Steroids and endometrial breakthrough bleeding: future directions for research.

Abnormal endometrial bleeding continues to be a significant problem for women using long-acting gestagens and not only reduces the use of these agents, thus restricting the options available to women, but also reduces the quality of their lives. This symposium addressed a range of basic and clinical studies that have tried over the past 3 years to define the problem. Two areas have been identified. The first is the structure of the blood vessels themselves and the second is the environment of the endometrium in relation to these vessels. This reflects a shift in research interest away from factors that simply control epithelial-mesenchyme interactions. The expression of angiogenic inhibitors and stimulators is being defined and the critical role of the matrix and the immunocompetent cells of the endometrium elucidated. The disappointing results of simple oestrogen supplementation were confirmed. Three broad areas of research were considered to be important for future studies. The first of these is not related to molecular and cellular function but rather to understanding better the attitudes of women to vaginal bleeding in the multicultural diverse situations in which this event occurs. It was recognized that a broader constituency was not interested in this problem with the increasing use of continuous combined regimes of hormone replacement therapy in the developed world. Studies that listen to and educate women about this problem are needed to ensure that these techniques are felt to be better owned by the women themselves. Molecular and cellular studies were identified that attempted to define the factors necessary for the development and maintenance of healthy, non-leaky vessels. These included studies of the pro- and anti-angiogenic agents expressed in endometrium and a definition of their interactions with matrix metalloproteinases in maintaining vessel integrity. Finally there was recognition of the need to understand how neutrophils traffic through the endometrium and to determine how they effect endometrial bleeding.