Endometriosis develops when tissue similar to the uterine lining grows outside the uterus, most commonly on the ovaries, fallopian tubes, and pelvic surfaces. It affects roughly 10% of reproductive-age women worldwide, about 190 million people. There is no single cause. Instead, several biological processes work together, and your individual risk depends on a combination of genetics, immune function, hormonal patterns, and environmental exposures.
Retrograde Menstruation: The Leading Theory
The most widely accepted explanation is called retrograde menstruation. During a normal period, some menstrual blood flows backward through the fallopian tubes and into the pelvic cavity instead of exiting the body. This backward flow carries small fragments of uterine lining tissue with it. If those fragments land on pelvic surfaces, they can implant, survive, and grow.
Here’s the catch: the majority of premenopausal women experience some degree of retrograde flow, yet only a fraction develop endometriosis. So retrograde menstruation alone doesn’t explain the disease. What seems to matter is the quality and quantity of the tissue that travels backward. Research published in The Journal of Clinical Investigation shows that endometrial tissue carrying certain genetic mutations and abnormal gene expression patterns is more likely to survive once it lands in an ectopic location. These molecular changes give the tissue a better ability to implant and respond to estrogen, fueling its growth.
Volume matters too. Women with structural abnormalities that block normal menstrual outflow (like an imperforate hymen or a vaginal septum) experience significantly more retrograde flow and develop endometriosis at strikingly high rates. Women with heavy menstrual bleeding also face higher risk, likely for the same reason: more tissue traveling to the wrong place.
Why Your Immune System Doesn’t Clear It
Normally, your immune system acts as a cleanup crew. When stray tissue ends up in the pelvic cavity, immune cells called macrophages should identify and destroy it. In women who develop endometriosis, this process goes wrong in a specific way.
Research from the Proceedings of the National Academy of Sciences reveals that not all macrophages behave the same. Macrophages that arrive from the bloodstream (derived from circulating immune cells called monocytes) actually work against endometriosis, trying to protect the pelvic cavity from lesion formation. But macrophages that travel with the endometrial tissue itself are “pro-endometriosis,” actively helping lesions establish. When researchers depleted the protective monocyte-derived macrophages in animal models, significantly more lesions formed.
Endometriosis also triggers continuous recruitment of new immune cells that behave differently from the macrophages normally present in the pelvic cavity. Instead of clearing the misplaced tissue, some of these cells promote a fibrotic healing response, essentially forming scar-like lesions rather than eliminating the tissue. It’s a repair process happening in the wrong context.
Genetics Account for About Half the Risk
Endometriosis runs in families. The heritability, meaning the proportion of disease risk attributable to genetic factors, is approximately 50%. The other half comes from environmental and lifestyle influences.
Genome-wide association studies have identified several chromosomal regions linked to increased susceptibility. These include gene variants involved in cell signaling and growth regulation on chromosomes 1, 9, and 12. Variants in genes associated with developmental pathways and immune signaling have also been replicated across multiple studies. No single gene causes endometriosis, but carrying several of these variants raises your baseline risk, likely by affecting how endometrial cells behave when they end up outside the uterus.
Stem Cells and Alternative Origins
Retrograde menstruation can’t explain every case. Endometriosis occasionally occurs in people who have never menstruated, in rare cases in men, and in locations far from the pelvis. This points to additional pathways.
One theory involves stem cells. The uterine lining contains several types of multipotent stem cells capable of developing into different tissue types. These progenitor cells can travel not only through the fallopian tubes during menstruation but also through blood vessels and lymphatic channels, potentially seeding distant sites. Bone marrow-derived stem cells may also contribute, migrating to ectopic locations and differentiating into endometrial-like tissue. This would explain the rare cases where endometriosis appears in the lungs, diaphragm, or other remote areas.
Another explanation, the metaplasia theory, proposes that cells lining the pelvic cavity can transform directly into endometrial-like tissue. These pelvic lining cells share an embryological origin with uterine tissue, so under certain triggers (possibly hormonal signals or chemical exposures), they may essentially “switch” their identity.
Menstrual Patterns That Raise Your Risk
Certain characteristics of your menstrual cycle correlate with higher endometriosis risk, largely because they increase lifetime estrogen exposure or the volume of retrograde flow.
- Early menarche: Starting your period between ages 8 and 11 carries greater risk than starting at 12 or later. Earlier onset means more years of menstrual cycles and cumulative estrogen exposure.
- Short or irregular cycles: Irregular menstrual cycles are associated with roughly double the risk of endometriosis. Shorter cycles mean more frequent periods and more opportunities for retrograde flow.
- Heavy periods: Greater menstrual volume sends more tissue into the pelvic cavity with each cycle.
- Severe period pain (dysmenorrhea): A personal history of significant menstrual pain, particularly in adolescence, is strongly associated with later endometriosis diagnosis. This may reflect early disease activity rather than being a separate risk factor.
Environmental Exposures and Estrogen Disruption
Endometriosis is an estrogen-dependent disease, meaning it needs estrogen to grow and persist. Environmental chemicals that interfere with estrogen signaling can tip the balance.
Dioxins and polychlorinated biphenyls (PCBs), industrial pollutants found in food chains and the environment, are the best-studied culprits. Women with plasma dioxin levels above the 75th percentile are 2.5 times more likely to have endometriosis and five times more likely to have severe disease compared to women with lower levels. These compounds boost local estrogen production in tissue by increasing the activity of an enzyme called aromatase, and they interact directly with estrogen receptors to activate estrogen-dependent genes. Exposure happens primarily through dietary fat, especially in meat, dairy, and fish from contaminated sources.
Why Diagnosis Takes So Long
Despite affecting one in ten women of reproductive age, endometriosis typically takes between 4 and 11 years from symptom onset to diagnosis. Several factors drive this delay. Symptoms like pelvic pain, painful periods, and pain during sex overlap with other conditions. Many women are told their pain is normal. And historically, definitive diagnosis required surgical confirmation, though updated clinical guidelines from the American College of Obstetricians and Gynecologists now aim to shorten this timeline by enabling earlier clinical diagnosis based on symptoms and imaging.
The disease can begin in adolescence, with some evidence suggesting that the process starts as early as the first menstrual cycles. Recognizing the pattern of risk factors, especially early menarche, severe period pain, and family history, can help identify it sooner.