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Abnormal Uterine Bleeding (AUB): Investigations and Management Across Age Groups

Definition and Classification (PALM-COEIN System)

Note: Postmenopausal bleeding is not included in PALM-COEIN and is considered its own distinct diagnosis. - Sabiston Textbook of Surgery, p. 2795

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Epidemiology

• AUB affects 10-30% of women of reproductive age
• ~20% of AUB is postmenarchal bleeding in adolescents (due to immature HPO axis)
• ~50% is perimenopausal bleeding related to incipient ovarian failure
• 75% of cases have no demonstrable organic cause and are anovulatory in origin
• Heavy menstrual bleeding is the presenting complaint in the majority - Goldman-Cecil Medicine, p. 2555

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General Investigations (All Age Groups)

• Amount, duration, and pattern of blood loss
• Prospective charting of bleeding days
• Last menstrual period, obstetric history
• Medications (OCP, anticoagulants, tamoxifen, hormones)
• Family history of coagulopathy

• Pelvic exam: tenderness, uterine size/mass, cervical lesions
• Papanicolaou smear
• Signs of anemia

• Full blood count + platelet count
• Coagulation profile (PT, APTT)
• Von Willebrand disease screening (if heavy bleeding since menarche, family history, or multi-system bleeding signs)
• Thyroid function tests (TSH)
• Fasting blood glucose
• Serum prolactin
• Pregnancy test (mandatory in all reproductive-age women)
• Cervical cancer screening if not up to date
• STI screening

• Pelvic ultrasound (2D/3D, or saline sonohysterogram): first-line imaging to assess uterine cavity, endometrial thickness, and ovaries
• Hysteroscopy: gold standard for direct visualization; combined with endometrial biopsy has greater sensitivity and specificity than either alone

• All women ≥45 years with AUB (including intermenstrual bleeding)
• Women <45 years with: unopposed estrogen exposure (obesity, PCOS), persistent AUB refractory to medical management, elevated familial cancer risk
• Postmenopausal bleeding with endometrial thickness >4 mm

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AUB by Age Group

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1. Adolescents (Menarche to ~18 years)

Etiology

• Anovulation is physiologic for an average of 18 months after menarche while the hypothalamic-pituitary-ovarian axis matures
• Menorrhagia in adolescents is most commonly caused by anovulation
• Up to 24% of adolescents with menorrhagia may have an undiagnosed bleeding disorder (e.g., von Willebrand disease, ITP) - this is a critical and often missed diagnosis
• Primary amenorrhea causes: pregnancy, chromosomal abnormalities (Turner syndrome, Swyer syndrome), hypothalamic hypogonadism, congenital absence of uterus/cervix/vagina, structural anomalies (transverse vaginal septum, imperforate hymen)

Investigations

• Complete blood count
• Coagulation profile (PT, APTT)
• Von Willebrand disease screening (essential if heavy bleeding from menarche)
• Pelvic ultrasonography (to document pelvic organ presence if amenorrhea)
• Chromosome analysis if clinically indicated (primary amenorrhea workup)
• Pregnancy test

Note: Endometrial biopsy is rarely indicated in this age group unless there is prolonged unopposed estrogen exposure or suspicion of malignancy.

Management

• Anovulatory bleeding / menorrhagia: Hormonal contraception (combined OCP) for cycle control - first-line
• Coagulation disorders: treat the underlying bleeding disorder specifically (tranexamic acid, desmopressin for vWD)
• Acute heavy bleeding: hospital admission, IV conjugated estrogens or high-dose OCP

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2. Reproductive-Age Women (~18-45 years)

Etiology

• Pregnancy complications (threatened/incomplete/missed miscarriage, ectopic pregnancy) - must always be excluded first
• Anovulatory disorders (PCOS, hyperprolactinemia, thyroid disease, Cushing's)
• Structural causes: uterine leiomyomas (most common benign gynecologic tumor, affecting up to 70% of women by age 50), endometrial polyps, adenomyosis
• Coagulopathy: ITP, von Willebrand disease
• Iatrogenic: OCP complications, IUD, anticoagulants
• Systemic disease: hepatic/renal failure, leukemia, endocrinopathies

• Menorrhagia: structural lesions, coagulopathy, hepatic/renal failure
• Polymenorrhea: luteal phase defect, short follicular phase
• Oligomenorrhea: prolonged follicular phase
• Intermenstrual bleeding: cervical pathology, IUD

