The Hidden Link Between Menopause And Gut Health | Cynthia Thurlow

0:00Dr Karan: As the menopause gets increasing attention in the health space, with more information available than ever, one piece of the conversation is still being missed. The menopause connection to gut health. That's why today's guest, Cynthia Thurlow, has written The Menopause Gut and is here to tell us why it matters. I was doing, at that time, doing a lot of diagnostic stool testing and I was like, why is every single woman dysbiotic? I'm Dr Karan and in this podcast I speak to the world's foremost experts in science and medicine to cut through the BS of modern health advice. Thanks as always to Loam Science for sponsoring the show, the world's first invisible fiber blend with clinical trials.

0:36Dr Karan: Cynthia Thurlow, you're a nurse practitioner and the importance of the menopause gut. Now, I think, as we've discussed very briefly, a lot of talk about perimenopause and the menopause, but the menopause gut, that conversation specifically, I've not really heard outside of your content too much, and as well as my own personal interest in that. Why does gut health suddenly become so important for women, specifically after 40? Yeah, you know, it's such an important part of the conversation that we have with our patients. But if we understand the role of hormonal changes and how that impacts gut motility, inflammation patterns, propensity for leaky gut, metabolism, it makes a great deal of sense why when we speak about the changes in progesterone and estradiol in particular, that it's not just speaking to brain effects, bone effects, heart effects, which are all very important, but I would say equally important, the gut microbiome conversation explains a great deal of the symptoms that women experience in midlife that aren't as easily explained by, and I say this with some frequency, just slapping on an estrogen patch and hoping that that's going to fix everything.

1:50So certainly for me, it explains why many women, despite being optimized on HRT, are still not feeling better. And it gives us an opportunity as clinicians to not only start the conversation a whole lot earlier, but make women aware of symptoms like bloating or changes in constipation or diarrhea habits, or even new underlying food sensitivities may become more problematic as they are navigating this midlife transition.

2:19Dr Karan: Yeah, I'm glad you mentioned the microbiome as a factor here because, you know, we have some human studies that suggest that menopause is associated with alterations in gut microbiota composition and in some cohorts, especially lower diversity and a microbiome becoming somewhat actually, funnily enough, more similar to that observed in men. But, you know, big but here, I guess we need more research. And this is one of the failings of, you know, researching women, where we don't have enough studies that fully identify what one universal menopausal microbiome looks like, and which I guess is fundamentally quite critical to what we're trying to talk about here.

2:56It really is. And what I find most interesting is there are so many inputs that influence the microbiome before women even get into perimenopause. I think about whether or not someone has dealt with a lot of chronic stress or PTSD or adverse childhood events, whether someone's been on multiple cycles of antibiotic therapy, or even, you know, certainly my generation, all of us were prescribed oral contraceptives for every menstrual irregularity known to man before we even think about contraceptive purposes. So I think that, you know, starting from birth, whether we're a vaginal delivery or a C-section, whether we are breastfed or formula fed, it imprints the microbiome.

3:38And we recognize that there are other points or inflection points in a woman's life that have a huge impact on the way the microbiome is shaped. And you very astutely stated, as women navigate menopause, our microbiome start to resemble that of a male. And so I always say that that's not a criticism of men, but that type of microbiome constituency is one that is not necessarily beneficial for women. And I think the more that we understand the microbiome and the inputs that impact it throughout a woman's lifetime, the more we can do to intervene at an earlier stage so that we're not trying to play catch up in midlife, which is typically what's happening.

4:18that when I'm talking to patients or even doing intakes, you know, someone's been on multiple rounds of antibiotics. If they were taking oral contraceptives for 20 years, if there's someone that has high ACE scores, I'm already thinking that their microbiome is a little bit at a disadvantage in midlife. It doesn't mean we can't, you know, provide inputs that can help change the terrain, but certainly speaks to the fact that this is a patient that is going to be set up for probably more autoimmunity and certainly someone I'm going to be taking a closer look at.

