Is Endometriosis Progressive?

A detailed ESSI review of disease biology, phenotype diversity, fibrosis, natural history, and the implications for timing of treatment.

Key Takeaways

• Endometriosis is best understood as a heterogeneous family of disease phenotypes rather than one single disorder with one universal trajectory.

• The literature supports progression in many patients, especially through increasing fibrosis, adhesions, anatomic distortion, endometrioma formation, and rising surgical complexity; however, progression is not inevitable in every patient.

• The recent Fertility and Sterility article by Yagur et al. strengthens the argument that disease stage may plateau while surgical complexity continues to rise with age, likely reflecting cumulative fibrosis and remodeling.

• At ESSI, our exceptionally low reoperation rates reinforce the importance of a comprehensive, durable surgical strategy rather than partial treatment.

Why this question matters

Patients are frequently told two opposite and equally misleading things about endometriosis: that it always gets worse, or that it is a static benign nuisance that can simply be watched indefinitely. The literature does not support either extreme. A more defensible position is that endometriosis often behaves as a progressive disease, but it does so unevenly, with distinct trajectories depending on lesion phenotype, age at presentation, inflammatory activity, fibrosis, symptom biology, fertility goals, and prior treatment.

The most important recent contribution to this discussion is the Fertility and Sterility study by Yagur and colleagues, which examined age-related trends in disease severity and surgical complexity using the AAGL classification system. In a cohort of 1,293 surgically treated patients, the prevalence of advanced disease increased with age, peaking in the 35-45-year group, while surgical complexity continued to rise even later. Endometriomas were more common in older age groups, whereas bowel disease did not show the same age relationship.

The central message of the paper is highly relevant for clinicians: even if stage plateaus, surgery can become progressively more difficult because fibrosis, adhesions, and anatomic remodeling continue to accumulate. It is exactly this distinction – between lesion count or stage on one hand and biologic or technical progression on the other – that should reshape how clinicians counsel patients. Endometriosis may progress not only by becoming more extensive, but also by becoming more fibrotic, more fixed, more anatomically disruptive, and therefore harder to treat well.

The most defensible answer: yes, but not uniformly

The best evidence-based answer to the question ‘Is endometriosis progressive?’ is yes, often, but not universally. The disease is chronic, inflammatory, estrogen-dependent, and biologically heterogeneous. In some patients, lesions remain relatively limited for years. In others, the disease evolves toward ovarian endometrioma, deep infiltrating disease, denser fibrosis, tethering of pelvic organs, and more technically demanding surgery.

Authoritative reviews from the New England Journal of Medicine, BMJ, and the 2022 ESHRE guideline all emphasize the heterogeneity of endometriosis and the fact that symptom burden, lesion burden, infertility, and response to treatment do not move in lockstep. That heterogeneity is precisely why simplistic messaging is unhelpful. A patient may have little visible progression but major pain amplification; another may have modest symptoms yet accumulating retroperitoneal scarring and organ distortion; another may mainly show ovarian disease affecting fertility.

Therefore, the clinically meaningful question is not whether all endometriosis always progresses. The real question is what type of endometriosis a given patient has, what biologic behavior it is showing, and what the likely next step in that trajectory will be.

What the recent Fertility and Sterility article adds

Yagur et al. studied pathology-confirmed endometriosis across four age groups and used the AAGL system not only to stage disease but also to capture surgical complexity. This is a major strength because older staging systems, particularly rASRM, do not fully communicate how difficult a case will be in the operating room.

The study found that advanced AAGL stage III-IV disease was more common with age and that the highest adjusted odds for complex surgery were seen after age 35, especially in patients older than 45 years. Endometrioma prevalence was also significantly higher in older groups compared with patients younger than 25 years. By contrast, bowel endometriosis did not show a significant age association.

