Endometriosis Inflammation: Why This Disease May Affect More Than Your Pelvis

Dr. Brighten: [00:00:00] What if I told you that one of the most common diseases affecting women isn't just causing pelvic pain? Hi, Meow. My new dog is making a podcast appearance. So this condition is quietly increasing the risk of cardiovascular disease. It's increasing the risk of autoimmune disease, chronic pain syndrome, and even certain ovarian cancers.

And here's the thing about this disease, m-medicine has been thinking about it all wrong for decades. So endometriosis has been taught as a condition where tissue that looks like the lining of the uterus grows outside of the uterus. Adenomyosis has been described as the same tissue growing into the muscle wall of the uterus.

And let's be real, some doctors still say, like, "Oh, it's just your period. It's just the endometrial lining that's migrating throughout your body." Now, while these original, uh, definitions are anatomically true, the, this is biologically incomplete. So the lesions are not the only aspect of the disease. [00:01:00] There are consequences of the disease, and if we only focus on removing lesions or suppressing symptoms, we're missing the really big story that's happening throughout the entire body with endometriosis and adenomyosis.

And today, I wanna challenge the way that many of us think about endometriosis and adenomyosis. By the end of this episode, my hope is you're gonna understand these conditions are now recognized as chronic inflammatory immune-mediated diseases, not just gynecological diseases.

And I want you to understand why this distinction completely changes how we should be caring for patients , and what patients should expect. We're also gonna discuss why inflammatory markers like C-reactive protein can fail us, what the evidence says about long-term risks like cardiovascular disease, autoimmune disease, and most importantly, what the research says about what we can do to reduce those risks.

So whether you're a clinician who wants to better understand these [00:02:00] diseases, or you're someone living with endometriosis or adenomyosis who's been told, "Everything looks normal. Oh, just worry about it if you wanna get pregnant. Oh, maybe you should just have a baby. That will heal it," this conversation is here to change the way that we think about your health because once you understand the biology, everything else is gonna begin to make sense.

Now, if you don't know who you're listening to right now, hi, I'm Dr. Jolene Brighten. I also have endometriosis and adenomyosis. It took me 29 years of menstruating before I got diagnosed, but I also happen to be board certified in naturopathic endocrinology.

I'm a nutrition scientist, a certified menopause practitioner, and I'm also a certified sex counselor.

And you are listening to the Dr. Brighten Show. If you can take a quick minute to hit the like button, subscribe, leave me a review, help share this with someone who needs it. This helps this podcast get out to everyone who needs it. All right, let's not hold this up. , Now, the first thing I wanna make really clear is endometriosis is not just the [00:03:00] lining of the uterus that has migrated to the wrong areas. It's not solely driven by retrograde menstruation. That may be a contributing factor, but given that 90% of women experience retrograde menstruation, but only 10% of them actually have endometriosis, plus we find endometriosis in men, we find endometriosis in people who've never had a period, we find endometriosis in people who don't even have a uterus, like, that's not explaining everything.

Now, adenomyosis, I like to call it endo's bestie or cousin, 'cause you really, like, rarely ever find them separate. They're almost always coming together What we know about adenomyosis, it used to be that it was like, oh, it's the lining of the uterus is just growing into the muscle body. Now research is saying, mm, not quite.

There's- it's a bit more distinct than that, and so it is like got attributes that are like the lining of the uterus, but it's not quite the same, which could mean, yes, it did grow in there, and then because it doesn't belong there, and the [00:04:00] immune system gets all hot and bothered, then the im- then the tissue starts to change.

Or it may be that those lesions were implanted there before you ever even got your period. Adenomyosis lacks even, like it has less funding. So endometriosis gets, like, no funding. Like, male pattern baldness or a penis that doesn't work, give 'em all the money. Give 'em all the money in the world, and I'm not saying that erectile dysfunction isn't something to pay attention to.

