Imaging in Abnormal Uterine Bleeding: Key Insights for Enhancing Radiologists' Expertise

Abstract

Abnormal uterine bleeding (AUB) is a common gynecological symptom experienced by approximately one-third of women at some point in their lives. There are various terminologies used to describe the symptoms of AUB, which can lead to inconsistency in interpretation. To address this, the International Federation of Gynecology and Obstetrics (FIGO) Menstrual Disorders Working Group established standardized terminology and definitions for different types of AUB in 2007. AUB can have both structural and nonstructural causes, and it is possible for more than one cause to coexist in a single patient. To categorize and evaluate the causes of AUB consistently, FIGO defined a classification system in 2011 known as the AUB system 2. This system is referred to by the acronym PALM-COEIN. “PALM” stands for the structural causes: Polyp (P), Adenomyosis (A), Leiomyoma (L), and Malignancy and hyperplasia (M). “COEIN” represents the nonstructural causes: Coagulopathy (C), Ovulatory dysfunction (O), Endometrial causes (E), Iatrogenic factors (I), and causes that are Not yet classified (N).

In this article, we review the standardized definitions and terminologies used to describe the symptoms of AUB and discuss the role of imaging and approach in identifying and classifying its causes.

Keywords

abnormal uterine bleeding - PALM COEIN classification - structural and nonstructural causes of abnormal uterine bleeding

Introduction

Abnormal uterine bleeding (AUB) is a comprehensive term that encompasses nongestational abnormal bleeding from the uterus in women of reproductive age. AUB is characterized by irregularities in the duration, volume, frequency, and/or regularity of uterine bleeding. Additionally, it includes postmenopausal bleeding, defined as any bleeding occurring after menopause in women who are not receiving hormonal therapy, as well as unscheduled or excessive bleeding in those undergoing hormonal therapy.[1]

Research indicates that approximately one-third of women will experience symptoms associated with AUB at some stage in their lives. This condition is most frequently observed in women during menarche and the perimenopausal phase.[2] Notably, up to 50% of affected women do not pursue medical evaluation.

In 2007, the International Federation of Gynecology and Obstetrics (FIGO) Menstrual Disorders Working Group established standardized terminology and definitions for various types of AUB (referred to as AUB system 1). The subsequent classification of the causes of AUB was undertaken in 2011 using the PALM-COEIN classification system (designated as AUB system 2).[1] [3] This initiative replaced previously employed, poorly defined, and often confusing terms such as menorrhagia, metrorrhagia, and dysfunctional uterine bleeding. An update to these classification systems was published in 2018.

Moreover, FIGO published recommended terminologies and definitions concerning myometrial abnormalities in 2015, followed by updates in 2021 through the Morphological Uterus Sonographic Assessment (MUSA) classification system.[4] [5] Furthermore, the FIGO ovulatory disorders classification system was introduced in 2022.[6] This review aims to elucidate the causes of AUB, their associated imaging features, and the differential diagnoses relevant to this condition.

Definition and Terminologies (AUB System 1)

A normal menstrual cycle is characterized by a frequency ranging from 24 to 38 days, 4.5 to 8 days, and a blood flow measuring between 5 and 80 mL. Additionally, the cycle length may vary by 2 to 20 days over 12 months. Deviations from these established parameters are classified as AUB.[1]

[Table 1] delineates the accepted definitions and terminology about various types of AUB, while [Table 2] provides a comprehensive overview of the acceptable abbreviations and their corresponding definitions.

Table 1 Summary of terminologies and definitions of various types of AUB

Parameters of the menstrual cycle and menstruation	Descriptive terms	Definitions
Frequency of cycle (d)	Frequent	< 24
	Normal	24–38
	Infrequent	> 38
Regularity of cycles - Variation over 12 months	Absent/amenorrhea	No bleeding in 90 days
	Regular	Variation: ± 2 to 20 days
	Irregular	Variation > 20 days
Duration of flow (d)	Prolonged	> 8
	Normal	4.5–8
	Shortened	< 4.5
Volume of blood loss (mL)	Heavy	> 80
	Normal	5–80
	Light	< 5

Abbreviation: AUB, abnormal uterine bleeding.

Table 2 Acceptable abbreviations describing menstrual symptoms

Abbreviation	Expansion	Definition
AUB	Abnormal uterine bleeding	Any deviation in menstrual flow/cycle
HMB	Heavy menstrual bleeding	Excessive menstrual blood loss that interferes with the physical, emotional, social, and material quality of life
HPMB	Heavy, prolonged menstrual bleeding	Excessive blood loss along with prolonged bleeding for > 8 days
IMP	Intermenstrual bleeding	Irregular episodes of bleeding occurring between otherwise normal menstrual cycles
PMB	Postmenopausal bleeding	Bleeding occurring > 1 year after the acknowledged menopause

AUB can be categorized into two types: acute and chronic. Acute AUB is defined as a sudden episode of bleeding in a nonpregnant woman that requires immediate medical intervention to avert further blood loss. In contrast, chronic AUB is characterized by abnormal bleeding from the uterine corpus that deviates from normal duration, volume, or frequency for the majority of the preceding 6 months.

