47.2 Abnormal Uterine Bleeding & Acute Menstrual Disorders

Terminology & Normal Menstrual Parameters

Abnormal Uterine Bleeding (AUB) is defined as any departure from the normal menstrual parameters regarding frequency, regularity, duration, or volume of menstrual blood flow in non-pregnant individuals of reproductive age. In 2011 (and updated in 2018), the International Federation of Gynecology and Obstetrics (FIGO) formally retired ambiguous historical terms—including "dysfunctional uterine bleeding (DUB)," "menorrhagia," "metrorrhagia," and "oligomenorrhea"—replacing them with standardized descriptive clinical terminology categorized under the PALM-COEIN classification system.

                  NORMAL MENSTRUAL CYCLE PARAMETERS (FIGO STANDARDS)

   Clinical Parameter              Normal Physiological Range        Abnormal Bleeding Terminology
   ═══════════════════════════════════════════════════════════════════════════════════════════════════════
   Frequency                       24 to 38 days                     < 24 days: Frequent
                                                                     > 38 days: Infrequent
                                                                     Absent: Amenorrhea (>=90 days)
   
   Duration                        <= 8 days                         > 8 days: Prolonged menstrual bleeding
   
   Regularity                      Cycle variation <= 7 to 9 days    Irregular menstrual bleeding
   (Shortest to longest cycle)                                       (variation >= 8 to 10 days)
   
   Volume (Patient-Determined)     Subjective: does not interfere    Heavy Menstrual Bleeding (HMB)
                                   with physical/social life         (interferes with physical, social,
                                   (historically <=80 mL blood loss) emotional, or material quality of life)
   ═══════════════════════════════════════════════════════════════════════════════════════════════════════

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The FIGO PALM-COEIN Classification System

The PALM-COEIN framework separates AUB etiologies into structural components (measurable by imaging or histopathology: PALM) and non-structural components (systemic, endocrinologic, or functional: COEIN).

                    THE FIGO PALM-COEIN CLASSIFICATION FOR AUB

   Category         Classification Component          Key Pathophysiologic Features & Presentation
   ═══════════════════════════════════════════════════════════════════════════════════════════════════════
   STRUCTURAL       P - Polyp (AUB-P)                 Endometrial or endocervical glandular outgrowths;
   (PALM)                                             presents with intermenstrual or postcoital spotting.
   
                    A - Adenomyosis (AUB-A)           Ectopic endometrial glands/stroma within myometrium;
                                                      globoid, symmetrically enlarged, tender boggy uterus;
                                                      severe dysmenorrhea and heavy cyclic menses.
   
                    L - Leiomyoma (AUB-L)             Benign smooth muscle neoplasms (fibroids);
                                                      firm, irregularly enlarged, nodular uterus;
                                                      Submucosal (Type 0-2) cause heaviest bleeding.
   
                    M - Malignancy & Hyperplasia      Endometrial hyperplasia with/without atypia or
                        (AUB-M)                       endometrial adenocarcinoma; postmenopausal bleeding.
   ───────────────────────────────────────────────────────────────────────────────────────────────────────
   NON-STRUCTURAL   C - Coagulopathy (AUB-C)          Systemic hemostatic defects; von Willebrand disease
   (COEIN)                                            most common; heavy bleeding since menarche.
   
                    O - Ovulatory Dysfunction         Anovulatory cycles (PCOS, perimenopause, obesity);
                        (AUB-O)                       unopposed estrogen causing irregular, painless bleeding.
   
                    E - Endometrial Primary           Primary hemostatic defects within endometrium;
                        Dysfunction (AUB-E)           regular ovulatory cycles with heavy cyclic bleeding.
   
                    I - Iatrogenic (AUB-I)            Exogenous hormones, copper/levonorgestrel IUDs,
                                                      anticoagulants, psychotropics causing hyperprolactinemia.
   
