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

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0:47Because Pepsi brings out more flavor, more fun, and more of the moment. Food deserves Pepsi. Grab a Pepsi Zero Sugar today. 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. 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.

1:30Adenomyosis 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 definitions are anatomically true, this is biologically incomplete. So the lesions are not the only aspect of the disease. 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.

2:11And today, I want to challenge the way that many of us think about endometriosis and adenomyosis. By the end of this episode, my hope is you're going to 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 going to 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.

2:52So whether you're a clinician who wants to better understand these diseases or you're someone living with endometriosis or adenomyosis who's been told everything looks normal, oh, just worry about it if you want to 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 going to begin to make sense. Now, if you don't know who you're listening to right now, hi, I'm Dr. Jolene Brighton. I also have endometriosis and adenomyosis. It took me 29 years of menstruating before I got diagnosed.

3:26But 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. Brighton 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 want to make really clear is endometriosis is not just the lining of the uterus. That has migrated to the wrong areas. It's not solely driven by retrograde menstruation.

4:05That 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 endos bestie or cousin because 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.

4:41Now research is saying, not quite. 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 be, yes, it did grow in there. And then because it doesn't belong there and the immune system that's all hot and bothered, 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, it has less funding. So endometriosis gets like no funding, like male pattern baldness or a penis that doesn't work, give them all the money. Give them all the money in the world.

5:19And 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, Like what we're going to 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.

5:55And that means honey. And I'm 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've 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, sometimes control the pain. We know as endometriosis patients, we don't always get that, but it's just like rinse and repeat.

6:36Find 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 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 want to take a step back because if endometriosis were simply misplaced tissue, why do some women develop extensive disease while others don't?

7:16Why 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, 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 that tissue is a problem, okay? But we also have to understand that it involves abnormalities in immune regulation, hormone signaling, inflammation.

8:02There's 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, T cells, those are going to 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.

8:51That helps explain why lesions that appear relatively small are producing profound pain. And then at the exact same time, because this is all happening at once, oxidative stress damages the surrounding tissue. fibroblasts become activated and those are what are going to 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.

9:36So 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 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.

10:16Brake lines are cut. Now, because doctors are always so focused on like, oh, estrogen is the problem and we think retrograde menstruation is a problem, that leads them to say, use the birth control pill, use GnRH agonists, 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. And that explains why endometriosis behaves like a chronic inflammatory disease instead of an isolated anatomical problem.

10:54And we haven't even touched on the HPA access dysregulation, the insulin resistance that can occur, because 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 going to develop outside the uterus, the ovaries, pelvic, peritoneum, 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.

11:35Okay, those are the components 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 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?

12:28When we start shifting our mindset away from just target the lesions to also understand the complete picture, the physiology, what's changed in their body, that starts to change everything. Now, I want to 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, how that lends itself to chronic disease progression? So I want to talk about one of the most common misconceptions I hear. It's that if inflammation is driving endometriosis, why is the CRP normal?

13:09And 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, 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.

13:51So let's think about like what happens when you sprain your ankle. because a lot of 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.

14:34Now 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 going to occur in the pelvis, in the peritoneal area around the lesions themselves within the microenvironment that the lesions create. So researchers, they've consistently demonstrated that elevated concentrations of inflammatory mediators, so these are what we talked about before, interleukin-1, interleukin-6, TNF-alpha, prostaglandins, even seeing activated macrophages and other immune mediators. In the peritoneal fluid surrounding endometriotic lesions, this is really, really common to see.

15:19So 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 HSCRP, which is highly sensitive CRP, and that's what we'll find elevated. So studies that are looking at CRP as a diagnostic tests for endometriosis, they've produced very inconsistent results. Some studies find mild elevations. Other studies find no meaningful difference. And there have been large studies that have shown that the high sensitivity CRP doesn't reliably predict who will later develop endometriosis.

16:07But that doesn't mean we can't use that as a test to understand if we have systemic inflammation going on. Ultra running shoes are all about space. The space to go further, to feel better, to do something you never thought possible. And this space starts with ultra fit. Unlike traditional running shoes, ultra fit gives toes more room to move naturally. So every step is strong, balanced, and comfortable. Whatever you're lacing up for, stay out there with ultra. Shop now at ultrarunning.com. That's A-L-T-R-A running dot com. Teens share everything. That may include the bacteria that can cause meningococcal disease known as meningitis.

16:49Even if your teen's been vaccinated in the past, they could still be missing meningitis vaccinations. Ask your teen's doctor or visit meningitis.com today. Sponsored by GSK. And just because we don't see a CRP elevated or an HSCRP, 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 pelvis itself? So that's an important clinical distinction. A normal CRP should never reassure us that endometriosis or adenomyosis isn't inflammatory.

17:32Instead, 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 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.

18:23There'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 HSCRP is elevated. Like I suspect this 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. 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 HSCRP, you're at like 1.2 and your doctor's like, that's normal.

19:07That's not too bad. 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 inflammation specifically in their pelvis or the localized areas with endometriosis and that it can be changing systems.

19:50It can be changing tissues. On the other end, someone can have an abnormal CRP and that may very well be driven from 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, how extensive the disease is. We just can't do that. 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?

20:38And the answer is, studies say, yeah, it appears to be true. So before we dive into the research, I want to make sure that 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. Certainly in the case of autoimmunity, it's very possible that there's shared genetics between these conditions. But I will say when we start seeing the same associations repeatedly across multiple countries in large prospective 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.

21:39And that's exactly where we are today with endometriosis. There is no longer just a handful of isolated studies. We are seeing very consistent patterns emerge. So I want to 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.

22:22And 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 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.

23:05Inflammatory 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.

23:40So although 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 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.

24:22So some of the observed risks 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 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 Orlissa. And let's just give this to you. And this is going to help your pain. Well, it may or it may not. It may not get you any relief. Those lesions are going to 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.

25:07Those 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 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 Dr. Cindy Mossbrocker talking about how Dr. Redwine testified during the trials because the makers of Vlupron, the makers of these GnRH agonists, they knew that some women never recovered their hormones to the level that they were previously.

25:56We'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 going to 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.

26:38So my whole point in this section of this episode is that 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.

27:13It's unfair to us that we never get that lead way. We can never just be like, oh, yeah, I just want to 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 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 certainly argue that side, but it's also just like really unfair. It's really unfair. It's short end of the stick, and I don't like it any more than you do.

27:48Let'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, 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.