What is the approach to assessing abnormal uterine bleeding, including definition, differential diagnosis, history, physical examination, investigations, empiric treatment, and indications for referral?

Approach to Assessing Abnormal Uterine Bleeding

Definition

Abnormal uterine bleeding (AUB) is bleeding from the uterine corpus that is abnormal in regularity, volume, frequency, or duration occurring in the absence of pregnancy. 1 This encompasses heavy menstrual bleeding, irregular menstrual bleeding, and intermenstrual bleeding. 2

Differential Diagnosis: PALM-COEIN Classification

The International Federation of Gynecology and Obstetrics developed the PALM-COEIN system to categorize causes into structural and non-structural etiologies. 1

Structural Causes (PALM) - Imaging-Detectable

• Polyp: Common in women over 40 years of age 3
• Adenomyosis: Frequent cause in premenopausal women, often coexists with fibroids, presents with heavy bleeding, dysmenorrhea, and dyspareunia 1
• Leiomyoma: Most common structural cause in women under 40 years with heavy menstrual bleeding 3
• Malignancy and hyperplasia: Most serious etiology, primary concern in postmenopausal women 4, 3

Non-Structural Causes (COEIN) - Not Imaging-Detectable

• Coagulopathy: Inherited bleeding disorders 1
• Ovulatory dysfunction: Common in perimenopausal women, includes polycystic ovary syndrome 1
• Endometrial: Primary endometrial disorders with molecular deficiencies in hemostasis regulation 3
• Iatrogenic: Exogenous hormones, intrauterine devices, anticoagulation therapy (approximately 70% of women on anticoagulation experience heavy bleeding) 3
• Not yet classified: Other causes not fitting above categories 1

History

Immediate Assessment

• Hemodynamic stability: Urgent evaluation required if bleeding saturates a large pad or tampon hourly for at least 4 hours 3
• Pregnancy status: All reproductive-age women must be tested for pregnancy (β-hCG) 3

Bleeding Pattern Characterization

• Regularity: Cyclical (predictable heavy menstrual bleeding) versus non-cyclical (irregular intermenstrual bleeding) 5
• Volume: Quantify pad/tampon usage per hour during heaviest flow 3
• Frequency: Cycle length and predictability 1
• Duration: Days of bleeding per episode 1

Risk Factors for Endometrial Cancer

• Age (particularly postmenopausal status) 4, 1
• Obesity, diabetes, hypertension 4
• Unopposed estrogen exposure 4
• Tamoxifen use 4
• Lynch syndrome or family history of endometrial cancer 4

Medication History

• Anticoagulation therapy (warfarin, direct oral anticoagulants) 3
• Antiplatelet agents (aspirin, clopidogrel) 3
• Hormonal contraceptives or hormone replacement therapy 3
• Intrauterine device presence 3

Associated Symptoms

• Dysmenorrhea and dyspareunia (suggests adenomyosis) 1
• Pelvic pressure or bulk symptoms (suggests leiomyomas) 1
• Signs of thyroid dysfunction or hyperprolactinemia 3

Physical Examination

• Vital signs: Assess for hemodynamic instability (tachycardia, hypotension) 3
• Abdominal examination: Palpate for enlarged uterus or masses 4
• Speculum examination: Visualize cervix and vagina to exclude cervical or vaginal sources of bleeding 4
• Bimanual examination: Assess uterine size, contour, mobility, and adnexal masses 4

Investigations

Laboratory Tests

• Pregnancy test (β-hCG): Mandatory in all reproductive-age women 3
• Thyroid-stimulating hormone (TSH): Screen for thyroid dysfunction 3
• Prolactin level: Evaluate for hyperprolactinemia 3
• Complete blood count: Assess for anemia from chronic blood loss 3
• Coagulation studies: If history suggests bleeding disorder 1

Imaging Studies

Combined transabdominal and transvaginal ultrasound with Doppler is the first-line and most appropriate initial imaging study for AUB. 3 This approach identifies structural causes including polyps, adenomyosis, leiomyomas, and endometrial hyperplasia/malignancy. 3

Transvaginal Ultrasound (TVUS)

• Primary imaging modality for evaluating endometrium and myometrium 4, 5
• Endometrial thickness <4 mm in postmenopausal women has nearly 100% negative predictive value for cancer 4
• Limitations include patient body habitus, uterine position, and presence of fibroids/adenomyosis obscuring visualization 4

