78: Your Gut Actually Controls Your Hormones – Menopause Truth with Cynthia Thurlow

I cannot even tell you how excited I am about this interview today. I have my dear friend Cynthia Thurlow, who is a nurse practitioner with over 25 years of clinical experience, an absolutely infamous TEDx Talk. She is an author, and the latest work is The Menopause Gut, and she breaks down fascinating ways that we will unpack during this interview on how the gut impacts your hormones, your inflammation, your aging, the age of menopause, everything that you've never actually heard, and the conversations that so need to be had in a digestible way that you can incorporate into your everyday life to improve outcomes, long-term health, healthspan, lifespan, all of it. So, so excited about this conversation. Let's dig in. Cynthia, thank you so much for joining the podcast. I am so grateful and excited that I get to be here with you in person. You're one of my favorite people in general, but so, so thrilled to talk about you, your upcoming book, your brilliance, menopause, all the things. So thanks for being here.

Yeah, McCall, I've been so excited to connect with you and, and be able to kind of have this conversation and do it in a way that is sort It's certainly very thyroid-centric.

Oh, I love that. I love that. So menopause is having a moment, right? Perimenopause is having a moment. We are so grateful. But you look at this in a bit of a different way. You look at it more as a systems shift, not simply like this decline in hormones. Can you tell me a little bit about that perspective?

Yeah, I think that it's a little too myopic if we solely focus on drops in progesterone, changes in testosterone, shifts in estrogen. I think it's a larger conversation, and that larger conversation really speaks to how the gut microbiome is a key player in longevity and aging, and how the health of that gut microbiome impacts every single system in the body. And if we're not thinking of it from a larger perspective, we're missing opportunities to help support our female patients. And I would say, in addition to that, I think it really comes down to starting the conversation earlier. You know, for those women that are listening that are maybe in their 20s and 30s, maybe in their early 40s, and they're like, menopause is a thousand years away, I want to tell you there's lots of things we can do proactively. And to the women that are already in menopause, the better that they can understand their bodies, the improvements in terms of quality of life metrics are exponential.

And I want to put a pin in that because I think we're going to circle back to that multiple times throughout this conversation. But how the gut and menopause, perimenopause are tied together is a conversation no one is having that is a key, key important factor as we move through this phase of life. So I love that. We will absolutely be coming back to that again and again. Talk with me a little bit about some of the earlier changes for people who aren't in menopause, people who might be in perimenopause or not even have ever thought about that because it happens earlier than we often realize. What are some of the earliest changes that you see that people should maybe be attuned to? Yeah, with regard to gut changes, perimenopause or gut changes. But what is like, oh, oh, maybe I need to be paying attention to this. Maybe this is an issue for me.

Well, I mean, I think when women are in their mid, mid to late 30s, menopause is 1,000 years away. And yet some of the subtle things that start to happen can be as simple as week before your menstrual cycle starts, you don't sleep quite as well. You might feel a little more anxious. You might feel like you have more mood disruptions. You may feel a little more depressed. We use the term anhedonia in clinical medicine to talk about how we have kind of the blahs. I don't really feel like great, but I don't really know specifically why that's happening. And that can start with those subtle shifts in progesterone preceding— before we even start talking about estrogen. So really starting there, and it could extend a little bit into your gut motility might not be the same because progesterone as well as estradiol are potent stimulators of our digestive system. And so progesterone is a smooth muscle relaxant, so you might feel like maybe you have alteration in bowel habits, maybe you have more loose stools, maybe you have more constipation, maybe you just feel a little bloated. Those can be very subtle shifts that we start to see at the very beginning. And because they are so subtle, we don't take an account for them. I know for myself personally, I had my second child at 36. I can assure you at 36, when I had a 2-year-old and a newborn, I was tired, I was anxious, I had a lot of anhedonia with the lack of sleep I was getting. And yet I was like, I thought I was too young to even be having this conversation. And so I think for a lot of women, it's the understanding These symptoms can start in your mid to late 30s. I think most women, probably it flies underneath the radar for many, many years, but at least knowing and having some degree of validation that that is a normal physiologic change that you may experience, it helps women ask for help a whole lot earlier.

And if they go in so nonspecific, it's really hard to pinpoint what they need to even be talking about. Well, you taught me something new about the alternating constipation and bowel movements. With hormone changes I didn't even know.

Cynthia, have I talked to you about what estradiol is so important for nitric oxide signaling? And the reason why I mentioned this is I love to like nerd out on the physiology, but nitric oxide is a potent vasodilator. And so when, when women say to me like, I feel like I get full much more easily, I don't understand why, I just feel like, I feel like I have a rock in my stomach, or I feel like I have these alterations in bowel habits, it can be a little bit of both. I mean, estradiol and nitric oxide is estradiol is going down. And for anyone that's listening, that's the most common form of estrogen our body makes prior to menopause. As though you see these alterations, and we know that estradiol levels can be 20 to 30% higher in perimenopause. So you can have some cycles where it's high, you can have cycles where it's lower, and you may have these intermittent symptoms that are actually occurring. But the more I understand about how the innervation of the gut is really dependent on the influx of these two key hormones and nitric oxide signaling, to me it's like, oh, this makes so much more sense. But like I never learned any of this in my training, as probably you didn't.

Oh my goodness, no. And it's so fascinating because it is on the forefront of our mind of supplementing nitric oxide, you know, supplementing with things to help your bowels move. But if we can get to the root cause and kind of influence hormones, then the sequela of that is so powerful in all these different ways.