The authors concluded that disease severity appears to peak and plateau, but surgical complexity continues to rise – a pattern they plausibly attribute to cumulative fibrosis, adhesions, and anatomic remodeling. This is an important refinement of the progression debate. Progression should not be reduced to whether a patient has ‘more spots’ of endometriosis over time. The more relevant issue may be whether lesions are maturing into scarred, retracted, vascularly altered, neuroinflammatory, anatomically disruptive disease that is harder to excise completely and safely.

Why stage alone is not enough

For many years, clinicians leaned heavily on the revised American Society for Reproductive Medicine staging system. While useful for certain purposes, it does not reliably capture deep disease, retroperitoneal fibrosis, bowel or ureteral complexity, or the technical burden of surgery. The AAGL 2021 classification was developed specifically to improve discrimination of surgical complexity, and it performs better in that regard than rASRM.

That distinction matters because a patient can have a stage label that looks stable while the actual operation becomes more difficult over time. Fibrosis can progressively obliterate tissue planes. Adhesions can tether the rectum, ureter, ovary, and pelvic sidewall. Endometriomas can alter ovarian architecture. Deep disease can induce more severe distortion than a superficial survey would suggest. Progression, in other words, may be better conceptualized as a combination of anatomic spread, fibrotic remodeling, and escalating technical difficulty.

A strong argument for different types of endometriosis

There is a compelling argument, supported by both clinical observation and the literature, that there are different types of endometriosis rather than one disease with one predictable natural history. At minimum, current classification frameworks distinguish superficial peritoneal disease, ovarian endometrioma, and deep endometriosis.

Increasingly, however, that tripartite model seems insufficient. A more clinically realistic view is that endometriosis includes several partially overlapping phenotypes with different biological behavior.

• One phenotype is superficial-predominant disease, which may remain limited in some patients yet still produce substantial pain.

• Another is ovarian endometrioma-predominant disease, which often appears to reflect lesion aging, repeated hemorrhage, and progressive fibrotic remodeling.

• A third is deep fibrotic disease, in which nodules, scarring, ureterolysis requirements, rectovaginal disease, and compartment distortion dominate the clinical picture.

• A fourth may be called pain-dominant or neuroinflammatory endometriosis, where symptom severity appears disproportionate to what is visible surgically or radiologically.

In many patients these patterns coexist, and adenomyosis may further modify symptoms, fertility, and response to treatment. The phenotype concept helps explain why the literature appears conflicting. If one study is enriched for young patients with superficial disease, another for referral-center surgical patients with deep disease, and another for expectantly managed ultrasound-detected nodules, the observed natural history will not be the same. The variability is not necessarily contradiction; it may reflect genuine biologic diversity.

Evidence supporting progression

Several lines of evidence support the idea that endometriosis is progressive in at least a substantial subset of patients.

• First, the Yagur study shows age-related increases in advanced stage, endometrioma prevalence, and especially surgical complexity.

• Second, the ovarian endometrioma literature provides some of the clearest biologic evidence for progression. Ding and colleagues compared adolescent and adult ovarian endometrioma lesions and found that adult lesions showed substantially more fibrosis and more advanced molecular and histologic features, supporting the view that ovarian endometrioma is a progressive process rather than a static cystic entity.

• Third, the fibrosis literature strongly supports a model of lesion maturation over time. The 2024 systematic review by Vissers et al. describes fibrosis as central to endometriosis biology, highlighting the role of myofibroblasts, platelets, TGF-beta signaling, nerves, and neuropeptides in lesion remodeling. That review is particularly important because it explains why clinical progression may be experienced as stiffness, retraction, adhesions, chronic pain, and increasing operative complexity even when disease does not obviously ‘spread’ in a simplistic geographic sense.

• Fourth, developmental and adolescent literature argues that early-onset disease can evolve toward more severe phenotypes. Brosens and colleagues proposed that early seeding and highly angiogenic lesions may create a more florid, progressive form of disease in young patients predisposed to severe endometriosis. Even where one disagrees with parts of that developmental model, it reinforces the point that disease timing and phenotype matter.

