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Podcast Transcript: Navigating Adenomyosis: From Misconceptions to Innovative Solutions

with Dr. Keith Isaacson

This episode of BackTable OBGYN features an extensive discussion with Dr. Keith Isaacson, a specialist in Reproductive Endocrinology and Infertility, regarding the complexities of diagnosing and treating adenomyosis, emphasizing surgery, medical treatments, and research in the field. You can read the full transcript below and listen to this episode here on BackTable.com.

Table of Contents

(1) Adenomyosis Overview: Prevalence, Symptoms & Fertility Impact

(2) Diagnosing Adenomyosis: Accuracy of Ultrasound & MRI

(3) Managing Adenomyosis: Treatment Options & Fertility Solutions

(4) Exploring the Relationship Between Endometriosis & Adenomyosis

(5) Funding Gaps in Women's Health & Adenomyosis Research

(6) Adenomyosis & Endometriosis: A Spectrum of Symptoms & Diagnostic Challenges

(7) Adenomyosis Syndrome Overlap with Other Conditions

(8) Advancing Adenomyosis Research: Insights from Leading Labs

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Navigating Adenomyosis: From Misconceptions to Innovative Solutions with Dr. Keith Isaacson on the BackTable OBGYN Podcast)
Ep 52 Navigating Adenomyosis: From Misconceptions to Innovative Solutions with Dr. Keith Isaacson
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[Dr. Mark Hoffman]
Hello, everyone, and welcome to The BackTable OBGYN Podcast, your source for all things obstetrics and gynecology. You can find all previous episodes of our podcast on Spotify, Apple Podcasts, and on backtable.com. Welcome back to another episode of BackTable OBGYN. This is your host, Mark Hoffman. Once again, I've got with me, Dr. Amy Park. Amy, how are you?

[Dr. Amy Park]
Good. How are you?

[Dr. Mark Hoffman]
Good. Clinic day, OR day, admin day. What were you up to today?

[Dr. Amy Park]
Yes, I had meetings all day.

[Dr. Mark Hoffman]
I'm getting used to that. This is my last week of actual full clinical schedule. Next week, it just becomes meetings, mostly meetings. All right. We have a great guest today. As usual, this is someone I've known for a long time. I think everybody knows [Dr. Keith Isaacson] Isaacson, reproductive endocrinology and infertility specialist and minimally invasive gynecologic surgeon at Newton-Wellesley Hospital, clinical director for MIT Center for Gynepathology Research. He's an associate professor of OBGYN at Harvard Medical School and past president of AAGL, SRS, and the AAGL Fellowship Board. Is that right, Keith?

[Dr. Keith Isaacson]
That's correct.

[Dr. Mark Hoffman]
Welcome to the show.

[Dr. Keith Isaacson]
Thank you for having me.

[Dr. Mark Hoffman]
Like we'd like to do for most of our guests, tell us about yourself, your practice, sort of how you got to be where you are and what you're up to in your day-to-day.

[Dr. Keith Isaacson]
Sure. I went to undergraduate school at Tulane University and then went to medical school at Emory in Georgia, then went to do my fellowship in reproductive endocrinology in University of Pennsylvania, which was heavily focused on reproductive surgery at the time before IVF, and then started my first job at Mass General and Harvard Medical School in 1989, and have been doing that ever since.

Starting in 2001, even though I still practice at Mass General and Brigham and Women's Hospital, I moved most of my practice to Newton-Wellesley Hospital because we had more opportunities for surgery. Starting in 2004, we began our fellowship for minimally invasive GYN surgery to the AAGL, and that is still going strong. Then from 2009, I started collaborating with Professor Linda Griffith at MIT for the Center for Gynecopathology Research to study really the origins of endometriosis and adenomyosis using organ-on-a-chip technology.

Today, still busy clinically, see patients Mondays and Tuesdays, do a lot of office hysteroscopy procedures. Wednesdays is my research day, try to spend most of it at MIT when I can. Thursday and Friday are either all-day surgery or surgery plus research. Then Saturday and Sunday, I try to make it to New Orleans to go visit my two-year-old grandson at least once a month.

