Abnormal uterine bleeding
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Abnormal Uterine Bleeding (AUB)
Definition and Normal Parameters
Abnormal uterine bleeding is bleeding that occurs in excess of or in addition to the normal menstrual cycle. Normal menses occurs every 24-38 days, lasts 4-8 days, and averages 35 mL blood loss. Bleeding lasting more than 7 days or exceeding 80 mL per cycle is considered abnormal.
AUB affects 10-30% of women of reproductive age and is a warning sign for endometrial cancer if it occurs in postmenopausal women. The older terms "menorrhagia," "metrorrhagia," "menometrorrhagia," and "dysfunctional uterine bleeding" have been replaced by the PALM-COEIN classification system (ACOG/FIGO, 2011).
PALM-COEIN Classification
The FIGO Working Group on Menstrual Disorders established this system to divide AUB causes into structural and non-structural categories.
PALM - Structural causes (diagnosed by imaging or histology)
| Entity | Key Features |
|---|---|
| P - Polyps (AUB-P) | Overgrowth of endometrial glands/stroma; sessile or pedunculated; inner "feeder vessel" on Doppler; up to 5% may undergo malignant transformation |
| A - Adenomyosis (AUB-A) | Endometrial glands within myometrium; associated with heavy, painful menses |
| L - Leiomyoma/Fibroids (AUB-L) | Most common benign gynecologic tumor; affects up to 70% of women by age 50; submucosal fibroids (types 0-2) most likely to cause AUB |
| M - Malignancy & Hyperplasia (AUB-M) | Endometrial carcinoma, sarcoma, hyperplasia; 90% of endometrial cancer patients present with bleeding |
COEIN - Non-structural causes
| Entity | Key Features |
|---|---|
| C - Coagulopathy (AUB-C) | Von Willebrand disease (most common), ITP, anticoagulant therapy; suspect if heavy bleeding since menarche or family history |
| O - Ovulatory dysfunction (AUB-O) | ~50% of AUB cases; anovulation leads to unopposed estrogen -> endometrial proliferation -> irregular shedding |
| E - Endometrial (AUB-E) | Primary endometrial disorders (chronic endometritis, abnormal local hemostasis); diagnosis of exclusion |
| I - Iatrogenic (AUB-I) | Hormonal contraceptives, IUCDs, anticoagulants, tamoxifen (induces uterine abnormalities in 10-40% of users) |
| N - Not otherwise classified | No identifiable cause |
Causes by Age Group
| Age Group | Common Causes |
|---|---|
| Prepuberty | Precocious puberty (hypothalamic, pituitary, or ovarian origin) |
| Adolescence | Anovulatory cycles (HPO axis immaturity), coagulation disorders |
| Reproductive age | Pregnancy complications, OCP side effects, coagulopathy, polyps, fibroids, tumors |
| Perimenopausal | ~50% of all AUB; incipient ovarian failure |
| Postmenopausal | Atrophy (most common), polyps, fibroids, endometrial hyperplasia/cancer |
About 20% of AUB is postmenarchal; 50% is perimenopausal; 75% of all cases have no demonstrable organic cause (anovulatory/dysfunctional bleeding).
Types of Bleeding Patterns
- Heavy menstrual bleeding (HMB / menorrhagia) - excessive flow at expected cycle time
- Intermenstrual bleeding (IMB) - between periods
- Postcoital bleeding (PCB) - after intercourse (raises concern for cervical pathology)
- Postmenopausal bleeding (PMB) - after 12 months without menses; always requires evaluation
Pathophysiology of Anovulatory Bleeding
Without ovulation, no corpus luteum forms and no progesterone is produced. Estrogen stimulates the endometrium unopposed, causing it to proliferate, become unstable, and shed irregularly. Common causes of anovulation include:
- HPO axis immaturity (menarche) or incipient failure (perimenopause)
- PCOS - most common cause in reproductive-age women
- Pituitary tumors secreting prolactin (disrupts GnRH -> reduces LH/FSH)
- Functioning ovarian tumors (granulosa cell tumors)
- Systemic disorders - obesity, malnutrition, hypothyroidism, hyperthyroidism, Cushing syndrome, Addison disease, diabetes, renal disease
- Luteal phase defect - insufficient progesterone from corpus luteum
Diagnosis
History
- Amount and duration of blood loss (prospective charting may be needed)
- Relation to cycle, coitus, or menopause
- Medications (hormones, anticoagulants, tamoxifen)
- Family history of bleeding disorders
- Symptoms of anemia
Physical Examination
- Pelvic exam: tenderness, mass, uterine enlargement
- Papanicolaou smear if due
- Signs of anemia in severe cases
Investigations
First line (all patients):
- Pregnancy test (always exclude first)
- CBC with platelets
- Pelvic ultrasound (2D/3D or saline sonohysterography)
- Cervical cancer screening (if not up to date)
- STI screening
Second line:
- Coagulation studies including von Willebrand screen - if bleeding since menarche, family history, or systemic bleeding symptoms
- Thyroid function tests
- Prolactin, fasting glucose
- Colonoscopy if colorectal pathology suspected
Endometrial Biopsy (Pipelle or hysteroscopic-guided)
Indicated in:
- All women ≥45 years with AUB
- Women <45 years with: obesity, PCOS, persistent or refractory AUB, unopposed estrogen exposure, family history of hereditary cancer syndromes
Postmenopausal bleeding: Pelvic ultrasound first; if endometrial thickness >4 mm, biopsy is indicated. (Note: the 4 mm cutoff may under-diagnose endometrial cancer in Black patients.)
