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BackTable / OBGYN / Article
Adenomyosis vs Endometriosis: Symptoms, Diagnosis & Treatment
Faith Taylor • Updated Nov 19, 2024 • 44 hits
Adenomyosis is a condition characterized by the growth of abnormal tissue within the uterine muscle, whereas endometriosis involves the presence of endometrial tissue outside the uterus. Despite this difference, adenomyosis and endometriosis share a significant overlap in symptoms, including pelvic pain, heavy bleeding, and inflammation making it difficult to distinguish between the two. This diagnostic ambiguity often leads to misdiagnosis or delayed identification, complicating treatment decisions and leaving patients without effective symptom relief.
Reproductive endocrinology and infertility (REI) specialist Dr. Keith Isaacson provides an overview of the relationship between adenomyosis and endometriosis as well as current research on diagnostic overlap, treatment options, and pathophysiology. This article features excerpts from the BackTable OBGYN Podcast. We’ve provided the highlight reel here, and you can listen to the full podcast below.
The BackTable OBGYN Brief
• Adenomyosis and endometriosis share overlapping symptoms with conditions like IBS and interstitial cystitis, where inflammation and crosstalk between pelvic organs can exacerbate pain and disrupt bowel and bladder function.
• Adenomyosis often goes undiagnosed due to its intramuscular location and symptoms, which are frequently misattributed to endometriosis or other conditions.
• Improved ultrasound and MRI techniques now provide more consistent evidence of adenomyosis, though diagnosis still lacks histological confirmation in the absence of hysterectomy.
• Hysterectomy can offer long-term relief from adenomyosis and endometriosis symptoms but is typically considered only for patients who are no longer considering pregnancy.
• Current treatments, including hormonal therapies and less invasive surgeries, can manage symptoms but do not address the root causes of adenomyosis and endometriosis.
• Due to a lack of suitable animal models, organoid models have been tissue engineered to replicate the peritoneal surface and uterine environment in order to research the disease mechanisms and inflammatory pathways in adenomyosis and endometriosis.
• To avoid surgical intervention and the negative side effects caused by hormonal treatments, clinicians are researching alternative treatment methods that would inhibit the inflammatory pathways that cause adenomyosis and endometriosis.
• Current research suggests a potential link between the reproductive microbiome and inflammation in adenomyosis or endometriosis, but more evidence is needed.
Table of Contents
(1) Adenomyosis vs Endometriosis: Differences in Symptoms, Diagnosis & Treatment
(2) The Role of Inflammation in Adenomyosis, Endometriosis & Other Pelvic Conditions
(3) Identifying Inflammatory Targets for Adenomyosis & Endometriosis Treatment
Adenomyosis vs Endometriosis: Differences in Symptoms, Diagnosis & Treatment
Adenomyosis and endometriosis often present with overlapping symptoms, such as dysmenorrhea and heavy menstrual bleeding, making accurate diagnosis challenging. Historically, adenomyosis was underdiagnosed due to its intramuscular location and the limitations of laparoscopy, which focused on visible lesions of endometriosis. Advances in imaging, such as MRI and ultrasound, now allow for the identification of changes consistent with adenomyosis, though confirmatory pathology remains rare and often unnecessary for treatment.
Clinicians are shifting toward a symptom-based management approach, reserving surgery for cases with bowel or bladder involvement when treating both of these conditions. Treatments like the Mirena IUD are increasingly favored over surgical or extensive hormonal interventions when symptoms suggest adenomyosis or mild endometriosis. Therefore treatment needs to be tailored to each individual patient's unique symptom set.
[Dr. Mark Hoffman]
You see adenomyosis and endometriosis as the same disease spectrum?
[Dr. Keith Isaacson]
No, I think people are confused. I think 95% of women who present with dysmenorrhea have adenomyosis. Just tell me physiologically how a spot of endometriosis on your bladder is going to cause painful period, cramping period. How does that happen? How does the spot of endometriosis on your bowel cause dyspareunia? It just doesn't make sense. The only reason we accepted that is because you did a laparoscopy and you couldn't see adenomyosis, right? It's in the muscle. If you can't see it must not be there, but that's just not the case. Now you can see changes that are consistent with it and it makes a big difference.
