Table 1.

Causes of Abnormal Endometrial Bleeding

Primary Defect	Examples
Impaired hemostasis.	Von Willebrand’s disease and other primary disorders of clotting exacerbate normal menstrual bleeding.
Impaired hemostasis with some derangement in blood vessels.	Anovulatory bleeding – absence of progesterone effects results in reduced endometrial stromal cell tissue factor and plasminogen activator inhibitor-1 production, increased matrix metalloproteinase activity and increased angiogenic factor expression. This creates vascular instability with greatly impaired hemostasis, each predisposing to break-through bleeding.
Aberrant blood vessels with normal hemostasis.	Long-term, progestin-only contraceptives reduce endometrial blood flow, and the resultant hypoxia and reactive oxygen species drive expression of angiogenic factors and perivascular MMP-2 production. This creates large, fragile, easily fractured superficial endometrial blood vessels held in place by a collapsing stromal extracellular matrix that promotes intermittent bleeding.
Aberrant blood vessels with normal hemostasis.	Myomas – are associated with long-standing increased angiogenesis and an increasingly estrogenic milieu which leads to dilated veins (venule ectasia) and increased arterial flow promoting menorrhagia.
Aberrant blood vessels with normal hemostasis.	Polyps – are associated with increased angiogenesis and focal vascular abnormalities leading to metorrhagia.