Causes of Metrorrhagia
Primary Classification Framework
Metrorrhagia (irregular uterine bleeding) should be systematically evaluated using the PALM-COEIN classification system, which divides causes into structural (PALM) and non-structural (COEIN) etiologies. 1, 2, 3
Structural Causes (PALM)
The structural causes represent discrete anatomic abnormalities that can be visualized on imaging or hysteroscopy:
Polyps: Endometrial polyps are benign growths that protrude into the uterine cavity and cause irregular bleeding 2, 4, 5
Adenomyosis: Endometrial tissue within the myometrium, frequently coexisting with fibroids, presenting with heavy menstrual bleeding, dysmenorrhea, and dyspareunia, particularly common in women in their 40s 2, 3
Leiomyoma (Fibroids): Benign smooth muscle tumors, especially submucosal fibroids that distort the endometrial cavity 2, 4, 6
Malignancy and Hyperplasia: Endometrial hyperplasia (with or without atypia), endometrial cancer, cervical cancer, vaginal cancer, vulvar cancer, oviduct malignancies, and granulosa theca cell ovarian tumors 2, 4, 6
Non-Structural Causes (COEIN)
These causes do not involve discrete anatomic lesions:
Coagulopathy: Bleeding disorders, most commonly von Willebrand disease, which should be suspected in all adolescents with menorrhagia and women with high-risk factors 7, 5, 6
Ovulatory Dysfunction: Chronic anovulation from polycystic ovary syndrome, uncontrolled diabetes mellitus, thyroid dysfunction (hypothyroidism), hyperprolactinemia, and use of antipsychotics or antiepileptics 1, 7, 6
Endometrial: Primary endometrial disorders not related to structural pathology 2, 3
Iatrogenic: Sex steroids, hypothalamic depressants, digitalis, phenytoin, anticoagulants, and intrauterine contraceptive devices 6
Not yet classified: Causes that don't fit into other categories 2, 3
Additional Systemic and Infectious Causes
Beyond the PALM-COEIN framework, consider:
Pregnancy-related complications: Threatened, incomplete, or missed abortion; ectopic pregnancy; trophoblastic disease; placental polyp; subinvolution of the placental site (pregnancy must be excluded first in all reproductive-age women) 3, 7, 6
Infections: Endometritis, salpingitis, severe vaginal infections 4, 6
Systemic diseases: Cirrhosis, coagulation disorders beyond primary coagulopathies 6
Traumatic lesions: Vaginal trauma, foreign bodies 6
Cervical pathology: Cervical polyps, cervical erosion, cervicitis, cervical ectropion 4, 6
Critical Diagnostic Principles
Three age-based rules must guide your evaluation:
Any abnormal bleeding in reproductive-age women should be considered pregnancy-related until proven otherwise 6
Any abnormal bleeding in perimenopausal or postmenopausal women should be considered malignancy until proven otherwise 6
Menorrhagia in adolescents should be attributed to coagulopathy until proven otherwise 6
Dysfunctional Uterine Bleeding
When all organic, iatrogenic, and systemic causes have been excluded through appropriate evaluation, the diagnosis of dysfunctional uterine bleeding (DUB) is made by exclusion. 1, 7, 6 This represents anovulatory or ovulatory bleeding without identifiable structural or systemic pathology.