Yeah. And I think the one thing that I've learned about nitric oxide with— as it pertains to estrogen, because estrogen— there's no hormone in the body, there's no neurotransmitter, there's no signaling molecule in the body that just has one role. And you're like, oh, well, this makes a great deal of sense. So when we were talking about some of those mood disruptions that women can experience, it's understanding that estradiol has an interplay with serotonin. So as estrogen's going down, serotonin goes down, which impacts not just serotonin as this potent neurotransmitter, also impacts melatonin, which is not just a sleep hormone. So we go back to that there's never a hormone, a neurotransmitter, signaling molecule that just has one role. They're all interconnected.

They really are. And that's the conversation we're not having yet that still needs to be had, right? Like we're simply equating hormones with hormone deficiency, replace the hormones, replace the deficiency, but the interweb of everything interconnected is still missing from that conversation.

Absolutely.

I want to pivot a little bit and before we circle back to the gut piece, I want to talk about ovarian aging, how it impacts mitochondria, how it impacts our metabolic signals, because those two are changes that we're seeing around perimenopause, around menopause. Tell me about these shifts in women's metabolism around this age, and it might even intertwine with gut. You're, you're the expert here, but we notice, hey, we're doing the same thing, but we're gaining weight. Hey, we have this midsection deposit or adiposity or fat deposits. What's going on there?

Yeah. So first and foremost, our ovaries— we are born with a finite amount of ovaries, unlike men that replenish sperm, I think, every 72 hours, if memory serves me correctly. And so our ovaries are aging with us. And so it's like helping women understand that part of what harkens this ovarian senescence or this unwinding is, number one, the most mitochondrial dense tissue in our entire body are our ovaries, not surprisingly. Number 2, they are aging right along with us. So whether we're 25, 35, 55, or older, those ovaries are kind of marching along. There are things that can speed it up, and I'm sure we'll probably talk about that. But if we're specifically speaking to this metabolic health derangement that starts in, you know, mid to late 30s, early 40s, it is really speaking to shifts in metabolic health. And that is important to understand because it's not just one thing that contributes. I think number 1, we're speaking to loss of muscle mass. You know, it's not just a body composition piece. It is understanding that our muscle are the most— well, I would say it's our largest glucose reservoir in our bodies. And if we aren't working against it, we will start losing muscle in our early 40s, and sometimes for a lot of us even earlier. So losing muscle mass equates with a loss of insulin sensitivity because this is one of many places our body can store glycogen. That's number one. Number two, it's also looking at the fact as these estrogen shifts, you know, whether it's higher in one cycle, lower in another, estradiol is a potent insulin, insulin sensitizing hormone. And so again, we go back to the piece, as we're losing estrogen, we are losing insulin sensitivity. We tend to be less physically active in our forties and fifties. And that can be because we're in the sandwich generation. We have aging parents, we have children that are getting a little more independent. Maybe we're in a job role where we are responsible for more people or have a larger piece of the pie, if you will. I feel like 40s is where a lot of women really step into their power. And so, you know, the other piece of it, you know, if your sleep starts getting bad, if you start not sleeping well consistently day to day, night to night, that impacts your insulin sensitivity. And if we look at the statistics, I think the meta-analysis I looked at from 2019, was looking at, for every hour less than 7 hours per night you are sleeping, your risk of insulin resistance goes up by 9 to 10%. So for anyone that's listening, we're not talking about 1 or 2 days out of the month where you— maybe you're traveling or your sleep is off, but it's the consistent patterns over time can really wreck sleep. And the other thing that I would say that definitely impacts that metabolic health piece that a lot of people aren't talking about, it— underlying trauma. So adverse childhood events, You know, there's this joint venture between CDC and Kaiser Permanente. Anyone that's listening can go online, you can take a look at these questions. I have a high ACE score. So we know women that tend to have higher ACE scores are at greater risk for poor metabolic health, more autoimmune conditions, more likely potentially to go into menopause a little bit earlier, and has a lot to do with that chronic dysregulation of the sympathetic nervous system. So most of us tend to run a little sympathetic dominant, which means We're very task-oriented. We're doing the to-do list. We, you know, we don't relax, we don't sit down, we're not having enough downtime. And so all these things can contribute to why we see not only early ovarian aging, but also this poor metabolic health piece. And I think for so many of us, it's just these subtle things that start to happen over time. A lot of women don't realize until their late 40s, they're like, why is my body composition not where I want it to be? I'm not doing anything differently. Why is it so much harder at 45 or 50 than it was at 25 or 30? And it has a lot to do with our physiology is changing. I don't use that as an excuse. I use that as a, let's provide some explanation so we can make some lifestyle changes that are going to impact this greater. And I would say the last thing that I think is helpful for people to know is that nutrition piece. You know, nutrition becomes a much more important component of how we age. And I think for a lot of people, you can't eat like you're 18. You really do have to change the way that you look at macronutrients, protein, carbohydrates, right types of carbs. I don't want to bastardize carbs. And certainly you're the thyroid expert. You can speak to the fact that there are women that need a little bit more discretionary carbohydrate to buffer and improve their thyroid function. And so I think that there's this very large conversation. It's not just about one thing, it's multiple things coming together. That really impact body composition.

I love it. And the things that you mentioned, are those the same things that kind of break down our mitochondria earlier, that shift that DNA, the energy production?

Definitely. And they can definitely contribute. I mean, we think about toxins. So I would say another thing that is smoking, alcohol use, and it's not just, you know, I have a drink once a month. It's the people that are drinking, as you know, there's a big mommy drinking culture. And so it's the choices that we make that can influence that mitochondrial health. And so I always go back to the basics. I always say major in the majors. Make sure that you are dialing in on, like, the nutrition quality, the sleep, the stress management, the exercise, because those are the foundational elements that most, if not all, of us really need to focus in on, as opposed to thinking it's one supplement or one intervention. Like, the cold plunge is not going to fix your mitochondrial issues. It's not going to fix that insulin sensitivity piece. It is— you have to major in the majors, and then you layer in the rest depending on what's appropriate for you.