It absolutely is. In my opinion, it is metabolic or cardiovascular disease until proven otherwise. But it's just to say that, like, what we're gonna go into today, incredibly debilitating disease, gets almost no funding, and then we have adenomyosis that gets even less funding. I mean, heck, doctors are just now starting to get trained in how to recognize it

And you know, I have to just share with you guys that my friend, Dr. Ram Cabrera, he has a dog that he named Endo, and I got a dog, and her name is Miel, and that means honey. And I'm [00:05:00] like, "Oh, I need to get a dog named Adno, and then we can have Endo and Adno, and then we could just, like, be best friends and hang out."

Anyhow, that's the nerdy part of me. Let's get back to the episode

Okay, if you're a clinician, I'm gonna say what needs to be said. We have been thinking about these diseases too small, too narrow. One of the biggest mistakes that medicine has made is treating endometriosis and adenomyosis as diseases of anatomy. It's find the lesion, remove the lesion, maybe use medications to suppress the lesion, uh, sometimes control the pain.

We know, uh, as endometriosis patients, we don't always get that, but it's just like rinse and repeat. Find the lesion, remove the lesion, control the pain, repeat. And that's a little like treating rheumatoid arthritis by only looking at swollen knuckles or by treating psoriasis as if it's simply a skin condition.

It's very, very limited

The visible lesion is not the disease in the sense of [00:06:00] how it's actually affecting and manifesting in the body what the patient's experience is. The lesion you can visualize, it's the manifestation of the disease. But I wanna take a step back, because if endometriosis were simply misplaced tissue, why do some women develop extensive disease while others don't?

Why do identical lesions produce debilitating pain in one woman and almost no pain in another? Why do some women continue to have symptoms even after seemingly successful excision surgery? And why do we consistently see higher rates of autoimmune disease, migraines, brain fog, irritable bowel syndrome, cardiovascular disease, uh, chronic fatigue, anxiety, depression, and other systemic conditions in women with endometriosis?

And the answer to that is that these diseases involve much more than just abnormal tissue growth. Yes, the tissue is a problem. I will argue the tissue is a problem, okay? But we also have to understand that it [00:07:00] involves abnormalities in immune regulation, hormone signaling, inflammation.

There are n- nerve growth and blood vessel formation. There's fibrosis. There's tissue repair happening. Endometriosis is a full ecosystem. The lesions are part of the ecosystem. Around those lesions, immune cells, including things like macrophages, mast cells, dendritic cells, uh, T cells, those are gonna release inflammatory cytokines, interleukin-1, interleukin-6, TNF alpha, prostaglandins, histamine.

Those inflammatory molecules recruit more immune cells. They stimulate new blood vessel formation through what is called vascular endothelial growth factor, or VEGF. They promote nerve growth into the lesions, a process called neuroangiogenesis. That helps explain why lesions that appear relatively small are producing profound [00:08:00] pain And then at the exact same time, 'cause this is all happening at once, oxidative stress damages the surrounding tissue.

Fibroblasts become activated, and those are what are gonna lay down excessive collagen. That creates fibrosis and scar tissue. Hormone signaling starts to change as well. So although endometriosis is often described as an estrogen-dependent disease, that is just part of the story. We don't tell the full endocrine story of endometriosis, and as a naturopathic endocrinologist, it drives me nuts because one of the defining biological features is progesterone resistance.

So normally, progesterone acts as a brake on inflammation. It helps regulate immune function. It opposes estrogen's proliferative effects. In endometriosis, the tissue becomes less responsive to progesterone. My theory is because there's so much inflammation. But, you know, I want you to [00:09:00] imagine, it's like trying to stop a car by pressing the brake pedal and then discovering the brake lines have been cut.

The brake is there, right? But the signal isn't getting through. So that's why when you think of progesterone may be there, you test in their blood. You're like, "Progesterone looks great." Yeah. Okay, the brake pedal, I can see it, but it's not doing its job. Brake lines are cut

Now, because doctors are always so focused on, like, "Oh, estrogen's the problem," a- and, and we think retrograde menstruation is the problem, that leads them to say, "Use the birth control pill, use GnRH agonist. Let's just shut down the hormones." The lesions are capable of producing estrogen locally. They increase aromatase activity.

