Episode 74
The Missing Link Behind Chronic Symptoms? Mast Cell Activation, POTS & Inflammation with Dr. Tania Dempsey
Mast cell activation syndrome isn’t widely recognized, but for many women, it may explain years of pain, fatigue, and hormone related chaos no one could solve.
I see a lot of patients who are struggling with fatigue, pain, and hormone symptoms that don’t seem to make sense on paper. And I’ve noticed a pattern but I wanted to talk to someone who lives in the complexity of it every day.
Dr. Tania Dempsey, is one of the few physicians who’s helped bring mast cell activation syndrome (MCAS) into the spotlight. Years ago, she was treating a patient who just wasn’t getting better until she stumbled on a paper about mast cells that changed everything. That one article led to a phone call, a new way of thinking, and a career shifting collaboration with one of the leading voices in the field.
In this conversation, we explore how MCAS shows up in gynecology especially in cases involving PCOS, perimenopause, and unexplained pelvic pain. We discuss why some patients are unusually sensitive to progesterone, how inflammation fuels insulin resistance, and what’s actually going on when mast cells become overactive. We also get into the clinical triad so many of us see MCAS, hypermobility, and POTS and how they often appear together in patients who are struggling to get answers.
Tania also talks about how she built her practice by spending more time listening to her patients and trusting that their symptoms meant something, even when the labs didn’t show it.
Highlights:
- What mast cells do and how they become overactive in MCAS.
- The overlooked link between PCOS, perimenopause, and mast cell dysfunction.
- Why some patients react badly to progesterone—and what to do about it.
- How GLP-1 drugs like Ozempic may help calm inflammation in MCAS.
- What to know before seeking a diagnosis or starting treatment.
If this episode opened your eyes or gave you language for what you’ve been going through, please subscribe, leave a review, and drop a comment. I’d love to hear what resonated most with you.
Dr. Dempsey's Bio:
Dr. Tania Dempsey, MD, ABIHM is a world-renowned expert in complex, multisystem diseases. As founder of the AIM Center of Personalized Medicine, in Purchase, NY, Dr. Dempsey uses functional and integrative medicine to get to the patient’s root cause(s) of illness and to help them find a path to optimum health. Her extensive knowledge and experience with Mast Cell Activation Syndrome, Mold, and Lyme and other Vector-Borne Diseases, has propelled her to the forefront of the medical community as a recognized and trusted speaker, researcher, advocate, and physician.
Dr. Dempsey is Board-Certified in Internal Medicine and Integrative and Holistic Medicine. She received her MD degree from The Johns Hopkins University School of Medicine and her BS degree from Cornell University. She completed her Internal Medicine Residency at NYU Medical Center.
She was recently elected to the Board of Directors of ILADS (International Lyme and Associated Diseases Society). She is also a member of the U.S. ME/CFS Clinician Coalition, the American Academy of Ozonotherapy, and ISSWSH (International Society for the Study of Women’s Sexual Health).
She is an accomplished international speaker, writer and thought leader and has 8 peer-reviewed articles in the medical literature. Her latest endeavor is cohosting the new podcast, Mast Cell Matters.
Get in Touch with Dr. Dempsey:
Get in Touch with Dr. Rahman:
Transcript
But I wanna, and I'll do your intro kind of after our thing is done. So then I'll use your information you sent over, your assistant sent over to do an introduction. So we can just start, kind of start talking a little bit. But, you know, I wanna talk about MCAS. I wanna actually talk a little bit about like, because I do a lot, know, half of my practice is menopause management. So really how the hormones interplay like either with PCOS or perimenopause and how so many of my MCAS patients have so much trouble with some of that. So I wanna get into that with you a little bit too.
Tania Dempsey, MD (:Yeah. Just having.
Tania Dempsey, MD (:Yeah, yeah, love talking about that.
Dr Sameena Rahman (:Awesome. Hi everyone. My name is Dr. Samin Arman. I'm gyno girl. Welcome back to another episode of Gyno Girl Presents Sex, Drugs and Hormones. Thank you for joining me on today's episode. You guys are gonna, you you heard in my introduction. It's gonna be very amazing talk to talk about a condition that's not talked about enough, but for those of us in this field that see a lot of various conditions, we see a lot of it. So welcome Dr. Tanya Dempsey.
Tania Dempsey, MD (:Thanks so much for having me. I can't wait to dive right in.
Dr Sameena Rahman (:Let's dive right in because I want to be caught, because you're just so knowledgeable on all of this stuff. you know, first of all, before we get into all of it, like, tell me kind of what brought you into the focus for today, because there's a lot that you focus on, but I want to just focus on mast cell activation and activation syndrome and how it kind of intersects with the stuff that we see as gynecologist sexual pain.
endometriosis and perimenopause, menopause, all the hormonal shifts that happen at various times in our lives, these fluctuating levels of hormones and how it impacts patients. tell our listeners how you kind of came into this world of MCAS.
Tania Dempsey, MD (:Yeah, it's actually an interesting journey. You know, I'm basically an internist by training. And so I was doing internal medicine for at least 12 years before I went on my own. And my interest really at the time was in women's health and polycystic ovarian syndrome, PCOS. So as an internist, that was really my passion because I really felt like those women were really not
Dr Sameena Rahman (:interesting.