[Dr. Mark Hoffman]
Sounds like a good balance.

[Dr. Keith Isaacson]
Yes, it's fun. It's fun. Thank you.

(1) Adenomyosis Overview: Prevalence, Symptoms & Fertility Impact

[Dr. Mark Hoffman]
Maybe later on, we can get into the, since you've discovered the origins of endometriosis, we were talking about that yesterday with my residents and it's like, the list of possible causes of endometriosis just keeps growing. Let's start with adenomyosis. What is adenomyosis?

[Dr. Keith Isaacson]
Adenomyosis is the presence of epithelial glands and stroma in the muscle of the uterus. It was a disease up until about, I'd say, six or seven years ago that was thought to affect only women in their late 30s up to menopause, that caused heavy menstrual bleeding, painful periods, and possibly painful intercourse. The reason we thought that it was only women who-- and we thought women who were multiparous, who had several children, were at higher risk for developing the disease. It turns out the only reason we thought that is because those were the women who were getting hysterectomies for their pain and heavy bleeding.

Certainly, if someone's in their 20s and having pain and heavy bleeding, they're not going to have the hysterectomy. The disease was diagnosed by histology, by taking out the uterus, and we happened to miss the disease in all the women who did not have a hysterectomy. With the advent of better MRI criteria and now ultrasound criteria to help us diagnose the disease, we realized that adenomyosis is present in women and girls as early as high school age. It turns out about 15% of girls in high school miss at least one to two days a month because of heavy or painful periods.

Now when you do ultrasound on them, you can see ultrasound evidence of adenomyosis. It's much more prevalent than we thought it was. It's now we understand that it affects all women in any reproductive age group. Certainly, probably the fact that they had had their children does probably not increase the risk of developing the disease. Everything we thought we knew about adenomyosis five years ago turns out to be wrong. We have to start over. We also know now that it impacts fertility with women with recurrent implantation failure, as well as early miscarriages and possibly even premature deliveries.


The most interesting part of this is that 80% of women who have adenometriosis present with painful periods, heavy cramping. We always thought that, okay, that's related to stage one or stage two endometriosis. You go in, you remove a low lesion on the ovary or the surface of the peritoneum, that that's going to improve. It turns out we just missed the adenomyosis in those patients. My personal bias is that adenomyosis is probably much more common and certainly presents with more common symptoms than endometriosis does. We had to have to rethink everything we thought we knew about endometriosis, as well as adenomyosis. That's where we are today.

[Dr. Amy Park]
Why would it cause infertility? Is it just produced like some bad juju? Can you explain it to me, a non-REI?

[Dr. Keith Isaacson]
Yes. I don't know about the bad juju part, but there's two parts of the myometrium of the uterus. There's the inner myometrium, which is thought to be represented in an MRI, as a junctional zone. Then there's the outer myometrium. They actually had different embryologic origins, where the inner myometrium is Müllerian in origin, and it responds to estrogen and progesterone receptors. It gets thick and thin throughout the cycle and has coordinated contractions. This inner myometrium in their proliferative phase of the cycle actually has these contractions that bring the sperm into the cavity.

In the second half of the cycle, it's either quiescent or it actually contracts to keep bacteria out of the cavity. If you disrupt that coordinated contraction, which adenomyosis does, type 2 myomas do, type 3 myomas do, that's one of the theories as to how it might impact infertility and implantation. It's just a theory. There's other theories that-- there's other juju that's been thrown out there, like the Hox10 gene, the homeopathic genes are also dysregulated in patients with adenomyosis. At the end of the day, there are a lot of theories as to why that's happening.

I think the data on looking at implantation failures in patients who have genetically screened normal embryos and even patients who have had donor embryo studies, those with adenomyosis have about a 50% lower rate of implantation and a higher miscarriage rate than those without adenomyosis. I think the fact that it impacts fertility now is no longer really controversial based on the data. The mechanism is still very, very much unknown.