If you look at all the papers and say, okay, how come women with stage one and stage two endometriosis got better after surgery? Look at the papers. Every single one of them, after surgery, they were put on hormonal suppression, every one. If you do surgery and then you put them on hormonal suppression, you should get better. Now do the same paper without putting them on hormonal suppression and see what happens. I don't think ethically you could do that.
[Dr. Amy Park]
Yes. I'm also surprised like how many hysterectomies I do for prolapse and then it feels like adenomyosis. It's so soft and then pathology does not reflect it. Then I do these hysterectomies for adenomyosis and the pathology doesn't reflect it either. To your point about how many slices they're doing or what have you, I've had that happen with the tubes as well where I had a patient, I took out her tubes, and then a year later she was diagnosed, or two years later, she had ovarian cancer. Then they went back and looked at the tubes and it was like, oh, it was there. Just kidding. Some [unintelligible 00:31:21] was there. I don't know if that's something more slices or AI or something could help with diagnosing that.
[Dr. Keith Isaacson]
It doesn't change the management at that point. The only time it's going to be helpful to do that is for research purposes and then you tell them to slice more and they'll find more. It doesn't change what you're going to do.
[Dr. Mark Hoffman]
Finding the true prevalence of the disease, I think, like you said before, is very valuable and powerful to say like, look, the people who have these symptoms, if you look hard enough, most of them will have some pathological evidence of an abnormality, right? That's something that--
[Dr. Keith Isaacson]
Yes and no. We got to be careful here too because I object to gynecologists and a lot of them are doing this who say, okay, by MRI and by ultrasound, you have adenomyosis. You don't have a pathology to prove it. Really the proper thing to tell a patient is you have changes that are consistent with it. I don't have a biopsy. I think it's there based on your symptoms. Which is another reason why the gynecologist needs to do the ultrasound, because you're the one who knows the symptoms, so you know what to look for. I still don't have a biopsy to prove it. Is it necessary to get a biopsy? It'd be great.
There's a study from Belgium where they used a spirotome to try to go in and get a biopsy hysteroscopically into the area where the ultrasound was abnormal. Again, it's only going to be done for research purposes because it really doesn't change your management. You're going to treat the symptom, not necessarily the fact that it's there. I think it'd be wonderful to know the true prevalence, but I don't know how important it is as long as by ultrasound we can show the changes and then act accordingly. I don't want to over-call it. I'm biased. Pretty much everybody in my practice has adenomyosis until proven otherwise. I have to be careful not to over-call it.
All the patients who come in with heavy bleeding and all those patients who we did endometrial ablations on, that was the interesting thing. It was contraindicated if they had adenomyosis. It was also contraindicated if they had a submucous myoma. Those are the only two things that cause heavy bleeding. The only patients getting the ablations were adenomyosis patients. Thank goodness we don't do many of those anymore either.
[Dr. Mark Hoffman]
Certainly, in my practice, there's a lot of people who are sad to see me because they failed. They didn't fail. The procedure failed them, but they have persistent symptoms. Guess what I'm trying to say when I say we want to understand the prevalence, not to make a diagnosis in everyone, but the same way when I have somebody who comes in with painful periods or pain with intercourse, like you said, telling them it's not normal, I can't diagnose endometriosis without surgery, does that mean I need to do surgery to treat you with continuous OCPs or norethindrone? No, because if I do the surgery and find it, the treatment's going to be the same.
If I do the surgery and don't find it, maybe you have adenomyosis and the treatment's going to be the same. Unless we're actively going in there to do something, if you feel better without surgery, is there a need for surgery in that particular patient at that point? I think there's some debate on that topic.
