Hormones and MCAS with Dr. Dempsey, Mast Cell Matters: Deep Dives on MCAS

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Jill Brook: Hello Mast Cell Patients and beautiful people who care about Mast Cell Patients. I'm Jill Brook and this is Mast Cell Matters, where we go deep on all things related to Mast Cell Activation Syndrome, or MCAS, with the help of our brilliant and beloved guest host, Dr. Tania Dempsey, world renowned top expert in MCAS and related comorbidities,

highly sought after physician, researcher, educator to other physicians, and everything. And we gotta hurry, though, because she's busy and she's only got 35 minutes with us. Dr. Dempsey, thank you for being here.

Dr. Tania Dempsey: Oh, thank you for having me.

Jill Brook: So today our topic is hormones and mast cells, another topic where you are the expert on this. We're so excited to have you and people have been writing in wondering about how hormones affect mast cells, how mast cells affect hormones,

what to expect with MCAS at puberty, menses, pregnancy and menopause, whether you have any treatment tips or ideas [00:01:00] about helping get through those times or flares related to hormones. We have a few specific questions about things in the hormone department if we have time, but there's so much to cover that I feel like we should throw it out to you to just start where you like to start when you're teaching people about

hormones.

Dr. Tania Dempsey: Yeah. I love, I love this topic. I, it's so important, and, and I think, I think where I'd like to start is just talk a little bit about the, the mechanisms, right? Let's talk about the biology of the mast cells and, and hormones. And I think if we start there and I love talking about that kind of stuff, I love educating.

I think it will start to make sense when we talk about the, the various developmental stages in a woman's life. I think we can sort of go through that. So if we think about mast cells you know, many people listening already kind of know that they are part of that the innate immune system, the primitive immune system.

They are in all tissue in the body. So they are there to, to [00:02:00] protect us from, you know, we'll call it the environment. So they not only protect us from the outside environment, but they also protect us from our internal environment. So they are really positioned in the body to respond to changes in lots of different things.

So, it just so happens that one of the things that mast cells can, can read because of receptors on their surface is hormones. So, mast cells have lots of mediators within them that they manufacture. We now know that they can manufacture over 1, 200 different mediators, not all, not all mast cells make 1, 200 mediators, but there are 1, 200 or more that have been identified.

There are hundreds of types of receptors that are on the surface of the mast cell. And so that the mast cell can, something can bind to that receptor, send a signal, and then the mast cell can degranulate and [00:03:00] release these various mediators. And some, some mediators are being released in granules, and some mediators are sort of, like, leaking out in a different way.

But in general, those mediators are inflammatory, for the most part. They have lots of different functions, but, but many, many of the functions sort of are in the inflammatory realm. And so, so the mast cells have on their surface receptors for estrogen, estradiol specifically. They have receptors for testosterone.

They have, they have receptors for progesterone. They have receptors for other hormones, and they have insulin receptors, which is another hormone in the body. And so, once you kind of think about that, it starts to make sense. So these receptors accept the hormone. I think about the receptor as almost like a satellite, [00:04:00] sort of, it's sitting on the surface and and let's say estrogen comes in and binds to that receptor, it's going to tell, it's going to send a certain signal to the mast cell.

And what the research suggests, at least in some rat and mice models, is that estrogen is, can be a stimulator, activator, of the mast cell. There's some research to suggest that progesterone may actually have some mast cell stabilizing qualities to it. And testosterone is a little bit fickle. It's actually not quite clear.

There's some research that suggests that it may be stabilizing, and in some cases it may be activating. And I think it really depends on a lot of things, to be honest. And I think it really does differ between men and women. So, so if you think about the mast cell reading changes, right, it reads changes in barometric pressure [00:05:00] on the outside, right?

It reads changes in, in anything like temperature, right? Or or or a new drug that you ingested. It can read changes in, in, in the hormone levels. So if we think about let's start at puberty. So, generally speaking, MCAS can be present before the hormones are active, but it's not uncommon for puberty to be a very critical turning point in a patient's life.

