Endometriosis doesn’t have a single known cause. Instead, several biological mechanisms likely work together to produce the disease, which affects roughly 10% of women of reproductive age worldwide. Despite decades of research, no one theory fully explains every case, and most experts now believe endometriosis results from a combination of genetic predisposition, immune system dysfunction, hormonal activity, and environmental exposures.
Retrograde Menstruation: The Oldest Theory
The most widely cited explanation is retrograde menstruation, first proposed in the 1920s. During a normal period, most menstrual blood exits the body through the cervix. In retrograde menstruation, some of that shed tissue flows backward through the fallopian tubes and spills into the pelvic cavity. Once there, fragments of endometrial tissue can attach to the surfaces of organs like the ovaries, bladder, or bowel and begin growing.
The problem with this theory on its own is that retrograde menstruation happens in up to 90% of menstruating women, yet only a fraction develop endometriosis. Something else has to determine why the tissue successfully implants in some women and gets cleared away in others. That “something else” appears to involve the immune system, hormones, and genetics, all of which are covered below. Retrograde menstruation also can’t explain rare cases of endometriosis in locations far from the pelvis, or cases that develop before a person ever has a period.
How the Immune System Fails to Clear Stray Tissue
In a healthy immune response, the body’s cleanup crew, particularly macrophages and natural killer (NK) cells, would identify and destroy tissue growing where it doesn’t belong. In women with endometriosis, this cleanup process is compromised in multiple ways.
Macrophages in the pelvic fluid of women with endometriosis are present in higher numbers than normal, yet they have reduced ability to actually destroy the rogue cells. As the disease progresses, these immune cells increasingly shift toward an anti-inflammatory state, pumping out signals that suppress the activity of other immune fighters rather than attacking the ectopic tissue. Essentially, the macrophages switch from attack mode to tolerance mode.
NK cells face a similar problem. In women with endometriosis, NK cells carry more inhibitory receptors on their surfaces, which act like brakes preventing them from killing the misplaced tissue. The chemical environment in the pelvis worsens this: elevated levels of certain inflammatory molecules suppress the NK cells’ ability to produce the toxic granules they normally use to destroy abnormal cells. Endometriotic cells also display surface molecules that directly inhibit NK cell activity, helping them avoid detection. The net result is that stray endometrial tissue escapes immune surveillance and is free to implant and grow.
Estrogen Fuels the Growth
Endometriosis is an estrogen-dependent disease. Endometrial-like tissue needs estrogen to survive and proliferate, and endometriosis lesions have developed their own supply lines. Normal endometrial tissue relies on estrogen produced by the ovaries, but endometriotic implants can manufacture estrogen locally. They do this through at least two biochemical pathways: one converts androgens (hormones typically associated with male traits but present in all bodies) directly into estrogen, while the other activates inactive estrogen compounds already circulating in the blood.
Research on tissue samples from over 100 surgically diagnosed patients found that the enzyme responsible for converting androgens to estrogen was detected in all endometriosis lesions and at higher levels than in healthy tissue. This local estrogen production creates a self-reinforcing cycle: the lesions make estrogen, which stimulates their own growth, which allows them to make more estrogen. It also helps explain why treatments that lower estrogen levels throughout the body can reduce symptoms but rarely eliminate the disease entirely.
Genetics and Family History
Endometriosis runs in families. If your mother or sister has it, your risk is 3 to 15 times higher than someone with no family history. Twin studies estimate that about 47% of the variation in who develops endometriosis comes from genetic factors, with the remaining 53% attributed to environmental influences. No single “endometriosis gene” has been identified. Instead, large-scale genetic studies across European and Japanese populations have found multiple regions of DNA that each contribute a small amount of risk. You inherit a combination of these genetic variants, and together they may influence how your immune system responds to stray tissue, how your body processes estrogen, or how easily endometrial cells attach to surfaces outside the uterus.
When Cells Transform in Place
Not all endometriosis can be explained by tissue traveling from the uterus to other locations. A theory called coelomic metaplasia proposes that cells lining the pelvic cavity can transform into endometrial-like tissue on their own. This is biologically plausible because the tissue lining the pelvis and the tissue lining the uterus both develop from the same embryonic source. Under certain triggers, possibly hormonal shifts or exposure to endocrine-disrupting chemicals, these cells may revert to a less specialized state and then redevelop as endometrial tissue.
This theory is especially useful for explaining cases that retrograde menstruation cannot: endometriosis in people who were born without a uterus, in young girls who haven’t yet started menstruating, or in the rare male patient. A related idea, the embryonic rest theory, suggests that small clusters of cells left over from fetal development can be activated later in life and develop into endometriotic lesions.
Spread Through Blood and Lymph Vessels
Endometriosis occasionally appears in locations far from the pelvis, including the lungs, diaphragm, and in extremely rare cases, the brain. Retrograde menstruation through the fallopian tubes can’t account for this. The lymphatic and vascular spread theory proposes that fragments of endometrial tissue enter the bloodstream or lymphatic system and travel to distant sites, much like cancer cells metastasize.
Supporting this idea, researchers have found endometrial tissue inside lymphatic vessels and lymph nodes. Women with endometriosis also have a higher density of lymphatic vessels in their uterine lining compared to women without the disease, which may make it easier for tissue fragments to enter the lymphatic system, particularly during menstruation. This mechanism likely explains only a small subset of cases, but it accounts for the ones that no other theory can.
Environmental Exposures
Environmental chemicals that interfere with hormones may increase endometriosis risk. The most studied are dioxins and polychlorinated biphenyls (PCBs), industrial pollutants that persist in the environment and accumulate in body fat over time. Women with higher blood levels of dioxin-like compounds are roughly 2.5 times more likely to have endometriosis and 5 times more likely to have severe disease compared to women with lower levels. These chemicals are thought to act through two pathways: they interfere with estrogen signaling, potentially amplifying the hormone’s growth-promoting effects, and they suppress immune function, reducing the body’s ability to clear misplaced tissue.
Dioxin exposure comes primarily through the food chain, especially animal fats in meat, dairy, and fish. Because these compounds accumulate gradually and endometriosis develops over years, pinpointing a direct cause-and-effect relationship is difficult. But the association is consistent enough that endocrine-disrupting chemicals are considered a contributing risk factor, particularly in women who are already genetically susceptible.
Why It Takes So Long to Diagnose
The average time from first symptoms to diagnosis ranges from 4 to 12 years. Part of this delay stems from the fact that symptoms like painful periods and pelvic pain overlap with many other conditions, and part stems from the historical requirement that endometriosis be confirmed through surgery. Updated clinical guidance from ACOG now allows for a presumptive diagnosis based on a patient’s history, symptoms, physical exam, and imaging, without requiring surgery first. This shift is designed to get people into treatment faster rather than waiting years for surgical confirmation. A presumptive diagnosis lets doctors begin medical treatment while continuing to evaluate, so patients can start feeling better sooner and access support resources earlier.