                    N - Not Otherwise Classified      Arteriovenous malformations (AVMs), isthmocele
                        (AUB-N)                       (cesarean scar defect), chronic endometritis.
   ═══════════════════════════════════════════════════════════════════════════════════════════════════════

Detailed Analysis of Structural Etiologies (PALM)

1. Endometrial & Endocervical Polyps (AUB-P):
   • Localized hyperplastic outgrowths of endometrial glands and vascular stroma projecting into the uterine cavity.
   • Typically benign (<2% harbor malignancy in premenopausal women; increases to 5% to 6% in postmenopausal women).
   • Presentation: Intermenstrual bleeding (spotting between cycles), postcoital bleeding, or light unscheduled spotting. Best visualized using Saline Infusion Sonohysterography (SIS) or diagnostic hysteroscopy.
2. Adenomyosis (AUB-A):
   • Ectopic presence of endometrial basalis glands and stroma invaginating into the myometrium, accompanied by reactive hypertrophy and hyperplasia of surrounding myometrial smooth muscle.
   • Demographics: Multiparous women typically in their late 30s to 40s.
   • Presentation: Progressive secondary dysmenorrhea (pain worsening over years) and heavy menstrual bleeding.
   • Physical Examination: The uterus is palpated as symmetrically enlarged, globoid, soft, boggy, and globally tender to palpation, rarely exceeding 12 to 14 weeks gestational size.
   • Imaging: TVUS reveals myometrial asymmetry, subendometrial echogenic linear striations, and myometrial cysts. Pelvic MRI demonstrating a thickened junctional zone >12 mm confirms the diagnosis.
3. Leiomyomas / Uterine Fibroids (AUB-L):
   • Monoclonal benign smooth muscle tumors of the myometrium. Classified by FIGO anatomical depth:
     • Submucosal (FIGO 0, 1, 2): Lie directly beneath the endometrium and distort the uterine cavity. Even tiny submucosal fibroids (<1 to 2 cm) cause profound, life-threatening heavy menstrual bleeding and severe anemia due to focal endovascular ulceration, increased surface area, and impairment of myometrial contractility.
     • Intramural (FIGO 3, 4, 5): Confined to the thick myometrial wall. Cause heavy bleeding and pelvic pressure once large.
     • Subserosal (FIGO 6, 7): Project outward from the serosa. Cause bulk symptoms (urinary frequency, pelvic fullness, hydronephrosis, constipation) but rarely alter menstrual blood volume.
   • Physical Examination: Palpation reveals a firm, irregularly enlarged, asymmetric, nodular, and non-tender uterus ("knobby" contour).
4. Endometrial Malignancy & Hyperplasia (AUB-M):
   • Encompasses Endometrial Intraepithelial Neoplasia (EIN / atypical endometrial hyperplasia) and Endometrial Adenocarcinoma (predominantly endometrioid histology).
   • Cardinal red flag: Any postmenopausal vaginal bleeding or prolonged abnormal bleeding in women with chronic unopposed estrogen exposure.

Detailed Analysis of Non-Structural Etiologies (COEIN)