AUB System 2

The AUB system 1 addresses the inconsistencies in terminology utilized to describe AUB. Nevertheless, discrepancies remain in the investigation and categorization of the causes of AUB, with several of these causes potentially coexisting in a single individual. In response to this issue, the FIGO has introduced the PALM-COEIN classification system.

PALM-COEIN is an acronym that categorizes the etiologies of AUB into two primary groups: structural and nonstructural. The “PALM” category encompasses structural causes that can be identified through imaging or histopathological examination: Polyp (P), Adenomyosis (A), Leiomyoma (L), and Malignancy and hyperplasia (M). The “COEIN” category comprises nonstructural causes, which include Coagulopathy (C), Ovulatory dysfunction (O), Endometrial causes (E), Iatrogenic factors (I), and causes that are Not yet classified (N).

This classification system has been developed with contributions from clinicians and researchers across 6 continents and over 17 countries. It facilitates a systematic approach to diagnosis, thereby enhancing clinical communication, research methodologies, and treatment strategies for AUB.

Endometrial Polyp: AUB-P

Endometrial polyps form when endometrial glands and stroma excessively grow within the endometrium. Endometrial polyps are primarily composed of epithelial tissue on the surface and have a predominantly vascular core. These polyps can be classified into three categories: sessile, pedunculated, or prolapsing. A prolapsed polyp may exhibit areas of squamous metaplasia, infection, or ulceration.[7]

These polyps can range from a few millimeters to several centimeters in diameter and may appear as single or multiple growths. Endometrial polyps can occur at any age but are most found between the ages of 40 and 49. Patients with endometrial polyps may either be asymptomatic or present with AUB, which is the most common symptom. The prevalence of endometrial polyps in reproductive-aged women experiencing AUB is estimated to be between 20 and 40%.[8] The most common patterns include menorrhagia and intermenstrual bleeding (IMB). The other symptoms are abdominal or pelvic pain and infertility. The location of the polyp, number, and diameter do not correlate with the reported symptoms.[9]

Chronic use of tamoxifen has been linked to the development of endometrial polyps, with an incidence rate ranging from 20 to 35%.[10] Additionally, hormone replacement therapy for menopausal symptoms may also contribute to the formation of endometrial polyps. Symptoms can include irregular bleeding and a thickened endometrium on ultrasound (US).[11]

While most polyps are typically benign, there is a small risk of them becoming malignant.[12] Malignant changes in endometrial polyps are associated with the patient's age, particularly in those over 60, and their menopausal status, especially in postmenopausal women. The other risk factors for malignant endometrial polyps include the size of the polyps, the presence of symptomatic bleeding, and polycystic ovary syndrome (PCOS).[13] The prevalence of malignant endometrial polyps is 4.47% in symptomatic postmenopausal females, compared to 1.51% in asymptomatic postmenopausal females.[14]

Imaging

Transvaginal US (TVS) represents the most utilized and effective technique for imaging pelvic structures. The findings from US examinations may occasionally be nonspecific, revealing either diffuse or localized echogenic thickening of the endometrium.[15] In patients presenting with postmenopausal bleeding, an endometrial thickness exceeding 4 mm is associated with the potential for endometrial pathology, including the presence of polyps.[11]

Saline infusion sonography (SIS) is a better method for evaluating the lesions within the endometrial cavity. It involves instilling about 5 to 30 mL of warmed saline into the cavity using a thin catheter during the proliferative phase of the menstrual cycle.

Endometrial polyps are more effectively visualized utilizing SIS, as the introduced fluid delineates the polyps distinctly. Moreover, SIS enhances the differentiation between submucosal fibroids and endometrial polyps by distinctly illustrating their respective positions within the endometrial layer. Specifically, endometrial polyps are observed to arise from the endometrial layer, whereas submucosal fibroids are positioned beneath this layer.[16]

The contraindications for SIS include the presence of active uterine or cervical infections, as well as pregnancy. Furthermore, SIS provides a superior evaluation of the adnexa and cornua in comparison to TVS.

During the TVS/SIS procedure, the following details are noted when the polyp is detected: the number and type of the polyp, its site of attachment within the endometrial cavity, and the presence and pattern of internal vascularity.

Submucosal polypoidal adenomyoma can resemble an endometrial polyp; however, it often contains cysts of varying sizes. These cysts, along with the stroma, may exhibit areas of focal hemorrhage, resulting in dark brown material filling the cystic spaces. On imaging, submucosal polypoidal adenomyoma typically shows cysts accompanied by myometrial invasion.[17]

In contrast, endometrial polyps usually have a smooth, bosselated surface and tend to appear fibrous when viewed in cross-section. They often possess small cystic spaces that reflect the dilation of glandular elements, but they do not exhibit myometrial invasion ([Figs. 1] and [2]).[18]

Fig. 1 Transvaginal ultrasound (A) and sonohysterosalpingography (B) images demonstrate a solitary, homogeneously hyperechoic intracavitary lesion with smooth outline arising from the posterior wall with preserved endomyometrial junction(marked by white arrows in A and B). Sonohysterosalpingography image of another patient (C) shows similar lesion demonstrating single vessel with no branching (marked by black arrow in C). These findings are consistent with endometrial polyp (abnormal uterine bleeding [AUB]-P).