Dr Sameena Rahman (:Yeah.
Tania Dempsey, MD (:taken seriously, they were struggling with so many various symptoms and no one was really getting to the root cause. And so I started thinking about it and I started treating it and I had some great success stories. But being in a multi-specialty practice where you have seven minutes to see a patient, it becomes impossible, right?
Dr Sameena Rahman (:Yeah. yeah. Impossible.
Tania Dempsey, MD (:So at some point, it's a longer story than that, but at some point, like in 2011, I said, I think I have it, that's it. I'm gonna go on my own and I'm going to start, I'm gonna see patients the way they deserve to be seen. Spend time with them, get a proper history, help them navigate the healthcare system. And actually when I started, I sort of thought...
Dr Sameena Rahman (:Yeah. Yeah. Yeah.
Dr Sameena Rahman (:Right.
Tania Dempsey, MD (:no one's really gonna come. So I'll just set up like a small little office and I don't really think that, you know, anyone's gonna follow me, right? So then like all the patients followed me and it grew really quickly. And then, know, inevitably when you're spending time with patients and you're really trying to understand the connections between things, because that's the way my brain has always been, inevitably you're going to start to discover things, right? That you never heard about.
Dr Sameena Rahman (:Yeah, yeah. You and I are serious. Yeah.
Dr Sameena Rahman (:Absolutely, yeah.
Dr Sameena Rahman (:Yes, yes,
Tania Dempsey, MD (:And so somewhere around 2014, I had this patient who had this layer of symptoms following a sort of upper respiratory infection and it was lasting months and I could not get her better. And I kept thinking, and she had a lot of hormonal issues, she had a lot of stuff and I kept thinking like I'm missing something. I don't know why she's not getting better. We've tried so many things and you know, it was one of those fortuitous
weren't that many articles in: Dr Sameena Rahman (:Mm-hmm.
Dr Sameena Rahman (:Yeah. Yeah.
Tania Dempsey, MD (:And the patient, actually, I spoke to the patient and I said, look, I think you have this thing. I don't really know much about it. Let me see if I could do more research. And she happened to have a family member who was in, I think at the NIH, and he actually said, you know, there's this guy, Dr. Lawrence Afrin, tell your doctor to reach out to him and he's gonna help. He's the world's expert in mass selectivation syndrome. And I said, all right, I'll try, I'll reach out to him. I don't think he's really gonna talk to me.
Dr Sameena Rahman (:Yeah. Yeah, exactly.
Tania Dempsey, MD (:And so of course, know, like, you know, two days later, he's on the phone with me for like almost two hours lecturing me on the last activation center and everything. And that was it. Like that was it. I just started to see it everywhere. started to understand how much it was connected to so many of the things that a lot of my patients were struggling with. And then a few years later, I was doing a podcast and I said,
Dr Sameena Rahman (:Yeah.
Dr Sameena Rahman (:Everywhere. Yes.
Dr Sameena Rahman (:Yes.
Tania Dempsey, MD (:I think like 90 % at least of my patients have this and he actually heard my podcast and he reached out to me and he said, wow, like kudos to you. He was at the University of Minnesota and, and, but he was very unhappy there because no one was taking this seriously and he was really, really struggling. So I said just very, very innocently in this, in this email, you should come to New York because I think in New York we're a little more open here and maybe we can, you know, work on this together or something. I said, kind of like,
Dr Sameena Rahman (:wow.
Dr Sameena Rahman (:Yeah. Yeah.
Tania Dempsey, MD (:Again, not really thinking much about. Next thing I know, he's like, we talk and two days later he's on a plane to New York to meet me. And within a month he's here practicing with me. And he is the world's expert in mass activation syndrome. So he's been with me since 2017. So, you know, obviously I've learned a lot from him. I've taught him a lot. We've worked together on papers. so like that's just, so now it's just, you know, it's.
Dr Sameena Rahman (:Not sure.
Dr Sameena Rahman (:Oh wow. Oh wow.
That's amazing!
Dr Sameena Rahman (:Yeah.
Dr Sameena Rahman (:Now it's like we just, all of us are working together. You know what's so interesting, Tony, is, know, I speak about this a lot on the podcast, because dealing with like vulvar, vulval vaginal disease and menopause and all these things, like take time, you have to listen to your patient. And before I had my own practice, I was really seeing, you know, in academics, seeing 30 patients a day. You don't have the time for, you know, this kind of thing. And I'm actually, I'm changing my practice model this summer to a concierge model, just so that I can spend more and more time. But the more time you spend with patients,
Tania Dempsey, MD (:What I do. Yeah.
Dr Sameena Rahman (:the more you can really dig into their history and try to understand them. I feel like listening to patients is actually such a small thing that we learned in medical school, but it's the biggest thing to help us really help navigate their care. I think that as private doctors, you always think about the big academic centers doing all the big stuff, but I do find that some of our smaller, we're the ones listening to the patients, getting the information, putting, making connections together.
Tania Dempsey, MD (:Yeah.
Dr Sameena Rahman (:Like it's just very interesting to think how the system is really meant to fail patients, especially female patients, I would say, like with all the issues that we have. And so.