It's not uncommon for me to start hearing stories, either from patients or from, you know, from when they look back in their history or from patients who are telling me about their children, that there's a time, you know, around,

it could be in girls, it could be maybe around 7 or 8, depending, I think, you know, with the girls going through periods earlier now, this is sort of shifting to, like, a little earlier, but, but, you know, let's say, [00:06:00] on average, it's probably more like 9 or 10 when there starts to be, be little bursts of, of of estrogen. There's bursts of hormones actually from the pituitary and the hypothalamus that's sort of getting the body ready to eventually like for the ovaries to eventually start to make hormones. So those little bursts of of, of hormones kind of start to kind of prime mast cells a little bit, start to sort of send these signals, hey, there's, you know, there's some changes, there's something going on.

And then right at what we call it menarche, or really at the start of the period, that's I think really when there's a there's a major shift. So now the ovaries are working, they're producing estrogen, they're producing progesterone, and they're producing some testosterone, and and the adrenal glands, I'm talking about in females, the adrenal glands also produce some hormones like DHEA that gets converted into testosterone.

And so with a [00:07:00] cycle, what we think about is in the beginning of the cycle there's a, there's a slowly rising level of estrogen because there's a follicle in the ovary that's starting to develop. This is the follicular phase. So you have little bits of estrogen kind of spurting out and the follicles, you know, developing.

But at that point I would say the majority of, of females in that, in that stage will say that they often feel okay, you know, because the levels are sort of not too high yet. As they approach ovulation, ovulation is when that follicle is developed, and, and now the egg can be released. At that point, estrogen levels go up much higher, and as soon as that egg is released, essentially the progesterone levels start to rise.

Now there's some progesterone already, but then it really starts to rise because the progesterone is sort of being produced from the follicle, after the egg is released. And so, the [00:08:00] progesterone starts to rise. And, and either because some women just don't make enough progesterone, or some women are making too much estrogen, or the mast cells are just too sensitive to those changes.

That, that phase, called the luteal phase, is when lots of women start to have symptoms. And so when in the start of admenarche, it could already start and then can develop over time to be more like PMS, can be, can be a sign of Mast Cell Activation Syndrome in some ways. Any kind of premenstrual sort of symptom, it could be, you know, mood disorders, depression, anxiety could be breast tenderness, could be pain, cramping could be actually, I've seen headaches, migraines.

I mean, basically, again, mast cells are everywhere. So any, anywhere that the mast cells are activated by these shifts in hormones can be enough to, to cause a flare. [00:09:00] So I would say in general, women are probably more at risk for Mast Cell Activation Syndrome, in some ways. And I would say that we know that there are lots of mast cells in the ovaries, in the uterus, in the, in the genitourinary tract, in the bladder.

All those, that whole area is ton, there are tons of mast cells. And we know also that during that menstrual cycle, there are different points where the the number of mast cells may, may increase, interestingly. We know that during pregnancy, there's definitely an increase in mast cells in the uterus.

And so, you can imagine that with these shifts in hormones, maybe shifts in mast cells, that that could potentially cause for some women, tremendous, you know, disability, tremendous illness related to their hormones. So, so I would say that the key, the [00:10:00] key times in a woman's life where it's going to be one is going to be in that

early before they get their period and right when they get their period to the teenage years. I want to talk about a syndrome called Polycystic Ovarian Syndrome, which often presents early in that time period and may be related to, well, is related to Mast Cell Activation Syndrome, not maybe, is. And we'll talk about that.

The other stage in life, we'll go back to that, but the other stage in life is definitely around that, like, sort of time when some women conceive and have pregnancies, and there's a whole host of things that can happen with mast cells during that time. And then, and then menopause, or perimenopause, is another time when there's huge shifts in, in hormones, which could then also serve as triggers for, for the mast cells.

Jill Brook: So it sounds like they're hugely related and that this is very relevant many times in life. So, yeah and I think you [00:11:00] probably also answered one listener's question. She had asked if a pituitary tumor could cause Mast Cell Activation Syndrome because it's making hormones squirt out at weird amounts at weird times.

Dr. Tania Dempsey: Yeah, yeah, I can see it being a trigger for sure. Whether it's cause, like a cause, or whether it's a exacerbating factor, it's hard to know, obviously, but I, but yeah, I'm sure they're, they're related. It does make sense.

Jill Brook: Okay, so what next? Do you want to talk about the PCOS or do you want, is there more to say first?