1. Coagulopathy (AUB-C):
   • Found in up to 20% of adolescents presenting with severe heavy menstrual bleeding at menarche requiring hospitalization.
   • von Willebrand Disease (vWD): The most common inherited bleeding disorder, transmitted primarily in an autosomal dominant pattern. Results from quantitative (Type 1, Type 3) or qualitative (Type 2) deficiency in von Willebrand factor, which mediates platelet adhesion to subendothelial collagen and stabilizes circulating Factor VIII.
   • Screening Questions: A structured clinical screening tool is positive if the patient has:
     1. Heavy menstrual bleeding since menarche;
     2. History of postpartum hemorrhage, surgery-related bleeding, or bleeding with dental work; OR
     3. Two or more of: bruising >=1-2 times/month, epistaxis >=1-2 times/month, frequent gum bleeding, or family history of bleeding symptoms.
   • Diagnostic Panel: CBC (platelet count typically normal), PT/INR (normal), PTT (normal or mildly prolonged), vWF antigen, vWF ristocetin cofactor activity, and Factor VIII coagulant activity.
2. Ovulatory Dysfunction (AUB-O):
   • Pathophysiologic Mechanism: In anovulatory cycles, no dominant follicle ovulates, and no corpus luteum forms. Consequently, progesterone is never produced. The endometrium is exposed to continuous, unopposed estrogen, stimulating unrelenting cellular proliferation without organized structural stroma.
   • Eventually, the hyperplastic endometrium outgrows its blood supply, leading to patchy, asynchronous tissue breakdown, fragile capillary rupture, and unpredictable, irregular, non-cyclic, and often prolonged, heavy bleeding.
   • Etiologies: Polycystic Ovary Syndrome (PCOS; triad of hyperandrogenism, ovulatory dysfunction, and polycystic morphology), perimenopausal transition (erratic follicular recruitment), adolescent post-menarche (immature hypothalamic-pituitary-ovarian axis), obesity (peripheral conversion of androstenedione to estrone by adipose aromatase), thyroid disease (hypothyroidism causing hyperprolactinemia), hyperprolactinemia, and hypothalamic amenorrhea (eating disorders, strenuous endurance exercise, psychological stress).
3. Endometrial Primary Dysfunction (AUB-E):
   • Occurs in individuals with regular, predictable, ovulatory 28-day cycles who nonetheless experience excessive heavy menstrual bleeding.
   • Driven by primary defects in local endometrial hemostasis: deficiency in local vasoconstrictors (endothelin-1, prostaglandin F2-alpha) or excessive local production of vasodilators (prostaglandin E2, prostacyclin) and tissue plasminogen activator (tPA).
4. Iatrogenic (AUB-I):
   • Breakthrough unscheduled bleeding induced by hormonal contraceptives (DMPA, progestin subdermal implants, levonorgestrel IUDs during the initial 3 to 6 months), copper IUDs (causes increased menorrhagia and dysmenorrhea), systemic anticoagulants (warfarin, DOACs), or psychotropic medications (antipsychotics that block dopamine receptors, inducing hyperprolactinemia and secondary anovulation).

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Diagnostic Evaluation & Endometrial Biopsy Thresholds

                  DIAGNOSTIC STEPWISE EVALUATION FOR AUB

   Step     Diagnostic Test                     Clinical Objective / High-Yield Pearl
   ═══════════════════════════════════════════════════════════════════════════════════════════════════════
   1.       Urine Pregnancy Test                MANDATORY FIRST STEP in ALL reproductive-age females.
                                                Excludes ectopic, miscarriage, or gestational trophoblastic.
   
   2.       Complete Blood Count (CBC)          Assesses severity of anemia; provides baseline platelets.
            Serum Ferritin                      Identifies iron deficiency BEFORE overt anemia develops.
   
   3.       Endocrine Panel:                    TSH rules out thyroid disease; Prolactin rules out
            TSH, Serum Prolactin                hyperprolactinemic anovulation.
   
   4.       Coagulation Panel (if indicated)    Ordered in adolescents with HMB or adults with positive
            vWF antigen, ristocetin, FVIII      bleeding screen; PT/PTT alone is INSUFFICIENT.
   
   5.       Transvaginal Ultrasound (TVUS)      Initial imaging modality of choice; assesses endometrial
                                                stripe thickness, polyps, adenomyosis, and fibroid mapping.
   
   6.       Endometrial Biopsy (EMB)            Tissue diagnosis to rule out endometrial carcinoma and
                                                atypical hyperplasia in stratified high-risk groups.
   ═══════════════════════════════════════════════════════════════════════════════════════════════════════

The Postmenopausal Bleeding Paradigm & TVUS Stripe Cutoff

[!WARNING] POSTMENOPAUSAL BLEEDING IS ENDOMETRIAL CANCER UNTIL PROVEN OTHERWISE Vaginal bleeding occurring >12 months after the cessation of menses in a postmenopausal woman requires aggressive, prompt diagnostic evaluation. Although benign atrophy accounts for 60% to 80% of cases, endometrial cancer is diagnosed in approximately 10% of postmenopausal bleeding presentations.

