DOI: 10.1148/rg.233025150
(Radiographics. 2003;23:703-718.)
© RSNA, 2003
US of Abnormal Uterine Bleeding1
Penny L. Williams, MD,
Sherelle L. Laifer-Narin, MD and
Nagesh Ragavendra, MD
1 From the Department of Radiological Sciences, University of California, Los Angeles, Center for the Health Sciences. Recipient of a Certificate of Merit award for an education exhibit at the 2001 RSNA scientific assembly. Received October 7, 2002; revision requested October 31 and received December 16; accepted December 16. Address correspondence to P.L.W., 10964 Wellworth Ave #102, Los Angeles, CA 90024 (e-mail: pennalee@hotmail.com).
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Abstract
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Any significant deviation from a woman’s established menstrual pattern may be considered abnormal uterine bleeding, and several factors direct evaluation of a patient with such bleeding. Premenopausal disorders that are well evaluated with ultrasound (US) include endometriosis, adenomyosis, and leiomyomas. A positive pregnancy test in a woman of childbearing age prompts a search for an intrauterine pregnancy. Possible complications that may contribute to bleeding include ectopic pregnancy; placental factors including position, trauma, and infection; gestational trophoblastic disease; preterm labor; and postpartum complications. Atrophic changes, hormonal status, and carcinoma are considerations in the postmenopausal patient with abnormal uterine bleeding. Foreign bodies, trauma, infection, polyps, and iatrogenic causes can be observed in all groups. Differential diagnoses for abnormal uterine bleeding in premenopausal, pregnant, and postmenopausal patients are well evaluated with US, and US techniques have greatly facilitated evaluation of pelvic disease. Urgent and emergent conditions such as ectopic pregnancy, placenta previa, and preterm labor are readily identifiable.
© RSNA, 2003
Index Terms: Genitourinary system, infection, 85.217 • Genitourinary system, neoplasms, 85.31, 85.32 • Pregnancy, complications, 85.82 • Uterus, hemorrhage, 854.413
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LEARNING OBJECTIVES
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After reading this article and taking the test, the reader will be able to:
- Describe an approach to evaluation of abnormal uterine bleeding on the basis of hormonal status.
- List common manifestations of abnormal bleeding that are specific to the pre-, peri-, and postmenopausal states.
- Identify urgent or emergent conditions that manifest as abnormal bleeding, such as ectopic pregnancy, placenta or vasa previa, and preterm labor.
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Introduction
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Any significant deviation from a woman’s established menstrual cycle can be considered abnormal bleeding. Such manifestations as bleeding between menses (metrorrhagia), irregular length of cycles with or without a variable duration and amount of bleeding (menometrorrhagia), or an increased number (polymenorrhea) or decreased number (oligomenorrhea) of bleeding episodes may be present. In addition, overall increased volume (menorrhagia) or, conversely, a reduction in blood loss per cycle (hypomenorrhea) is included in this description (1,2). Malignancy must be excluded as a cause of bleeding in peri- or postmenopausal patients.
Multiple factors contribute to highly sensitive and specific findings at ultrasonography (US). Results of careful laboratory and clinical evaluation of the patient with abnormal bleeding guide treatment and direct imaging studies. Other aspects of the patient’s history should also be determined: Has the patient undergone recent surgery or instrumentation? Is there a history of unusual exposures, including diethylstilbestrol exposure in utero? Are coexisting medical conditions present? Differentiating abdominal and pelvic conditions that may mimic pelvic pain or vaginal bleeding, such as cystitis or genitourinary calculi, is useful. Coupled with a thorough history, the patient’s hormonal status then helps provide a directed study.
In this article, we present a comprehensive review of characteristic appearances of processes that may manifest as abnormal uterine bleeding. Differential diagnoses for conditions in premenopausal, pregnant, and postmenopausal patients are discussed and illustrated with relevant US findings.