Dr. Tania Dempsey: Yeah, let's talk about, let's talk about PCOS because this is a syndrome that can affect, depending on whose numbers you're looking at, but let's talk about my numbers, probably one in four or one in five women. That's a huge number, right? 20 25%, I would say. And, and, it is something that what I find super interesting is that when I started practicing [00:12:00] medicine when, and when I first started, I joined my first practice back in 1999.

So I guess I'm, I'm going to be celebrating 25 years in, in practice. Actually, it's probably more, so it's closer to 30 if I include medical school and residency and all that stuff. But in any case, I've always been interested in women's health. And so when I first started practicing I really kind of was, was really focused on women's health.

But I did not know about Mast Cell Activation Syndrome. And so what started happening is because I'm focusing on women and women's health, and I had an interest in hormones, I, you know, started seeing more and more patients who, who has these, we'll call it hormonal imbalances. You know, they would come in and they would have acne, or they would have increased hair growth on their body, or their face, or in places that were unwanted.

Or they would have acne and hair, or they would have hair loss, or they would have trouble losing weight, or they were having trouble gaining weight, and they had acne, or they [00:13:00] had fertility issues, or they had migraines. And so what happened was a perimenstrual or premenstrual migraines. So I started paying attention to these different symptoms and started to understand more and more about this syndrome.

And the more women I saw, the more women I tested, the more I, the more I realized that they had this syndrome. And it's characterized, it's one of those syndromes that first of all, Polycystic Ovarian Syndrome is a total misnomer. PCOS is sometimes what people call it, or PCOS. It, it implies that it's is caused by cysts on the ovaries.

But, but in fact, it's probably caused by insulin resistance, which can lead to cysts on the ovaries, or can lead to no cysts on the ovaries. And so there's some women who have this who do not have cysts. And there's some women that have cysts that don't have polycystic ovarian syndrome. So it [00:14:00] is a syndrome characterized by abnormal hormone levels, typically elevated testosterone, sometimes elevated estrogen levels, maybe lower progesterone levels, they almost always have, and I would say, I would go so far as almost 100%, have some insulin resistance effects, or some markers for insulin resistance, and there are different degrees to it.

Some very severe, some, some so severe that they're developing diabetes, and some very mild, but enough to keep the syndrome kind of going. And so what we know about it is that insulin insulin binds the mast cells. Insulin is what tells your, tells your cells to bring sugar into the cells after you've eaten something.

So your pancreas produces insulin. When you eat something that, that has sugar in it or gets broken down to sugar, the cells have to absorb it. The cells can't [00:15:00] absorb it unless the insulin binds to it and tells the cell to bring the glucose in. So mast cells have tons of, tons of that. And so we, tons of receptors, it's very sensitive to insulin and that insulin itself can cause the mast cells to, to react.

Insulin also goes to the ovaries and tells the ovaries, make more testosterone as of now you have some hormonal stuff happening from the insulin. You have the mast cells more stimulated by the insulin. And you have like a perfect storm. You have hormonal stuff causing mast cells to be worse. You have insulin stuff causing mast cells to be worse.

And, and for some women, it manifests in these various ways. And, and we don't know why, it's a syndrome. So some women will have weight issues or hair issues or acne issues or all the issues together. And and so the interesting thing is, sort of to bring the, the, the, the sort of story full circle, so I started, I had this interest in, in [00:16:00] PCOS, I saw, I was identifying the insulin resistance, then the paper started coming out that, that there was insulin resistance as the root, but I was so bummed that I, I didn't publish those papers, but I saw that before it was even in the literature.

Right? I'm just saying, I'm just saying, I saw it before anybody said it, but okay. So, I, I started noticing that, that there were other symptoms that a lot of these women had. Many of them had asthma, or allergic phenomena, or migraines. Or they had you know, a variety of other mast cell, now I recognize as mast cell symptoms.

Basically, every organ system could be affected. And I started to, sort of, start to question, what is that association, why? And I would see more thyroid problems, and I would see more, you know, like cysts or abnormal growth of different, you know, maybe they have thyroid nodules or they [00:17:00] had things that you know, now I understand is aberrant growth and development, you know, from the, from the mast cells release of the various mediators.

