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Why Your Endometriosis Pain Can Feel So Unrelenting

Understanding TGF‑β may help you make sense of inflammation, fibrosis, and future treatment options

By Dr Steven Vasilev
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If you live with endometriosis, you’ve probably noticed something that doesn’t make sense on the surface: pain that keeps coming back, bowel or bladder symptoms that feel “tethered,” and flare patterns that don’t always match what your scans show. You might even be told your disease is “mild,” while your day-to-day life feels anything but.


One helpful way to make sense of this is to understand that endometriosis lesions often don’t behave like simple “implants.” They can act more like active wounds that keep trying to heal—creating inflammation, new blood vessels, and scarring (fibrosis). Recent evidence looking across many studies points to a family of signaling proteins (the TGF-β superfamily) as one of the drivers behind that “sticky, scarring, persistent” behavior. This isn’t an immediate new treatment you can start tomorrow, but it can absolutely help you make more informed choices: which symptoms are likely driven by fibrosis, why hormones help some people more than others, and what to ask your clinician when pain persists.


What this means in real life: inflammation + fibrosis can be a pain engine


TGF-β (especially TGF-β1 and TGF-β2) shows up at higher levels in many endometriosis-related places—blood, peritoneal fluid, peritoneal tissues, and lesion tissue—in a lot of studies, though not all results match perfectly. The practical takeaway isn’t “go test your TGF-β.” The takeaway is this:


When endometriosis is actively promoting adhesions, invasion, immune disruption, and fibrosis, you may feel:

  • Pain that becomes more constant (not just during periods)
  • Deep pain with sex, bowel movements, urination, or certain movements
  • A sensation of pulling/tightness—sometimes worsening over time
  • Symptoms that don’t correlate well with cyst size or superficial findings


Fibrosis matters because scar-like tissue can produce nerve growth factors which increases the number of microscopic nociceptive (pain sensing) nerve endings, irritate nerves, restrict organ mobility, and maintain inflammation. That can also help explain why some people feel worse over the years—even if lesions aren’t “spreading everywhere.”


So… is there a treatment that “blocks TGF-β” for endometriosis?


Not in routine clinical care right now.


You may see headlines implying that “blocking TGF-β cures endometriosis.” That’s not where the evidence is. The strongest message from this body of research is that these pathways are promising future targets, but they’re not yet established, safe, endometriosis-specific treatments you can ask your doctor to prescribe today. In addition, blocking the nerve sensation is not a "cure" anyway. But it is something that will reduce pain and help people feel better in the future.


That said, understanding these pathways can still help you make better decisions with the tools we do have now—because many current treatments are indirectly aimed at the same downstream results: reducing inflammation, suppressing lesion activity, and limiting progression/recurrence.


Where this connects to your current options (and how to think about them)


Even without a “TGF-β blocker,” you and your doctor are often trying to calm the same processes that TGF-β-related signals appear to amplify, indirectly.


Hormonal suppression (pill, progestins, IUD, GnRH options)


If your symptoms improve on hormonal treatment, that can be a sign that cycling inflammation and bleeding within lesions is a major driver for you. Hormonal suppression can reduce pain for many patients, but it may be less effective when pain is already heavily driven by fibrosis, adhesions, and nerve involvement—because scar tissue doesn’t simply melt away when hormones are suppressed.


Practical implication: if you’ve tried multiple hormonal options and pain remains high, it’s reasonable to discuss whether your symptom pattern suggests deep disease, adhesions, or significant fibrosis, and whether imaging and/or surgical consultation makes sense.


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Surgery (especially excision) and the “recurrence” conversation


TGF-β–linked processes include adhesion and invasion behaviors, plus fibrosis. This supports what many patients experience: endometriosis is not just “extra tissue,” it can be biologically active in ways that promote persistence.


Practical implication: when discussing surgery, it’s worth asking not only “Can you remove the lesions?” but also:

  • “What is your approach to deep disease, fibrosis and adhesions?”
  • “What’s your plan to reduce recurrence risk afterward?”

Post-op hormonal suppression is often suggested for recurrence prevention (when pregnancy isn’t the immediate goal). Your best plan depends on your symptoms, fertility goals, and surgical findings. However, even if the scientific proof is not the greatest, the overall consensus is that in most cases doing something is better than nothing. This can range from compounded bio-identical progesterone, to oral forms of progesterone, to synthetic progestins and so on.


