“Studying endometriosis is like nailing Jell-O to a tree.” Donna Vogel, MD, Ph.D., 2000
The origins of endometriosis include many concepts. For me from 1970 to 1992, the question of origin had one answer: retrograde dissemination of endometrium during menses, implantation during a window of opportunity, and growth.
In 1992, it was apparent that congenital misplacement was needed for some endometriosis. By 2016, I used five concepts and theories and the last time I counted, it took 23 concepts and theories to begin a discussion and many more to continue. Currently the window of opportunity is highest in adolescents. It can be speculated that it might be like acne and may have to do with neuroimmune maturation. There are more concepts, hypotheses, theories, and speculations than solid findings. There is no one answer that covers all the questions. The review covers some of the possibilities.
One concept of the origin is a discussion of the origin of the recognition of signs and symptoms. Nezhat et al. reviewed pelvic symptoms reported by Egyptians in 1855 BC. Knapp’s review of the 17th description of pelvic “ulcers” with symptoms suggesting endometriosis may be the first anatomic description. The first histologic description was by Rokitansky in 1860. There were many early names for “endometriosis” before this term was suggested by Sampson in 1925.
A second concept of origin regards the cell or substance of origin. The potential cells of origin included the endometrium, misplaced precursors during embryonic development, peritoneum undergoing metaplasia, and bone marrow stem cells. In addition to possible cells, there may be substances that induce metaplasia in other cell types. Those substances may be inflammatory products such as cytokines, Schwann cells, Levander substances or Merrill factor.
A third concept is how endometriosis, a mullerian disease, gets to a site outside of its expected mullerian area. For endometrium, that means mullerian-type tissue is outside of the uterine cavity where babies grow. A similar disease, adenomyosis, has that type of tissue outside the cavity but in the uterine muscular wall. When tissue like endometrium is found outside the uterus, it is commonly called endometriosis. However, Sampson noted that endometriosis was different than endometrium “both in structure and in function.” The common definition of “ectopic tissue like endometrium” does not include that the original tissue and endometriosis have biochemical, immunologic, epigenetic, and other differences. Alternate definitions include considerations for inflammation, fibrosis, epigenetic modifications, bleeding, and other characteristics. There is no single definition that satisfies all scientists, physicians, or patients.
The fourth concept is what causes the transition from a cell or origin to endometriosis. The initiator for that transition may be the inflammatory action of estrogens, withdrawal of progesterone preceding menses, infection, trauma and repair or other possibilities. The development of medicines or holistic health habits that prevent this transition may offer the best chance of preventing the progression of endometriosis. Early clinical diagnosis and treatment was associated with a limitation to mild endometriosis over 10.2 years by Knox, et al. None of the adolescent patients in that study developed moderate or severe endometriosis. Waiting 6 to 10 years for a diagnosis that requires surgery may be avoidable. Early treatment of pain is the correct management of pain and may decrease problems with endometriosis. Although this may not be useful for those with long delays and deep endometriosis, it might be for their daughters and other young adolescents.
As can be seen in the short summary, the origin of endometriosis is a complex subject. My monograph “Endometriosis Concepts and Theories” has more than 650 references for readers interested in research or in additional information.
References are available on request. Email danmartinmd@gmail.com