They had inflammation, they had a lot of inflammation. And so when I started understanding MCAS, I was actually still looking at those two diseases, sort of, or syndromes separately, and I was sort of like, okay, they have PCOS, oh, and they have MCAS. And then one, one day, the light bulb went off, and I started, I did this deep dive on PubMed, paper after paper after paper, starting to help me really put together that in fact, it's probably the same syndrome.

Jill Brook: Wow, so that's kind of hopeful maybe, because does that imply that the PCO treatments can help somebody's MCAS or that the MCAS treatments can help somebody's PCOS?

Dr. Tania Dempsey: A hundred percent. Yes. Yes, exactly. So, for some women, we can go at this through a hormonal lens. [00:18:00] For some, we can go at it through an insulin resistance lens and work on their insulin resistance. And, and for some, we can go at it from an MCAS lens. And, and, and sometimes we have to do all of those things. So you can see, I have, I have patients who take, for instance, Metformin.

Metformin is a pretty standard treatment for, for Polycystic Ovarian Syndrome. It helps control the insulin resistance. It can help with the weight. It can help lower testosterone levels, which then help with some of the other symptoms. It's sometimes used in conjunction with other treatments. But the interesting thing about Metformin is it's a mast cell stabilizer.

And why is it a mast cell stabilizer? Because it's helping insulin levels and, and in that way it's helping the mast cells. So we're putting, so I was putting women on Metformin and, and now by the way, Metformin is, is being looked at as an anti-aging drug, longevity drug. There's lots of interesting [00:19:00] stuff about Metformin.

I've been prescribing it for 25 or plus, you know, 25 plus years. And, and many women, if I started them early enough and we monitored them, they never really developed the full spectrum of MCAS. And, and some women, you know, they need more than Metformin or they can't tolerate Metformin. And I'm certainly not going to say that everyone should be on it.

That's not what I'm saying. I'm saying that depending on the patient and depending on where you intervene, you can affect these, all these systems in different ways. And that's what makes it exciting. So if patients only think about it from an MCAS perspective and think, okay, I have a hormone problem and I need to control my MCAS, it limits what you can do, right?

But if you say, okay, I have MCAS and I have hormone problems and they're linked, so I can go at it, again, from the hormonal side and stabilize hormones, and in the PCOS realm, for younger women, it may be, it could be [00:20:00] birth control pills, it could be IUDs, it could be things like spironolactone, which is a diuretic that blocks testosterone, there are other

like anti androgens we call them that block testosterone. There are lots of things. They're not right for everybody, right? So that's not what I'm saying. But we have all these different treatments that for some can stabilize the mast cells enough. And for others, we're still going to have to go in and give them an H1, H2, or some other some other intervention.

When women are in the approaching perimenopause, and they also have PCOS. It becomes a little bit trickier. There's wilder swings in hormones during, for, for women with PCOS who are then going through menopause. And so sometimes they need progesterone to control the sort of what we see as low, lower progesterone levels.

They often need more insulin resistance help, and they need improved insulin [00:21:00] sensitivity. So that's where it could be Metformin. There are other drugs now available that do other things, and one of the drugs that I'm really excited about are the GLP 1 agonists. These are the glucagon like

peptides that that everybody sort of has been hearing about. Ozempic, Mounjaro are some of the names. Wegovi, Zepbound, those are the brands of the various ones, and they're FDA approved for, for diabetes, and now they're FDA approved for, for weight loss. They are very powerful mast cell stabilizers and they are not only probably binding GLP 1 receptors on the mast cell, but they're also controlling the insulin resistance, which is a big driver of mast cell activation syndrome.

So this is, and, and, and in doing that, by the way, it does seem to help some women's hormonal symptoms. It's not, it's not not helping. It's not [00:22:00] for everyone. There are lots of side effects and you know, we can do maybe, I think we should do like a whole podcast on GLP 1 to be honest. But I think that I think it's showing promise and I think that for, for a lot of women, when other interventions are invoked and when we have some, some control over the hormones and we add that in, it's sort of, it's a really nice,

I don't know how we put it, just the last step in kind of stabilizing the body, and then and then of course, from an anti aging perspective, from longevity, there's so many things I can talk about from GL, about GLP 1s, but I think they are helping a lot of perimenopausal women who are suffering from insulin resistance and these hormonal swings.

