Content provided by
Matt Cook, MD
Guest experts
Betsy Greenleaf, DO, FACOOG (Distinguished)
- Peptide treatments for pelvic health conditions such as sexual function and urinary tract health.
Matthew Cook, M.D.
Welcome everybody to the Peptide Summit. My name is Doctor Matt Cook. And I’m really delighted to be here with Doctor Betsy Greenleaf today. She’s an osteopathic doctor and she’s a Premier Women’s Health expert. She’s a bestselling author, entrepreneur, inventor and business leader, specializing in Female Pelvic Medicine and Reconstructive Surgery for over 20 years. She’s a trailblazer as the first female in the United States to become board certified in urogynecology. You may not know this, but that’s a very high level of achievement, so, that’s super awesome. She possesses professional reputation that’s led to her being sought after by medical societies associations and corporations to provide lectures teaching and advanced training. She was honored by the title of Distinguished Fellow of the American College of Osteopathic Obstetricians and Gynecologists for her service and dedication to the field in 2018. And she holds committee positions on many national women’s health organizations. She is in a board examiner for the American Osteopathic Board of Obstetrics and Gynecology and serves as a spokesman for the American Osteopathic Association. I’m gonna get tongue-tied if I keep reading this. And then, she was recently awarded the Future of Healthcare Impact Award at the prestigious Mindshare Summit, 2021 for her TED-like talk on the brain-gut-vagina connection. So, this seems like a good place to start.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah.
Matthew Cook, M.D.
Honestly, I’m delighted to talk to you. I was actually talking to another urologist and I got my signals mixed up and so I said, “Oh, what do they wanna talk about?” My staff said, pelvic pain. And I go, “Oh my God, I can’t wait to have this talk because I used to work at a surgery center and I’d never met a urologist that even remotely wanted to talk about pelvic pain.” And I sat down, and they go, “Oh no, you have the wrong one. I don’t wanna talk about pelvic pain. I wanna talk about all this other stuff.” And it was an amazing conversation. I go, “Who’s the person that you’re gonna talk about pelvic pain?” And they go, “Oh, you’re talking to her tomorrow. She’s super awesome.” And I think, pelvic pain is probably one of the defining problems of the specialty of urology and in general, for humanity. And then, it’s also interesting when there’s a specialty that doesn’t like to take care of a problem, that it does. It’s interesting. So, welcome to the podcast. I’m so happy to meet you.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Thank you so much. I’m so excited to be here. It’s so funny when you read all those things. I keep thinking, gosh, I haven’t accomplished much in my life, and then you read this I’m like, wow, wait a minute, I’ve done some stuff .
Matthew Cook, M.D.
Aint that crazy?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah, yes.
Matthew Cook, M.D.
Crazy. And then, you’ve been a trailblazer. I love that you were able to be the first woman what was it like? Tell me about, how was it? When I was in medical school, I remember clearly like it was yesterday. These three women came up to me and they go, “We need to be clear about one thing.” And I go, “What’s that?” They go, “Gynecology is a women’s field and you can’t go into it.” That was on my first day. And so then, I go, “Okay.” It was interesting. It was kind of a… And so then, they go, “Are we clear on that?” And I would go, “Yeah.” And they go, “Okay, good.” So, then they go, “We’re gonna get along great. And you’re gonna do good on this rotation.” That was my gynecology rotation–
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Oh, that’s such a shame.
Matthew Cook, M.D.
At the University of Washington. But I loved it. I still loved it. But I think, gynecology is the hardest field than medicine because it’s so stressful and everything. So, how was it for you actually? You didn’t listen to any of the naysayers and then becoming the first. What was it like to go through that journey?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
It’s funny, ’cause it’s a good thing and bad thing. ‘Cause I have a tendency to be a little spunky and not listen and follow the rules. So, it was a long road, but it was fun too. Urogynecology is a funny field because it’s been around since about the 70s. So, it’s pretty new but it was never a board-certified specialty because the urologist and the gynecologist could never agree on how to set up the board exam process. So, it took years and years for that to finally occur. Even a lot of people don’t even know what urogynecology is. I remember when I told my mom for the first time like, “Oh, I’m gonna do some more training. I’m doing urogynecology.” She thought it was like Euro Disney. Like it was some fancy European gynecology and I’m like, “No, it’s urology having to do the bladder and pelvic health and gynecology dealing with women’s parts.” So, it’s a nice combination this field but there’s only about 1,500 of us across the country right now.
Matthew Cook, M.D.
Oh, really?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah.
Matthew Cook, M.D.
So, what would be the top three or four things that a gynecologist would see in normal clinical practice?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah, well, we talked about pelvic pain but I have to say that with pelvic pain even as a gynecologist, there’s not a lot that practice it, because it can be a very difficult condition to treat. So, most uronology will deal with incontinence. So, leaking if you cough, laugh, sneeze or you have to run to get to the bathroom or prolapse where the vagina has dropped and it can’t get back up syndrome. We have these ligament that hold things up and things start drooping and dropping from either childbirth or lifting heavy objects or straining or the recurrent urinary tract infections. Those tend to be the top three that most uronology take care of. But then, there’s also some of the pain syndromes like interstitial cystitis which is an inflammatory condition in the the bladder. And then, there’s a number of us that do pelvic pain or specialize specifically in pelvic pain too.
Matthew Cook, M.D.
Okay, that’s amazing. So, then tell me, how do you define and how do you think just at the beginning from 30,000 feet how do you think about pelvic pain?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
I think, it’s very difficult. And just in general, let’s just talk about pelvic health for a minute, in general. 80% of all women will have a pelvic health condition at some point in their lives. And what drives me crazy is that nobody talks about it because our culture’s still just so hung up with talking about anything acknowledging the pelvis as it is. I know I’m constantly getting shut down on Facebook and Instagram for posting anything having to do with pelvic health because it’s not in community standards. And people just automatically assume that they’re the only ones that have this problem or it’s normal or that, “This is just a part of being a woman.” And so, unfortunately I think just in general when we look at pelvic pain on a whole it’s not talked about a lot. So, unless you’re suffering from it people don’t know that it’s even a thing and that something can be done about it. And then you go into, what are the causes? It’s amazing, people will be fine, fine, fine. All of a sudden, they get pelvic pain and it just sneaks up on you and it can be devastating.
It can affect not just that person physically but can effect their relationships. It’s gonna affect their work performance. Say you have a mom who’s suffering with pelvic pain. She’s gonna be more snippy with her kids. She’s definitely not gonna be engaging with her partner. So, it really affects that whole person. And in that too, with pelvic pain it’s usually not one cause. It’s not like, “Okay, this happened we’ll do this and you get better.” Usually, there’s so many things that come into that. I always talk about with just health in general that total health is like a three-legged stool. You have body, mind, spirit. And if all those legs on that stool are not equal, that stool’s gonna fall off, fall over. So, if you have problems physically and you go to the doctors a lot of times and we have the tools to fix the physical part. But if there’s not any addressing of the mental and spiritual aspect, which a lot of that work as practitioners, we can guide them into what they need to do. But that’s work that patients really need to do on their own. And that’s how they’ll ultimately get better from these conditions.
Matthew Cook, M.D.
I gotta go back to this. So, they shut you down for not being community standards. And in what way?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
I know.
Matthew Cook, M.D.
What would be a type of thing that they would shut you down on?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Well, the word vagina would be the big one. So, Facebook doesn’t like that. That one I always get blocked. Apparently Instagram, I got deleted off Instagram this summer, like completely deleted. And I’m like, well, wait a minute, there’s a lot. Even though Instagram and Facebook own each other or Facebook owns Instagram there’s a lot of people that say the word vagina. You got the vagina whisperer. There’s a lot of vagina people out there on Instagram but apparently, that wasn’t the issue. All we can guess because my poster pretty they’re educational is that, the word you, on Instagram is actually goes against their anti-bullying policies. So you can’t say, have you ever and then connect that with something that has to do with race, religion, gender, sexual orientation, or medical condition. And I had a post and it said, it was a funny post. It said, “Have you ever?” And it had a cat licking themselves. And then, the post was all about feminine itching.
Matthew Cook, M.D.
Oh.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
So, we think that, that got me deleted.
Matthew Cook, M.D.
Oh, no, that’s good.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
I’m back and I’m building it back on up again.
Matthew Cook, M.D.
Okay, your band.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yes.
Matthew Cook, M.D.
A band gynecologist living on the edge, I love it.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yes, yeah.