Investigations

• Mandatory: Pregnancy test first
• FBC, coagulation studies, TFTs, prolactin, fasting glucose
• Pelvic ultrasound +/- saline sonohysterogram
• Endometrial biopsy: if age ≥45, or age <45 with risk factors (obesity, PCOS, persistent AUB, family history of endometrial cancer, tamoxifen use)
• Hysteroscopy: if focal lesion suspected, or biopsy insufficient
• Cervical cytology + STI swabs

Management

• Endometrial ablation: effective for persistent bleeding; not 100% effective (29% eventually require hysterectomy at 60 months in RCTs)
• Uterine artery embolization (UAE): for fibroids; ~31% ultimately require hysterectomy in RCTs
• Hysteroscopic polypectomy: for endometrial polyps
• Myomectomy: fibroid-preserving surgery
• Hysterectomy: reserved for failure of/intolerance to medical therapy; always requires endometrial sampling before proceeding; dilation and curettage alone is NOT an effective means of controlling bleeding

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3. Perimenopausal Women (~45 years to menopause)

Etiology

• Most common: Anovulation due to declining ovarian follicle numbers and decreasing inhibin B levels
• Structural lesions (fibroids, polyps) remain common
• Increasing risk of endometrial hyperplasia and carcinoma
• Bleeding disorders

Investigations

• Endometrial biopsy is mandatory in all perimenopausal women with AUB to exclude endometrial hyperplasia/cancer
• Risk factors for endometrial cancer: nulliparity, diabetes, obesity
• Pelvic ultrasound (endometrial thickness)
• Hysteroscopy + biopsy if focal lesion suspected
• FBC, TFTs, coagulation studies

Management

• Non-smokers: Combined OCP for cycle control (most effective)
• Smokers (increased thrombotic risk - avoid estrogen): Cyclic progestin to provide regular withdrawal bleed
• Levonorgestrel IUD: excellent option for heavy menstrual bleeding + contraception
• If malignancy/hyperplasia excluded: same options as reproductive-age women
• Hysterectomy if medical therapy fails

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4. Postmenopausal Women

Etiology (in order of frequency)

1. Endometrial/vaginal atrophy (most common) - thinning due to estrogen deficiency
2. Endometrial polyps
3. Endometrial hyperplasia
4. Endometrial carcinoma (10-20% of cases) - 90% of endometrial cancer patients present with postmenopausal bleeding
5. Uterine fibroids/adenomyosis
6. Medications: HRT, anticoagulants
7. Cervical carcinoma
8. Tamoxifen use: increases endometrial polyps, hyperplasia, cancer risk; doubles risk after 1-2 years, quadruples after 5 years (time-dependent, dose-independent)

Investigations

1. Pelvic ultrasound - assess endometrial stripe:
   • Endometrial thickness ≤4 mm: endometrial cancer effectively excluded (biopsy may be avoided)
   • Important caveat: the 4 mm cutoff has been shown to under-diagnose endometrial cancer in Black patients - clinical judgment required
   • Endometrial thickness >4 mm: endometrial biopsy indicated
2. Office endometrial biopsy (Pipelle): excellent sensitivity; if cervical stenosis prevents access, surgical procedure may be indicated

• Focal lesion suspected on imaging
• Difficulty visualizing endometrium
• Persistent bleeding despite normal ultrasound

Management

• Atrophic vaginitis/endometrial atrophy: topical estrogen therapy
• Endometrial polyps: hysteroscopic polypectomy
• Endometrial hyperplasia without atypia: progestins (cyclic or continuous)
• Atypical hyperplasia/carcinoma: surgical staging (hysterectomy + BSO ± lymph node dissection)
• HRT-related bleeding: adjust or discontinue HRT
• Aromatase inhibitors (anastrozole, letrozole, exemestane): may reverse tamoxifen-induced endometrial abnormalities

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Management of Acute Heavy Bleeding (Emergency)

1. Admit to hospital
2. IV access + IV fluid resuscitation
3. Transfusion if anemia is profound
4. IV conjugated estrogens: 25 mg IV every 4 hours for up to 3 doses until bleeding ceases; start simultaneous oral progestin (medroxyprogesterone acetate 5-10 mg for 10 days)
5. If stable but profuse: oral OCP (1 pill q6h × 5-7 days) - bleeding should cease within 24 hours; warn patient about heavy withdrawal bleed 2-4 days after stopping
6. If bleeding continues despite medical therapy: surgical curettage
7. Hysterectomy in refractory cases

