Diagnosis of postmenopausal bleeding begins with the
patient evaluation by the professional. The doctor will ask for a detailed
history of how long postmenopausal bleeding has occurred. A woman can assist
the doctor by keeping a record of the time, frequency, length, and quantity of
bleeding. She should also tell the doctor about any medications she is taking,
especially any estrogens or steroids.
After taking the woman's history, the doctor does a pelvic
examination and PAP test. The doctor will examine the vulva and vagina
for any signs of atrophy, and will feel for any sign of uterine polyps.
Depending on the results of this examination, the doctor may want to do more
extensive testing.
Definitions
The following definitions are valuable
when evaluating diagnostic tests:
- Sensitivity-the proportion of persons
predicted to have a disease to those that actually have it.
- Specificity-the proportion of persons who do
not have the disease, those who are predicted not to have the disease, as
well as the proportion of persons correctly identified with the disease.
- Accuracy-the degree to which a measurement
represents the true value of the attribute that is being measured.
- Positive
predictive value-the
probability that a person with a positive test result has the condition.
- Negative predictive value-the probability that a person with a negative test result does not have the condition.
Invasive diagnostic procedures
Hysteroscopy
The most invasive diagnostic method, hysteroscopy, is considered the gold
standard in the evaluation of PMB. A gynecologist performs this procedure with
the patient under anesthesia. Hysteroscopy entails a visual examination of the
uterine cavity using endoscopic equipment.
Although hysteroscopy can be performed in the
outpatient setting, it requires anesthesia and a gynecologist skilled in the
procedure. The accuracy of hysteroscopy is most useful in making the diagnosis
of cancer when compared to other types of endometrial disease. In one case
series of 181 patients, the sensitivity was 96.6% and the specificity 100% when
hysteroscopy was used in conjunction with EMB. However, even
hysteroscopy has limitations. Although efficient in the detection of
pathological intrauterine lesions, it is only moderately successful in
determining physiological changes such as proliferative endometrium or
endometrial hyperplasia. This underscores the importance of tailoring the
evaluation of PMB to the individual patient, as well as combining diagnostic
methods when appropriate.
Two types of hysteroscopy are available. One uses a rigid scope with a
fluid distending medium, and at least heavy sedation is necessary. The other
type uses a flexible fiberoptic cable and carbon dioxide as distending medium.
The former is used for diagnosis and for procedures such as endometrial
ablation and resection of fibroids and uterine septa. The latter is much more
suited for diagnosis because only simple biopsies and removal of polyps are
possible. Flexible hysteroscopy can also be used in an office setting because
no anesthesia or sedation is needed.
Office hysteroscopy is ideal for direct visualization of the endometrial
cavity. If polyps are suspected, hysteroscopy can easily be used to confirm the
presence of a polyp and possibly even remove it. Suspicious endometrial areas
can be detected, and directed endometrial biopsy can be done.
Office hysteroscopes are available in several diameters; the most common
are 3 and 4 mm. The 4-mm scopes have an operating port through which biopsy
forceps or scissors can be advanced. Antiseptic solution is used to prepare the
patient, and a cotton swab dipped in lidocaine is put into the cervical canal.
The scope is gently inserted into the uterine cavity, and carbon dioxide is
used as a distending medium. Usually, countertraction on the cervix is
necessary to help guide the scope through the canal. Inspection of the cavity
can be done quickly and usually does not cause much, if any, patient
discomfort. Biopsy specimens can be obtained from suspicious areas, either
under direct vision or with an endometrial biopsy cannula guided by knowledge
of the site of the lesion.
The chief advantage of hysteroscopy is direct visualization of the
pathologic tissue; thus, an appropriate biopsy specimen can be obtained.
Hysteroscopy, especially operative hysteroscopy, is the “gold standard” against
which all other methods of endometrial assessment are compared. It has
supplanted dilation and curettage in this respect because of the ability to
visualize the biopsy site.
A major disadvantage of office hysteroscopy is that it cannot be used in
patients with cervical stenosis—these are the same patients who cannot undergo
biopsy. It also cannot be used in patients who are actively bleeding, which
impairs the ability to visualize the cavity. Office hysteroscopy can be
moderately expensive because of the cost of the equipment. Nonetheless, it is
still less expensive than dilation and curettage.
In summary, office hysteroscopy can serve as the final “arbiter” when
neither biopsy nor ultrasound examination offers a suitable explanation for
bleeding.
The widespread use of hysteroscopy, and the ability
to perform it on an outpatient basis, has resulted in a reduction in the use of
D & C for the evaluation of PMB. Indeed, some authors suggest that D &
C should not be used as a diagnostic or therapeutic option for patients with
PMB.