Fig. 2 Transvaginal ultrasound (A) and Doppler (B) images demonstrate a solitary hyperechoic intracavitary lesion with regular cysts, color score of 2 and preserved endomyometrial junction (marked by black arrow in A). T2 axial (C) and postcontrast sagittal T1 fat-saturated (D) magnetic resonance imaging (MRI) images show a well-defined polypoidal lesion limited to the endometrial cavity with regular nonenhancing cystic areas within with maintained subendometrial enhancement (marked by white arrow in C and black arrow in D) (abnormal uterine bleeding [AUB]-P).

While endometrial carcinoma can also show myometrial invasion, it rarely contains cysts. Therefore, when both cysts and myometrial invasion are observed, submucosal polypoidal adenomyoma should be considered. Magnetic resonance imaging (MRI) can help differentiate between these three entities.[18] [19]

Imaging thus plays a vital role in predicting the malignant potential of a polyp thereby guiding further management.

Adenomyosis (AUB-A)

Adenomyosis is a benign gynecological condition that primarily affects multiparous women between the ages of 30 and 50. While many individuals with this condition remain asymptomatic, it may present with symptoms such as AUB, dysmenorrhea, chronic pelvic pain, and dyspareunia.[10]

The prevalence of adenomyosis exhibits considerable variation, ranging from 5 to 70%, depending on the diagnostic methods employed, with an average prevalence estimated at 20 to 30%.[20] The precise etiology of adenomyosis remains unclear; however, potential risk factors include hyperestrogenism and a history of surgeries, such as cesarean sections and dilatation and curettage. The hallmark of adenomyosis is the presence of ectopic endometrial glands and stroma within the myometrium, accompanied by hypertrophy and hyperplasia of the smooth muscle.[21]

Imaging

Diagnosis of adenomyosis typically involves various imaging modalities, including TVS and MRI. TVS is generally the initial imaging technique utilized for evaluating patients presenting with AUB. The MUSA group has established a consensus on the terminology to be used when documenting US findings related to myometrial lesions. The US report should encompass the following features: the presence or absence of adenomyosis, its anatomical location, classification as focal or diffuse, cystic versus noncystic nature, involvement of uterine layers, and the extent and dimensions of the lesion.

The findings of adenomyosis can be categorized into direct and indirect features.[5] Direct features, observable through US imaging, are characteristic of adenomyosis, whereas indirect features result from the presence of ectopic endometrium within the myometrium ([Fig. 3]).

Fig. 3 (A and E) Transvaginal ultrasound image of a patient with pain during menstruation showing globular enlargement of the uterus with heterogeneous myometrial echoes, indistinct endomyometrial junction (black dotted line in A) with tiny myometrial cysts (black arrows in A and E), and hyperechogenic islands (white arrows in A and E), consistent with diffuse adenomyosis. Volume contrast image (VCI) in E better depicts the findings. (B) Transabdominal ultrasound image shows asymmetrical thickening of anterior myometrium (marked by white dotted lines in B) with heterogeneous myometrial echoes and hyperechogenic islands consistent with anterior wall adenomyosis. (C and D) Transvaginal ultrasound and Doppler images show an ill-defined heterogeneous focal lesion with thin lines of posterior shadowing (marked by white stars in (C) and (D) and diffuse vascularity consistent with adenomyoma (abnormal uterine bleeding [AUB]-A).

The direct US features indicative of adenomyosis include:

• Myometrial cysts

• Hyperechoic islands

• Echogenic subendometrial lines and buds

The indirect features may present as:

• A globular uterine shape

• Asymmetric thickening of the myometrium

• Fan-shaped shadowing

• Translesional vascularity

• An irregular and interrupted junctional zone (JZ)

It is crucial to note that in the absence of direct features, the presence of indirect features alone does not provide conclusive evidence for the diagnosis of adenomyosis. Furthermore, a regular and uninterrupted JZ is a reliable indicator of the absence of this condition.[22] [Table 3] shows the classification and reporting guidelines for adenomyosis.

Table 3 Classification and reporting guideline for ultrasound features of adenomyosis

Criteria	Ultrasound features
Presence or absence of adenomyosis	Look for the direct and indirect features using the MUSA criteria
Location	Anterior, posterior, right lateral, left lateral, and fundal
Differentiation	Focal if > 25% of the circumference of the lesion is surrounded by normal myometrium Diffuse if < 25% of the lesion is surrounded by normal myometrium Mixed type if both focal and diffuse adenomyosis coexist
Presence or absence of cysts	Cystic - presence of cysts, which are anechoic or low-level echoes and surrounded by an echogenic rim   Noncystic adenomyosis - absence of cysts
Uterine layer involvement	Involvement of junctional zone (inner myometrium, Type 1), middle myometrium (Type 2), or outer myometrium (Type 3)
Extent	Mild (< 25% affected), moderate (25–50%), or severe (> 50% affected).
Size of lesion	Measured and documented in the plane of the largest diameter of the largest lesion. If more than 1 adenomyotic lesion is present in different locations, the sum of volumes of different lesions should be taken into account to assess the total extent

Abbreviation: MUSA, Morphological Uterus Sonographic Assessment.