Matthew Cook, M.D.
So, consider it like you can… I don’t know. This may be a starting point. Let’s say my elbow was sore and this is an interesting one. It’s pretty easy to compartmentalize that I might be sitting here and my… This kinda hurts, but I can basically totally focus. And then, I have an idea that there’s pain but I can work my way through that. But if you have pain, basically that is in your chest or your pelvis, it’s so connected to that sense of identity that it becomes overwhelming and it begins to affect mental, emotional, spiritual, I think. And so, then that leads to the three legs end up getting off. And when you have two or three of those things going on it seems like it compounds on itself.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah, and it feeds, it definitely feeds into itself because then, you start building up the anxiety and you start getting stressed because you’re uncomfortable. And we know that stress and anxiety will produce hormones that go, like cortisol which can then lead to leaky gut which can then lead to more inflammation which can then go back into, well now, I have more pain. And then, I also like to explain to patients too that when they’re having a pain condition especially if it’s pelvic pain, not to put off and be like, okay, this is nothing. Or it’s gonna go away on its own. Because the longer you put it off, the more you increase your risk of developing chronic pain. I have this picture that I do in this lecture. And it’s basically a picture of somebody taking a hammer to your hand. And if you take a hammer to your hand and you go, “Ouch!” And you’re like, okay that’s a one time event. It hurts. We wanna have pain in our life because then I’m gonna be like, okay, I’m gonna pull my hand away from that hammer. But if you have chronic pain that keeps happening over and over again and we’re not exactly sure what’s causing it that’s like somebody taking a hammer to your hand constantly, again and again and again. And over time, what ends up happening with that, is now we have those nerve cells from your hand that are going up your arm to your brain and now you’re upregulating your pain receptors all the way along that cord to the brain.
So now, three months later, six months later I come and I touch you with a feather you are gonna go, “Ouch!” And you think I’m touching you with a hammer because you have more pain receptors in your arm, in your spinal cord, in your brain so you’re gonna to perceive more pain. And this is why it drives me insane too as a doctor that practices gynecology and pelvic health. Still gynecology, as a whole, is still backwards when it comes to pelvic pain because so many women end up getting hysterectomies or like, well, you’re having pain let’s just cut something out. And I’m always like, well, that doesn’t work when someone’s got a leg that’s bothering them and we amputate their leg. They still have that phantom limb pain because you still have the receptors in your spinal cord and your brain. And so, the same thing happens with pelvic pain. Surgery and cutting out body parts should be the last thing and we should be focusing more on ways to downregulate those receptors which there’s been a number of studies showing anything from the treatments that we talk about here. Peptides can help with that. Even things like meditation, yoga. They’ve actually done studies where they looked at the brains of people with chronic pain and they physically had changes in their brain. And they could see somebody’s brain that had chronic pain and someone who had not pain and look at those brains. And then, they put them just through an eight-week course of meditation and those people with chronic pain their brain structurally improved and they also reported less pain. So, there are so many different things that can be done.
Matthew Cook, M.D.
Yeah, even I feel like we spent from 2000 to 2014, ’15 almost 24 hours a day doing yoga and mindfulness and meditation and traveling all around the world while we were doing integrative medicine and injections also. And when I look at it now, I feel like basically for chronic pain there’s almost needs to be a curriculum.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yes.
Matthew Cook, M.D.
Of all of these wellness mindfulness meditations and basically a curriculum that basically is a lifestyle of how to balance yourself. And then in parallel to that, on the other side then there’s all of these modalities that we do. But there’s a whole bunch of stuff in the middle. And maybe we can take that as a starting point because when I mentioned pelvic pain when we were talking before the show started you said, “Oh, I like to work on the gut.” And I think, that’s central to that whole lifestyle piece. Why is it that you go there? Why was that your first place? I was intrigued and happy to hear you say that.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
It’s funny and that’s something I’ve figured out as years have gone on. I always quote Hippocrates which always amazed me in 440 BC he said, “Let food be thy medicine.” And I’m like, wow, how did he knew that back then? And yet, we still are not doing that, as a whole as Americans. In fact, as Americans on a whole, in general we’re still eating a lot of fast food and still having a lot of chronic conditions. But it’s just been over the years through my studies like constantly looking for answers for patients that when I started looking into the gut I really started finding more answers especially for those chronic pelvic pain patients where I had tried every injection, every medication and everything I could think of and nothing was working. And I tripped across this idea of the pelvic health. And it’s been a game changer. So, with the idea of, so many of our neurotransmitters are made in the gut. 90% of our serotonin is made in the gut. And that’s the hormone that helps us feel happy. GABA is made in the gut, and so that can help. That’s another neurotransmitter. 85% of our immune system is made in our gut. And so, a lot of times too when I see the pelvic pain patients not only they have pelvic pain they usually have anxiety. They usually have depression. They’re usually are getting recurrent infections. And so, I start with the gut though you can get in the circular argument that it could be stress that affects the gut ’cause they go hand in hand. But this idea that whether it’s food we’re eating like inflammatory food, like sugar, dairy, gluten processed foods or if it’s stress. Now because of chronic stress we’re throwing off our gut. That you develop leaky gut, and I explained it to patients. It’s like that protective mechanism that protective layer of the intestines gets damaged.
And now, you get these little gaps in the intestines where food and toxins from our food can get into our body and now cause inflammation. And in one person, that might cause arthritis and in another person that might cause worsening of heart disease. And in another person, that causes the pelvic pain. So, I think everybody’s inflammation shows up in different ways and in some people We’ll see it with pelvic pain. I always like to go back to the basics and look at their diet and look at what they’re eating and if they’re drinking enough fluids and if they’re getting enough sleep and decreasing stress in their lives. But then, I also love to test their microbiome of the gut. Because we know that certain overgrowths of bacteria will aggravate that inflammation and lead to leaky gut. And I’m finding that certain things that we do to try to rebalance the gut is showing our patients are getting improvement in their pelvic pain. One thing is like simple… I like to do the testing ’cause I think I’m still in that medical mindset. I wanna see the answers, I wanna see the labs. But I’ve had some patients who just don’t wanna pay for the labs because they can be pricey. Not all insurances cover them. So, some patients will be like, “Well, let’s just do something. And then, if that doesn’t work, then I’ll do the labs.” And so, sometimes, just adding a glutamine supplement into their diet will help calm the gut down and will help to heal that lining of the gut.
Matthew Cook, M.D.
100% I don’t know when this, maybe in 2012 or something. But you ever have a moment that you remember like it happened about four minutes ago?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
All the time.
Matthew Cook, M.D.
And then, to think about, I was in the hormone module at the Institute of Social Medicine, which is a great one. And they’re going through the biochemistry. And so, it was so complex and I was like, “God, this is amazing, I can’t even believe it.” And then, they popped up this picture and it was a picture of the pelvic floor bowl. And so, then they show the uterus and then they showed the colon right next to each other. And then, basically, it was blown up. And then, the diagram shows the inflammation and the leaky gut and how when there’s inflammation then inflammation in the colon then you show all of these inflammatory cytokines and mediators going over and basically attacking the uterus and causing inflammation in all of those pelvic floor structures. And I think that, that is a central and defining cause of inflammation in pelvic floor structures that can lead to pain, I think. And would you agree?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Oh, definitely, definitely. ‘Cause they all share similar nerves.
Matthew Cook, M.D.
Yeah.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Especially known for years with interstitial cystitis which is an inflammatory condition of the bladder that there’s this gut pelvic connection but they’ve never been able to actually say why. And so, they’ve always connected to food and they’re like, “Oh, well, acidic foods may be causing your problem,” where I’m finding it’s more leaky gut and in some people, histamine-releasing foods that may be causing the problem.
Matthew Cook, M.D.
Right, and so then… I was trying to delay this until later, but then, one thing that you will see is you’ll see a lot of people with complex illness in the mold and Lyme spectrum that end up with an inflamed immune system. And one of the side effects of an inflamed immune system is that the mast cells are a little overactivated. And so, then, patients that have a little bit of an overactivated mast cell we call that mast cell activation or mast cell activation syndrome can be real susceptible to histamine.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yes.
Matthew Cook, M.D.
