Why Does Endometriosis Happen?

No unifying theory yet explains where endometriosis comes from. Backward menstrual flow carries endometrial tissue into the pelvis, but more has to happen for disease to take hold. The misplaced cells must escape the immune system, attach to the pelvic lining, and keep growing. Research has revealed several well-supported hallmarks of the disease: genetic predisposition, estrogen dependence, progesterone resistance, and inflammation. A separate theory, called Müllerian rests, starts before birth. It holds that cells left behind as the reproductive tract forms can grow into lesions once estrogen rises at puberty. Growing evidence suggests endocrine-disrupting chemicals may affect both who develops the disease and how severe it becomes.

Endometriosis is tissue similar to the uterine lining growing in places it does not belong. On the peritoneum behind the uterus. On the bladder. On the ovaries. On the bowel. Sometimes on the diaphragm or around the heart. It behaves like a benign cancer. It grows, spreads, creates its own blood supply, grows its own nerve fibers, and feeds itself hormones. The disease creates an inflammatory environment in the pelvis that can damage eggs, sperm, fallopian tubes, and the uterine lining itself.

An estimated 10% of reproductive-age women are affected. Among women with infertility, the number is far higher.

The question patients ask most is simple: why me?

No single theory explains every case. But we know far more than most women are told.

Leading Theories on What Causes Endometriosis

Retrograde Menstruation

The oldest theory, proposed by Dr. John Sampson in 1927, suggests that menstrual blood flows backward through the fallopian tubes and deposits endometrial cells in the pelvis. These cells then implant and grow.

The problem: up to 90% of women experience retrograde menstruation. Only about 10% develop endometriosis. Retrograde flow also cannot explain endometriosis found in fetuses, in men, or in distant locations like the chest cavity or brain. Something else determines who develops disease and who does not.

Immune Dysfunction

In a healthy pelvis, the immune system clears misplaced cells. In women with endometriosis, this clearance fails. But it is not simply that the immune system is too weak. It is linked to the nervous system, and they are both dysregulated. Without proper support, immune system triggers (such as stress) can accumulate over time, similar to a repeated bee sting allergy, producing more and more inflammation with each cycle. After years or decades of unaddressed triggers, the result is massive pelvic inflammation that, in some cases, can damage everything in its path or vicinity.

This explains why endometriosis behaves like a chronic inflammatory condition exacerbated by stress.

Hormonal Environment

Endometriosis is estrogen-dependent. The implants produce their own estrogen. They create a local hormonal environment that feeds their own growth. This is one reason the disease is self-perpetuating.

Progesterone resistance plays a role too. Normal endometrial tissue responds to progesterone. Endometriosis tissue often does not. The implants can even create decoy progesterone receptors. This resistance allows the disease to survive in a hormonal environment that should limit its growth.

Environmental Factors

With research still being preliminary and not "causal," converging epidemiologic, animal, and mechanistic data link higher exposure to endocrine disrupting chemicals (EDCs) especially phthalates, BPA, dioxins, and PCBs to increased risk and severity of disease. EDC sources can include certain plastics, canned food linings, fragranced products, and high-fat animal foods. These chemicals can mimic estrogen, impair ovarian function, and promote inflammation and blood vessel growth ("angiogenesis").

Trans fats demonstrate some of the clearest links to modifiable endometriosis risk. A large prospective study of 1,199 laparoscopically confirmed cases found that women in the highest quintile of trans-unsaturated fat intake (for example fried fast foods and baked goods made with partially hydrogenated oils) had about a 48% higher risk of endometriosis than those in the lowest quintile, while higher omega-3 fats (for example fatty fish like salmon, plants and seeds like walnuts) were associated with lower risk.

Multiple human studies show that regular alcohol intake (> 1-2 drinks a day) is associated with higher circulating estrogen and increased estrogen-sensitive cancer risk. Alcohol appears to 1) increase aromatase activity (converting androgens to estrogens) and 2) slow hepatic estrogen clearance, because the liver prioritizes clearing ethanol over estrogen. A systematic review and meta-analysis of 15 studies found that any alcohol intake was linked to a higher risk of endometriosis compared with no alcohol intake (summary relative risk 1.24). Given alcohol's tendency to increase estrogen and systemic inflammation, it is biologically plausible that alcohol could worsen endometriosis for some women.

Embryologic Origin of Endometriosis

Dr. David Redwine proposed that some women develop with endometriosis-like implants already present in the pelvis from embryologic development. Because the reproductive and urinary tracts share a common origin during fetal development, abnormal cell placement during this process could explain why endometriosis appears in consistent anatomical patterns. This theory helps account for cases that retrograde menstruation cannot, including rare cases in men.

Genetic Risk Factors for Endometriosis

Endometriosis runs in families. The mothers and sisters of women with the disease face a sevenfold higher risk. The disease is not inherited in a simple pattern, but the susceptibility clearly is. Genetic factors influence immune response, hormonal metabolism, and inflammatory signaling.

What Gets Missed

Most explanations stop at theory. The clinical reality is more urgent.

Endometriosis takes a median of nine years to diagnose. Nine years of progressive disease. Nine years of pain dismissed as normal. Nine years of fertility quietly declining.