Tania Dempsey, MD (:it's awful. And I got, don't know about you, but you know, I was always the one that wanted to spend time with patients because I always understood the connections. I can't tell you how many times my attendings would sit me down. And this is what they would say, Tonya, you're not going to succeed in medicine. You're just not, you cannot spend time with patients. Right. And I would like to come home and be like, my God, I'm not going to succeed. You know, this is awful. Right. huh.
Dr Sameena Rahman (:Yeah.
Dr Sameena Rahman (:Yes.
Yes, I know it's so true actually.
Tania Dempsey, MD (:What I say is ha, you know?
Dr Sameena Rahman (:now what? now what?
Tania Dempsey, MD (:It's like, that's the very reason, right? That I'm successful is because, because I understood, you know, they would say to me, you have to concentrate on one problem. You know, if they have a headache, they have high blood pressure, they have joint pain, you pick one and you tell them to come back for the others. And I would say to them, but I think these things are all connected. I don't think it's one problem. And how can you do that to the patient, right? It's just such a disservice. it drives me crazy.
Dr Sameena Rahman (:Yeah.
Dr Sameena Rahman (:Right, right.
It's so, yeah, so true. And I think, you know, even like, as you know, don't practice obstetrics anymore, but I just remember when I was in it, they're like, you can't spend that much time with your gyne patients, you know, like you gotta get in and out and like, you know, you gotta keep going and 40 patients and you know, the OB patients need you. And you know, they did at the time, but like, I'm just, you know, it's the mentality of how these, that's why.
There was an article that just came out, I just spoke to Kylie Walsh about it, about medical gas lighting for women with vaginal disorders and JMA yesterday. And it really went through like all the things that we hear all the time that women experience over and over again, like, know, relax, have a glass of wine, do all the things that, you know, because they don't have the time or the ability to really sit with the patients and kind of, you know, put on your detective hats and figure out what's going on.
Tania Dempsey, MD (:young
Tania Dempsey, MD (:It's ridiculous.
Tania Dempsey, MD (:think about it.
Dr Sameena Rahman (:But that's amazing, I love that story. Well, let's talk about what is, for some people who listening, maybe have, know, I know some of them are mast cell patients, so they're listening, but there are people out there that are gonna be like, what the hell is mast cell activation? So tell us, what the hell is mast cell activation?
Tania Dempsey, MD (:Yeah.
Tania Dempsey, MD (:Bye.
Right? Yeah, right. So, you know, the mast cells, just to give a little more background, right, mast cells are white blood cells. And, you know, as a lot of other white blood cells in our body, they're helping you, you know, fight infection, help you help to protect you from the environment. And the difference between mast cells, though, is that they're not really in the bloodstream like other white blood cells, they're actually in all your tissue and organs and
And they're really in all these locations that are in contact with the environment. Again, they are first line of defense. They are part of what we call like the primordial, the primitive immune system. they're, they're, cells are in lots of animals, not just humans, right? They're really ancient, ancient immune cells. And they're really like really supposed to help us, right? They're really supposed to help fight stuff off, right? If something is bad, sees
a toxin, it sees an infection, it sees something that is different, it's going to react. That's sort of the normal response of a mast cell. And the way that mast cells react is they manufacture different chemicals and they explode and they release these chemicals. And some people might have heard of one of the chemicals that mast cells make is histamine.
stamine is really one of over: Dr Sameena Rahman (:Yeah.
Tania Dempsey, MD (:is often mast cell driven, right? So if you think about right now is there's so much pollen in the air, at least here in New York. And so, know, mast cell response would be, okay, you see pollen, you're allergic to it. The mast cells in your nose, in your eyes, then your respiratory tract explode. They release histamine, these chemicals and causes swelling. And then that causes like the tissue swells and then you sneeze and then your eyes water and then you can't breathe.
So that's a typical mast cell response to an allergen. But mast cells are in the respiratory tract, they're in the GI tract, they're in all your connective tissue, in your ligaments and in your tendons, in your joints, they're in the nervous system, they're in the GU system, they're in the bladder, they're in the uterus, they're in the vulva, they're in the vagina. What? Yeah.
Dr Sameena Rahman (:about the vestibule a lot. my list, right.
Tania Dempsey, MD (:wherever they are seeing a trigger, and it's not always allergic. Some of these triggers are not allergies, but the cell sees it, something is different, and it responds. So I want to distinguish, everyone has mast cells, and everyone's mast cells will release chemicals or degranulate.
at certain times of their life. Okay. So you get COVID, you get the flu. There are lots of circumstances when what would happen in a normal person who doesn't have mast cell activation syndrome, the mast cells explode, release the chemicals, try to fight the infection, recruit the rest of the immune system to come in and fight as well. And then the mast cells reset. And then they just wait for the next attack. In mast cell activation syndrome,
Dr Sameena Rahman (:Right. Right.
Tania Dempsey, MD (:those patients have at a base level leaking of the mast cell. The mast cell is like releasing these inflammatory chemicals, even when there isn't much going on. And then when the trigger comes, they go crazy, they degranulate, and then they don't reset. they become...
Dr Sameena Rahman (:right?