Yeah, and it's interesting. I think something that most people don't realize is our mitochondria are made of DNA, just like our DNA, completely separate DNA. But just like we age, when we age, our regular DNA breaks down. The exact same thing is happening with our mitochondria, and they're such a powerful force for our health. And so protecting our regular physiology, our regular DNA, bleeds into also protecting those mitochondria, which will help us in every aspect of aging. I mean, right? I wanna switch gears a little bit. I want to talk about the microgenderome and why female metabolism diverges in midlife and how it can be related to the gut. Yeah. Tell me some thoughts on that.

Yeah, it was interesting when I was reading the book, I came across a term I had never heard of before, and yet it makes so much sense. So when we talk about the microgenderome, we're really speaking to when young men and women are born. Their microbiomes are fairly similar, right? Obviously, they're not perfectly aligned, but they're very similar until puberty. So this influence of key hormones like testosterone and estrogen and progesterone— and let me be clear, testosterone is a pretty important hormone for women as well. I think people think it's just a man's hormone. It is actually an important hormone, and men also need a little bit of estrogen. It's that Goldilocks effect— not too much, not too little. And so we look at 3 key times in a woman's life where the microbiome— so the gut microbiome is 40 trillion bacteria, viruses, fungus, protozoa that are contained in the large intestine or the colon. And so we see these diverse shifts in puberty, pregnancy, and perimenopause. So the three Ps. And watching this kind of shift in the microbiome is, is expected in relationship to alterations in these very important hormones. What I find so fascinating is there's not enough discussion around this because we do see these significant shifts. But it's also understanding that the irony is that in menopause, a woman's microbiome starts to resemble a male's again. And so life kind of comes full circle. It doesn't mean it's perfectly aligned, but we start seeing alterations in diversity. We start seeing alterations in inflammation. And so life kind of comes full circle as those hormones start to kind of level off. And, you know, it's interesting. The research is certainly looking like we're heading in the direction that HRT at some point will be playing a larger role in helping to optimize the microbiome. We're not there yet, but certainly the research looks like it's heading in that direction.

That is really cool.

Yeah, the microgendarium. It's a new term for a lot of people.

Today is the first day I've ever said that word, so thank you for the introduction. And then this obviously impacts fat distribution. How does it impact inflammation, just tied to our gut microbiome in general?

Yeah, so there's certain— so when we look at the key changes that we see as we're navigating this perimenopause transition, It's like, number one, we get changes in diversification of keystone bacteria. So the bacteria that make up the bulk of the microbiome. So things like Bifidobacterium lactobacillus, we start seeing a reduction in them and an increase in inflammatory species. So that's kind of number one. Some of its changes and alterations in those microbial diversification. It's also, you know, shifts in oxidative stress. It's shifts in insulin or insulin sensitivity that all drive this. It's understanding that our immune system ages right along with us. And so when we talk about aging, we can't not talk about the immune system, which I'll be the first person to say that immunosenescence is a fancy way of describing the aging of the immune system. And when we look at, like, as an example, the small intestine is one cell layer thick. Guess what happens if we're eating a standard American diet, we're chronically stressed, uh, we're exposed to a bunch of like chronic toxins. We open up the little lock and key mechanism of the protective barrier. And right alongside that is the immune system. So what happens when we develop leaky gut, which is a real thing, small intestinal hyperpermeability for those who want to hear the like technical vernacular, we provoke an immune response. You know, it's right alongside that, that gut barrier. And that can lead to underlying food sensitivities, a lot of inflammation. I'm sure a lot of your patients will say foods I've always been able to eat no longer agree with me. There's a reason why that happens.

Fascinating. We're going to talk about a new word, another new word, the estrobolome. It's all new vocabulary today. So I want to talk about estrobolome, why estrogen behaves so differently in midlife women, even when technically if you run labs, the levels might look the same, but it seems to be acting differently in our bodies. Can you tell me a little bit about that?

Yeah. So this is really an estrogen processing center in the microbiome. And I think for a lot of people, they're like, oh, I have a bowel movement every day, or I poop every day, and therefore I must— my detoxification efforts must be pristine. But again, it's these changes. We have more inflammatory bacteria. Not everyone that is trying to process and package up this extra estrogen and get rid of it, usually through bile, helps break down and emulsify fats, but also very important for working with estrogen. So as estrogen declines, we start to un— kind of unwind this, uh, pre-estrobolone process. But if we're not packaging the stuff up, if we're not getting rid of it through our stool, uh, or our poop, uh, just to keep it light, we can recirculate the estrogen. And so sometimes women will say, I'm in menopause, but I have all these symptoms that certainly suggest that I've got a higher level of estrogen. So maybe they have tender breasts, maybe they are weight loss resistant, maybe they have a lot more brain fog symptoms. And so the estrobolone becomes very important for helping to break down and use as a recycling process in the body. But think about it, we have endogenous estrogen, so what our body makes. We also have exogenous estrogen, so estrogen in making chemicals. Think about the microplastics in our water. I share this just to kind of identify that we can get exposure outside the body as well as exposure inside the body, and sometimes that can be magnified. So the estroma lobe becomes very important, and there's ways that we can look at this either through stool testing or looking at beta-glucuronidase, which is this very important enzyme that helps us break down the estrogen and be able to package it up and get rid of it. There's certainly genetics that play a role. Some people don't do as good of a job with detoxification. And let me be very clear, our body detoxifies through breathing, sweating, urination, defecation. All these things are the way that our body should optimally work. But we have our liver as a primary site for detoxification, and then the gut. And so again, we go back to why the digestive system becomes a really important player in how we break down and metabolize hormones the health of the microbiome all becomes very circuitous. I always say, again, it goes back to there's never one part of the body that just has one role. They're really like playing supportive roles in some instances and then primary roles in others.

