Endometriotic disease: the role of peritoneal fluid

Peritoneal fluid and the intraovarian milieu are a specific microenvironmen t. Peritoneal fluid originates mainly as an ovarian exudation product cause d by increased vascular permeability, with cyclic variation in volume and s teroid hormones which are always higher than in plasma, It contains large a mounts of macrophages and their secretion products, and has a large exchang e area with plasma through the peritoneum? which is highly permeable for sm all molecules, Diffusion becomes virtually zero for molecules,vith a molecu lar weight of >100 000 Da, In women with the luteinized unruptured follicle (LUF) syndrome, concentrations of oestrogens and progesterone are much low er in the luteal phase. Endometriosis is associated with sterile low-grade inflammation, increased concentrations of activated macrophages and many of their secretions, such as cytokines, growth factors and angiogenic factors . Concentrations of CA-125 and of glycodelins are also increased, secreted locally by the endometrial cells, Natural killer (NK) cell function decline s, possibly mediated by glycodelins or local intercellular adhesion molecul e (ICAM)-1 shedding, The ovary is also a specific microenvironment, with st eroid hormone concentrations 1000-fold higher in follicles than in plasma, Endometrial and superficially implanted cells are influenced by peritoneal fluid concentrations so that local environment, rather than inherent cellul ar differences could explain differences between superficial endometriosis and eutopic endometrium. Differences between superficial implants and endom etriotic disease, deep infiltrating or cystic ovarian endometriosis, may th us arise via different endocrine environments. Superficial endometrial impl ants are regulated by peritoneal fluid factors, whereas deep endometriosis and cystic ovarian endometriosis are influenced by blood or ovarian factors . The endometriotic disease theory considers superficial endometriotic impl ants and their remodelling as a physiological process in most women, and co ncentrates on the causes of severe endometriosis such as differences in the eutopic endometrium from women with and without endometriosis (which may i ndicate hereditary differences), the invasiveness of some endometriotic cel ls irt vitro, focal 'shielding' of endometriotic foci by adhesions, and inh ibition of NK activity by ICAM-1 and glycodelins. Endometriotic disease is thus seen as a benign tumour, The type of cellular lesion, hereditary and i mmunological environments and local hormone concentrations in the ovary and in peritoneal fluid, will decide expression as cystic ovarian endometriosi s, deep endometriosis or adenomyosis externa, and whether the latter is ass ociated with adhesions.