4:50Dr Karan: Yeah, I guess actually to your point that you've just made, maybe it's actually less about the gut suddenly becoming more important at 40, 45, but actually that hormonal ecosystem around the gut, which maybe has begun to change in response to some of those lifestyle factors and exposures throughout a woman's life earlier on as well, which is accelerating the change in hormonal atmosphere, which then has a knock-on effect on the microbiome. And to that point as well, people often talk about, and you've spoken about, these accelerated aging, the perception of accelerated aging someone might feel during menopause.

5:27Dr Karan: Why is that? Because I guess it's not one organ changing, but again, the hormonal transition being experienced by almost every organ. So what is really driving that feeling? Yeah. I think it's very bio-individual, Just like I will say to patients that in puberty, every one of us probably had a very different time navigating puberty. Some people were more hormonal. Some people were more emotional. Maybe some women had more acne or more weight gain. Same thing with perimenopause. I think that there are a constitution of symptoms that are associated with the perimenopausal to menopausal transition, things like fatigue and brain fog, certainly digestive changes.

6:05But at the root of a lot of these symptoms are changes to our immune system, changes to inflammatory patterns. There is certainly changes to digestive capacity and a lot of symptoms that I think really point to two or three key things that are happening in a woman's body. We know that irrespective of the degree of hot flashes a woman experiences or digestive changes, that at the basis of aging is inflammation, this process of immunosenescence, that the immune system is aging right along with us, whether we're aware of it or not. I think there's also significant alterations in metabolism. We recognize that women are losing probably 3 % to 8 % of muscle mass that period from 40 to 49.

6:57And I would imagine that if a woman has been very metabolically healthy, has a good amount of muscle mass heading into those years, she'll be on the lower side. But certainly here in the United States, where we have a population that's largely not metabolically healthy, the loss of skeletal muscle mass is really catastrophic. And so we're getting alterations in insulin sensitivity with the loss of muscle mass. as estrogen is, depending on the woman is peaking and declining as we're losing estradiol, we are also losing insulin sensitivity. And so there's multiple things that are coming together that create the perfect storm of that menopausal transition that for many women is as unique as they are, because I can tell you, if you look at the research, the most commonly reported symptoms during the menopausal transition are things like fatigue and brain fog.

7:47There are some vasomotor and hot flash symptoms, weight loss resistance and things like that. But I have women that their predominant symptom is tinnitus, or they have a lot of itching in their ears, or they are experiencing a lot of vaginal dryness and painful sex. And so I think it really speaks to the fact that our bodies, there are some consistencies as these hormones are declining. And I also think that there's a component of bio-individuality that maybe in my traditional training, we didn't speak to this enough. And it's also why some women will feel like the perimenopausal transition is relatively rocky and others will feel like they navigated their 40s effortlessly.

8:29And it's not to place shame or blame on any woman. It's just, I think there are multiple factors that come together. And this is where the lifestyle piece becomes critically important. You know, how you sleep, how you manage your stress, what's your nutrition like? I know you You speak a lot to the nutritional piece. And then, you know, are you exercising? I think those four foundational elements to me have been shown in my practice patterns that those are the four biggest levers that will influence the degree of symptoms that women are experiencing then.

9:00Dr Karan: Yeah, you mentioned a lot of, you know, really important things there about perimenopause space. You're seeing that shift towards reduced lean mass, accelerated bone loss, altered glucose dysregulation, vasomotor symptoms and changes in sleep. And actually this is backed up by a 2026 review that describes perimenopause as a period of metabolic vulnerability with increased risk of visceral fat gain and other changes in lean tissue, all of those things without actually any major changes in body weight composition. But also bearing in mind that there are estradiol receptors in the gastrointestinal tissue.

9:39Dr Karan: And we know that the GI system is such an important powerhouse, not just in, you know, digestion, but nutrient absorption, regulating blood sugar, insulin sensitivity, also via various, you know, gut liver axes and gut immune signaling, someone's immune health, insulin sensitivity, all of those things, it starts to slowly make sense why alterations in the hormonal level and a drop off in the estrogen in that perimenopause stage would also have significant perturbations on almost every organ that's associated with the GI system. Yeah, it's interesting to me that there has not been enough reflection on digestive organs because it explains a great deal.