Saline Infusion Sonohysterography

• Sensitivity of 96-100% and negative predictive value of 94-100% for uterine and endometrial pathology 4
• Distinguishes between leiomyomas and endometrial polyps with 97% accuracy 4
• Indicated when TVUS demonstrates focal endometrial abnormality 4
• More accurate than TVUS alone for detecting endometrial polyps and submucous leiomyomas 2

MRI Pelvis

• Consider when ultrasound incompletely visualizes the uterus or findings are indeterminate 4
• Multiplanar capability and excellent tissue contrast allow endometrial visualization even with fibroids/adenomyosis 4
• Sensitivity up to 79% and specificity up to 89% for endometrial cancer 4
• Sensitivity 78% and specificity 93% for adenomyosis 4
• Diffusion-weighted imaging sequences should be included to improve sensitivity and specificity for uterine pathology 4
• Gadolinium-based IV contrast is preferred 4

CT Pelvis

• No role in initial or follow-up imaging evaluation of AUB 4

Endometrial Sampling

• Indicated in patients with increased risk for endometrial cancer (age >45 years, obesity, diabetes, unopposed estrogen exposure, failed medical management) 4
• Preferred over dilation and curettage due to lower invasiveness, safety, and cost 4
• Sensitivity affected by lesion type (focal versus diffuse), size, and location 4
• Consider when endometrium cannot be completely evaluated by ultrasound 4

Hysteroscopy

• Reference method for definitive diagnosis with direct visualization and biopsy capability 2
• Indicated when medical treatment fails or imaging is inconclusive 4
• Diagnoses focal lesions potentially missed by endometrial sampling 4

Empiric Treatment

Acute Heavy Bleeding (Hemodynamically Stable)

• Parenteral estrogen: High-dose IV conjugated estrogen 6
• Multidose combined oral contraceptive regimen: Monophasic pills taken multiple times daily 6
• Multidose progestin-only regimen: Oral progestins at high doses 6
• Tranexamic acid: Non-hormonal antifibrinolytic agent 6

Caveat: Avoid NSAIDs and tranexamic acid in patients with cardiovascular disease due to association with MI and thrombosis. 3

Chronic Heavy Menstrual Bleeding (Normal Uterus)

First-line medical management should be attempted before invasive therapies. 1

• Levonorgestrel-releasing intrauterine system: Highest efficacy for heavy menstrual bleeding 6, 7
• Combined oral contraceptives: Effective for reducing bleeding symptoms 1, 6
• Continuous oral progestins: Progestin-only contraception 6
• Tranexamic acid: Non-hormonal option, particularly effective with fibroids 3, 6
• NSAIDs: May be combined with hormonal methods to decrease menstrual bleeding 6

Leiomyoma-Related Bleeding

• GnRH antagonists (elagolix, linzagolix, relugolix): Reduce bleeding symptoms and fibroid volume 1
• GnRH agonists: Reduce bleeding and fibroid volume, typically used preoperatively 1, 6
• Note: Medical menopause with GnRH agonists/antagonists is temporary; symptoms return after discontinuation 1

Special Populations

Patients on Anticoagulation

• Progestin-only methods preferred 6
• GnRH agonists can be used 6
• Reassess indication for ongoing antiplatelet therapy and consider discontinuation if appropriate 3

Inherited Bleeding Disorders

• All hormonal methods and tranexamic acid are effective 6

Indications for Referral

Urgent Referral

• Hemodynamic instability despite initial management 3
• Bleeding saturating large pad/tampon hourly for ≥4 hours 3

Gynecology Referral

• Failed medical management: Persistent symptoms after 3-6 months of appropriate medical therapy 4, 1
• Endometrial sampling showing hyperplasia or malignancy 4
• Postmenopausal bleeding with endometrial thickness ≥4 mm 4
• Structural abnormalities requiring surgical intervention: Large or symptomatic fibroids, submucous fibroids, adenomyosis refractory to medical management 1
• Suspected endometrial cancer: Postmenopausal bleeding, risk factors present, abnormal imaging 4, 1
• Incomplete ultrasound evaluation requiring hysteroscopy or advanced imaging 4

Surgical Options After Failed Medical Management

• Endometrial ablation: Not first-line; requires informed consent regarding long-term complications (Asherman syndrome, cervical stenosis, delayed cancer diagnosis) 4
• Hysterectomy: Definitive treatment providing complete resolution of symptoms when medical management fails or is contraindicated 1; most common treatment for fibroids in the United States 1; provides significantly better health-related quality of life compared to other therapies 1