Jill Brook: Wow, that's amazing. Also, because we've discussed on this podcast that in the POTS literature there have been some studies from Dr. Chabau's lab showing that POTS patients had twice the insulin level in [00:23:00] response to a glucose challenge compared to healthy controls. This is like young, lean, fit, you know, relatively fit people who should not be having an insulin response that high.

And so that is making me wonder again about connections between POTS and MCAS and insulin and, oh my goodness.

Dr. Tania Dempsey: I think the insulin piece is, is huge. And, and, again, insulin is a hormone, so we're talking about hormones today, so we have to talk about that hormone. And I think that it is, the more we understand about it and how it interacts with other hormones and other cells, the more you start to understand that, that I think that this is a big, we'll call it a root cause problem for, that may be driving POTS, may be driving MCAS, or at least, at least exacerbating, you know, but I do wonder about it.

It'd be great to do a study to really look at the incidence of PCOS specifically in this population of POTS and MCAS, you know, and I would, I would bet it's probably much [00:24:00] higher than the general population.

Jill Brook: Wow. And that's also exciting because there's so many lifestyle things you can do to help reduce insulin. And that would be another topic for another day, and I don't know what the effect size is compared to some of these drugs, but...

Dr. Tania Dempsey: Oh no, the effect size is huge. I'm so glad you brought that up, Jill, because, you know, I, yes, I'm talking about like drugs, right, but the reality is that your lifestyle is, is as important, if not more important in some cases. So exercise burns sugar, controls insulin release, or makes the cells more sensitive to the insulin.

Because part of the problem with insulin resistance is that the cells stop responding to the insulin and the, and so the cells can't bring the sugar in. So they're not responding to the insulin. And so there's more sugar circulating in the bloodstream. And the more sugar that you have circulating in the bloodstream, the more sugar you have involving, they're involved in a process called [00:25:00] glycation.

So sugar is sticking to lots of things, glycating things and causing aging and, and, and inflammation. And one of the markers that we test in our blood that's a marker for glycation is the hemoglobin A1C level, which is looking at hemoglobin and your hemoglobin, which is like part of your red blood cell, and looking to see how much sugar is sticking to it.

And when the number goes up, it says that you're, you are, you're not absorbing the sugar into your cells well, that means that your insulin is, your cells are insulin resistant. And so by exercising you can improve the sensitivity of the cells to insulin and drop the sugar level. And, and, you know, obviously that's a, that can have a profound effect in all the things that we're talking about here.

But there's exercise. I will tell you the other thing that can help control insulin are things like red light therapy. Things that help the mitochondria [00:26:00] can be, can be helpful. So there are lots of things, you know, infrared sauna, red light, things in that realm. And and then eating a lower carbohydrate diet.

I mean, you're a nutritionist, so, so you could probably speak to this, right? There are lots of different ways to, to eat. And I would say, in general, this population, the population we're talking to here, is definitely more sensitive to a carbohydrate load and when we talk about carbohydrates we're talking about things that turn to sugar in the body.

They can be really good healthy foods but they may not be right for you because of the body's inability to really break down the sugar and and, and making it the insulin work harder and then it causes all these problems. So, generally speaking, a lower carbohydrate diet does help.

Jill Brook: Yeah, and then there's been some fascinating findings about time of day, and eating the exact [00:27:00] same carbohydrates later in the day will create a bigger insulin spike than eating them early in the day, and they think that it has to do with just the body clock, and the, the, you know, the...

Dr. Tania Dempsey: Cortisol, probably, all these other factors. Yeah, that makes sense.

Jill Brook: Wow, exciting.

Okay, so we only have you a couple more minutes. I want to be mindful of your time. Are there any other big points to say?

Dr. Tania Dempsey: Okay, so let's see, we, we covered, yeah, so let's, let's also cover menopause and, and hormone replacement therapy, because this comes up a lot. So once menopause hits and, and estrogen levels actually, you know, kind of, plummet There can be lots of symptoms related to that. In some cases, some women feel better because their mast cells are not being triggered by changes in their estrogen.

