Diagnostic Approach to Abnormal Uterine Bleeding - Endometrial Causes

Initial Evaluation and Diagnostic Algorithm

The American College of Radiology recommends transvaginal ultrasound as the first-line imaging study to identify structural endometrial causes, with a critical threshold for endometrial thickness of ≥5 mm in postmenopausal women, which requires endometrial tissue sampling, as thickness ≥4 mm has nearly 100% negative predictive value for cancer 1, 2
For patients with risk factors for endometrial cancer, including age >45 years, postmenopausal status, obesity, diabetes, hypertension, unopposed estrogen exposure, tamoxifen use, or Lynch syndrome, endometrial tissue sampling is mandatory 3
The initial evaluation should include testing β-hCG in all reproductive-age women before proceeding with further evaluation, and assessing hemodynamic stability, with urgent evaluation needed if bleeding saturates a large pad/tampon hourly for ≥4 hours 3

Saline Infusion Sonohysterography (SIS) is recommended when initial TVUS demonstrates a focal endometrial abnormality, with a sensitivity of 96-100% and accuracy of 97% in distinguishing leiomyomas from polyps 2, 4
MRI Pelvis with gadolinium-based IV contrast is considered when the uterus is incompletely visualized by ultrasound or findings are indeterminate, with a sensitivity and specificity of up to 79% and 89% in identifying endometrial cancer 1, 2, 5
Endometrial biopsy is mandatory in high-risk patients, including those with age >45 years, postmenopausal status, obesity, diabetes, hypertension, unopposed estrogen exposure, tamoxifen use, or Lynch syndrome 3

The American College of Radiology recommends medical therapy as first-line treatment after diagnosis, unless contraindicated or structural pathology requires surgery, with options including combined oral contraceptives, cyclic progestins, levonorgestrel-releasing intrauterine system, NSAIDs, and tranexamic acid 3
Referral to gynecology is indicated when endometrial sampling shows hyperplasia or malignancy, failed medical management, or postmenopausal bleeding with endometrial thickness ≥4 mm 3

The American Academy of Family Physicians recommends proceeding directly to endometrial tissue sampling via office endometrial biopsy when ultrasound and hormones are normal but abnormal uterine bleeding persists, and if this fails to yield a diagnosis or symptoms persist, advance to hysteroscopy with directed biopsy 6
Office endometrial biopsy has a 10% false-negative rate, so a negative result in a symptomatic patient must be followed by fractional dilation and curettage (D&C) under anesthesia, as per the National Comprehensive Cancer Network 7

Saline Infusion Sonohysterography (SIS) has 96-100% sensitivity and 94-100% negative predictive value for detecting focal endometrial pathology that standard ultrasound may miss, with 97% accuracy in distinguishing polyps from submucosal fibroids, according to the American Academy of Family Physicians 6

Hysteroscopy with directed biopsy is indicated when medical treatment fails or when endometrial sampling is non-diagnostic, as it allows direct visualization of the endometrial cavity and endocervix to diagnose focal lesions possibly missed by blind endometrial sampling, as recommended by the American Academy of Family Physicians and the National Comprehensive Cancer Network 6, 7
Endometrial biopsy may not be accurate for diagnosing malignancies of the uterine wall, such as mesenchymal tumors or endometrial stromal neoplasms, according to the National Comprehensive Cancer Network 7