MRI, due to its superior soft tissue resolution, facilitates the differentiation between adenomyosis and leiomyomas, as well as other uterine pathologies. The sequences most commonly employed include T2-weighted imaging in axial, coronal, and sagittal planes, along with T1-weighted imaging in axial and sagittal planes. It is pertinent to note that the use of contrast MRI does not yield any additional diagnostic information for adenomyosis.

Recently, a classification system for MRI findings has been proposed by Kobayashi and Matsubara,[23] which encompasses five distinct parameters:

1. Affected area: This parameter differentiates between internal myometrium (internal adenomyosis, which involves the inner one-third of the uterine wall) and external myometrium (external adenomyosis).

2. Pattern: Adenomyosis is categorized as either diffuse or focal.

3. Size: This is classified into three volumetric categories: less than one-third, less than two-thirds, or more than two-thirds of the uterine wall.

4. Location: The location is specified as anterior, posterior, left-lateral, right-lateral, or fundal.

5. Presence of concomitant pathologies: This includes the absence of additional conditions, peritoneal endometriosis, ovarian endometrioma, deep infiltrating endometriosis (DIE), uterine fibroids, or other relevant pathologies.

Internal adenomyosis is further subdivided into three types: focal, diffuse, and superficial. The focal and diffuse types are associated with JZ hypertrophy, whereas the superficial type is not associated with JZ hypertrophy. External adenomyosis involves the outer myometrium, extending to the serosa, while sparing the JZ. This form of adenomyosis is frequently observed in young nulliparous women and is often associated with deep pelvic endometriosis (DIE), making it distinguishable from endometriotic deposits when DIE coexists.

On MRI, the characteristic features of both internal and external adenomyosis manifest as ill-defined areas of T2-weighted hypointensity, attributed to smooth muscle proliferation, alongside multiple T2-weighted hyperintense foci. Small cystic regions may also be present. In T1-weighted imaging, small areas of T1 hyperintensity may be observed within the adenomyotic regions, indicating the presence of hemorrhage. [Fig. 4] shows the MRI features of adenomyosis. Adenomyomas typically present as well-defined, heterogeneous lesions confined within the myometrium, without involving the JZ or the serosa.[24]

Fig. 4 T2 sagittal magnetic resonance imaging (MRI) image (A) globular enlargement of the uterus with diffuse thickening of junctional zone with multiple myometrial cysts (marked by white arrows in A) consistent with diffuse adenomyosis. T2 oblique axial MRI image (B) of the uterus shows an ill-defined T2 hypointense area with multiple tiny T2 hyperintense cysts within the posterior myometrium extending from the junctional zone (marked by white star in B) consistent with focal adenomyosis. T2 sagittal MRI image (C) shows diffuse thickening of the junctional zone with subendometrial T2 hyperintense lines (marked by black arrow in C) involving the anterior wall consistent with adenomyosis (abnormal uterine bleeding [AUB]-A).

Leiomyoma

Benign fibromuscular tumors of the myometrium are often referred to by various terms, including “fibroid,” “leiomyoma,” and “myoma.” According to the FIGO, the term “leiomyoma” is regarded as the most precise designation. Leiomyomas represent the most common benign tumors of the uterus and are frequently asymptomatic. However, they may contribute to AUB, particularly when located in a submucosal position.[25]

Imaging

Diagnosis of leiomyomas typically occurs through the identification of an enlarged uterus or pelvic mass during clinical examination. The initial and preferred method of investigation for diagnosing leiomyomas is US, which may be conducted via transabdominal and/or transvaginal approaches. TVS is recognized for its increased sensitivity in detecting small leiomyomas or submucosal leiomyomas, especially in patients with obesity.[26] Literature suggests that the sensitivity and specificity of US in the identification of fibroids exhibit considerable variability, ranging from 24 to 96% for sensitivity and from 29 to 93% for specificity. SIS has been shown to provide significantly higher sensitivity (85–91%) and specificity (83–100%) in detecting abnormalities such as polyps, submucosal fibroids, and adhesions.[26]

MRI is noted for its superior sensitivity (88–93%) and specificity (66–91%) in detecting fibroids and differentiating them from focal adenomyosis.[26] Furthermore, MRI findings are reproducible and capable of accurately defining the extent of fibroid degeneration.

US

On US, leiomyomas present as well-defined solid masses characterized by a whorled appearance, posterior shadowing, and circumferential vascularity. The MUSA consensus opinion describes the classical imaging features of fibroids and points to differentiate them from adenomyosis.[4]

The US report should encompass the total uterine volume, the number of leiomyomas, the volumes of up to four leiomyomas, and their specific locations as per the FIGO classification. This classification delineates the relationships of the fibroids with the endometrium and serosa, as well as the uterine wall (anterior, posterior, right or left lateral wall, or fundal region) and their vertical positioning (upper or lower uterine segment). The anatomical location of fibroids is a critical parameter in predicting bleeding symptoms, with submucosal fibroids demonstrating a greater association with an increased risk of bleeding than their size.

