It is not clear at what stage the transformation of endometrium, or any cell of origin such as stem cells or coelomic cells (see those theories below), to endometriosis begins.Proofs in support of the theory is based on retrospective epidemiological studies that an association with endometrial implants attached to the peritoneal cavity, which would develop into endometrial lesions and retrograde menstruation; and the fact that animals like rodents and non-human primates whose endometrium is not shed during the estrous cycle dont develop naturally endometriosis contrary to animals that have a natural menstrual cycle like rhesus monkeys and baboons.Retrograde menstruation alone is not able to explain all instances of endometriosis, and additional factors such as genetics, immunology, stem cell migration, and coelomic metaplasia (see "Other theories" on this page) are needed to account for disseminated disease and why many individuals with retrograde menstruation are not diagnosed with endometriosis. In addition, endometriosis has shown up in people who have never experienced menstruation including cisgender men, fetuses, and prepubescent girls. Further theoretical additions are needed to complement the retrograde menstruation theory to explain why cases of endometriosis show up in the brain and lungs. This theory has numerous other associated issues.Researchers are investigating the possibility that the immune system may not be able to cope with the cyclic onslaught of retrograde menstrual fluid. In this context there is interest in studying the relationship of endometriosis to autoimmune disease, allergic reactions, and the impact of toxic materials.
Historically, women with these symptoms were treated with leeches, straitjackets, bloodletting, chemical douches, genital mutilation, pregnancy (as a form of treatment), hanging upside down, surgical intervention, and even killing due to suspicion of demonic possession. Hippocratic doctors recognized and treated chronic pelvic pain as a true organic disorder 2,500 years ago, but during the Middle Ages, there was a shift into believing that women with pelvic pain were mad, immoral, imagining the pain, or simply misbehaving. The symptoms of inexplicable chronic pelvic pain were often attributed to imagined madness, female weakness, promiscuity, or hysteria. The historical diagnosis of hysteria, which was thought to be a psychological disease, may have indeed been endometriosis. The idea that chronic pelvic pain was related to mental illness influenced modern attitudes regarding individuals with endometriosis, leading to delays in correct diagnosis and indifference to the patients true pain throughout the 20th and into the 21st century.Hippocratic doctors believed that delaying childbearing could trigger diseases of the uterus, which caused endometriosis-like symptoms. Women with dysmenorrhea were encouraged to marry and have children at a young age. The fact that Hippocratics were recommending changes in marriage practices due to an endometriosis-like illness implies that this disease was likely common, with rates higher than the 5-15% prevalence that is often cited today.