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Jill Brook: Hello fellow mast cell patients and lovely 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 wonderful guest host, Dr. Tania Dempsey, Johns Hopkins Med School graduate. mast cell expert, physician, researcher, and very generous person who donates her time to be here educating us today.

Dr. Dempsey, thank you for coming and which of your fascinating colleagues did you bring with you today?

Dr. Tania Dempsey: Well, I'm thrilled to have Dr. Jill Krapf here with us. She's a board certified OB/GYN specializing in female sexual pain disorders, and director of the Centers for Vulvovaginal Disorders Florida in Tampa, Florida. She is active in research and has published chapters and peer reviewed articles on vulvodynia and vulvar lichen sclerosus.

She's an associate editor for the textbook Female Sexual Pain Disorders, the Second Edition. [00:01:00] She's a fellow for the International Society for the Study of Vulvovaginal Disease, ISSVD, and a fellow and board member of the International Society for the Study of Women's Sexual Health , which is actually where I met her for the first time.

And she serves on the educational committee and the social media committee. She's the author on the trade book When Sex Hurts, Understanding and Healing Pelvic Pain. And she's on social media @jillkrapfmd. Welcome.

Jill Brook: Welcome.

Dr. Jill Krapf: Thank you for having me. I'm so excited to be on this podcast and to talk about this topic.

Dr. Tania Dempsey: So wonderful to, to have you here. I love the work that you're doing. What I'd love to start with is really just you know, hear a little bit about your journey to this area of medicine. Can you, can you tell us how you got here?

Dr. Jill Krapf: Yes. So like anything else, it was pretty much I was at the right place at the right time. So when I was finishing my residency, I was a chief resident, [00:02:00] which is basically like a glorified scheduler. So I was creating all the schedules for surgery and the clinics, and we were really short staffed one day, and so I had to basically go down to the operating room and join one of the private docs who was doing a surgery. And we usually would send, you know, a, a, a junior resident, but it was, it was me that was joining him that day. And good thing it was because it turned out to be Dr. Andrew Goldstein, who is one of the world's experts in vulvodynia and lichen sclerosus.

And so he happened to be doing a vestibulectomy that day. And so we spent the surgical case together, just discussing all of the work that he was doing, both clinically and research wise. And so it was just so interesting that I was about to graduate and take care of patients on my own, and I just had no idea about any of these pain conditions or skin conditions in this area.[00:03:00]

So I ended up spending some time with him in his clinic, learning from him. And then I just caught the bug. I spent as much time as I possibly could. I thought I wanted to be a dean or something like that, so I was doing a medical education fellowship the year after I graduated residency as an OB/GYN, and I was working part-time to pay my way.

And so I essentially spent as much time with him as I could, and I did two unofficial fellowships that year, one in sexual health and dysfunction, and the other one in medical education. After that, I used all of those pearls to basically start the Center for Sexual Medicine at George Washington University and revive it, because it had not been active since the 1970s.

So as a junior faculty member, I was starting this big branch and they paired me up with this urologist who was an older gentleman who tried to retire. He had a private practice for 40 some years, tried to [00:04:00] retire, his wife basically said you need to go back to work. And so we were like this dynamic duo and he was seeing all the men with erectile dysfunction, and I was seeing all the women who had to deal with their partners once they got better from their erectile dysfunction. And so he taught me a lot about business and and everything. And so we ran that center for a number of years. I trained some nurse practitioners. My journey's brought me a few other places in academic medicine and then Dr. Goldstein reached out and said, hey, do you want to work for me? And I said, of course. So I moved back to DC and I ran the Center for Vulvovaginal Disorders in DC for a number of years, and then I ended up moving to Tampa and starting my own practice here in Tampa. So I've been running that for a little over two years at this point.

Dr. Tania Dempsey: Wow. That's a, that's a great journey. And it just goes to show you that once you're, you are faced with these complex [00:05:00] cases and you start to think, right, it, then it just, you know, it just takes, takes over.

Dr. Jill Krapf: Well, that's why I love it so much. I, I did full breadth OB/GYN for a number of years, for majority of my career. But I really love the challenge of seeing a patient with a complex pain condition and really thinking about how the body works, to figure out what is going on and then how do we treat it? And treating everyone as an individual I think is really important as well.

