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Massachusetts General Hospital
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Volume 3 Issue 4 - April 2005
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Ultrasound in the Evaluation of Abnormal Vaginal Bleeding

  • Bleeding in post-menopausal women is abnormal and is the most common presenting symptom for
    endometrial cancer

  • Nearly all endometrial cancer (96%) is associated with a thickened endometrium
    (>4mm in post-menopausal women), which can be measured by transvaginal ultrasonography

  • Saline infusion sonohysterography is a sensitive technique for the detection of focal lesions but
    does not provide histological data

  • Gynecologists recommend that the imaging work-up of abnormal bleeding in post-menopausal
    women should always be supplemented with histological information


Post-Menopausal Bleeding
The Saline Infusion Sonohysterography Procedure
Menorrhagia
Scheduling
Further Information
References

A
lthough most abnormal vaginal bleeding is caused by hormone imbalance, it can be indicative of disease including polyps, myomas, endometrial hyperplasia, and cancers of the cervix and endometrium.  In post-menopausal women, the greatest concern is endometrial cancer, which is now the most common gynecological cancer. Therefore, it is important to determine the cause of all cases of post-menopausal vaginal bleeding. More than 90% of the cases of endometrial cancer occur in women over 50 and this disease accounts for approximately 10% of the cases of vaginal bleeding in post-menopausal women.

Post-Menopausal Bleeding

Transvaginal Ultrasound (TVUS)
The first step in evaluation post-menopausal bleeding may be a TVUS or an endometrial biopsy. Although TVUS is the least sensitive and specific examination for the diagnosis of cancer, it is more sensitive than biopsy for the detection of other abnormalities, such as polyps and fibroids, that are more commonly the cause of bleeding. It is also the least invasive method and results in little or no discomfort for most patients. Endometrial cancer causes the endometrium to thicken, which appears as a thickened hyperechoic stripe in transvaginal US images. The thickness of the endometrial stripe can be measured accurately and it has been estimated that 96% of post-menopausal women with endometrial cancer will have an endometrial stripe greater than 4 mm. At this threshold the false positive rate is 50%. TVUS can also show if the endometrial lining is very thin. If so, the bleeding may be due to endometrial atrophy.

Causes of Vaginal Bleeding in
Post-Menopausal Women
Polyps 30%
Sub-mucosal fibroids 30%
Endometrial atrophy 8%
Hyperplasia 4-8%
Endometrial carcinoma 10%

Women who are being treated with tamoxifen are at increased risk of developing endometrial cancer but TVUS can be misleading in these patients. Tamoxifen can cause sub-endometrial cyst development, which makes the endometrium appear thickened in transvaginal sonograms. However, the sub-endometrial cystic tissue can be differentiated from the endometrium itself in saline infusion sonohystograms.
 
Transvaginal ultrasound of a postmenopausal woman with vaginal bleeding shows an abnormally thickened endometrium. Endometrial biopsy revealed atrophic endometrium.
 
Transvaginal ultrasound of a postmenopausal woman with vaginal bleeding shows an abnormally thickened endometrium. Endometrial biopsy revealed atrophic endometrium.

Endometrial Biopsy (EMB)
Gynecologists recommend that EMB be selected as an initial screening test for the evaluation of post-menopausal bleeding. Alternatively, it can be performed if the thickness of the endometrial stripe is >4 mm in post-menopausal women and >16 mm in pre-menopausal women. In addition, it should be performed if the endometrial stripe is <4 mm is post-menopausal women and no cause for bleeding has been identified by TVUS (or TVUS and saline infusion sonohysterography) because there is a small risk (1.2%) of endometrial cancer in these women.

Saline Infusion Sonohysterography (SIS)
Saline infusion sonohysterography (SIS) is a very sensitive ultrasound technique for detecting focal lesions because a small volume of saline (<20 ml) is used to distend the uterine cavity in order to improve visualization of the endometrial surface. SIS is a minimally invasive alternative to hysteroscopy and is appropriate for further evaluation of patients in whom a focal abnormality is suspected from TVUS as well as patients in whom no cause for the bleeding has been identified after biopsy and TVUS. In addition, SIS may be useful when a thickened endometrium has been identified by TVUS because SIS can differentiate between diffuse and focal thickening.

It should be pointed out that if the cause of bleeding cannot be identified after SIS and EMB and if bleeding persists in a post-menopausal patient, it is possible that the results from ultrasound imaging and biopsy are false negatives. Therefore, the patient should be referred for hysteroscopy and endometrial biopsy even if her endometrial stripe is <4 mm.  If the hysteroscopy-guided biopsy is negative, the post-test probability of endometrial cancer is 0.5%.


