The pathophysiology of dysfunctional uterine bleeding

Dysfunctional or abnormal uterine bleeding is a common but significant problem in women’s health. Women may be affected at various times throughout their reproductive years due to the different types of abnormal uterine bleeding that can occur. Some of the causes include bleeding disorders such as Von Willebrand’s disease and thrombocytopenia or anatomical problems such as the presence of uterine leiomyomas, polyps, adenomyosis, or cancer. Hormonal disturbances due to anovulation can cause abnormal uterine bleeding in perimenarcheal girls or women entering the perimenopause. The use of more effective, long-acting progestin contraceptives has also led to an increased incidence of abnormal uterine bleeding in women. This chapter focuses on the cellular and molecular mechanisms that are thought to contribute to the etiology of abnormal uterine bleeding. An overview of the normal menstrual cycle is first presented. A review of current hypotheses for two main causes of abnormal uterine bleeding, first in response to hormonal disturbances due to anovulation or progestinonly contraceptives and, secondly, due to anatomical factors, will follow. This overview will highlight the importance of matrix metalloproteinases (MMPs) and local changes in the immune environment within the endometrium in regulating the structural integrity of the cell and vascular structures. Loss of this structural integrity appears to be the underlying causative factor in the onset of abnormal uterine bleeding, regardless of the initial abnormality. An increased understanding of the mechanisms involved in blood vessel destabilization and bleeding in the endometrium will lead clinicians to explore new types of therapies for treatment of this condition.