So I'm very lucky in my practice because I have the time to be able to spend with each patient to figure this out, to be a medical detective, if you will. And really, you know, really find something that's going to work so patients actually get better. So it's been very rewarding.

Dr. Tania Dempsey: And I think that the work that you do and, and in social media and everywhere where you're trying to spread the awareness, I think is so critical, 'cause I think that there are probably so many women out there who suffer in silence [00:06:00] because they don't know that there is actual treatment or they are embarrassed, or, I mean, I'm sure there's so many different, you know, reasons why it kind of goes undetected for so long for some.

Dr. Jill Krapf: It, it sure does. And, and honestly, you know, with social media, that has been a journey of being in the right place at the right time as well. So I left academic medicine in 2019, and then I started my social media. And when I started it, I thought, who is going to want to hear of these conditions? Right? How many people can be out there?

And it was really funny because when you start an Instagram, I'm, you know, a little old, older, and so I didn't grow up with Instagram or have that, you know, Facebook was just coming out after I graduated college. So I was like, I had to learn all of these things. But when I started my Instagram, I just, I had to invite people because you have to invite people to get it going.

So I thought, oh no, all of my college and high school friends are gonna learn everything about, [00:07:00] about vulvar pain conditions. But they beared with me and, and it, it caught, you know, it caught steam, but it was a really good timing because it was right when the awareness about these things on social media was expanding because then COVID hit and then once COVID hit, people couldn't really go in to see doctors and they were really turning to social media to get answers and people had more time on their hands and they were researching.

And so, and so things really ballooned after that. That's when the lichen sclerosus support network also caught speed. And so we kind of worked together for awareness on that condition as well. And we were also working on the, the book When Sex Hurts during that time. So it's, it, it always amazed me with, with Instagram, with every milestone I just couldn't believe like, how could 10,000 people be interested in this? How could 30,000 people be interested in this? And but it really has changed the landscape of these conditions because now people do go to Reddit, they [00:08:00] go to Instagram, they go to social media, the Facebook support groups. This is where people are going to get information, especially when they don't feel heard and they don't feel that their, their straightforward sources, like their general OB/GYN or their primary care doctor really knows a lot about these conditions. Then they're really seeking it out.

And I actually love that. I love an informed patient. I love an educated patient. When patients say they did their research, that's my favorite patient. I love those patients because they have a background in it. For many years I was a clerkship director, so I was teaching medical students how to be OB/GYNs.

I did that for a number of years in two academic settings, and when I went into private practice focusing just on vulvovaginal disorders, I really missed the teaching aspect, and that's why I started teaching on social media. And then I really started honestly teaching my patients, because I could [00:09:00] have a hairstylist who knows more about vulvodynia because she has it, even the pathophysiology, than most medical students, residents, or even physicians. So it's really, it's really incredible being, being able to teach people and really having them understand their condition, because I think when you understand your condition, you understand the why behind the treatment plan, and you are more likely to stick to a treatment plan.

Dr. Tania Dempsey: Absolutely. Yeah. Education is key and that's why I do the work that I do as well. Right? The more you can teach people out there how to recognize symptoms in themselves, how to find the help that they need, right? You empower people and that's what, that's what I love to do. It sounds like you love to do that too, right?

Dr. Jill Krapf: Exactly, and especially with these conditions, and I'm sure the conditions that you treat are, are just the same, people feel that their power has been taken from them because they're not living the life that they want to live, and they're thinking [00:10:00] about these conditions or what their restrictions are or what is going to cause a flare or what they can't do. Right. And when it comes to conditions that I treat, there's an extra layer because you can't talk about it, right? You can't say, my vagina hurts. Like, you can't tell your employer. You know, you just, you have all of the, this suffering that is silent. It's silent suffering, and that makes it even harder.

And so it's, it's just when you give somebody the why behind something, or the explanation of why a flare may occur or some of the tools in your toolbox, we often talk about tools in your toolbox for these conditions. When you're feeling pain, you reach into your toolbox and here are the things that you can do.

It really gives power back to the patient, and that's the most important part.

Dr. Tania Dempsey: Yeah. Yeah, absolutely. So you've mentioned, you know, pain disorders and you've [00:11:00] mentioned lichen sclerosus, you know, vulvodynia or vestibulodynia. So let's sort of dig in a little bit, and so tell us a little bit about the more common, I mean, I know there are a lot of different pain disorders, but the more common ones that you see and maybe help us understand them a little bit better on how, you know, people would present or or feel.