(2) Diagnosing Adenomyosis: Accuracy of Ultrasound & MRI

[Dr. Mark Hoffman]
When you say diagnosed, though, like you said earlier, we're diagnosing it historically pathologically. That's what I was taught in residency. Now we have a lot of ultrasound reports and MRI reports that are reading adenomyosis. How accurate are ultrasound and MRI in diagnosing adenomyosis?

[Dr. Keith Isaacson]
The short answer to that question is approximately 80% accurate. If you look at these studies that were done well by Caterina Exacoustos in Italy, Danielle Luciano here in Connecticut, when they actually did the study where they looked at ultrasound criteria and then compared it to their histologic data on hysterectomy, they were able to find that about 80% of the time. That data is actually hard to reproduce, so we've looked at it in our patients, others have looked at it and find it closer to 40% to 50% of the time. The key is how many slices the pathologist does. When Caterina Exacoustos did her study, she asked the pathologist to get at least 15 slices of the uterus.

A normal uterus will have about five or six slices. If you actually do more slices, you'll find it more often. The fact that it's not on the pathology report is not really an indicator that it's not there, it's just that he didn't ask the pathologist to take enough slices.

[Dr. Mark Hoffman]
It reminds me of the fallopian tube, and we had the guests come on talking about fallopian tube cancer and how much of the ovarian cancer that we think of historically, the high-grade epithelial ovarian cancer, started in the tubes, and we just didn't really take many slices to even look for premalignant lesions. Not that it's not there, it's just that we're maybe not looking for it enough.

[Dr. Keith Isaacson]
Exactly.

(3) Managing Adenomyosis: Treatment Options & Fertility Solutions

[Dr. Mark Hoffman]
The other thing that is, I think, challenging for a lot of us, though, is that if we have ultrasound or MRI findings suggesting adenomyosis, then what? Obviously, infertility treatments can vary state by state. I'm in a state that is very different than Massachusetts, where you are in terms of coverage, but also with symptoms. Let's start with symptoms. I know how you treat adenomyosis is a little bit different, probably, than a lot of people treat adenomyosis, but what are the traditional treatment options for adenomyosis for symptoms, and then what are you doing differently in the same question for infertility?

[Dr. Keith Isaacson]
Let's go back a little bit just to the diagnosis, because what you'd have is, let's say you have a 25-year-old patient, which is not uncommon, who's had debilitating, painful periods, really since menarche, since she started her periods, and she's been told by her pediatrician and by her gynecologist who gets an ultrasound, that everything is normal, and they make it sound like, it's all in your head. This is normal. When you do the ultrasound yourself, and you see some of the criteria that are consistent with adenomyosis, and I tell them, I'm not proving that you have it, because I don't have a biopsy. I'm just saying you have changes that are consistent with adenomyosis.

Just the relief you see on their face like, okay, I'm not crazy, really is part of the treatment. It's just recognizing there is an explanation to their painful periods, the suffering they've had for the last 10 years, where they were told everything's normal, just suck it up. My collaborator, Linda Griffith, she had the same issue with adenomyosis endometriosis, is a professor at MIT, and they told her, they said, look, we'll give you a couch to put in the bathroom. When you have pain, you can go lay down on the couch. That was their answer. She also had breast cancer, and they gave her six months off. She says the adenomyosis was much more debilitating than the breast cancer. This is what they're dealing with.

I just want to explain that the recognition of it, just the acknowledgment that there is something that can explain their pain, is half of the treatment. The other half of the treatment is, your options are clearly, it's either medical or surgical or do nothing. Medically is the most common, where ideally one of the levonorgestrel IUDs is placed, because it's thought that the progestin that's absorbed by the myometrium is going to be suppressive, and it helps if they're not having a period. The data show that it does help 80% of the time, and the 15% to 20% that have it removed is not necessarily because the symptoms didn't go away, it's just that they didn't like the side effects.

If that doesn't work, then you have to try other types of suppression that may or may not have big side effects. You may try something like norethindrone, Aygestin, you may try a progesterone-only birth control pill, but when they take the pill, the key is to do it continuously, where they don't get a period, not where they're getting it cyclically. Then the last option is obviously surgical, and surgery, assuming they want to maintain their fertility, is very challenging. I don't do it at all for pain or heavy menstrual bleeding, but we will do it for fertility on rare occasion.