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Summary Table: AUB by Age Group

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• Sabiston Textbook of Surgery, 21st ed. (PALM-COEIN, postmenopausal workup)
• Goldman-Cecil Medicine (epidemiology, anovulatory management)
• Textbook of Family Medicine, 9e (life-cycle approach, age-group management)
• Berek & Novak's Gynecology (surgical management, hysterectomy indications)
• Bailey and Love's Short Practice of Surgery, 28th ed. (structural/non-structural classification, tamoxifen)
• Recent meta-analysis: Comishen et al. 2025 - J Thromb Haemost - etiology and diagnosis of heavy menstrual bleeding across adolescent and adult patients (PMID 39617186)

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AUB in the OPD: Case-Based Approach Across Age Groups

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🏥 CASE 1 - Adolescent (Age 14)

Presenting Complaint

• Menarche: 3 months ago
• Cycles: irregular, every 18-35 days
• Duration: 10-12 days per episode
• Clots: large clots passed
• Associated: pallor, fatigue, mild dizziness
• No sexual activity
• No prior medical history
• Family history: mother has "heavy periods," uncle has a bleeding disorder

What You're Thinking in OPD

1. Physiologic anovulation (HPO axis immaturity - normal for 18 months post-menarche)
2. Coagulopathy - Von Willebrand disease is present in up to 13-24% of adolescents with menorrhagia; the family history here is a red flag
3. PCOS (less likely this early)
4. Hypothyroidism

"The first described case of von Willebrand's disease was in a 13-year-old who died as a result of uncontrollable uterine bleeding." - Tintinalli's Emergency Medicine

OPD Examination

• Pallor of conjunctivae and nail beds
• No hirsutism, acne, acanthosis nigricans (argues against PCOS)
• No petechiae or ecchymoses (but does NOT rule out vWD)
• Pelvic exam: deferred (not sexually active, no indication)
• Abdominal exam: no masses

Investigations

Diagnosis

Management

• Iron supplementation (ferrous sulfate 200 mg TDS with vitamin C)
• If Hb < 7 g/dL or hemodynamically unstable: admit for IV iron or transfusion

• Combined OCP (30 µg ethinylestradiol + levonorgestrel): 1 tablet every 6 hours × 5-7 days → then taper; bleeding should stop within 24 hours
• Tranexamic acid (antifibrinolytic): reduces bleeding by 30-55%; can be used acutely and long-term
• Desmopressin (DDAVP): intranasal or IV; releases stored vWF from endothelial cells - specific for vWD type 1

• Combined OCP cyclically (first-line for ongoing cycle regulation)
• Levonorgestrel IUD: reduces heavy bleeding by up to 90%; FDA-approved for heavy menstrual bleeding; appropriate for adolescents (insertion under local anesthesia if needed)
• Continuous progestin (norethindrone, DMPA) if OCP contraindicated

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🏥 CASE 2 - Reproductive Age (Age 28, PCOS)

Presenting Complaint

• LMP: 3 months ago
• Cycles: oligomenorrheic (4-5 cycles/year)
• Episodes: heavy, prolonged when they occur
• Associated: weight gain, hirsutism, acne
• Married 2 years, not conceived
• No contraception

What You're Thinking in OPD

OPD Examination

• BMI: 32 (obese)
• Hirsutism (Ferriman-Gallwey score)
• Acanthosis nigricans at nape of neck
• Acne
• Pelvic exam: uterus normal size, no masses

Investigations

"Patients younger than 45 years old with unopposed estrogen exposure such as those with obesity and ovulatory dysfunction with persistent AUB should be biopsied." - Sabiston Textbook of Surgery, p. 2794

Diagnosis

Management

• Combined OCP (first-line): regulates cycles, opposes estrogen, treats hirsutism and acne
• Levonorgestrel IUD: excellent option - provides endometrial protection + heavy bleeding control
• Cyclic progestin (medroxyprogesterone acetate 10 mg/day × 10-14 days every 1-3 months): minimum 4 withdrawal bleeds per year to prevent endometrial hyperplasia
• Metformin: treats insulin resistance; may restore ovulation in PCOS
• Weight loss: restores ovulation in up to 50% of obese PCOS patients

• Ovulation induction: clomiphene citrate 50 mg days 2-6 (first-line)
• Letrozole: increasingly preferred in PCOS (better live birth rates)
• Metformin + clomiphene: if clomiphene-resistant