Dr. Jill Krapf: Yes. So pretty much everybody that comes to see me has the same entry complaint, like the beginning complaint. It burns down there. Everybody burns down there. Some people have pain with intercourse as well, as a manifestation, some people have itch, some people have redness or swelling or discomfort or rawness, however you wanna describe it.

But there's discomfort in this area. And so when we're looking at that, the general term for that is vulvodynia. So Odynia was the little known Greek goddess of pain, like allodynia, an abnormal pain response, so vulvodynia is [00:12:00] an abnormal pain response of the vulva. But that is pretty broad. That's the whole area. So it's really hard to kind of pinpoint. So most people do not have pain of the entire area. Most people have pain of the opening of the vagina called the vestibule. It's kind of like the foyer of the vagina, like churches and synagogues, theaters have vestibules. So it's, it's that opening area that really houses the urethra, where the urine comes out, the glands that produce our natural lubrication, and anything that goes in the vagina needs to pass through that area. And so most people have what we call the vestibulodynia. So pain of that area. But even, even classifying it that way, we're still not talking about cause. That doesn't reveal what is causing that pain. We can be a little more descriptive and call it provoked vestibulodynia, meaning [00:13:00] pain at the opening when it's touched, right. And we're getting a little closer. But in general, vulvodynia or vestibulodynia by definition does not have an identifiable cause, which is very frustrating because how do you know how to treat something when you don't know what causes it? But my, my hope is that in my lifetime, there will be no more vulvodynia, meaning there will be no more unidentified vulvar pain. Because there are causes to everything, everything. And so there are also causes to vulvodynia and provoked vestibulodynia. So when we're talking about pain at the opening, generally the most common causes, or what we call associated factors can be broken down into four different buckets.

One is hormone related, and we can see this in different age groups. The most common, of course, is related to menopause. But we can also see this in perimenopause. We can see this with different [00:14:00] medications that can kind of mimic that process. And we can see it in lactation, so breastfeeding, and, and the postpartum period as well. But it's all the same idea and it's the same process that's going on. So hormonal is one bucket of cause.

Another bucket is muscle related. So when the muscles of the pelvic floor and the superficial muscles under this area, this opening area, which are like a hammock or a sling, when those are tight, it's restricting blood flow, right?

Anytime we're restricting blood flow, then the overlying tissue of course is affected. So blood carries oxygen from our lungs, nutrients from our gut, and hormones from our ovaries if our ovaries are still working. And so when there's a tightness of the muscle, then the tissue can be affected and that can be a factor.

The third bucket of cause is nerve related. You can have the big nerves that come from the lower spine, those wrap under the [00:15:00] pelvic floor muscles and then they provide innervation or feeling to this entire area. And so you can have irritation of the pudendal nerves or other nerves that are coming in from the top or the bottom, and that can create symptoms as well.

And then you also have the nerve fibers at the vestibule, which is where we get into your realm a little bit, a little bit, because that has to do with nerve proliferation, but then also mast cell proliferation. And then we really get into your realm because the fourth bucket of cause is inflammation. And the inflammation bucket out of all of those buckets, the inflammation bucket is the one that we know the least about and we really don't understand at all. Because everything causes inflammation, even hormonal and muscular causes, like, you know, they cause inflammation at the tissue level, right? And so everything comes down to inflammation. So there's identifiable things like autoimmune skin conditions like lichen [00:16:00] sclerosus and lichen planus that we can see with our eyes, we can biopsy and get a diagnosis.

And then of course there's yeast infections and outward bacterial infections and the effect of those. There's also inflammatory discharge that can come down called DIV or desquamative inflammatory vaginitis. So we're getting a little bit of a handle on the different types of inflammation that can be at play.

But then there's this whole idea of mast cell proliferation and nerve proliferation and all of these things that is just, it gets into a very gray area with what we understand and what we don't understand.

Dr. Tania Dempsey: So in that area, I mean, we had the pleasure of working together on a, on a white paper, really just trying to see if there are treatment options for this area, which is it's provoked neuroproliferative vestibulodynia.

Dr. Jill Krapf: Yes. That's a mouthful. So basically pain at the opening with [00:17:00] touch due to increased nerve fibers. And so, this is the trickiest one to treat because these patients are severe in this area. They can typically have never been able to insert a tampon. They have never been able to have intercourse.