So would you say that maybe perhaps in perimenopause, when our body is increasing estrogen production, we tend to have like perimenopause rage, the insomnia, the agitation, the breast tenderness, all of those things. Do you think that's in part because our gut is disrupted around that same age and is no longer efficiently excreting estrogen?

Absolutely. I would be the first person to say that if you are experiencing any symptoms, you have to be looking at the gut as a primary driver. In fact, whether it's hot flashes, whether it's bloating, whether it's digestive issues, whether it's anxiety, poor sleep, the research certainly suggests the gut is playing a key role. And things like, we have the vagus nerve that communicates between the gut and the brain. So when people tell me they're anxious, depressed, they can't sleep, I'm like, all right, what's going on? Because there's this communication superhighway between these two very important parts of our bodies. It's not there for no reason. And I'm sure probably when you were still seeing patients in the hospital, how many of my patients 20 years ago had their vagus nerve severed during surgery, generally accidentally, but how important that communication pathway is for people.

Right. And then that then influences metabolism and inflammation influences all of these things. Like, it's so inherently tied together in this holistic way that, again, no one's really talking about that. We need to have these conversations. So tell me a little bit about some action steps that women could take for— to support in perimenopause, specifically in menopause. To support their gut integrity, to protect their estrobolome, their metabolic sensitivity, etc.?

Yeah, well, I think number one, I always say you start with the foundations. Like, number one, we know sleep is a primary driver of health. Really focusing in on figuring out why your sleep is so poor, and this goes for everybody, but understanding that poor sleep is going to lead to poor metabolic health. We know it can lead to leaky gut. I remind people, if you're chronically stressed, you're probably going to be— it's going to influence your sleep significantly. And we know cortisol is not a bad hormone. It gets this terrible rap, but I remind people that cortisol is catabolic. So it not only does it break down muscle, it influences the immune system. So you're more likely to deal with leaky gut, more autoimmune conditions. You're more likely to be dealing with opportunistic infections. If you're wondering why you're chronically getting sick all the time, very likely we're talking about a chronic stress, poor quality sleep piece. I also think a great deal about nutrition. And for the, anyone that's been living underneath a rock, protein is having a moment. Protein is still very, very important. And we know we need more with the aging process, actually not less. And by more, I mean no less than 100 grams a day. So if you are an intermittent faster, please, please, please make sure that you're getting in a minimum of 100 grams of protein a day. You probably need more than that. And then looking at like key players that are helpful for the estrobolome. So like cruciferous vegetables, bitter foods are going to be very important. So like bitter greens, citrus fruits, we know can be very, very beneficial. Making sure that you have not normalized not pooping every day. I can't tell you how many people fall into my lap, literally, that are— they think it's normal to poop 2 or 3 times a week. And I'm like, no, we got to fix that too. Because if we're dealing with someone that's in perimenopause and they're having this recirculation of estrogen, they don't feel good, they're weight loss resistant, they're bloated, they have a lot of brain fog. It's helping them understand that that detoxification piece becomes very important. I would also say exercise. I mean, let's be clear, strength training we know is going to be important for maintaining muscle mass, but we know that people that are physically active tend to sleep better, they tend to be able to manage their stress better. Uh, also important for— I remind people, like, taking a walk 5 to 10 minutes after you eat can help with blood sugar regulation. Not to mention mental health. So I always say grab someone that you like and have a walk with them. It's a good way to connect with others. And then we start layering in like larger pieces and looking at gut health testing. I would say every woman should have stool testing done at least once or twice a year. Why do we do that? Because I actually like to look at, is there a lot of dysbiosis, which is effectively weeds in the garden, if you will, things that don't belong, non-beneficial bacteria. Are there latent infections? Are you able to break down and emulsify fats? Because you will actually— it's something called steatocrit, but it's a marker that lets me know, are you able to break down your fat? And for a culture that was fat-phobic for a long time, we still have people that are fearful of consuming fat, so their body has gotten a little lazy in the process. Do you need digestive enzymes? Is your calprotectin high? Is there a lot of inflammation? Like, should we be looking a little deeper? I've referred plenty of people on to gastroenterology when they've had findings on a stool test that are certainly suggestive of bigger issues as opposed to the stuff that I'm speaking to. So looking at stool testing, getting really granular about hormone replacement therapy, which we know is going to be beneficial sooner rather than later, thinking about— if we're talking about poor metabolic health, and certainly there's a lot of women in perimenopause that are lost, you know, they're like, I don't know what's going on with my body. I was certainly there 10 years ago. First person to say is, and you know, the option of utilizing very powerful drugs called GLP-1s that I know you talk a lot about. The women that are on HRT plus GLP-1s, we know have improved body composition, and we know tend to feel and do a whole lot better from a metabolic health perspective. So I start thinking about peptides, I start thinking, and I, when I say peptides, not peptides from the corner grocery store, like from a licensed medical provider that knows what they're doing and is going to personalize and tailor these for you. I start thinking about low-dose naltrexone. Um, I know that's something that we're both a huge fan of, this immune-modulating, very low dose of a medication that we're just starting to really understand the ramifications. But how many of my patients— women are 4 to 5 times more likely to develop autoimmune conditions in middle age. And so quieting that, that inflammatory response, quieting the immune system— I'm sure we can unpack what's changing in the immune system, but to kind of give people like some high-level things. I would say the other thing is for a lot of women, they don't deal with their stuff until middle age. So maybe you experienced a lot of adverse childhood events as a child, maybe you had a bad boyfriend in college or after college, maybe you had a bad marriage. If you don't deal with your stuff, it will find a way to find you in middle age. And so this is where I think 70% of the divorces are initiated by women, and I think a lot of that could be a combination of many things, and I am not a clinical psychologist or a psychiatrist, but I certainly have a lot of friends who've been through this, and I've been able to see this through the eyes of many, many patients. I think helping people understand that dealing with your stuff is critically important because chronic stress, as I've already mentioned, can erode your immune system, can be catabolic. But if you don't deal with this, as you have all these alterations in neurotransmitters and hormones, it's going to make perimenopause and menopause a whole lot harder. And so I think for many women, they find their voice in perimenopause and menopause.

