Sunday, March 25, 2012

Diagnosing Post Menopausal Bleeding

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.

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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


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.

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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.

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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:
  1. Performing a pelvic examination to determine whether the uterus is anteverted or retroverted.
  2. Inserting the speculum, and swabbing the cervix with antiseptic.
  3. 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.
  4. 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.
  5. 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.

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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.


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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