Anything that touches this area is excruciatingly painful. And so when you talk about they could have muscular issues going on. They could have hormonal issues going on as well, but you just can't even get to the treatment of those things because it is so severe. And so the best we have for this treatment is removing this tissue. And that's called a vulvar vestibulectomy. And these nerve fibers are very shallow in the vestibule, so we can remove the tissue of the vestibule, sew the area back together. But there's very few people that do this surgery. So there's an access issue. You have to have the right diagnosis. [00:18:00] So if you have somebody that has a tight muscle cause, or an, or a higher nerve pudendal, nerve related cause, and you remove the vestibule, you're gonna make those muscle reasons and nerve reasons worse. So you have to have somebody who's diagnosing this correctly.

You have to have a good surgeon. And then the recovery time is quite extensive for a procedure like this. So there's a lot of barriers here. And so there's a big motivation to try to find other options for this condition beyond just removing the tissue or removing the area.

Dr. Tania Dempsey: What I found interesting and really fascinating is that the biopsies of the tissue that you've removed, you and your colleagues have removed, if they're stained the way we stain mast cells, right, it's a CD117 type of staining. There are a few other stains that you use as well. You find those mast cells basically around the [00:19:00] nerves. The nerves and the mast cells are intimately connected in these tissues, right. And so that's how I sort of got involved in this, right, because we were trying to figure out are there ways to treat this from a mast cell lens and are the mast cells somehow causing the proliferation of the nerve fibers or is it vice versa, right? That's what we don't know.

Jill Brook: So, in what you were just talking about Dr. Dempsey, that you find a high proliferation of mast cells, is that only in the people with pain or everybody's nerves in that area have a lot of mast cells around them.

Dr. Jill Krapf: So, no, so these are in the specimens of people who have had vestibulectomies. So the area was removed because they have neuroproliferative vestibulodynia, and I believe there have, these are all very small studies, too, we have to recognize that they're, they're very small numbers in these studies, but I believe they have compared the the samples, the tissue specimens of people with [00:20:00] vestibulodynia to people who have had tissue removed for other reasons, and they do not have the same picture of neuroproliferation and mast cells as people who have provoked vestibulodynia due to, you know, neuropathic causes.

Dr. Tania Dempsey: Do you think those patients that have this condition were exposed to something either early in life, or an early childhood that may have caused the mast cells to, to become activated, to release the cytokines and the mediators that they release that then call those nerve bundles into, into that area and cause pain. Do you think there's an initiating event?

Dr. Jill Krapf: This is debated. So what's very interesting, okay, there's a few interesting points here. Number one, of course, neuroproliferative vestibulodynia, what we're talking about, can either be primary or secondary, so primary, we typically call that congenital because we [00:21:00] believe that there could be, you know, some factor as that, as, as you are describing.

And what supports that is we actually find an association between umbilical sensitivity, so sensitivity of the belly button and congenital neuroproliferative vestibulodynia. And that makes sense because the urachus connects these two, so there's a neurologic connection between these two areas. Now, this isn't an everyone, but there is a higher rate of people with belly button sensitivity, so that would be very interesting, and it's a possibility it would support that hypothesis.

Now, there's another idea and a lot of the animal research really leans on on this or, or tries to replicate this. There's an idea that there is a connection between yeast infections [00:22:00] exposure and this process. So there's, it's almost like a spark or a trigger. There's something in yeast that initiates this and you know, it's hard to say whether that exposure is very young, creating a primary or even kind of a congenital like picture, or whether that exposure could be late or creating a secondary picture.

The tricky part about that is that a lot of these conditions, remember in the beginning I said everyone feels burning, rawness, discomfort. There's only one type of nerve receptor in the vestibule. It's a C-afferent nociceptor . So everything is going to feel very similar to someone. And of course, a yeast infection is what we often leap to because it's the first thing that our doctors check for. It's what we're socialized to think about when we have discomfort in this area as females. And so it's really difficult because I see a lot of patients that [00:23:00] will say, oh yes, I've had recurrent yeast infections, and I've tried to treat them over and over and maybe I get, you know, a little relief, but it never fully goes away. But the funny thing is, when I go in and I get a swab or a culture, it's always negative. So, we don't know, we don't know how much of it could be like a socialization aspect or if it's truly yeast or if it's not.