The FIGO PALM-COIEN classification system for leiomyomas comprises primary, secondary, and tertiary categorizations. The primary classification addresses the presence or absence of leiomyomas, irrespective of their number, size, or location. The secondary classification differentiates fibroids based on the presence or absence of submucosal components, categorizing them as submucosal (SM) or other (O) leiomyomas. Furthermore, the tertiary classification introduces additional categorizations for submucosal, intramural, subserosal, and transmural locations.[27] [Fig. 5] shows the US features of intramural, subserosal, and submucosal fibroids.

Fig. 5 Transvaginal ultrasound image (A) shows a well-circumscribed hypoechoic lesion within the myometrium—intramural International Federation of Gynecology and Obstetrics (FIGO) class 4 fibroid (white arrow) and similar lesion adjacent to serosa with < 50% myometrial component—FIGO class 6 subserosal fibroid(black arrow) (abnormal uterine bleeding [AUB]-L_O). Transvaginal ultrasound image (B) shows a well-defined hypoechoic lesion in the anterior wall extending to the endometrial cavity with < 50% intramural component and disruption of endomyometrial junction (marked by white arrow)—FIGO class 1 submucosal fibroid (AUB-L_SM).

Applying the FIGO classification in the imaging assessment of leiomyomas enhances the correlation between clinical symptoms and imaging features, thereby improving confidence in identifying the underlying etiology. The FIGO classification further helps in determining the appropriate management for each subtype, guiding the choice between minimally invasive and surgical techniques. [Table 4] presents the FIGO classification of fibroids according to their location. [Fig. 6] shows the various FIGO classes of fibroids.

Table 4 FIGO secondary and tertiary system of classification of leiomyomas

Secondary system	Tertiary system: FIGO class	Definition
SM - Submucous	0	Pedunculated intracavitary with stalk diameter ≤ 10% of the mean diameter of leiomyoma
	1	Submucosal with < 50% intramural component
	2	Submucosal with ≥ 50% intramural component
	3	Contacts endometrium, 100% intramural
0 - Other	4	Intramural
	5	Subserosal with ≥ 50% intramural
	6	Subserosal with < 50% intramural
	7	Pedunculated subserosal with stalk diameter ≤ 10% of the mean diameter of the leiomyoma
	8	Other (e.g., cervical/ parasitic, etc.)
Hybrid - Contacts both the endometrium and serosa	Two numbers separated by a hyphen   E.g., 2–5	First number - relationship with the endometrium Second number - relationship with serosa   2–5: Submucosal and subserosal, each with < 50% submucosal and subserosal components, respectively

Abbreviation: FIGO, International Federation of Gynecology and Obstetrics.

Fig. 6 (A) T2 axial magnetic resonance (MR) image shows multiple well-defined predominantly T2 hypointense lesions (marked by white stars in A) in submucosal location with > 50% intramural component—International Federation of Gynecology and Obstetrics (FIGO) class 2 submucosal fibroids. (B) T2 sagittal MR image shows a well-encapsulated T2 hypointense lesion within the posterior myometrium (marked by white star in B)—FIGO class 4 intramural fibroid. (C) T2 sagittal MR image shows a similar posterior to the uterus with pedicle attached to the posterior wall of the uterus (marked by white star in C)—FIGO class 7 pedunculated subserosal fibroid. (D) T2 sagittal MR image shows a well-encapsulated heterogeneous lesion arising from the fundus of the uterus with hyperintense areas within (marked by white star in D)—FIGO class 7 pedunculated subserosal fibroid with degeneration. (E) T2 axial magnetic resonance imaging (MRI) image shows a well-defined pedunculated intracavitary lesion with pedicle attached to left lateral wall (marked by white star in E)—FIGO class 0 submucosal fibroid (abnormal uterine bleeding [AUB]-L_SM,O).

MRI

MRI is indicated in cases where US findings are indeterminate or before the planning of uterus-sparing interventions such as myomectomy or uterine artery embolization, as it provides accurate information regarding vascularity and the extent of degeneration. Furthermore, MRI is the imaging modality of choice for follow-up assessments following uterus-sparing treatments.[28]

In MRI examinations, typical leiomyomas exhibit hypointensity on T2-weighted images, isointensity on T1-weighted images, and demonstrate no diffusion restriction along with heterogeneous postcontrast enhancement. In instances of degeneration, fibroids may present with heterogeneous signals or increased signal intensity on T2-weighted images, accompanied by minimal or absent enhancement. Cellular leiomyomas are characterized by intermediate signal intensity on T2-weighted images, evidence of diffusion restriction, and pronounced enhancement after contrast administration.