10:26It explains why as women are navigating a decline in progesterone first, then estradiol, they start seeing changes in smooth muscle contractility. You know, women will say to me, I have more bloating. I have more indigestion. I have more constipation. And constipation for my midlife women appears to be a larger issue. But it's also understanding on the other side that estradiol is important for nitric oxide signaling. And so when you think about declines in progesterone, declines in estradiol, and all of a sudden women are dealing with more bloating and more feeling like their digestion just isn't working quite as effectively, not to mention the fact that estradiol is also involved in bile acid synthesis.

11:12So women are suddenly becoming fat malabsorbed because they're not able to effectively break down fat in their diet. And you being a surgeon, you know this probably better than anyone. We see a lot of propensity for gallbladder disease in midlife women. And I think that it is not just a reflection of our modern day lifestyles. I also think it's these changes in these key hormones that are helping with motility, not to mention the fact that, and I jokingly talk about fiber as the new F word, here in the United States, fiber in some ways has been vilified. And yet I think it's such an important part of the conversation because as our hormones are declining and we're getting changes in short chain fatty acid production, which are very important, potent signaling molecules, fiber becomes an even more critically important part of the conversation.

12:04And so when I have patients say to me, well, fiber helps with bowel regularity. I'm like, yes, it has many, many things. But did you know that our intake of fiber is important for a lot of different things, including bone support? Like there's a conversation always around how women are really at risk the first five years of menopause for increasing osteoclastic activity. So this decline in estrogen just means that there's more osteoclastic activity bone breakdown, but there are actually short chain fatty acids that can be supportive for bone health. And I think that's part of the conversation that when I'm talking to women about all of the changes that are occurring, diversity, inflammatory patterns, more leaky gut, it's also saying, hey, did you know there's a gut bone access?

12:52And that's always an interesting little factoid that I don't think gets enough emphasis. But to your point, there's a larger piece of the conversation that I think the more we can understand about how the gut is an inflection point for the rest of the body, the more that we can understand our bodies and be able to help our patients navigate midlife with greater awareness and also, quite frankly, more targeted support, whether it's nutritional support, supplementation support, helping them understand that taking HRT may, in fact, in later years when we have more research, may be part of the conversation to actually support the microbiome itself vis-a-vis these other components.

13:34Dr Karan: Yeah, that's actually really important because I guess there's a huge level of education needed to, you know, really make the average layperson understand the role of fiber. You mentioned that and, you know, it's linked to the gut bone axis and all these other things, the production of short-chain fatty acids. A lot of people still have this very simplified understanding of fiber that, you know, it helps with maybe stool bulk and regularity, helps you have number twos, but actually that is the least important thing it probably does. All of these downstream consequences of how fiber is fuel for the bacteria and how the bacteria ferment fiber to produce molecules, to your point, which are anti-inflammatory, antioxidant, which can reduce chronic low-glody inflammation, which can have some benefit on bone, have some benefit on the gut lining of a woman in perimenopause.

14:27Dr Karan: So that layer of education is probably in most parts missing. Yeah, I know. It's interesting because I feel like as I was promoting the book earlier this year, I had some podcast hosts that would actually say to me, I love your work. I think your book is great, but we can't talk about fiber. And I thought that was so interesting because I said, if you really look at the research, you would understand that, yes, there is a bio-individual approach. And yes, some of my patients tolerate a lot of fiber, some don't tolerate as much. But if you understand what's happening in the gut as we are navigating the decline in hormones, you would understand this becomes an even critically, more critically important intervention.

15:07Not just the protein memo that I think most of us have heard loud and clear over the last few years, but fiber is equally important, if not more impactful because of all the things that you also astutely mentioned, you know, mucus production, which protects the lining, endogenous GLP-1 regulation, you know, GLP-1 drugs are having this incredible moment right now. And I can't think of a drug class that's probably changing the narrative of conversations more than this drug class, certainly in my lifetime. But equally important to that is this nutritional piece that I think is missing for a lot of people.

