steadily due to increase in obesity and
excess estrogen along with multiple other factors.31 Type I
endometrioid adenocarcinoma accounts for more than 75%
of all cases and typically presents early as progression of
endometrial intraepithelial neoplasia and is confined to the
uterus and can be diagnosed by TVUS, EMB, or D&C with
hysteroscopy. On sonogram, endometrial cancer can appear
as a diffuse process with abnormally thickened endometrium
or as a focal polypoid mass (Fig. 8). In 759 women with
endometrial cancer, the mean EMT on TVUS was 20 mm32
(Fig. 9). When a TVUS demonstrates a thin distinct uniform
endometrial thickness of 4 mm or less the incidence of ma­
lignancy is 1 in 1000 with a 99.5% negative predictive
value.6 Using an endometrial thickness of 4 mm as the cut-
off, missed 5-fold more cases of uterine cancer in Black
women compared to White women which may be due to
Black women having a higher prevalence of myomas and
non-endometrioid cancer.33 Type II endometrial cancer may
not be excluded by a thin EMS on a sonogram. A review of
52 cases of type II endometrial cancer found that 17% had
Endometrial Stripe can substitute Endometrial Thickness
(EMS) < 4 mm and had an indistinct endometrium.34 Type II
endometrial cancers (high grade, papillary serous, clear cell
or carcinosarcoma) are not related to estrogen exposure or
endometrial hyperplasia. These cancers are diagnosed later in
523
life and typically present with extrauterine disease and have a
more advanced stage with poorer prognosis.35
Evaluation of a Patient With Post
Menopausal Bleeding
Endometrial Sampling
Historically an operative D&C was used to sample the en­
dometrium in evaluating a woman with PMB (Table 2).10,36
D&C missed endometrial lesions mainly polyps in 10% of
cases and only sampled less than 50% of the uterine
cavity.37 In 1985, D&C was replaced by performing an in
office endometrial biopsy initially performed with a Vabra
metal aspirator and was replaced with more tolerable plastic
flexible disposable device the Pipelle. The Pipelle demon­
strated adequate sampling in 97%, but malignancy was
detected in only 83% of pre-hysterectomy patients. En­
dometrial sampling obtained with Pipelle missed 54% of
cancer in tumors that do not occupy more than 50% of the
cavity or are localized to polyps.38 Blinded endometrial
sampling by D&C or endometrial biopsy is better for de­
tecting a global diffuse process. EMB is more cost effective
as an initial test in populations with a higher risk of en­
dometrial cancer > 15%.39 EMB failed to produce adequate
sample 16% of the time and had 84% sensitivity in
524
Table 2 Post-menopausal Bleeding Work-up Flowchart10,36
predicting endometrial hyperplasia and cancer with 94%
PPV.40 EMB may be painful and difficult to obtain in
women who have a stenotic cervix or an EMS < 5 mm where
there is only a 27% probability of obtaining an adequate
sample.41 In women with lower risk of endometrial cancer
and in women with possible benign endometrial abnorm­
alities, TVUS may be a better initial approach.
Transvaginal Ultrasound
American College of Obstetricians and Gynecologists and
the Society of Radiologists in Ultrasound recommend
starting the evaluation of PMB with either a TVUS or EMB
(Table 2). The most recent American College of Ob­
stetricians and Gynecologists Committee Opinion re­
commends using TVUS as the initial evaluation of PMB, if
US reveals thin distinct EMS of 4 mm or less, an EMB can be
avoided. If the EMS is greater than 4 mm, endometrial
histologic sampling is required. If there is persistent vaginal
bleeding or an insufficient EMB, a further evaluation with
sonohysterography or office hysteroscopy with endometrial
sampling is indicated.6 Ultimately the evaluation must ex­
clude endometrial hyperplasia or cancer and may be ne­
cessary to proceed to Operative Hysteroscopy with directed
sampling.
Sonohysterography
SIS uses sterile saline infused into the endometrial cavity
via a transcervical catheter to distend the uterus allowing
better visualization of endometrial pathology while per­
forming a TVUS. TVUS alone has 56% sensitivity and
S. Hurtado and M.K. Shetty
73% specificity for evaluation intracavitary pathology.42
In SIS, fluid is instilled slowly while performing a TVUS
scanning longitudinal and coronal planes and carefully
assessing the endometrial echo and surrounding hy­
poechoic junctional zone and inspecting every portion of
the uterine cavity looking for focal lesions such as polyps,
hyperplasia, or cancer.43 Sonohysterography can distin­
guish between focal and uniform thickening of the en­
dometrium and can detect structural abnormalities as
effectively as hysteroscopy.42 A study of women with
PMB and EMS > 5 mm found SIS comparable in accuracy
of detecting polyps to that of hysteroscopy.44 Sonohys­
terography can be performed with minimal costs and is
well tolerated by patients with minor side effects. A
prospective study of 1153 women ages 23-64 found side
effect to be pelvic pain in 3.8%, vagal symptoms in 3.5%,
nausea in 1%, post-procedure fever in 0.8%, and 7%
failed to complete the sonohysterography but were suc­
cessful in a second attempt when analgesics or para­
cervical block was used for patient comfort and effective
cervical dilation.45 If the SIS shows diffuse endometrium,
an endometrial biopsy can be performed with the same
intrauterine catheter after the egress of fluid, however if
SIS detects a focal lesion a hysteroscopic procedure with
directed biopsy can be scheduled.
Hysteroscopy
Hysteroscopy is the new gold standard in diagnosing and
treating intrauterine pathology.46 Hysteroscopy allows for
direct visualization of the uterine cavity and targeted
Post-Menopausal Bleeding 525

