Non-Structural Causes of Abnormal Uterine Bleeding
The non-structural causes of AUB are classified by the COEIN acronym: Coagulopathy, Ovulatory dysfunction, Endometrial disorders, Iatrogenic causes, and Not yet classified. 1, 2, 3
The COEIN Classification System
The FIGO PALM-COEIN system divides AUB into structural (PALM) and non-structural (COEIN) etiologies, with COEIN representing conditions that cannot be assessed by imaging. 1, 3
C - Coagulopathy
- Includes inherited and acquired bleeding disorders that affect hemostasis 1, 3
- Von Willebrand disease is the most common coagulopathy causing AUB, though often underdiagnosed 4, 5
- Adolescents presenting with menorrhagia should be screened for coagulopathies until proven otherwise 5
- Other coagulation disorders include platelet dysfunction, factor deficiencies, and acquired conditions from anticoagulation therapy 1, 6
- Approximately 70% of women on anticoagulation therapy experience heavy menstrual bleeding 6
O - Ovulatory Dysfunction
- Represents anovulatory bleeding patterns that lead to irregular, unpredictable bleeding 2, 3
- Common causes include polycystic ovary syndrome (PCOS), which is the most frequent etiology 7, 4
- Endocrine disorders causing anovulation: uncontrolled diabetes mellitus, thyroid dysfunction (both hypothyroidism and hyperthyroidism), and hyperprolactinemia 2, 4
- Hypothalamic dysfunction from stress, excessive exercise, or eating disorders 2
- Premature ovarian failure and primary pituitary disease 2
- Medications affecting ovulation: antipsychotics and antiepileptics 4
- Perimenopausal women commonly experience anovulation as a cause of AUB 3, 6
E - Endometrial Disorders
- Primary endometrial disorders involve molecular deficiencies in the regulation of endometrial hemostasis 1, 6
- These represent local endometrial factors affecting bleeding control mechanisms at the cellular level 1
- Distinct from structural endometrial pathology like polyps or hyperplasia 8
I - Iatrogenic
- Bleeding caused by exogenous gonadal steroids (hormonal contraceptives, hormone replacement therapy) 1, 3
- Intrauterine devices (IUDs), particularly copper IUDs, can cause increased bleeding 1, 6
- Anticoagulant medications (warfarin, direct oral anticoagulants, heparin) 1, 5
- Antiplatelet agents (aspirin, clopidogrel) 6
- Other medications: digitalis, phenytoin, hypothalamic depressants 5
- Tamoxifen use increases risk of endometrial pathology and bleeding 6
N - Not Yet Classified
- Represents other causes that don't fit into the above categories 1, 3
- May include rare or poorly understood etiologies requiring further investigation 9
Critical Diagnostic Considerations
Before diagnosing non-structural AUB, pregnancy must be excluded in all reproductive-age women using β-hCG testing. 2, 6
Essential Laboratory Workup
- Thyroid-stimulating hormone (TSH) and prolactin levels should be measured to exclude endocrine causes 2, 6
- Coagulation screening is mandatory for adolescents with menorrhagia, women with high-risk factors, and those failing medical or surgical therapy 5
- Complete blood count to assess for anemia from chronic blood loss 8
Key Clinical Pitfall
Non-structural causes cannot be diagnosed by imaging—they require clinical history, physical examination, and targeted laboratory testing. 1 Imaging is used to exclude structural pathology, not to diagnose COEIN causes. 1, 3
Age-Specific Considerations
- Adolescents: Coagulopathy should be the primary consideration until proven otherwise 5
- Reproductive age: Ovulatory dysfunction (especially PCOS) and iatrogenic causes are most common 3, 4
- Perimenopausal women: Anovulation is frequent, but endometrial sampling is needed at lower thresholds due to increased cancer risk 2, 3
- Postmenopausal women: Any bleeding requires evaluation for malignancy, though systemic causes should still be considered 3, 6