Endometriosis is a condition where tissue similar to the uterine lining, the endometrium, grows outside the uterus. These growths are most often found in the pelvic region but can appear elsewhere. The pathophysiology of endometriosis explains the functional changes caused by the disease, including how these misplaced tissues establish themselves, grow, and produce symptoms.
Theories on the Origin of Endometrial Lesions
The most widely accepted theory for endometriosis is retrograde menstruation. This suggests that during menstruation, some endometrial cells flow backward through the fallopian tubes into the pelvic cavity. Instead of being cleared away, these cells attach to pelvic organs and grow. For endometriosis to develop from this common process, the cells must also evade the immune system and establish a blood supply.
Other theories propose different origins. Coelomic metaplasia suggests that cells lining the pelvic organs can transform into endometrial-like cells. The Müllerian remnant theory posits that endometrial tissue develops from leftover embryonic cells. Researchers are also investigating the role of stem cells in forming this ectopic tissue. The development of endometriosis is likely not due to a single cause, but a combination of factors.
The Role of Hormones and Inflammation
Once established, the growth of endometrial lesions is driven by hormones, particularly estrogen. Estrogen fuels the proliferation of these ectopic tissues, which explains why symptoms often align with the menstrual cycle. This dependency is also why treatments frequently aim to suppress ovarian function. The lesions can also produce their own estrogen by expressing an enzyme called aromatase, creating a local supply that stimulates further growth.
This hormonal activity is linked to chronic inflammation. The ectopic tissues produce inflammatory substances, such as prostaglandins and cytokines, creating a self-perpetuating cycle. This inflammation helps the lesions survive and spread while also directly causing pain. The pelvic environment in women with endometriosis is rich in these inflammatory mediators.
Immune System Dysfunction
The persistence of endometrial lesions is linked to an altered immune response. A healthy immune system would recognize and eliminate cells growing in abnormal locations. In endometriosis, this surveillance system breaks down, making the body less effective at clearing the displaced endometrial cells.
This dysfunction involves several immune cells. For instance, natural killer (NK) cells show reduced effectiveness in destroying abnormal cells. Similarly, macrophages, which normally clean up cellular debris, may behave differently, promoting inflammation and cell growth instead of removing the ectopic tissue. This altered immune environment allows the endometrial implants to survive and thrive within the pelvic cavity.
Mechanisms of Pain and Infertility
The pain from endometriosis stems from inflammatory and neurological factors. The chronic inflammation created by the lesions irritates surrounding tissues and nerve endings. Over time, lesions can develop their own nerve supply, a process called neurogenesis, increasing their sensitivity. These nerves are continuously stimulated by inflammatory mediators, leading to chronic pelvic pain and painful periods.
Infertility can result from mechanical and biochemical disruptions. Adhesions and scar tissue from chronic inflammation can distort pelvic anatomy, blocking fallopian tubes or interfering with ovulation. The inflammatory environment within the pelvis is also biochemically hostile to reproduction. This can impair both fertilization and the successful implantation of an embryo.