Histamine and foods. And so then, I’ve had some people have go from being able to eat anything to almost able to eat nothing. And so, then there’s a lot of mass salt diets out there that… Let’s put up a link to maybe a couple… I’m gonna make a note of the list. But then, also, I think there’s a fairly big concordance and an overlap of people that have Lyme disease with pelvic floor pain. Have you seen that?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah, I definitely have seen that. And I think you’re saying that the mechanism is you have some first injury to the system and maybe that’s a tick bite and the body’s now upregulating all these other factors in becoming inflamed. And like you said, some people that’s why I think with Lymes you see so many different ranges of symptoms and anywhere from neurologic symptoms to arthritis to even the pelvic floor symptoms. So, I’ve definitely had patients with that.
Matthew Cook, M.D.
And what you said was really good because if you go back to my analogy of, okay here’s the colon and it’s super inflamed let’s say, because of what we call the worst diet in the world is the standard American diet.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah.
Matthew Cook, M.D.
Then, you’ve got the bladder in the front and the uterus in the middle. But then, what you said is they all share the same nerves. And so, basically, these nerves that are coming up basically from the sacrum and from the bottom. When three things share the same nerves if one thing gets inflamed then the nerves to all three end up getting inflamed. Have you seen that?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah. Oh, yeah. And that’s why I tend to see a lot of, especially in patients with vaginitis they’re more likely to get recurrent urinary tract infections or urinary symptoms. And then, also those people tend to come in with irritable bowel. Or for example, somebody with interstitial cystitis Somebody comes into me with like, all right, “I have pelvic pain or I’m urinating frequently,” and they start telling me things like, “Oh, and I also have irritable bowel and I also have arthritis and I also have TMJ.” And any one of these, it could be not all of ’em but they come and they… “And I also get migraines and I get headaches.” And I’m going, alright there are some underlying inflammatory issue and that the pelvis isn’t necessarily the problem. It’s just the symptom of a larger problem that’s going on.
Matthew Cook, M.D.
Right, and so then, this is why I was excited to talk to you, because I’m basically the same as you. And so, it’s funny, you talked about oh, what field should you go to? So, we went into totally different fields but then, we’re gonna see the same patients because I’m gonna see those people for headaches and nerve pain. But then, when I’m talking to them they tell me the exact same thing. And then, you see endometriosis at all?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah, yeah, I do too.
Matthew Cook, M.D.
Okay, okay. So, then, we’d have to talk about that. But let’s start since we were talking about interstitial cystitis. So, I wanna just run through a handful of these conditions. So, I have somebody with interstitial cystitis. Say just a little bit about what that is, and then, we’re gonna talk through how you think about it and how you like to treat it. And then, maybe, we can talk about things that you use could be peptides, could be something else and we run through it. So, we’ll start there.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah. It’s a mouthful to say, so a lot of people call it IC, for short. And in traditional medicine it’s really a diagnosis by exclusion. It’s because they don’t… Even though it was discovered in the late 1800s they still know nothing about it compared to what we knew in the 1800s. So, this is something that I’ve also developed over time. There’s theories that it may be genetic. Theories that it may be related to gut inflammation. There’s theories that it’s related to acidic foods but nobody really knows. And it can present itself as recurrent urinary tract infections or that feeling like you’re having a recurrent urinary tract infection like burning when you’re peeing urgency, frequency, or even other pelvic pain. And typically, what we see when we’re looking… Well, that’s the other thing is that you can look in someone’s bladder, but you can’t always see it because it can be a microscopic inflammation. And the theory is that the GAG layer which is the protective layer of the bladder somehow doesn’t repair itself. It gets damaged. Nobody exactly knows, but it’s almost like you get microscopic paper cuts in the bladder. And so, I say to people if I poured salt water on your finger and your finger was fine, you’d be like, “Oh, alright whatever, it’s salt water.” But if I poured salt water on your finger and you had a paper cut, that would hurt. And that’s what interstitial cystitis is like. So, sometimes we can go in there, we see ulcers and if you see an ulcer, that’s pathognomonic like that is interstitial cystitis. But a lot of times, the majority of people we don’t ever find a specific cause there’s nothing that we can test for it.
Matthew Cook, M.D.
Now, when you say, go in so then, one thing just so what gynecologist do which is amazing is you guys have little tiny cameras that are smaller than this pen.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah.
Matthew Cook, M.D.
Then they can stick a catheter very carefully into the bladder and then look around.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yep, just take a little peek.
Matthew Cook, M.D.
Just like a surgeon looks inside a shoulder
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah.
Matthew Cook, M.D.
And does arthroscopy. so you could take a look in there, which is an interesting thing to think about. And then, what would be, in your experience your top three things in terms of effectiveness in terms of treating people for IC?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah, so, I always start with diet even though that’s traditionally what you’re supposed to do but I think, a lot of times, it gets overlooked and people jump right to medicine. But I always look at diet and typically I always start people on a histamine, a low histamine diet because of the upregulation of the mast cells. Then, we know that if you take a biopsy of somebody with interstitial cystitis they will have more mast cells in their tissue. So, we know that those mast cells that release histamine are just going crazy. Though, is it low histamine diet always the answer for everybody? No, but then, like I said, I then go to gut and I look at the gut microbiome and I’m like, let me try to get the things I know under control, under control. So I’m like, okay, let me check their gut microbiome if their bacteria yeast is off. I’ve been surprised with the number of parasites I’ve found on people when I do that gut testing. ‘Cause when I was taught medical school parasites were things like, you went to another country and you drank some water and then you got parasites. I never thought I would find it on a regular basis here in people. And I remember even before I got into integrative medicine and my integrative medicine friends were telling me about parasites and I have a look at ’em like they were crazy. I’m like, that’s not real. That doesn’t happen. But I’m surprised at how much I find with that, and the imbalances of the bacteria and the yeast.
Matthew Cook, M.D.
It’s interesting both at A4M which is one of the good educational systems and institute of emotional medicine. And basically, everywhere you go whenever you meet the people that are into gut health they always say, “By the way, we’re the most important.” Like all of those other people that we’re more important than them ’cause you have to fix us if you wanna get better.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah.
Matthew Cook, M.D.
And then you think that, and you think for people like you and me, we do whatever we do and so we’re loving. Well, okay, that’s fine. But then in retrospect I still, every single day I learn something about the gut. Every single day, I have five to 10 conversations about GI things and I felt like I’m just steadily getting better every month. And yes, I see parasites all the time. Yes, it’s this incredible journey and I can’t believe how important the mast cell diet is for some people. So, I echo everything that you just said.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah, and I definitely think, to start with even if it’s not a mast cell diet it’s get them off the inflammatory foods with, you know. Hey, I was a sugar junkie forever. I loved my sweets. And then, finding out that sugar is more addictive than morphine, there were studies where they gave rats sugar and then they gave ’em morphine and then they gave ’em a choice and they went for the sugar every single time. When I found out about that, I was like, “You know what, I’m not letting sugar take over my life anymore.” Not that I don’t eat it, I have it every once in a while but I’m not like… I used to eat something sugary every single day. So, we really get those inflammatory foods outta the diet. And then, I think a lot of times combination, lifestyle of course, if we’re not sleeping enough then we’re not healing trying to get that decrease at sympathetic nervous system by decreasing stress and then doing things to boost the parasympathetic nervous system which lets you that rest, digest, reproduction, healing. And then, there’s a whole bunch of things. I actually will even, if we have to go the medicine route I often will start with mast cell blockers. So, things that are typically used for, when you think asthma. I was forced into finding those and using antihistamines and mast cell blockers because one of the medicines that’s been used for years to help heal the bladder called Elmiron which happens to be a peptide, which is interesting. It’s been on the market for years and it’s a peptide.
That, they all of a sudden, became really expensive. And especially in patients that are Medicare patients because it’ll cost ’em like $600 a month to get that prescription. And there’s not an alternative on the market. So I was like, alright, look at the mechanism and like alright let’s try putting you on montelukast singular and see if that helps. And so, that did seem to help some people. I like to try to do things as naturally as possible. And so, even getting involved in the peptides I’ve really been fascinated with the use of peptides for interstitial cystitis. And I love BPC-157. Because once again going back to the gut so what is it? Body protective complex that’s made naturally in gastric juices and it’s naturally in our intestines. And it’s one of the few peptides that you don’t have to inject. You can take orally. So, I started using that with patients and not only seeing improvement in their gut health but then seeing less anxiety and depression in them and less perceived pain. And so, that’s one of the ones I like . And then going back to Elmiron as a prescription peptide it’s very expensive but you can get it compounded ,from pharmacies into an injectable form, which I’ve used either having patients inject themselves into their thigh. It’s also used a lot in arthritis we’ve even actually put it into the bladder whether it’s just washing it into a bladder with a little straw catheter or actually going into the bladder and injecting it into the wall of the bladder itself.
