What are the differential diagnoses and recommended investigations for a 37‑year‑old woman with heavy menstrual bleeding and continuous per‑vaginal bleeding for ten days (approximately four pads per day)?

Differential Diagnoses for Heavy Menstrual Bleeding in a 37-Year-Old Woman

In a 37-year-old woman with 10 days of heavy per-vaginal bleeding (4 pads/day), the most likely diagnoses are uterine fibroids (leiomyomas), endometrial polyps, adenomyosis, ovulatory dysfunction, or coagulopathy—with structural causes accounting for approximately 50% of cases in this age group. 1

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Differential Diagnoses by Category

Structural Causes (PALM)

• Uterine fibroids (leiomyomas) are the most common structural cause of heavy menstrual bleeding in women under 40 years of age. 1

• Endometrial polyps become increasingly common in women approaching 40 and should be strongly considered in this age group. 1

• Adenomyosis frequently presents with heavy menstrual bleeding, dysmenorrhea, and dyspareusis, typically affecting women in their 40s but can occur in the late 30s. 2

• Endometrial hyperplasia or malignancy must be excluded, particularly given the patient's age (≥35 years) and prolonged bleeding pattern; risk factors include obesity, diabetes, hypertension, unopposed estrogen exposure, and chronic anovulation. 1, 3

Non-Structural Causes (COEIN)

• Ovulatory dysfunction (oligo-ovulation or anovulation) commonly causes irregular, heavy bleeding in reproductive-age women and warrants evaluation for underlying endocrine disorders. 1

• Coagulopathy, particularly von Willebrand disease, is more common than many clinicians realize and should be considered in any woman with menorrhagia, especially if bleeding has been heavy since menarche or if there is a personal or family history of bleeding disorders. 4, 5

• Primary endometrial disorders involving molecular deficiencies in endometrial hemostasis regulation can cause heavy menstrual bleeding without identifiable structural abnormalities. 1

• Iatrogenic causes include intrauterine devices, anticoagulation therapy (approximately 70% of women on anticoagulation experience heavy menstrual bleeding), and exogenous hormones. 1

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Essential Investigations

Immediate Laboratory Tests

• Pregnancy test (β-hCG) must be performed first in all reproductive-age women with abnormal uterine bleeding to exclude pregnancy complications, including ectopic pregnancy and trophoblastic disease. 1, 2, 6

• Complete blood count with platelets to assess for anemia (given 10 days of heavy bleeding) and thrombocytopenia. 2

• Thyroid-stimulating hormone (TSH) and prolactin levels to evaluate for endocrine causes of ovulatory dysfunction. 1, 2

• Coagulation profile (PT, aPTT, bleeding time) should be obtained if the patient has a history of easy bruising, prolonged bleeding after minor procedures, family history of bleeding disorders, or menorrhagia since menarche. 6, 4, 5

First-Line Imaging

• Combined transvaginal and transabdominal ultrasound with Doppler is the most appropriate initial imaging study for identifying structural causes such as polyps, adenomyosis, leiomyomas, and endometrial hyperplasia/malignancy. 1, 3

• Saline infusion sonohysterography (SIS) should be performed if focal lesions are suspected or if standard ultrasound inadequately visualizes the endometrium; SIS has 96–100% sensitivity and 94–100% negative predictive value for detecting endometrial pathology and can distinguish polyps from submucous fibroids with 97% accuracy. 1, 3

Endometrial Sampling Indications

• Endometrial biopsy is indicated in this 37-year-old patient if:

  • Endometrial thickness ≥10 mm on ultrasound 3
  • Risk factors for endometrial cancer are present (obesity, diabetes, hypertension, chronic anovulation, PCOS) 1, 3
  • Bleeding persists despite initial medical management 1
  • The patient is ≥35 years with persistent or recurrent undiagnosed bleeding 3

• Pipelle or Vabra endometrial sampling has extremely high sensitivity (99.6% and 97.1% respectively) for detecting endometrial carcinoma. 3

Advanced Diagnostic Procedures

• Hysteroscopy with directed biopsy should be performed if:
  • Initial endometrial biopsy is inadequate, non-diagnostic, or negative but symptoms persist 1, 3
  • Focal lesions (polyps, submucous fibroids) are identified on imaging 3, 2
  • Bleeding continues despite appropriate medical therapy 2

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Clinical Pitfalls to Avoid

• Never assume dysfunctional uterine bleeding without first excluding structural causes, pregnancy complications, and coagulopathy through appropriate testing. 4

• Do not rely on endometrial biopsy alone to rule out focal lesions, as blind sampling has a 10% false-negative rate and frequently misses polyps and submucous fibroids. 3, 2

• Always screen for coagulopathy in women with menorrhagia who fail medical or surgical therapy, as von Willebrand disease and other bleeding disorders are underdiagnosed. 4, 5

• Recognize that 4 pads per day for 10 consecutive days represents significant blood loss that warrants urgent evaluation for hemodynamic stability and anemia. 1

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Recommended Investigation Algorithm

1. Immediate: β-hCG, CBC with platelets, assess hemodynamic stability 1, 2

2. Within 24–48 hours: TSH, prolactin, combined transvaginal/transabdominal ultrasound with Doppler 1, 3, 2

3. If risk factors or abnormal ultrasound: Endometrial biopsy (Pipelle or Vabra) 3

4. If focal lesions on ultrasound: Saline infusion sonohysterography 1, 3

5. If coagulopathy suspected: PT, aPTT, bleeding time, von Willebrand factor assay 4, 5

6. If initial workup negative but bleeding persists: Hysteroscopy with directed biopsy 3, 2