Female Reproductive & Breast

Abnormal uterine bleeding: PALM-COEIN workup

Clinical Overview and When to Suspect Abnormal Uterine Bleeding

— Normal cycle: frequency 24–38 days, regularity variation ≤7–9 days, duration ≤8 days, volume that does not interfere with quality of life

— Heavy menstrual bleeding (HMB): >80 mL/cycle or patient-reported impact (soaking pad/tampon hourly, passing clots >1 inch, anemia)

— Intermenstrual bleeding (IMB), postcoital bleeding, and amenorrhea also fall under AUB umbrella

— PALM (structural, imaging/histology-defined): Polyp, Adenomyosis, Leiomyoma, Malignancy/hyperplasia

— COEIN (nonstructural): Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic, Not otherwise classified

— Any postmenopausal bleeding (PMB) → endometrial cancer until proven otherwise

— AUB in a woman ≥45, or <45 with unopposed estrogen risk (obesity, PCOS, tamoxifen, anovulation, Lynch syndrome, nulliparity, diabetes) → must sample endometrium

— Adolescent with HMB since menarche → screen for inherited bleeding disorder (von Willebrand in ~13%)

— Reproductive-age with irregular cycles → think anovulation (AUB-O), pregnancy, thyroid, hyperprolactinemia

Abnormal uterine bleeding (AUB) = bleeding from the uterine corpus that is abnormal in frequency, regularity, duration, or volume in a non-pregnant reproductive-age woman

Terminology shift: FIGO replaced "menorrhagia," "metrorrhagia," "DUB" with descriptive terms and the PALM-COEIN classification

When to suspect/escalate workup:

Step 3 management: First step in any reproductive-age woman with AUB is a urine or serum β-hCG, then CBC; pregnancy reclassifies the entire differential and the bleeding is not labeled AUB by FIGO definition.

Board pearl: PALM-COEIN is not a severity score — it is a structured etiology checklist so you don't anchor on fibroids and miss an endometrial cancer or a clotting disorder. Document the dominant cause and any coexisting contributors (e.g., AUB-L,O).

Presentation Patterns and Key History

— Heavy (HMB): soaking through pad/tampon every 1–2 h, double protection, nocturnal changes, clots, iron-deficiency symptoms (fatigue, pica, restless legs)

— Irregular/AUB-O: unpredictable intervals, often light then prolonged, classic for anovulation at extremes of reproductive life (perimenarchal, perimenopausal), PCOS, hypothyroidism, hyperprolactinemia

— Intermenstrual/postcoital: think cervical/endometrial pathology — polyp, cervicitis, ectropion, cervical cancer

— Postmenopausal bleeding: any bleeding ≥12 months after last menses

— Onset since menarche, family history of bleeding, easy bruising, epistaxis, postpartum hemorrhage, dental bleeding → AUB-C (coagulopathy), especially vWD

— Galactorrhea, headaches, visual changes → prolactinoma

— Cold intolerance, weight gain, constipation → hypothyroid AUB-O

— Hirsutism, acne, obesity, infertility → PCOS

— Dysmenorrhea + dyspareunia + bulky tender uterus → adenomyosis

— Bulk symptoms (urinary frequency, constipation) → leiomyoma

— Anticoagulants, copper IUD, levonorgestrel implant, tamoxifen, antipsychotics, SSRIs → AUB-I (iatrogenic)

Quantify the bleeding pattern using FIGO descriptors, not legacy jargon:

Targeted history pearls:

Pregnancy and STI risk assessment is mandatory: sexual activity, contraception, last menstrual period, prior STIs, partners

Cancer risk modifiers to capture: age ≥45, BMI ≥30, diabetes, Lynch/HNPCC family history, prolonged unopposed estrogen, tamoxifen, chronic anovulation, nulliparity

Board pearl: A teenager with HMB since menarche requiring transfusion has roughly a 1 in 4 chance of an underlying coagulopathy — order vWF antigen, vWF activity (ristocetin cofactor), factor VIII, PT/PTT, platelets before starting hormonal therapy if feasible, because OCPs raise vWF and obscure the diagnosis.

Key distinction: Regular heavy cycles = think structural (PALM) or coagulopathy; irregular cycles = think ovulatory dysfunction (AUB-O). This single branchpoint guides the next test.

Physical Exam Findings and Hemodynamic Assessment

— Tachycardia, orthostatic drop (>20 mmHg SBP or >10 mmHg DBP, HR rise >30), pallor, delayed capillary refill → active significant blood loss

— Hgb <7 g/dL or hemodynamic instability → ED triage, type & screen, IV access, fluids, transfuse

— BMI, acanthosis nigricans, hirsutism, acne → PCOS phenotype

— Thyromegaly, bradycardia, dry skin → hypothyroidism

— Bitemporal hemianopsia, galactorrhea → pituitary

— Petechiae, mucosal bleeding, ecchymoses → coagulopathy or thrombocytopenia

— Conjunctival pallor, koilonychia, glossitis → chronic iron deficiency

— Suprapubic mass extending above pubic symphysis suggests an enlarged fibroid uterus; size often described in "weeks-size"

— Tenderness raises concern for PID, adenomyosis, degenerating fibroid

— Speculum: identify source (vaginal vs cervical vs uterine), look for cervical polyps, friable ectropion, visible mass, lacerations, retained foreign body, IUD strings

— Bimanual: uterine size, contour (irregular/bulky → fibroid; globular tender → adenomyosis), adnexal masses, cervical motion tenderness

— Rectovaginal: posterior cul-de-sac nodularity (endometriosis), rectal mass

Vitals first — AUB can be a hemorrhagic emergency:

General/systemic:

Abdominal exam:

Pelvic exam is mandatory in all AUB:

Do not skip the pelvic in PMB or postcoital bleeding — a friable cervical lesion is cervical cancer until biopsied, not a Pap target.

