Fleischer, Arthur C. M.D.
Professor of Radiology and Radiological Sciences, Professor of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee, U.S.A.
The author has disclosed that he has no significant relationship with or financial interest in any commercial companies pertaining to this educational activity.
Address correspondence and reprint requests to: Arthur C. Fleischer, MD, Professor of Radiology and Radiological Sciences, Professor of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, TN 37232-2675.
Objectives: After reading this article and completing the posttest, the learner should be able to:
* Explain the role of transvaginal sonography in the evaluation of women with endometrial disorders.
* Describe additional procedures such as sonohysterography.
Transvaginal sonography (TVS) has assumed a pivotal role in the evaluation of women with endometrial disorders. 7 The detailed resolution of TVS and the enhanced depiction of the endometrium with saline infusion sonohysterography (SIS) offers important information concerning the potential for abnormality of the endometrium in symptomatic and asymptomatic women. In most patients, clinical decisions such as whether to perform a biopsy or alter hormone replacement regimens are now based on sonographic findings.
Occasionally, the sonographic examination of the endometrium is equivocal or incomplete and magnetic resonance imaging (MRI) may be needed. This may occur in patients with fibroids that distort the endometrium or in women in whom adenomyosis is suspected. Contrast-enhanced MRI is particularly helpful in establishing the presence and extent of myometrial invasion in patients with endometrial carcinoma.
This overview describes some of the technical factors that influence the accuracy of TVS of the endometrium and the typical sonographic findings in endometrial disease. The limitations of this diagnostic modality are also presented with suggestions for alternative procedures and methods that may reduce diagnostic uncertainty.
The endometrium is a nongeometric shape and therefore is difficult to characterize by one linear measurement. However, most investigators have attempted to quantitate this dynamic mucous membrane by measurement of its bilayer thickness in the long-axis of the uterus (Fig. 1). This measurement is readily obtained in most patients and is usually reproducible (±1–2 mm) between examiners. 4,12 Proper measurement of the bilayer thickness requires empiric adjustment of the imaging plane by the sonographer to optimize its sonographic depiction. The endometrium can be studied in the short-axis with particular attention to the area where the endometrium invaginates into the cornual regions (Fig. 2). Calculation of an endometrial volume (ml) can be obtained by multiplying the long (sagittal) axis, short (anteroposterior) axis, and width by 0.5 (formula for a prolate ellipsoid). Newer scanners that have three-dimensional imaging can also be used to quantitate the volume (ml) of the endometrium.
Saline infusion sonohysterography can be performed if there is uncertainty concerning the intactness or texture of the endometrium or surrounding myometrium. 17 This technique uses a flexible plastic catheter with an introducer (Akrad, Cranford, NJ), which is placed at the external cervical os. The catheter is then advanced through the introducer into the endometrial lumen. Once in place, small amounts of saline (3–5 ml) are instilled. The intraluminal fluid acts as an excellent contrast for depicting the endometrium and inner myometrium.
The normal endometrium of a premenopausal or perimenopausal woman is quite different from that of a postmenopausal woman. Transvaginal sonography of the endometrium in a woman of childbearing age reflects changes in thickness and texture that correlate with histologic findings in various phases of the menstrual cycle (Fig. 3). During the menstrual phase, the endometrium becomes irregular and intraluminal blood and/or sheets of sloughed endometrium can be seen. Endometrial peristaltic waves are directed toward the cervix during menses and toward the fundus in midcycle. These can be recognized by recording the sonographic examination on videotape and playing it back in the fast-forward mode. The relatively thin (3–5 mm) and hypoechoic inner myometrium is typically seen surrounding the basal layer of endometrium. The endometrium thickens (up to 5–7 mm) and becomes more echogenic during the proliferative phase. Within 2 to 3 days before and after the midcycle, or expected time of ovulation, the endometrium has a multilayered appearance with the basal layer echogenic and the hypoechoic inner functional layer, separated by the thin and echogenic amedian echo arising from refluxed mucus. During the secretory phase, the endometrium thickens (up to 14 mm) and becomes echogenic, probably as a result of stromal edema and distended glands. Enhanced through-transmission resulting from stromal edema can be observed in some patients approximately 8 days before the onset of menses. Spiral vessels within the endometrium can be seen with color Doppler sonography, particularly in the secretory phase (Fig. 4).