Evidence arguing against a simple universal progression model

At the same time, the literature does not support the idea that all endometriosis inevitably worsens in a linear fashion. One of the most informative studies in this regard is the 2023 expectant-management series by Knez et al., which followed women with deep pelvic endometriosis using serial ultrasound. Over a median follow-up of 666 days, a substantial proportion of women had static disease, a smaller group progressed, and a smaller group regressed. This is not the picture of a disease that behaves identically in every patient.

Similarly, Bourdon et al. showed that among adult women older than 24 years undergoing surgery, phenotype distribution did not significantly vary with age from 25 to 42 years. Their findings suggest that at least in adulthood, some aspects of phenotype may stabilize rather than continue to evolve in a simple stepwise fashion. This does not negate progression; it suggests that certain transitions may occur earlier, followed by a period of relative phenotypic plateau.

Taken together, these studies support a more nuanced model: some disease evolves early, some disease stabilizes anatomically, some disease continues to fibrose and become harder to treat, and some patients show little measurable structural progression over the interval studied.

Progression may occur in several dimensions

A practical way to reconcile the literature is to think of progression in at least three dimensions:

1. Anatomic progression: increasing lesion burden, endometrioma formation, deeper infiltration, or additional compartment involvement.

2. Fibrotic progression: increasing scarring, adhesions, and tissue-plane obliteration.

3. Pain-system progression: peripheral sensitization, central amplification, bowel-bladder cross-sensitization, fatigue, and wider symptom burden.

This framework is clinically useful because it explains why symptom severity is often poorly correlated with stage, why some patients with relatively limited disease are deeply symptomatic, and why others may have deceptively quiet symptoms despite accumulating surgical complexity.

Why the ‘multi-system disorder’ framing matters

Recent authoritative reviews have argued that endometriosis should increasingly be reframed as a multi-system disorder rather than a lesion-only pelvic disease. Griffiths and colleagues, for example, emphasized links between endometriosis and pain pathways, gastrointestinal symptoms, infertility mechanisms, and broader inflammatory biology, and explicitly proposed that better care may come from treating it as a multi-system disorder. The BMJ review by Horne and Missmer similarly emphasizes multimodal, interdisciplinary care for what is clearly more than a purely anatomic problem.

This framing matters for the progression debate because a patient may be progressing clinically without obvious new lesions. Neuroinflammation, cross-talk with bowel and bladder symptoms, pelvic floor dysfunction, fatigue, and multisite pain may all intensify the disease burden. In other words, progression can be biological and functional, not only topographic.

Implications for fertility and timing of treatment

The fertility implications of progression are complex. Not every patient with endometriosis requires immediate surgery, and overtreatment can be as harmful as undertreatment. However, certain phenotypes – particularly ovarian endometrioma, deep disease affecting tubo-ovarian anatomy, progressive fibrosis, and severe pain with organ distortion – can create a narrower window for optimal intervention.

That does not mean earlier is always better in a simplistic sense. It means timing must be individualized. Age, symptoms, ovarian reserve, imaging findings, fertility goals, prior surgeries, and the likelihood of durable expert excision all matter. The ESHRE guideline explicitly emphasizes individualized management and recognizes the complexity of balancing pain, fertility, recurrence, and patient priorities.

For the fertility-focused patient, the question is not merely whether disease exists, but whether waiting is likely to preserve options or reduce them. In some patients, delay allows anatomy to become more distorted and surgery to become more complicated; in others, conservative management is entirely reasonable. This is exactly why phenotype-based expertise matters.

The ESSI perspective

At ESSI, we believe the most accurate clinical statement is that endometriosis is frequently progressive, but progression is phenotype-specific, time-dependent, and patient-specific. Some disease is relatively indolent. Some evolves early and then stabilizes. Some is dominated by endometrioma and fibrosis. Some is characterized more by neuroinflammatory pain than by overt anatomical spread. Some becomes markedly more difficult to treat because fibrosis, adhesions, and compartment distortion continue to accumulate.

