Although the exact cause is still unknown, there are a number of factors which influence the development of the disease. The most likely explanation is that women menstruate backwards through the tubes into the pelvis and the cells of the uterine lining then implant and grow. Although 70% of women do menstruate through the tubes, only 10% develop the disease so this is only a partial explanation of why it develops. The majority of women have a natural defence, killing the cells of the menstrual fluid before they implant.

Women who develop endometriosis have reduced ability to kill these cells or a reduced ability to stop their growth after they implant in the pelvis. These defence systems involve the immune system. Sometimes the disease will develop in the absence of the uterus and this must result from normal cells lining the pelvis changing to the same cells that line the uterus and thus forming endometriosis.

Much research is currently focused on the genetics of endometriosis. It appears that there is a genetic predisposition to endometriosis if a first degree female relative has endometriosis (mother or sister), the chance of developing endometriosis is 30%.