At this point in time we do not know what causes endometriosis. When considering the origin and manifestation of a disease we need to consider the factors that determine whether a woman develops the condition or not and, of those women who do develop
At this point in time we do not know what causes endometriosis. When considering the origin and manifestation of a disease we need to consider the factors that determine whether a woman develops the condition or not and, of those women who do develop the disease, the factors that determine how severe her disease ultimately is (how symptomatic, how aggressive, how invasive and how extensive).
Until now several theories of the origin and disease manifestation of endometriosis have been proposed. The aim of a theory of origin is to present an explanation that adequately accommodates all that we know about the disease. Generally, the best-fit theory is adopted and used to guide and predict treatments and outcomes. Over time if new information becomes available the best-fit theory may be surpassed or replaced by another competing theory or alternatively may be adapted in order to accommodate the new findings.
Perhaps one of the most popular and enduring theories of origin is that of retrograde menstruation, transportation, and implantation. This is the belief that endometriosis occurs through a process of endometrial tissue flowing back through the fallopian tubes during menstruation, entering the pelvic cavity and implanting and invading the surfaces of the pelvic structures.
Retrograde menstruation, however, is a common phenomenon that occurs in 90% of women yet only 10% of women develop endometriosis and the refluxed material only contains minimal deposits of endometrial tissue. Furthermore, endometriosis consists of tissue that is similar but not identical to the native endometrium that lines the uterus, suggesting that it is not a mere autotransplant. Other phenomena about the disease that cannot be adequately explained by this theory include the presence of endometriosis in stillborn female fetuses, in women without a functional uterus and in a small number of men undergoing treatment for prostate cancer. The theory of retrograde menstruation predicts that the disease will recur after surgery and worsen over time with each menstrual flow, yet surgical excision of endometriosis has been found to effectively remove the disease in most patients with true disease recurrence being rare. Studies examining the extent of disease across different age groups of patients have failed to find an increase in disease with age.
Research reveals that women with endometriosis are at increased risk of also having various autoimmune disorders, including allergies, systemic lupus erythematosus, Sjögren’s Syndrome, rheumatoid arthritis, and multiple sclerosis. Based on this finding a hybrid theory was developed that extends upon Sampson’s theory of retrograde menstruation. As mentioned above, retrograde menstruation occurs in around 90% of women yet only a minority ever develop endometriosis. It has been hypothesized that an underlying immune dysfunction interferes with the body’s natural ability to clear up this refluxed tissue from the pelvis and therefore the tissue is allowed to establish itself and proliferate, resulting in endometriosis. This line of argument suffers many of the same limitations as the original theory of retrograde menstruation. While autoimmune disorders are more common in women with endometriosis, many women with endometriosis do not have any such disorders. Another important question is whether immune dysfunction truly precedes the onset of endometriosis or rather is it a result of the disease process itself. Endometriosis triggers an ongoing immune response, which over time could moderate or disrupt immune function, altering an individual’s propensity to developing autoimmune disorders.
The theory of Mülleriosis is the notion that endometriosis is already laid down during embryonic development and remains dormant until later in life when changes in hormones (such as during puberty or pregnancy) trigger the disease to become active and symptomatic. During embryonic development tissue is laid down and differentiated into the various pelvic organs and structures that form the pelvis, including the reproductive organs. In women with endometriosis, something goes awry during this process and tissue that would ordinarily be restricted to the inside of the uterus ends up developing in locations outside the uterus. A helpful analogy is that of a chef who is following a recipe for a full course dinner. He has all of the right ingredients but the recipe contains mistakes and some of the ingredients that should belong in the starter end up in the desert and some ingredients intended for the dessert end up in the main course. In the development of the reproductive organs HOX genes determine which tissue develops where. It is possible that abnormalities in these genes, whether spontaneous or inherited, result in coding errors that in turn result in the presence of aberrant endometriotic tissue outside the uterus (endometriosis). This theory can explain why the disease has been observed in infants and prepubescent girls, as well as the presence of other types of aberrant tissue that may co-occur with endometriosis, such as endocervicosis (tissue similar to the cervix found outside the uterus) and endos