This is why we reject both complacency and alarmism. Patients should not be told that all endometriosis will inevitably march toward catastrophe, but they also should not be falsely reassured that persistent symptoms, enlarging endometrioma, worsening imaging, or increasing pelvic fixation are inconsequential. The right approach is individualized assessment, expert imaging when appropriate, fertility-aware planning, and surgery designed for completeness and durability when surgery is indicated.

Importantly, at ESSI our exceptionally low documented reoperation rates over the long term reflect the value of phenotype recognition, comprehensive operative planning, attention to retroperitoneal and compartment-based disease, and a commitment to durable rather than partial treatment.

Bottom line

The question is not whether endometriosis is progressive in an abstract all-or-none way. The better question is how a specific patient’s disease is behaving. The literature now supports a mature, nuanced conclusion: endometriosis often progresses, but not uniformly; progression may manifest through fibrosis and surgical complexity even when stage plateaus; and the disease likely includes multiple phenotypes with distinct trajectories.

For clinicians, that means abandoning simplistic counseling. For patients, it means demanding an evaluation that takes phenotype, symptoms, fertility goals, and imaging seriously. And for surgeons, it means recognizing that the cost of delay is not always a bigger lesion count – it may be harder surgery, more distorted anatomy, and a narrower therapeutic window.

References

1. Yagur Y, Schneyer RJ, Hamilton KM, et al. Is endometriosis a progressive disease? Examining age-related trends in disease severity and surgical complexity. Fertility and Sterility. 2026;125(3):477-487. doi:10.1016/j.fertnstert.2025.09.024.

2. Zondervan KT, Becker CM, Missmer SA. Endometriosis. N Engl J Med. 2020;382(13):1244-1256. doi:10.1056/NEJMra1810764.

3. Horne AW, Missmer SA. Pathophysiology, diagnosis, and management of endometriosis. BMJ. 2022;379:e070750. doi:10.1136/bmj-2022-070750.

4. Becker CM, Bokor A, Heikinheimo O, et al; ESHRE Endometriosis Guideline Group. ESHRE guideline: endometriosis. Hum Reprod Open. 2022;2022(2):hoac009. doi:10.1093/hropen/hoac009.

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6. Vissers G, Hehenkamp WJK, Donnez O, et al. The role of fibrosis in endometriosis: a systematic review. Hum Reprod Update. 2024;30(6):706-750. doi:10.1093/humupd/dmae023.

7. Ding D, Liu X, Duan H, et al. Evidence in Support for the Progressive Nature of Ovarian Endometriomas. Endocrinology. 2020;161(5):bqaa033. doi:10.1210/endocr/bqaa033.

8. Griffiths MJ, Horne AW, Gibson DA, Roberts N, Saunders PTK. Endometriosis: recent advances that could accelerate diagnosis and improve care. Trends Mol Med. 2024;30(9):875-889. doi:10.1016/j.molmed.2024.06.008.

9. Nezhat CR, Oskotsky T, Robinson JF, et al. Real world perspectives on endometriosis disease phenotyping through surgery, omics, health data, and artificial intelligence. NPJ Womens Health. 2025;3(1):8. doi:10.1038/s44294-024-00052-w.

10. Brosens I, Gargett CE, Guo SW, et al. Origins and Progression of Adolescent Endometriosis. Reprod Sci. 2016;23(10):1282-1288. doi:10.1177/1933719116637919.

11. Knez J, Bean E, Nijjar S, et al. Natural progression of deep pelvic endometriosis in women who opt for expectant management. Acta Obstet Gynecol Scand. 2023;102(10):1298-1305. doi:10.1111/aogs.14491.

12. Bourdon M, Maignien C, Marcellin L, et al. Distribution of endometriosis phenotypes according to patients’ age in adult women with surgical evaluation. Hum Reprod. 2024;39(10):2259-2267. doi:10.1093/humrep/deae180.