ABNORMAL UTERINE BLEEDING (AUB) - Complete Notes

---

1. DEFINITION & TERMINOLOGY

• AUB = any bleeding from the uterus that differs from normal menstruation in regularity, frequency, duration, or volume in non-pregnant women.
• The old terms "menorrhagia," "metrorrhagia," "menometrorrhagia," and "dysfunctional uterine bleeding (DUB)" should be abandoned. DUB is no longer an accepted diagnosis.
• FIGO and ACOG recommend the PALM-COEIN acronym for standardized nomenclature.

Normal Menstrual Parameters (Table)

• Mean duration of menses: 4.7 days; 89% of cycles last ≤7 days.
• Blood constitutes ~50% of menstrual fluid on average.
• Pregnancy must always be excluded first in reproductive-age women presenting with AUB.

---

2. PALM-COEIN CLASSIFICATION (FIGO System)

• PALM = Structural causes
• COEIN = Non-structural causes

---

PALM - STRUCTURAL CAUSES

---

P - POLYPS (AUB-P)

• Endometrial polyps are focal overgrowths of endometrial glands and stroma projecting into the uterine cavity.
• Clinical features:
  • Intermenstrual bleeding (most characteristic)
  • Heavy menstrual bleeding (HMB)
  • Irregular bleeding
  • Postmenopausal bleeding
  • May cause dysmenorrhea
  • Associated with tamoxifen use
  • Associated with infertility
  • Most endometrial polyps are asymptomatic
• Epidemiology:
  • Incidence increases with age throughout reproductive years
  • Found in 5.8% of asymptomatic premenopausal women and 11.8% of asymptomatic postmenopausal women (Danish study)
  • 1-year spontaneous regression rate: ~27% (smaller polyps more likely to resolve)
• Diagnosis:
  • Suspected on TVS: endometrial thickening, vascular feeder vessels
  • Confirmed by: hysteroscopy, sonohysterography (SIS), or endometrial biopsy/D&C
  • Sonohysterography is especially helpful for intrauterine polyps
• Risk of malignancy:
  • Premenopausal: very low (0.2-24% premalignant; 0-13% malignant - range from various studies)
  • Postmenopausal with bleeding: higher risk
  • Tamoxifen-associated polyps have higher malignant potential
• Management:
  • Hysteroscopic polypectomy (treatment of choice)
  • Removal may improve fertility in infertile patients
  • Asymptomatic polyps: watchful waiting is acceptable (spontaneous regression possible)

---

A - ADENOMYOSIS (AUB-A)

• Presence of endometrial glands and stroma within the myometrium, at least 2.5 mm from the basal endometrium (histologic definition).
• Traditionally a histologic diagnosis (at hysterectomy) - this made prevalence data unreliable.
• Now included as a structural cause because it can be diagnosed pre-hysterectomy with improved imaging.
• Clinical features:
  • Heavy menstrual bleeding (HMB)
  • Dysmenorrhea (secondary, progressive)
  • Tender, boggy, symmetrically enlarged uterus ("globular uterus")
  • Symptoms worsen with increasing parity and age
• Diagnosis:
  • Ultrasound criteria: heterogeneous myometrium, myometrial cysts, asymmetric myometrial thickening, poor definition of the endometrial-myometrial junction (JZ)
  • MRI: junctional zone thickness >12 mm (gold standard imaging)
  • Definitive: histology on hysterectomy specimen
• Management:
  • Medical: LNG-IUS (Mirena - most effective), GnRH agonists, COCPs, progestins, NSAIDs
  • Surgical: Hysterectomy (definitive); adenomyomectomy (fertility-sparing, technically challenging)

---

L - LEIOMYOMA (AUB-L)

• Benign smooth muscle tumors of the uterus; also called fibroids/myomas.
• Epidemiology:
  • Occur in up to 50% of women >35 years - most common tumors of the female genital tract
  • Cumulative prevalence >80% in Black women and ~70% in White women (ultrasound-based)
  • Incidence varies 30-70% depending on diagnostic method used
• Classification by location (FIGO leiomyoma subclassification system):