And you kind of term that and talk about it as immunosenescence. Tell me how that immune resilience or immunosenescence shifts specifically in this perimenopause-menopause time. Why are we so much more vulnerable at this age to experience autoimmunity, to experience inflammation, to experience poor immune function.

Yeah, it's so interesting to me, and I am not an immunologist, but I will tell you I learned a lot about the immune system, more than I ever wanted to know, as I was writing the book. And so we have two main arms to the immune system. There's kind of very basic part of the immune system, you know, you get a cut, you know, it's a very non-specific part of the immune system that kind of gets activated, whether it's cilia in your nose or mucus or the skin barrier layer. It's designed to just protect you. It's very basic. It's not customized. You know, like we talk about customization. Then we have the acquired immune system, which is— we think about B lymphocytes, the T lymphocytes— is very specialized, heavy-duty immune system protection layer that usually has to kind of— it takes a little longer for it to go into effect, but it can be very effective and very important. What changes in our immune system, especially with this loss of estrogen, is that all of a sudden we get these alterations in, they call them Th1 and Th2, and it's really looking at T helper. This is a very, very specialized part of the acquired immune system. So like the kind of like the graduate school part of the immune system, and it starts to shift. It starts to shift so that we are less likely to see a response from vaccines. We are more likely to see more inflammation. We are more likely to see more opportunistic infections, and this flip tends to drive more inflammation. So women, by virtue of our gender, become much more susceptible to autoimmunity. And what's interesting is most of the autoimmune conditions, women make up a disproportionate amount of the individuals diagnosed with autoimmune conditions, but it really ramps up in middle age. And I remind people that this immunoaging or immunosenescence is really speaking to every part of our body starts to age a little faster with these changes in sex hormones, but Estrogen is a potent immune-modulating hormone, and yet another reason why hormone replacement therapy is so critically important for women at this stage. I would say, like, whether women choose to take HRT or not, they need to make a fully informed decision. But I think the immune system is probably not a big indicator. Like, people think about, I want to protect my brain, I want to protect my bones, I want to protect my heart, and I'm like, I get it, the immune system is invisible. And for a lot of us, we're like, I don't worry about my immune system, it'll protect me. It also explains why 5 years ago, 6 years ago now, during the midst of the pandemic, a lot of people that had the worst outcomes from the pandemic and COVID were individuals that were older. And it had a lot to do with this immune senescence— immunosenescence. So not as vibrant, not as quick to respond, doesn't do as stellar of a job. Yet another indication of why we need to take care of our gut and really be thinking about hormone replacement therapy.

So when we think about the elderly people who are immunocompromised, right, a lot of these shifts that you're mentioning are happening potentially earlier in women and beginning to happen around middle age at these big hormonal changes.

Yes.

Yeah. And we always think about it as like the elderly, the really old people, but it happens earlier than we're willing to.

It's happening slowly. And so just think about it. It's like a slow building. Imagine like a little fire. And it's just kind of building, building, building. And it's like the longer we go without estrogen, progesterone, testosterone, the worse it gets. And I think for a lot of individuals, they're like, the immune system's not sexy, I don't really understand it. I'll be the first person to say, like, the amount of information that I now understand about the immune system, like, blows my mind because I don't even think I was tested on the amount of information that I know now. But it just reinforces why we need to have these conversations to say You know, when we're talking about the gut microbiome, when we're talking about magnification of symptoms, magnification of disease processes that come out of these hormonal changes, it's like we need to really talk about why all of a sudden women, like, you know, why we see women in the ICU with urosepsis. That can be from a variety of things, but not the least of which, they just cannot mount as effective of an immune response like they did at 25 or 30. And so if we want to keep our elderly population healthy, we need to start in our 40s and 50s having these kinds of conversations so that clinicians and lay public are like, hey, that makes sense to me. I— this is why I need to major in the majors, and I need to have conversations about gut testing and HRT and peptides and things like that.

And so what can happen if you do get on board with HRT is you can actually— of course, you get the improvements in all these symptoms and hot flashes and vaginal dryness and brain and heart heart and cancer, but you can also improve your immune system?

It's looking like that. It's suggestive. Now, I don't want to speak like— I'm not a researcher, but certainly it would suggest that if we are replenishing hormones— and this doesn't mean a whiff of an estrogen patch, like, I want to be really clear, there are people out there that are on like 0.025 milligrams of an estrogen patch. I'm like, that's probably not going to protect your bones, let alone your immune system. But we know that you're going to get conferred benefits if we're getting, you know, if we're gonna need a 6 picogram, 60 picograms, 100 picograms you can probably assume that you're going to be replacing those estradiol levels high enough that you will probably get some conferred benefits to the immune system as well. Because we're really looking at this aging process. It's an inflammatory process that just unwinds, that hits every single system in the body. And I think the messaging about HRT— and I don't mean to get on soapbox— is it's a very important one. But the larger question is, you know, what are the amounts that we need to be replenishing these hormones at to protect the brain. We haven't gotten that information yet. We have a sense of what it should be for heart. We have a sense of what it should be for bone. But I think as more research is done, we will be able to better pinpoint where do those levels actually need to be to confer improvement. And I don't think we have that answer yet, certainly, because the immune system is nebulous. There's not just like one thing to test if you're trying to look at the immune system. You can look at inflammatory markers, as we both know, but it's a little less tangible as opposed to like a tangible organ.