It's really interesting. I definitely have women who will tell me that their allergies, their [00:28:00] other mast cell symptoms, their migraines, lots of other things may get better when all of a sudden their estrogen drops. But then they might have some other symptoms related to low estrogen. Estrogen affects the bones and bone density, can affect the heart, can affect the joints.

So a lot of women start to notice that they feel more creaky, and like they have more joint pain. They might have a harder time with their weight, interestingly. They may have more difficulty with like they start gaining weight in the midsection, they become more insulin resistant at that point and so the challenge is, and there are, there are studies that show that in, in mice actually it's been shown in mice and in rats that during menopause when the mast cells can get quiet and when you introduce hormones again, like through hormone replacement therapy, you can stimulate the mast cells back to kind of where they were before, which could be potentially problematic for [00:29:00] some women.

So the challenge is to figure out how to give the women who need hormone replacement therapy the hormones that they need without activating their mast cells at the same time. There are some women that you give them hormones and because it's a steady state that we do with menopause, you just sort of like estrogens every day.

Their mast cells are very happy. That actually helps them, helps a lot of things. They feel better, their fatigue is, is improved, their energy, all that. There's all the stuff that, that can improve for some women, but there's some that any amount of estrogen is irritating to them. And so we have to figure out, you know, when is hormone replacement therapy right?

Are there other things that we can do? I mean, and I didn't even mention the, the main symptom that lots of women get is hot flashes, which is a huge, huge symptom of menopause. And so, you know, there are newer drugs now that can manage that without hormones. [00:30:00] So it's a lot of like trying to figure out the, it's really, I like to take the personalized medicine approach to women here, right?

And what I would say is that I'm a big believer that hormones could be really great for some women and hormones could be really bad for other women. And so we just have to make sure that we, you know, figure out what's right. for, for you, you know. And then lastly, the last thing that I'll mention, which I think probably deserves another podcast, another, another episode, is the link between the Mast Cell, Mast Cell Activation Syndrome and Endometriosis, which is a, a huge, you know, problem could be autoimmune linked, it could be it's definitely linked to hormonal imbalances and linked to Mast Cell Activation Syndrome.

And that would be really interesting to explore and think about. Maybe we can get an Endometriosis expert to, to come on and talk about that because I think that's really important too. And it is related to these things that we're talking about.

Jill Brook: And forgive me for giggling, but when [00:31:00] we get on this topic, I think about how I've heard you and some of your colleagues talk about mast cell stabilizers and antihistamines in all interesting parts of the body. And I don't know if that comes up in Endometriosis, but I always have to giggle.

Dr. Tania Dempsey: Well, right. So for some women who have, I'm sorry. It's so funny. We did write that paper where we talked about like douches and suppositories and things to control mast cells in the uterus or in the vagina. So I mean there's so much to cover on this, on this topic. So it probably deserves another, another episode to cover some of this stuff.

But, but yeah, the fact is that, and that's an interesting point, that in some women who have excessive bleeding, they have more, more pain and cramping with their, with their period, some, sometimes, you know, in bed for, for days with severe symptoms. So, sometimes we go after it through the mast cell realm, and so we can use systemic mast cell stabilizers, we can use mast cell stabilizers that you can insert into the [00:32:00] vagina, for instance.

And I have patients who use a suppository that's compounded with Diphenhydramine, which is Benadryl, or compounded with Cromolyn or, you know, we've done them in a few different ways. And and, I've seen it control excessive bleeding in between, you know, especially when women are having cycles that are really irregular and they're bleeding when they shouldn't be.

I've seen it help that. I've seen it help with sometimes when there's pain. You know, so sometimes you have to, it is hormonally driven, but you have to go at it through the mast cell side, and sometimes it's driven, right, and you have to go after through the hormone side. So, and sometimes all the above, right?

So, I'm glad you brought that up.

Jill Brook: These are the types of pearls that people are never going to, you know, hear if they don't get to hear it from somebody as experienced as you. So thanks a million. We know you have to go. We'll let you go. We're so excited to do this again soon. And hey listeners, that's all for today, but we'll be back again next week with a normal episode [00:33:00] of the POTScast.

And we'll be back again soon with more Mast Cell Matters. With Dr. Tania Dempsey. Thanks so much. Take care. Bye bye.