CCS pearl: In an unstable AUB patient, sequence on the CCS as: two large-bore IVs → CBC, type & cross, coagulation panel, β-hCG → IV crystalloid → transfuse PRBCs if Hgb <7 or symptomatic → IV conjugated estrogen 25 mg q4–6h or high-dose oral progestin → GYN consult. Do not order outpatient ultrasound first.

Board pearl: A "10-week-size" irregular uterus on bimanual in a 42-year-old with HMB is AUB-L (leiomyoma) until imaging proves otherwise, but you must still rule out coexisting hyperplasia with sampling if she has risk factors.

Diagnostic Workup — Initial Labs and Imaging

— Urine/serum β-hCG (rule out pregnancy and complications: ectopic, miscarriage, GTD)

— CBC for anemia and thrombocytopenia

— Ferritin if HMB — iron deficiency precedes overt anemia

— TSH for AUB-O

— Prolactin if amenorrhea/oligomenorrhea or galactorrhea

— Cervical cancer screening (Pap ± HPV) per USPSTF if due

— STI testing (gonorrhea/chlamydia NAAT) in sexually active <25 or with risk factors, or any cervicitis

— PT, aPTT, fibrinogen, vWF antigen, vWF ristocetin cofactor activity, factor VIII, platelet count

— Consider platelet function testing if initial labs negative but suspicion high

— Avoid drawing during active estrogen therapy (falsely normalizes vWF)

— Assess endometrial thickness, fibroids (number, location by FIGO 0–8 classification), adenomyosis features (heterogeneous myometrium, asymmetric walls, subendometrial cysts), adnexal pathology

— Postmenopausal endometrial thickness ≤4 mm has a very high negative predictive value for endometrial cancer; >4 mm in PMB → tissue sampling

— Premenopausal cutoffs are not validated; thickness alone does not exclude pathology

Universal first-tier tests in any non-pregnant AUB:

Coagulation screen when history suggests AUB-C (HMB since menarche, family history, postpartum hemorrhage, dental/surgical bleeding):

Imaging — transvaginal ultrasound (TVUS) is the first-line imaging modality:

Saline-infusion sonohysterography (SIS) if TVUS is nondiagnostic or focal lesion suspected — best for polyps and submucosal fibroids (FIGO type 0/1/2).

Step 3 management: In a 52-year-old with one episode of PMB, the correct next step is TVUS or endometrial biopsy — both are acceptable first lines per ACOG; biopsy is preferred if risk factors are high or imaging access is delayed.

Board pearl: A normal TVUS does not exclude endometrial pathology in a premenopausal woman; if AUB persists, proceed to biopsy regardless of stripe thickness.

Diagnostic Workup — Advanced and Confirmatory Studies

— Any postmenopausal bleeding

— Age ≥45 with AUB

— Age <45 with persistent AUB and risk factors: obesity, chronic anovulation/PCOS, tamoxifen, unopposed estrogen, Lynch syndrome, failed medical therapy

— Atypical glandular cells on Pap

— Office Pipelle is first line; sensitivity ~90% for endometrial cancer when adequate sample obtained

— EMB nondiagnostic, insufficient, or benign but bleeding persists

— Focal lesion on SIS/TVUS (polyp, submucosal fibroid)

— Persistent PMB despite negative blind sampling — focal lesions are missed by Pipelle in up to 10%

— Diagnostic gold standard for intracavitary pathology and allows simultaneous resection (see-and-treat)

— Map fibroids before myomectomy or uterine artery embolization

— Distinguish adenomyosis from fibroid when management differs

— Suspected malignancy staging

— Androgens (total testosterone, DHEAS, 17-OHP) if virilization

— FSH/LH/estradiol if suspected primary ovarian insufficiency (<40 y/o with amenorrhea)

— Liver/renal panel if chronic disease suspected (impair clearance of estrogens, cause coagulopathy)

— Endometrial hyperplasia without atypia → progestin therapy, repeat sampling

— Endometrial intraepithelial neoplasia (EIN)/atypical hyperplasia → hysterectomy preferred (concurrent carcinoma in ~40%); fertility-sparing high-dose progestin only in selected cases

— Endometrial carcinoma → gyn-onc referral, staging

Endometrial biopsy (EMB) indications — sample the endometrium when cancer/hyperplasia risk is meaningful:

Hysteroscopy with directed biopsy/D&C when:

MRI pelvis:

Additional targeted testing:

Histology categories that change management:

Board pearl: Pipelle has a false-negative rate for focal lesions — if bleeding persists after a "benign" biopsy, the next step is hysteroscopy, not reassurance.

Key distinction: SIS evaluates cavity contour (best for polyps/submucosal fibroids); MRI evaluates myometrium (best for adenomyosis and fibroid mapping).

Risk Stratification and First-Line Management Logic

— Is she hemodynamically stable?

— Is she pregnant?

— What is the most likely PALM-COEIN category?