Matthew Cook, M.D.
Okay, that’s amazing. That’s super good. I love the idea that BPC-157 orally for these patients because then if, and that goes along back to my… This is a good one because we think similarly on the one hand we’re having this mechanistic conversation which is, is that if we turn inflammation off in the gut then that’s gonna affect leaky gut and that’s gonna affect everywhere where leaky gut is affected. On the other hand, also doing something in the gut. If we decrease leaky gut in that area of the colon right by the bladder, maybe that’s gonna actually take away the trigger that’s causing some of that inflammation. Just for the future, there’s this whole category of peptides that are bioregulator peptides. And so, then there’s one for almost every organ and there’s one for the bladder called . And so, have you ever tried that?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
No, that’s when I haven’t tried, that’s–
Matthew Cook, M.D.
So then this is gonna be part of a… We’re gonna engage with each other and I’m gonna send you some patients and then we’re gonna start talking because of that, I’ll be curious over time to see if that one has any benefit. On the peptide front it’s interesting BPC-157 generally is super amazing. Very rarely, I’ll see some mast cell activation from it but I never see the mast cell activation orally. And then, KPV is a real good peptide for mass activation. And there’s some formulations that will combine KPV and BPC which are really good. And when you think about overall inflammation in the body have you ever done much with stem cells or regenerative medicine?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
I was, until the FDA got crazy about it. And then, I got a little nervous .
Matthew Cook, M.D.
That was good. But, we have some clinics outside of the country that we send people to. And so, I’ve treated people with interstitial cystitis with culture extended expanded stem cells where you give 100 million or 200 million stem cells. And we’ve seen benefits with that. People who were doing even adipose stem cell cases. And I’ve reviewed a lot of cases of adipose stem cell cases for which is the one that they took away. That was one that I had trained a lot in, and spent a lot of time with my mentor, Bob Alexander doing. And that was helpful, kinda before that went a little bit by the wayside for a while. Although some of my international colleagues are still doing it quite a bit. And those are all things that also regulate immune function, regulate inflammation. And then while bigger things, stem cells and exosomes smaller things, KPV I’ve noticed all of those are quite helpful for regulating mast cell activation which then is central to things like Lyme and complex illness but it’s also central to potentially things I see. So you see how deeply complex its conversation is, it’s just like it’s staggering. And you can see if you had a hundred dollars visit that you had 15 minutes for, and then you had somebody that has something of that complexity and there’s not a drug that’s covered by insurance that solves the problem. And we know there’s not a drug that’s covered by insurance that solves this problem. Then those patients are fundamentally way late.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah, oh no, definitely. And it is such a shame with the stem cells and the exosomes because they have such amazing healing properties. We’ve done things where we’ve actually injected it into the walls of the bladder or I’ve had patients who had non-healing ulcers for years in their bladder and injected into those and that got them to heal.
Matthew Cook, M.D.
With them both?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah, yeah.
Matthew Cook, M.D.
So then that just goes to show you this is like a missionary appeal to a regulatory and oversight agencies. Like you’re listening to gynecologist that has… And we see the same type of things. And so then this is just a forecasting the future of medicine. So then what you would do is you would stick a catheter in and then look at that ulcer. And then, you would basically inject basically stem cells into the wall of the bladder where that inflammation was, is that right?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah, yeah. And then we get it to heal. And then, I even used stem cells for incontinence. So when I trained, I trained unfortunately during the time that vaginal mesh was a big thing and that’s when it first came out. That’s when I started my training. So, we were putting in vaginal mesh left and right and left and right. And as the years went on, I was like, I need other options. And so I was using, at that time we were using stem cells that we were injecting under the urethra for stress incontinence. And patients were getting improvement in their incontinence without having to have a piece of mesh put in there. We’re doing other surgery. They used to make, they don’t make it anymore. They were these sheets of tissue that were either liver derived or there was ones that were amniotic sac derived. And so, they had stem cells in them and we’d almost use ’em as a graft to place them under the bladder to help lift and repair the bladder. And they would heal so nicely. But they got taken off the market.
Matthew Cook, M.D.
Yeah, I thank you for saying that. So, if you said what would be the worst thing to do to somebody in the world that I know of? It’s like my MRI had a list of 50 things. One of ’em would be those vaginal mesh operations. Tell me about, why that’s not a great option.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah, you know what? it’s funny because that’s a whole can of worms. Mesh itself isn’t necessarily bad because we’ve been using mesh since 1980s for hernias. But the problem is, when you’re dealing with the vagina is that the vagina’s not a sterile place. It has its own microbiome. So, starting at about 10 years ago I started looking into issues with the mesh and I’m like, okay, wait a minute. Let’s start testing the microbiome doing a swab of the vaginal microbiome. And I would not implant a mesh until I balanced that microbiome. And then those patients had less issues. So, then from that standpoint ’cause you would get what’s called erosions or extrusions. So this mesh would get basically infected with bacteria. And now, that’d be sitting under the tissue and smoldering and causing all these other inflammation. They’re seeing the same thing. I have a really good friend who is one of the number one breast implant explanters in the world and this idea of this breast implant illness and he’s finding that it’s not necessarily that the implant it’s that when he’s going in there now doing this advanced microbiome test on these implant beds after he takes it out he swabs there and he is finding all these crazy bacteria. And so it’s that bacteria that’s getting introduced into the body and really kinda just sitting there, and causing this long term inflammation that, that’s maybe causing what they’re terming as breast implant illness, and not everybody gets it because not everybody has these bacteria.
Matthew Cook, M.D.
Right.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
The other thing with mesh was the problem and I will tell you straight out. I was a trainer for some of the companies to implant these things. And it was very frustrating to see that they would basically bring in doctors, sell it to them and be like, “Oh, this is easy. Anybody can do it.” Send them to a weekend course and learn how to do it on a cadaver once. And if you were lucky, you got your hands on the cadaver. Sometimes it would be 20 doctors around a cadaver and you couldn’t even get there. And then they would go in, send you off into the world and be like, “Okay, go and plant these things.” So, the other problem with the vaginal mesh really was, there was a lot of people implanting them that really didn’t have the knowledge and the skill in pelvic reconstructive surgery. And if you don’t put it in the right place now you’re gonna affect the pudendal nerve. And this is where I see a lot of pelvic pain issues. And so, the other thing I forgot to bring up with pelvic pain is this theory of it may be a chronic regional pain syndrome. So, with chronic regional pain syndrome we see issues where someone’s spinal cord or something upstream of where they’re sensing the injury or sensing the pain, something upstream is injured. And now, all those nerves going downstream become inflamed and you get that mast cell release and all that. So, that’s actually another theory behind interstitial cystitis, it may almost be a chronic regional pain syndrome of the bladder if there’s something else higher or even like I see with pelvic pain. ‘Cause I see a lot of pelvic pain where it’s not in the pelvis. It could be a problem with a hernia disc in their back or I find a lot of hip disorders.
Matthew Cook, M.D.
Mm hm.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
So, they’ve injured their hip. I’ve seen a lot of women who’ve injured their hips pushing when they’re having a baby because I don’t think we were naturally meant to be giving birth laying on our backs with our knees to our ears. That’s a position because it makes it easy for us doctors to control and catch the baby. But a really naturally, we’re probably meant to be standing up and using gravity to help bring the baby out. And so, I’ve seen where people have torn their labrums so that material around their hips and they don’t have hip pain but they have pelvic pain and they have vulvodynia, which vulvodynia is a fancy word for pain in the vagina or vulva. So and once again, those vulvodynia, these chronic vaginitis that are not infectiously caused interstitial cystitis it tend not to be their own condition themselves they’re as symptoms of something else that’s going on.
Matthew Cook, M.D.