They're creating a self-sustaining inflammatory environment, and rather than relying solely on circulating estrogen, the lesions are generating their own hormonal fuel. That explains why endometriosis behaves like a chronic inflammatory disease instead of an isolated anatomical problem, and we haven't even touched on the HPA [00:10:00] axis dysregulation, the insulin resistance that can occur, 'cause this is also a phenomenon in those with endometriosis and adenomyosis.

Now, adenomyosis, it shares many of these same biological characteristics. The primary difference isn't the underlying biology as much as it's the location. So endometriosis lesions, they're gonna develop outside the uterus, the ovaries, pelvic peritoneum, so the lining of the abdomen, bowel, bladder, diaphragm, pelvic structures.

It can really be anywhere in the body. With adenomyosis, there's endometrial glands and stroma, okay? Those are the components, uh, that are like the endometrial lining. Those invade the muscular wall of the uterus. That triggers inflammation, fibrosis, abnormal uterine enlargement, heavy bleeding, pain. It's a different location.

Super similar biology, though. So both of these diseases involve chronic immune activation. Both of them [00:11:00] demonstrate inflammatory cytokine signaling, abnormal tissue repair, fibrosis, altered nerve growth. Both disrupt normal hormone signaling. When we understand that, we can stop asking, like, "Where's the lesion?"

and then stopping there, right? We can ask, "Where's the lesion, and what biological environment allowed this disease to develop and persist, and how has this disease changed this body's environment?" When we start shifting our mindset away from just target the lesions to also understand the, the complete picture, the physiology, what's changed in their body, that starts to change everything.

Now I wanna talk about CRP, C-reactive protein, a blood marker of inflammation. This episode was requested by listeners who said, "Can you talk to us about adenomyosis, endometriosis, CRP elevation, chronic inflammation, [00:12:00] how that lends itself to chronic disease progression?" So I wanna talk about one of the most common misconceptions I hear.

It's that if inflammation is driving endometriosis, why is the CRP normal? And that's a fair question, and it highlights one of the biggest limitations of using blood tests to understand chronic inflammatory disease. So CRP, which is known as C-reactive protein, it's produced primarily by the liver in response to inflammatory signals, particularly that interleukin-6 that I talked about before.

It's an excellent marker of systemic inflammation in many situations. We use it to help assess infections, uh, inflammatory conditions like inflammatory arthritis, cardiovascular disease. Like, there's a number of conditions we use it for. But CRP is not a direct measure of what's happening inside specific tissue

So let's think about, like, what happens when you sprain your ankle, 'cause a lot of [00:13:00] endometriosis patients, adenomyosis patients also have connective tissue disorders. You've likely had a sprained ankle. So you sprain your ankle really bad, swollen, warm, inflamed. Immune cells are rushing into the injured tissue, cytokines are released, blood vessels become leaky, more permeable, pain fibers are firing, all right?

They're activated, yet unless the injury is severe, your CRP may barely change. Okay, why is that? Because the inflammation is primarily local, and this same concept can apply to endometriosis lesions. Now, that doesn't mean that that inflammation isn't going systemic, but it may not be at the level where a CRP can catch it.

Much of the inflammatory activity is gonna occur in the pelvis, in the peritoneal area, around the lesions themselves, within the microenvironment that the lesions create. So researchers, they've [00:14:00] consistently demonstrated that elevated concentrations of inflammatory mediators, so these are what we talked about before, interleukin-1, interleukin-6, TNF-alpha, prostaglandins, um, even seeing macrophages and other immune mediators in the peritoneal fluid surrounding endometriotic lesions, this is really, really common to see.

So in other words, the tissue itself is inflamed. Immune system is activated. Yes, biology is altered, but that doesn't always translate into this dramatic rise in CRP circulating throughout the bloodstream. Sometimes we can look at hs-CRP, which is highly sensitive CRP, and that's what we'll find elevated.