— IV conjugated equine estrogen 25 mg q4–6h up to 24 h (most rapid) — contraindicated in VTE history, active breast cancer, smoker >35

— High-dose oral progestin: medroxyprogesterone 20 mg TID × 7 days, or norethindrone acetate 5–10 mg q4h tapered

— Combined OCP taper: monophasic 35-µg ethinyl estradiol pill TID × 7 days then daily

— Tranexamic acid 1.3 g PO TID × up to 5 days — useful adjunct, especially if hormones contraindicated

— Intrauterine Foley balloon tamponade for refractory bleeding while arranging definitive care

— AUB-O (anovulatory): cyclic or continuous progestin, COCs, or levonorgestrel IUD (LNG-IUD); treat underlying thyroid, prolactin, PCOS

— AUB-L (leiomyoma) submucosal: hysteroscopic myomectomy; intramural with HMB: LNG-IUD, GnRH antagonists, UAE, myomectomy

— AUB-A (adenomyosis): LNG-IUD first line; definitive = hysterectomy

— AUB-P (polyp): hysteroscopic polypectomy

— AUB-M (malignancy/hyperplasia): progestin vs hysterectomy by histology and fertility goals

— AUB-C: desmopressin (vWD type 1), tranexamic acid, LNG-IUD, hematology co-management

— AUB-E (endometrial): tranexamic acid, NSAIDs, LNG-IUD

— AUB-I: modify offending drug/device

Triage AUB by three parallel questions:

Acute heavy bleeding pathway (stable, non-pregnant):

Chronic AUB pathway — match therapy to PALM-COEIN bucket:

Step 3 management: The LNG-IUD (52 mg) is first-line non-surgical therapy for HMB across most PALM-COEIN categories — reduces bleeding 70–95% and treats simple hyperplasia without atypia.

Board pearl: Always treat iron deficiency in parallel with the bleeding cause — oral iron 65 mg elemental every other day improves absorption and tolerance.

Pharmacotherapy — First-Line Drug Regimens

— First-line for HMB; reduces blood loss ~90% at 6–12 months

— Approved for endometrial protection on estrogen therapy; treats hyperplasia without atypia

— Contraindications: pregnancy, active pelvic infection, distorted cavity (large submucosal fibroid), known/suspected malignancy of cervix or endometrium, unexplained AUB before workup completed

— Counsel on irregular bleeding/spotting for first 3–6 months

— Reduce bleeding ~40–50%, regulate cycles, treat AUB-O

— Avoid in: migraine with aura, smoker ≥35, hypertension uncontrolled, VTE history, breast cancer, <21 days postpartum, active liver disease

— Cyclic medroxyprogesterone 10 mg × 10–14 days/month for AUB-O

— Continuous norethindrone, DMPA injection, etonogestrel implant

— High-dose oral progestin (megestrol, MPA) for hyperplasia without atypia

— 1.3 g PO TID during menses (max 5 days)

— Reduces bleeding ~40%; non-hormonal — ideal for women avoiding hormones or with contraindications

— Avoid with combined hormonal contraceptives (theoretical thrombosis risk) and in active thromboembolism

— Reduce bleeding 20–40% and treat dysmenorrhea; start at onset of menses

— Short-term for fibroids preoperatively or to bridge to menopause

— Add-back estrogen/progestin to prevent bone loss if >6 months

Levonorgestrel IUD 52 mg (Mirena/Liletta):

Combined hormonal contraceptives (COCs, patch, ring):

Progestin-only options:

Tranexamic acid (antifibrinolytic):

NSAIDs (mefenamic acid 500 mg TID, naproxen):

GnRH agonists/antagonists (leuprolide; elagolix, relugolix combo):

Desmopressin (DDAVP) 0.3 µg/kg IV/SC or intranasal for vWD type 1 acute bleeding; not effective for type 2B or 3.

Step 3 management: A 28-year-old with HMB, BMI 22, no comorbidities, desires contraception → LNG-IUD. Same patient desires pregnancy soon → tranexamic acid ± NSAIDs during menses.

Board pearl: Never give unopposed estrogen to a woman with an intact uterus chronically — it drives hyperplasia and cancer.

Procedures and Surgical Management

— Polypectomy for AUB-P

— Myomectomy for FIGO type 0/1 submucosal fibroids (type 2 if <50% intramural component, experienced surgeon)

— Diagnostic hysteroscopy + directed biopsy when blind EMB inadequate

— Risks: uterine perforation, fluid overload (hyponatremia with hypotonic media), infection, Asherman syndrome

— For HMB in women who have completed childbearing, normal cavity, benign histology

— ~80% reduction in bleeding, ~40% amenorrhea

— Contraindications: desire for fertility, postmenopause, endometrial hyperplasia/cancer, prior classical C-section, IUD in place

— Must rule out hyperplasia/cancer first; pregnancy after ablation is high-risk (PAS, IUFD) — concurrent contraception or sterilization

— Interventional radiology; for symptomatic fibroids when uterine preservation desired but fertility not actively pursued (fertility outcomes mixed)

— Contraindicated in pregnancy, active infection, suspected malignancy

— Fertility-preserving definitive option for fibroids

— Risks: bleeding, adhesions, recurrence ~25%, possible cesarean delivery in future pregnancies

— Definitive cure for AUB; indicated for failed medical therapy, atypical hyperplasia, malignancy, large symptomatic fibroids, refractory adenomyosis

— Route: vaginal > laparoscopic > abdominal when feasible (ACOG preference)

— Decision must include ovarian conservation discussion (premenopausal women: conserve ovaries unless BRCA/Lynch)

Hysteroscopic procedures (cavity-preserving, fertility-sparing):

Endometrial ablation (radiofrequency, thermal balloon, cryo):

Uterine artery embolization (UAE):

Myomectomy (abdominal, laparoscopic, robotic):

Hysterectomy:

CCS pearl: For acute life-threatening AUB unresponsive to IV estrogen/progestin and tranexamic acid, escalate to intrauterine balloon tamponade → uterine artery embolization → emergent hysterectomy; do not delay surgical consult while titrating medications.