Yeah. So, then that’s a lot that you just said and I agree to that 100% of that. We take care of a lot of complex regional pain syndrome and so I’ll just give you a little thing on this that I think is a interesting one. Imagine if you were just living your life and the typical thing is this in a hand or an ankle and an extremity, and then somebody was gotten in an accident and maybe what they did in their life and the one thing that brought them emotional peace was running for example, and then they got in this accident and now they can’t run. So then there’s a big psychological overlap of you take away your greatest thing. And then now that you’re in pain, and then what happens is that those feed back and forth on each other and then that turns you into an inflammatory neuropathic situation where you get stuck in fight or flight and you get decreased blood flow to that area. And so then what happens is all of a sudden you start to get skin changes and pain and decreased blood flow and decreased oxygen and all of those things happening in there and then, it just gets progressively worse. And there’s a reason I’m leaning into this because then so then, that goes on and on and on. And so, then next thing you know we as anesthesiologist would do nerve blocks to reset, fight or flight, but they were never very effective. I remember at my surgery center one of the women that worked at the front desk said, “Dr. Cook, this person’s been here 37 times those don’t work do they?” And I was, “Well, they kind of work.” And then interestingly, it was what drove me into doing what I do.
And then the regenerative medicine works quite a bit better for those problems all those are very difficult problems. So, then that’s part one of my response. Part two is, I suffered with the same thing that you talked about because what would happen is for the most part, I had the best surgeons that worked at my surgery center but then I would get people that came in and just took that course. And then, I were about the same age and so then I had all of those people that just took that course and were operating all of those women who were putting those meshes in. And the real thing on complex regional pain syndrome is, you think you’re just having a simple thing you think you’re just gonna have a little mesh put in it’s gonna be no big deal and then, you’re gonna go back and have an amazing life. Now, and I remember as we were going on this guy says to me, Doctor Vase des he goes, “Dr. Cook, do you know that 1% of those meshes get infected every year, for the rest of your life? There’s a 1% chance every year that’s gonna get infected.” That’s with a hernia. So, if your microbiome is not balanced or something goes sideways on you the pelvic is gonna be much more likely. So, then you imagine all of a sudden inflammation, decreased blood flow, all of those things that I was just talking about in the ankle imagine if that happens in your pelvis. That’s pelvic pain. But there’s a lot more of emotional connection to the pelvis than there is to the ankle.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah, yeah.
Matthew Cook, M.D.
Interesting, huh?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
And then when, once you have pelvic pain so then you talk about like how does that affect your sex life? And then that becomes a big circular thing. Because if you have pain every time you have sex you’re not gonna wanna have sex which could then or actually when it comes to muscle spasms in the pelvic floor so, you have sex, it’s painful. So, your muscle spasm because they’re trying to protect you so, they’re trying to splint against something. And now, what ends up happening is those muscle spasms now become the trigger of the pain because now you’re getting decreased blood flow into those spasm and the muscles, and that itself now causes pain. And then that triggers your muscles to spasm more. And then it affects your sex drive and it just becomes this whole horrible circle of pain. It’s miserable, unfortunately and it’s sometimes very difficult to break. And that’s why, so the medical term vaginismus which is a spasmed pelvic vaginal the muscles around the vagina that, once again I don’t believe when I find a spasm pelvic floor I don’t believe that the muscles themselves are the problem. I think, there’s something else triggering and the muscles are just trying to splint to protect you but in that protection they’re then becoming pathologic.
Matthew Cook, M.D.
If somebody came to you with those symptoms what have you found that’s helpful? I’ll say my thoughts too.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah, well, having worked years and years and years in insurance there was the pathway I used to take And now, that I no longer work in insurance system but the pathway of insurance was like pelvic physical therapy, heat stretch massage anything you would do if your leg was spasmed. But for the people that are just really severely severely spasmed, Botox worked really well. And then, actually the truth is, though Botox can be covered by insurance I actually like Xeomin better because I talk about Botox and Xeomin. So, Botox is an older molecule and it has complexing proteins on it. And they found that some people are developing antibodies against that complexing protein which has no clinical significance other than the fact it’s there. So, this is why, especially women or people who get it cosmetically if they’re getting it repetitively all of a sudden they’re like, “Oh, the Botox doesn’t work anymore.” Well, that’s ’cause you have antibodies against it where so a normal molecule which is found in the brand named Xeomin doesn’t have that complex in protein. It tends to work better And with repetitive use, it seems just to keep working.
Matthew Cook, M.D.
Are you familiar with the idea of what some people call the O-Shot that Doctor Runels came up with–
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah, PRP.
Matthew Cook, M.D.
You wanna define what that is?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah, so using platelet-rich plasma injections are also great. They’re they’re wonderful. So, you take your blood and you spin out the red blood cells and you’re left with this nice golden colored fluid which has a lot of growth factors and healing factors in it. And it’s used in orthopedics all the time. They’re injecting it to joints and knees and all sorts of things to help with pain but it can also be a great modality for helping with not only healing but also with helping pain in the pelvic area. So, whether that’s your near nerve or whether you’re doing it in into the muscle.
Matthew Cook, M.D.
It’s interesting. So then if you think about trying to reset nerves and we go back to this my initial picture of the pelvic bowl. So, then one thing that we do a lot in this population is we’ll do what’s called the caudal epidural which is the same thing that I used to do. They wouldn’t let me do gynecology but I did do a lot of obstetric anesthesiology. So, I still got to be around the babies, which I like. But so then we’ll do an epidural kinda down by the tailbone. And then, that will get all of those pelvic nerves and with something anti-inflammatory and regenerative that’s kind of with growth factors to calm down the nerves. We will have people lie on their sides and do an ultrasound guided injection by the pudendal nerves. And will come basically deep the proximal gracilis muscle right at the pelvic floor. And then, when we do nerve hydrodissection around nerves in the groin then what we inject is actually gonna work its way up into the pelvis, through the pelvic lymph nodes. And so, then that can affect those things. And then interestingly I think peptides are gonna be part of that conversation and BPC-157 you can inject it subcutaneously in your belly or you can do it in your, I always say the gluteal somebody told me yesterday, into your booty but we’ll use BPC-157 for nerve headed assertion of the pelvic nerves. And that’s been profoundly helpful for some people. And so, then suddenly, you hear all of the interesting things you do and you suddenly begin to realize oh, there are a lot of options for people.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah, and you brought up also that idea of hydrodissection. I’ve seen too where we’ve tried things we’ve tried steroid injections, we’ve tried this. And sometimes there’s the idea of maybe they have a little scar tissue in the area and sometimes will go in where they’re having nerve pain and flood it with just something as simple as saline.
Matthew Cook, M.D.
Yeah.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
You put a whole bunch of saline because that’s basically gonna separate all that tissue without having to go in there and do surgery ’cause especially for pudendal nerve issues I’ve seen where people have had pudendal nerve releases where they go with surgically and basically filet their buttocks.
Matthew Cook, M.D.
Yeah.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
And , that’s like a last resort but even then, I could probably count on one finger at the time I’ve seen that be successful.
Matthew Cook, M.D.
Oh yeah. I’ve seen or talked to more than a hundred people that have had that surgery. I’ve never had anyone got remotely any benefit. And if you said, I’ve never even heard of anybody that had any benefit of a surgical approach to nerve compression. Whereas what we’re doing is we’re taking a needle and then putting in between two muscles and then using the fluid. And you were mentioning that you use dextro sometimes.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah.
Matthew Cook, M.D.
Saline sometimes. People use everything from peptides to growth factors anything, lots of different solutions. And so, I’m really glad that you mentioned that. And then, just kin of back for completeness the interesting idea is this, that if you imagine the… If we were doing a pelvic exam and then in between the urethra and the vagina you can actually go in and there’s a tissue plane there and so, you can do a hydrodissection of that tissue plane which fundamentally is the tissue plane between the vagina and the bladder. And so, then I’ve been doing PRP and growth factor treatments there for a long time and was a teacher for Doctor Runels we really like him. He’s been a very influential person in the field. I have done tons and tons of ultrasound guided peptide injections for men, for sexual health and I think, and I’m just gonna throw this out to you I think, that there’s gonna be a big future in BPC and potentially other peptides to be used in that tissue plane kind of like quote unquote what they call an O-Shot and I think that could be an area that you could help a lot of people with.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
I love that idea. Yeah, I haven’t tried the BPC specifically in that area but now that you’re saying it, I’m like, ooh, that would work.
Matthew Cook, M.D.
The reason is because, if you have elbow pain and you take BPC-157 subcutaneously generally it’ll be helpful if you inject it in your booty. However, if you pinch some subcutaneous tissue and you can get it right there right where the area is, it works 10 times better. And so, then, I’ve had a great experience 100% of the time with doing peptides and in a particular BPC all over, very close to the pelvis. And so, then that’s an intriguing a very intriguing and interesting idea.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
I wanna ask you because I’m pretty confident in using peptides in most people but only population of people that I have reservation. And because I can’t find any information that supports it or not is, in the cancer population. So, I’m not sure what to do with those patients.
