What If Endometriosis Is Not Just Hormonal? Scientists Are Looking at Bacteria
New findings suggest endometriosis may involve a far more complex chain reaction than doctors once thought.
Endometriosis has spent decades being treated like a medical mystery women were simply supposed to endure.
Endometriosis is a chronic, often painful disease where tissue similar to the lining of the uterus grows outside the uterus, frequently on pelvic tissues, ovaries, and fallopian tubes. These implants respond to hormones, leading to inflammation, scar tissue, and symptoms like severe pelvic pain and infertility. There is no known cure, but management includes pain relief, hormones, and surgery.
For years, the dominant explanation for endometriosis has centered on retrograde menstruation, the idea that menstrual blood flows backward through the fallopian tubes and into the pelvic cavity. The problem, as researchers have kept pointing out, is that retrograde menstruation happens in most women, while endometriosis affects about 10% of women of reproductive age. That gap has never fully made sense.
Now, a growing body of research is asking a more unsettling question: what if the missing piece is not just hormones, genetics, or inflammation, but bacteria?
A 2023 review published in iScience argues that bacterial factors are emerging as an important frontier in understanding the pathogenesis of endometriosis. The authors write that the disease is shaped by a complex interplay of classical theories, hormonal dependence, immune dysregulation, and what they describe as the “emergence of bacterial factors associated with endometriosis.”
In plain language, the science is moving toward a broader view of the disease, one that treats endometriosis less like a single-cause disorder and more like a biological chain reaction.
For years, the old explanation never fully answered the biggest question
According to the iScience review, Sampson’s retrograde menstruation theory remains the most widely accepted explanation for how endometrial-like tissue reaches places outside the uterus. And that theory still explains a great deal. But it cannot explain everything.
The authors argue that retrograde menstruation is observed in almost all women, except those with fallopian tube obstruction. Yet endometriosis affects roughly 10% of reproductive-age women. In other words, the mechanism may be common, but the disease is not.
That is why researchers have kept returning to other theories. Some have focused on coelomic metaplasia, the idea that certain cells transform into endometrial-like cells. Others have examined stem or progenitor cells, which may help explain how a small subset of menstrual tissue becomes especially capable of implantation, proliferation, and survival outside the uterus. The iScience review notes that endometrial side population cells account for about 2% of endometrial cells, which could partially explain why the disease is far less common than retrograde menstruation itself.
Still, none of those theories alone has settled the question. So the field kept moving.
The new endometriosis findings are pointing toward bacteria, and that changes the conversation
According to the iScience review, advances in next-generation sequencing have enabled the detection of bacteria in areas once assumed sterile, including the uterus. That means the evidence suggests that crosstalk between the genital microbiota may be involved in the pathogenesis of endometriosis.
The review describes a growing body of work around what earlier researchers called the “bacterial contamination hypothesis.” In that model, bacteria-contaminated menstrual blood could carry endotoxins into the pelvic cavity via retrograde menstruation. Those endotoxins, especially lipopolysaccharide (LPS) from Gram-negative bacteria, may then activate macrophages and trigger inflammation via Toll-like receptor 4 signaling.
Then, while endometriosis is already understood as an inflammatory disease, if bacteria are helping create or intensify that inflammatory environment, they may be doing far more than simply coexisting with the condition. They may be helping shape it.
The authors write that these bacterial factors can alter the microenvironment in the early stages of endometriosis development, leading to lesion formation. That is a major shift in perspective. It suggests the disease may begin to take shape earlier and involve more biological players than the older models could fully account for.
One bacterium keeps showing up in the endometrium of patients with endometriosis
Among the most striking findings is the growing attention around Fusobacterium.
According to the iScience review, researchers found that 64% of patients with endometriosis were positive for Fusobacterium in the endometrium. The review describes this as a potentially important clue, because the bacterium may induce a phenotypic transition in endometrial fibroblasts, transforming the local tissue environment in ways that help lesions form.
In the endometrium, bacterial presence appears to attract macrophages. Those macrophages then shift into an M2 state and produce transforming growth factor beta (TGF-β). In that TGF-rich environment, endometrial fibroblasts can transform into myofibroblasts. According to the review, those transformed cells are better able to adhere, migrate, and proliferate at ectopic sites, which helps drive lesion development.
A 2024 Human Reproduction opinion piece takes that finding seriously, even as it urges caution. It calls the 2023 Muraoka study a report that “raises the possibility that bacterial infection, especially those of the genus Fusobacterium, may be the cause of endometriosis, at least in certain women.” It also says the study offered “a seemingly plausible explanation” for the gap between the widespread occurrence of retrograde menstruation and the much lower prevalence of disease.