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Premenopausal Patients
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The secretory phase of the menstrual cycle occurs when estrogen levels peak and the endometrium is prepared for implantation of a fertilized ovum. If pregnancy does not occur, progesterone levels surge and endometrial breakdown follows, leading to menstruation (2). The normal premenopausal endometrial thickness is reported to be 2–4 mm after menses with an echogenic appearance. At ovulation, the endometrium appears layered and is 10–14 mm thick. After ovulation, the endometrium resumes a more uniform echogenic appearance and ranges from 10 to 14 mm in thickness (3) (Fig 1).
In the absence of pregnancy, increased emphasis is placed on systemic factors to explain dysfunctional bleeding. Many pharmaceutical agents are known to cause abnormal uterine bleeding, including medications for treatment of hirsutism, digitalis, phenytoin, antidepressants, hormones for hormone replacement therapy, tamoxifen, anticoagulants, and corticosteroids (1). Bleeding disorders such as platelet deficiency, prothrombin deficiency, and Von Willebrand disease contribute significantly. Increased free estrogens due to lack of metabolism of sex steroids and hypoprothrombinemia as the result of hepatic cirrhosis may trigger bleeding (Fig 2). Hypothyroidism and polycystic ovarian disease are also classically associated with menstrual disturbances (Figs 3, 4). Finally, malpositioned, migrating, or perforating intrauterine devices (IUDs) should be suspected when there is a history of IUD use (Fig 5).
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Figure 3. Transverse US image of a hyperstimulated ovary shows multiple enlarged follicles up to 3 cm in diameter, some of which contain debris, which is consistent with hemorrhage.
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Endometriosis is the presence of functioning endometrial tissue outside the uterus. It may be located in the broad ligament, ovary, fallopian tube, intestine, bladder, or posterior cul-de-sac. The more localized form is known as an endometrioma, which can be distinguished from a hemorrhagic cyst when it is present separate from the ovary. Cystic collections of echogenic blood products can be seen (Fig 6). Often, fluid-debris levels are noted (Fig 7). However, the diagnostic requirements for identification of endometriomas with US differ among investigators. Patel et al (4) performed an independent review of US features for distinguishing endometriomas and other adnexal masses and concluded that "the presence of diffuse low-level internal echoes is the important feature that helps discriminate an endometrioma from other lesions" and "cystic US features (definable wall and increased acoustic transmission) did not improve diagnostic performance once diffuse low-level echoes had been recognized."
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Figure 7. Sagittal US image shows a multiloculated mass with fluid-debris levels, which was initially thought to be a tubo-ovarian abscess. A surgical specimen demonstrated endometriomas.
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Adenomyosis is a related condition in which there is functional endometrial tissue within the myometrium. The US appearance of adenomyosis includes myometrial cysts, ill-defined areas of myometrial echotexture, heterogeneous and distorted myometrial echotexture, and a globular or enlarged uterus with asymmetry (5–7) (Fig 8).
Leiomyomas, which are also called fibroids, affect nearly one-fourth of women of reproductive age. Leiomyomas are more prevalent among black women than among white women. The most common symptom is heavy vaginal bleeding. Since a leiomyoma is a proliferation of smooth muscle surrounded by a pseudocapsule, unopposed estrogens may accelerate its growth. Leiomyomas are characterized by the layer they occupy, whether submucosal (or subendometrial), intramural within the myometrium, or subserosal (Figs 9, 10). Intramural lesions do not involve the endometrial cavity, whereas submucosal lesions are intracavitary and are best detected with saline hysterosonography. Leiomyomas are often heterogeneous in echogenicity and attenuate sound. Hypoechoic areas within a leiomyoma may represent cystic degeneration (Fig 11).
Uterine artery embolization is a definitive therapy for uncontrollable bleeding. When leiomyomas are devascularized, they undergo infarction with the resultant formation of small nitrogen bubbles in the leiomyoma. These bubbles appear as multiple punctate echogenic foci, giving the leiomyoma a speckled appearance (Fig 12). Tranquart et al (8) observed that uterine artery embolization resulted in "marked reduction in fibroid size and disappearance of intra-fibroid vessels without reduction in uterine vascularization [that is] well depicted by sonography."