Matthew Cook, M.D.
So, then that’s a million dollar question and it’s my most difficult answer and I don’t have an easy answer for it but then here’s how I think about it. Okay, there are a handful of peptides that will promote angiogenesis that means that they will promote blood flow and to some extent blood vascular health. That’s obviously a great thing and that’s something that we’re always trying to push but at the same time we’re not trying to push it too much because if there was a cancer, cancer could utilize hypothetically that angiogenesis. On the other hand, there are certain peptides and the thymosin alpha 1 has been controversial just because I think, it’s helpful for COVID and so, people don’t want the people to talk about it. But then the theory on that one is that, it’s not a 10 outta 10 anti-cancer but it has some mildly anti-cancer benefits. It turns out a vast majority of pain, is immune pain. Okay, is immune related or has an immune component to it. And vast majority of even nerve pain that is inflammatory will have an immune component to it. So, then my friend, John Fransua who’s a great and heroically interesting person called me and he goes, “Thymosin alpha 1 is good for nerves.” And whenever he tells me something like that, it’s probably almost for sure true. And that’s just because he talks to people he’s on the street 24 hours a day talking to people. So, if he tells me that, it’s almost always true. So, then I started doing some nerve hydrodissection where I would put thymosin alpha 1 in people who had cancer and nerve pain and I was trying to do something and so then the way that I mitigated it in my mind is, okay well, I’m gonna avoid these thymosin beta-4 and BPC, the ones that promote a lot of angiogenesis because those are probably the two best for just straight up nerve pain and there’s even some patents out for thymosin beta-4 for neuropathy.
However, so then I say, well, I know that there’re certain things that I could use and so, if somebody had pelvic cancer would I be okay with putting thymus and they had a lot of pelvic pain? Would I be okay with thymosin alpha one either in the pudendal nerve or in between the vagina and the bladder? Yes. And, so then, from there you began to find some things that you would feel safe about and this is just my intellectual logic. Now, then step two is to say is angiogenesis that big of a problem? And then, what’s the state of the cancer? Is the cancer in remission, and it’s gone and it’s five years out? In which case I would probably just say no problem is fine to do. Are you in that, in between area? And so then it’s kinda like a board exam I think, the answer depends. And then we have to develop a better clinical understanding of cancer integrative things that can be done What’s our model of it? How do we think about it? And in general, I would say that’s the most controversial difficult overwhelming topic of the day compared to everything else that we do. And so, it’s not a perfect answer but what I do is, I work around the corners and try to find things that I feel are safe.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah, this is what I love because I think, unfortunately we’ve gotten away from the art of medicine. And I think, that medicine still is so much an art. That’s why we always say the practice of medicine because I think, the more you do medicine the better and better you get at it and the more that you can critically think about it. And sometimes I get really nervous about them pushing toward evidence based medicine. So, it’s nice to have evidence but I don’t like what I’m seeing it do to people. And this is not everybody you still have critical thinkers out there, but I also see a lot of people that are like robots. And they’re like, “Oh, it’s the evidence says to do this.” Well, you know what? We know that people’s bodies don’t follow textbooks.
Matthew Cook, M.D.
Evidence based medicine actually works amazingly well for simple problems.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah.
Matthew Cook, M.D.
And it works very well for problems that have one or two components but then it works horribly for things that have 10 components. Now, then speaking of things that have 10 components we’re later in the podcast but you mentioned that you take care of endometriosis. And so, then to me that’s my hardest condition or one of the harder ones but I’ve got a couple little things in the background that are interesting to tell you. What’s been your experience with that? And what helps? And how’s that done?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
I will tell you too, they are probably the most complicated also. And complicated too, in that we still don’t know 100% the mechanism of why this happens in people. And I have to say I’ve seen the rates of this go up over the years. And at first I thought, well maybe just cause I’m seeing those patients and then I’m like, “No, I’ve seen the rates are going up.” One of my theories behind why I think the rates are going up is I think we’re being exposed to a lot of more endocrine disruptors in our environment whether that’s from plastic bottles or household cleaners with toxins. And so, we know that those endocrine disruptors trick the body into thinking that estrogen and they a bind to your estrogen receptors and I think, I saw something like 80 times that of your natural estrogen. So, we see a lot of the women that have endometriosis and even polycystic ovarian syndrome I’ve seen that also increase over the years that they tend to be in this paper estrogen state. And now, the interesting about estrogen is, estrogen is a neurotransmitter, and people don’t always think about it as a neurotransmitter. And we’ve seen that the higher your estrogen is, the more likely you are to sense pain. So, we know that high estrogen level and pain perception is higher because of estrogen’s effect on nerve transmission.
Matthew Cook, M.D.
But now tell me, back up, that was really good. How would you define endometriosis? And then how would you define polycystic ovarian?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah, so, endometriosis is… So every month when a woman is menstruating they build up this nice tissue and blood vessels and the uterus to create a nest if a pregnancy was to take place. And so, when a pregnancy doesn’t take place the body’s like, “Eh, I don’t need that.” It sloughs off, and that’s the period. It’s the blood, it’s the old tissue, it’s gone. Well, in people with endometriosis that tissue instead of getting out of the body and sloughing off, somehow gets back into the body. There’s a couple mechanisms that have been theorized of why that happens. Sometimes they think maybe the pressure of the cervix is too tight, and now, instead of coming out where’s pressure gonna go? What if there’s too much pressure or the least amount of pressure go back out the fallopian tubes into the abdomen. And now, that tissue has no place to go and it attaches itself to different organs and it responds every month, like it would period, it would build up in response to estrogen and it would bleed off causing pain. And then we’ve also seen where it’s actually has gotten into places that people are like, “How do you get endometriosis in your lungs?” They’ve found it in strange places on people.
And the thoughts are that maybe somehow it can metastasize meaning somehow that tissue instead of getting out gets maybe into a lymphatic system or into a blood vessel and now ends up some other strange place in the body and is growing and responding to hormones every month. So, that’s what the endometriosis is, where polycystic ovarian syndrome is a syndrome in where women tend to make, you know they develop an egg every month and the egg is in a little cyst and the cyst ruptures and that’s ovulation. Well in polycystic ovarian syndrome these women tend to get a lot of follicles that are developed and they get a lot of cysts in their ovaries but it’s really a derangement of estrogen and a hormone called DHEA. They tend to have very high levels of both of those issues but they also have a lot of metabolic problems where they have issues with the hormone metabolism they also tend almost be prediabetic or even diabetic and tend to have a very high cortisol level. So, there’s all this big derangement in the hormones associated with that condition.
Matthew Cook, M.D.
And so then, how do you like to treat those?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
So wow. Alright. So, I’m try think which one to pick first. So, a lot of times I’m doing hormone testing on those… I love the DUTCH tests. I love the dried urine tests even though I was trained that… Well, I wasn’t trained in traditional medicine. Traditional medicines like, “Hey, look at your hormones on blood,” but we know blood is only like a snapshot of what your hormones are at that moment that they take the blood. It’s not really an indicator of what your tissue is doing. So, saliva is technically more accurate but I don’t get them metabolites. I can’t see how your body’s metabolizing hormones. So, that’s why I love the dried urine where it looks at hormone levels and it looks at how you’re metabolizing it it looks at your adrenal gland hormones we can look at your stress hormones and cortisol so, it looks at a whole bunch of things. So, I usually start off with, let’s look at where the hormones are and how are they doing? Once again, I always go back to the gut I’m always looking at gut. I think, pretty much everybody that walks through my door I’m looking at their gut health to look for things that may be more inflammatory if they’re having some sort of inflammatory issue.
And then the endometriosis is so so tough. I no longer do surgery on those cases I send them elsewhere because even though the literature’s showing that, even though you do surgery on it it’s really not ideal because you can have some… The surgery doesn’t really help and you can end up having more problems ’cause of the surgery. Surgery is definitely indicated if you have scarring of the fallopian tubes and you’re trying to get pregnant that may be or even infertility treatments to help you get pregnant ’cause they can get scarring. The polycystic ovarian. I’m just thinking a lot of hormone balancing and then having to treat they tend to have hair issues. So, then it’s like, okay, what are we using to… We’re using a lot of topicals if they’re having problems with, they’re getting balding ’cause sometimes these women end up getting… Their testosterone gets so high that they start to bald as opposed to get a hairy body.
Matthew Cook, M.D.