So studies that are looking at CRP as a diagnostic test for endometriosis, they've produced very inconsistent results. Some studies find mild elevations, other studies find no meaningful difference, [00:15:00] and there have been large studies that have shown that the high-sensitivity CRP doesn't reliably predict who will later develop endometriosis.

But that doesn't mean we can't use that as a test to understand if we have systemic inflammation going on. And just because we don't see a CRP elevated or an hs-CRP, that doesn't mean inflammation isn't present.

What that means is that CRP is asking the wrong question. It's asking how much inflammation do we have throughout the whole body, so what's the whole body inflammatory burden, rather than the localized immune dysfunction occurring within the pa- the pelvis itself. So that's an important clinical distinction.

A normal CRP should never reassure us that endometriosis or adenomyosis isn't inflammatory. Instead, a normal CRP reminds us that blood biomarkers don't always reflect what's happening within the localized tissue in the area. And if you're a clinician [00:16:00] listening, we have to avoid reducing complex biology to a single laboratory value, because a patient can have profound inflammatory disease while the CRP, the ESR, the CBC, the HSCRP, even routine imaging all appear normal.

So we can't rely too heavily on those tests because we're gonna risk dismissing the very patients who need us most. One of the most important shifts that we can make is recognizing that inflammation exists on multiple levels. So there can be the localized inflammation that is absolutely changing the tissue, changing the biology, causing pain.

There's regional immune activation, and then there's the systemic inflammatory burden, and those are not all always the same thing, not always happening at the same time

Now, if you're listening to this, you're someone who's like, "But my CRP is elevated, my hs-CRP is elevated, like I suspect this [00:17:00] is related to my adenomyosis, endometriosis," absolutely fair. That could be. If you're asking, well, like if we can't measure a CRP, like we measure it, there's no inflammation, uh, you know, what is putting this person at risk for cardiovascular disease, for example.

So just because we can't catch it on the CRP, or maybe, you know, the hs-CRP, you're at like 1.2 and your doctor's like, "That's normal, that's not too bad," that's, that's elevated. But there's that low-grade chronic inflammation that we know can be problematic and can have health consequences over time. If you have an elevated CRP and that's happening over multiple lab draws, so you have repeat lab draws, it stays elevated, that is certainly concerning, and it may very well be related to endometriosis and adenomyosis.

So I know this can feel confusing, but the big takeaway here is that someone may have a normal CRP, but they're still dealing with significant [00:18:00] inflammation, specifically in their pelvis or the localized areas with endometriosis, and that it can be changing systems, it can be changing tissues. The other, on the other end, someone can have an abnormal CRP, and that may very well be driven from their en- their endometriosis, adenomyosis.

What I want you to understand is we cannot look at one lab value and determine everything about this patient's experience, the progression of the disease, um, how extensive the disease is. We just can't do that. Like this, these are imperfect labs

And certainly we shouldn't use just one lab value and tell patients that their pain is in their head and nothing is wrong

Okay, now that we've established that endometriosis, adenomyosis are chronic inflammatory immune-mediated diseases, the next logical question is, does that biology translate into meaningful long-term health consequences? And the answer is studies [00:19:00] say, yeah, it, it appears to be true. So before we dive into the research, I wanna make sure that we, we separate this important distinction that every clinician should definitely understand

Most of the data that I'm about to discuss comes from observational studies. That means these studies identify associations. They cannot, on their own, prove that endometriosis causes cardiovascular disease, that it's causing autoimmune disease, or any other condition. Uh, certainly in the case of autoimmunity, it's very possible that there's g- shared genetics between these conditions.

But I will say when we start seeing the same associations repeatedly across multiple countries in large perspective cohorts with biologically plausible mechanisms, our confidence levels can increase that we're looking at something that's clinically meaningful, and that we need to pause in our patient care and really consider this.