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Figure 12. Longitudinal US image shows multiple echogenic foci throughout the uterine fundus with "dirty" shadowing posteriorly, an appearance consistent with air bubbles. The patient recently underwent embolization for a uterine leiomyoma.
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Infection of the female reproductive tract may be secondary to ascending infection from the vagina or cervix; direct extension from appendiceal, diverticular, or postsurgical abscesses; or puerperal or postabortion complications. Hematogenous spread is rare. Endometritis can be detected with US. Gas and fluid can often be identified in a thickened endometrial cavity (Fig 13). Vaginitis, cervical erosions, and cervicitis may be evaluated at clinical pelvic examination.
Fluid-filled fallopian tubes, pyo- or hydrosalpinx, are well demonstrated with US (Figs 14, 15). Low-level echoes are more commonly encountered in pyosalpinx due to the higher protein content of the debris within the tube. Overall, serpentine, dilated tubes are typically present, which may be anechoic or contain low-level echoes. In general, the tube may be seen coursing from the ovary to the uterus. This entity may be further complicated by a tubo-ovarian abscess, in which a multiloculated appearance of the ovary is found, with the loculi containing simple fluid or debris (Fig 16) (11). Hyperemia of the ovarian tissue is typically present.
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Figure 16. Sagittal US image shows a complex mass in the right adnexa that contains cystic components with internal debris, a solid component, and multiple septa. The mass represented a tubo-ovarian abscess.
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Cervical carcinoma is an additional consideration (Fig 17), especially in a sexually active patient, and is best evaluated at clinical examination.
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Figure 17. Sagittal US image of a patient who underwent hysterectomy shows a large, heterogeneous, midline mass. The mass appears cystic and contains echogenic foci that produce ring-down artifact, which likely represent gas. Pathologic analysis demonstrated squamous cell carcinoma of the cervix.
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Pregnant Patients
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US examination of the pregnant patient with bleeding begins with confirmation of an intrauterine pregnancy. Visualization of a gestational sac containing a yolk sac equates with an intrauterine pregnancy (Fig 18).
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Figure 18. Sagittal US image of the uterus shows a tiny (3-mm-diameter) fluid collection (arrow) in a patient with a positive pregnancy test. The fluid collection was confirmed to be a 4.7-week intrauterine pregnancy.
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Ectopic pregnancy occurs with a prevalence of 1.4% and accounts for one-fourth of maternal deaths. Vaginal bleeding, a palpable adnexal mass, and pelvic pain make up the classic clinical triad. Risk factors include infertility, prior ectopic pregnancy, a history of tubal surgery, and prior pelvic inflammatory disease (PID). Kamwendo et al (10) studied standardized population statistics and the prevalence of ectopic pregnancy and PID between 1970 and 1997. They determined that agreater than twofold increase in ectopic pregnancy occurred between 1970 and 1985 and since then the prevalence had declined by 30%. Admissions for PID continuously increased from 1970 through 1975, with a peak prevalence of 3.2 per 1,000 women. The prevalence subsequently declined to a low of 0.5 per 1,000 women in 1997. Kamwendo et al (10) concluded that "reduction of PID was strongly associated with a decline of ectopic pregnancy."
The majority of ectopic pregnancies are tubal (95%), with the ampulla being a more common location than the isthmus. Interstitial (cornual) ectopic pregnancies occur in the intramural portion of the tube as it traverses the uterine wall and appear as an eccentric gestational sac surrounded by a thin myometrial mantle (Fig 19). Interstitial ectopic pregnancies often rupture later than other types of ectopic pregnancies and may cause massive intraperitoneal hemorrhage (4). Ovarian ectopic pregnancies are rare, making up only 0.5%–1% of ectopic pregnancies. Coexistent intrauterine and ectopic pregnancy is very rare, occurring in 1 in 7,000–30,000 cases (11). Cervical ectopic pregnancies (Fig 20) are also rare (0.1%) and need to be distinguished from abortion in progress with serial examinations. In patients who have undergone cesarean section, implantation can take place in the uterine scar. Management of a pregnancy implanted in a cesarean section scar is identical to that of a traditional ectopic pregnancy. In addition, an intrauterine pregnancy may occur concomitantly with the presence of an IUD (Fig 21), and this possibility must be considered.