If there's a focal lesion in that junctional zone or that inner myometrium, and the patient's had a history of recurrent implantation failure, then we'll go ahead and resect that lesion hysteroscopically. The largest series of doing this is out of the Ukraine, and it was 20 patients. They had good success in 20 patients. That's a pretty small series. That Ukrainian series was done after the war, so they're still doing it. That's the largest series. Then there's a series out of Japan, where they actually do it by laparotomy, where they resect the whole back wall of the uterus and then do a flap. That works for fertility, but it also has about a 6% chance of a uterine rupture in pregnancy.

[Dr. Mark Hoffman]
Now is this like an adenomyoma we're talking about here? Because a lot of times we look at imaging or look at MRIs, and it looks a little more diffuse. There's not necessarily a specific focal lesion. A lot of us who do myomactomies will take out a myoma that turns out comes back an adenomyoma. It just didn't look and feel right, and it's a little squishy. That's a little bit easier for me to understand as opposed to more diffuse adenomyosis.

[Dr. Keith Isaacson]
Yes. I'm not sure there is such a thing as an adenomyoma. By definition, an adenomyoma is a fibroid that has a pseudocapsule that has glands in it. I don't see that very often. What I see is you're going in for a fibroid, and it's actually just crunchy tissue with no clear plane, and all that is just diffuse adenomyosis in the myometrium. It's not really a fibroid. It doesn't have a pseudocapsule. What they're doing by laparotomy typically is just debulking that. You're not removing all of it. They've had good pregnancy rate success, but again, the risk of the uterine rupture is a little high. I'm not sure.

[Dr. Mark Hoffman]
How many were in that series in Japan? Pretty small as well.

[Dr. Keith Isaacson]
Oh, heck. No. It was much larger. They've done over 1,000 patients. Yes.

[Dr. Mark Hoffman]
Talk to us about hysteroscopic surgery for adenomyosis.

[Dr. Keith Isaacson]
It has to be a focal lesion. You identify it by ultrasound, and then I try to confirm it by MRI. Then I do ultrasound guidance when I'm doing the resectoscopic procedure. You go with a bipolar loop electrode with a resectoscope, and you actually shave out the adenomyosis in that area, that focal area. It's usually about one, one and a half centimeters. Sometimes it's a cyst, which is very easy to see, which is like shelling out an endometrioma. You actually go into the cyst, and it's old blood in it, and you just have to get out the cyst wall. That part is very straightforward.

The harder ones is when it actually looks like glands, it looks like that adenomyosis that you saw by a laparotomy when you did a myomectomy, but it's just right underneath the endometrium. You want to resect that until you get to normal myometrium, and you do that with ultrasound guidance. I've been offering that to patients who have focal adenomyosis. They're select patients that have recurrent implantation failure, but I can't really tell you what the success rate's going to be yet. My series is no more than 20 as well. That's just not enough to make a-- The patients really have nothing else. It's either that, or they're told to do a gestational carrier. It's easy to tell somebody that, but it's also somewhere between $250,000 and $500,000. It's not available to a lot of people.

[Dr. Mark Hoffman]
I didn't realize it was that expensive. That's incredible. Ultrasound guidance, you're using abdominal ultrasound or transvaginal? I know you reproductive endocrinologists will sometimes use ultrasound for IVF and things like that. Normally I would use abdominal ultrasound for something like that.

[Dr. Keith Isaacson]
You have to use abdominal ultrasound for guidance during surgery. You have them fill the bladder, bring in a transabdominal ultrasound probe, and then it's helpful to see about-- particularly if you know where you're looking ahead of time, based on MRI and transvaginal ultrasound, you have a pretty good idea of where you're going to be going, but you don't want to resect any of the-- You want to resect as little endometrium as possible so that you get the best guidance you can. That's why I use all three.

[Dr. Mark Hoffman]
Are you giving them any estrogen or anything afterwards to protect aligning, to prevent Asherman's, and things like that?