Well, a good friend of mine who has the same last name as me, his name’s Andrew Cook he’s one of the top two people in the world for doing the endometriosis surgery. And just randomly that was something that I did in my anesthesia career. So, another one of these things was like back in the day but like of brutal surgeries that exist in mankind. That’s like in the top 10 because they do it through a scope now. But basically if you imagine my conversation of the, here we go back to this ball of the pelvic floor. And so, then the front you’ve got the bladder and in the middle, you’ve got the uterus. So, imagine what you just said, something happened and some endometrial tissue went up the uterus and somehow got out into the pelvic floor. Every time estrogen comes along then that grows almost like a tumor that’s in inside of the abdomen and then, it goes back down when after the period happens but so then every month it’s almost like there’s multiple tumors going on and we would look in there and then you would see basically black all over the pelvic floor that looks like blood. He said the only thing that correlates with a negative surgical outcome 100% of the time is Lyme disease.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Oh.
Matthew Cook, M.D.
And so, then this was a very interesting data point for me and so, it’s an important thing because guess what? We’ve been talking about infections that’s causing immune problems in the gut potentially that causes an immune problem in the uterus. And so, but these fields talk so little that, normally gynecologists are probably not talking to people in integrative health for the most part one of my best friends we helped, had Lyme disease we did Ozone Dialysis and all of these things and basically got it into remission and then the endometriosis calmed down and then she had a surgery and then ended up being pregnant and so, the baby’s like a year old now. So, I have some big wins on the surgery side. We have people who’ve gone to Mexico and done the culture-expanded stem cells. And so, then reporting back that endometriosis and mast cell symptoms are going down. And so then, I think that we hesitate to even talk about endometriosis ’cause it’s so difficult and yet I love somebody like you that’s kind of out on the front lines with that, because I think that the regenerative medicine conversation, that that’s one there’s a bunch of conversations that like, it doesn’t really matter. You could do just like 19 things and they all work but then some of these big problems they need a total solution they need the lifestyle package that one takes all hands on deck.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah, definitely. And definitely more than one specialist because there’s just so much that goes into that. So, what you were saying.
Matthew Cook, M.D.
Take me maybe in conclusion take me through to another direction. Tell me about your experience of helping people with sexual health and how’s that been?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
That’s really interesting because I can’t tell you ever since Viagra came out, women are like, “Where’s our pill? Where’s our pill?” And this is something I’ve been arguing with them I was like, “Listen, Viagra doesn’t put you in the mood. All it does is affect blood flow.” And I can’t tell you how many times I went to Pfizer and said, “You guys are studying the wrong thing.” ‘Cause they did try to study Viagra for women as to help with sexual libido. And I’m like, “You can’t study libido with that pill.” I’m like, “You could do a great study to look at blood flow and improvement in fitting of the vagina and improved lubrication.” Because I actually have used Viagra. I’ve used Cialis. I’ve used all those medications in pelvic pain patients. Especially pelvic pain patients who have spasmed pelvic floor muscles because you were once again talking about the pelvic floor muscles and when they spasm so much it cuts off the blood flow and their tissue on top of it gets really this pale look to it and they have pain with intercourse and so I’ve been like, “Well, let’s try if we can increase the blood flow to your pelvic floor maybe we can get some those muscles to relax and make sex more comfortable.” So, I’ve had women very successfully use those medications for intercourse and with the side effect it’ll increase blood flow to the clitoris it’ll increase blood flow to the labia so, they have increased sensitivity they increase lubrication, less pain. Now, the problem is, those pills are expensive and insurance definitely will not cover it for a woman. So, then I was forced to start finding alternatives. So, then I started using a lot of L-arginine. So, L-arginine works in a very similar manner. It it a little bit different, but it helps with blood flow and nitric oxide production in that tissue. So, that can also help especially and also with patients topically, they can use it. I will have them use a cream with a little maybe magnesium in there.
Matthew Cook, M.D.
To put on the clitoris or vagina or both?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah. And then, so then the other thing goes, okay so then everybody was like, “Well then I want the pill that’s gonna put me in the mood.” And I’m like, “Well, that gets a lot more difficult because of the way sex drive is, not everybody has the same thing that puts them in the mood.” This is why I always tell people your brain is your important sex organ. If you don’t stimulate the brain nothing else down below is gonna work. And there’s actually some really interesting research from Rosemary Basson I’ve been trying to interview her forever. She’s hard to get a hold of, but she took the traditional Masters and Johnson’s graph that we always see you get arousal, desire and then arousal and then plateau and then orgasm and resolution which was amazing work when Masters and Johnson’s came out with it. But it doesn’t really, especially for women doesn’t really explain the experience of women. And so, Rosemary Basson took that model and she turned it into all these interconnecting circles which the biggest thing for… Not every case, but the biggest thing and especially I’m gonna generalize this to women is that you’d have to have the willingness before the desire and the arousal.
So, a lot of people are still stuck in this idea of, I want it to be like I was 18 where you just look at me and I’m like, we’re rolling around in the waves which I never understood the beach and the wave thing because I’m like, “Where’s that sand getting into?” But you still can have spontaneous desire but Rosemary Basson’s work has shown that for majority women if they just go through the steps with a willing partner that’s gonna be like, “Okay, we can stop.” You’re not like a race where we gotta get to the end but that if they just go through the steps then all of a sudden, then the arousal comes first and then the desire to have sex and then, they have a good sexual experience. And so, usually when I start with patients I start with that idea and I’m like, “Okay, let’s start with that first and see if that makes a difference.” And I have a lot of women that come back and they’re like, “Wow, you’re right.” Sometimes you ask them, “When who have sex is it enjoyable?” And they’re like, “Yeah, once I get into it.” Well that’s ’cause that’s the Rosemary Basson model. So, but then we have some fun peptides for this. So, with the medications that are on the market before peptides, well peptides been around but before that, we had what they call the pink pill which I’m blanking out on the name right now but it’s made by a company called sprout and it was a pill that, couple different companies had it. And it was supposed to be a pill that was gonna put women in the mood but it got rejected a number of times by the FDA and… Addyi that’s it called It’s Addyi.
Matthew Cook, M.D.
Addyi, yea
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
A-D-D-I-Y-I or something like that yeah, Addyi. So, it got rejected a number of times from the FDA. And then, what ended up happening was this small startup company, sprout took it over and they really keyed into social media and women’s movement and they basically strong armed the FDA into passing it by saying that the FDA was being sexist for not passing it but in reality it’s not the greatest drug in the world. So, it’s something you have to take every single day. You can’t drink alcohol on it because there’s a risk of passing out. And it really didn’t increase the number of satisfying sexual experiences that much over placebo anyway in the study which is, sex is a very hard thing to study anyway. But in some people who take it and they love it and it works great. But I also say placebo if you believe in anything and it’s gonna work. So, you wonder how much of the placebo effect but then we talk about peptide. So, there’s actually a prescription peptide on the market for women which is called, Vyleesi is the brand name but it’s bremelanotide, which I always have fun saying.
So, bremelanotide is a peptide that, before it was used in research and it was used clinically from compounded but now it’s a actual prescription but it affects the melanocortin-4 receptor which is an interesting receptor because I’m like this receptor is responsible for skin coloration, sexual desire and food satiation so if you feel full or like… So people that have defects in that receptor we know sometimes it’s associated with overeating disorders so, it’s weird to me that’s I still haven’t figured out why all of those three things are on that receptor? Like why is that? Why are they connected? But I think that peptide has been really interesting you can take it basically prior to sex and either the prescription form it’s an injectable that has to be done 30 to 45 minutes before a sexual activity. And that can actually help basically put people in the mood. It has been used for years before that as a nasal spray.
Matthew Cook, M.D.
What dose do you like as an injectable?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
You know what? A lot of times I try to put it I’ve been putting it through insurance to try to get people covered and it comes as one… That’s a good question ’cause by least it just comes as one dose.
Matthew Cook, M.D.
We usually use one milligram.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Okay, ’cause I’ve seen anywhere from the nasal sprays in the compounded anywhere from one to two.
Matthew Cook, M.D.