Still, the same paper also refuses to oversimplify the science. Its authors ask the obvious questions: Is Fusobacterium a cause of endometriosis, or a consequence of it, or both? Is the infection triggering disease, or is endometriosis creating an environment where the bacterium can thrive? Those questions remain unresolved.
Hormones and immunity still sit at the center of the disease
The bacterial research does not replace what doctors and researchers already know about hormones and immune dysfunction. It adds another layer.
According to the iScience review, endometriosis remains an estrogen-dependent disease. Endometriotic lesions often exhibit abnormal aromatase expression and an imbalance in estrogen receptor signaling, particularly ERβ, which promotes inflammation. At the same time, progesterone receptor expression is often suppressed, producing what researchers describe as a progesterone-resistant state.
Progesterone usually helps counterbalance estrogen’s proliferative effects. When progesterone signaling weakens, that balance breaks down.
Then there is the immune system. The review describes endometriosis as a disease in which immune dysregulation facilitates the adherence, infiltration, and proliferation of ectopic endometrial cells. M2 macrophages, fewer cytotoxic natural killer cells, and T-cell imbalances all seem to help create a permissive inflammatory environment rather than shutting down lesion growth.
So when researchers bring bacteria into the picture, they are not tossing out the older science. They are trying to understand how these systems talk to each other. Hormones, immunity, inflammation, and microbiota may all be acting together.
The antibiotic question is where things get hopeful and complicated
According to the iScience review, several animal studies suggest that antibiotics may reduce lesion growth in endometriosis models. The Muraoka team’s work also found that antibiotic treatment aimed at Fusobacterium reduced lesions in mice. The 2024 Human Reproduction piece describes that result as a “tantalizing possibility” for new non-hormonal therapies, especially in a field where drug development has been slow and frustrating.
That hope is real. Current treatment options for endometriosis remain limited. The iScience review notes that surgery can reduce ovarian reserve, hormonal therapies can carry adverse effects, and many options are not viable for patients trying to get pregnant. The prospect of a non-hormonal treatment targeting a specific stage of the disease process would be a major breakthrough.
But the same papers also warn against getting carried away.
The Human Reproduction article is especially careful here. It notes that broad-spectrum antibiotics kill bacteria indiscriminately, potentially eliminating microbes that are neutral or even protective. It also raises questions about whether antibiotic effects seen in mouse models will translate cleanly to human endometriosis, especially in more advanced disease. The authors write that “many issues are still unresolved,” and they are right to say so.
So yes, antibiotics are part of the conversation now. No, they are not a magic bullet.
The new diagnosis conversation is changing too, even as delays remain brutal
The science is shifting, but patients are still living with the consequences of a medical culture that has taken their pain far too lightly for far too long.
According to KY3, new endometriosis guidelines have created hope for faster diagnosis and expanded treatment options. The report notes that many patients wait an average of 10 to 14 years without a diagnosis. One patient interviewed said she had symptoms from age 15 and spent nearly two decades suspecting endometriosis before receiving a proper diagnosis.
That aligns with the larger pattern. Diagnosis still takes an average of 8 to 12 years. It also points to a familiar problem: menstrual pain remains normalized by families, culture, and sometimes physicians themselves. Severe pain gets psychologized, minimized, or rerouted into other diagnoses before endometriosis is ever seriously considered.
New imaging methods may help, but they still miss some forms of the disease, especially at later stages. So while it is true that science is moving forward, it is also true that patients are still paying for decades of dismissal.
For Latinas, the problem is often worse
Latinas in the United States have lower reported diagnosis rates for endometriosis than non-Hispanic white women. In some studies, prevalence among Hispanic women ranges from about 2.7% to 7.4%, compared with 11.1% to 17.0% in non-Hispanic white women. But that lower diagnosis rate does not necessarily mean lower disease burden. It may instead reflect underdiagnosis, delayed access to care, and structural inequality.
Latinas are often diagnosed at an older age, on average about 3.8 years later than non-Hispanic white women. Some research further suggests Hispanic patients are more likely to present with advanced Stage III or IV disease, which is exactly what you would expect in a system that keeps delaying diagnosis.
So when new science opens fresh paths to understanding endometriosis, that progress is key for Latina patients. A disease that already takes years to diagnose becomes even harder to catch when healthcare access is unequal, when symptoms are normalized, and when people are less likely to be heard early.