[Dr. Keith Isaacson]
No. No. If they have normal estrogen levels, and this is true in patients with Asherman's as well, adding more estrogen doesn't help. The only time to give estrogen is when they're hypoestrogenic, breastfeeding, or something like that. No, there's no reason to give supplemental. The beauty is, it's like a submucous myoma. If you're only resecting one wall, you tend not to get Asherman's. The only time you get the Asherman's with myomectomies is when you're resecting two opposing myomas.

[Dr. Mark Hoffman]
I've heard some opponents of global endometrial ablation for that reason, that if you do hemiablation and just use the old rollerball and do half, your chance of getting an Asherman's is so much lower because you don't have two burned sides opposing the other, and it sounds like it's the same theory.

[Dr. Keith Isaacson]
Right. That's exactly right. Plus, you don't want to resect too much endometrium. You want to keep it focal, or the interest of the patient. Because the other alternative for treating this in patients trying to get pregnant is two to three months of a GnRH agonist prior to a frozen transfer. The data's pretty good that your embryo implantation rate is about 50% of what you would expect if they have adenomyosis in the endometrium. If you pretreat with a GnRH agonist for two to three months, and then you go through the frozen embryo transfer protocol, you'll get your implantation rate back to normal. Let's say it's normally 30%, 15% without treatment, you treat them, and it's back to 30%.

Again, the ones that I do surgery are the ones who say, oh, bad as well. I always try the medical treatment first. The only time I do the surgery is when their next step is they were told to have a gestational carrier. I feel like we have nothing to lose, because I don't think it's a risky surgery. I do think it just helps that you-- if you're fast-sawed with a resectoscope, because the tissue shavers won't work for this. If you're pretty good with a resectoscope, it's pretty straightforward.

(4) Exploring the Relationship Between Endometriosis & Adenomyosis

[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.

(5) Funding Gaps in Women's Health & Adenomyosis Research

[Dr. Amy Park]
Do you think that the White House initiative to put more funding into women's health research will help? It's been woefully underfunded. I think NICHD has now a program officer who's now the gynecologic branch chief who's interested in fibroids and endometriosis. It seems way more promising, quite frankly, for complex gynecologic surgery conditions than urogynecology in a way, to be honest, looking at the way things are going. I agree about the medications. It just seems like Mirena, OCPs, how come we can't have some sort of immune modulator?

[Dr. Keith Isaacson]
You have to understand the pathway, and that's what we're trying to do. That pathway has not been worked out. You have to understand the pathway before you can interrupt it. That's the goal of these models, is to try to do that. Your point about funding is so huge. Jill Biden was here last week or two weeks ago for that, to promote that new funding opportunity. We'll see if they put their money where their mouth is, because we've heard this before. if you have breast cancer, ovarian cancer, anything with oral cancer, you're going to get huge funding. They look at endometriosis, fibroids as benign conditions, and they don't fund them where they're not benign.

They are incredibly disruptive and malignant. They may not be metastatic, but they're malignant. I hear that they're going to go with this new funding and new initiative for women's health. We hope you're right, but so far the funding has been horrible. Also, the publications, if you look at-- I think [unintelligible 00:27:45] shows a slide where in the last five years there's been over 2,000 publications on Viagra, and there's been less than 300 on adenomyosis. It's just, they go where the, I guess, where the money is. I don't know.

[Dr. Mark Hoffman]
When the people voting for where the money goes are primarily interested in Viagra for personal reasons based on what's important to them personally, yes, it is. That's been the hardest thing for me lately is when patients ask me, what we can do, and the answer is, we don't know enough. Here's what we know. I wish we could tell you more, but there's just not enough information. Grateful that you guys are working on an aspect of it.

[Dr. Keith Isaacson]
There are things we can do. I think, again, we can work with our pediatricians. We can work with the primary care docs, that here's the things that are normal and not normal. If you have a patient who's in high school, who's missing school, send her to an adolescent gynecologist who's aware of possible adenomyosis. Teach the gynecologist how to do the ultrasounds themselves because the radiologists don't know how to do this. It's not being taught. They don't know the MISC criteria. They're not aware of picking up adenomyosis by MRI if it's not a thick injunctional zone. We have a lot of work to do just making people aware, and that's stuff we can do now, and we should be doing now. I think that'll go a long way.