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Figure 19. Coronal US image of the uterus shows an eccentrically located gestational sac containing a yolk sac in the right cornual region (arrow). There is a thin (2-mm) myometrial mantle.
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Figure 21. Sagittal US image of the left adnexa shows an echogenic focus within the peritoneum (arrow) caudal to the left ovary (OV). The patient has an intrauterine pregnancy, and her IUD could not be located at clinical examination. A corresponding coronal US image showed a linear echogenic structure in the peritoneum, which was consistent with an IUD that had perforated the myometrium.
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When ectopic pregnancy is evaluated with US, an echogenic adnexal ring with trophoblastic tissue lining the tube may be seen. Free fluid or clot present in the cul-de-sac is included in the spectrum of findings. Tubal hematomas can appear as a complex adnexal mass. Visualization of an embryo with a detectable heartbeat within the adnexa confirms the diagnosis (Figs 22, 23). A pseudo–gestational sac or decidual casts coupled with ß–human chorionic gonadotropin levels greater than 1,800 mIU/mL without a demonstrable yolk sac should be looked on as very suspicious for ectopic pregnancy.
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Figure 22. Coronal US image shows an echogenic ring (arrow), which is consistent with an ectopic gestational sac containing a yolk sac and demonstrated cardiac activity. Complex fluid, consistent with hemoperitoneum, surrounds the structure.
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When an intrauterine pregnancy is present, multiple additional factors are considered as the embryo develops. First-trimester bleeding complicates nearly 25% of all pregnancies, half of which end in spontaneous abortion. A gestational sac noted in two different positions during serial examinations serves to document an incomplete abortion or abortion in progress (Fig 24). Lack of cardiac activity with a mean sac diameter greater than 15–18 mm at endovaginal examination is highly suggestive of fetal demise (9) (Fig 25).
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Figure 24a. (a) Sagittal US image shows fetal demise in the uterine fundus (arrow). (b) Longitudinal US image obtained the next day shows the gestational sac in the lower uterine segment (arrow), an appearance consistent with an abortion in progress.
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Figure 24b. (a) Sagittal US image shows fetal demise in the uterine fundus (arrow). (b) Longitudinal US image obtained the next day shows the gestational sac in the lower uterine segment (arrow), an appearance consistent with an abortion in progress.
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Various causes of abnormal uterine bleeding include entities such as subchorionic hemorrhage, infection, abnormal placental position, and trophoblastic disease. Subchorionic hemorrhage is the result of venous bleeding at the placental margin. Small, contained hematomas are usually insignificant, whereas large hematomas are associated with fetal demise (Figs 26, 27). Infection may be introduced into the uterus after rupture of the membranes, resulting in chorioamnionitis. If the placenta covers or abuts the internal cervical os, it is known as placenta previa or partial placenta previa, respectively (11) (Fig 28). When vessels traverse the os, vasa previa is present (Fig 29). An overdistended bladder may simulate this appearance and is a well-known imaging pitfall. During the first or second trimester, if vasa or placenta previa is identified, rescanning in the mid–third trimester is recommended to reevaluate placental location, as migration of the placenta can occur. Different mechanisms explaining apparent placental migration have been proposed. Atrophy of less well-vascularized portions of the placenta implanted over the cervical os with migration of other placental areas to more richly supplied regions has been suggested. Growth of the uterine fundus relative to the lower uterine segment may also occur (12–14).
Trophoblastic disease is the result of dispermic fertilization of an empty ovum, usually 46,XX, with no fetal tissue present. A "bunch of grapes" appearance with hydropic villi and trophoblastic hyperplasia is seen at US. In the first trimester, a large echogenic mass with multiple cystic spaces is noted within the endometrial cavity (Fig 30). Involvement of the myometrium constitutes an invasive molar pregnancy (Fig 31), whereas malignant extrauterine expression is termed choriocarcinoma. Hydropic placental degeneration may simulate molar disease, as the chorionic villi are engorged, but trophoblastic proliferation is absent (Fig 32).