And that's exactly where we are today [00:20:00] with endometriosis. There is no longer just a handful of isolated studies. We are seeing very consistent patterns emerge. So I wanna start with the cardiovascular disease aspect because when we consider what is the number one threat to women's health, cardiovascular disease is the number one killer of women

Historically, cardiovascular disease hasn't been part of the conversation surrounding endometriosis, but my goodness, should it be? Absolutely. So there have been several large studies, and there's also been reviews that have demonstrated that women with endometriosis have a higher incidence of cardiovascular events, and that is including ischemic heart disease, hypertension, stroke, and other adverse cardiovascular outcomes

There was a really big study that came out of Denmark, and it followed women diagnosed with endometriosis over several decades, and what it demonstrated is [00:21:00] that there's a significantly higher long-term risk of cardiovascular disease in endometriosis women compared with women who do not have an endometriosis diagnosis.

Now, why might this be happening? There are several biologically plausible mechanisms. So the first is what we've already been talking about. It's the chronic inflammation. Inflammatory cytokines don't just remain isolated forever, okay? Just because I said, like, they can have localized inflammation doesn't mean that they don't go travel the body, going on their little escapades, okay?

So what you need to understand is that over time, persistent inflammatory signaling, it can contribute to endothelial dysfunction. It's the lining of the blood vessels. It can impair nitric oxide production, increase oxidative stress, and that can accelerate atherosclerotic plaque formation, so plaques in the blood vessels.

The second thing is that there's altered estrogen signaling. So although en- [00:22:00] endometriosis is considered an estrogen-dependent disease, the hormonal environment is not normal. We see progesterone resistance, altered estrogen metabolism, local estrogen production within the lesions. These hormonal a- alterations may influence vascular health in ways that we still don't understand.

And going along with that is third, there's treatment-related factors. So women with severe endometriosis are more likely to undergo repeated pelvic surgery, oophorectomy, removing of the ovaries, or experience earlier menopause. We know that premature loss of ovarian hormones is independently associated with increased cardiovascular risk, so some of the observed risk likely reflects not just the disease itself, but also the consequences of treatments, treatments that doctors are sometimes so flippant about.

And this is why you hear me say time and time again, she is more than endometriosis. You have to [00:23:00] see the whole patient, because a doctor might be like, 'Let's give you Lupron. Let's give you a GnRH agonist. Let's get you Orilissa. Um, and, and let's just give this to you, and this is gonna help your pain.' Well, it may or it may not.

It may not get you any relief. Those lesions are gonna make their own estrogen. So they're giving you these drugs that stop you from being exposed to your own hormone production from your ovaries. Those very hormones are what protect the cardiovascular system, and we know this from looking at research, that when we lose our estrogen, we are at a higher risk for cardiovascular disease.

And so I think that really should give clinicians pause. Before you reach for a GnRH agonist, you should really ask, like, "What are the long-term consequences of this treatment, and is it worth the risk? Will the benefits outweigh the risk?" The answer might be yes. In a certain situation, the answer might be yes.

But when I think about [00:24:00] Dr. Cindy Mosbrucker talking about how Dr. Redwine testified during the trials, because the makers of Lupron, the makers of these GnRH agonists, they knew that some women never recovered their hormones to the level that they were previously. We're talking about, like, 20-something-year-old gals trying to, like, you know, lay down that bone, never recover their hormones to what they should be, and yet this isn't commonly known

it really gives me pause in this. And so while the disease itself can be putting us at risk, the treatments, the treatments may be pushing us further into risk as well. And I'm not saying that makes treatments bad. I'm not saying that everybody with endometriosis is gonna get cardiovascular disease. I'm just saying we need to be asking these questions.

We need to be pausing, and we need to be developing better treatments for endometriosis, because my God, menopause or surgery, that's some BS in 2026.

So my whole point in this section of this episode is that [00:25:00] endometriosis should prompt us to think about cardiovascular prevention earlier than we would otherwise, because the women who are at risk appear to be women under the age of 40. We shouldn't be waiting until midlife to discuss lipid management, blood pressure, exercise, sleep, nutrition, metabolic health.

