Endometriosis is Associated with 661 Other Conditions
Could we finally understand endometriosis subtypes?
Those with endometriosis know that it is never just endometriosis. It’s endometriosis and migraines. Endometriosis and autoimmune disease. Endometriosis and allergies. Endometriosis and a connective tissue disorder.
And no two people with endometriosis present the same. They have different symptoms, different patterns of other co-occurring conditions, different experiences, and different treatment plans that work best for them. Because of that, the process of managing endometriosis is often trial and error. Due to the heterogeneity of the disease even healthcare professionals are playing the guessing game when it comes to treatment for those living with endometriosis.
However, a landmark new study of over 43,000 people may have just cracked open the door to something the endometriosis community has been waiting decades for.
This Study Was Groundbreaking
The researchers (Khan et al., 2025) took already existing data from the health records of over 43,000 endometriosis patients, and matched them to people without endometriosis but the same age, gender, race and ethnicity. For each endometriosis case, they found 30 controls.
Crucially, they also accounted for a bias that some people think arises in endometriosis research: people with endometriosis go to the doctor more. More appointments can mean more diagnoses - not because the conditions are truly more common, but because they're being caught. Some think this could be why those with endo are usually diagnosed with so many other conditions.
But, they are proved wrong - the researchers controlled for this directly, meaning the associations they found are real, not just a result of those with endometriosis having more frequent healthcare visits.
They looked at two timeframes: all diagnoses across a patient's entire medical history, and diagnoses that appeared before endometriosis was officially confirmed. That second group is where some of the most important findings emerged.
The Findings: Endometriosis is Linked to 661 Other Conditions
The comorbidities
The researchers confirmed staggering rates of co-occurring conditions.
If someone had endometriosis, they had significantly higher odds of also experiencing these conditions:
Adenomyosis - 181x higher odds
Interstitial Cystitis - 16x
Ehlers-Danlos syndrome - 7x
PMDD - 5x
Autoimmune disease - 5x
Vulvodynia - 9x
Migraine - 4x
Allergy - 3x
Fibromyalgia - 6x
Depressive disorder - 3x
Incontinence - 5x
Chronic pain - 7x
Connective tissue disorder - 5x
Hashimoto’s - 3x
Sciatica - 4x
Tinnitus - 4x
BRCA1 or 2 gene mutation - 8 to 9x
Insomnia - 4x
Chronic gastritis - 6x
Vitamin D deficiency - 4x
Iron deficiency - 6x
These are some examples, there’s actually 661 overall. These findings are devastating, but they also provide important evidence for reasons detailed at the end of this article.
Does Endometriosis Have "Comorbidity Cluster” Subtypes?
Researchers also found that those with endometriosis naturally grouped into meaningful phenotypic subtypes, which may reflect different biological mechanisms or disease trajectories.
Up to 31 different groupings emerged, each defined by a different constellation of co-occurring conditions. Some were dominated by autoimmune disorders. Others by mental health conditions, pregnancy complications, cancer-related diagnoses, urinary tract conditions, or skin disorders.
Critically, it’s thought that some of these aren't just downstream consequences of having endometriosis - there may be shared underlying biology rather than one condition causing the other.
What researchers have suggested is that "endometriosis" may be an umbrella term covering partly biologically distinct subtypes. The same diagnosis can mean very different things depending on which cluster a patient falls into - certain different underlying mechanisms, different comorbidity patterns, different disease trajectories.
This would explain one of the most frustrating realities of this disease: why treatments that work well for some - do nothing for others.
A Separate Subtype Finding “The Endotypes”
We did some digging elsewhere to look into the possibility that endometriosis has distinct biological subtypes. Simancas-Racines et al., 2026 have recently proposed six biological endotypes, meaning underlying disease subtypes defined by a different dominant biological mechanism:
1. Inflammation dominant
The dominant mechanism is the flooding of inflammatory signals, contributing to body-wide symptoms and lesion progression.
2. Immune dysregulated
The dominant mechanism is that your immune cells are actually protecting lesions instead of clearing them.