15:41We've demonized carbohydrates, at least here in the United States in many ways. But another really essential part of that conversation is speaking to the importance of fiber at a very substantive level. I mean, the one thing I was not surprised by, but I was surprised by as I was writing the book and really looking at the research was for every person that tells me fiber is irrelevant, I'm like, there's far too much research that's suggesting that it is one of the most important interventions that we can do. And when a patient says to me, I don't tolerate fibrous foods, I always say, then what's going on with your gut microbiome?

16:17Because you should be able to. And certainly, you know, life imitates art. And I think for many of us as clinicians, when we're on the other side, you know, I had an instance in 2019 where I spent a protracted amount of time in the hospital, had six weeks of antibiotics, antifungals, my gut was a wreck, but I lived. And so I tell people it took me probably 18 to 24 months to tolerate fiber in my diet again, but it was because my gut microbiome had been wiped out in response to taking powerful antibiotics to save my life. And so I always say that's the point that I always like patients to understand is that when someone states to me that they don't tolerate fiber, my first question is what's going on in your microbiome that has created an environment where you are not tolerating fiber because we should be able to.

17:05Dr Karan: Yeah, because, you know, there's a lot of people out there who are thankfully beginning to understand the values of fiber, but there's still a significant cohort of people who are stuck in this narrative that they're intolerant to fiber. and for me whenever I hear someone say they're intolerant to fiber I always think that that's unlikely to be a problem with fiber but actually something with your own internal gut terrain where you are not acclimatized or your colon is not acclimatized to fiber because of a number of things you know medication associated disruption to the microbiome hormonal factors other comorbidities inflammatory bowel disease where it's just not had the time and the consistent and exposure to fibers slowly over a long period of time where the gut bacteria and the colonic lining have adapted.

17:56Dr Karan: Because even someone who is seemingly intolerant to fiber can probably learn to adapt to that over a long extended period of time. So actually it's about how do we landscape your internal garden first to make fiber make sense. And it's usually a timing and exposure problem rather than a fiber problem. Absolutely. And it's interesting. I will share this transparently. I had some microbiome testing done a few months ago, and I knew before the results even came back that inulin was going to be a problem for me because I have had to, you know, with teeny tiny doses of inulin, targeted inulin. And sure enough, I don't have the appropriate bacteria to be able to metabolize and break down inulin.

18:41And so the recommendation to me was, not surprisingly, I need to kind of build up a tolerance. It's like almost like building a muscle that for many people, they need to build the muscle to be able to properly break down and metabolize certain, whether it's resistant starch or other types of fibers. And for every single one of us, there's probably an N of one where if we were aware of, you know, what it's almost like fertilizer, it's like targeted fertilizer. What are the specific things we need to be adding to our gut so that we are able to tolerate different types of fibers? Because it is that important.

19:19I would say it is top tier recommendations for every single person that I interact with or engage with. In fact, I have adult sons now and we were having a conversation about this the other night and I was saying, it is really important that you are giving your body a variety, not just protein, not just having targeted carbohydrates, but being very specific about phytonutrients and different types of fibers. And I think my 18 year old might've finally gotten the message. But I think for everyone listening, it's just helpful to understand that for each one of us, we might need something slightly different.

19:56And that's OK.

19:58Dr Karan: I want to talk about something that's quite personal to me and about some medical conditions that I suffered from. I used to have high cholesterol and fatty liver disease, and that primarily stemmed from a severe lack of fiber in my diet. And on my quest for finding the perfect fiber supplement over the last few years that could help me add more fiber into my diet, I couldn't find one. that ticked all the boxes that I wanted and the high bar that I set for myself. So it built Loam Science. What I'm most proud of is not the product. I know that's great, but it's the fact that we've run two clinical trials on it, two randomized controlled trials, which is far more than the vast majority of supplements on the market will ever do.

20:33Dr Karan: And we've got even more coming because I'm a doctor first and foremost and a scientist. And I wanted to build something that I could actually stand behind with data and not just rely on good branding. So if you want to understand what's inside Loam Science and why, the science is all on the website and the link is in the show notes. Now, there's a lot of interest in the last few years, especially as the interest in gut health and microbiome has increased. Something specific to women, and it may be relevant to the perimenopause space as well, is the estrobola. Now, this is like a subset of bacteria within the microbiome, which have estrogen and progesterone regulating effects.