[Dr. Keith Isaacson]
Right. I think if it's dysmenorrhea, which again, is the primary complaint for 80% of the patients with endometriosis, then a Mirena makes more sense than a continuous pill to me. I encourage them to go that route as opposed to a pill, and some will accept it and some won't. That's how at least seeing the ultrasound evidence or the MRI evidence changes my practice a little bit. Then the ones that I reserve for laparoscopy are the ones that have bowel symptoms, bladder symptoms, things that are clearly at least symptomatologically, whatever, is outside the uterus.
[Dr. Amy Park]
It's so interesting because I'm sort of adjacent to the field, but it's like pre-op diagnosis, still challenging. No blood tests or anything. It's imaging. Pregnancy, those patients who are desiring fertility or uterine preservation, treatment is still challenging. Pathophysiology, we still don't know. I do have to say when I do a hysterectomy for the adeno patient, they are really satisfied. They're like the happiest patients once they're done. It's just so interesting to me that nothing has changed. Why? The funding. The imaging has gotten better, I will say, for the ultrasound and the MRI, and MRI has gotten cheaper and it's a little easier to get covered. We've talked a lot this show about what's the best patient-centric options. We're sort of not having a lot of options. It feels so bleak.
[Dr. Keith Isaacson]
I don't disagree, but I think we're going in the right direction. If we get funding, that's even going to be better. I go back to where we were in 1972 and [unintelligible 00:36:44]. I don't know if you guys know [unintelligible 00:36:45], but he was a pioneer mixed surgery, reproductive endocrinologist out of Houston. In 1972, he wrote a book and in his book, I always give this in my lectures, he said, endometriosis is a disease of upper-class white women who have a desire to excel. They're high-maintenance women.
[Dr. Amy Park]
Wow.
[Dr. Keith Isaacson]
Wait a minute. No, he says they dress impeccably and they're demanding. Okay. That's what he said. Those are the patients at risk for endometriosis in 1972. What was the reason for that? Because they're the only ones that got laparoscopy. It wasn't available to everyone. It was the upper-class white women who demanded it. That's where we are with adenomyosis, well, at least maybe five years ago. That we were so wrong as far as who it impacts only because we're making the diagnosis by hysterectomy. I do think in the last five years, just to look as your glass as half full instead of half empty, we've made a lot of progress.
I'm hoping in the future we'll have meetings that are called endometriosis meetings are called adenomyosis meetings because I think it has a much greater impact on a woman's life than the actual stage one, stage two endometriosis.
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The Role of Inflammation in Adenomyosis, Endometriosis & Other Pelvic Conditions
The apparent relationship between adenomyosis and endometriosis may indicate inflammatory crosstalk among pelvic organs, including the bowel and bladder. This phenomenon, often observed in visceral cross-sensitization, may underlie overlapping syndromes such as irritable bowel syndrome (IBS) and interstitial cystitis in patients with these uterine disorders. While surgical interventions like hysterectomy often alleviate bowel symptoms associated with adenomyosis, the precise mechanisms remain unclear.
Research into the role of the reproductive microbiome has suggested possible bacterial influences on inflammation, yet methodological limitations hinder definitive conclusions. Dr. Isaacson emphasizes the importance of hypothesis-driven research in understanding these connections, advocating for a structured approach over broad exploratory studies.
[Dr. Amy Park]
Let me just ask also about, endo, I know there's this whole crosstalk, visceral cross-sensitization. Do you see that as much with adenomyosis? I don't know. It doesn't seem as prevalent, but I was just wondering.
[Dr. Keith Isaacson]
Crosstalk in what way?
[Dr. Amy Park]
Ashley Gubbels is here and she's our pelvic pain specialist. She always talks about the bladder and bowel crosstalk and how there's a lot of syndromes that overlap. It doesn't seem like the adenomyosis does that as much, but I don't know, because you guys are seeing them more.
[Dr. Keith Isaacson]
I think it does. This is what my collaborator, Linda Griffith is-- she's passionate about. She's convinced that a lot of women who are presenting with this irritable bowel syndrome, particularly any bowel symptoms, they get worse with your period, maybe related to the inflammation that's right in the uterus, which is right up to the right adjacent to it. We don't have any proof of it, but I do think there is a camp that agrees 100% that there's crosstalk, particularly between the bowel and the adenomyosis.