3. Hormone resistant
The dominant mechanism is progesterone resistance. Progesterone should normally help slow lesion growth. When lesions become resistant to it, they grow unchecked in response to estrogen overproduction, and hormonal therapy is less effective. This is why some people try hormonal treatment after hormonal treatment and nothing works, or it becomes less effective over time (it’s not in your head).
4. Angiogenesis driven
The dominant mechanism is lesions forming new blood vessels, building their own blood supply to grow and spread.
5. Neuroimmune-pain dominant
The dominant mechanism is high nervous system involvement, and pain pathways becoming sensitised. This is why pain severity doesn’t always match lesion size, and it comes along with chronic pain issues.
6. Fibrosis-predominant
Adhesions, scarring and tissue hardening are dominant, driving a whole new set of symptoms.
Importantly, every person with endometriosis has all of these mechanisms to some degree. What differs between the endotypes is which mechanism ends up becoming the *dominant* feature driving the disease. This is really important, as it can aid in choosing what will be the most effective treatment for managing that person's endo to start with, instead of throwing all the generic options at it and hoping for the best. Precision medicine for endometriosis isn’t here yet, but the map is being drawn.
If we were to match up the two studies described, these endotypes could give insight into the biological engine behind the clinical clusters Khan et al. identified. An immune dysregulated endotype, for example, could explain why some people with endometriosis cluster so strongly with autoimmune disease. A neuroimmune-pain dominant endotype could explain the chronic pain syndrome and fibromyalgia cluster.
Could Endo Have Predictive Biomarkers?
One of the most clinically significant findings from Khan et al. came from looking at what conditions appeared before an endometriosis diagnosis. Two stood out:
•Migraine: People with endometriosis were twice as likely to have experienced migraines before their diagnosis. Migraine may be an early signal, and given emerging evidence of shared neuroinflammatory pathways between the two conditions, this isn't surprising.
•Cancer antigen 125 (CA-125). Elevated CA-125 levels appeared almost 18 times more often in people before their endometriosis diagnosis compared to controls. CA-125 is already used informally in clinical practice to support endometriosis diagnosis. This data adds weight to that.
Both findings point toward a future where endometriosis could be identified earlier, before years of dismissed symptoms and delayed referrals.
What the Future Holds
The average diagnostic delay for endometriosis is still 8-12 years. The other major problem is that even when someone is diagnosed, treatments are guesswork, and most of the time inadequate. Studies like this one are part of what can change that.
First of all, this evidence is important for reducing the diagnostic delay. With awareness that endometriosis is more likely to show up in someone who has the above conditions, doctors may be able to recognise warning combinations and think to investigate endometriosis sooner.
Secondly, subtype-informed care also matters for tailored treatment. If we know the dominant biological mechanism driving someone’s endometriosis, it can help in selecting what will be the most effective treatment for managing that person's endometriosis to start with, instead of “guesswork” by attempting generic options one after the other, hoping for the best.
An example: chronic pain is one of the most debilitating features of endometriosis, and it remains poorly managed for many. But pain driven by neuroinflammation requires different intervention than pain driven by fibrosis or immune dysregulation. Knowing which mechanism is dominant isn't just academically interesting - it's the difference between a treatment that works and years of trial and error.
Finally, we now have even more evidence of the following important information: Endometriosis is not a reproductive disorder with side effects. It is a systemic (whole-body) inflammatory disease. This study, with over 43,000 patients across six medical centres, is the kind of evidence that should make that impossible to ignore.
References
1. Khan et al.Comorbidity analysis and clustering of endometriosis patients using electronic health records. Cell reports. Medicine. 2025. https://www.sciencedirect.com/science/article/pii/S2666379125003180
2. Simancas-Racines D, Jiménez-Flores E, Montalvan M, Horowitz R, Araujo V, Reytor-González C. Endometriosis as a Systemic and Complex Disease: Toward Phenotype-Based Classification and Personalized Therapy. Int J Mol Sci. 2026 https://pubmed.ncbi.nlm.nih.gov/41596555/