Sensitivity, Specificity, Positive and Negative Predictive Values
for Endometrial Cancer in Post-Menopausal Women


Sensitivity Specificity PPV NPV
Transvaginal Ultrasound (TVU) 67% 56% 7% 97%
Endometrial Biopsy (EMB) (blind)* 87% 98.5% 82% 99.1%
Saline Infusion Sonohysterography (SIS) 89% 46% 16% 97%
Hysteroscopy and Biopsy 86% 99.2% 100% 99.5%
*Numbers include inadequate samples as negative
(Clark, TJ, Mann, CH et al. 2002; Critchley, HO, Warner, P et al. 2004; Clark, TJ, Voit, D et al. 2002)


Techniques for the Evaluation of Abnormal Vaginal Bleeding


Advantages Disadvantages
Transvaginal Ultrasound (TVUS) Minimal patient discomfort post-test

probability of endometrial cancer is 1.2% if endometrium <4 mm
If endometrium is thickened, need biopsy to confirm diagnosis
Endometrial Biopsy
(EMB)
Provides histological diagnosis of cancer May fail due to cervical stenosis

May fail to provide sufficient tissue for histology

11% False negative rate
Saline Infusion Sonohysterography
(SIS)

Surveys entire uterus

More sensitive than TVUS for detecting focal abnormalities of endometrium

May detect focal thickening of endometrium

More sensitive than hysteroscopy for detecting fibroids

May cause cramping sensation

Treatment not possible

Positive findings require histological confirmation

Hysteroscopy Can biopsy and/or remove focal lesions

More sensitive than SIS for polyp detection

Patients describe procedure as markedly unpleasant

View may be obscured



Sonohysterography reveals an endometrial polyp originating from the posterior wall of the uterine fundus. Color doppler demonstrates the vascular stalk (arrows).  This was resected hysteroscopically.
 
Sonohysterography reveals an endometrial polyp originating from the posterior wall of the uterine fundus. Color doppler demonstrates the vascular stalk (arrow).  The polyp was resected hysteroscopically.

Menorrhagia
SIS is also appropriate for the evaluation of ovulating women with menorrhagia. In these women, the examination should be performed within the first week following the end of menstruation. At this point in the menstrual cycle the endometrium is in the proliferative stage and is relatively thin. Therefore, abnormalities are less likely to be obscured. SIS is contraindicated if the patient is pregnant, has a pelvic infection, or has unexplained pelvic tenderness.
  The Saline Infusion Sonohysterography Procedure
SIS is generally a well-tolerated procedure although some women experience mild to moderate cramping either during the insertion of the catheter into the cervix or during the infusion of saline into the uterus. Therefore, patients should be advised to take medication that they use for normal menstrual cramps approximately one hour prior to the examination. If the patient is allergic to latex products, it is important to provide that information in advance of the examination because it is necessary to prepare somewhat differently to accommodate these patients.

SIS takes approximately one hour and is performed by a radiologist experienced in this technique with the assistance of an ultrasound technologist. First, a TVUS evaluation is performed to image the uterus, endometrium, and ovaries. Then a speculum is introduced into the vagina, the cervix is cleaned and a small balloon catheter (3 mm) is inserted through the vagina into the center of the cervix using sterile technique. Once in place, the balloon is inflated to secure it in position and the speculum withdrawn. The TVUS device is then reinserted and approximately 10-20 ml of sterile saline is gently infused into the uterus while real-time images are observed. The entire uterine cavity is surveyed and representative images acquired. This phase of the examination lasts 10-15 minutes. In some cases, women experience cramping during the first 24 hours following SIS. If this occurs, they should continue to take medication for menstrual cramps.


Scheduling
  Further Information
Transvaginal ultrasound may be performed at Mass General West Imaging in Waltham, in Chelsea, and on the main MGH campus. However, saline infusion sonohysterography is only performed on the main campus. Appointments at all locations can be scheduled by calling 617-724-XRAY(9729). In addition, transvaginal (pelvic) ultrasound but not sonohysterography can be ordered through the web-based Radiology Order Entry system, http://mghroe .

  For further questions on ultrasound, please contact Susanna Lee, M.D., Ph.D., Assistant Radiologist in the Abdominal Imaging and Intervention Division, at 617-726-8396. In addition, further information on the evaluation of abnormal vaginal bleeding can be found at the MGH Primary Care Office Insite website.

We would like to thank Linda Duska, M.D., gynecological oncologist and Isaac Schiff, Chief of the Obstetrics and Gynecology Service at MGH for their advice on the work-up of abnormal vaginal bleeding in the preparation of this article.




This article provided useful information about the appropriate use of imaging studies:


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References
   

Critchley, HO, Warner, P, Lee, AJ, Brechin, S, et al. (2004) Evaluation of abnormal uterine bleeding: comparison of three outpatient procedures within cohorts defined by age and menopausal status. Health Technol Assess 8: 1-139

Goldstein, RB, Bree, RL, Benson, CB, Benacerraf, BR, et al. (2001) Evaluation of the woman with postmenopausal bleeding: Society of Radiologists in Ultrasound-Sponsored Consensus Conference statement. J Ultrasound Med 20: 1025-1036

O'Neill, MJ. (2003) Sonohysterography. Radiol Clin North Am 41: 781-97

Shipp, TD. (2005) Does ultrasound have a role in the evaluation of postmenopausal bleeding and among postmenopausal women with endometrial cancer? Menopause 12: 8-11