[Dr. Amy Park]
Is it just a central sensitization or we just don't know? Same nerves? [crosstalk]
[Dr. Keith Isaacson]
I don't know. It's again, the thing to follow when you do the hysterectomy for adenomyosis, a lot of the bowel symptoms go away. I don't know the mechanism.
[Dr. Mark Hoffman]
When I talk to patients about interstitial cystitis or IBS and endo, we know they're commonly co-diagnosed, and treating one oftentimes makes the other better. Like you said, we can give birth control pills, and a lot of times their bowel symptoms get better or their bladder symptoms get better. It's these chronic pelvic inflammatory conditions with no known cause, but clearly, the neighbors are pissed off. If one person's inflamed and angry, the neighbors aren't going to be too thrilled either.
[Dr. Keith Isaacson]
Yes…The difference is endometriosis, you can get a histologic diagnosis. You can't get that with irritable bowel. I'm not sure you can really get it with interstitial cystitis. That's somewhat debatable. Those two are a little more subjective versus objective, but the endometriosis at least you can document. I agree. I think at the end of the day, I think it's going to be an inflammatory condition on all of them. The inflammation pathway, believe it or not, just hasn't been worked out with endometriosis and adenomyosis.
[Dr. Mark Hoffman]
I've read a few articles about the microbiome, the reproductive microbiome. We've had people come on the show and talk about the urinary tract microbiome and why people thought urine was sterile. Obviously, there's talk there. That was one of the questions I asked. I think he said, what about the reproductive microbiome? Why do we think that's sterile? Why would it be sterile? Sperm gets up there. There's obviously a connection between the vagina and the pelvic cavity, right, the peritoneal cavity, because otherwise there'd be no reproduction. There's some early, early, early studies about certain bacteria that are more prevalent in women with endometriosis and also could potentially explain the adenomyosis. It's all inside the uterus too. Do you think there's any connection there? What are your thoughts on that?
[Dr. Keith Isaacson]
It's not the way I like to do science. Microbiome is now a research tool. What we're doing is let's take that research tool and apply it to a condition and see if we can find a connection. The way I would prefer the science be done is let's come up with a hypothesis, which bacteria or how the microbiome could actually cause endometriosis or impact adenomyosis, and then look for it. It's the same problem. The reason we didn't get anywhere in the last 20 years for endometriosis wasn't because we weren't looking at inflammatory cytokines or monokines, but everybody had their favorite one. They would say, okay, my lab focuses on IL-6.
I'm going to look at IL-6 and endometriosis and come up with a hypothesis. That's not the right way. You're not going to get anywhere in science if you do research that way. You need to come up with a hypothesis first that has some scientific basis to it, then use your research tools to either confirm or deny that hypothesis. I don't know if I'm making sense, but that's how I see the microbiome right now. I haven't seen anyone come up with a real hypothesis. They say, there's a research tool, let's just throw it at endometriosis, see what comes out. I'm not a fan of that approach personally. Hopefully, I'm wrong and they'll find something.
[Dr. Mark Hoffman]
No, I appreciate your input. Again, that's why we like having guests like you on the show, because I'm not a scientist. This is stuff that to me, I think a lot of us out there that are doing this work, that are taking care of patients that, like we said, don't have the answers, we're very glad there's people like you out there that are doing the science, that are trying to figure this out in a way that can result in an answer.
Identifying Inflammatory Targets for Adenomyosis & Endometriosis Treatment
Traditional treatments for adenomyosis and endometriosis, such as surgery and hormonal suppression, have seen little progress over the past three decades, often failing to address the root cause of these diseases. Current research efforts are focused on developing organoid models using tissue engineering, which replicate the peritoneal surface and uterine environment. These models enable researchers to manipulate cytokines, monocytes, and inflammatory pathways to better understand disease mechanisms. Their ultimate goal is to identify specific inflammatory targets that can disrupt the disease process without the adverse effects of hormonal therapies. This emerging approach focuses in on the inflammatory nature of these conditions and highlights the need for treatments that move beyond surgical and systemic hormonal interventions.