Board pearl: Endometrial ablation before ruling out hyperplasia/cancer is a board trap — always biopsy first in any AUB candidate ≥45 or with risk factors.

Special Populations — Elderly, Renal, and Hepatic Impairment

— Any PMB requires evaluation — endometrial cancer prevalence ~10% in PMB

— First-line: TVUS (≤4 mm endometrial stripe reassuring) or endometrial biopsy

— Persistent or recurrent PMB despite thin stripe → hysteroscopy with directed biopsy

— Sources beyond endometrium: atrophic vaginitis (most common cause), cervical/vulvar lesions, urethral caruncle, anticoagulation, hormone therapy

— Treat atrophic vaginitis with vaginal estrogen after malignancy excluded

— Unscheduled bleeding in first 6 months of continuous combined HRT is common; persistent beyond 6 months → workup

— Tamoxifen users: endometrial polyps, hyperplasia, sarcoma risk — TVUS stripe cutoffs unreliable; biopsy any bleeding

— Tranexamic acid requires dose reduction in renal dysfunction (CrCl <50 → reduce; CrCl <10 → avoid or markedly reduce)

— NSAIDs avoided in CKD stage ≥3 (worsen GFR, hyperkalemia, hypertension)

— LMWH/anticoagulant-related AUB: assess renal clearance, consider dose adjustment or agent switch (apixaban preferred in CKD)

— Uremic platelet dysfunction can contribute → DDAVP, dialysis optimization

— Impaired estrogen metabolism → relative hyperestrogenism, endometrial hyperplasia risk

— Coagulopathy from synthetic dysfunction → check INR, fibrinogen, platelets

— Avoid estrogen-containing regimens in active hepatic disease; favor LNG-IUD or tranexamic acid (caution with renal coexcretion)

— Confirm appropriate INR/drug levels; AUB does not automatically mean overdose

— Switch warfarin → DOAC if persistent HMB (apixaban lower HMB than rivaroxaban)

— LNG-IUD safe and effective; combined estrogen contraindicated

Postmenopausal women (the highest-stakes group):

Hormone therapy users:

Renal impairment:

Hepatic impairment:

Anticoagulated patients (very common Step 3 stem):

Step 3 management: A 68-year-old on apixaban with one episode of vaginal spotting still gets a full PMB workup — anticoagulation does not explain away endometrial cancer.

Special Populations — Adolescents and Reproductive-Age Subgroups

— Anovulatory cycles from immature HPO axis are common but not a default diagnosis when bleeding is heavy

— HMB requiring transfusion or hospitalization → screen for bleeding disorder before starting hormones: CBC, PT/aPTT, vWF panel, factor VIII, platelet function

— First-line management: COCs (taper for acute bleeding), progestin-only if estrogen contraindicated, tranexamic acid, iron repletion

— Avoid endometrial biopsy in adolescents unless persistent unexplained bleeding with risk factors; cancer is rare

— Address contraception, STI screening, confidentiality (state-specific minor consent laws)

— Chronic anovulation → unopposed estrogen → hyperplasia/cancer risk elevated

— Ensure withdrawal bleed every 1–3 months with cyclic progestin, COCs, or LNG-IUD

— Address metabolic comorbidities (insulin resistance, OSA, dyslipidemia)

— EMB if AUB persists despite therapy or if ≥45, BMI ≥30 with prolonged amenorrhea

— Cycles become irregular as ovarian reserve declines; ovulatory dysfunction is common but cancer prevalence rises sharply

— Age ≥45 with AUB → endometrial sampling regardless of pattern

— LNG-IUD bridges to menopause; provides contraception and endometrial protection

— First trimester: ectopic, miscarriage, GTD, subchorionic hematoma

— Second/third trimester: placenta previa, abruption, vasa previa, preterm labor

— β-hCG first in any reproductive-age woman with bleeding — boards repeat this relentlessly

— Lochia normal up to 6–8 weeks; heavy or recurrent bleeding → retained products, endometritis, subinvolution, choriocarcinoma

— Progestin-only methods preferred for contraception during lactation

Adolescents (perimenarchal, first 2–3 years):

PCOS:

Perimenopause (40s–early 50s):

Pregnancy-related bleeding (not classified as AUB but on the differential):

Postpartum and breastfeeding:

Board pearl: In an adolescent with HMB, do not dismiss as "anovulation" without considering von Willebrand disease — it is the most common inherited bleeding disorder and is overrepresented in this group.