• Key point: Submucosal myomas (Type 0, 1, 2) are most likely to cause AUB
• Number and size of leiomyomas do NOT reliably predict occurrence of bleeding
• Clinical features:
  • Most leiomyomas are asymptomatic
  • AUB (HMB) - most common symptom in symptomatic women
  • Pelvic pressure/bulk symptoms
  • Pelvic pain / dysmenorrhea
  • Urinary frequency (compression)
  • Infertility, recurrent miscarriage (especially submucosal)
• Mechanism of AUB in leiomyomas: not fully established; theories include:
  • Increased endometrial surface area
  • Vascular distortion/engorged subendometrial veins
  • Impaired uterine contractility
  • Local prostaglandin and fibrinolytic changes
• Diagnosis: TVS (first-line), SIS/sonohysterography (for submucosal), MRI (mapping multiple fibroids), hysteroscopy (Type 0/1/2)
• Management:
  • Medical: LNG-IUS, tranexamic acid, NSAIDs, COCPs, GnRH agonists (pre-operative uterine shrinkage)
  • Interventional: UAE (uterine artery embolization), MR-guided focused ultrasound (MRgFUS)
  • Surgical: Hysteroscopic myomectomy (submucosal), laparoscopic/open myomectomy, hysterectomy (definitive)
  • Hysterectomy reserved for symptomatic patients not desiring future fertility

---

M - MALIGNANCY AND HYPERPLASIA (AUB-M)

• Includes endometrial hyperplasia (with or without atypia) and endometrial/cervical/vaginal malignancy.
• Endometrial Hyperplasia:
  • Driven by unopposed estrogen stimulation
  • Spectrum: simple hyperplasia → complex hyperplasia → atypical hyperplasia → endometrial carcinoma
  • Atypical hyperplasia has the highest malignant potential (~30% progress to cancer if untreated)
  • Risk factors: obesity, PCOS, anovulation, exogenous estrogen, tamoxifen, nulliparity, late menopause
• Endometrial Cancer:
  • Most common gynecologic malignancy in developed countries
  • Postmenopausal bleeding = endometrial cancer until proven otherwise
  • Risk: endometrial thickness >4 mm on TVS in postmenopausal women warrants biopsy
• Cervical Cancer:
  • Abnormal uterine or vaginal bleeding is the most frequent symptom
  • Visible cervical lesion → biopsy directly (do NOT await cytology, which may be falsely negative due to tumor necrosis)
  • Also evaluate vaginal walls carefully when AUB is present
• Diagnosis: Endometrial biopsy (office), D&C, hysteroscopy with biopsy

---

COEIN - NON-STRUCTURAL CAUSES

---

C - COAGULOPATHY (AUB-C)

• Systemic disorders of hemostasis that impair clot formation.
• Prevalence: 5-20% of women with HMB have a previously undiagnosed bleeding disorder.
• Most common: Von Willebrand disease (VWD) - most common inherited bleeding disorder in women.
• Also: thrombocytopenia, platelet function disorders, factor deficiencies, liver disease (impaired clotting factor production).

• Heavy menstrual bleeding since menarche
• Family history of bleeding disorder
• Epistaxis in the last year
• Bruising without injury >2 cm diameter
• Minor wound bleeding
• Oral or GI bleeding without anatomic lesion
• Prolonged or heavy bleeding after dental extraction
• Unexpected postoperative bleeding
• Hemorrhage from ovarian cyst
• Hemorrhage requiring blood transfusion
• Postpartum hemorrhage, especially delayed >24h
• Failure to respond to conventional management of menorrhagia

• CBC + platelet count
• PT, activated PTT
• Von Willebrand factor (VWF) - ristocetin cofactor activity + antigen
• Factor VIII
• Fibrinogen
• Refer to hematologist

• Tranexamic acid (antifibrinolytic - first line for VWD-related HMB)
• DDAVP (desmopressin) for VWD Type 1
• VWF concentrates for VWD Type 2/3
• LNG-IUS
• COCPs
• Avoid NSAIDs

---

O - OVULATORY DYSFUNCTION (AUB-O)

• Most common cause of AUB in reproductive-age women
• Formerly called "dysfunctional uterine bleeding" (DUB) - this term is now abandoned