Tania Dempsey, MD (:they come to a point where the threshold now is actually kind of lower, which means that it doesn't take as much to get them triggered again and it becomes like a vicious cycle. And so the way that we think about Massive Activation Syndrome is that it is a multi-system, okay, so it usually involves multiple parts of the body and it's an inflammatory condition. Okay, the inflammation part of this is pervasive and the inflammation could be
Dr Sameena Rahman (:Sure, yeah.
Dr Sameena Rahman (:Yes.
Tania Dempsey, MD (:in a specific area of the body. It could be systemic, it often is systemic. And there are like three themes that we think about with Mass Effectivation Syndrome, right? It's the inflammation, plus minus allergic phenomena. And I say plus minus because there could be allergy, doesn't have to be allergy, could be allergic symptoms that are not allergy, and then plus minus, and we'll call it dystrophisms.
Dr Sameena Rahman (:Good.
Tania Dempsey, MD (:And dystrophisms are like abnormal growth and development. So some MCAS patients have like lumps and bumps and cysts and little like, like pomas or little, or thyroid, thyroid cysts or ovarian cysts or right. So like things that are growing abnormally. And that's because mast cells, when they're working well, are involved in growth and development. And we know that, that they're actually supposed to help us.
So I think of mast cells as like this dichotomy of they're good, we need them, there's a lot of good stuff that we cannot do without, but when they become dysfunctional and they're not reacting appropriately, that's when they set people up for this kind of storm of symptoms.
Dr Sameena Rahman (:And so for those listening, why is a gynecologist so interested? Well, you know, I do sexual medicine and I do menopause care. And so I find that, and we've all seen now this link, this one of some sort of triad that you guys, we call it the triad of mast cell and POTS and hypermobile disorders, right? So can we talk a little bit about that and how it's related? Well, actually, before you talk about that, what's the best way to diagnose mast cell activation syndrome? Is that?
Tania Dempsey, MD (:So number one is the clinical picture and really getting a very, very good history. I sometimes take three hours to take a history on a patient. It's about really understanding. First, you really need to understand the health of their mother when they were pregnant with them. That sets up the immune system. That sets up a lot of things on how the mast cells work from a very early age, whether there was trauma within the mother.
Dr Sameena Rahman (:picture.
Dr Sameena Rahman (:Yeah. Yeah.
Tania Dempsey, MD (:was malnourished, whether the mother was, you some people don't know that part of the history, but I take the history all the way from the health of the mother. And then through the course of their life, other events that changed things, do they remember a specific episode where things changed enough that they know that, you know, they were not the same? You know, often people can remember, you know, I was in Costa Rica and I got diarrhea and after that I never recovered.
Dr Sameena Rahman (:Yes. There's always a Sentinel event, right? Almost. Yeah.
Tania Dempsey, MD (:Right? That's right. That's right. So first, that history is really important. And that gives us a little bit of a clue. OK, this is a patient who could have mast selectivation syndrome. We try to do testing. In my office, we have it set up. We have a refrigerated centrifuge. A lot of the things that we test for are the mediators that the mast cells release, these chemicals. These chemicals tend to be, we call it thermolabials. So they're heat sensitive.
So we use the refrigerated centrifuge when we're spitting blood or whatever, because we want to make sure that everything stays cold. We have them collect urine. The urine has to stay cold. And we're trying to measure, trying to find these chemicals that mast cells release. And that suggests if we find these chemicals that the mast cells are activated. That gives us a clue. We can do biopsy samples. There are lots of different ways. It's complicated, right? And I would say there are some people who...
Dr Sameena Rahman (:Yeah.
Tania Dempsey, MD (:are going to be able to go through the formal testing. And there are some people who just based on their symptoms, we're going to have to start treating, right? So it's a little bit complicated. I wish there was a better way to diagnose, but right now that's kind of what we do.
Dr Sameena Rahman (:Yeah. Okay. And so the link, when do you think this was sort of, was just observationally people notice. I mean, I think I started noticing in my office a few years ago and then I was like, there's stuff in the literature on it. know, like, so is that, cause I know you're part of the, mass cell, what's it called? The symp, the group of people that get together for.
Tania Dempsey, MD (:There is, right, we have a Masselle group and actually we just formed a nonprofit organization. This is hot off the press, hot off the press, like literally just happened. We're waiting for our formal 501c3 designation, but the organization is IS MCAS, International Society for Masselle Activation Syndrome. And we're really excited. So there's more to come on that. That's brand new.
Dr Sameena Rahman (:wonderful. Yes.
Dr Sameena Rahman (:Tania Dempsey, MD (19:09.022)
So yes, we have a group of people who are really interested in understanding the mass cell, researching, trying to provide more support for patients. So that's what we're trying to do. But what was your question about? Billings, yeah. Yeah.
Dr Sameena Rahman (:about how the links that we've associated with some of these other conditions and how they relate.
Tania Dempsey, MD (:Yeah, so there are lots of conditions, right? So there's the triad that you mentioned that we, know, there needs to be more research, and I'll be honest, and the research in the literature has been a little bit inconclusive, but I can tell you anecdotally, it's not inconclusive. But that triad of mass selectivation syndrome, hypermobility syndrome, or EDS, POTS seems pretty strong.
From my perspective, it's interesting if you look at it from a hypermobility specialist, they may say something different. If you look at it from a pot specialist, they may say something different. My lens is the mast cell. So I think the mast cell is the driver for the most part. That the mast cells are, there's tons of mast cells in the connective tissue. They release a number of chemicals, enzymes that break down connective tissue like elastase.