And I think we're just behind the curve a little bit still because we've spent decades kind of demonizing hormone replacement. And so it was sort of this orphan child that we didn't really look into. We didn't value, we didn't do research on. And obviously we're hitting our renaissance at this point, I hope. But it takes years, as you know, as we know, to get that new data, to get the information out for people to do the studies. And we're just that's sadly, crazy enough, scraping the surface at this point, right?

Yeah, absolutely. And I think we go back to— we're building awareness around this topic, which is great, but I still think there's a degree of conservative management. Like, I will use an example. I took the North American Menopause Society exam. Did it test whether or not I could prescribe hormones in a really great way? It was like, yeah. So it's still very conservative. I think they're doing a great job building awareness. But I think that there are still people practicing so conservatively, probably not there yet. How many women will mention on social media, like I'm sure they do for you, some of the symptoms they experience. I'm like, clearly your estradiol's not where it should be. Clearly your progesterone's not where it should be. Clearly insert whatever hormone it is that we're talking about, thyroid hormone, appetite regulatory hormones. It's clear that we're not where we should be because you're still having symptoms or certainly symptoms suggestive of suboptimal levels.

Yeah, we're living in these extremes. One is way overmedicated women that are being put on crazy amounts of hormones or testosterone. And I've literally had multiple women come into my practice with a testosterone over 2,000, over 1,200, and those are not reversible symptoms.

If they've got— for anyone who's listening, you can see the people that have got supraphysiologic testosterone on board because they're voice changes, their jawline changes, their physiology, right, their hair starts falling out. Clearly, that's not our problem, because this is my hair. For anyone who likes to ask me if I have extensions, which no judgment if people do, I think it's great. But the point of why I'm suggesting is you can tell when people have supraphysiologic testosterone, and that clitoris enlargement, those voice changes, sometimes those hair changes and other things that happen, sometimes those are not reversible. And that's kind of scary. So I think that we have to be— it's like finding— it's like the Goldilocks effect. Like, we want enough of the hormone to replace to be able to ameliorate symptoms and confer protection. We don't want too much, and we don't want too little. And I think, at least with the estrogen piece, I see far too many women that are on like a whiff of hormone, and I'm like, that isn't going to help you. That's why you're having all these genitourinary symptoms. That's why you're having all these body composition changes, because you're on such small dose, it's probably not doing much.

Right. And I think we'll hopefully evolve out of that. I think clinicians are still maybe practicing with one foot in, one foot out of the belief system that, hey, hormones are protective, they're safe in most every case. They're still stuck and tied to the Women's Health Initiative, the fear-based kind of propaganda that we've been living in for the last few decades.

Absolutely.

I want to circle back to something you've mentioned quite a few times, and it's stress. Whether that's trauma, whether it's work, whether it's kids, whatever it is. Talk to me about how stress impacts menopause, gut, the age of menopause, our symptoms associated with them, or perimenopause.

It's interesting to me, I've had a lot of conversations on my podcast with different clinicians. Many of them are licensed medical professionals, and it's pretty clear that for certain women, whether it's the amount of adverse childhood events they experienced, and we have no control over that, you know, what we grew up within. So you have to give your circumstances grace, or they had very stressful jobs or went through a really bad marriage or war-stricken parts of the world. I mean, just sometimes things we cannot control over a period of time. We know that stress can— so there's specific things that we know can age our ovaries faster. Some of it's genetic. Sometimes there's autoimmune components. Sometimes it's chronic stress. Sometimes it's someone was delivering babies for 15, 20 years in the middle of the night and the stress of like having overnight deliveries and not getting enough sleep can be a big driver. If you've been smoking for a long time, we know that can accelerate the aging of the ovaries. If you're a big drinker, you know, toxins in general, uh, can be huge impetus. But what I find fascinating is this cortisol. As I've mentioned, it's not a bad hormone, but chronic cortisol activation, chronic stress, chronic sympathetic dominance, we know can accelerate aging of the ovaries. And so I find that interplay really interesting because when I say to women that stress, like acute stress is great, like I'm sure right now if we measured our cortisol, we're excited, we're talking, it's up a little bit because it's help— it helps us keep alert and engaged and we aren't struggling with word finding and things like that. But like chronically elevated cortisol over time can deplete and I've mentioned impacts the immune system, is catabolic, can be very detrimental for metabolic health. You know, keeping your glucose raised will keep your insulin up. And again, it just becomes this kind of circuitous piece. But when I look at the research on adverse childhood events and how that impacts ovarian aging, I find that interesting and also disturbing because for so many women, it's understanding that We can't control our childhood. We can't control the past. We can only control going forward. But how many women actually need to spend time gearing their bodies down and demonstrating to their bodies that they're in a safe space, demonstrating that they're in a safe space so they can manage this cortisol dysregulation? You know, Dr. Sarah Gottfried talks about PINE, so this psychoimmunology neuroendocrine system and how it's all interplayed. And so helping us understand that when we're speaking about perimenopause and menopause, it really begs this larger conversation of how are you going to age? What is your longevity going to be like? What is your gut microbiome going to be like? Heavily influenced by this chronic stress piece. There was actually a study that I read that looked at women who were sexually abused, who went on to have children that were sexually abused. And that research suggested these women go into menopause 8 years earlier. But that's one, like, extreme. But how many other women had significant adverse childhood events and then go into menopause at 45, 46, 47, 48, which is still considered to be normal, you know, anywhere between 45 and 55 is normalized, but they're on that lower end of that curve. And so you start to wonder how much influence— is it bio-individual influences combined with they had the right amount of stress and trauma at a specific time in their lives that kind of accelerated the unwinding of this DNA piece of this acceleration of aging of that very mitochondrial dense and rich tissue. That to me is a really exciting conversation. Also disturbing because how many of us— when I think about family members who went into menopause at 47, 48, 49— I have a GYN colleague, 43, and they talk about like stressful job, lots of childhood trauma, and how that's influenced how early they went into menopause. And so I think a lot of people aren't per se having those larger conversations, because whatever's normal is normal. If, you know, if you're premature to go into menopause before 40, or if it's early before 45, we're like, okay, we understand that. But 46 is still pretty early. 47 is pretty early. 48 is pretty early to me. So the conversation is, is it susceptibility plus or minus life circumstances probably contributing?

