Endometriosis happens when tissue similar to the uterine lining grows in places it shouldn’t, like the ovaries, pelvic walls, and sometimes even the lungs. It affects roughly 10% of reproductive-age women worldwide, about 190 million people, yet the average time to diagnosis still ranges from 4 to 12 years. No single cause has been identified. Instead, several biological mechanisms likely work together, and understanding them helps explain why the condition is so variable in who it affects and how severely.
Retrograde Menstruation: The Leading Theory
The most widely accepted explanation is called retrograde menstruation. During a period, some menstrual blood flows backward through the fallopian tubes and spills into the pelvic cavity, carrying small fragments of uterine lining with it. These fragments can land on the ovaries or the surfaces of the pelvic walls, implant there, and respond to hormonal cycles just like the tissue inside the uterus. Over time, repeated episodes of backward flow after each ovulatory cycle allow more tissue to accumulate and establish itself.
The obvious problem with this theory on its own: the majority of premenopausal women experience retrograde menstruation, yet only a fraction develop endometriosis. Something else has to determine why certain women’s bodies allow those stray cells to survive and grow while others clear them without issue.
The Immune System’s Role
One major factor appears to be immune surveillance. Normally, the immune system recognizes misplaced cells and destroys them. In women with endometriosis, this cleanup process seems to falter. Research published in Frontiers in Immunology found that women with the condition had significantly reduced activity in natural killer cells, the immune cells responsible for identifying and eliminating rogue tissue. At standard testing ratios, natural killer cell effectiveness was about 26.6% in women with endometriosis compared to 33.3% in women without it.
At the same time, the uterine lining in women with endometriosis showed higher concentrations of a type of immune cell called macrophages. Rather than clearing the misplaced tissue, these macrophages appear to fuel inflammation, creating an environment where endometrial fragments can more easily take hold. The combination of weakened immune attack and heightened inflammation helps explain why retrograde flow leads to disease in some women but not others.
Lesions That Make Their Own Estrogen
Estrogen is the primary fuel for endometriosis, and the lesions themselves have a disturbing trick: they can produce their own supply. Normal endometrial tissue depends on estrogen circulating in the bloodstream, rising and falling with the menstrual cycle. But endometriotic lesions contain enzymes that convert other hormones into active estrogen right at the site of the growth.
Research in Frontiers in Molecular Biosciences showed that estrogen levels inside lesions remain constant regardless of where a woman is in her cycle, even as circulating estrogen levels fluctuate. This local estrogen production creates a self-sustaining loop: the lesion makes estrogen, the estrogen promotes the lesion’s survival and growth, and the inflammatory environment reinforces the whole process. This is one reason endometriosis can be so persistent and difficult to treat.
Cell Transformation Without Retrograde Flow
Retrograde menstruation can’t explain every case. Endometriosis has been documented in people who have never menstruated, including rare cases in men. An alternative theory, called coelomic metaplasia, proposes that cells lining the pelvic cavity can transform into endometrial-like tissue on their own. These cells share a common embryonic origin with uterine lining cells, so under the right triggers, particularly estrogen exposure and inflammatory signals, they may essentially switch identity.
This transformation pathway helps account for cases that don’t fit the retrograde model and may also explain why endometriosis sometimes appears in locations far from the pelvis.
Stem Cells and Blood-Borne Spread
A newer line of evidence points to stem cells from bone marrow. Researchers at Yale found that women who received bone marrow transplants for leukemia later had donor-derived cells in their uterine lining. This was the first demonstration that cells from outside the reproductive system could travel through the bloodstream, settle in distant locations, and differentiate into endometrial tissue. If stem cells can do this under normal conditions, it could explain how endometriosis develops without any backward menstrual flow at all.
Endometrial cells can also travel through lymphatic channels and blood vessels. This vascular and lymphatic spread is the most plausible explanation for endometriosis showing up in truly remote locations: the lungs, diaphragm, kidneys, spleen, nasal lining, and even the spinal canal. Women with lung involvement can experience cyclical coughing up of blood timed to their periods, and spinal involvement has been linked to seizures that follow the menstrual cycle.
Environmental Chemical Exposure
A growing body of evidence connects endometriosis to environmental chemicals that interfere with hormonal signaling. Four types of compounds have the strongest links: industrial chemicals found in older electrical equipment and building materials, dioxins released by industrial burning, bisphenol A (BPA) found in certain plastics, and phthalates used as plasticizers in packaging, cosmetics, and household products.
These chemicals activate multiple pathways inside cells that promote inflammation, estrogen activity, cell survival, and tissue invasion, essentially mimicking the same biological conditions that allow endometriosis to establish itself. Lead exposure has also been associated with increased risk, with one analysis finding a 74% higher likelihood of endometriosis in women with elevated lead levels. While the exact dose-response relationships are still being refined, the overall evidence strongly suggests that cumulative exposure to these chemicals plays a contributing role.
Surgical Transplantation
Endometriosis can also result from direct physical transplantation of cells during surgery. During a cesarean section or other pelvic procedure, endometrial cells can be inadvertently carried to the incision site, where they implant and grow. Scar endometriosis after cesarean delivery occurs in roughly 0.03% to 0.4% of cases. The risk is about 3.3 times higher after cesarean section than after episiotomy. Though the overall incidence is low, this mechanism is well documented and explains cases where endometriosis appears precisely at a surgical scar, sometimes years after the procedure.
Why Multiple Causes Matter
No single theory explains every case of endometriosis. The current understanding is that these mechanisms overlap. A woman might experience retrograde menstruation that her immune system fails to clear, while her lesions produce their own estrogen supply, and environmental chemical exposure amplifies the inflammatory signals that help those lesions thrive. Genetic factors influence several of these pathways, which is why the condition tends to run in families.
This complexity is also why diagnosis takes so long. Symptoms vary depending on where lesions develop and which mechanisms are dominant, ranging from severe pelvic pain and heavy periods to infertility, bowel and bladder symptoms, or in rare cases, symptoms in distant organs that seem completely unrelated to the reproductive system.