What is the differential diagnosis and treatment for metrorrhagia?

Differential Diagnosis for Metrorrhagia

Primary Diagnostic Consideration: Endometrial Malignancy

In any patient presenting with metrorrhagia, endometrial carcinoma must be excluded first, as approximately 90% of patients with endometrial carcinoma present with metrorrhagia, most commonly in the postmenopausal period. 1

Structural/Anatomic Causes

Benign Uterine Pathology

• Uterine fibroids (leiomyomas) are the most common structural cause, particularly submucosal fibroids which distort the endometrial cavity and increase surface area for bleeding 2. Note that serosal fibroids do NOT cause menorrhagia as they project outward and do not affect the endometrial cavity 3
• Endometrial polyps are especially common in women over 40 years of age and require sonohysterography or hysteroscopy for reliable diagnosis 4
• Adenomyosis (invasion of endometrial tissue into myometrium) often coexists with fibroids and causes both menorrhagia and dysmenorrhea 2

Malignant Pathology

• Endometrial carcinoma must be excluded in women ≥35 years or younger women with risk factors (obesity, diabetes, unopposed estrogen, Lynch syndrome, tamoxifen use) 1
• Uterine sarcomas (mesenchymal tumors) may not be accurately diagnosed by endometrial biopsy alone 1

Systemic/Coagulation Disorders

• Von Willebrand disease and other coagulopathies should be evaluated in women with menorrhagia and bleeding from other sites 2
• Platelet dysfunction including thrombocytopenia can cause menorrhagia through impaired hemostasis 2
• Thyroid dysfunction (both hypothyroidism and hyperthyroidism) can cause ovulatory abnormal uterine bleeding 5

Endocrine/Anovulatory Causes

• Polycystic ovary syndrome (PCOS) leads to chronic anovulation with irregular bleeding and prolonged unopposed estrogen stimulation 5
• Hyperprolactinemia causes anovulatory bleeding 5
• Uncontrolled diabetes mellitus contributes to anovulatory patterns 5

Iatrogenic Causes

• Copper intrauterine device (Cu-IUD) is associated with increased menstrual bleeding compared to hormonal IUDs 2
• Antipsychotic or antiepileptic medications can cause chronic anovulation 5

Dysfunctional Uterine Bleeding

• Idiopathic menorrhagia accounts for approximately 50% of cases where no pathology is found at hysterectomy 6. Abnormal levels of prostaglandins or the fibrinolytic system in the endometrium have been implicated 6

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Essential Diagnostic Workup

Mandatory Initial Evaluation

• Complete blood count to assess for anemia 2
• Thyroid function tests to exclude thyroid dysfunction 2, 5
• Pregnancy test must be performed first to exclude pregnancy-related bleeding 7

Age-Specific Endometrial Sampling

Endometrial biopsy is mandatory in: 1, 2

• All women ≥35 years with metrorrhagia
• Women <35 years with risk factors for endometrial cancer (obesity, diabetes, PCOS, Lynch syndrome)
• Women with recurrent anovulation
• Women with excessive bleeding unresponsive to medical therapy

Critical caveat: A negative endometrial biopsy in a symptomatic patient has a 10% false-negative rate and must be followed by fractional D&C under anesthesia 1

Imaging Studies

• Transvaginal ultrasound is the first-line imaging modality for structural assessment 2, 4
• Saline infusion sonohysterography or hysteroscopy provides superior evaluation for endometrial polyps and submucosal fibroids, which are insufficiently diagnosed by ultrasound alone 4
• MRI provides superior evaluation of adenomyosis 2

Coagulation Studies

• Evaluate for von Willebrand disease and other coagulopathies in women with menorrhagia plus bleeding from other sites (epistaxis, easy bruising, prolonged bleeding after dental procedures) 2

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Treatment Approach

First-Line Medical Management

Medical management should be trialed before any invasive intervention. 3

Hormonal Options

• Levonorgestrel intrauterine device (LNG-IUD) is first-line treatment, demonstrating high effectiveness for reducing heavy menstrual bleeding with efficacy comparable to endometrial ablation or hysterectomy 3, 8, 4
• Combined oral contraceptives are effective for regulating cycles and reducing bleeding 3, 8
• Oral progestins for 21 days per month are effective for ovulatory bleeding 5. However, cyclic progestogens do NOT significantly reduce menstrual bleeding in women who ovulate 4

Non-Hormonal Options

• Tranexamic acid (antifibrinolytic agent) reduces menstrual blood loss by 20-60% 8, 4, 6
• NSAIDs (particularly mefenamic acid) reduce menstrual blood loss by 20-60% and provide symptomatic relief 3, 4, 6

Surgical Management

Surgical treatment is indicated after failure of medical management or when clear structural causes are identified. 9, 5

Conservative Surgical Options

• Hysteroscopic myomectomy is the treatment of choice for submucosal pedunculated fibroids <5 cm, with shorter hospitalization and faster recovery 8
• Hysteroscopic polypectomy for endometrial polyps 5
• Endometrial ablation is an option for women who do not desire future pregnancy, with >95% patient satisfaction 8, 6
• Uterine artery embolization (UAE) is an alternative to surgery with high clinical success, though 20-25% symptom recurrence occurs at 5-7 years 3, 8

Definitive Treatment

• Hysterectomy is the most definitive treatment with 90% satisfaction at 2 years, but should be reserved for failed medical management or when fertility is complete 3, 8, 5

Special Population Considerations

• In women with severe thrombocytopenia, oral progestins may be useful, but avoid depot medroxyprogesterone acetate (DMPA) due to irregular initial bleeding and 11-13 week irreversibility 8
• Progestins should not be used for more than 6 months to prevent meningioma development 8
• In women with endometrial hyperplasia without atypia, treat with cyclic or continuous progestin 5
• Women with hyperplasia with atypia or adenocarcinoma require referral to gynecologist or gynecologic oncologist 1, 5