There certainly are people with vestibulodynia that do not have a history for yeast as well, so it doesn't completely explain everything. The other thing that we don't know, and I'm actually curious what your answer is here. We used to think that once this process happened, that the horse was out of the barn, that it could never be modified or reversed. It was only gonna go in one direction. And that really supported surgery as a definitive treatment for this as well. But I can tell you in [00:24:00] practice, I have had a number of patients that I was convinced were neuroproliferative vestibulodynia, congenital even, and I recommended surgery for them.

They decided for whatever reason not to do surgery or to do secondary measures in the meantime because of, you know, finances or life or healing process, whatever the reason. And they have had some, they've had improvement. Even people that I thought had neuroproliferative vestibulodynia. So the question is, with processes that you see, is there any, is there any chance for reversal?

Dr. Tania Dempsey: Right. And that's what I, that's what I'm curious about as well. And so, I'm curious, and this is why, you know, working together on the, the Vulvodynia Summit and trying to, to brainstorm together, are there things that we can do with my, you know, from my lens of the mast cell, that if you intervene soon enough in the [00:25:00] process and you were able to stabilize mast cells, could you stop the neuroproliferative aspect of the condition, right?

That's, that's the, that's the burning question.

Dr. Jill Krapf: That's the question. You know, it's, you know, if, if this process is initiated by something that can be modifiable or if we can modify it in any way, you know, can we decrease the nerve proliferation down to levels that are acceptable? And this is something that we, we just, we don't know.

Dr. Tania Dempsey: But there are some people looking already, and I'm curious about what you would use outside of surgery, but I know, I know there was a study that we discussed and, and the author of the study, you know, remotely joined our summit. It was about ketotifen use in in neuroproliferative vestibulodynia. So maybe you could talk a little bit about that and then some other treatment options that you're looking at.

Dr. Jill Krapf: So ketotifen is not something that we routinely [00:26:00] use, unfortunately. I think that it is one of the therapeutics that we identified as a, a possibility. I believe with ketotifen, the study that Dr. Bornstein did really the, the important part was that it was more preventative or it had to be used very early in the process.

And that was, that's the sticking point with something like ketotifen, which I think makes it actually very, very promising. If we're able, you know, if we're able to prevent this, that would be amazing. I mean, that's better than waiting, waiting until someone has it and treating it. But you know, that would be that would be an important part.

The main conservative measures that we have for neuroproliferative vestibulodynia, that we do have a bit of research, and it's scant, I mean, this is not good research. There's, they're not randomized control trials here. But basically we've looked at topical gabapentin for, for nerve. It's, you know, it works about [00:27:00] 60% of the time to a level of 80% relief. So it's kind of hit or miss. Clinically, it's hit or miss. I feel like it, there's a chance of it working better with secondary neuroproliferative vestibulodynia more so than primary or congenital. It also depends on the other factors involved.

And then the other thing that we have is actually a capsaicin which, if that sounds familiar to you, it's probably because it's the active ingredient in chili peppers. And it's a topical that's typically used for back pain or nerve related pain in different areas. We can put it in this area. It burns a lot. It's a regimen where you have to put it on, wash it off immediately, and you build up over the course of days to weeks. But it, what it does essentially is it drains the battery of the nerve, and so when you apply it, all of that substance P is released all at once.

You wash it off [00:28:00] and then you apply it the next night and then you know, it essentially because all that substance P is being released so much, it, it can't build up as fast as it was released. And so you drain the battery of these nerve receptors and so it does work. It's a medication and a treatment plan that requires a lot of counseling and a lot of preparation.

And not everyone can do it. I've really only used it in very specific cases where people have tried everything else. And generally with secondary neuroproliferative vestibulodynia, never primary or congenital. It would just be too uncomfortable. So those, those are the ones that we kind of have, which aren't great.

Not great at all. You can see why we generally do surgery because it's more definitive in these cases. And I do wanna stress that, out of all the causes of vestibulodynia, the neuroproliferative ones are, are much more rare. So it's not the majority, it's not even, it's maybe, you know, it's [00:29:00] less than 10%, maybe 5% of, of what we're seeing.