21:15Dr Karan: In perimenopause and menopause, we know that there are hormonal shifts which will have knock-on effects on the gut and there may be some changes to microbial diversity. Have you noticed any clinical implications that could suggest that that change in the gut environment in perimenopause would also have some knock-on effect on the gut bacteria which regulate estrogen levels as well? Because could that also explain the increased risk of low-grade gut inflammation and the associated symptoms like bloating, constipation, diarrhea in some cases, and general abdominal pains and issues? Absolutely. The estrobilome is really interesting.

21:56It's this very targeted bacteria in the gut flora that are responsible for breaking down and helping to package up excess estrogen. Of course, I'm oversimplifying this, and this is where the conversation around poop is very important. But I think that the estrobilome is oftentimes this missing link to part of the conversation, because if you are not packaging up sufficient amounts of estrogen and getting rid of it in the body, it can be recirculated. And this can drive a lot of the symptoms that women are experiencing in midlife, brain fog, breast tenderness, heavier cycles, weight loss resistance, constipation and bloating.

22:36for me, it is part of the conversation to make sure that we have a good sense of how effectively we're able to break down estrogen and package it up. I always say package it up like a present and poop it out. The other side of it is if we have too little estrogen that is being recirculated, that can also drive symptoms. So this Goldilocks effect of the perfect amount of estrogen that is excreted versus recirculated becomes a larger part of the conversation because it can drive a lot of symptoms. For women that are experiencing a lot of the symptoms of low estradiol, so you can also have brain fog, but you can have a great deal of whether it's urinary tract infections or painful sex or vaginal dryness or some of these symptoms that are suggestive.

23:26The dry skin, I always say that some symptoms can mimic one another, but on the other side of this conversation is really speaking to the fact it's this Goldilocks effect, wanting to make sure that the astroblum is optimized. But here's the thing that many people don't talk about is that I feel like women in midlife are dealing with aging parents. If they have children, their children are a little older. I always say bigger kids, bigger problems. Maybe they're in a position where they have more work responsibility or they have a terrible commute. So we acknowledge the impact of stress. And so I've seen countless examples of women in midlife that feel like they're doing all the right interventions.

24:05They're focusing on sleep. They're taking HRT if that's appropriate for them. They're eating a nutrient-dense diet. They're moving their bodies. And they're trying to figure out what is the missing link. And more often than not, it's stress. Because chronic stress, as I remind a lot of people, chronic stress is different than acute stress. If you were to measure my cortisol levels and yours right now, we're engaged in this conversation. They're probably up a little bit to keep us awake and alert. However, chronic stress over time can be caustic in the body and it can contribute to digestive related issues, you know, and it can make the strobilome more inflammatory.

24:42It can make a lot of the mechanisms in the microbiome not work quite as efficiently or even the digestive system. So stress more often than not is a larger piece of the puzzle when we're working on symptoms for women. And I've seen clinically a lot of patients that, you know, on paper, they look like they're doing a lot of right things, but it's this chronic stress piece that leads to more muscle breakdown, leads to more leaky gut, leads to more inflammatory patterns that can lead to more digestive issues that we can also see manifesting in the estrobilome itself.

25:15Dr Karan: Yeah. I've come across, you know, a lot of animal and mechanistic work that suggests that estrogen can influence the tight junction proteins, which hold the lining of the cells together that you mentioned before, the mucus layer, that regulation, short chain fatty acids, you mentioned as well, crucial for that, intestinal permeability, the gaps between the cells, and estrogen deficiency in perimenopause could adversely affect those pathways. And I think it's really telling, and a problem really, that we don't have an abundance of human data in the literature that can demonstrate that specific dysbiosis and clinically meaningful changes in intestinal permeability and systemic disease.

25:57Dr Karan: All of that is limited. However, you're seeing this on a regular basis in your clinic. So there's a real discrepancy between what practitioners and experts like you are seeing as a consequence of deranged changes in gut health and perturbations in gut health and the link between menopause and actually going out and researchers testing a cohort of women in perimenopause and menopause, triangulating their clinical symptoms with hormones, with gut microbiome testing in a lab setting. And that's really needed because I feel like right now, obviously, there are all these lifestyle factors you mentioned, you know, stress reduction, resistance training, nutrition, fiber, all those things are hugely important, relatively easy, cheap levers that, you know, people can action in their life.

