What Is an Endometrial Lesion and What Causes It?

An endometrial lesion is any abnormal growth or area of tissue involving the endometrium, the lining of the uterus. The term is broad on purpose: it covers everything from a harmless polyp bulging into the uterine cavity to a patch of endometrial-like tissue growing on an ovary, to a precancerous thickening of the uterine lining itself. What causes these lesions depends heavily on which type you are dealing with, but a handful of shared drivers keep turning up across the spectrum, including hormonal imbalance, immune system dysfunction, and genetic susceptibility. Understanding the different forms and their overlapping roots helps make sense of a diagnosis that can otherwise feel vague and alarming.

The Main Types of Endometrial Lesions

When a doctor says “endometrial lesion,” they could be referring to several distinct conditions. The differences between them matter because each has its own risk profile, symptoms, and treatment path.

Endometrial polyps: Overgrowths of endometrial glands and tissue that protrude into the uterine cavity. They are benign, affect both reproductive-age and postmenopausal women, and can cause heavy or irregular bleeding, though in some women they produce no symptoms at all and may even shrink on their own.¹
Endometriosis: Endometrial-like tissue that establishes itself outside the uterus, commonly on the ovaries, fallopian tubes, or pelvic lining. It affects roughly one in ten reproductive-age women and is a leading cause of chronic pelvic pain and infertility.²
Adenomyosis: Endometrial tissue that grows into the muscular wall of the uterus rather than staying within the lining. It causes the uterus to enlarge and often produces heavy, painful periods.
Endometrial hyperplasia: An abnormal thickening of the uterine lining driven by excess estrogen without adequate progesterone. The atypical form, which involves cellular changes, is considered precancerous.³
Endometrial cancer: Malignant growth originating in the uterine lining. Most cases begin as abnormal glandular proliferation and develop through stages of increasing cellular abnormality.

Because the word “lesion” simply means an area of abnormal tissue, hearing it in a report is not, by itself, a reason to panic. The clinical significance depends entirely on which kind you have and whether it is causing problems.

How Endometriosis Lesions Take Hold

Of all endometrial lesions, endometriosis is the one that generates the most questions about cause. The leading explanation remains retrograde menstruation: during a period, some menstrual tissue flows backward through the fallopian tubes and into the pelvic cavity. The catch is that this backward flow happens in the vast majority of menstruating people, with estimates ranging from 76% to 90%, yet only about 10% develop endometriosis.⁴ That gap tells researchers that retrograde menstruation is necessary but not sufficient. Something else determines whether those refluxed fragments get cleared away or dig in and form lasting lesions.

One recent proposal focuses on oxygen levels. Menstrual shedding is itself an event involving restricted blood flow and then reperfusion, so the tissue leaving the uterus is already primed by low-oxygen conditions. If transient, localized low-oxygen zones exist in the pelvic cavity when that tissue arrives, the fragments may activate survival pathways that help them persist instead of being destroyed.⁴ This “hypoxia gatekeeper” idea helps explain why lesions appear in some women and not others, even when the amount of backward menstrual flow is similar.

Retrograde menstruation also cannot account for every form of the disease. Endometriosis has been documented in the lungs, the brain, and in people who have never menstruated. Alternative or complementary explanations include the spread of endometrial cells through lymph or blood vessels, the transformation of other cell types into endometrial-like tissue, and the involvement of stem cells that may be present in ectopic locations and capable of regenerating endometrial tissue on their own.⁵ No single theory covers all types of lesions, which is why researchers increasingly think the disease has multiple routes of origin depending on where and how it manifests.

What Drives Adenomyosis

Adenomyosis looks like a close cousin of endometriosis, but the mechanism is different because the endometrial tissue invades inward rather than outward. The most widely accepted explanation is that repeated micro-injuries at the boundary between the endometrium and the underlying muscle layer allow endometrial cells to push deeper into the uterine wall.⁶ This “tissue injury and repair” model fits with the observation that adenomyosis is more common in women who have had uterine surgery or multiple pregnancies, both of which involve mechanical stress to that boundary.

Other proposed pathways include the transformation of stem cells already residing in the muscle wall, infiltration of endometrial cells from the outer surface of the uterus via retrograde menstrual fluid, and hormonal disruption that pushes cells to behave abnormally.⁷ As with endometriosis, no single mechanism fully explains every case, and it is likely that several of these processes can operate in parallel.

The Hormonal Engine

Estrogen and progesterone are the two hormones that regulate the normal monthly cycle of the endometrium: estrogen makes it grow, and progesterone reins in that growth and prepares the lining for a potential pregnancy. When the balance between these two signals goes wrong, endometrial lesions of many kinds become more likely.