And so I think that the mast cells activating in the connective tissue is damaging them, so to speak, making them maybe weaker or, know, or stretchier or whatever we see with hypermobility. And from the POS perspective, you know, sort of the same thing, lots of mast cells in the vasculature, in the nervous system. And so probably there is some interaction there causing patients to have more
Dr Sameena Rahman (:Yeah. Yeah.
Tania Dempsey, MD (:postural orthostatic tachycardia syndrome, or even just more generally dysautonomia. So we know those are linked, but what we now understand is that there are lots of other conditions that seem to be linked. I have this graphic that I use a lot when I lecture, and it's like 11 or 12 different things now that are all connected. Definitely endocrine disorders, insulin resistance, polycystic ovarian syndrome.
Dr Sameena Rahman (:Yeah.
Tania Dempsey, MD (:I can tell you is very, very closely linked. I have yet to find a PCOS patient who does not have now selectivation syndrome. That's how strong that link is.
Dr Sameena Rahman (:Do you think it's the meaty, because it's the inflammation that's caused probably leading to insulin resistance, which then is causing all the PCOS symptoms, right?
Tania Dempsey, MD (:And I think that the insulin resistance then also feeds back and makes the mast cell activation syndrome worse, and it becomes a vicious cycle.
Dr Sameena Rahman (:gotcha. Okay. All right. That's very interesting.
Tania Dempsey, MD (:which is why sometimes it's harder to treat than you would think. For some patients, you treat their insulin resistance, you put them on metformin, you do all this stuff, and yet it's not really moving the needle. And so that's where you say, I think I have to focus more on the mast cell piece of this because there's something I have to stop this inflammatory cycle. So hormones are a big,
Dr Sameena Rahman (:Yeah, absolutely.
Tania Dempsey, MD (:piece of the puzzle for a lot of patients. And we certainly know that when you look at it, when you get a history, the times in a woman's life where Mass Effectivation Syndrome is most likely to present would be puberty, Postpartum, perimenopause. Like, you know? So that's important, we should talk. Totally.
Dr Sameena Rahman (:Yeah.
Dr Sameena Rahman (:Yeah. Yeah. Postpartum.
Dr Sameena Rahman (:Yeah. Classic. Roller coasters or lack of hormones or increase of hormones or, know, that's interesting because I do find that in my perimenopausal patients with MCAS that it's very hard to, well, perimenopause is like a roller coaster for everyone. And I feel like if you throw in the mast cell stuff, like it's a little bit harder to tweak their symptoms. Like the estrogen may seem too much too soon or, you know,
Tania Dempsey, MD (:Right?
Dr Sameena Rahman (:progesterone is better than you thought. So how do you kind of approach that and what are your thoughts around sort of like estrogen, progesterone, how they relate?
Tania Dempsey, MD (:Yeah.
I think the key is this, that mast cells are really, they're geared towards measuring changes. So it's not always the actual thing that's the problem, like the actual estrogen or the actual hormone. It's the shift in it, the delta. The same with barometric pressure.
Dr Sameena Rahman (:The Delta, yeah.
Tania Dempsey, MD (:you know, change in weather, right? So it's these things that the mast cell is reading. so, but beyond that, we know that estrogen tends to be a little bit more activating. We know that the mast cell has receptors on their surface, over 300 different receptors. We know there are estrogen, we know there's progesterone receptors and testosterone receptors and thyroid receptors and insulin receptors.
Dr Sameena Rahman (:Hmm.
Tania Dempsey, MD (:and the list goes on. So we know that the hormones can bind to the mast cell and some studies, particularly done in mice and rats, show that the estrogen seems to be a little more activating and the progesterone seems to be more stabilizing, but it's not always for the individual patient that clear, right?
Dr Sameena Rahman (:All right.
Tania Dempsey, MD (:And so we're not mice and we're not rats, so we have to dig with the grain of salt. So it's so nuanced. So I have patients and past patients who do very well with estrogen, even though you would think that it would be more activating for them. But in the perimenopausal or menopausal stage, steady state estrogen might be okay for them because it's not fluctuating, right?
Dr Sameena Rahman (:late exactly yeah it's so nuanced actually
Yeah.
Dr Sameena Rahman (:in the post-menopausal.
Tania Dempsey, MD (:But then in the progesterone, you would think, well, progesterone is stabilizing, right? So you're combining it with the estrogen, right? Theoretically, that should be good for them. And then I have those patients who cannot tolerate progesterone in any form. We've tried it, oral, topical, whatever. And for whatever reason, progesterone for their mast cells is not right, right? And so then becomes, if they have a uterus, right, and we're trying to give them estrogen,
Dr Sameena Rahman (:Yeah, yeah.
Tania Dempsey, MD (:We have to sort of figure out how to balance it. So it's not easy. I think there are different ways to do it. Sometimes it's about, they have to take progesterone, but we don't have to do it as often if they're on lower dose estrogen, right? have, yeah, you probably know more about this than me, but I think there are like tricks to the trade to get patients and women to not suffer. It's all about like trying to find the right.