Dilation
and curettage
Dilation and curettage was long considered the “gold
standard” for the diagnosis and treatment of postmenopausal bleeding but is no
longer because of the “blind nature” of the procedure. It is now usually done
in conjunction with hysteroscopy in order to visualize the endometrial cavity
both before and after curettage, to assess the site of possible pathologic
tissue, and to evaluate the effectiveness of curettage.
Dilation and curettage is a relatively simple
procedure to perform. Because the patient has undergone anesthesia, stenotic
cervices can be dilated. It is also often therapeutic, and no additional
bleeding episodes occur after the operation. These advantages are negligible,
however, in light of the cost and inconvenience of the procedure. Thus,
dilation and curettage should be reserved for those patients with a
suspiciously thick endometrial stripe in which tissue cannot be obtained with
any other modality or when the cause of bleeding cannot be determined with use
of any of the less expensive methods. Even then, operative hysteroscopy is
preferable if equipment and expertise are available. Operative hysteroscopy is
substantially more accurate than dilation and curettage in the assessment of
the endometrial cavity and any possible lesions.
Endometrial biopsy
Endometrial biopsy, although less invasive than D
& C or hysteroscopy, is more invasive than ultrasonography. A flexible
catheter is introduced into the uterus and the endometrial sample is obtained
by gentle suction. Endometrial biopsy
allows the doctor to sample small areas of the uterine lining, while cervical
biopsy allows the cervix to be sampled. Tissues are then examined for any
abnormalities. This is a simple office procedure. Many family practice clinicians routinely perform EMB.
A widespread method of
endometrial sampling involves use of a flexible tube (3 mm in diameter) that is
inserted through the cervical canal. Examples of such tubes are the Pipelle
sampler and Z-Sampler. With these tubes, an obturator is withdrawn, and then
suction is created in the tube, and tissue can be obtained. This type of sample
is more easily interpreted by the pathologist than that obtained by simply
collecting cells.
The technique for endometrial
sampling is straightforward and can be achieved in 5 main steps:
- Performing a pelvic examination to determine whether the uterus is
anteverted or retroverted.
- Inserting the speculum, and swabbing the cervix with antiseptic.
- Attempting to advance the catheter. If the catheter cannot be
advanced easily, grasping the cervix with a tenaculum and using this
approach for countertraction. If the procedure is still unsuccessful, a
probe or a small dilating sound should be inserted into the uterus.
Putting a “bend” in the catheter may be necessary if the uterus is
severely flexed.
- Quickly pulling the obturator as far out as possible and movg the
catheter in and out while rotating it around its axis. Performing this
maneuver for at least 10 seconds.
- Withdrawing the catheter and expelling the sample onto blotter paper and putting the sample in a bottle of fixative.
In a recent
systematic quantitative review, EMB has appeared to be only moderately accurate in diagnosing endometrial
hyperplasia. With a positive EMB test, the probability of endometrial
hyperplasia on endometrial tissue sampling obtained by hysteroscopy or D &
C under anesthesia was 57.7%. A positive test also increased the probability of
carcinoma from 14% to 31.3%, while a negative test decreased it to 2.5%. Additional
endometrial testing should be performed when symptoms persist, or when
intrauterine abnormalities are suspected, even in the presence of a negative
result.
Another
concern with the use of EMB is its negative predictive value. A positive test
with EMB is a more definitive test of endometrial cancer than a negative test
is for ruling it out.
The specificity
of EMB is 99.1%, the sensitivity 84.2%, the accuracy 96.9%, and the positive
and negative predictive values 94.1% and 93.7%, respectively. This demonstrates that a diagnosis of endometrial
cancer on biopsy is definitive and should lead to treatment. A negative biopsy,
however, may require further evaluation, especially if symptoms persist.
Lastly, 16.1%
of the time, the sample obtained is "insufficient for diagnosis."
This is perhaps due to lack of provider expertise in the technique or
insufficient endometrial tissue in women with an atrophic endometrium. Should
this occur, further evaluation is probably needed.
After examining the tissues collected by an
endometrial biopsy or D & C, the doctor may order additional tests to
determine if an estrogensecreting tumor is present on the ovaries or in another
part of the body.
The cost of endometrial biopsy, including the
pathologist's fee, varies by institution. The sampling devices are inexpensive,
physician time to perform the procedure is less than 10 minutes, and tissue
sampling is straightforward. The charge is usually between $125 and $300.
Non-invasive diagnostic procedures
Ultrasonographic
Measurement
With concerns about the
rising cost of health care, vaginal probe ultrasound is increasingly being used
more than endometrial biopsy to evaluate women with post-menopausal bleeding. Ultrasonographic measurement of the
endometrium, a commonly used diagnostic tool for PMB, entails inserting a probe
attached to a transducer into the vagina. The transducer then measures the
endometrium to the nearest millimeter. The endometrium looks like a stripe
under sonography, hence the term "endometrial stripe" (EMS).