In older women, the identification of recent or rapidly enlarging lesions, heterogeneous signal intensity with hemorrhagic or necrotic areas, diffusion restriction within the lesion, and signs of invasion into adjacent tissues should raise clinical suspicion for leiomyosarcoma.[29]

Endometrial Malignancy/Hyperplasia (AUB-M)

Endometrial hyperplasia is the abnormal proliferation of endometrial stroma and glands, which is representative of an entire spectrum of endometrial variation, ranging from mild atypical glandular proliferation to obvious neoplasia.[30]

Hyperplasia and neoplasms form an important component of the long list of etiologies of AUB, especially in women in the reproductive age group.[30] The primary purpose of the PALM-COEIN system is to categorize the etiologies of AUB, and on further identification of specific etiologies, such as endometrial hyperplasia, classification according to the World Health Organization (WHO) classification systems must be performed.[3]

The classification of endometrial hyperplasia according to the revised WHO classification system, 2014,[3] is as follows:

• (1) Hyperplasia without atypia

• (2) Atypical hyperplasia/endometrioid intraepithelial neoplasia

Hyperplasia without atypia is a form of benign proliferation that spontaneously regresses once the internal hormonal stimulus is corrected. Only about 1 to 3% of the times do these progress to invasive disease when there is uncontrolled prolonged exposure to the hormonal stimulus. On the other hand, atypical endometrial hyperplasias exhibit mutations within them that are characteristic of invasive malignancies. Understandably, close to 60% of these harbor concurrent malignancies or are at extremely high risk of developing invasive cancers.[31]

The fundamental etiology of these hyperplasias is a hormonal imbalance with unopposed estrogen stimulation and simultaneously inadequate progesterone levels. Some of the conditions which result in this underlying imbalance are polycystic ovarian syndrome, metabolic syndrome, nulliparity, tamoxifen therapy, corpus luteum insufficiency, Lynch syndrome, or improper hormonal supplementation in postmenopausal patients.[32] Also, about one-third of endometrial carcinomas are known to begin as hyperplasias.[30]

Accordingly, management of hyperplasia without atypia is based on conservative measures with lifestyle modifications and oral contraceptives spearheading the management protocol, with rare cases requiring preventive hysterectomy. Contrarily, patients with atypical hyperplasia and endometrioid intraepithelial neoplasia are candidates for upfront total hysterectomy, with very rare indications for conservative management.[32]

Certain other nonendometrial etiologies are also known to present as AUB. One such is carcinoma of the cervix, which is usually seen in middle-aged women, usually with certain high-risk factors and known to commonly present as IMB or post-coital bleeding. There are also other malignancies, such as leiomyosarcoma (secondary malignant transformation of uterine fibroids), which are also known to present with AUB with associated sudden interval increase in size of the fibroid.[25]

Imaging

Ultrasound

Utilization of US has become an indispensable component of routine gynecological assessment.[33] More so, when it comes to detailed evaluation of the uterus, especially the endometrium, higher resolution and a more dynamic and focused imaging is necessary with use of transvaginal sonography.

The endometrial thickness is the primary feature that points to endometrial hyperplasia in the absence of an obvious lesion. The limit beyond which the endometrial thickness is considered pathological differs according to the menstrual status and phase of the menstrual cycle as detailed in [Fig. 7].[33] [34] [35]

Fig. 7 Endometrial thickness in various age groups and various phases of menstrual cycle.

A more streamlined US evaluation and interpretation algorithm of the endometrium has been put forth with the use of the consensus opinion from the International Endometrial Tumor Analysis (IETA) group aiding in predicting the risk of different endometrial pathologies.[36] In addition to the quantification of the endometrial thickness, the following other aspects are also to be assessed:

• (1) Endometrial thickness

• (2) Echogenicity/uniformity

• (3) Midline

• (4) Outline

• (5) Color score

• (6) Vascular pattern

• (7) Endomyometrial junction

MRI

MRI is an extremely sensitive modality with excellent soft tissue resolution that helps to better delineate the endometrium and the adjacent JZ. This is most beneficial in the assessment of malignancies and gauging the extent of deeper uterine infiltration. The regular protocol consists of T2-weighted, T1-weighted, diffusion-weighted imaging, and dynamic postcontrast images with axial, coronal, and sagittal planes planned in line with the endometrial alignment.[37]

The uterine anatomy is best appreciated on a T2-weighted image and is homogeneously T2 hyperintense, surrounded by a low-signal intensity JZ and intermediate-signal intensity myometrium.[37]

Contrast enhancement is usually a relative assessment of the myometrium, and myometrial enhancement usually varies with the phase of the menstrual cycle. The postmenopausal endometrium and myometrium are usually atrophic with an indistinct JZ.[37] A thickness of 4 mm with no focal changes is usually considered normal for a postmenopausal woman with a < 1% risk of development of cancer. Preoperative pelvic MRI is known to have a moderate sensitivity and specificity in identifying invasion to the myometrium in endometrial cancer and a rather weak predictive value when used to assess the absence of myometrial invasion, thus guiding in triaging and managing endometrial neoplasia.[38] [Figs. 8] and [9] show the US and MRI of simple endometrial hyperplasia without atypia and endometrial carcinoma, respectively. [Table 5] summarizes the reporting checklist for structural causes of AUB.