As opposed to the premenopausal endometrium, the endometrium of normal postmenopausal women is thin (<6-mm bilayer thickness) and is slightly echogenic when compared with the myometrium because it is mostly composed of the basalis layer. The endometrium of obese patients may be thicker than this because of peripheral conversion to estrogen in the patient's adipose tissue. The hypoechoic layer beneath the endometrium, representing the inner myometrium, may be less apparent in postmenopausal women than in premenopausal women. The endometrial interface can appear thickened if there is a large amount of trapped, inspissated, intraluminal mucus.
In the women of childbearing age, because the endometrium reflects the influence of circulating estrogen and progesterone, it is important to compare the sonographic appearance of the endometrium with the presence of follicles or corpora lutea in the ovary. One should realize that some corpora lutea may not be sonographically apparent as cystic masses within the ovary. Their rim of vascularity can be recognized with transvaginal color Doppler sonography, as well as by its characteristic low-impedance flow Doppler waveforms. In postmenopausal women, it is not uncommon to detect small cystic adnexal masses in asymptomatic women. These may represent inclusion cysts and typically do not correlate with endometrial findings seen on TVS.
The most frequent indication of TVS of the endometrium is for evaluation of women with postmenopausal bleeding. Any postmenopausal bleeding episodes need to be evaluated because 10% to 15% of these women will have endometrial carcinoma, a disease that is readily curable and usually detected in an early stage. 10
The data from several large studies indicate that endometrial thickness less than 5 to 6 mm is associated with endometrial atrophy, and biopsy is not needed. 6,8 If the endometrium is more than 5-mm thick (Figs. 5,6), bleeding may be associated with a histologically abnormal endometrium (hyperplasia or cancer). However, one needs to realize that the positive predictive value of an endometrium more than 6 mm is less than the negative predictive value of TVS (ability to exclude disease). In other words, TVS has superb accuracy in excluding disease but less accuracy in establishing that there is a definite histologic abnormality when the endometrium appears thickened.
Polyps typically appear as echogenic masses within the endometrial lumen. They can contain punctate cystic areas that represent related glandular elements within the polyp. It may be necessary to perform SIS to confirm the initial TVS impression and to show the pedicle of the polyp. It is important to realize that approximately 3% of polyps contain cancer. 18
Carcinomas may show irregular endometrial/myometrial borders, indicating myometrial invasion (Fig. 6). If there is a suspicion of invasion, contrast-enhanced MRI can accurately assess the presence and extent of invasion.
A recently published meta-analysis showed high accuracy (99% probability) of TVS for the exclusion of carcinoma if the endometrium measured less than 5 mm and had a normal texture. 19 This accuracy could also be applied to women using hormone replacement therapy (HRT).
