Objectives: To review the morphological and molecular events responsible for uterine bleeding in health and disease.
Methods: Review of pertinent literature focusing on the histology and pathophysiology of normal and abnormal uterine bleeding (AUB).
Results: The seat of normal menstrual bleeding is located in the upper two-thirds of the endometrial mucosa and is recognized by tissue necrosis, disruption of microvasculature, migratory leukocytes and platelet/fibrin thrombi in microvessels. The molecular events responsible for tissue and vascular breakdown are related to the release of proteolytic lysosomal enzymes of endometrial cell and inflammatory cell origin. In cases of AUB, tissue breakdown is located in the superficial layer (subsurface) of the endometrium. It is either focal (breakthrough bleeding) or diffuse (withdrawal bleeding). It is initiated by either chronic endometritis and/or microerosions or vascular fragility due to structural abnormalities of microvessels. Endometritis and microerosions occur in otherwise normal endometrium, polyps, submucosal leiomyomata, atrophy and cancer (organic causes). Primary vascular alterations are found in hyperestrogenic-type endometria, i.e. anovulatory dysfunctional uterine bleeding (DUB) and progestational-type endometrium, i.e. progestational contraceptives and combined, continuous hormonal replacement therapy (HRT) (non-organic causes). Ovulatory DUB and coagulation disorders are not appreciated histologically. These are related to impaired vasoconstriction and fibrinolysis and impaired coagulation factors, respectively.
Conclusions: Histology may contribute to better understanding of the mechanisms of action that initiate, regulate and lead to AUB. Better insight may trigger in the development of therapeutic procedures that could either prevent or control vascular breakdown which results in unexpected uterine bleeding.