26:44Dr Karan: But what if we're missing an additional paradigm of helping to treat some symptoms of perimenopause that could be gut derived? Yeah, it's so interesting because when I think back even 10 years ago, and I was doing at that time doing a lot of diagnostic stool testing, and I was like, why is every single woman dysbiotic? I mean, there was varying degrees of severity. But now I fully understand and appreciate that as estrogen is declining, it is just ramping up our propensity for those tight junction separation, leaking food particles into the bloodstream, driving inflammatory patterns, triggering the immune system.

27:21You know, for a lot of women explaining, you know, why are we looking at markers of inflammation that are elevated in midlife? And women are telling me in most instances, they're not particularly symptomatic, but I think that the research is needed and also the greater awareness because I think that a lot of midlife conversations have been whittled down to bone, brain, and heart effects. And I remind people all the time that we have progesterone and estradiol receptors throughout our bodies. It is not just localized to bikini medicine. And I think the gut really is this underappreciated component that is a signaling hub of literally of activity diffusely across the body.

28:02You know, why do we see four to five times greater propensity for autoimmune conditions in midlife women? I think that decline in estradiol and the propensity for leaky gut is driving a great deal of this. And if we could intervene earlier, or even understanding how the influence of antibiotic therapy appropriately used in midlife, there are probably more interventions that we need to do either concurrently or right after antibiotic administration to lessen the net impact on the microbiome itself and the sequelae that come along with that.

28:36Dr Karan: Do you think that association between menopause and increasing rates, as you described, of autoimmune disease, could an element of that be explained by some degree of unmasking that happens when you do get those hormonal shifts and a drop in estrogen and then the negative influence on the gut microbiome and thus, you know, the gut immune axis, there's almost a degree of loss of that protective function. And actually what could have been there for decades has actually just been exacerbated and more likely to clinically manifest where it may be, it was like in a subclinical threshold for a number of years.

29:14Dr Karan: And then the sudden, you know, changes in the hormonal environment fully unmask those symptoms. No, I absolutely think that it can be. And I I think this is an interesting part of the conversation, especially because I've seen so many women that before they even get to menopause, they had psoriasis in their 20s. They had alopecia areata in their 30s. In their 40s, they developed Hashimoto's. And so we know that once you've had one autoimmune condition, so to your point, I think that we can prime that gut immune access to make it much more susceptible. In fact, I would be the first person to say that in a traditional kind of allopathic environment, we were never making those connections.

29:57And it's really been the last 5, 10 years that we acknowledge, you know, it's almost like a series of dominoes. Like the dominoes just start to fall and it creates the perfect environment to have more autoimmunity expressed. And certainly during my training, which now is more than 20 years ago, I think a great deal about how autoimmune was thought about very differently than it is now. And now we've got long haul COVID and chronic Lyme and there's just more and more diagnoses that are coming about. So I think that this midlife transition just opens up more opportunities and more susceptibility to this gut immune access having greater degree of dysregulation when the protective effects, when we think about estradiol as an immune modulatory hormone, the protective effects really fall aside because a woman in menopause or even perimenopause, even on HRT, you're never going to have the heightened response of estradiol like you do throughout a menstrual cycle.

31:04I mean, it really does open up a degree of vulnerability in midlife and beyond for women.

31:09Dr Karan: What are some of the most common signs that you see from a gut perspective, signs and symptoms that you would see when women hit that perimenopause stage? I would say most commonly bloating and constipation. I mean, I do see some alterations. It's also a time when a lot of women are diagnosed with irritable bowel syndrome, which I think about as like a bucket diagnosis. I'm like, that's helpful to a point, but let's look at what's going on. I would say that the proximity of the gut to the vaginal vault is certainly one where we're seeing more vaginal dryness cyclically. We're seeing more chronic, you know, we're seeing more urinary tract infections.