• High-dose progestins (medroxyprogesterone acetate 10-20 mg daily continuously × 3-6 months)
• Repeat biopsy in 3-6 months

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🏥 CASE 3 - Reproductive Age (Age 35, Fibroids)

Presenting Complaint

• Cycles: regular, every 28 days
• Duration of heavy flow: 7-8 days (previously 4)
• Clots: large clots
• Associated: pelvic pressure, urinary frequency, constipation
• Parity: G2P2 (two previous normal deliveries)
• No oral contraceptive use

What You're Thinking in OPD

OPD Examination

• Pallor
• Abdomen: uterus palpable abdominally, irregular, firm, non-tender (14-16 week size)
• Bimanual: enlarged irregular uterus, no adnexal masses

Investigations

Diagnosis

Management

• GnRH receptor antagonists (oral):
  • Elagolix 300 mg twice daily, OR
  • Relugolix 40 mg daily
  • Reduce uterine/fibroid volume; used for 6-12 months; side effects: hypoestrogenic symptoms, bone loss
• Levonorgestrel IUD: good for submucosal-free uterus; less effective if large/multiple submucosal fibroids
• Tranexamic acid (1 g TDS × 4 days/cycle): reduces flow by ~50% without affecting fertility
• NSAIDs (mefenamic acid 500 mg TDS): modest effect on flow; useful for dysmenorrhea
• Iron supplementation to correct anemia before surgery

"Uterine artery embolization vs hysterectomy: 31% of those randomised to UAE ultimately underwent a hysterectomy." - Berek & Novak's Gynecology, p. 1411

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🏥 CASE 4 - Perimenopausal (Age 48)

Presenting Complaint

• LMP: 3 weeks ago
• Cycles: irregular (18-60 day intervals) for 12 months
• Recently: one episode of prolonged heavy bleeding
• Associated: hot flushes, night sweats, mood changes
• BMI: 29 (overweight)
• No HRT
• Nulliparous (G0P0)

What You're Thinking in OPD

• Nulliparity ✅
• Overweight ✅
• Anovulatory cycles (unopposed estrogen) ✅
• Age >45 ✅

OPD Examination

• BP, BMI documented
• Thyroid: normal
• Pelvic exam: uterus slightly enlarged, no adnexal masses
• No vaginal lesions

Investigations

"Evaluation of a perimenopausal woman with abnormal bleeding should include an endometrial biopsy to exclude endometrial hyperplasia or cancer." - Textbook of Family Medicine, 9e

Diagnosis (scenarios based on biopsy result)

• Non-smoker: Combined OCP (low-dose 20 µg) - cycle regulation + contraception
• Smoker / VTE risk: Cyclic progestin (medroxyprogesterone acetate 10 mg × 14 days/month)
• Levonorgestrel IUD: excellent option - endometrial protection + heavy bleeding control
• Hot flushes: consider low-dose HRT or SSRIs if vasomotor symptoms significant

• Progestin therapy (continuous or cyclic)
• Repeat biopsy in 3-6 months
• LNG-IUD is superior to oral progestins for regression of hyperplasia

• Urgent referral to Gynaecological Oncology
• Hysterectomy + BSO + staging (standard treatment)

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🏥 CASE 5 - Postmenopausal (Age 62)

Presenting Complaint

• Last menstrual period: 8 years ago
• Now: one episode of light fresh bleeding (2 days)
• No HRT currently
• Past history: hypertension, type 2 diabetes, BMI 34
• No abdominal pain, no fever

What You're Thinking in OPD

• Hypertension ✅
• Type 2 diabetes ✅
• Obesity (BMI 34) ✅
• Age >55 ✅
• This patient has the classic endometrial cancer profile

"Of patients diagnosed with endometrial cancer, 90% experience postmenopausal bleeding." - Sabiston Textbook of Surgery, p. 2795

"Between 10% and 20% of all postmenopausal bleeding is caused by malignancy." - Textbook of Family Medicine, 9e

OPD Examination

• Abdomen: no masses, no hepatomegaly
• Pelvic examination: atrophic vaginal mucosa (pale, dry - suggests atrophy), no vulval lesion, cervix appears normal
• Bimanual: uterus slightly bulky, no obvious adnexal mass

Investigations - URGENT PATHWAY

Management Based on Findings

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Quick OPD Summary Card

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