Suppressive medications are often the first and only response. They reduce symptoms by shutting down the cycle. They do not treat the disease. They do not stop it from spreading. When a woman stops the medication to conceive, she often discovers the endometriosis has been progressing silently the entire time.

What Actually Treats It

Excision surgery removes endometriosis at the root. Not burning the surface. Not destroying only what is visible. Excision cuts beneath the implant and removes the tissue completely. The distinction matters. Ablation leaves deeper disease behind and causes thermal damage that creates new scar tissue. Published data shows recurrence rates varying from 6% to 67% at five-year follow-up. In a prospective study of 620 patients, optimal excision achieved a long-term repeat surgery rate of just 2.5%. In teenagers, complete excision produced zero disease recurrence, with or without postoperative hormonal suppression. Outcomes depend on surgical skill and technique, even within excision. A single surgeon who specializes in optimal excision performed every operation in the 620-patient study.

Effective excision is more than cutting. Half the procedure is finding and removing disease. The other half is reconstructive work and adhesion prevention. Without these protocols, scar tissue often reforms after surgery, which can compromise both fertility and pain outcomes.

After excision, many women conceive naturally. No embryo laboratory. No high-dose ovarian stimulation. The disease is treated and the body's own reproductive function is restored.

One center surveyed women after surgery for stage III or IV endometriosis. Of the 206 who responded, 93.2% reported complete or partial symptom relief. What is often called "recurrence" is usually persistence from incomplete surgery. After excision, targeted support including bioidentical progesterone, cycle monitoring through charting, anti-inflammatory nutrition, and pelvic floor therapy helps restore full function. The question is not "how do we manage this for the rest of her life?" It is "what does her body need to function optimally?"

Can Endometriosis Be Treated If the Cause Is Unknown?

We cannot yet prevent endometriosis. We do not have a single, clean answer for why it happens. What we do have is enough understanding to stop waiting and start treating the disease in front of us.

If you suspect endometriosis but have not been diagnosed, our Endometriosis Self-Survey can help you assess how much suspicion to have about your symptoms.

References

1. Zondervan KT, Becker CM, Missmer SA. Endometriosis. N Engl J Med. 2020;382(13):1244-1256. PubMed

2. Sampson JA. Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol. 1927;14(4):422-469. doi:10.1016/S0002-9378(15)30003-X. RRM Library

3. Halme J, Hammond MG, Hulka JF, et al. Retrograde menstruation in healthy women and in patients with endometriosis. Obstet Gynecol. 1984;64(2):151-154. PubMed

4. Signorile PG, Baldi F, Bussani R, et al. Ectopic endometrium in human foetuses is a common event and sustains the theory of müllerianosis in the pathogenesis of endometriosis. J Exp Clin Cancer Res. 2009;28(1):49. PubMed

5. Martin JD Jr, Hauck AE. Endometriosis in the male. Am Surg. 1985;51(7):426-430. PubMed

6. Lu C, et al. Chronic stress blocks the endometriosis immune response by metabolic reprogramming. Int J Mol Sci. 2023;25(1):29. PubMed

7. Bulun SE, Yang S, Fang Z, Gurates B, Tamura M, Sebastian S. Estrogen production and metabolism in endometriosis. Annals of the New York Academy of Sciences. 2002. doi:10.1111/j.1749-6632.2002.tb02767.x. PMID: 11949967. PubMed

8. Burney RO, Giudice LC. Pathogenesis and pathophysiology of endometriosis. Fertil Steril. 2012;98(3):511-519. PubMed

9. Redwine DB. Was Sampson wrong? Fertil Steril. 2002;78(4):686-693. PubMed

10. Moen MH, Magnus P. The familial risk of endometriosis. Acta Obstet Gynecol Scand. 1993;72(7):560-564. PubMed

11. Pugsley Z, Ballard K. Management of endometriosis in general practice: the pathway to diagnosis. Br J Gen Pract. 2007;57(539):470-476. PubMed

12. Piriyev E, Wegner K, Radosa JC, et al. Reproductive capacity and recurrence of disease after surgery for moderate and severe endometriosis. Arch Gynecol Obstet. 2020;302(1):261-270. PubMed

13. Yeung P Jr, Mohan A, Gavard JA. The long-term rate of repeat surgery after optimal excision surgery of endometriosis at a single tertiary referral center. Acta Sci Women's Health. 2025;7(1):03-12. Full Text

14. Yeung P Jr, Sinervo K, Winer W, Albee RB Jr. Complete laparoscopic excision of endometriosis in teenagers: is postoperative hormonal suppression necessary? Fertility and sterility. 2011. doi:10.1016/j.fertnstert.2011.02.037. PMID: 21420081. PubMed

15. Birnbaum LS, et al. Endocrine disrupting chemicals and endometriosis. Fertil Steril. 2016;106(4):911-919. PubMed

16. Missmer SA, Chavarro JE, Malspeis S, et al. A prospective study of dietary fat consumption and endometriosis risk. Hum Reprod. 2010;25(6):1528-1535. PMC

17. Parazzini F, Cipriani S, Bravi F, Pelucchi C, Chiaffarino F, Ricci E, Viganò P. A metaanalysis on alcohol consumption and risk of endometriosis. American journal of obstetrics and gynecology. 2013. doi:10.1016/j.ajog.2013.05.039. PMID: 23707678. PubMed