• Absence of ovulation → no progesterone production
• Unopposed estrogen → continuous endometrial proliferation
• Endometrium outgrows its blood supply → focal breakdown → irregular, dyssynchronous shedding
• Low estrogen: irregular, prolonged, light bleeding
• High sustained estrogen: episodes of amenorrhea → followed by sudden, acute, heavy bleeding

• PCOS is the most common single cause of anovulatory AUB - diagnosed in 5-8% of adult women; associated with obesity, insulin resistance, androgen excess, cardiovascular risk
• Thyroid disease must always be excluded (TSH screening)
• POI (Primary Ovarian Insufficiency): AUB can be the presenting symptom; diagnosis often delayed; occurs in ~1% of women by age 40

• Treat underlying cause
• Cyclical progestins (10-14 days per cycle)
• COCPs (regulate cycle, reduce blood loss)
• Metformin (for PCOS with insulin resistance)
• Ovulation induction if fertility desired
• LNG-IUS

---

E - ENDOMETRIAL (AUB-E)

• AUB in ovulatory women with no identifiable structural or systemic cause - attributed to primary endometrial disorder.

• Deficiency of vasoconstrictors:
  • Reduced endothelin-1
  • Reduced prostaglandin F2α (PGF2α)
• Excess of vasodilators:
  • Increased prostacyclin (PGI2)
  • Increased prostaglandin E2 (PGE2)
• Impaired fibrinolysis: increased plasminogen activator activity → excess clot dissolution → HMB
• Inflammation/Infection:
  • Chronic endometritis can cause HMB
  • Chlamydial cervicitis → intermenstrual bleeding, postcoital spotting
  • PID/salpingitis can manifest as HMB
  • Endometritis: HMB + increased pain in a woman with previous light flow

• Endometrial biopsy to exclude hyperplasia/malignancy
• Endometrial culture (if infection suspected)
• Hysteroscopy
• Diagnosis of exclusion after ruling out structural causes

• NSAIDs (reduce PGE2 and PGI2, shift prostaglandin balance toward vasoconstriction; reduce blood loss by 20-50%)
• Tranexamic acid (antifibrinolytic; reduces HMB by ~50%)
• LNG-IUS
• COCPs
• Antibiotics if endometritis/chlamydia confirmed
• Endometrial ablation (if no further fertility desired)

---

I - IATROGENIC (AUB-I)

• AUB caused by exogenous hormones or medical treatments.

• Combined oral contraceptives (COCPs):
  • Breakthrough bleeding in 30-40% during first 1-3 months - expectant management (almost always resolves)
  • Caused by: missed pills, inconsistent use, drug interactions, smoking, low-dose formulations
  • Usually managed by reassurance; changing formulation if persistent
• Progestin-only methods (DMPA, POP, implant, LNG-IUS):
  • High rates of initial irregular/unpredictable bleeding
  • Varying rates of amenorrhea over time
  • Counsel patients BEFORE prescribing - women unwilling to tolerate irregular bleeding may not be good candidates
  • Management: reassurance, short course of estrogen supplementation (for DMPA-related bleeding), NSAIDs
• Contraceptive patch and vaginal ring:
  • Also associated with breakthrough bleeding
  • Non-daily delivery may improve adherence despite irregular bleeding
• Irregular bleeding on hormonal contraception ≠ always hormonal cause:
  • Screen for Chlamydia - one study showed higher rate of C. trachomatis in women with irregular bleeding on OCP

• Anticoagulants (warfarin, heparin, DOACs) → HMB
• Antipsychotics/dopamine antagonists (risperidone, metoclopramide) → hyperprolactinemia → anovulation → AUB
• Tamoxifen → endometrial polyps, hyperplasia, carcinoma
• Intrauterine device (copper IUD) → HMB (mechanism: local prostaglandin release)

---

N - NOT YET CLASSIFIED (AUB-N)

• A category for:
  • Causes not yet fully discovered
  • Rare and less-understood entities

• Myometrial hypertrophy (diffuse or segmental - distinct from adenomyosis)
• Arteriovenous (AV) malformations of the uterus:
  • Rare, potentially life-threatening cause of sudden, profuse AUB
  • Usually acquired (post-procedure: D&C, myomectomy, CS scar) or congenital
  • Diagnosis: color Doppler TVS (turbulent arteriovenous flow), MRI/MRA, angiography
  • Management: UAE (treatment of choice), surgical ligation, hysterectomy
• Other rare causes pending further classification