And that makes me think, you know, whenever I think back on my own life, whenever I'm in incredibly stressed, I can literally look at pictures of myself and am almost unrecognizable. I almost did this 2016 trend on social, you know, and I looked back and I'm like, wow, I look 10 years older than I look right now.

Yeah.

And so I almost wonder if we can retrain our nervous system, if we can shift our stress response, does that shift our physiology? Can we reverse and undo the damage that's been done?

Well, I mean, this isn't my area of expertise, but like intellectually, I would think that there are a lot of conferred benefits. Like, I always say that I think many of us look like the duck paddling across the water. Like, we look calm on the outside and then underneath we're paddling furiously. So I think it's relearning maladaptive patterns. It is making yourself do not disturb. It is creating more boundaries in your personal life. It is removing toxic people from your life. It is, you know, getting really clear about what your life's purpose is. I think a lot of women, as they are losing estrogen, find that they lose their people-pleasing tendencies. And so all of a sudden they're like, oh, the I Don't Care Club, right? And I mean, that resonates so much. It's like, I so don't care about so many things. And some of it's generational. Like, there are clearly things that my generation is very fixated on right now, and maybe other generations are not, but I think finding your voice is part of that healing your nervous system. But it requires work because your nervous system is wired early. Like, I can tell you that I can read, I can— like, what is my superpower? How did I become a really good nurse and nurse practitioner? I can read a room. I know exactly what that patient needs. I know exactly what that room needs. I know exactly what people expect of me. And that is exhausting. And so that's how my nervous system got wired from the trauma that I grew up in as a child. And so has it made me who I am today? Absolutely. But do those tendencies have to get— I have to work on that every single day. Like, you have to be willing to do the work, and that usually includes therapy. It may include medication for an individual. I'm not necessarily saying you have to do an ayahuasca binge. It's never something I've done. That would not be the right thing for me. But I think for people, you have to have a degree of exploration. Like, what is it that I need to do? What is the work that I personally need to do to help unwind the way that my nervous system is wired? Like, is my nervous system ever going to be as peaceful as a Buddhist monk? No.

Right.

That would probably not be realistic. But can I ensure that my nervous system thinks I'm safe? Can I make sure the environment that I live in makes my nervous system feel safe? Can I make sure that I've created boundaries around things in my personal and professional life that make me feel safe? Absolutely. And I think that clarity is something that is the gift of these middle-age years for many women. All of a sudden they're like, I'm so clear about what I will and will not accept anymore. And I think for many women, that is an enormous gift if they lean into it. Like, it's not like the life just gives it to you. It's like you have to do the work. Be willing to do the work, and then implement said work. And then if you do that, then I think the— it's an endless amount of benefits for the rest of your life.

[Speaker:ELIZABETH_HALE] I totally agree. I feel like something happened when I turned 40 that just put me into that state, and it's life-changing. It's so freeing. But still, I do think at the same time, we can be stuck in that cycle of nervous system activation, and it just takes It takes everyday work to get out of it.

Yeah. Well, I, it's interesting. I interviewed a guest on my podcast at the end of 2025, and he's someone I followed on social media for a long time, Jerry Wise, and he's absolutely amazing. But his content resonates with me because he talks about narcissism. And narcissism resonates with me because I have a narcissistic parent. And the more I started understanding of how that parent had influenced my behavior and the trajectory of my life. The more I realized that the safest and healthiest thing I could do was have no contact with this parent. And I know people have a very visceral response when they hear about that. And I said, but you have to understand that for me personally, one of the greatest gifts I have given myself in the past year is having no contact with this person. It's not an avoidance. I'm still doing my work, but my nervous system will never and is never going to be capable of being around that individual. And not being horrifically triggered. And that's sad. But by the same token, when you talk about how at 40 the gift was you, you know, had this newfound freedom, 50, it's like take it times 1,000.

Oh, really?

Yes. Yay.

Yes.

It's like you kind of, you feel very centered. You're like, I know exactly what I need to be doing. So I think for a lot of individuals listening or watching, I'm sure that resonates. And it doesn't mean that you have to go to that extreme. I just offer that as a, like, personal reflection to help people understand that It doesn't have to go to that extreme, but like sometimes those choices that you make are really for your health and the safety of your body.

I love that. And I love that it reframes these seasons not as negative, that there's a lot of hope, there's a lot of benefit, there's a lot of things that we can look forward to. Absolutely.

Yeah.

I'd be remiss if I didn't ask you, tell me about your thoughts on fasting. During peri, during menopause? Because if you guys don't know, Cynthia is also a fasting expert. If you haven't seen her TED Talk, you should absolutely go check it out because it's incredible and she's brilliant in this regard. But I know that this is an evolving conversation. It is a conversation that's unique and never one-size-fits-all. So tell me what you think.

