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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)