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Figure 30a. Coronal (a) and sagittal (b) US images show an irregular mass with multiple cystic spaces that fills the uterine cavity, an appearance consistent with a hydatidiform mole.
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Figure 30b. Coronal (a) and sagittal (b) US images show an irregular mass with multiple cystic spaces that fills the uterine cavity, an appearance consistent with a hydatidiform mole.
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Figure 31a. Gray-scale (a) and color (b) transverse US images show a complex solid and cystic mass (arrow) in a portion of the endometrial cavity that extends into the anterior myometrium.
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Figure 31b. Gray-scale (a) and color (b) transverse US images show a complex solid and cystic mass (arrow) in a portion of the endometrial cavity that extends into the anterior myometrium.
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Figure 32. Coronal US image of the endometrial echo complex shows a thickened, heterogeneous endometrium with multiple cystic components (arrow), an appearance consistent with hydropic placental degeneration.
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Preterm labor can result from cervical incompetence, and cervical length provides an accurate indicator for preterm labor. Cervical factors such as incompetence and preterm labor must be recognized. Cervical length at transabdominal imaging should be greater than 3 cm. Minor dilatation of the cervix can produce "funneling" or"beaking" of the internal os, indicating cervical incompetence (Figs 33–35). With progressive cervical dilatation, an "hourglass" deformity of the lower uterine segment or bulging of membranes through the endocervical canal may be identified (Fig 36).
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Figure 33. Longitudinal US image of the cervix shows membranes and a fetal lower extremity in the vagina. This appearance is consistent with cervical incompetence, as the patient was not having contractions.
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Figure 36. Sagittal US image of a patient with a 25-week intrauterine pregnancy who presented to the emergency department with contractions. The cervix (CX) is dilated and a fetal lower extremity and membranes bulge into the vaginal canal (VAG), an appearance consistent with preterm labor.
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Persistent vaginal bleeding following delivery may be secondary to various factors. Infection in the endometrial cavity, endometritis, affects 2%–3% of patients after vaginal delivery, but the prevalence may be as high as 85% after cesarean section (11) (Fig 37). Uterine rupture and uterine atony may have similar presentations, including fever, pain, or severe vaginal bleeding. Retained products of conception are the most commonly encountered cause of excessive bleeding after childbirth. The endometrium is usually markedly thickened and may be highly vascular at color and power Doppler imaging, demonstrating high-velocity, low-resistance arterial flow (Fig 38). This entity may also manifest as a focal, heterogeneous mass expanding the endometrial cavity.
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Figure 37. Sagittal US image of the uterus obtained 3 days after childbirth shows echogenic foci producing ring-down artifact in the lower uterine segment (arrow), an appearance consistent with gas in the endometrial cavity.
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Figure 38. Sagittal US image of the uterus shows a heterogeneously thickened endometrium. Low-resistance arterial flow is present. Pathologic analysis demonstrated retained products of conception.
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Peri- and Postmenopausal Patients
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The peri- and postmenopausal endometrial thickness is normally less than that in the premenopausal patient. During menopause, the endometrium primarily consists of a thin basalis layer, and the measurement of the endometrial echo complex represents the apposition of the two basal layers. Atrophic change occurring in menopause demonstrates an endometrial echo complex less than 5 mm thick composed of sclerotic blood vessels and glands (15) and is the most common cause of postmenopausal bleeding (Fig 39). Normally 5–7 mm thick, the postmenopausal endometrial stripe may be nonpathologically increased to 8–10 mm thick if the patient is using hormone replacement therapy (3,16–22).