Dr Sameena Rahman (:Yeah. And I think we see that progesterone sensitivity a lot in patients who have PMDD, the premenstrual dysphoric disorder. So one of the things that I like to do is really, if they have a progesterone sensitivity, they can't tolerate any progesterone, but they're doing well on the estrogen, is use the FDA approved Duave, which is like oral premarin, but benzotoxicene, which is a selective estrogen receptor modular. So they get the uterine protection.
Tania Dempsey, MD (:Yeah!
Dr Sameena Rahman (:because they're blocking the estrogen at the uterus, and they're not getting actually any stimulation of their breasts. So they like that, especially if they have breast cancer or history or whatever in their family.
Tania Dempsey, MD (:Yeah, no, it's a great, yeah, it's a very, very interesting product. Absolutely.
Dr Sameena Rahman (:Yeah. so do you think that if you add, like, for some of these patients, we know insulin resistance starts in perimenopause for so many people when you these fluctuating levels. Do you think the metformin piece can be like a different factor that might be helpful because it promotes anti-inflammatory factors or helps with that?
Tania Dempsey, MD (:Yep.
Tania Dempsey, MD (:I love metformin. I mean, I've been using metformin in my patients since I started practicing and since, you know, my interest in PCOS from very early on, I was using metformin. So I think for a lot of women, absolutely, metformin was always my go-to. You know, now we have these GLP-1 agonists, and I have to talk about you a little bit. We have a paper that we're about to submit for publication. It's a 50-patient case series.
Dr Sameena Rahman (:Yeah. Yes.
yeah.
Dr Sameena Rahman (:Okay.
Tania Dempsey, MD (:on the use of GLP-1 and mass selectivation syndrome. So it will be published soon, but I can't say too much. what I can say is that our data is pretty compelling. It's really mind-blowing. I don't want to generalize. It's definitely not the right drug.
Dr Sameena Rahman (:let's hear it. I want to hear this.
Thank you very much.
Tania Dempsey, MD (:for everyone and I certainly have patients who are not tolerated or shouldn't take it. So I wanna say that just cause I think people hear this and they say, know, give me ozempic or manjarum. But at microdosing, sometimes you can avoid some of these really bad side effects and mast cells have GLP-1 receptors. They have GI.
Dr Sameena Rahman (:Yeah.
Dr Sameena Rahman (:Yes.
Tania Dempsey, MD (:key receptors, which are the two agonists that are in like terzepatide or mangiaro. And so they look like they can stabilize mast cells and they have some anti-inflammatory properties as well. Obviously also help with insulin resistance. So, you know, I still have the patients where I think metformin is going to be a better choice for them. I have patients, I actually have patients who are on both. You know, some of them, let's say have been on metformin
Dr Sameena Rahman (:huh.
Tania Dempsey, MD (:for some time because I've been treating them. I have patients I've been treating for 15, 20 years, even before my own practice, they followed me. they have PCOS, I have them on metformin. They get to the perimenopausal phase where the metformin is not doing enough anymore for them. Then we're layering on maybe a little GLP-1. mean, obviously we're doing other things as well, but it's really fascinating.
Dr Sameena Rahman (:Yeah, it is a fascinating drug. mean, even in the world of sexual medicine, I think we're seeing so many potential changes in how the GLPs work in your brain and how it affects your dopamine pathways and all the things. Like it's very, it's a very interesting drug actually. And I think it has some compelling evidence and potential uses in a lot of things. So it's an exciting time for so many.
Tania Dempsey, MD (:Correct. Correct.
Tania Dempsey, MD (:It's exciting. mean, again, it's not right for everyone. I'm hopeful that there will be better formulations with time that maybe will have less side effects. There are just going to be patients who are just not able to tolerate even at the microdosing level. And some of those patients are disappointed, you know, and I feel bad. I'm like, okay, well, let's wait and see if we can find something else. So, yeah.
Dr Sameena Rahman (:you
Dr Sameena Rahman (:Yeah. Tell me what do you think of when you come, when you talk about PCOS and MCAS, like, you know, I've always sort of considered PCOS to be something you're genetically predisposed to and that, you know, you likely have, I mean, although it doesn't fit the criteria for some patients, right? Some patients have no significant metabolic dysfunction in their family. And so, you know, you think about the ones that are like thinner and they don't have all the typical phenotypes. So.
Tania Dempsey, MD (:Right.
Dr Sameena Rahman (:I'm wondering if that mass cell is the missing piece, because sometimes I'm like, well, there's not that much metabolic dysfunction in their family. they don't fit the, you know, but they have all the symptoms that are consistent with the PCOS diagnosis. I mean, do you think that people have a hereditary predisposition to MCAS? Is that what you think it is? Or do think they're exposed to, like, you know, with some of the theories around vestibulodynia and congenital neuroperliferative,
Tania Dempsey, MD (:Yeah. Yeah.
Dr Sameena Rahman (:Are they exposed to something at like a really young age in the diaper region and that's caused mess cells to become apparently active? Or is it because they have this genetic predisposition and therefore they don't tolerate the things that normally, you know what I'm saying? Like it's so nuanced or complicated.
Tania Dempsey, MD (:Bye.