Fig. 8 Transvaginal ultrasound (A) and magnetic resonance imaging (MRI) images (B) show diffuse thickening of endometrium with preserved endomyometrial junction (marked by black arrows in A) and regular midline (marked by white arrow in B). Histopathology was simple endometrial hyperplasia without atypia (abnormal uterine bleeding [AUB]-M).

Fig. 9 Transvaginal ultrasound (A and B) and Doppler images of a patient with postmenopausal bleeding showing an irregular isoechoic mass within the endometrial cavity (marked by white star in A and B) with indistinct endomyometrial junction in the posterior aspect (marked with black arrows) with multifocal vascularity and a color score of 4 (marked by white arrows in C). Note the preserved endomyometrial junction in the anterior aspect (marked by white arrows in B). T2 sagittal (D) and postcontrast T1 fat-saturated magnetic resonance imaging (MRI) images (E and F) show a heterogeneously enhancing mass within the endometrial cavity with myometrial invasion (marked by white arrows in D) and interruption of subendometrial enhancement in the posterior aspect (marked by black arrows in E and F)—consistent with myometrial invasion (abnormal uterine bleeding [AUB]-M).

Table 5 Reporting checklist for structural causes of AUB

Polyp (AUB-P)	Dimension Location Number Morphology
Adenomyosis (AUB-A)	MUSA features - Direct and indirect features Location (anterior/posterior/lateral wall/fundal) Differentiation - Focal/Diffuse/Mixed (> 25% myometrium/< 25%) Cystic/noncystic Uterine layer involvement (JZ/middle/outer myometrium) Disease extent (mild/moderate/severe) Measurement of lesion size - The Largest dimension of the largest lesion
Leiomyoma (AUB-L)	Classification Total uterine volume No of leiomyoma (1/2/3/4/> 4) Volume of up to 4 leiomyoma Location – Ant/post/lat/central, vertical plane – upper/lower half/both Endometrial contact
Endometrial malignancy/hyperplasia (AUB-M) - Based on International Endometrial Tumor Analysis (IETA)	Endometrium: Thickness Echogenicity/Uniformity Midline Outline Color score Vascular pattern EMJ Intracavitary fluid: Thickness and echogenicity Intracavitary lesion: Total endometrial thickness and three dimensions Extent Echogenicity Outline Color score Vascular pattern Bright edge Synechiae

Abbreviations: AUB, abnormal uterine bleeding; JZ, junctional zone; MUSA, Morphological Uterus Sonographic Assessment; EMJ, endo myometrial junction.

Coagulopathy (AUB-C)

The term “coagulopathy” denotes a systemic disorder that impairs hemostasis. It is estimated that approximately 13% of women who suffer from bleeding disorders exhibit menorrhagia, with von Willebrand disease identified as the most prevalent condition contributing to this phenomenon.[39] Furthermore, patients who are undergoing anticoagulant therapy often present with AUB, particularly in the form of heavy menstrual bleeding (HMB). The frequency with which these coagulopathies contribute to AUB in symptomatic women remains uncertain. Nevertheless, it is imperative to take these conditions into account when assessing patients with AUB, particularly in the absence of underlying pelvic pathologies.[3]

Ovulatory Disorders (AUB-O)

Ovulatory disorders represent a common etiology of AUB and arise from episodic or chronic dysfunction of the hypothalamic-pituitary-ovarian axis.[40] These disorders are characterized by unpredictable menstrual bleeding patterns and varying degrees of flow. The clinical manifestations can differ significantly, ranging from amenorrhea to infrequent or light bleeding, as well as episodes of unpredictable and excessively HMB that may necessitate medical intervention. In certain instances, AUB associated with ovulatory disorders is attributed to the absence of regular cyclic production of progesterone from the corpus luteum due to anovulation, or irregular ovulations resulting from luteal out-of-phase follicular events occurring in the later stages of reproductive years.[41]

Diagnosis of ovulatory disorders is often achievable through a comprehensive assessment of menstrual history and clinical presentation. Presenting symptoms may include delayed menarche, infrequent or irregular menstruation, primary or secondary infertility, and hirsutism. Additional diagnostic methods for ovulatory disorders include the measurement of basal body temperature, the use of ovulation predictor kits to assess urine luteinizing hormone levels, and the evaluation of progesterone levels.

Upon confirming the presence of an ovulatory disorder, the subsequent step involves categorizing the disorder into one of the four primary classifications as delineated by the FIGO classification system for ovulatory disorders. The secondary classification refines the identification of the specific type of abnormality within a designated anatomical category, while the tertiary classification elucidates the specific causative factors contributing to the ovulatory disorder.[6] [Table 6] shows the FIGO ovulatory disorders classification.

Table 6 FIGO ovulatory disorders classification system

Primary classification	Secondary classification
Type I: Hypothalamic	Genetic Autoimmune Iatrogenic Neoplasm   Functional Infectious/Inflammatory Trauma/Vascular   Physiological Idiopathic Endocrine
Type II: Pituitary
Type III: Ovarian
Type IV: PCOS	Diagnosed and classified as recommended by the sinternational PCOS network

Abbreviations: FIGO, International Federation of Gynecology and Obstetrics; PCOS, polycystic ovary syndrome.

