Differential Diagnosis of Prolonged Menstruation
Prolonged menstruation (>7 days) requires systematic evaluation for structural, hormonal, coagulopathic, iatrogenic, and systemic causes, with pregnancy and malignancy being the most critical to exclude immediately. 1, 2
Structural/Anatomic Causes
- Uterine fibroids (leiomyomas) - particularly submucosal fibroids that distort the endometrial cavity 2, 3
- Endometrial or endocervical polyps - benign growths that cause irregular bleeding patterns 2, 4
- Adenomyosis - endometrial tissue within the myometrium, more common in perimenopausal women 3, 5
- Endometrial hyperplasia - from prolonged unopposed estrogen stimulation 6, 4
- Endometrial or cervical malignancy - must be excluded, especially in women >35 years or with risk factors 2, 4
- Intrauterine device (IUD) complications - particularly copper IUD displacement or malposition 7, 2
Hormonal/Endocrine Causes
- Anovulatory bleeding/dysfunctional uterine bleeding - disruption of the hypothalamic-pituitary-ovarian axis leading to irregular endometrial shedding 8, 4
- Polycystic ovary syndrome (PCOS) - chronic anovulation with prolonged unopposed estrogen 9, 4
- Thyroid dysfunction (hypothyroidism or hyperthyroidism) - affects menstrual regularity and flow 8, 4
- Hyperprolactinemia - from pituitary adenomas or medications 8, 4
- Relative Energy Deficiency in Sport (RED-S) - paradoxically can cause both amenorrhea and irregular prolonged bleeding in female athletes 10, 9
- Perimenopausal transition - erratic ovulation leading to irregular bleeding patterns, especially ages 40-50 5
Coagulopathies
- Von Willebrand disease - the most common inherited bleeding disorder, present in up to 20% of women with heavy menstrual bleeding 2, 4
- Platelet dysfunction or thrombocytopenia - requires complete blood count with platelet assessment 2, 8
- Other inherited coagulation disorders - Factor deficiencies, though less common 2
Iatrogenic/Medication-Related Causes
- Hormonal contraceptives - particularly progestin-only methods (implants, IUDs) causing irregular bleeding patterns 7, 11
- Anticoagulant therapy - warfarin, NOACs (rivaroxaban particularly associated with prolonged menstrual bleeding) 12
- Psychotropic medications - antipsychotics and antiepileptics that affect the hypothalamic-pituitary axis 8, 4
- Intrauterine devices - copper IUDs commonly cause heavy/prolonged bleeding, especially in first 3-6 months 7, 2
Systemic/Medical Conditions
- Pregnancy complications - incomplete spontaneous abortion, ectopic pregnancy, or gestational trophoblastic disease 2, 8
- Chronic liver disease - impairs estrogen metabolism and coagulation factor synthesis 8
- Chronic kidney disease - causes platelet dysfunction and uremic bleeding 8
- Diabetes mellitus - particularly when uncontrolled, affects ovulatory function 8, 4
- Morbid obesity - causes abnormal estrogen cycling from peripheral conversion 8
Infectious Causes
- Pelvic inflammatory disease (PID) - from sexually transmitted infections causing endometritis 1, 2
- Chronic endometritis - can cause irregular bleeding patterns 6
Critical Pitfalls to Avoid
Always rule out pregnancy first - perform hCG testing in all reproductive-age women before pursuing other diagnoses 2, 3. Screen for cervical pathology early with speculum examination and Pap smear to exclude cervical cancer or dysplasia 8, 3. Consider endometrial sampling in women ≥35 years with recurrent anovulation, women <35 with endometrial cancer risk factors, or any woman with bleeding unresponsive to medical therapy 4. Don't overlook coagulopathies - obtain detailed bleeding history (easy bruising, gum bleeding, family history) and consider coagulation studies when clinically indicated 2.