Complications and Adverse Outcomes

— Fatigue, exercise intolerance, restless legs, pica, hair loss, cognitive impact, impaired work/school performance

— Severe anemia (Hgb <7) → transfusion, IV iron (ferric carboxymaltose, iron sucrose) when oral fails or is too slow

— Persistent iron deficiency despite repletion → investigate ongoing loss and malabsorption

— Acute heavy AUB can cause hemodynamic collapse; requires resuscitation, transfusion, and bleeding control

— Massive transfusion thresholds and 1:1:1 ratios apply if ongoing hemorrhage

— Unopposed estrogen environments (PCOS, obesity, tamoxifen, anovulation) → hyperplasia spectrum

— Atypical hyperplasia/EIN coexists with carcinoma in up to 40% at hysterectomy

— Missed work/school, social withdrawal, sexual dysfunction, depression, anxiety

— Step 3 commonly tests recognition that QoL impact alone justifies treatment

— LNG-IUD: expulsion, perforation (~1/1000), unscheduled bleeding, ovarian cysts

— COCs: VTE (3–4× baseline), stroke, MI (smokers >35), hypertension

— Tranexamic acid: rare VTE

— Endometrial ablation: post-ablation syndrome, hematometra, late-onset pain, missed/delayed cancer diagnosis

— UAE: post-embolization syndrome, premature ovarian failure (~5%), pyometra

— Hysterectomy: bleeding, ureteral injury, VTE, infection, vaginal cuff dehiscence, premature menopause if ovaries removed

Iron-deficiency anemia — most common and underappreciated complication:

Hemorrhagic shock:

Endometrial hyperplasia and carcinoma:

Reduced quality of life and mental health impact:

Treatment-related complications:

Cardiovascular and bone consequences of long-term high-dose GnRH agonists without add-back: hypoestrogenism, bone loss, hot flashes

Step 3 management: Persistent menorrhagia + Hgb 8 in a 35-year-old → start LNG-IUD or COC and iron simultaneously; recheck Hgb at 6–8 weeks and ferritin at 3 months.

Key distinction: Treating the bleeding is not the same as correcting the anemia — both must be addressed and tracked separately.

When to Escalate Care — ICU, Consult, and Inpatient Triage

— Hemodynamic instability (HR >110, SBP <90, orthostasis)

— Hgb <7 g/dL or symptomatic anemia (chest pain, dyspnea, syncope)

— Active heavy bleeding not controlled with outpatient measures

— Suspected ectopic pregnancy or GTD

— Coagulopathy with active bleeding

— Need for IV estrogen, transfusion, or intrauterine tamponade

— Massive transfusion requirement

— Hemorrhagic shock unresponsive to initial resuscitation

— DIC complicating bleeding

— Post-procedural complications (uterine perforation with peritonitis, fluid overload, embolic complications)

— GYN: any AUB requiring procedure, suspected malignancy, refractory bleeding, pregnancy of unknown location

— Gyn-oncology: confirmed endometrial cancer, atypical hyperplasia/EIN, complex hyperplasia with concerning features

— Hematology: suspected/confirmed bleeding disorder, anticoagulation management during heavy bleeding, refractory anemia

— Interventional radiology: candidate for UAE, life-threatening bleeding bridge to surgery

— Endocrinology: refractory PCOS, prolactinoma, complex thyroid

— ED-to-floor: ensure type & screen current, anticoagulant reconciliation, GYN consulted

— Floor-to-discharge: confirm follow-up in 1–2 weeks, prescribe iron, contraception counseling, document advance care preferences if elderly

Emergency department / inpatient admission criteria:

ICU triage:

Consultation pathways:

CCS pearl on the inpatient floor: After stabilization, sequence: NPO if surgery imminent → continue IV fluids, monitor I/O, serial CBC q6–12h → IV iron or transfusion → transition IV estrogen to oral combined OCP or progestin → GYN evaluation for definitive therapy → social work for transportation/follow-up barriers.

Transfers of care risk points:

Step 3 management: Stable AUB with Hgb 9, normal vitals → outpatient workup (TVUS, labs, EMB if indicated) and start medical therapy; do not admit if patient can follow up reliably.

Board pearl: "Soaking a pad per hour for >2 hours" is the validated threshold suggesting active heavy bleeding warranting urgent evaluation — pair with vitals and Hgb.

Key Differentials — Same-Category Causes (Within PALM-COEIN)

— Focal endometrial overgrowth; common in 40s–50s and on tamoxifen

— TVUS: focal echogenic lesion; SIS confirms; hysteroscopic resection curative

— Cervical polyps: visible on speculum, can cause postcoital/intermenstrual bleeding

— Ectopic endometrial glands/stroma in myometrium

— Multiparous women 35–50; dysmenorrhea + HMB + globular tender uterus

— MRI most sensitive; LNG-IUD first-line; hysterectomy definitive

— Submucosal (FIGO 0–2) most likely to cause HMB even when small

— Intramural/subserosal contribute to bulk symptoms; race (Black women), age, family history risk factors

— Imaging: TVUS first; MRI for mapping

— Medical: LNG-IUD, COCs, GnRH antagonists with add-back; surgical: myomectomy, UAE, hysterectomy

— Endometrial hyperplasia without atypia → progestin

— Atypical hyperplasia/EIN → hysterectomy (or high-dose progestin if fertility-desired with close surveillance)

— Endometrial adenocarcinoma → gyn-onc, staging surgery

— Cervical cancer (postcoital/IMB) → colposcopy/biopsy, not Pap if visible lesion

— Uterine sarcoma → rapidly growing fibroid, especially postmenopausal

— Always sample endometrium if risk factors present, even with obvious fibroids

— Polyps and adenomyosis frequently coexist

— Focal cavity lesion → polyp or submucosal fibroid → SIS/hysteroscopy

— Diffuse thickened endometrium → hyperplasia/cancer → biopsy

— Globular heterogeneous myometrium → adenomyosis → MRI

— Discrete myometrial mass → fibroid → TVUS/MRI

AUB-P (Polyp):

AUB-A (Adenomyosis):

AUB-L (Leiomyoma):

AUB-M (Malignancy and hyperplasia):

Coexistence is common — a patient may have both a fibroid and hyperplasia; don't anchor:

Imaging-to-pathology mapping:

Board pearl: A "fibroid uterus" in a 55-year-old with bleeding is not the diagnosis until endometrial sampling rules out malignancy — postmenopausal fibroids should not grow, and growth raises sarcoma concern.