Pain care that treats your nervous system too


When inflammation and fibrosis have been present for years, your nervous system can become sensitized (pain pathways become overprotective). This doesn’t mean pain is “in your head.” It means your body has been living with repeated threat signals.


Practical implication: a complete plan may need more than hormones or surgery alone—think pelvic floor physical therapy, neuropathic pain medications for central nervous system desensitization when appropriate, trauma-informed care, and targeted strategies for flares.


Why results vary so much from person to person


One frustrating theme in endometriosis research is inconsistency. Even within this area, while many studies report higher TGF-β levels in certain compartments, at least one reported lower TGF-β1 expression in ectopic endometrium—suggesting real biological diversity. In other words, the molecular drivers of endometriosis are likely different from person to person. It is not likely one disease that affects everyone the same way, meaning endometriosis is not one uniform disease.


Practical takeaways for your next appointment


Use this as a script to steer the conversation toward what actually improves your quality of life:

  • “Do my symptoms sound more consistent with inflammation, deep disease, adhesions, or pelvic floor involvement?”
  • “If fibrosis/adhesions are suspected, what imaging is most useful for my situation, and what might it miss?”
  • “What’s our timeline to decide if this treatment is working—and what’s the next step if it isn’t?”
  • “If I’m considering surgery, what is your experience with excision of deep disease, fibrosis and adhesions? What outcomes should I realistically expect?”
  • “What’s our plan for recurrence prevention after surgery (or if I delay surgery) given my fertility goals?”


Reality check: what we still don’t know (and how to protect yourself from hype)


This pathway-based research supports the idea that fibrosis and immune signaling are part of endometriosis progression—but it does not prove that one molecule “causes” endometriosis in humans, nor does it give you a validated diagnostic blood test today.


The most useful way to apply this information is to reframe your care:

  • Persistent symptoms may reflect active biology, not personal failure or “low pain tolerance.”
  • If a treatment only targets one aspect (like cycling hormones), you still need strategies for fibrosis/adhesions, pelvic floor dysfunction, and nervous system sensitization.
  • Promising targets are coming, but right now the best results typically come from individualized, multi-tool care—and from clinicians who take your symptoms seriously even when tests are imperfect.

References

  1. Xu, Li, Lin, Lin, Ji. The role of TGF-β superfamily in endometriosis: a systematic review. Frontiers in Immunology. 2025.. DOI: 10.3389/fimmu.2025.1638604

Quick Answers

What is endo belly?

“Endo belly” is the common term patients use for the severe bloating and abdominal swelling that can happen with endometriosis. It’s often described as a belly that looks or feels suddenly distended—sometimes within hours—and may come and go in waves, frequently worsening around a period but not always. Importantly, this can mimic weight gain even when the underlying issue is swelling, fluid shifts, or gastrointestinal distension rather than true fat gain.


Endometriosis can irritate tissues in the pelvis and abdomen and can also affect (or “talk to”) the bowel, which helps explain why many people notice constipation, diarrhea, cramping, or a tight, pressured abdomen alongside pelvic pain. You can have significant digestive symptoms even when routine GI testing looks normal, because endometriosis often involves the outer surface or deeper layers around the bowel rather than the inner lining.


If endo belly is a major part of your symptom pattern—especially when it comes with painful bowel movements, cyclical flares, or persistent pelvic pain—our team can help you sort out what’s driving it and what treatment options are most likely to bring relief. Explore our educational resources, and if you’re ready, reach out to schedule a consultation so we can review your history and build a plan around your goals.

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What are signs endometriosis has returned after surgery?

Endometriosis “returning” after surgery can show up as symptoms that improve for a while and then gradually (or suddenly) come back months or even years later. The most common signal is the return of your familiar pattern—cyclical pelvic pain, worsening period pain, pain with intercourse, or pain that starts spreading beyond where it used to be. Some people also notice bowel or bladder symptoms re-emerge (pain with bowel movements, rectal pressure, urinary urgency or bladder pain), especially if those organs were involved before. New or increasing fatigue and activity limitation can be part of the picture, but the key is a clear change from your post-op baseline.


It’s also important to know that recurrent pain doesn’t always equal recurrent disease. Even after complete excision, the nervous system can stay “turned up,” and pelvic floor dysfunction, adhesions, or central sensitization can keep pain going or make normal sensations feel painful—so we think in terms of patterns, triggers, and timing rather than a single pain score. If symptoms are returning, our team can help you sort whether you’re in a true recurrence lane (improved, then returned) versus persistent pain that never fully settled, and decide when imaging (such as ultrasound or MRI) is useful—particularly for tracking ovarian endometriomas. If you’re noticing a shift back toward your old symptoms, reach out to schedule a consultation so we can build a clear, long-term follow-up plan with you.