• TVUS Endometrial Stripe Measurement:
  • Stripe <= 4.0 mm: Carries a >99% Negative Predictive Value (NPV) for endometrial adenocarcinoma. If the ultrasound confirms a thin, smooth, homogeneous stripe <=4 mm and bleeding has completely stopped, invasive tissue biopsy can be safely deferred with close clinical observation.
  • Stripe > 4.0 mm (or heterogeneous, indistinct, irregular stripe, or persistent/recurrent bleeding): Mandates immediate Endometrial Biopsy (EMB) to obtain histologic tissue confirmation.

Formal Clinical Indications for Endometrial Biopsy (EMB)

According to ACOG and family medicine board guidelines, outpatient pipelle endometrial biopsy is strictly indicated in:

1. All postmenopausal women presenting with abnormal vaginal bleeding and an endometrial stripe > 4 mm (or unmeasurable/blind stripe on TVUS);
2. All women aged >= 45 years presenting with abnormal uterine bleeding (first-line diagnostic test before instituting long-term medical therapy);
3. Women aged < 45 years with abnormal uterine bleeding who possess risk factors for chronic unopposed estrogen exposure:
   • Chronic anovulation or Polycystic Ovary Syndrome (PCOS);
   • Severe obesity (BMI >= 30 kg/m²; marked peripheral aromatization of estrone);
   • Nulliparity or early menarche / late menopause;
   • Tamoxifen therapy (selective estrogen receptor modulator with antagonistic breast effects but agonistic endometrial pro-proliferative actions);
   • Lynch Syndrome (Hereditary Non-Polyposis Colorectal Cancer [HNPCC]; carries a 40% to 60% lifetime risk of endometrial carcinoma; annual endometrial screening begins at age 30 to 35);
   • Persistent abnormal uterine bleeding despite conservative medical therapy.

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Medical Management of Chronic Abnormal Uterine Bleeding

Once structural malignancy is excluded, medical therapy serves as the primary management strategy.

                  MEDICAL PHARMACOTHERAPY REGIMENS FOR CHRONIC AUB

   Therapeutic Agent           Dosage & Administration              Mechanism & Clinical Pearl
   ═══════════════════════════════════════════════════════════════════════════════════════════════════════
   Levonorgestrel IUD          52 mg device (Mirena / Liletta)      GOLD STANDARD for HMB;
   (LNG-IUD)                   Intrauterine placement; lasts 8 yrs  reduces blood loss by 70-90%;
                                                                    induces marked endometrial atrophy.
   
   Combined Oral               Monophasic COC (30-35 mcg EE)        Stabilizes endometrium via estrogen;
   Contraceptives (COCs)       Daily oral tablet                    progestin prevents hyperproliferation;
                               (cyclic or extended cycle)           regulates cycles and reduces loss by 50%.
   
   Oral Progestins:            10 to 20 mg PO daily continuously    Atrophies endometrium; ideal in PCOS
   Medroxyprogesterone (MPA)   OR 10 mg PO daily for 12-14 days/mo  or when estrogens are contraindicated
   Norethindrone acetate       5 to 15 mg PO daily continuously     (hypertension, thrombophilia, smoker >=35).
   
   Tranexamic Acid (TXA)       1,300 mg PO three times daily (TID)  Antifibrinolytic; reversible plasminogen
   (Non-Hormonal)              taken ONLY during heavy menses       inhibitor; reduces blood loss by 40-50%;
                               (maximum 5 consecutive days)         preferred for women seeking conception.
   
   NSAIDs:                     Naproxen 500 mg PO BID OR            Inhibits cyclooxygenase; shifts balance
   (Non-Hormonal)              Ibuprofen 600-800 mg PO TID          to vasoconstrictive PGF2-alpha;
                               taken with onset of menses           reduces blood loss by 25-30% + relieves pain.
   ═══════════════════════════════════════════════════════════════════════════════════════════════════════

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Acute Severe Abnormal Uterine Bleeding: Emergency Stabilization

Acute severe AUB is defined as an episode of substantial uterine hemorrhage requiring immediate medical or surgical intervention to prevent acute hemodynamic collapse, symptomatic severe anemia, or shock.

