What are the differential diagnoses for a female patient of reproductive age presenting with persistent heavy menstrual bleeding?

Differential Diagnoses for Heavy Menstrual Bleeding in Reproductive-Age Women

The differential diagnosis for persistent heavy menstrual bleeding in a reproductive-age woman should be systematically organized using the PALM-COEIN classification system, which divides causes into structural (PALM) and non-structural (COEIN) etiologies. 1, 2, 3

Structural Causes (PALM)

P - Polyp (Endometrial Polyps)

• More common in women over 40 years of age 2, 4
• Can be visualized on transvaginal ultrasound, though saline infusion sonohysterography has 96-100% sensitivity for detection 2

A - Adenomyosis

• Frequent cause in premenopausal women, particularly those in their 40s 2, 3
• Presents with heavy menstrual bleeding, dysmenorrhea, and dyspareunia 3
• Can be visualized on imaging studies 2

L - Leiomyoma (Uterine Fibroids)

• Most common structural cause in women under 40 years of age 2, 4
• Submucous fibroids are particularly associated with heavy bleeding 1

M - Malignancy and Hyperplasia

• Endometrial hyperplasia or carcinoma must be excluded 1, 2
• Most serious etiology, particularly in postmenopausal women 2
• Risk factors include obesity, diabetes, hypertension, unopposed estrogen exposure, tamoxifen use, and Lynch syndrome 2

Non-Structural Causes (COEIN)

C - Coagulopathy

• Up to 20% of women with heavy menstrual bleeding have an underlying inherited bleeding disorder 5
• Von Willebrand disease is more common than many physicians realize 6
• All adolescents with menorrhagia should be screened for coagulopathy until proven otherwise 6
• Clots ≥1 inch diameter, low ferritin, and "flooding" (changing pad/tampon more frequently than hourly) predict bleeding disorders 7

O - Ovulatory Dysfunction

• Includes oligo-ovulation and anovulation causing irregular, heavy bleeding 1, 2
• Underlying causes to evaluate include: 1
  • Adolescence and perimenopause
  • Hyperandrogenic conditions (PCOS)
  • Hypothalamic dysfunction
  • Hyperprolactinemia
  • Thyroid disease
  • Primary pituitary disease
  • Premature ovarian failure

E - Endometrial

• Primary endometrial disorders with molecular deficiencies in regulation of endometrial hemostasis 2
• Local endometrial dysfunction without structural abnormality 1

I - Iatrogenic

• Approximately 70% of women on anticoagulation therapy experience heavy menstrual bleeding 2, 3
• Oral anticoagulants (particularly rivaroxaban) cause abnormal bleeding in 9-14% of reproductive-age women, with prolonged bleeding (>8 days) in 27% 2
• Intrauterine devices (copper IUD can worsen bleeding) 2
• Exogenous gonadal steroids 2
• Antiplatelet therapy 2

N - Not Yet Classified

• Other causes not fitting into above categories 2

Critical Diagnostic Pitfalls to Avoid

• Always perform pregnancy testing first in all reproductive-age women—pregnancy complications (threatened abortion, ectopic pregnancy, trophoblastic disease) must be excluded 3, 6
• Women with personal or family history of bleeding, flooding, or prolonged menses require hematology referral for coagulopathy evaluation 7
• Endometrial biopsy combined with vaginal sonography is reliable for hyperplasia/carcinoma but insufficient for diagnosing polyps and fibroids—these require sonohysterography or hysteroscopy 4
• Cervical pathology (polyps, erosion, cervicitis, malignancy) must be excluded by speculum examination 2, 6
• Systemic diseases including hypothyroidism, cirrhosis, and coagulation disorders can present as heavy menstrual bleeding 6