31:48quite a bit of brain fog because there's this enteric nervous system and a communication pathway between the gut and the brain via the vagus nerve. So I would say if there's a lot of inflammation in the gut, it oftentimes will get referred to the brain. So we can see changes in mood. So definitely more depression, more anxiety, more irritability as the alteration in neurotransmitters is kind of happening as these hormones are declining or seeing ebbs and flows and hormones. But those are the most common things. I would also say things like reflux suddenly become problematic for some women that are more susceptible to it, sometimes without a pattern, which can be very frustrating.

32:28And obviously, you know, here in the United States, we're seeing higher rates of colorectal cancer. So when women are having persistent symptoms that are not easily explained, I'm always thinking, what are the things we need to rule out first? And as I tell women screening colonoscopy by 45. But if a woman's having particularly persistent symptoms of bloating, constipation, or diarrhea, or alternating between both of those, and concomitant other symptoms, maybe family history of early colorectal cancer, those are the people that I'm thinking about. We need to rule out something more significant or serious.

33:06And then with everyone else, it's really fine-tuning. But the digestive symptoms, I don't think are talked about enough. And they're frankly oftentimes minimized. They're like, oh, bloating, that's not a big deal. I would say if there's a cyclical pattern to it, then we need to investigate that. You know, if you have a flat stomach in the morning and then you look six months pregnant by evening, there's probably more going on that we need to be looking at. But those are some of the more common things that I'm seeing.

33:31Dr Karan: One topic I'm fascinated by is the gut-brain axis. And that's something that we've covered extensively on this show with many experts. And this is particularly prevalent. There's a particularly prevalent conversation when it comes to menopause, I feel, because, you know, there is a lot of cognitive and neurological symptoms that are reported. Can you tell us what's happening in the body that causes these mental changes and increases in issues like anxiety and brain fog? Yeah, I think sometimes the first symptoms women are experiencing in perimenopause are alterations in sleep, but also concurrently changes to baseline anxiety, but also depression and irritability.

34:10And for a lot of people to understand that progesterone is an example, this very important hormone, which in most instances is the first hormone that we see declining in early perimenopause, is also important for one of our main inhibitory neurotransmitters, which is GABA. And so if the bulk of our neurotransmitters are actually produced in the gut, if we're seeing alterations in hormones, starting with progesterone, we may see more anxiety, depression, and irritability. And thinking thoughtfully on the contrary side of that is estradiol. Estradiol is important for serotonin and dopamine. And so what I oftentimes will see, patients will start reporting a degree of irritability, changes in alterations and sleep patterns, more depression and anxiety.

34:55and something that is a change for them. But acknowledging that a lot of the emphasis, or certainly when I went through my medical training, was that a lot of the drug therapies that are designed to address anxiety, depression, irritability are utilized to function on brain patterns, but actually the bulk of the neurotransmitters are actually produced in the gut. The vagus nerve is an important signaling apparatus in the body, longest nerve in the body. But when I'm thinking about the changes that are happening in midlife, it's acknowledging that if there's a lot of inflammation, so if someone is eating a standard American diet and isn't getting enough sleep and chronically stressed, you know, most of the information, the afferent receptors are going up to the brain.

35:43So when we talk about butterflies in the stomach, and a lot of people say, well, that's just the, you know, that's just the gut. Well, no, actually, it's transmitting valuable information up to the brain. But again, as these hormones are declining, as we're getting alterations in these key neurotransmitters, that can drive a lot of the neurologic and mental health issues, effects that were happening. Not to mention the fact that these hormones are responsible for inflammatory patterns as well and acknowledging how important it can be to talk about lifestyle, to talk about the importance of bringing these symptoms to your healthcare practitioner, because I see a lot of women in midlife, and I'll give you an example, a lot of women who are appropriately prescribed an anti-anxiety agent, or they're prescribed an antidepressant, when in fact, what they actually need is the hormone to be replaced, actually alleviate the symptoms that they're experiencing.

36:37So from my perspective, there's twofold issues. There's changes in hormones that are driving inflammatory patterns. There's also change in neurotransmitter production that can be a reflection of gut health, but it can also be a reflection of these changes in and alterations in hormones and midlife. So there's usually multiple things coming together. And then a third thing is the lifestyle piece, because if we're eating a nutrient dense whole diet, you know, with good amounts of protein, healthy fats, phytonutrient dense foods, adequate amounts of fiber. Ideally, things should be better off than for someone that's eating the kind of standard hedonistic environment that we're living in.

