Abnormal uterine bleeding : mechanisms and management
Luteal regression progesterone withdrawal, vasoconstriction of uterine vessels with ischaemia, hypoxia, necrosis are important events in the initiation of menstruation. Local factors, possibly released from endometrial inflammatory type cells, may also be involved. A family of enzymes, matrix metalloproteinases, identified within human endometrium are involved in tissue breakdown via actions on the extracellular matrix. Vasoactive substances, such as vascular endothelial growth factor, which stimulate angiogenesis are also present within the endometrium. Both factors may be important in initiation and regulation of menstruation, and have a role to play in the aetiology of abnormal uterine bleeding. Exogenous sex steroid hormones, oestrogen and progestogen, are commonly prescribed as contraceptives or hormone replacement therapy. Breakthrough bleeding is a common side-effect limiting their use. This thesis aims to identify local endometrial factors which may be involved in breakthrough bleeding in pre and post menopausal women exposed to hormone replacement and the levonorgestrel intrauterine releasing system. Expression of endometrial sex steroid receptors, matrix metalloproteinases (MMPs); and vascular endothelial growth factor (VEGF) will be identified. Menorrhagia, blood loss over 80 ml per cycle, leads to significant morbidity but is rarely measured out with clinical trials. Endometrial gland apoptosis is increased in women with such subjectively heavy losses. This thesis will identify if this increase is also seen in women with objectively measured menorrhagia when the endometrium is otherwise histologically normal. The management of women with aberrant patterns of uterine bleeding is based on endometrial assessment. This thesis will look particularly at a new method of endometrial sampling, the Tao Brush compared to the gold standard outpatient sampling device, the Pipelle. A clearer understanding of the role of these local control mechanisms, an improved ability to identify women with heavy blood losses and better sampling methods will allow rational and effective management of women with abnormal uterine bleeding.