Endometrial hyperplasia is the result of unopposed estrogens on the endometrium. It is most commonly encountered in perimenopausal women. Prolongation of the proliferative phases of the menstrual cycle leads to abnormal growth of the uterine lining, which can result in irregular bleeding. At US, endometrial hyperplasia appears as echogenic thickening that follows the uterine contour. Tiny cystic spaces may be seen. This finding must be differentiated from retained products of conception or blood clots on the basis of the clinical history or the presence of a vascular nidus. Endometrial polyps, endometrial carcinoma, and submucosal myomas can have a similar appearance (Fig 40).
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Figure 40. Longitudinal US image of the uterus in a postmenopausal patient shows a markedly thickened, heterogeneous endometrium with cystic spaces, which is suggestive of hyperplasia or a polyp. Pathologic analysis demonstrated a polyp.
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Endometrial polyps may be identified as small, pearl-shaped, echogenic masses. They are generally asymptomatic but may cause menometrorrhagia. At saline infusion hysterosonography, they may appear smoothly marginated and tend to project off of a stalk (3,15,23) (Figs 41, 42). A single feeding vessel may be present. Pathologically, endometrial polyps are excrescences of endometrial tissue (3,24). They have a small to moderate malignant potential, and hysteroscopy or curettage is the treatment of choice. One study reported that 23.8% of endometrial polyps had premalignant changes (complex and atypical hyperplasia), whereas 1.5% of the polyps had undergone frank malignant degeneration (25).
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Figure 41a. (a) Transverse US image of the uterus shows a markedly thickened, heterogeneous endometrial echo complex (arrow). (b) Transverse image from saline hysterosonography shows multiple endometrial polyps (arrow).
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Figure 41b. (a) Transverse US image of the uterus shows a markedly thickened, heterogeneous endometrial echo complex (arrow). (b) Transverse image from saline hysterosonography shows multiple endometrial polyps (arrow).
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In recent years, tamoxifen has become more widely used in treatment of estrogen-sensitive breast cancers. Tamoxifen may cause abnormal uterine bleeding and has a nonspecific US appearance. Tamoxifen-induced changes include endometrial hyperplasia and endometrial polyps, which appear as hyperechoic or heterogeneous solid tissue with multiple cystic spaces (15,26). Subendometrial cysts may also be noted (Fig 43).
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Figure 43a. (a) Transverse US image of a patient being treated for breast carcinoma shows that the endometrium is thickened and heterogeneous, containing multiple tiny cystic spaces. (b) Transverse image from saline hysterosonography shows a large tamoxifen-induced polyp.
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Figure 43b. (a) Transverse US image of a patient being treated for breast carcinoma shows that the endometrium is thickened and heterogeneous, containing multiple tiny cystic spaces. (b) Transverse image from saline hysterosonography shows a large tamoxifen-induced polyp.
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Endometrial carcinoma is most common in the postmenopausal age group and is most prevalent in women over 50 years of age. Hypertension, obesity, polycystic ovarian disease, diabetes, and colon or breast cancer are risk factors in addition to age. Clinically, bleeding is often accompanied by a watery discharge (2). At US, smooth or masslike thickening of the endometrium is present, which may have a heterogeneous echotexture (Fig 44). The differential diagnosis includes endometrial hyperplasia, endometrial polyps, and submucosal leiomyoma (15). Suspicion is high when a postmenopausal endometrium greater than 10 mm in diameter is encountered. Serologic measurement of cancer antigen 125 levels may be helpful in following the course of endometrial carcinoma, including preoperative evaluation and postoperative surveillance (28,29).
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Conclusions
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Differential diagnoses for causes of abnormal vaginal bleeding in premenopausal, pregnant, and postmenopausal patients are well evaluated with US, and US techniques have greatly facilitated evaluation of pelvic disease. Urgent and emergent conditions such as placenta previa, ectopic pregnancy, and preterm labor are readily identifiable. Hormonal status, including results of hormone replacement therapy, has demonstrable effects on the endometrium and plays a large role in investigation of the causes of abnormal uterine bleeding.
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Footnotes
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Abbreviation: IUD = intrauterine device
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References
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Abstract
LEARNING OBJECTIVES