And so, you know, it's really a small proportion that we're referring to surgery anyway. But very important. Very important. And then when it comes to other therapeutics that we identify. The other one was luteolin. And so we'll have to see, I mean, these are just things that, you know, we just don't as gynecologists, we just have not had much experience with it. Certainly not as much as you have. And so that's what we need your help, to know, you know, would this be possible? What can be compounded in a topical form? Obviously topical is going to be, better for our purposes when it, when we're talking about vestibulodynia. So that's where this is so exciting to, to look at these potential treatments, especially ones that have been around for so long but have not been utilized for this purpose.

Dr. Tania Dempsey: No, absolutely. What I would be curious about is how many patients who have a [00:30:00] pain, a, a vulvar pain disorder, have overlap with the, the patients that I'm seeing? You know, they may have more systemic symptoms or they may have POTS or EDS. I'm curious about the overlap, not just in the neuroproliferative, you know, realm, but just in general in pain syndromes.

Do you think there is an overlap with other chronic complex conditions?

Dr. Jill Krapf: There is absolutely an overlap. And so what we started realizing, and we were kind of realizing this all along, we just didn't put it together until a few years ago, is that our patients that were coming in with really, really tight, severe pelvic floor dysfunction, so their pelvic floor is just seized, right? And that's going to have effects on the tissue as well as the nerves, the pudendal nerves, and the bigger nerves. Not necessarily nerve fibers, but of course there's an element of that as well, [00:31:00] because when tissue is not getting blood profusion, there's going to be an element of other things that are going on as well.

But what we realized is that a lot of these patients had hypermobility, and so we started realizing that these patients have some form of connective tissue disorder. They might not be meeting criteria for Ehlers-Danlos, but they certainly had something on that spectrum especially in their hips. And they had sacro iliac joint dysfunction, and they had, there was this picture that started to develop and it makes sense because when your joints are loose, your muscles have to be tight to hold everything together. It's a compensation mechanism. The other thing we were seeing that's very interesting is a lot of these patients they had disc herniations and these spinal pathology, and they were young.

They had the spines of like 80 year olds and they're 30. And so we started putting all of this together. And [00:32:00] then that has nerve related effects, right? Which, and then muscle effects and it just goes right down the chain. And it all leads to the vulva apparently, at least with the patients that we're, that I'm seeing.

And so we started putting together a connection between Ehlers-Danlos and connective tissue disorders and vulvodynia. And then of course, a lot of these patients have POTS as well, so vascular effects, which makes sense because there's connective tissue in everything. And then you know, there's also this connection with mast cell activation.

And this is where we struggle because these patients don't meet criteria for Mast Cell Activation Syndrome in its most specific sense. You know, they're not anaphylactic, but these are patients that are sensitive, right, to many different things. You know, they break out into hives. They break out into rashes. So we started asking the questions, and when we started asking the questions, we started finding [00:33:00] that there's a big connection between these vulvar disorders and pain conditions and all of these whole body symptoms and conditions as well.

Same with Sjogren's. With Sjogren's we found, obviously, it's an issue of the glands, so they were having issues with their eyes, their mouth, and of course, where do you have glands? At the vestibule, the vulvar vestibule. So they were all struggling with a lot of dryness, but they're not telling their rheumatologist about their vaginal dryness.

So it really wasn't getting picked up. And then the gynecologist wasn't putting it together because they don't know about Sjogren's. So that's why the crosstalk is so important with these conditions.

Dr. Tania Dempsey: That's right and I think it's really important that's that you are starting to put it all together. You're not just looking at this one area of their body. Well you are, right, you're concentrating on that one area, but you're starting to understand how everything is connected, and I think that's really the most important piece of this, [00:34:00] is to see how everything is connected. Because I always think about it, we only have one body. There can't be 10 different conditions going on in the body that are not related on some level, right. And so that's why I think that work is really, really important. We're gonna have to team up and do some research because I think that, you know, the data you have and the data we have, oh my gosh.

Dr. Jill Krapf: It's no, it's incredible. And when you start thinking outside of your area, you know, unfortunately in medicine we're trained in silos. And so when you start thinking outside of your area, it's actually incredible. I mean, even connections, like people who are jaw clenchers, who have TMJ, they are more likely to have tight pelvic floor muscles.

So if you're clenching here, then you're clenching down there too. It's incredible. I had one patient, this illustrates it beautifully, she had awful jaw clenching, and she was actually getting a lot of orthodontics to correct her jaw. Every time she had an [00:35:00] adjustment in her orthodontics, she had a pelvic floor flare. Every single time.

Dr. Tania Dempsey: Wow. I mean, it makes sense, right?