Tania Dempsey, MD (:Yeah. no, no, for sure. But the way I think about it is that I think there is some kind of genetic vulnerability. Like we're never going to find a gene. There's no gene for Mass Effectivation Syndrome, but I think it's a vulnerability. And then because very frequently you will see other family members who have some symptoms. They may not be as severe, but they have some, you know, flavor.
Dr Sameena Rahman (:Mm-hmm.
Dr Sameena Rahman (:Yeah.
Tania Dempsey, MD (:of it. So you know that there's something in the family. But I do believe that it is exposures over time that bring it out. So I agree with you. think that's why I take the history from birth or actually from the pregnancy of the mother or before the mother got pregnant because exposures in the mother, things like petrochemicals.
pesticides, you know, there are all these different environmental factors that may already predispose them very early on, you so they have, the mother has a toxic load and then the baby is being exposed to these toxins. Then they're born and then maybe there's an additional exposure from something, whether it's a diaper, whether it's, you know, the baby powder with talc in it or whatever else, you know. And then, you know, I think
Dr Sameena Rahman (:Yeah.
Dr Sameena Rahman (:Great, all right.
Tania Dempsey, MD (:You what I love is I have a colleague at UT San Antonio whose life's work, her name is Dr. Claudia Miller. Her life's work is in a condition known as tilt, toxicant induced loss of tolerance. And essentially it's chemical intolerance, okay, or chemical sensitivity. And she has this great graphic of an iceberg. And so what she says is that,
There's a susceptible person, right? They're like low down on this iceberg and they get some kind of exposure to something. Then they become the sensitive person. And they don't even realize they're more sensitive, but then there's some low level exposures to various things until they break through the water. Right now, the iceberg is out and now they are the sick patient.
Dr Sameena Rahman (:Yeah.
Tania Dempsey, MD (:And for many years in her career, like she didn't understand the mechanism of that. She could explain tilt, she could find the things that were causing this condition tilt, but she didn't know the mechanism. And then she came across some of Dr. Affran's work, she came across some of my work, some of our papers.
And so we started collaborating with her and we did a study together and basically it showed that the root cause of this chemical intolerance was mast cell activation syndrome. And so now when I show that like iceberg, when I use that for my lectures, basically it's explaining the mast cells. The mast cells get primed, then they get more exposure and then boom, they're out. So when you think about congenital neuroproliferative,
Dr Sameena Rahman (:Yeah.
Tania Dempsey, MD (:I think that absolutely you're right. Maybe there's a susceptibility that we don't know about. We can't identify that because there's no gene that causes it, but then there's an exposure and then their mast cells start to proliferate along with the nerves. And so I think that that's a very common problem that I think that...
Dr Sameena Rahman (:Yeah.
Thank
Tania Dempsey, MD (:that explains why people are having that. And then if we go back to PCOS, I think that a lot of these patients with PCOS, if you really look at their history and get that history, many of them will say, yeah, I lived, I grew up, I was a baby in a moldy apartment or moldy home. So they had some kind of exposure to toxins there. They had some kind of trauma.
They had, you know, these are the ones I'm talking about that maybe don't have a family history of PCOS, right? There's something else that's bringing out this inflammatory condition.
Dr Sameena Rahman (:Right? Interesting. Yeah, that's so interesting. Do you get a sense of, I mean, what the prevalence of something like MCAS is?
Tania Dempsey, MD (:Yeah. There's one study and I really wish that somebody else would do more studies on it, but there was a study done in Germany. And, the thought is that the German population is probably similar to the US population. And they estimated that 17 % of their population have MCAS. Now, I would say that study was from 2017. And I would say that there does seem to be a rise in MCAS.
post COVID, post COVID vaccine. I think we're just seeing a lot more of it. So I would venture to guess without, know, sort of off the record that we're probably 20%, if not more. And that's, know, one in five people have some feature of M-Cas.
Dr Sameena Rahman (:I'm very, very sorry to be right now. Yeah, that's interesting because I think it's so, because you're right, because of the predominance of where mast cells are and how they impact like so many systems that it'd be really hard to say that some of these systems aren't effective. And it's interesting that some systems are effective and some won't, right? Like, so have some patients with, I know they have neuroplastic vestibulodynia that was caused by some sort of inflammatory reaction.
Tania Dempsey, MD (:Yeah.
Dr Sameena Rahman (:to high dose over the counter fluconazole or something, like one of the, like tricozol, sorry. they might've had that reaction, but they don't have any other, like they don't have allergy, they don't have the typical allergic stuff, they don't have the other stuff. And so it's interesting as to whether or not they would respond well to some of these medications. Let's talk about treatment actually, like what do you do for some of these patients with cell activation?
Tania Dempsey, MD (:right. Yeah, yeah, yeah.
Tania Dempsey, MD (:Yeah. Yeah.
So the number one, step one thing that we need to think about is eliminating triggers. So if there are things that are continually making the mast cells get activated, you really do have to kind of start there. And that's where you really work with the patient to understand, is there a medication they're taking that has some kind of filler in it that is irritating the mast cell? Are they living in mold?
Dr Sameena Rahman (:Thank
Tania Dempsey, MD (:Do they have some kind of chronic infection? Are they using personal care products that are, know, fragrance, that have fragrances? You know, what is the actual trigger, right? And sort of work on that. And then for treatment, it's all about stabilizing the mast cell and blocking the effects of the chemicals that the mast cells make. So we often try antihistamines, you know, with the thought that maybe histamine is one of the chemicals that they're releasing.