(6) Adenomyosis & Endometriosis: A Spectrum of Symptoms & Diagnostic Challenges

[Dr. Mark Hoffman]
You see adenomyosis and endometriosis as the same disease spectrum?

[Dr. Keith Isaacson]
No, I think people confused, because I think they ignored, 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.

(7) Adenomyosis Syndrome Overlap with Other Conditions

[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.

[Dr. Mark Hoffman]
Yes, I don't know.

[Dr. Keith Isaacson]
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.

[Dr. Keith Isaacson]
We hope it works.

(8) Advancing Adenomyosis Research: Insights from Leading Labs

[Dr. Mark Hoffman]
What are the other big labs around the country doing? What are the other directions people are taking that are interesting to you?

[Dr. Keith Isaacson]
It's a great question. May he rest in peace, Rob Taylor, had a great lab going. He's passed away about a month and a half ago. I know Hugh Taylor's doing some work in Yale, looking at the different approaches to this. They're doing good work. Fazleabas in Michigan State. There are some good labs looking at this. They're all different approaches, but at least again, the approach that I hope people will do is let's deconstruct the lesion so we can understand it first. Then as we reconstruct it, we can look for therapeutics that'll interfere with the process.

[Dr. Mark Hoffman]
It's fascinating. It is.

[Dr. Keith Isaacson]
That's my life. There you go. You got it. That and flying.

[Dr. Mark Hoffman]
Still flying?

[Dr. Keith Isaacson]
Still flying.

[Dr. Mark Hoffman]
Do you fly yourself down to New Orleans?

[Dr. Keith Isaacson]
I do. I do. No, I have a dog I fly with.

[Dr. Mark Hoffman]
Can you get there nonstop?

[Dr. Keith Isaacson]
I can get back nonstop. I usually have to make one stop going there because of the headwinds. One of these days I'll stop in Kentucky. I'll look at the fuel prices.

[Dr. Mark Hoffman]
The races are going to start soon in April. [unintelligible 00:44:57] a great time to be in Lexington to fun weekend. Come anytime. All right. Thanks so much. Amy, anything else?

[Dr. Amy Park]
Yes. Thank you so much. I'm just a curious person. I just love hearing your perspective and I'm actually really heartened by the fact that you and Dr. Griffiths are collaborating. Because I think that's where the richness of the clinical and the basic science research and the translational research and really elucidating the pathways, that's where the breakthroughs are going to come through.

[Dr. Mark Hoffman]
It's a really nice article about her, right? What paper was that in? The Globe or was it The New York Times?

[Dr. Keith Isaacson]
Yes.

[Dr. Mark Hoffman]
If you've not read it, Amy, it's awesome.

[Dr. Keith Isaacson]
No, just the collaboration is unique. That's why I feel lucky to be in this area because I go there just given the clinical problem and then I'm surrounded by all these geniuses. I understand about 25% of what they're saying, but I learned something every time I go. We're just doing this amazing 3D histology work on adenomyosis and this label-free three-photon imaging of adenomyosis using the laser. It's just phenomenal. It's fun to watch. I'm just telling you.

[Dr. Mark Hoffman]
I have no idea what you just said, but it sounds very cool.

[Dr. Keith Isaacson]
I'll show you some pictures, but it's fun to watch.

[Dr. Mark Hoffman]
That's great. That's great. It's always a pleasure catching up.

[Dr. Keith Isaacson]
Thanks, guys.

[Dr. Mark Hoffman]
Good to see you. Thanks again for your time. Thanks for joining us.

Podcast Contributors

Dr. Keith Isaacson discusses Navigating Adenomyosis: From Misconceptions to Innovative Solutions on the BackTable 52 Podcast

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 discusses Navigating Adenomyosis: From Misconceptions to Innovative Solutions on the BackTable 52 Podcast

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 discusses Navigating Adenomyosis: From Misconceptions to Innovative Solutions on the BackTable 52 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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