Uterine bleeding is part of a complex process that includes the activation of homeostatic mechanisms coupled to regeneration of the uterine lining. The cell biology of normal menstruation is not completely understood. Recent evidence suggests that hormone withdrawal leads to down regulation of uterine cell genes that control growth and differentiation, programmed cell death, and the coordinated release of matrix metalloproteinases and other proteins that degrade and remodel the extracellular matrix and promote stem cell proliferation leading to regeneration of the uterine lining. The endometrium also produces proteins that govern homeostasis in a hormonally controlled fashion. These processes may become deregulated when ovarian hormone production is suboptimal during puberty or the perimenopausal period, when anovulatory cycles are associated with irregular and/or excessive bleeding. Furthermore, the mechanisms of the abnormal bleeding that leads women to discontinue the use of contraceptives such as IUDs and “progestin-only” methods are known to be different from those associated with normal menses.
Although primary cultures of uterine cells and malignant endometrial cell lines have been investigated for a number of years, systems that replicate the complex interaction between epithelial, stromal, and vascular cells of the uterus have yet to be devised. This has thwarted the cellular and molecular exploration of the process of normal menstruation and dysfunctional uterine bleeding. This difficulty is further complicated by the lack of appropriate animal models for abnormal bleeding.