Doctors still can’t point to one cause of endometriosis. The World Health Organization says the causes are unknown. But years of research have turned up several strong clues.
In endometriosis, tissue like the uterine lining grows outside the uterus, causing inflammation and scar tissue. So where does that tissue come from?
This guide covers the main theories, what the numbers say, and what you can do with that information.
There’s No Single Cause
England’s NICE describes a condition whose exact cause isn’t known but is hormonemediated, which ties it to menstruation. Most experts now think several factors work together: menstrual flow, genes, hormones, and the immune system.
NICE also notes that stakeholders see delayed childbearing as a possible risk factor. That’s a clue, not a cause.
Retrograde Menstruation
This is the oldest and best-known theory. During a period, some menstrual blood flows backward through the fallopian tubes into the pelvis. Cells in that blood can then take root and grow. A physician named J.A. Sampson first proposed the idea in 1927.
Today, researchers read it a bit differently. The retrograde blood may carry progenitor cells that remember the uterine development program and restart it in the wrong place.
It’s still the leading explanation. One review calls it the only theory that explains where lesions usually appear. A 2022 paper in Fertility and Sterility argued that DNA evidence now supports it. But there’s a catch. More than 90% of women have retrograde menstruation, yet only about 10% develop endometriosis. Something else must tip the balance.
Other Theories
Retrograde flow can’t explain everything. Lesions sometimes appear far from the pelvis. WHO says endometriosis can occur in the abdomen and chest, and the genomics review notes rare cases above the diaphragm, such as the lungs or even the brain.
That’s why scientists also study other ideas, including metaplasia and spread through blood and lymph vessels. Metaplasia means that normal cells change into endometrium-like cells. None of these has fully replaced Sampson’s theory.
Genetics and Family History
Endometriosis runs in families. Sibling studies put its heritability at about 50%. WHO also notes that people with endometriosis are more likely to have a family history of it.
Scientists have linked about 30 genes to the condition. Yet each risk variant carries a relative risk below 1.4, and the identified genes explain less than 10% of the heritability. Researchers call this “missing heritability.”
Size matters here. A meta-analysis of 11 studies, covering 17,045 cases and 191,596 controls, found 19 variants linked to endometriosis. Each one nudges risk up only a little.
Here’s the practical takeaway. Ask your mother, sisters, and aunts about severe period pain or trouble getting pregnant. Share what you learn with your doctor. A relative with endometriosis raises your odds, but it doesn’t guarantee you’ll get it.
Hormones, Especially Estrogen
Endometriosis is fueled by estrogen, and the details are surprising. A 2025 review notes that circulating estrogen levels don’t differ between women with and without endometriosis. But the lesions and the uterine lining of affected women have higher local estrogen levels. So a normal blood test doesn’t tell the whole story.
Lesions can also make their own estrogen. A 2025 review explains that an enzyme called aromatase shifts the balance from progesterone toward estrogen and promotes lesion growth.
Progesterone normally balances estrogen. The 2025 review on the uterine lining also points to progesterone resistance as a possible factor in impaired endometrial health. That’s also why many treatments target hormones. WHO lists combined hormonal contraceptives, progestins, and GnRH analogues among the common options. The
Immune System and Inflammation
Your immune system may fail to clear stray tissue. WHO says emerging research links endometriosis to immune dysregulation. People with it also have higher rates of lupus, multiple sclerosis, and inflammatory bowel disease.
That same lining review found that macrophage and Th17 immune profiles lean proinflammatory in endometriosis. That may help explain the chronic inflammation behind the pain.
Before Birth and the Environment
A 2026 hypothesis in Human Reproduction Open proposes “hyperestrogenic imprinting.” It suggests that daughters of women with endometriosis are exposed in the womb to a different hormonal environment, which may leave lasting changes. That’s an idea under study, not proven fact.
Genes and early development may also explain why some teens get symptoms soon after their first period. A 2025 review found genetic and epigenetic predispositions contribute significantly to endometriosis in adolescents.
Environmental links are also unproven. A genomics review found no convincing causal environmental factor, though scant evidence points to BPA, phthalates, and organochlorines.
Can You Prevent It?
Not yet. WHO states there is no known way to prevent endometriosis. That means it isn’t your fault, and you should be wary of anyone who promises a prevention plan. WHO adds that early diagnosis and good care may slow or halt progression.
Since prevention isn’t possible, some women focus on general wellness. One example is Endo Wellness from Real Science Nutrition, a nitric oxide-based formula that works with the body’s own systems for circulation, metabolism, and hormone function. It can’t prevent endometriosis or change its causes. Check with your doctor before adding any supplement.
What to Do With This Information
- Ask relatives about painful periods, fertility trouble, or an endometriosis diagnosis.
- Track your symptoms for two or three cycles.
- Ask whether a pelvic ultrasound makes sense. WHO says imaging such as ultrasound is used to diagnose endometriosis.
- Don’t wait it out. WHO reports an average time to diagnosis of 4 to 12 years.
Crux of the Matter
Endometriosis likely starts with a mix of menstrual flow, genes, hormones, and immune factors. No single one explains it. Knowing that helps you spot patterns, share your family history, and speak up sooner. Early answers matter most.