37:19The other thing that I would mention is this conversation around fiber and how when we consume fiber, it's fermented in large intestine or colon. Our body produces these short chain fatty acids. And one of the really important ones is butyrate. Butyrate can actually cross the blood brain barrier. And so kind of reminding people that there's multiple things coming together in midlife that are actually driving a lot of these mental health effects.

37:42Dr Karan: Yeah. And I guess we've covered many of those things already about the levers that someone can use in their life to overcome or alleviate some of the symptoms as it pertains to the gut in perimenopause. How much does that deviate from general gut health optimization information at any stage of life for anyone, man or woman, but also specifically, if you were giving a checklist specifically for a perimenopausal woman to really stabilize and improve gut symptoms, what would that look like? Yeah, I think that's a really important question. I would say that I think midlife physiology lends itself that there are conversations about protein for satiety and healthy fats for healthy hormone production.

38:33Again, satiety, blood sugar stabilization. The fiber piece is certainly an important one. Talking about hydration, I mean, something that is so simple but can influence, you know, dehydration can drive headaches, it can drive brain fog. You know, part of my life I spent in cardiology. And so dehydration was something that was problematic and drive a lot of the energy issues that we see in midlife. Certainly part of the conversation is alcohol. You know, it's interesting to see how the pendulum has started to swing the opposite direction about alcohol, that the alcohol effects, health effects are underrepresented in most instances.

39:12But in midlife in particular, seeing how many of my patients have to change their relationships with alcohol, because alcohol can lead to more leaky gut symptoms, can drive a lot of dysbiosis, can disrupt sleep, can impact blood sugar regulation. So alcohol and changing our relationship with alcohol or having a frank conversation about the health effects of alcohol becomes a larger piece of the conversation. I would say, you know, the ultra processed food piece that, you know, nutrient density becomes certainly more critically important in midlife, you know, maintaining muscle mass, being able to, you know, help promote healthy gut flora.

39:53But the standard American diet and those ultra processed foods with the emulsifiers, additives, you know, sometimes you hear the terminology of frankenfoods, we know that they can be detrimental to health long term. And for a lot of my patients who are dealing with changes in body composition that they're particularly unhappy about, helping them understand that the ultra processed foods that tend to be high in sugar, low in nutrient value, tend to be highly inflammatory, are just not the right constituency for health over time. I mean, it doesn't mean if you're traveling and you have a protein bar in an airport that you're going to derail all your health, but it's the 80-20 of long-term effects of, you know, what ultimately is going to be most beneficial.

40:39So those are some of the high point, the things that I think about become much more important. You know, the protein leverage hypothesis about, you know, hitting those protein needs because we actually need more protein with age, you know, having the conversation about fiber, especially in light of the benefits of fiber, especially for the microbiome, become a larger portion of the conversation. And I would say hydration, alcohol, processed foods become that much more important to have key areas kind of addressed with patients so they understand they can make better and more informed choices.

41:13Dr Karan: Yeah, I think it's really important, you know, is a lot of really enlightening things that you cover with regards to menopause broadly, but also, you know, narrowing down on the gut, because there's a lot of interest in gut health right now, a lot of information about gut health protocols and routines. And whilst there may be some commonalities between a general gut health routine, and the menopause gut and how to alleviate symptoms, such as, you know, fiber, sleep, exercise, all those things. You know, there's some really interesting things which are specific to the menopause gut, which, you know, you cover a lot in your book.

41:47Dr Karan: So definitely urge a lot of people to, you know, pick up and read that. And Cynthia, thank you so much for, you know, just covering in detail, both in your content online, in your book, and in this conversation as well, about the menopause gut, because there are people talking about menopause and there are people talking about the gut, but there are very few people talking about both. And I think you're probably, you know, N of one when it comes to that, certainly from what I've seen. So thank you so much. Thank you. Thank you. I appreciate that. Thanks for having me.