Utilizing the modified Rotterdam criteria, the diagnosis of PCOS may be established if at least two of the following criteria are met: (1) evidence of clinical or biochemical hyperandrogenism, (2) indications of oligoanovulation, and (3) observation of polycystic ovarian morphology via US, after ruling out other relevant conditions. The US criteria for diagnosing polycystic ovarian morphology include the presence of a minimum of 20 follicles per ovary and an ovarian volume of at least 10 cm³. [Fig. 10] shows polycystic ovarian morphology in US. This diagnosis is typically made through transvaginal ultrasonography employing a transducer frequency of 8 MHz or greater.[40] Usage of simple, easily available, and cost-effective modality such as US in evaluation of ovulatory dysfunction helps in identifying the ovarian etiology and thereby improves the clinical acumen.

Fig. 10 Transvaginal ultrasound images of a patient with irregular cycles show enlarged right (A) and left (B) ovaries (marked by white stars in A and B, respectively) with volume > 10 mL, thickened stroma, and multiple small < 9 mm peripherally arranged follicles (abnormal uterine bleeding [AUB]-O, TYPE IV, polycystic ovary syndrome [PCOS]).

Endometrial (AUB-E)

In instances where identifiable causes for AUB are not apparent, local endometrial pathologies may be influencing endometrial hemostasis. The etiology typically involves hormonal imbalances within the uterus. A local deficiency of vasoconstrictors, such as endothelin-1 and prostaglandin F2α, may result in excessive bleeding by promoting the production of plasminogen activators, which facilitate the lysis of blood clots.[42] Concurrently, there tends to be an increased synthesis of prostaglandin E2 and prostacyclin (I2), both of which serve as potent vasodilators and possess antiplatelet aggregation properties.[43]

In addition to local hormonal disturbances, various conditions may contribute to AUB, presenting as IMB or prolonged menstrual bleeding. These conditions may include infections and inflammatory processes in the endometrium, such as chronic endometritis; however, the precise mechanisms underlying these conditions remain poorly understood.[44] For women with normal ovulatory function, the diagnosis of local endometrial pathology as a causative factor for AUB is generally established through a process of exclusion, occurring only when no structural causes have been identified.

Iatrogenic (AUB-I)

Iatrogenic factors contributing to AUB include intrauterine devices (IUDs) and various medications. Breakthrough bleeding (BTB) refers to unscheduled bleeding during treatment with gonadal steroids, such as estrogens and progestins, which are primarily used as contraceptives in oral, transdermal, vaginal, or injectable forms. BTB often occurs due to decreased levels of these steroids resulting from poor adherence to the medication regimen.

Additionally, certain medications, including tricyclic antidepressants and phenothiazines, can alter dopamine metabolism by decreasing serotonin uptake, leading to reduced inhibition of prolactin release. This may result in anovulation and irregular vaginal bleeding.[3]

Certain IUDs, particularly the levonorgestrel intrauterine system, may also induce unscheduled vaginal bleeding within the initial 3 to 6 months of use, potentially leading to premature removal of the device.[45]

Not Yet Classified (AUB-N)

The conditions categorized within this group include chronic endometritis, arteriovenous malformations, isthmocele ([Fig. 11]), and myometrial hypertrophy. The role of these conditions in AUB remains inadequately defined, necessitating their classification in this category. It is essential to gather further evidence in the future to appropriately assign these conditions to a more accurate classification.[3]

Fig. 11 (A) Transvaginal ultrasound image of the uterus shows a myometrial defect in the anterior wall of the lower uterine segment at the site of cesarean scar with clots within communicating with the endometrial cavity(black arrow)—consistent with isthmocele. T2 sagittal (B) and T1 fat-saturated sagittal (C) magnetic resonance (MR) images demonstrate the isthmocele with T1 and T2 hyperintense contents suggestive of clots within (black arrows in B and C) (abnormal uterine bleeding [AUB]-N).

[Fig. 12] summarizes the clinical and imaging approach to AUB.

Fig. 12 Clinical and imaging approach to abnormal uterine bleeding (AUB).

Conclusion

Standard terminologies, definitions, and structured imaging methodologies are essential for the accurate identification of the causes of AUB, facilitating effective management, enhancing patient outcomes, and supporting clinical research efforts. US represents the initial diagnostic modality of choice for patients presenting with AUB, owing to its widespread availability and capability to assess the endometrium, myometrium, and adnexal structures. Additionally, sonohysterosalpingography can provide further evaluation of the endometrial cavity and lining. MRI offers superior contrast for soft tissues, serving as a valuable tool for complex problem-solving.

The role of imaging evaluation is pivotal in differentiating between structural and nonstructural etiologies of AUB. Structured reporting using PALM-COEIN with imaging checklists ensures consistent communication with gynecologists and improves patient outcomes.

Conflict of Interest

None declared.

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Publication History

Article published online:
15 January 2026