Key distinction: Hyperplasia without atypia = medical management acceptable; atypia/EIN = surgical (hysterectomy) is standard.

Key Differentials — Other-Category Causes (COEIN and Beyond)

— vWD (most common), platelet function disorders, ITP, factor deficiencies, leukemia

— Acquired: liver disease, anticoagulants, antiplatelets, uremia

— Workup: PT, aPTT, fibrinogen, vWF panel, platelet count and function

— PCOS, thyroid disease, hyperprolactinemia, hypothalamic dysfunction (stress, low BMI, athletes), perimenopause, primary ovarian insufficiency, Cushing, congenital adrenal hyperplasia

— Pattern: irregular, unpredictable; absent mid-cycle progesterone

— Diagnosis of exclusion: regular ovulatory cycles with HMB and no structural cause

— Proposed mechanisms: local prostaglandin/fibrinolysis imbalance, endometrial infection (chronic endometritis)

— Treat with tranexamic acid, NSAIDs, LNG-IUD

— Hormonal contraceptives (especially first 3 months, missed doses), DMPA, implant, copper IUD (heavier menses)

— Anticoagulants, antiplatelets, SSRIs, antipsychotics (via hyperprolactinemia), tamoxifen

— Herbals: ginkgo, ginseng, dong quai

— Manage by adjusting agent, adding tranexamic acid, or switching contraceptive

— Arteriovenous malformations, cesarean scar niche/isthmocele, chronic endometritis, müllerian anomalies

— Vaginal/vulvar lesions (atrophy, trauma, neoplasm, lichen sclerosus)

— Cervical (cervicitis, ectropion, polyp, cancer)

— Urinary tract (hematuria mistaken for vaginal)

— GI (hemorrhoids, anal fissure, IBD)

— Always localize source on speculum exam

— Ectopic, threatened/incomplete/missed abortion, GTD, placenta previa, abruption

AUB-C (Coagulopathy):

AUB-O (Ovulatory dysfunction):

AUB-E (Endometrial):

AUB-I (Iatrogenic):

AUB-N (Not otherwise classified):

Non-uterine sources masquerading as AUB:

Pregnancy complications (not AUB by definition, but must exclude):

Step 3 management: A 30-year-old with monthly HMB, regular cycles, normal TVUS, normal labs → AUB-E; start tranexamic acid during menses or LNG-IUD.

Board pearl: "Irregular cycles" → think COEIN; "regular heavy cycles" → think PALM or C/E within COEIN.

Secondary Prevention, Discharge Plan, and Long-Term Management

— Continue chosen hormonal therapy (LNG-IUD placed, COC daily, progestin) with clear taper instructions if applicable

— Oral iron 65 mg elemental every other day (better tolerated, better absorbed than daily); add vitamin C; recheck Hgb in 4–6 weeks, ferritin at 3 months

— Tranexamic acid PRN with menses if appropriate

— Anticoagulant reconciliation: confirm indication, dose, agent — switch to apixaban or LNG-IUD pairing if HMB is anticoagulation-driven

— PCOS, obesity, chronic anovulation: cyclic progestin every 1–3 months, continuous progestin, COC, or LNG-IUD

— Tamoxifen users: monitor with biopsy of any bleeding (TVUS stripe unreliable)

— Hyperplasia without atypia on progestin: repeat EMB at 3–6 months, then every 6–12 months until regression × 2

— Atypical hyperplasia treated medically (fertility-sparing): EMB every 3 months; hysterectomy after childbearing or if persistence/progression

— Lynch syndrome: annual EMB + TVUS starting age 30–35; consider risk-reducing hysterectomy after childbearing

— Weight loss in obesity/PCOS reduces anovulation and cancer risk

— Glycemic control, smoking cessation, blood pressure control

— Bone health if on GnRH agonist long-term: DEXA, calcium/vitamin D, add-back therapy

— Many AUB treatments are also contraceptives — align with reproductive goals

— Endometrial ablation requires reliable concurrent contraception or sterilization (pregnancy after ablation is high-risk)

Discharge medications after acute AUB stabilization:

Long-term endometrial protection in unopposed-estrogen states:

Cancer surveillance after hyperplasia treatment:

Lifestyle and risk-factor modification:

Contraceptive counseling:

Vaccinations and screening continuity (Step 3 emphasis): HPV vaccination through age 45 case-by-case, cervical cancer screening per USPSTF, mammography, lipid screening.

Step 3 management: A 38-year-old discharged after LNG-IUD placement for AUB-L should be told to expect 3–6 months of irregular spotting, return for string check at 4–6 weeks, and follow up at 3 and 6 months with Hgb and symptom review.

