Endometriosis and Angiogenesis
Endometriosis and Angiogenesis
Professor Stephen K. Smith
Head of the Department of Obstetrics & Gynaecology, University of Cambridge,
member Endozone Editorial Advisory Board
Whilst the problem of endometriosis may becoming more known by the general
public, the cause of the disease remains unclear. Several points seem to be
- Retrograde menstruation increases the chances of developing the disease
- All women who menstruate can have endometrium in the peritoneal cavity
- It is not known why some of these women go on to develop endometriosis
One suggestion is that either because of the tissue itself or because of
other factors in the peritoneal cavity, women who develop the disease have a
higher capacity to grow blood vessels around the explants compared to women who
do not get the disease.
The process of new blood vessel development is called angiogenesis.
Peritoneal fluid taken from women with endometriosis has a greater ability to
stimulate endothelial cell proliferation than fluid removed from women without
the disease. This fluid contains several agents known to stimulate new blood
vessel development. The levels of one of these agents, vascular endothelial cell
growth factor (VEGF-A) is increased in the fluid when fresh tissue is deposited
at menstruation. Other agents including tumour necrosis factor (TNF) are also
increased in the fluid in women with the disease compared to women who do not
have the disease.
The source of these agents is interesting. Increased amounts of protein are
not found in the explants themselves, rather cells of the immune system
(macrophages, t-lymphocytes and natural killer cells) seem to be the principal
source. It is not known if these agents are increased before the onset of the
disease or as a consequence of the disease.
Several studies have shown an abundant supply of blood vessels to the
endometriotic explants, at least those found on the peritoneal surface and on
the ovaries. In other situations, pieces of tissue will not survive if they are
larger than about 1 m 2. If they are to survive, they need to develop a blood
supply. Presumably this basic physiological tenant still applies to
There is considerable interest in the field of cancer for attacking these
blood vessels as a means of preventing the growth of tumours. A similar strategy
may be successful for endometriosis. Normal angiogenesis occurs in adults in
wound healing but otherwise, endothelial cells are quiescent and may last for
two to three years. This is not the case in the endometrium. Along with the
ovary, this is a privileged site where physiological angiogenesis occurs on a
monthly basis. It is this need of the tissue to re-grow on a monthly basis that
may be making endometrium so effective in growing at ectopic sites.
Whilst this work is very new (if not the idea), it may be possible to develop
treatments that block blood vessel growth and cause the regression of
endometriotic nodules. This treatment could be given alone or after surgical
removal of significant deposits of endometriosis. The results of studies in our
laboratories and those of others may thus lead to new treatment options for
women with endometriosis.
Professor Stephen Smith was appointed Head of the Department of Obstetrics
& Gynaecology at the University of Cambridge in 1988 and has obtained
research grants worth over £6M. He is Head of Service for Women's Health at
Addenbrooke's Hospital. He is a Fellow of the Royal College of Obstetricians
& Gynaecologists, a Fellow of the Institute of Biology, and a member of many
learned societies. He is a member of the Scientific Steering Committee of the
World Health Organisation, a member of the Organising Committee for the World
Congress of Endometriosis 2000, and President of the Board of Trustees of The
National Endometriosis Society. Professor Smith is a leading expert on the
subject of endometriosis and is invited to give lectures all over the world. He
has over 180 publications in peer reviewed journals.