What is on the differential diagnosis for Abnormal Uterine Bleeding?

Key differentials include Pregnancy-related bleeding (threatened/spontaneous abortion, ectopic, GTD), Cervical pathology (polyp, cervicitis, malignancy), Vaginal/vulvar source, Urinary or GI source, Endometrial hyperplasia or carcinoma, Coagulopathy (von Willebrand, platelet dysfunction), Thyroid dysfunction or hyperprolactinemia.

What are the high-yield PANCE pearls for Abnormal Uterine Bleeding?

Any postmenopausal bleeding requires evaluation for endometrial cancer (endometrial biopsy or TVUS — endometrial thickness >4 mm warrants biopsy). The levonorgestrel-releasing IUD reduces menstrual blood loss by ~80-90% and is the most effective medical therapy for AUB without structural pathology. Endometrial ablation does not provide contraception and is contraindicated in women desiring future fertility. Adolescents with heavy menses at menarche should be screened for von Willebrand disease. Tamoxifen causes endometrial proliferation, polyps, and increases endometrial cancer risk — any bleeding warrants biopsy.

Reproductive · PANCE / PANRE

Abnormal Uterine Bleeding

Written & clinically reviewed by Ryan Busch, PA-C · Updated August 2026 · Report an error

Bleeding outside normal volume, regularity, frequency, or duration — classified by PALM-COEIN.

Also known as: AUB, menorrhagia, metrorrhagia, menometrorrhagia, dysfunctional uterine bleeding, heavy menstrual bleeding

Overview

Bleeding from the uterine corpus that is abnormal in volume, regularity, frequency, or duration occurring in the absence of pregnancy. The PALM-COEIN classification (FIGO 2011) divides causes into structural (Polyp, Adenomyosis, Leiomyoma, Malignancy/hyperplasia) and nonstructural (Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic, Not otherwise classified).

Epidemiology

Affects 10-30% of reproductive-age women; common cause of outpatient gynecology visits and accounts for ~20% of hysterectomies.

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Question 1ReproductiveMedium

A 44-year-old woman has heavy irregular uterine bleeding for several months. Hemoglobin is 8.9 g/dL. Which of the following complications is most likely?

AAnemia of chronic inflammation
BIron deficiency anemia
CThalassemia trait microcytic anemia
DFolate deficiency megaloblastic anemia

Reveal answer & full explanation

Correct answer: B — Iron deficiency anemia

AAnemia of chronic inflammation
BIron deficiency anemia✓
CThalassemia trait microcytic anemia
DFolate deficiency megaloblastic anemia

Why Iron deficiency anemia is correct

Months of heavy menstrual blood loss depletes iron stores faster than they can be replaced, producing a microcytic anemia.
The hemoglobin of 8.9 g/dL after chronic bleeding fits a slow, ongoing loss rather than an acute event.
Confirming with ferritin and a CBC guides oral iron repletion and a bleeding workup.

Why the others are wrong

Anemia of chronic inflammation — Requires an underlying chronic infection, inflammatory, or malignant process this patient does not have, and ferritin runs normal or high rather than low (mimic trap).
Thalassemia trait microcytic anemia — Trait gives lifelong mild microcytosis with a near-normal hemoglobin and a disproportionately high red cell count, not a new fall to 8.9 g/dL during months of menorrhagia.
Folate deficiency megaloblastic anemia — Chronic bleeding causes IRON loss and a microcytic picture, whereas folate deficiency is macrocytic and nutritional (wrong-anemia-mechanism trap).

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Risk factors

Anovulation (extremes of reproductive age — adolescence, perimenopause; PCOS)
Obesity (peripheral conversion of androgens to estrogen)
Coagulation disorders (von Willebrand disease most common in adolescents with heavy menses)
Anticoagulant therapy
Endometrial hyperplasia/cancer risk: age >45, unopposed estrogen, tamoxifen, Lynch syndrome
IUDs and hormonal contraception (iatrogenic spotting)

Pathophysiology

Structural causes distort or replace endometrium (polyps, fibroids, malignancy). Anovulation removes the cyclic progesterone-driven decidualization that normally produces orderly shedding, leaving disorganized estrogen-stimulated endometrium prone to breakthrough bleeding. Coagulopathies impair primary hemostasis at the endometrial level.