Hysteroscopy combined with endometrial biopsy improves sensitivity and specificity over either alone.
Management
Medical (First Line)
Anovulatory / ovulatory bleeding:
- Combined OCP - one pill every 6 hours x 5-7 days for acute heavy bleeding; cyclically thereafter for prevention
- Progestins - medroxyprogesterone acetate 5-10 mg x 10 days; norethindrone 5 mg daily
- NSAIDs - for ovulatory HMB (reduces prostaglandin-mediated bleeding)
- Tranexamic acid - antifibrinolytic; effective for HMB
- Levonorgestrel-IUD (LNG-IUD / Mirena) - highly effective for both HMB and dysmenorrhea
- GnRH agonists / antagonists - for fibroid-related AUB: elagolix 300 mg twice daily or relugolix 40 mg daily
Acute profuse bleeding (hemodynamically stable):
- IV conjugated estrogens 25 mg every 4 hours (up to 3 doses) until bleeding ceases
- Start progestin simultaneously; expect withdrawal bleeding 2-4 days after stopping
Surgical
Endometrial sampling should always be performed before hysterectomy. D&C is not an effective long-term treatment and is not required before hysterectomy.
| Indication | Procedure |
|---|---|
| Refractory AUB, no desire for fertility | Endometrial ablation (29% ultimately require hysterectomy at 5 years) |
| Symptomatic fibroids | Myomectomy, uterine artery embolization (UAE), or hysterectomy |
| Endometrial/uterine polyps | Hysteroscopic polypectomy |
| Medical therapy failure, endometrial malignancy | Hysterectomy |
UAE vs Hysterectomy - A 2024 meta-analysis (Peng et al., Sci Rep 2024, PMID 39164326) confirms UAE is effective for fibroid-related AUB but ~31% of patients ultimately need hysterectomy.
Postmenopausal Bleeding - Special Considerations
Any bleeding in a postmenopausal woman is abnormal until proven otherwise:
- Most common cause: atrophic endometrium/vaginitis (estrogen deficiency)
- Most feared cause: endometrial carcinoma (90% of cases present with bleeding)
- Other causes: polyps, fibroids, adenomyosis, HRT, anticoagulants
Special Populations
Tamoxifen users - Induces uterine abnormalities in 10-40% of women: endometrial polyps, hyperplasia, cancer, and rarely uterine sarcomas. Requires enhanced surveillance.
Anticoagulated women - A 2026 meta-analysis (Taree et al., J Thromb Haemost 2026, PMID 41791665) specifically addresses the high rate of AUB in women on anticoagulation for VTE.
Black women and fibroids - Incidence 2-3x higher, earlier onset, larger/more numerous tumors, more severe symptoms. The 4 mm endometrial thickness cutoff for biopsy avoidance in postmenopausal bleeding may under-diagnose cancer in this group.
Prognosis
Most cases resolve with effective intervention. The prognosis depends on the underlying cause. Anovulatory bleeding in adolescents and perimenopausal women generally has a favorable outcome with medical treatment. When AUB signals malignancy, prognosis depends on stage at diagnosis.
Sources: Sabiston Textbook of Surgery, Goldman-Cecil Medicine, Robbins & Kumar Basic Pathology, Bailey & Love's Short Practice of Surgery, Berek & Novak's Gynecology, Rosen's Emergency Medicine, Tintinalli's Emergency Medicine.
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