Acute Resuscitation Principles

1. Establish airway, breathing, circulation (ABCs);
2. Place two large-bore (14- to 16-gauge) peripheral IV lines;
3. Initiate rapid crystalloid infusion (Normal Saline or Lactated Ringer's);
4. Draw stat type and screen / crossmatch (prepare 2-4 units of packed red blood cells [PRBCs]), complete blood count, coagulation studies (PT/INR, PTT, fibrinogen), and a stat point-of-care pregnancy test;
5. Assess for signs of hypovolemic shock (hypotension, resting tachycardia >110 bpm, orthostatic dizziness, pale cool extremities, oliguria).

Pharmacologic Protocols for Acute Hemorrhage

               EMERGENCY MEDICAL PROTOCOLS FOR ACUTE SEVERE AUB

   Protocol Option             Dosage & Route                       Clinical Mechanism & Instructions
   ═══════════════════════════════════════════════════════════════════════════════════════════════════════
   Intravenous Conjugated      Premarin 25 mg IV every 4 to 6       RAPID VASOSPASM & RE-EPITHELIALIZATION;
   Equine Estrogens (CEE)      hours for up to 24 hours             promotes immediate clotting cascade and
                               (maximum 3 to 4 doses)               endometrial regrowth. Once bleeding
                                                                    stops, MUST transition to oral progestin!
   
   High-Dose Oral Combined     Monophasic 35 mcg EE COC:            TAPER SCHEDULE: Estrogen stabilizes the
   Contraceptive Taper         1 tab PO TID x 7 days                lining; progestin prevents further loss.
                               THEN 1 tab PO BID x 7 days           Provide scheduled antiemetic (ondansetron)
                               THEN 1 tab PO daily x 7-14 days      to combat high-dose estrogen nausea.
   
   High-Dose Oral Progestin    Medroxyprogesterone acetate (MPA)    PROGESTIN STABILIZATION; indicated when
   Monotherapy                 20 mg PO TID x 7 to 10 days          estrogens are strictly contraindicated
                               OR Norethindrone 5-10 mg PO TID      (active VTE, severe uncontrolled HTN).
   
   Tranexamic Acid (TXA)       10 mg/kg IV (max 1,000 mg) q8h       ANTIFIBRINOLYTIC STABILIZATION; highly
   Intravenous / Oral          OR 1,300 mg PO TID                   effective adjuvant; preserves fibrin clots.
   ═══════════════════════════════════════════════════════════════════════════════════════════════════════

Mechanical & Surgical Interventions for Refractory Bleeding

• Intrauterine Balloon Tamponade:
  • Rapid bedside mechanical compression of bleeding endomyometrial vascular channels.
  • Technique: Insert a sterile 26 to 30 French Foley catheter (or specialized Bakri postpartum balloon) through the dilated cervix into the endometrial cavity. Inflate the balloon with 30 to 50 mL of sterile saline until resistance is met. Apply gentle downward traction and tape the catheter to the patient's inner thigh. Maintain in place for 12 to 24 hours alongside prophylactic broad-spectrum antibiotics. Provides rapid tamponade when medical pharmacotherapy is taking effect or while preparing the operating room.
• Emergent Dilation and Curettage (D&C):
  • The definitive emergency surgical intervention for acute uterine hemorrhage in patients who are hemodynamically unstable, presenting in active shock, or refractory to initial medical therapy.
  • Mechanically debulks necrotic, hyperplastic tissue, allows endomyometrial vasospasm, and immediately obtains vital tissue for histopathologic exclusion of malignancy.
• Uterine Artery Embolization (UAE) or Emergent Hysterectomy:
  • Reserved for life-threatening, intractable hemorrhage refractory to D&C and intrauterine balloon tamponade.