---

3. DIAGNOSIS OF AUB - SYSTEMATIC APPROACH

History

• Menstrual pattern: onset, frequency, duration, volume, regularity, passage of clots
• Intermenstrual/postcoital bleeding
• Pregnancy history (exclude pregnancy)
• Contraceptive/medication use
• Bleeding history since menarche (suggests coagulopathy)
• Systemic symptoms: thyroid, weight changes, galactorrhea, hirsutism/acne (PCOS)
• Family history of bleeding disorders
• Sexual history / STI risk

Physical Examination

• BMI, signs of androgen excess, galactorrhea, thyroid
• Pelvic exam: uterine size/tenderness, cervical lesions, adnexal masses

Laboratory Studies (Novak's)

• Mandatory: β-hCG (exclude pregnancy), CBC (anemia, thrombocytopenia)
• Routinely consider: TSH, chlamydia testing
• If coagulopathy suspected: PT, aPTT, VWF antigen + ristocetin cofactor activity, Factor VIII, fibrinogen, platelet function (in collaboration with hematologist)
• Blood glucose / fasting insulin if PCOS suspected

Imaging

• TVS (transvaginal ultrasound): First-line imaging
  • Uterine size, fibroid mapping, endometrial thickness, ovarian morphology
  • Endometrial thickness in postmenopausal: >4 mm warrants biopsy
  • In premenopausal: ET measurements less reliable (varies with cycle)
• Sonohysterography (SIS): Best for intrauterine lesions (polyps, submucosal fibroids)
• MRI: Adenomyosis (JZ >12mm), complex fibroid mapping, pelvic masses
• CT scan: Not routinely useful for AUB evaluation

Endometrial Sampling - Indications

• Age >35 with AUB
• Any age with risk factors for endometrial hyperplasia/cancer (obesity, PCOS, anovulation, nulliparity, tamoxifen use)
• Failure to respond to medical therapy
• Postmenopausal bleeding
• Persistent intermenstrual bleeding

• Office endometrial biopsy (Pipelle - first line)
• D&C (limited therapeutic benefit; for 1st cycle only)
• Hysteroscopy with directed biopsy (gold standard for intrauterine pathology)

Hysteroscopy

• Gold standard for visualizing intrauterine pathology
• Diagnostic + therapeutic (polypectomy, myomectomy, endometrial ablation)
• Particularly useful for submucosal fibroids and polyps

---

4. MANAGEMENT OF AUB

Medical Management

Surgical Management

Note: D&C is NOT an effective long-term treatment for AUB - therapeutic benefit is limited to the first menstrual period only. Endometrial ablation or hysterectomy are preferred surgical options.

---

5. SPECIAL SITUATIONS IN AUB

AUB in Adolescents

• Most common cause: anovulation (normal in first 1-2 years post-menarche)
• Coagulopathy (especially VWD) must be screened for - higher prevalence in adolescents with HMB
• Structural causes (PALM) are much rarer than in older women
• Pregnancy must be excluded

AUB in Perimenopausal Women

• Cycles become increasingly irregular due to anovulation
• Common causes: anovulation, fibroids, polyps, thyroid disease
• Must exclude endometrial pathology

AUB in Postmenopausal Women

• Postmenopausal bleeding (PMB) = endometrial carcinoma until proven otherwise
• Most common cause: atrophy (75-80% of cases)
• TVS: ET >4 mm requires biopsy
• Other causes: polyps, hormonal therapy, cervical/vaginal pathology

AUB in Pregnancy

• Must always be excluded with β-hCG
• Causes: threatened/missed/incomplete abortion, ectopic pregnancy, gestational trophoblastic disease

---

6. QUICK SUMMARY TABLE - PALM-COEIN

---

Sources: Berek & Novak's Gynecology, 16th Ed. (Chapter 10 - Benign Gynecologic Conditions; Chapter 26 - Hysteroscopy); Williams Gynecology 4th Ed. (supplementary content on structural causes and surgical management). FIGO AUB Classification 2011 (Munro et al., Int J Gynaecol Obstet 2011;113:3-13).