[Dr. Mark Hoffman]
Talk to us about endometriosis and adenomyosis. I know with your lab, maybe you can go into a little bit more detail about what y'all have learned or what y'all are finding in sort of the relationship between endometriosis and adenomyosis.
[Dr. Keith Isaacson]
Yes, the lab focus is really a little different, and that is, as you're aware, with endometriosis and adenomyosis, there's no good animal model. Because the only animals that get spontaneous endometriosis are the monkeys, and it's almost impossible to study monkeys. There were a couple chimpanzee populations, one in Kenya, one locally in the past, but they're just too expensive. You just can't do it anymore. All the other animal models looked at rabbits and rodents, and this endometriosis was falsely created surgically, but these are not animals that cycle on a monthly basis, so the validity of those animal models is probably very little.
The whole idea was, could we-- What Professor Griffith has done in the past, she's a tissue engineering person, so she grew the first human ear, actually, in a mouse that was just transplanted out to a human. She's grown bladder, she's grown bowel, now she's trying to grow liver. I went to her in 2009, and I said, can you grow a perineal surface so that we can study endometriosis, and can you grow a uterus so we can study adenomyosis? That is where we are with this. This technology has developed, instead of growing whole organs like you would an ear or bowel or bladder, it's all done on an organ on a chip, which is organoid models.
Now these organoid models, they're working, they're being perfused with oxygen and blood, and now we're at the point where you can add and subtract various cytokines and monocytes and inflammatory factors to really just study the behavior. Even though I'd love to say we were further along to understand the disease, we're trying to build the model so that we can understand the disease. Because I truly think our goal here is not to really overwhelm women hormonally who are suffering from endometriosis and adenomyosis. If this is truly an inflammatory disease, then there should be some pathway in the inflammation that you could interrupt that's going to treat the disease without suppressing them, without putting on megadose progestins, all the horrible things that they have to go through.
That's the goal of the research, and we're just about at the point now where we're going to start testing some inflammatory inhibitors to see how it works in the model. That's where we are. It's really exciting work, but is it going to be clinically useful in the next five years? Probably not, but it's going to help. If you think back on it, Mark, you're not as old as me, but we haven't progressed in the last 30 years in this disease. We're still treating with continuous pill. I think our understanding of who suffers from endometriosis and adenomyosis is better than it was 30 years ago. As far as treatment, it's identical, it hasn't changed. I don't think surgery is the answer, and currently hormonal suppression is not the answer.
[Dr. Mark Hoffman]
Do you feel the same way about endometriosis?
[Dr. Keith Isaacson]
Absolutely. Even more so with endometriosis, yes.
[Dr. Mark Hoffman]
We had this conversation at our resident gynecology conference, and just the longer I've done this, the less I think surgery is the answer. I love AAGL, and it's afforded me many of my professional opportunities, but a lot of the folks there are so focused on the surgical treatment. To me, it's a microscopic disease, and I've talked about this on the show a number of times, but reading The Emperor of All Maladies and understanding how those early surgeons were just cutting more and more away until they understood, this may be at the cellular level. This is not something that we can cure with a knife. The longer I've done this, the more I think we're chipping away at like an infection as opposed to actually treating the cause.
Podcast Contributors
Dr. Keith Isaacson
Dr. Keith Isaacson is a minimally invasive gynecologic surgeon with Mass General Brigham Newton-Wellesley Hospital in Newton, Massachussetts.
Dr. Amy Park
Dr. Amy Park is the Section Head of Female Pelvic Medicine & Reconstructive Surgery at the Cleveland Clinic, and a co-host of the BackTable OBGYN Podcast.
Dr. Mark Hoffman
Dr. Mark Hoffman is a minimally invasive gynecologic surgeon at the University of Kentucky.
Cite This Podcast
BackTable, LLC (Producer). (2024, April 30). Ep. 52 – Navigating Adenomyosis: From Misconceptions to Innovative Solutions [Audio podcast]. Retrieved from https://www.backtable.com
Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.
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