HORMONE REPLACEMENT Therapy: Tamoxifen
Transvaginal ultrasound has an important role in women with unscheduled bleeding while undergoing HRT or tamoxifen. Endometrial thicknesses greater than 6 mm will usually require biopsy for complete workup because of the increased incidence of polyps and cancer associated with this medication. 14,15 Tamoxifen use may be associated with the presence of punctate cystic spaces in the inner myometrium, presumably representing reactivated adenomyomas. 9 Cystic areas within the endometrium, however, may represent obstructed glands within a polyp. The endometrium may appear thickened because of areas of microscopic cystic atrophy. 16
Patients using tamoxifen may exhibit thickened endometria (up to 8 mm) that may be negative on biopsy. This may be caused by the cystic glands (cystic endometrial atrophy) adding to apparent endometrial thickness. If the integrity and/or texture of the endometrium are still in question, one is encouraged to evaluate further with SIS. 1
There are a variety of regimens for HRT. Most use a combination of estrogen and progesterone. Newer medications such as Raloxifene (Lilly Pharmaceuticals, Indianapolis, IN) are selective estrogen receptor modulators. The endometrial thickness in patients undergoing HRT is similar to that for postmenopausal women who are not using medication (<6 mm; within 1–2 mm). 11 One should be aware that the endometrial thickness in women using combined cyclic HRT may vary up to 3 mm, depending on when the TVS is performed. The endometrium is thinnest after the progesterone exposure. 14
Occasionally, negative biopsy specimens can be obtained even though the endometrium appears thickened on TVS. This may occur with polyps that are not adequately sampled or in areas of focal rather than diffuse abnormality. Cystic atrophy is another cause of apparent thickening on TVS and a negative biopsy specimen. 16 In this condition, multiple interfaces are created in areas of microscopic cystic change. If there is a question about the texture or integrity of the endometrium, SIS should be performed (Fig. 8). In one study, one out of six women with a negative biopsy specimen was found to have an endometrial abnormality on SIS. 5
Transvaginal sonography can be used to determine which patients with biopsy-proven cancer can undergo simple hysterectomy versus those who require more extensive operations. Invasive tumors disrupt the integrity of the hypoechoic inner myometrium, whereas noninvasive tumors do not 3 (Fig. 5). If the TVS results are inconclusive, contrast-enhanced MRI should be performed.
OTHER ENDOMETRIAL DISORDERS
Bleeding that occurs in the premenopausal woman is usually associated with poor luteal phase function. It may also be associated with submucosal fibroids and/or adhesions, both of which are clearly defined on SIS (Figs. 7,8). Submucosal fibroids tend to displace the endometrium, and it may be difficult to delineate the endometrium in some women with fibroids; SIS should be used to delineate the endometrium and its relationship to the fibroids. Rarely, fibroids located in the cervix and/or lower corpus may complicate introduction of the SIS catheter. An MRI may be an alternative diagnostic modality in these cases.
Initial experience with transvaginal color Doppler sonography shows the capability of assessing myometrial and endometrial blood flow. Color Doppler sonography can detect the main feeding vessels of a polyp. However, it is thought that both benign and malignant endometrial disorders may result in focal areas of increased vascularity. Changes in uterine blood flow have been reported during HRT and tamoxifen. Perhaps, color Doppler sonography could direct biopsy of the most vascular area of the endometrium where there is the highest probability of obtaining pathologic tissue. Three-dimensional sonography can be used to depict endometrial disorders such as polyps. It may also be useful in women whose endometrium is distorted by fibroids or a uterine malformation. 13
Transvaginal sonography is the primary diagnostic modality for the evaluation of women with abnormal uterine bleeding. Even though it is not histologically specific, TVS provides a means to differentiate between those women who need endometrial biopsy and those who do not, and among women who require more extensive surgery than simple hysterectomy. Transvaginal sonography has a major role in evaluating women who experience bleeding who are using HRT or tamoxifen. The positive predictive value of TVS is less than its negative predictive value, making it an important test in the triage of women with postmenopausal bleeding. Finally, the positive effects of TVS and SIS as a means to contribute to diagnostic decision-making in women with postmenopausal bleeding has been conclusively shown. 2
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17. Parson A, Cullinan JA, Goldstein S, Fleischer AC. Sonohysterography, sonosalpingography and sonohysterosalpingography: A text-atlas of normal and abnormal findings. In: Fleischer AC, Manning FA, Jeanty P, et al., eds. Sonography in Obstetrics and Gynecology, Ed. 5. Stamford, CT: Appleton & Lange, 1996:931–68.
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© 2001 Lippincott Williams & Wilkins, Inc.