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Can I keep working with endometriosis?

Yes—many people with endometriosis keep working, but it often requires a realistic plan around symptoms like pain, fatigue, brain fog, heavy bleeding, and unpredictable flares. Work becomes harder when endometriosis pain isn’t just “period pain,” but a complex, whole‑nervous‑system experience that can persist throughout the month and sometimes continues even after partial treatments. If your job performance is being affected, that’s not a personal failure—it’s a sign your symptoms need more targeted evaluation and a clearer strategy.


In our practice, we think about work in two parallel tracks: managing symptoms so you can function day to day, and treating the underlying disease when it’s driving ongoing inflammation, adhesions, or organ involvement. Depending on your situation, this may include a structured pain management approach (often multimodal) and, when appropriate, excision surgery planning based on a careful review of your history, imaging, and prior operative/pathology reports. If you’re wondering what’s realistic for you—whether that’s staying at work with accommodations, reducing hours temporarily, or planning time off for treatment—reach out to schedule a consultation so our team can review your records and help you map out next steps.

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How do I document endometriosis for work accommodations?

Documenting endometriosis for work accommodations starts with creating a clear paper trail that connects your diagnosis (or suspected diagnosis) to specific functional limits at work. Keep a simple symptom log for at least 4–8 weeks: date, symptom (pelvic pain, fatigue, bowel/bladder pain, heavy bleeding), severity, duration, triggers, and exactly what work tasks were affected (missed shifts, reduced standing tolerance, inability to sit, concentration issues, frequent bathroom breaks). Save objective documentation too—operative and pathology reports if you’ve had surgery, imaging reports when available, ER/urgent care notes, medication or treatment history, and any workplace attendance or performance impacts that occurred during flares.


For an accommodation request, what usually helps most is a concise clinician letter that focuses on work restrictions rather than extensive medical detail—e.g., need for flexible scheduling during flares, ability to work from home at times, breaks for pain management/restroom access, limits on prolonged standing/sitting, or intermittent leave when symptoms are unpredictable. If you’re pursuing disability benefits, the same principle applies: decision-makers look for consistent records over time showing that symptoms significantly interfere with your ability to perform job duties, since endometriosis isn’t automatically classified as a disability.


Our team can help you organize the records that best support your case and, when appropriate, provide medical documentation that reflects the reality of your symptoms and functional limitations. If you’d like, reach out to schedule a consultation so we can review what you already have and identify what additional documentation would be most useful for workplace accommodations.

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How do I explain endometriosis to my employer?

It often helps to keep your explanation simple and work-focused: endometriosis is a chronic inflammatory condition where tissue similar to the uterine lining grows outside the uterus and can cause significant pelvic pain, fatigue, and GI or bladder symptoms. Symptoms can flare unpredictably and aren’t always limited to your period, which is why you may need flexibility at certain times. You don’t need to share intimate details—just the functional impact (for example: pain, fatigue, and medical appointments can affect attendance, sitting/standing tolerance, or concentration).


If you’re requesting support, be specific about what would help you do your job well, such as intermittent time off for flares, the ability to work from home when symptoms spike, scheduled breaks, or flexibility around medical visits and potential procedures. Many patients find it useful to frame this as a long-term health condition with variable days rather than a one-time illness, and to document patterns of symptoms and missed work so your needs are clear.


If you’d like, our team can help you describe your condition and anticipated care in a medically accurate way that supports workplace accommodations, especially if symptoms are affecting your ability to function consistently. You can also explore our educational resources on endometriosis and work impacts, and reach out to schedule a consultation if you’re looking for a clearer plan for diagnosis and treatment.

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Have a question?

Dr. Steven Vasilev delivers best-in-class endometriosis guidance and a personalized treatment plan—built on evidence and your unique biology.


Led by Steven Vasilev, MD—an internationally recognized endometriosis specialist & MIGS surgeon—Lotus Endometriosis Institute is virtual-forward, with many patients traveling nationally for care. Clinical evaluation and surgical treatment are provided in California.

Santa Monica, CA

2121 Santa Monica Blvd, Santa Monica, CA 90404

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Arroyo Grande, CA

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