Dr Sameena Rahman (:Yeah. Yeah.
Tania Dempsey, MD (:So it could be natural antihistamines, it could be pharmaceutical. Over the counter, we have four antihistamines that are non-sedating, then Claritin, Zyrtec, Allegro, Zizyl, Benadryl, which is sedating, but can be very helpful for some people. We have, those are H1 blockers. There are a few actually that are prescription. There are a few that we get from Canada that we can't get here.
We have H2 blockers like sigmatidine or tagamide or famotidine. Sometimes combining those together can be very helpful. If histamines not their problem, then a lot of times these antihistamines won't help. So we have a long list of various compounds, again, both natural and pharmacologic that are designed to address
Dr Sameena Rahman (:Yeah.
Tania Dempsey, MD (:the dysfunctional mast cell at some level. Sometimes it is literally like we know it's binding to the mast cell and trying to send it a signal like stop, like a GLP-1. Sometimes it's mechanisms that we don't really fully even understand like low-dose naltrexone. Sometimes it's drugs with combination effects, like they have some antihistamine effect, but then they also do something to stabilize the mast cell like ketadipine.
Dr Sameena Rahman (:Yeah. Yeah.
Tania Dempsey, MD (:So, and again, most of the things we're using are oral, could be IV theoretically like Benadryl or Zyrtec. But in the case of things like neuroproliferative vestibulodinia, we're looking at, as part of this sort of consortia where we're looking at, are there mass cell targeted therapies that can be applied topically, potentially? That's right. That's right.
Dr Sameena Rahman (:Yes.
Dr Sameena Rahman (:Yeah. thought ketatophene
Tania Dempsey, MD (:which showed some promise, some preliminary data did show some promise. So I think, and for, we did publish a paper in 2018 that looked at various conditions like dyspareunia, was dyspareunia, menorrhagia, it was like a whole, few different, I'm sorry.
Dr Sameena Rahman (:Endometriosis.
Tania Dempsey, MD (:Yeah, I think there was endometriosis and there was one more condition and we used, it was a case series and we used various modalities to treat. Sometimes we used suppositories of various mast cell target therapies. Sometimes we used douching, sometimes we oral preparations. And my case was a woman with PCOS and menorrhagia.
who took Claritin and Pepsid and like stopped her menorragia. was like that she couldn't stop for months and months and months. So sometimes it's like a simple intervention like that. And so we published on that. I do think that there are lots of different ways you can try to calm down the mess.
Dr Sameena Rahman (:wow.
Dr Sameena Rahman (:Yeah. Yeah. Some of us just trial and error, right? Because we don't know which ones they will respond to. Yeah. I mean, obviously, this is an emerging field, and I think it'll continue to evolve. And so we will keep asking the questions and doing the research. Well, what kind of advice would you give someone that's kind of suffering with what they think is mast cell activation and where to find the help they need?
Tania Dempsey, MD (:Exactly. Exactly.
Tania Dempsey, MD (:Yeah. So, you know, there are thankfully a lot of resources now, you know, even the stuff that I put out there, you know, on social media, blog posts. I try to just keep the education going. so, but there are lot of colleagues who are also sort of doing the same thing. So I feel like now is a better time than ever, right, to at least get some information to read about it.
Now, the issue we have is just finding practitioners who are willing to treat. And what I say is this, you don't need a mast cell specialist. Well, you might need a mast cell specialist, but what you really need is a practitioner who's willing to listen and willing to learn. Because there many of us who are willing to teach as long as that person is open. So if you have somebody who doesn't know about mast cell activation syndrome, but
But it's interested in learning and interested in helping you as a patient get better, right? There are lots of us who will talk to and train those practitioners to help their patients. So again, I think it's getting better. Our goal is to educate more and more people so that they can treat more patients. There are not enough of us out there clearly doing this work.
But, you know, like I said, I think that there's a lot of information. so unfortunately, it falls on the patient to advocate for themselves. Yeah.
Dr Sameena Rahman (:Absolutely. And I think that's really important when it comes to any of the stuff that we talked about is at the end of the day, it's like, it's your health and you have to actually get to the resources and find the best thing that you can do for yourself because, you know, no one's going to save you unfortunately, you know, like at the end of the day, it really is our own. We have to advocate for ourselves and our own health and all the things. So, well, thank you, Tanya. I really appreciate you being on today. I know, you know, this was great. There's so much we could talk about. We could go on forever.
Tania Dempsey, MD (:I know.
Tania Dempsey, MD (:Yeah.
Thanks, Simina.
Well, we get to have a good talk for hours, I think.
Dr Sameena Rahman (:Yeah, yeah. So I'll have to have you back on, but I appreciate you coming in to give us some of the 101 basics. And I can't wait to hear your research when it's published, so I'll look out for it on social. And I'll keep in touch with what's happening with Ishwish. But thank you once again. Thanks for listening, everyone. My name is Dr. Sumita Raman, gyno girl. Remember, I'm here to educate so you can advocate for yourself. Join me for the next episode.
Tania Dempsey, MD (:Yeah, of course.
Tania Dempsey, MD (:Yeah, that's literally.