Dr. Jill Krapf: It makes sense. That's the thing. So when we start taking a step back and thinking about how does the body work at the most basic level, then we can really put our detective hats on and we can figure out these conditions and we can help our patients in many ways, because if you're a rheumatologist and you have a patient, you know, and you're asking the questions, you might refer someone more readily to a gynecologist to really help with a condition that she would never bring up to anybody, even maybe her doctor.

Dr. Tania Dempsey: Wow. Have so many questions now, but what I'd love to talk a little bit about is our, our audience definitely is very, very interested in hormones and the connection with obviously the immune system. I think about hormones a lot. I treat a [00:36:00] lot of perimenopausal, menopausal women, but I also treat women, you know, younger who also have hormonal issues, right, so it spans the, the, the lifespan. So what I'm curious about is, you know, your approach. You mentioned obviously that some of these conditions are hormonally based. So yeah, talk a little bit about what your approach is for that.

Dr. Jill Krapf: Yes. So hormones are a big part of my role. I'm also certified by the Menopause Society as well, and so I have a good grasp on whole body hormone therapy as well as local hormone therapy. And these two things are very different because they have different aims, they have different benefits, they have different risks associated with them as well. And so when we're talking about local meaning the vulva, the vestibule, which we talked about and the vagina, there's two kind of ideas when it comes to this. So obviously there's physiologic, you know, life events or circumstances or conditions, if [00:37:00] you will. That are going to lead to hormonal changes.

And the one that we always think of is perimenopause and menopause, obviously, but there's others as well, such as postpartum, lactation. We call this genitourinary syndrome of menopause, which is the newer term for vulvovaginal atrophy. I agree, it sounds better. And it also includes the urinary system as well, which is very important because the bladder and urethra has the same receptor status, if you will, or kind of, how it's categorized as the vagina and the vestibule. There's a lot of similarities there, and so I'm glad that we have a, a term that encompasses it. But the problem is that it really, really steers us towards menopause, and it's not as inclusive for these other younger women who are having the same process, but just have a different reason for it. It's not necessarily menopause. It could be a medication, an anti [00:38:00] testosterone medication that they're taking, or another reason. And so, and so that's, that's a part of it. The other interesting thing, and this isn't really published anywhere, but the, when the, when the pelvic floor muscles are tight, it's not only limiting blood flow, but the blood carries hormones, if the ovaries are working. So in these younger women who are cycling regularly and ovulating and you do if you test their blood, their estradiol and their estrogen levels are normal and everything looks fine, but when you look at the vestibule, they look like a post-menopausal woman.

So what's going on there? It's because their muscles are tight, impeding blood flow, impeding hormone to the overlying tissue at the vestibule and the glands that produce our natural lubrication. And then that's affecting glandular function as well as tissue at that level. And so we can see a [00:39:00] menopausal or perimenopausal picture in someone that may have regular periods.

And then when they go, unfortunately to their general doctor, they're going to be disregarded because the doctor's going to say, well, you have a regular period. You can't have this effect. We don't always know what we're looking for either. The glands, these glands, you know, we, we do a good job of doing a Pap and things like that, but we don't always do a good job at looking at the vulva including the clitoris, including the vestibule. Most people don't even know what a vulva vestibule is. So, you know, so that, that, that is education right there for our colleagues and really looking for where the pain is because 90% of pain with insertion or with sexual activity, dyspareunia is what we call it, is actually at insertion and it involves the vestibule and most of it is hormonal and muscular, a majority of it.

The other interesting thing is the role of testosterone. So we often think of estrogen as the only [00:40:00] hormone, but it's not. It's not the only sex hormone. We have estrogen, we have progesterone, we have testosterone, and then we have a slew of other ones that we could go into in the pathways, right?

But with testosterone, women have testosterone. Men have estrogen in addition to testosterone. We all have both. And testosterone is very important for women. And what's very interesting is these glands at the vestibule and the vestibule in general has more androgen receptors. So this is some research that's just coming out, and it's very interesting. We're actually putting together a review on this right now to really delve into both the animal and the human research on this. But the vagina has a lot of estrogen receptors. We all know that because we know about vaginal estrogen. But actually there's testosterone receptors in the vagina, and as we get down to the opening or the vestibule, there's a ton of androgen receptors.