Follow-Up, Monitoring Parameters, and Counseling

— 4–6 weeks after initiation of new therapy or after acute episode: assess bleeding pattern, side effects, anemia recovery

— 3 months: confirm response; reassess Hgb and ferritin

— 6 months: if persistent bleeding despite first-line therapy, escalate workup (repeat imaging, hysteroscopy, biopsy)

— 12 months: routine maintenance check; annual exam

— LNG-IUD: string check at 4–6 weeks, then annually; expulsion symptoms (cramping, increased bleeding, palpable IUD)

— COCs: BP check at 3 months and annually; reassess VTE risk factors yearly; screen for new migraines with aura

— Tranexamic acid: review symptoms of VTE; renal function annually

— GnRH agonists/antagonists: bone density at 6–12 months if continued, lipid panel; add-back therapy adherence

— Iron therapy: Hgb at 4–6 weeks, ferritin at 3 months; if no response, reassess adherence, ongoing loss, malabsorption (celiac, H. pylori)

— Persistent or recurrent bleeding despite 3–6 months of appropriate therapy → repeat TVUS, SIS, or hysteroscopy with biopsy

— New risk factors emerge (weight gain, tamoxifen start, family history of Lynch) → resample

— Realistic expectations: LNG-IUD irregular spotting first 3–6 months; COCs may take 2–3 cycles to regulate

— Red flags requiring urgent return: soaking a pad/hour for ≥2 hours, syncope, severe pain, fever, suspected pregnancy, IUD expulsion

— Sexual and reproductive goals revisited at each visit

— Mental health screening — AUB strongly impacts depression/anxiety scores

Standard follow-up cadence:

Monitoring parameters by therapy:

When to repeat workup:

Counseling content (document on CCS):

Quality measures and value-based care touchpoints (Step 3 health-systems flavor): avoid unnecessary hysterectomy when LNG-IUD is viable; document shared decision-making; minimize repeat imaging by sequencing tests correctly the first time.

Board pearl: A patient who "failed" COCs for HMB often was nonadherent or used a low-estrogen formulation — reassess adherence and try LNG-IUD before surgery, except when malignancy is present.

Ethical, Legal, and Patient Safety Considerations

— Hysterectomy in young women: must document thorough discussion of fertility loss, alternatives (LNG-IUD, ablation, UAE, myomectomy), surgical menopause risk if oophorectomy

— Endometrial ablation: explicit counseling that pregnancy afterward is contraindicated and high-risk; concurrent contraception or sterilization decision

— Sterilization: 30-day Medicaid consent rule still relevant in many states; document timing

— Minors: state-specific consent laws for contraception and STI care; confidentiality with caveats (mandatory reporting)

— AUB in an adolescent may reveal sexual abuse, trafficking, or intimate partner violence — screen privately, separate from caregiver

— Unexplained bruising or bleeding patterns in elderly women → elder abuse evaluation

— Document and report per state law

— Anticoagulation reconciliation at every handoff; AUB plus DOAC requires explicit GYN + prescriber communication

— Discharge from ED after acute AUB without scheduled GYN follow-up is a closed-loop failure — most common malpractice driver in missed endometrial cancer

— Postmenopausal bleeding dismissed as "atrophy" without endometrial evaluation is a recurring litigation pattern

— Treatment choice must align with fertility goals; do not default to hysterectomy because it is "definitive"

— Respect refusal of blood products (e.g., Jehovah's Witness) — use IV iron, tranexamic acid, cell salvage, erythropoietin; document in advance directive

— Black women have higher fibroid burden, earlier age of presentation, and historically higher rates of hysterectomy — ensure equal access to uterus-sparing options

— Insurance coverage of LNG-IUD vs surgery — advocate for medical therapy when clinically equivalent

— Missed cancer on initial biopsy or false-reassurance from TVUS alone → disclose, repeat workup, document

Informed consent edge cases:

Mandatory reporting and abuse screening:

Transition-of-care safety:

Reproductive autonomy and shared decision-making:

Health equity considerations:

Disclosure of errors:

Step 3 management: A 47-year-old with PMB whose TVUS shows 3 mm stripe should still receive an explicit return-precaution conversation: recurrent bleeding mandates EMB regardless of prior reassuring imaging.

Board pearl: Failure to biopsy PMB is one of the highest-yield gynecologic malpractice scenarios — never close the loop on PMB without tissue or documented thin stripe + return precautions.

High-Yield Associations and Rapid-Fire Clinical Facts

• PALM-COEIN mnemonic: Polyp, Adenomyosis, Leiomyoma, Malignancy/hyperplasia	Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic, Not classified
• First test in any reproductive-age AUB: β-hCG, then CBC
• First imaging: TVUS; best for polyps/submucosal fibroids: SIS; best for adenomyosis and fibroid mapping: MRI
• PMB endometrial stripe cutoff: ≤4 mm reassuring; >4 mm or persistent bleeding → biopsy
• Sample endometrium when: age ≥45, age <45 with risk factors, any PMB, atypical glandular cells on Pap, persistent AUB despite therapy, tamoxifen + bleeding
• First-line non-surgical HMB therapy: LNG-IUD 52 mg
• Adolescent HMB: screen for vWD before hormones if severe
• Anovulation cocktail to remember: PCOS, thyroid, prolactin, perimenopause, hypothalamic, POI
• Tamoxifen → endometrial polyps, hyperplasia, cancer, sarcoma; TVUS stripe unreliable
• Atypical hyperplasia/EIN → coexisting carcinoma ~40% → hysterectomy preferred
• Acute heavy bleeding meds (stable): IV conjugated estrogen, high-dose progestin, COC taper, tranexamic acid
• Tranexamic acid + COC combination → avoid (VTE concern)
• Endometrial ablation contraindications: desire for fertility, hyperplasia/cancer, postmenopause, IUD in place
• Lynch syndrome surveillance: annual EMB + TVUS from age 30–35; risk-reducing hysterectomy after childbearing
• Most common cause of PMB overall: endometrial/vaginal atrophy — but always rule out cancer first
• Most common cause of HMB in adolescents: anovulation; most commonly missed: vWD
• Rapidly enlarging postmenopausal "fibroid" → suspect leiomyosarcoma
• Copper IUD: causes heavier menses; LNG-IUD: causes lighter menses/amenorrhea
• DDAVP works in vWD type 1, not type 2B (worsens thrombocytopenia) or type 3
• Board pearl rapid-fire: PMB = biopsy. Anovulation = progestin protection. HMB + iron deficiency = treat both. Bulky uterus + dysmenorrhea = adenomyosis. Submucosal fibroid + HMB = hysteroscopic myomectomy.
• Key distinction: AUB is a symptom and classification, not a diagnosis — every case requires assignment to a PALM-COEIN bucket.