Those conversations need to be happening with these women in their 20s. As soon as you're diagnosed, these conversations should happen, and it's the unfortunate truth. You know, I talked about this in my endometriosis reset course, if you were a part of it, you heard me say it, is that it's unfair. It's unfair to us that we never get that lead way.

We can never just be like, "Oh yeah, I just wanna like binge eat fast food and party on the weekends," or anything like that, and then be able to recover from it easily. We don't get that. We don't get that kind of flexibility in our lives. In some ways, it is saving us. I think there's, there's, there's something to be said about the silver lining of how it gets us to support our bodies in the way that ultimately leads to health.

We can [00:26:00] certainly argue that side, but it's also just, like, really unfair. It's really unfair. Short end of the stick, and I don't like it any more than you do

Let's shift to autoimmune disease, because another striking finding across the literature is that there's increased prevalence of autoimmune disease. Women with endometriosis are more likely to be diagnosed with autoimmune thyroid disease, hi, it's me, Hashimoto's, rheumatoid arthritis, systemic, lupus, uh, Sjogren's disease, inflammatory bowel disease.

These also ride along with endometriosis, as does multiple sclerosis, pernicious anemia, and other immune-mediated disorders. And what the research tells us is that women with endometriosis, they're about twice as likely to carry at least one autoimmune diagnosis compared to women who do not have endometriosis. Does this mean that endometriosis causes autoimmune disease, or that endometriosis is an autoimmune disease? No, we don't have evidence for that right now, and it doesn't look like endometriosis is necessarily causing autoimmune disease, and it's not [00:27:00] an autoimmune disease. It, it has some shared components, but it is its own little hell beast on its own, okay?

So what a more likely explanation is, is that these conditions, they share underlying mechanisms, so they may be involved in immune dysregulation, altered, uh, immune cell function, impaired immune tolerance, chronic macrophage activation, it's the Pac-Man of the immune system, and then there's the persistent inflammatory signaling.

So in other words, these diseases, autoimmune disease and endometriosis, adenomyosis, they may arise from overlapping biological pathways rather than just one disease directly causing another. Now, if you are a clinician, the practical implication is pretty straightforward here.

If you have a patient with endometriosis and they develop new symptoms that don't fit neatly into that endometriosis picture, maybe the fatigue is getting worse, they have joint pain, dry eyes, uh, numbness, tingling in their fingers, toes, neuropathy. There may be thyroid [00:28:00] symptoms, unexplained gastrointestinal complaints.

Resist the temptation to attribute everything to endometriosis. Sometimes another immune-mediated disease is developing right alongside endometriosis, and so maintaining a broader differential diagnosis is gonna serve patients a lot better than being like, "Endometriosis, that's all I can see. That's all she is.

That's all this could be." We always have to ask what if, what else?

We need to be prioritizing prevention of other diseases outside of endometriosis alongside treating endometriosis because ultimately success shouldn't be measured on whether the patient's pain has improved this month alone, and it shouldn't be measured whether we think we got all the lesions alone.

Getting all the lesions in surgery may be impactful for preventing cardiovascular disease, but if this person's diet, alcohol intake, smoking, uh, you know, lifestyle overall, the way they're moving their body [00:29:00] isn't dialed in, then we're not really gonna get the outcomes that we wanna see

So rather than just focusing on the lesions, I would challenge healthcare that we should be measuring our outcomes on whether we have helped a woman build a healthier trajectory for the next 30 years. I think that's the future of women's health, and I believe that is where the science is taking us, and it's just time for providers to step up and give women with endometriosis and adenomyosis the care that they deserve.

As always, thank you for being here with me. It is an honor to share time with you week after week. It is not lost on me that your time is one of your most precious, valuable assets, so thank you again. If you can take a moment to share this with someone who needs it, like, subscribe, comment, do all of the things that help this podcast, I would appreciate it so much, and I will see you next week.