So obviously I've been known for intermittent fasting for the past 10 years, and I still think it's an important strategy Full stop. Personally, my thoughts have shifted quite a bit. I have spoken very transparently that my father's death was really a powerful catalyst to changing my perspective. And why was that? Because one of the things contributed to my father's death was this significant loss of muscle mass that led to frailty. Frailty led to falls, and then the falls led to his death. And being part of his last 2 weeks of his life and and dealing with hospice and being in the ICU with him and, and dealing with all that, it really weighed heavily on me. And I kept thinking to myself, I look like my dad, female version of my dad. I'm like, if I don't change what I'm doing, I'm going to be potentially at the same risk that he is. And so I think for a lot of individuals, it's helping them understand, number one, that you don't want to lose muscle mass at the expense of intermittent fasting. Because muscle is precious currency. So if you have a wide enough feeding window in which you can have 100 grams of protein at a minimum, great. I don't know a lot of women that can do that with a short, tight feeding window, so 4 to 6 hours. So I've kind of evolved from there to something that I, I call digestive rest, which is really just 12 hours of not eating that everyone can do, including my young adult sons. That are super athletic and muscular. And I think most, if not all, women can benefit from— you're still giving yourself time where you're not eating. It's not as extreme. You might have an 8 to 10 or 11 hour feeding window. They can get 2 to 3 meals in. They're getting plenty of protein in. And I just think when we're, we're looking at this metabolic health piece and we're looking at the sarcopenia piece, which is this muscle loss with aging, We really have to get granular. Can you eat enough protein? And for every time I say this, I always get some angry person out there who says, "I can have one meal a day and get 100 grams of protein." Okay, I don't know any other women that can, but good for you. Yeah, I don't know anyone who can. So I think it really begs this larger conversation of, can you get enough protein into your feeding window? If the answer is no, widen your feeding window. If the answer is yes, great, just make sure you're getting body composition checks a few times a year so that you can monitor muscle mass loss, because that's the larger piece. The other thing that I want to add to that is if you are not metabolically healthy, which we know is most Americans, 92 to 93%, you probably would benefit from some degree of intermittent fasting or a compressed feeding window episodically, not maybe daily. And if you're a younger woman, you know, that you have to really abide by where you are in your cycle. And even in perimenopause, Where are you in your cycle? Because there's a time to fast and a time not to fast. But I find the intermittent fasting fervor over the past 8 to 10 years, I think, has gotten to a fevered pitch where a lot of people are just simply not eating or they're not eating enough. And there's this degree of orthorexia that goes along with this. And so I never want the message to be don't nourish your body because we know how important that is for hormones. How important that is for maintaining muscle mass, how important that is for maintaining independence. So when I talk about not losing muscle, what people in their 30s and 40s are not thinking about, and probably in their 50s, is that what leads to a loss of muscle is a loss of independence, because frailty leads to falls, and falls lead to bad things like either never coming home or head bleeds or other things. And so unfortunately, fortunately, after 25 years of being in clinical medicine, I can tell you I've seen at all. And that's what people aren't thinking about when they're younger, because it's like menopause. Menopause is 1,000 years away, I don't have to think about this. Loss of independence is 1,000 years away, I don't need to think about this. You do, you need to think about it right now.

You really do, because now is the time that you influence that risk. Later, every 5 years, it gets so much harder to— Exactly. I love that. Well, thank you for speaking to that. I want you to tell us a little bit about The Menopause Gut, your book that's coming out. I'm I'm so incredibly excited. Clearly, this is a deeper conversation that needs to be had, but share with our listeners a little bit about it.

Thank you. So The Menopause Gut is really probably the thing I'm most proud of that I've done professionally, because I have this incredible opportunity to sit down with all these experts. And I kept saying to my editor, I was like, no one's talking about the gut microbiome. And really, it, it's instrumental in every single organ system, every single cell of the body. So Yes, menopause, perimenopause are having a moment, but this is a unique lens. And I think both for clinicians and the lay public, it's a really great book because it walks you through what's happening with our ovaries, what's happening with our immune system. It talks about bone health, something we didn't even talk about, but the health of our bones are dependent on the gut-bone axis. It walks you through all the things, the interventions that I think are really helpful, which it's all about majoring the majors, but it's also looking at the influence of the WHI and hormone replacement therapy and supplements and I briefly touch on peptides. I didn't want to go down that rabbit chute, but to me it is like a love letter to women, really helping them understand their bodies in a way that's really accessible. In fact, my editor was in my ear the entire time reminding me I'm not writing a scientific journal and I'm not writing a textbook. So we really make it accessible. But also it's a book that you're going to want to have a physical copy of because there's so much information. It's so information dense. And then We have recipes in the back, which I'm really proud of. Um, Beth Lipton and I collaborated again, and these are gut-centric things. We talk about pre and postbiotics. We talk about all the nutrient-dense foods that we know based on research are really beneficial for the gut. So to me, it's a love letter to women.

We need that.

Yes.

So thank you for it, and thank you. I know you are always an incredibly well-researched writer, clinician, advocate, all of it. So thank you for taking the time, the energy, and the effort to compile all of that wisdom, all of that brilliance into something that's so accessible and usable for women.

Thanks for having me.

Yeah. Tell our listeners where they can find more from you about your book, social, all of it.

Yeah, I would say easiest to go to my website. So www.cynthiathurlow.com. You can listen to Everyday Wellness. You can also get links to The Menopause Gut. And I would say The Menopause Gut is available everywhere books are sold. I always say if you have a brick-and-mortar business in your community, please go give them your business. But obviously Amazon, Barnes Noble, Target, Books-A-Million, and etc., etc. I'm active all across social media. I'm probably most active still on Instagram. I do have a YouTube channel, a Substack, which is slowly but deliciously growing. It's kind of a cool place to be. I am on X where I can be a little snarky, and then also TikTok, although admittedly I need McCall's TikTok recommendations to kind of get a fire lit to get me going, but I'm kind of everywhere.

We'll work on that for sure. Please pick up The Menopause Gut. I'm so excited to share it with you today and to experience it myself and get my hands on it. So thank you so much for taking the time and being here, Cynthia.

Thanks for having me.