Clinical presentation

Symptoms

Heavy menstrual bleeding (>80 mL/cycle, >7 days, or self-reported impact on QOL)
Intermenstrual bleeding (between predictable menses)
Postcoital bleeding (think cervical pathology)
Irregular cycles (<21 or >35 days, or variable >7-9 days cycle-to-cycle)
Postmenopausal bleeding — always abnormal until proven otherwise

Signs / physical exam

Pallor, tachycardia, orthostasis in acute heavy bleeding
Enlarged or irregular uterus (fibroids, adenomyosis)
Cervical lesion or polyp on speculum exam
Signs of androgen excess (PCOS), galactorrhea (prolactinoma), thyromegaly

Differential diagnosis

Pregnancy-related bleeding (threatened/spontaneous abortion, ectopic, GTD) — Always check hCG first
Cervical pathology (polyp, cervicitis, malignancy) — Speculum exam, Pap testing, cervical biopsy
Vaginal/vulvar source — Atrophy, trauma, foreign body, malignancy
Urinary or GI source — Hematuria, hematochezia masquerading as vaginal bleeding
Endometrial hyperplasia or carcinoma — Postmenopausal bleeding or any AUB with risk factors → endometrial biopsy
Coagulopathy (von Willebrand, platelet dysfunction) — Heavy menses since menarche, easy bruising, family history
Thyroid dysfunction or hyperprolactinemia — Menstrual irregularity; check TSH, prolactin

Diagnostic workup

Labs

Urine or serum hCG — first test in any reproductive-age woman
CBC, ferritin
TSH, prolactin
Coagulation studies (PT/PTT, vWF panel) if heavy bleeding since menarche or family history
GC/CT testing in at-risk patients

Imaging

Transvaginal ultrasound — first-line for structural assessment
Saline-infusion sonohysterography or hysteroscopy — for suspected intracavitary lesions
Endometrial biopsy indicated for: age ≥45 with AUB, age <45 with risk factors (obesity, chronic anovulation, tamoxifen, Lynch syndrome, unopposed estrogen), any postmenopausal bleeding, or persistent AUB despite medical therapy

Diagnostic algorithm

Category	Cause	Hallmark
P (structural)	Polyp	Intermenstrual bleeding; SIS/hysteroscopy
A (structural)	Adenomyosis	Heavy painful menses; boggy uterus; MRI
L (structural)	Leiomyoma	Heavy menses, bulk symptoms; TVUS
M (structural)	Malignancy / hyperplasia	Postmenopausal or risk-factor bleeding; biopsy
C (nonstructural)	Coagulopathy	Heavy menses since menarche; vWF panel
O (nonstructural)	Ovulatory dysfunction	Irregular cycles; PCOS, thyroid, prolactin
E (nonstructural)	Endometrial	Primary endometrial hemostasis disorder
I (nonstructural)	Iatrogenic	Hormones, anticoagulants, IUDs
N (nonstructural)	Not otherwise classified	AVMs, cesarean scar, other rare causes

FIGO PALM-COEIN classification of abnormal uterine bleeding.

Treatment

First-line

Address structural cause if identified (polypectomy, myomectomy, etc.)
Nonhormonal: NSAIDs (mefenamic acid, ibuprofen, naproxen) — reduce flow ~20-50%
Tranexamic acid 1.3 g TID × up to 5 days per cycle — reduces flow ~40-60%
Hormonal: combined OCP, progestin-only pills, levonorgestrel IUD (most effective medical option), depot medroxyprogesterone

Acute heavy bleeding (hemodynamically stable)

High-dose IV conjugated estrogen 25 mg q4-6h
Or high-dose oral COCP taper (e.g., one pill TID × 7 days then taper)
Or oral medroxyprogesterone 20 mg TID × 7 days then taper
Tranexamic acid as adjunct

Acute heavy bleeding (hemodynamically unstable)

ABCs, IV access, fluids, transfusion as needed
IV conjugated estrogen
Intrauterine tamponade with Foley balloon, D&C if medical therapy fails
Uterine artery embolization or hysterectomy as last resort

Surgical (refractory)

Endometrial ablation — appropriate only if childbearing complete; not for hyperplasia/cancer
Hysterectomy — definitive

Complications

Iron-deficiency anemia
Missed diagnosis of endometrial hyperplasia or cancer
Impaired quality of life, work absenteeism
Hemodynamic instability in acute hemorrhage

PANCE pearls

Any postmenopausal bleeding requires evaluation for endometrial cancer (endometrial biopsy or TVUS — endometrial thickness >4 mm warrants biopsy).
The levonorgestrel-releasing IUD reduces menstrual blood loss by ~80-90% and is the most effective medical therapy for AUB without structural pathology.
Endometrial ablation does not provide contraception and is contraindicated in women desiring future fertility.
Adolescents with heavy menses at menarche should be screened for von Willebrand disease.
Tamoxifen causes endometrial proliferation, polyps, and increases endometrial cancer risk — any bleeding warrants biopsy.

References

ACOG PB 128 — ACOG Practice Bulletin No. 128: Diagnosis of Abnormal Uterine Bleeding in Reproductive-Aged Women
ACOG PB 557 — ACOG Committee Opinion 557: Management of Acute Abnormal Uterine Bleeding in Nonpregnant Reproductive-Aged Women
FIGO PALM-COEIN — FIGO Classification System for Causes of Abnormal Uterine Bleeding (Munro et al., Int J Gynaecol Obstet 2011)

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