Table 3 International Federation of Gynecology and Obstetrics Staging System for Endometrial Cancer, 200952
FIGO Stage

Stage IA Tumor confined to the uterus, no invasion or invasion of less than one-half of the myometrial
thickness.
Stage IB Tumor confined to the uterus with invasion of more than one-half of the myometrial thickness.
Stage II Tumor invades the cervical stroma but does not extend beyond the uterus.
Stage IIIA Tumor invades the uterine serosa or adnexa.
Stage IIIB Vaginal and/or parametrial involvement.
Stage IIIC Tumor has spread to pelvic or para-aortic lymph nodes.
Stage Pelvic lymph node involvement.
IIIC1
Stage Para-aortic lymph node involvement (with or without pelvic nodes).
IIIC2
Stage IVA Tumor invasion of the bladder and/or bowel mucosa.
Stage IVB Distant metastases including abdominal metastases and/or inguinal lymph nodes

sampling of background endometrium or lesions and can be
performed in the office or operating room. Operative hys­
teroscopy is typically reserved for removing polyps or
myomas, and for patients that cannot tolerate office pro­
cedure and requires general anesthesia. Hysteroscopy is
more cost effective and efficient requiring less time and
faster recovery for the patient and has higher patient sa­
tisfaction.47,48 Handheld systems, such as EndoSee hys­
teroscope, allow for office-based point-of-care diagnostic
hysteroscopy that are easy to use, more economic, and re­
quire minimal patient preparation.49 Complications, such
as infection, perforation, fluid overload, and bleeding, are
higher with operative hysteroscopy compared to diagnostic
hysteroscopy 0.95% vs 0.13%.46 The risk of tumor dis­
semination with SIS and hysteroscopy is similar and it is
unclear if transport of malignant cells from the endometrial
cavity to the pelvis result in implantation, persistence, or
recurrence of tumor. In small case series, malignant cells
were found in the pelvic fluid in 6%-7% of women with
known carcinoma who underwent SIS prior to hyster­
ectomy.49 A meta-analysis found no significant difference in
positive peritoneal cytology in women who had a diagnostic
hysteroscopy with an odds ratio of 1.64 [95% CI 1.0-2.8].50
The method of sampling the endometrium is less important
if the plan is definitive treatment with hysterectomy, as in
cases where cancer is highly suspicious use of preoperative
CT or MRI can be employed (Figs. 6 and 7).
MRI in Post menopausal Bleeding
Hysteroscopy is the best method in evaluation of uterine
cavity in women with premenopausal and post-menopausal
bleeding; but more invasive. MRI is the best method for
detection of submucous myoma especially when the cavity
is large or tumor is small. In the post-menopausal group
with bleeding, the sensitivity of MRI was 88.24%, 3D
hysterosonography 88.24%, and hysteroscopy 88.24%; the
specificity of MRI was 69.23%, 3D hysterosonography
84.61%, and hysteroscopy 84.61%; and the degree of
agreement with histopathology was 0.60 for MRI, 0.72 for
3D hysterosonography, and 0.73 for hysteroscopy
(p = 0.000, 0.000, and 0.000, respectively).51 Magnetic re­
sonance imaging is considered the most accurate imaging
technique for preoperative assessment of endometrial
cancer afforded by its excellent soft tissue contrast resolu­
tion. EC appears hypo to isointense on T1-weighted images
and hyperintense or heterogenous on T2-weighted images
relative to normal endometrium with enhanced post in­
travenous gadolinium. Endometrial cancer has restricted
diffusion and demonstrates high signal intensity on diffu­
sion weighted images and low signal intensity on the ap­
parent diffusion coefficient maps. When the tumor invades
less than 50% of the myometrial thickness places, the stage
at IA and at IB of there is more than 50% myometrial in­
vasion. The depth of myometrial invasion is best measured
on the axial oblique images that are acquired perpendicular
to the endometrial cavity. A dynamic contrast–enhanced
MRI allows to determine the presence of uninterrupted
enhancement of the subendometrial zone which is best at
35-40 seconds after contrast injection. This finding is cri­
tical in those patients where fertility sparing management is
being considered. Delayed dynamic contrast–enhanced MRI
images obtained 4-5 minutes after injection are helpful for
identifying cervical stromal invasion.52-54 Table 3 outlines
the staging of endometrial cancer.52
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