Endometrial stripe is commonly used when referring to endometrial measurements.
An EMS measurement > 5 mm is considered abnormal. This was determined by
multiple studies of EMS measurements. Measurements > 5 mm were highly
correlated with a histologic diagnosis of endometrial cancer.
Sensitivity of
the EMS test was recently reported to be 91% and specificity was 58%. Using pretest and posttest probabilities in a
hypothetical patient, the pretest probability of endometrial cancer in the
presence of abnormal bleeding was calculated to be 10%. With a positive test
result (EMS > 5 mm), the probability of cancer increases to 19%. However,
with a negative test result (EMS <=5 mm), the probability decreases to 1.7%.
These results indicate that a normal finding is as valuable as an abnormal
finding in ultrasonographic screening for endometrial cancer.
Although TVUS
measurement of the EMS is a useful, highly sensitive and noninvasive test, it
has its limitations. Some investigators have determined that EMS has a low
positive predictive value for cancer. This is especially true in women taking
hormone therapy (HT) and tamoxifen (Nolvadex), or women with recurrent or
postmenopausal bleeding that occurs long after menopause.
Although the
EMS measurement offers a noninvasive and potentially cost-effective method of
evaluating PMB, there are factors associated with its use that are problematic.
If the EMS is inaccurately measured > 5 mm (a false positive result), the
patient will be subjected to further invasive tests such as D & C or
hysteroscopy in order to obtain endometrial tissue for histological assessment.
Similarly, if the EMS is inaccurately measured <=5 mm (a false negative
result), then the diagnosis and treatment of endometrial cancer may be delayed.
Endometrial
stripe measurement should not be used to evaluate premenopausal women with
abnormal bleeding. An EMS measurement > 5 mm in premenopausal women may be
normal due to hormonal influences. Likewise, patients with multiple risk
factors for endometrial cancer should have further evaluation of PMB, even if
their EMS measurement is <=5 mm.
It is
difficult to ascertain the sensitivity and specificity of EMB, compared to
ultrasonography because an accurate reference standard for EMB does not exist.
The main limitation of EMB is a high rate of inadequate sampling, making
additional tests necessary.
Patients who are taking tamoxifen may have atypical ultrasonographic
findings. In such women, a common finding is an endometrial stripe that appears
to be extremely thick. This is due to a change in the myometrium under the
endometrium that mimics the ultrasonographic appearance of thickened
endometrium. This may lead to an unnecessary biopsy. If bleeding occurs in a
woman who is taking tamoxifen, however, a biopsy should be performed.
The advantage of transvaginal ultrasonography is that it can be performed
in almost every woman. An ultrasound machine and the expertise to analyze the
images obtained are necessary. The charge for a scan is similar to that for an
office endometrial biopsy. The time needed to obtain the measurement is also
comparable.
Sonohysterography
Another important diagnostic tool that has recently come into use is
saline sonohysterography. This out-patient procedure allows a visual evaluation
of the uterine cavity. A
salt water (saline) solution is injected into the uterus with a small tube
(catheter) before the vaginal probe is inserted. The presence of liquid in the
uterus helps make any structural abnormalities more distinct. It is useful in diagnosing intracavitary
lesions such as polyps, leiomyoma, and masses. It does not, however, provide a
histologic diagnosis. This test is highly sensitive (97%), and also has a high
negative predictive value (94.3%) when combined with EMB. It is important, however, to recognize the
limitations of this test. Additional diagnostic testing, such as EMB and/or hysteroscopy,
is needed when there is persistent bleeding or a need for a histologic
diagnosis based on the patient's history.
Sonohysterography is also
useful for the detection of submucous fibroids, which can create the appearance
of a thickened endometrium until saline is infused. After saline infusion, the
stripe covering the fibroid can be clearly delineated and measured. The
fibroids can also be measured serially for growth. One study found
sonohysterography to be superior to routine transvaginal scanning and
hysteroscopy for assessing size, site, and growth of fibroids.
Furthermore,
sonohysterography can detect focal areas of endometrial thickening, which raise
the index of suspicion that an actual pathologic condition is present.
Endometrial sampling is necessary in such cases. Sampling can be done with
directed endometrial biopsy, hysteroscopy, or dilation and curettage.
In summary, a
negative EMS measurement (<=5mm) should be followed by additional tests such
as EMB or hysteroscopy in high-risk patients or patients with persistent
symptoms. A positive EMS measurement (> 5 mm) should be followed by
additional tests to identify a cause for the ultrasonographic abnormality such
as polyps, hormone use, leiomyoma, or endometrial cancer. The EMS should not be
used as a screening tool in premenopausal women. It is important to use the
correct diagnostic tools to assess each patient, according to their individual
needs and histories.
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