In endometriosis, the displaced tissue typically shows estrogen dominance combined with resistance to progesterone. Instead of responding normally to progesterone’s “slow down” signal, the tissue keeps growing under estrogen’s influence.⁸ This same imbalance shows up in atypical endometrial hyperplasia, where prolonged exposure to estrogen without adequate progesterone leads to abnormal glandular overgrowth and the cellular changes that can precede cancer.³ It also plays a role in adenomyosis, where aberrant local steroid hormone signaling is one of the recognized contributing mechanisms.⁷

This hormonal thread is why so many treatments for endometrial lesions target the estrogen-progesterone axis. Hormonal contraceptives, progestins, and drugs that suppress estrogen production can shrink lesions or slow their growth, although they do not eliminate the underlying tendency to form them.

Immune Dysfunction and Inflammation

A healthy immune system clears misplaced tissue. In endometriosis, that clean-up process fails. Growing evidence points to macrophages, a type of immune cell, as central players. The macrophages found inside endometriotic lesions do not destroy the wayward tissue the way they should. Instead, they release a cocktail of inflammatory signals, growth factors, and tissue-remodeling molecules that actually help the lesions survive and expand.⁹

These dysfunctional macrophages promote chronic inflammation around the lesion, stimulate the growth of new blood vessels to feed it, interact with nerve fibers in ways linked to pain, and contribute to the fibrosis (scarring) that makes advanced endometriosis so difficult to treat. The immune environment does not just fail to prevent the lesion; it actively supports it. This is one reason endometriosis behaves more like an inflammatory disease than a simple case of tissue in the wrong place.

How Lesions Build Their Own Blood Supply and Nerve Network

For an endometriotic lesion to survive outside the uterus, it needs its own blood supply. Lesions achieve this through angiogenesis: the sprouting of new blood vessels from existing ones. At the same time, nerve fibers grow into and around lesions in a process that appears tightly coupled to blood vessel growth. Nerves within lesions can produce signals like vascular endothelial growth factor that guide blood vessel formation, and blood vessels in turn support the nerves.¹⁰

This nerve-vessel partnership is not just an architectural curiosity. The nerve fibers that grow into endometriotic lesions are thought to be a major contributor to the pain the disease causes. Ovarian hormones, especially estrogen and progesterone, modulate the production of nerve growth factor and brain-derived neurotrophic factor within the lesions, linking hormonal fluctuations directly to changes in nerve density and pain signaling.¹¹ This helps explain why pain from endometriosis often tracks with the menstrual cycle but can also become chronic: once a nerve network is established inside a lesion, it does not necessarily disappear during hormonal lulls.

Tissue Remodeling and Invasion

Endometrial cells that land outside the uterus face a physical barrier: the surrounding tissue. To implant and grow, they need to break down the extracellular matrix, the scaffold of proteins that holds tissues together. This breakdown is carried out by a family of enzymes called matrix metalloproteinases (MMPs). In women who develop endometriosis, the regulation of these enzymes appears to go haywire, with abnormally high MMP activity enabling ectopic endometrial tissue to invade and establish itself.¹²

Both the enzymes and their natural inhibitors show elevated levels in endometriotic lesions compared to normal endometrium, suggesting that the entire tissue-remodeling system is ramped up rather than simply unbalanced in one direction.¹³ This overactive remodeling is one reason deep infiltrating endometriosis can burrow into organs like the bowel and bladder, causing far more damage than superficial lesions on the peritoneal surface.

Oxidative Stress and Iron

Menstrual blood that ends up in the pelvic cavity does not just deliver endometrial cells. It also delivers red blood cells, which break down and release iron. Excess iron can catalyze chemical reactions that generate reactive oxygen species, molecules that damage cells and the tissue around them. This oxidative stress destroys patches of the peritoneal lining, creating adhesion points where ectopic endometrial cells can latch on and grow.¹⁴

Animal studies have reinforced this link. Injecting red blood cells near endometriotic lesions in mice increased the growth of those lesions, while administering an iron-chelating agent (a drug that binds up excess iron) inhibited it.¹⁴ This iron-oxidative stress pathway operates alongside the immune and hormonal mechanisms already described, and it highlights how the peritoneal environment itself, not just the wayward tissue, contributes to lesion formation.

Genetics and Epigenetics

Endometriosis runs in families, and researchers have long suspected a genetic component even though no single gene causes the disease. The exact genetic contributors remain limited in what they explain on their own, but recent progress has come from studying epigenetics: heritable changes in gene activity that do not alter the DNA sequence itself.¹⁵

In endometriotic tissue, several important genes are switched on or off abnormally through epigenetic marks. Some genes involved in progesterone signaling and tumor suppression are silenced by excessive methylation, while others involved in inflammation and estrogen production are activated by the removal of methylation marks.¹⁶ Changes in enzymes that manage DNA methylation, histone modification, and other aspects of chromatin structure are consistently found in endometriotic lesions compared to normal endometrium.²

What makes epigenetics particularly interesting is that it connects the hormonal and immune threads of the disease. Epigenetically altered gene expression affects steroid hormone production and signaling, immune regulation, and the identity and function of endometrial cells, all pathways already implicated in how lesions form and persist.¹⁵ In other words, epigenetic changes may be an upstream switch that trips multiple downstream problems at once.