Board Question Stem Patterns

Stem 1 — Adolescent HMB: 15-year-old, menarche age 12, soaking pads hourly, Hgb 7, family history of postpartum hemorrhage → Answer: vWF antigen/activity, factor VIII (then IV fluids, transfuse, IV estrogen or high-dose progestin; tranexamic acid). Distractor: "start COCs immediately" — would obscure vWD testing if drawn afterward.

Stem 2 — PMB: 58-year-old, BMI 34, diabetes, one episode of spotting, TVUS stripe 8 mm → Answer: endometrial biopsy. Distractor: repeat TVUS in 3 months, Pap smear, hormone therapy.

Stem 3 — PCOS with prolonged amenorrhea then heavy bleed: 32-year-old, BMI 38, irregular cycles since menarche → Answer: endometrial biopsy first (rule out hyperplasia), then progestin or COC. Distractor: start metformin only.

Stem 4 — Fibroid uterus: 42-year-old with HMB, 12-week irregular uterus, Hgb 9, desires uterine preservation → Answer: LNG-IUD or GnRH antagonist with add-back, MRI to map for myomectomy if symptomatic. Distractor: hysterectomy as first answer.

Stem 5 — Tamoxifen patient with spotting: 62-year-old breast cancer survivor on tamoxifen, vaginal spotting, TVUS stripe 6 mm → Answer: hysteroscopy with biopsy (TVUS unreliable on tamoxifen).

Stem 6 — Postcoital bleeding: 28-year-old, friable cervical lesion → Answer: colposcopy with biopsy, not Pap. Distractor: "repeat Pap in 1 year."

Stem 7 — Anticoagulated patient with AUB: 45-year-old on rivaroxaban for VTE, HMB → Answer: switch to apixaban or add LNG-IUD; full AUB workup including EMB if risk factors.

Stem 8 — Acute hemorrhage: 30-year-old, soaking pads, BP 88/52, HR 118, Hgb 6 → Answer: IV access, crystalloid, transfuse, IV conjugated estrogen, GYN consult. Distractor: outpatient TVUS.

Stem 9 — Atypical hyperplasia/EIN biopsy: 50-year-old, completed childbearing → Answer: total hysterectomy. Fertility-desired variant: high-dose progestin + close surveillance.

Stem 10 — Failed first-line therapy: 38-year-old, AUB-E on tranexamic acid still bleeding heavily → Answer: LNG-IUD; if completed childbearing and normal cavity/histology, ablation is reasonable.

Board pearl: When the stem highlights age ≥45, obesity, PCOS, tamoxifen, Lynch, or PMB, the answer almost always involves endometrial sampling somewhere in the workup.

One-Line Recap

AUB workup is anchored by β-hCG first, then a structured PALM-COEIN classification that pairs targeted history and TVUS with endometrial sampling whenever age, risk factors, or postmenopausal status raises cancer concern, guiding therapy from LNG-IUD and tranexamic acid through hysteroscopic, ablative, or definitive surgical management.

Workup spine: β-hCG → CBC/TSH/prolactin/ferritin → TVUS → SIS or hysteroscopy for focal lesions → endometrial biopsy when age ≥45, risk factors, or PMB → coagulation panel when history suggests bleeding disorder, especially adolescents with HMB since menarche.

Therapy spine: LNG-IUD is the first-line non-surgical option across most PALM-COEIN categories; tranexamic acid and NSAIDs for ovulatory HMB and women avoiding hormones; COCs for AUB-O with contraceptive need; high-dose progestin or IV estrogen for acute bleeding; hysteroscopic resection for polyps/submucosal fibroids; ablation when childbearing complete and pathology benign; hysterectomy for atypical hyperplasia, malignancy, or refractory disease.

Special-population spine: adolescents — screen vWD; PCOS — cyclic progestin endometrial protection; perimenopause — always sample; PMB — biopsy or thin TVUS stripe with rigorous follow-up; tamoxifen — biopsy any bleeding regardless of stripe; anticoagulated — full workup, switch to apixaban + LNG-IUD if HMB persists.

Safety spine: never start hormones without ruling out pregnancy and malignancy in at-risk patients; never close PMB without tissue or thin-stripe documentation plus return precautions; treat iron deficiency in parallel with bleeding control; align therapy with the patient's reproductive goals and document shared decision-making — these are the recurring Step 3 board, CCS, and malpractice triggers in abnormal uterine bleeding.