So then, that acts on the hypothalamus and so that’s very upstream. So, you begin to see why it could affect the gut and the skin and all of these things. What do people tell you when you give them that? If they take, let’s say they take that, as an injectable or as an nasal both from an arousal perspective and then from within intercourse what do people tell you they experience with that?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
People are really loving it though the only downside is, like in the literature it has up to a 40% chance of nausea so, it’s really not good if you’re gonna be like, “Okay, I wanna be in the mood, but I’m nauseous.” Though at the same time, I don’t think I have personally my own experience with patients I don’t think I’ve seen as high as 40% with the nausea but that can happen. That really kind of puts a damper on being in the mood. But I think, patients have really said that they are really enjoying it and that it’s boosted their sex lives though. Though I’m finding that in general patients are using it but they’re not necessarily depending on it all the time it’s almost like they’re using it for a while and almost like getting over this hump of that mental stress of like, “Oh,” putting themselves on pressure a lot of pressure to have sex. And then, they use this medicine for a while and then they start letting go of some of their inhibitions and kind of start getting to the point where they’re like, “Oh, I don’t need the medicine anymore. I’ve developed this better relationship with my partner and now I’m able to do things without having to use the medications.”
Matthew Cook, M.D.
Yeah, so then can I tell you when just, this one is so interesting and it has taken me a while to wrap my head around this. So, then we were talking in the pre-show sort of about VIP which is another peptide that regulates the brain.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah.
Matthew Cook, M.D.
And so, it’s another one that’s kind of, and I actually think, and we’re gonna do this next time I talk to you ’cause I can’t wait to talk to you in about a week but we’re gonna talk about mold and pelvic stuff because I think there’s gonna be a big overlap there. But what happens is this, imagine if you take people with complex illness and mold you detox ’em for a while and you do these things and then eventually if you get them where their visual contrast test is negative and their inflammation in their brain’s down they take this peptide called VIP and then they take it and they’re fine. And then it regulates basically inflamed genes calms ’em down, and then people start to feel a lot better. That’s like the cliff notes of how to fix mold. So then now, imagine if you give VIP which has a brain bio regulator, too early it can cause flushing and headaches and a variety of problems and so then in the mold world, there was this conversation of you gotta this whole long journey of getting people better and so then they can start doing so. Now this is a long ended story but this is gonna be totally worth it for you. So then now, imagine what we’ve discovered is that there’s a bunch of all of the bio regulators you can do before VIP and then BPC-157 and the immune peptides kind of calm things down. So, we have this peptide oriented approach towards mold that helps people get better. You get them through all of that stuff and then you give them VIP and they’re fine. But then that gives you this indication that there are some people that if you give the peptide too early to, they’ll have trouble it turns out that population of people who… And PT-141 is related a little bit to melanotan which also causes nausea.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Oh, yeah.
Matthew Cook, M.D.
But then it turns out that, like VIP and I think this is because it has an effect on the hypothalamus, PT-141, which is bremelanotide tongue twister, in the sick population they’ll get sometimes bad headaches along with the nausea and it behaves a little bit like VIP.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Ooh, okay.
Matthew Cook, M.D.
So then, and it’s important to say it, because you’re my sexual health guru and I have seen that, and then when it happened people are like, “What happened?” And especially it is kinda like, if you thought you were gonna do something for sex and it was gonna be super fun and then all that happens that’s crazy. But then, what happens is, what I have found is, if you regulate the brain and you get everything dialed back down then they can take it. And then, I have seen, but then I’m gonna ask you this, so, for guys if they take it, and if you take it before dinner, a lot of times like almost during dinner, you’ll have a 1/3 of erection. It’s just kind of more blood flow which I think, it just surprises you instead of, just kind of puts you into an arousal space. And I don’t know if you’ve seen that in women. I think, my sense is kind of similar to that. And then, I 100% totally agree with you that a lot of times just getting into that space and finding, oh, okay, Oh, okay. I can get back into that space suddenly that teaches your brain how to do it and you don’t have to take it all the time but it could be like a crutch that’s helpful in the beginning.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Yeah, yeah definitely. You also brought up, we were talking about inflammation and there’s also connection between inflammation and sex drive. And they’re actually finding that, and this is another thing I do in my office all the time is I will do vaginal microbiome testing because one of some of the theories is now is that, if the vaginal microbiome is off that’s gonna create this inflammatory state in the vagina that the body’s gonna sense and they’re thinking it’s through the vagus nerve but they haven’t been able to prove it yet. That there’s gonna be this feedback glued to the brain saying like, oh, this is not an ideal time to reproduce ’cause your brain doesn’t know the difference that’s between you wanna reproduce and you wanna have fun. So, it’s going to then dampen those hormones and peptide productions that would be associated with reproduction, hormone health and even sex drive. So, I’ve definitely seen that from the reproductive standpoint where I fixed someone’s microbiome who couldn’t get pregnant for years and all of a sudden got pregnant without even thinking about it. But I’m starting to now, ’cause this is something that’s really within the last year come to my attention, and so, I’m starting to do this and that I’m finding that patients are like, “Hmm.”
Matthew Cook, M.D.
What company do you use for the microbiome testing?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
I’ve used a couple different ones but the one I’m really really happy with and really excited right now is Microgen.
Matthew Cook, M.D.
Okay.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
So, yeah, that’s the one ’cause they’re using… I’ve used PCR testing probably for the last I think what, 12 years but they take it a step further. So, PCR looks for the DNA presence in the bacteria but then, there’s this more next generation sequencing. So, it will report every single thing that’s there. So, sometimes there’s coming back with bacteria that when you look up in the literature they know that it exists, but they don’t know why. So, it’s actually been fun to kind of watching these patterns of bacteria that I’m finding and not just be… In medical school we’re taught that Gardnerella is what causes bacterial vaginosis. When in fact in the last couple years I’ve found that specifically there’s ones that are like Megasphaera and Gardnerella and then there’s two there’s bacterial vaginosis associated bacteria number one and two, they haven’t even named them. So, that was really fun to find that in, like when we do the PCR test and now I’m getting reports where there’s bacteria I’m like, “I have never in my life heard of any of this stuff.” And I’m constantly trying to look it up. So, I think, we’re getting much clearer. There’s a lot of research going on right now in vaginal microbiome.
Matthew Cook, M.D.
Okay, well, so then I have to ask you then, if that’s the case A, how do you rebalance the microbiome? And then B, how do you treat bacterial vaginosis since you brought that up?
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
So, and I think, this is another reason why the traditional gynecologic world they see a lot of issues with recurrent vaginitis because they’re not treating all the bacteria that’s present. So, once again, I go back to the gut because I’m like, if the gut is in balance the vagina is in balance. Because of the rectum and the vagina’s so close together no matter how well people clean bacteria gets passed back and forth. So, I see this especially with yeast and those patients who get recurrent yeast infections and you’re treating ’em and you’re treating ’em treating them. I will tell you probably with 99% certainty they probably have gut yeast that is not getting cleared up.
Matthew Cook, M.D.
100%
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
So, you know that we’re seeing necessarily these types of bacteria for vaginosis but we’ll see other things, that they have a high E. Coli or high Enterococcus which is, those are two that are really associated a lot with urinary tract infections. But they’re getting into the bladder by way of, they have to be in the vagina first. So, when we see one thing throw it off it’s gonna throw everything off. So, then these other bacteria start showing up. The other thing that has a big role in that, is low estrogen. So, low estrogen from somebody who’s on birth control who’s postmenopausal, who’s breastfeeding or just at a baby. When you have low estrogen state the vaginal wall thins out. And when that thins out, it stops producing… You stop getting glycogen production which is produced by the sloughing off, of healthy tissue. So, our tissues grow and it dies and they slough off. Well, if you don’t get that sloughing off, lactobacillus, which is the healthy bacteria in the vagina loses its food source. And so, now the lactobacillus starves to death. Lactobacillus keeps the vagina healthy by producing peroxide in a very acidic environment so that it keeps away those other bacteria in yeast. Now, all of a sudden you don’t have any lactobacillus pH changes, everything changes like once one bacteria comes in, the whole thing gets shifted. So, yeah. So that was really complicated.
Matthew Cook, M.D.
That was good. So, then it’s the highlight of my week to interview you. You are the greatest of all time.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Oh, thank you.
Matthew Cook, M.D.
So impressed by everything that you’re doing and you’re a trailblazer and I’m super grateful that you’re sharing all of this stuff and thinking about it. And so, I look forward to sharing patience with you and working with you and learning together about what is happening with people ’cause you’re obviously an amazing physician. So, thank you.
Betsy A.B. Greenleaf, DO, FACOOG, FACOG, FPMRS, FAAOPM, MBA
Thank you so much.
Matthew Cook, M.D.
Okay, well this has been the Peptide Summit and Matt cook with Doctor Betsy Greenleaf and have an amazing w
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