Environmental Chemicals and Endometrial Lesions

A growing body of research examines whether endocrine-disrupting chemicals (EDCs), substances in the environment that interfere with hormone signaling, increase the risk of endometrial lesions. Compounds that have drawn the most attention include bisphenol A and its analogs, phthalates, dioxins, polychlorinated biphenyls (PCBs), per- and polyfluoroalkyl substances (PFAS), and parabens. Reviews of the literature have linked these chemicals to faulty signaling mechanisms involved in the initiation or progression of uterine disorders including endometriosis, uterine fibroids, adenomyosis, and endometrial hyperplasia.¹⁷

The evidence is strongest for the four chemicals most thoroughly studied in relation to endometriosis specifically: PCBs, dioxins, BPA, and phthalates. These compounds appear to activate multiple intracellular pathways associated with inflammation, estrogen signaling, cell survival, and tissue invasion, all processes directly involved in endometriotic lesion establishment.¹⁸ That said, population-based studies in humans often produce mixed results, partly because exposure levels are hard to measure accurately and because people are exposed to many chemicals simultaneously rather than in the controlled single-compound doses used in animal studies.¹⁹ The weight of the evidence suggests these chemicals contribute, but pinning down exactly how much risk any one compound adds to any one person remains difficult.

When Lesions Become Precancerous or Cancerous

Most endometrial lesions are benign. Polyps rarely turn malignant. Endometriosis, despite being a chronic, sometimes aggressive condition, carries a low overall risk of transformation into cancer. But the relationship between endometrial lesions and malignancy is more nuanced than a simple yes-or-no answer.

Atypical endometrial hyperplasia is the clearest precancerous condition. Driven by prolonged unopposed estrogen, it involves abnormal gland growth with cellular changes that represent a recognized step on the path toward endometrial cancer.³ Women diagnosed with this condition are typically offered close monitoring or treatment specifically to prevent progression.

Endometriosis and cancer have a more complicated relationship. A study characterizing deep infiltrating endometriosis lesions from 39 patients found that about a quarter harbored somatic mutations in known cancer driver genes, including KRAS, PIK3CA, and ARID1A. Yet deep infiltrating endometriosis rarely becomes cancerous. The researchers concluded that somatic mutations may participate in the disease process of endometriosis itself without necessarily leading to malignant transformation.²⁰ Finding cancer-associated mutations in a benign lesion is unsettling on the surface, but it reflects the broader reality that cancer requires not just one mutation but a cascade of failures in growth control. Most endometriotic lesions never complete that cascade.

How Endometrial Lesions Are Detected

Detection methods depend on the type and location of the lesion. For lesions inside the uterus, such as polyps and hyperplasia, transvaginal ultrasound is usually the first-line tool. Power Doppler ultrasound, which visualizes blood flow patterns, can help distinguish between polyps and other benign growths like submucous fibroids with high specificity.²¹ If the ultrasound findings are ambiguous or a tissue sample is needed, hysteroscopy (inserting a small camera into the uterus) allows direct visualization and biopsy.

For endometriosis, diagnosis has historically required surgery because the lesions sit outside the uterus and can be subtle. Transvaginal ultrasound and MRI have both improved to the point where they can detect deep infiltrating endometriosis in many locations with similar accuracy. Both modalities perform best at identifying lesions on the rectosigmoid (the lower portion of the large intestine), where pooled sensitivity reaches about 85% for each, and are less reliable for detecting disease in other pelvic compartments.²² Superficial endometriosis on the peritoneal surface remains difficult to see on any imaging and often still requires laparoscopy for definitive diagnosis.

One frustrating reality of endometrial lesion diagnosis: symptoms do not always correlate neatly with what imaging or surgery finds. Some women with extensive endometriosis have minimal pain, while others with small lesions are debilitated. And for endometrial cancer, bleeding and spotting appear to depend more on local tumor progression than on factors like hormone receptor status or histological subtype, meaning that symptom severity is an unreliable indicator of how advanced a lesion is.²³

An Evolutionary Angle on Menstruation and Endometriosis

One question that occasionally surfaces in the research literature is whether endometriosis is, in some sense, a byproduct of human evolution. In primates, the endometrium underwent an unusual adaptation: it decidualizes spontaneously each cycle, thickening and transforming in preparation for an embryo before an embryo even arrives. Most other mammals only decidualize in response to an actual early pregnancy. The trade-off of spontaneous decidualization is menstruation: when no embryo implants, the thickened lining is shed.²⁴ Menstruation, in turn, creates the conditions for retrograde flow and the possibility of ectopic implantation. From this perspective, endometriosis may be an unintended consequence of a reproductive strategy that evolved to optimize embryo implantation. The disease is essentially an evolutionary side effect, a vulnerability built into the system rather than something introduced from outside it.

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