What is the differential diagnosis for menorrhagia?

Differential Diagnosis for Menorrhagia

The differential diagnosis for menorrhagia should be systematically categorized into structural uterine pathology, systemic coagulation disorders, endocrine dysfunction, and iatrogenic causes, with approximately 50% of cases having no identifiable structural pathology at hysterectomy. 1

Structural/Anatomic Causes (PALM Classification)

Uterine Pathology

• Uterine fibroids (leiomyomas): The most common structural cause, particularly submucosal fibroids which distort the endometrial cavity and increase surface area for bleeding 2, 3
• Adenomyosis: Invasion of endometrial tissue into the myometrium, often coexisting with fibroids and causing both menorrhagia and dysmenorrhea 2
• Endometrial polyps: Benign growths that can cause irregular and heavy bleeding 4, 5
• Endometrial hyperplasia: Results from prolonged unopposed estrogen stimulation, particularly in chronic anovulation; carries increased risk for endometrial cancer 5
• Endometrial or uterine malignancy: Must be excluded, especially in women ≥35 years with risk factors 5

Systemic/Coagulation Disorders

Hematologic Causes

• Von Willebrand disease: The most common inherited bleeding disorder causing menorrhagia 5
• Platelet dysfunction: Including thrombocytopenia, which can cause menorrhagia through impaired hemostasis 2
• Other coagulopathies: Factor deficiencies and acquired bleeding disorders 4, 6

Clinical Pearl: Women with menorrhagia and bleeding from other sites (epistaxis, easy bruising, dental bleeding) should be evaluated for coagulation disorders. 2

Endocrine Dysfunction

Hormonal Causes

• Chronic anovulation: Leading cause of irregular heavy bleeding from unopposed estrogen; includes polycystic ovary syndrome (PCOS) 5
• Thyroid dysfunction: Both hypothyroidism and hyperthyroidism can cause menorrhagia 4, 5
• Hyperprolactinemia: Disrupts normal ovulatory cycles 5
• Diabetes mellitus (uncontrolled): Associated with anovulatory bleeding 5

Iatrogenic Causes

Medication-Related

• Anticoagulant therapy: Warfarin, heparin, direct oral anticoagulants 6
• Antipsychotic medications: Can cause hyperprolactinemia and anovulation 5
• Antiepileptic drugs: May disrupt normal menstrual cycles 5
• Copper intrauterine device (Cu-IUD): Associated with increased menstrual bleeding compared to hormonal IUDs 2

Dysfunctional Uterine Bleeding (DUB)

Diagnosis of Exclusion

• Ovulatory DUB: Regular heavy bleeding without identifiable pathology, accounting for approximately 50% of menorrhagia cases 1
• Abnormal prostaglandin levels: Increased PGE2 and decreased PGF2α in endometrium 7, 1
• Abnormal fibrinolytic activity: Excessive endometrial fibrinolysis preventing normal clot formation 7, 1

Special Population Considerations

Glycogen Storage Disease Type I

• GSD I-associated menorrhagia: Results from platelet dysfunction and acquired von Willebrand-like disease secondary to metabolic abnormalities 2
• Bleeding tendency manifests as menorrhagia in reproductive-age females with this metabolic disorder 2

Systemic Lupus Erythematosus

• SLE with severe thrombocytopenia: Can cause menorrhagia; severity depends on platelet count and clinical manifestations 2

Key Diagnostic Approach

Essential initial workup includes: Complete blood count to assess for anemia (menorrhagia causes iron deficiency in 20-25% of reproductive-age women), thyroid function tests, and endometrial sampling in women ≥35 years or younger women with risk factors for endometrial cancer. 8, 5, 6

Imaging evaluation: Transvaginal ultrasound is first-line for structural assessment; saline infusion sonohysterography or MRI provides superior evaluation of endometrial cavity and adenomyosis. 2, 5

Coagulation screening: Indicated when history suggests bleeding disorder (heavy bleeding since menarche, family history, bleeding from other sites). 5, 6