There's also estrogen receptors, but I think there's more androgen receptors, especially at the [00:41:00] glands. And this makes sense because it's homologous. The vestibule is homologous to the male prostate. The male prostate. So think about it. So as we're forming in the womb to either male or female, the same structure either encloses and becomes a prostate rich in androgen or testosterone receptors and the ejaculate forms inside of it. Or in females, it stays open, and then those glands secrete natural lubrication or ejaculate, almost like a car wash.

But the idea is the same. And so it makes sense that the vestibule would need more testosterone. And this is something that we need much more research on, but we've been doing clinically for decades. It's just, the studies are not, the studies are not there for this. The good news is there is a newer medication that's vaginal [00:42:00] DHEA. Yes, is the precursor to estrogens and testosterone. And so it would make sense that this would have effect not only in the vagina, because it's a vaginal suppository, but some of that filters down to the vestibule and it's quite effective. We don't have the studies to show this, but clinically we believe it's more effective than vaginal estrogen alone because of that androgen component to it.

Dr. Tania Dempsey: Love that. That, that explanation was so, it was excellent. It was, I mean, I know this stuff. But the way you described it was, is perfect for our audience. And I think it just nailed down, like for me, honed in on that, that concept. That's a very, very important concept.

Dr. Jill Krapf: Well, it's important for all of us. I mean, we know how to talk about this in medical ways, right? Like we know how to read the studies and it's almost like translation. Sometimes I feel like I'm, I'm a translator because this is the level of detail that I get into with my patients. I talk about pathophysiology. I talk about [00:43:00] anatomy. I talk about embryology with my patients, and guess what, they get it. They understand. It doesn't matter if you're a realtor or a a, you know, a scientist, like in fact, sometimes my medical people don't understand it as much as the lay person. But no, it's it's important though that we understand these concepts because then we can think outside the box.

Then we can start developing approaches and how to, even if we have the medications available, how do you use them? How often do you use them? How do we make the most effective? How do we limit side effects, right. It's not just about the tool, it's about how you use the tool.

Dr. Tania Dempsey: That's wonderful. I mean, obviously we can, we can talk about so much more, but I know that, that your time is limited and I just so appreciate you being here. Any last words and how can people find you?

Dr. Jill Krapf: Yes. So, my last words are that there are causes for everything. There are [00:44:00] causes for vulvar pain, for genital pain. We will find more in time, but in, in the meantime, if you look at how the body works, we can identify a cause or a bucket of cause to get somebody in the right direction. Because once you know the cause, or more accurately the causes, because it's overlapping is the reality, there's not a magic pill, right? Never. And so once you know the causes, you can create a focused treatment plan that is actually going to work. And so that's what I want people to take away from this. And that we're working on it, right? We're, we're actively working on it.

And so the book that I wrote with three of my colleagues with Dr. Andrew Goldstein, Dr. Irwin Goldstein, and Dr. Caroline Pukall, we wrote the book When Sex Hurts. And it's not just about intercourse or sex, it's about vulvovaginal genital pain, right? And so anybody can benefit from reading [00:45:00] this book. It's, it's, it's a trade book, but it has references, so even clinicians would benefit. There's analogies similar to analogies that I'm using when I talk about this in this podcast. There's patient stories that really highlight what we see in the office to make it very real. And so I really encourage people to check that out if they want a really deep dive and learn more about these conditions, even if it is not in their area, and especially if it's not in their area. I want my internal medicine, rheumatologist, endocrinologist, like all, you know, everybody would benefit. If you see female patients, you're probably seeing patients with these conditions. So I think it's really it's really beneficial.

And then, my practice is in Tampa, Florida. I'm the director of the Center for Vulvovaginal Disorders, Florida. I am accepting patients. Obviously would love to see anybody, and if anybody would like to make an appointment they can find me on social media, which is probably the easiest way.

I'm on [00:46:00] Instagram, jillkrapfmd.

Dr. Tania Dempsey: I'm thrilled to have you here today and thanks so much for making the time.

Dr. Jill Krapf: Absolutely. Thank you so much.

Dr. Tania Dempsey: Thank you.

Jill Brook: Dr. Dempsey and Dr. Krapf, thank you so much. This has been some amazing information today. We're so grateful for your time and your expertise. Listeners, we will put those links in the show notes so that you can find everything easily. And that's all for now, but we'll be back again next week with another episode.

And until then, be well, may your mast cells be good to you and please join us again soon.