Menopause Was Never Just Hormones

I think in many ways the gut is really the missing link for middle-aged women. And, uh, my kind of catchphrase these days is if you think perimenopause and menopause is just slapping on an estrogen patch, you're really missing out on a much more nuanced conversation.

I am so excited to be back with everybody once again, to have my friend and colleague Cynthia Thurlow here. We have a great conversation about her new book, All Things Female Gut Hormones. She is becoming a thought leader and expert in the field of women's hormones, particularly gut-related. So I think you're really going to enjoy today's conversation. I'm going to talk a little bit about her and then we'll dive right into, um, today's conversation. So for those of you who don't already know Cynthia, who's been on the podcast several times and is a friend of the pod, she is a nurse practitioner, host of Everyday Wellness Podcast, author, and international speaker. She's got over 15 million views on her TEDx her second TEDx speech, which is, which is about intermittent fasting and health and wellness. Cynthia is a globally recognized expert in perimenopause, menopause, intermittent fasting, has been featured on Fox, ABC, Medium, Entrepreneur. She's even got her own Substack, which is putting lots of some really cool information out there. So we'll talk about that a little later on today's conversation, but her mission is to help empower women to live their most optimal lives in perimenopause, menopause, and beyond. And her most recent book, The Menopause Gut: Balance Your Microbiome to Reclaim Your Health in Midlife and Beyond. We're gonna be talking about a lot of topics in the book. Um, today's conversation is interesting to you, you like it, I would recommend getting the book because she takes a deep dive into this. One of the things that I really think is interesting with Cynthia's first book that, um, I had her— heard her explain really well was the idea of how women's hormones change throughout their cycle. And actually during the middle part of perimenopause, beginning part of perimenopause, how actually your diet can change. It was really interesting. I was— it was the first time I actually had seen that in a book and written that, even though it intuitively made sense. So this book, she actually dives into gut health bacteria and actually how your gut health, particularly in this, this, this, this, this timeframe, are super important. So with that, I'm super excited to have Cynthia on the podcast today. And Cynthia, why don't you start? Many of my, my people already know you. Why don't you give us a little background of who you are and how you got from, you know, a cardiac nurse practitioner to now being an expert in women's hormones, and particularly as the gut as it relates to women's hormones.

Yeah, so to give listeners some perspective, I spent 20 years in ER medicine and cardiology, first as an ER trauma nurse in inner city Baltimore, and then later in clinical cardiology until about 10 years ago when I was the typical Type A, had too much stress in my life, worked out a little too hard, probably carb restricted a little too much, had a husband who traveled a lot, had young kids. I hit the wall of perimenopause, and I feel like in many ways, you know, life imitates art. And so for me, I really needed to make a substantial shift in my personal life. And it started with— I loved cardiology. I love everything about the heart, but I felt like I was no longer being challenged, and I was far more interested in talking about lifestyle as medicine. And at the time, 10 years ago, that was kind of unusual. In fact, my Colleagues and peers would say things like, "We have this NP in our practice who likes to talk about nutrition." So I left traditional allopathic medicine 10 years ago, kind of created initially my own little lifestyle as medicine practice, and started attracting women just like myself, women in perimenopause and menopause who felt like the kind of traditional allopathic model was missing the mark for them personally. And so, you know, from that, I created one-on-one programs and group programs. Along the way, I did a couple of TED Talks, which led to some other really cool things happening. But I think for me, understanding the gut microbiome really started in 2018. And I had gone on this romantic vacation with my husband. You know, Morocco was like, oh, we're going to go to Morocco and southern Spain. My husband and I ate the same food. And guess what? One of us got violently ill and the other one did not. And I don't think at the time I understood the dynamics that were happening with a decline in hormones. Even though in 2018, I was 47, it's understanding that at that stage, I was probably on the kind of the slow train to menopause. So when I got so violently sick, when I was exposed to what we arguably would believe now is probably Giardia that stayed with me for a few months and then led to a lengthy hospitalization, a lot of those reactions that my body had were really in the setting of less estrogen, the impact on the immune system, the impact of, you know, probably a large bolus of endotoxin, which is what caused the kind of reactive symptoms that I was experiencing. And so, that was the first clue that maybe, maybe there's more to perimenopause and menopause than we were originally taught. It's not just about bone health, brain health, heart health. It is really a multi-system impact of this decline in hormones and neurotransmitters. And so, that was the first kind of like, Okay, this is unusual. And then, you know, working with patients and looking at diagnostic testing and understanding that why am I seeing changes in inflammatory patterns, even at a gut level? Why am I seeing so much, so many more issues with digestion, as well as detoxification? And no, we're not talking about a program in a box, we're talking about the actual ability detoxifying our bodies. And so the more that I got curious, and the more people I brought onto the podcast, it just reaffirmed for me that there are dynamic shifts in the microbiome and the gut overall that are impacting how well we feel or do not feel. And it also explains why— and I'm sure you hear this in your practice, across social media, in our DMs, on our podcast, in clinic— people will say to me, I'm sleeping, I'm managing my stress, I'm eating a healthy diet, I'm exercising, I'm on HRT, why do I still feel bad? And so, I think it just brings another— I would say it's like this onion, we're peeling back a layer to better understand what's happening in our physiology. And, I think it really speaks to this kind of more nuanced conversation that is more than just replenishing hormones. It's a bigger conversation than that. [Speaker:AARON_HARTMAN] Yeah.

Well, I think it's interesting to the point, it used to be that when you talked about cutting-edge female hormone stuff, it was simply hormone replacement. It was your thyroid's off, take your your Nature thyroid, your compound thyroid or whatever. Your adrenal's off, take your glandular extract or whatever. Your hormone's off, slap on a patch. And that worked for 10 or 15 years, but then realized, oops, there's a next level. Then we kind of— next level is there's this hierarchy. Let's focus on, you know, balancing all hormones, not just one. And then I'm actually referring to this now as holistic hormonal health because it's like realizing it's not just hormone replacement or hormone optimization, you have to look at the whole picture, which that gut is literally at the whole entire, entire base of it. And I love what you said, a program in a box. I'm like, oh my gosh, like that is like all the rage, right? Everybody wants the quick fix, like the thing that worked for the last 30 people or whatever. And in this world that you're kind of referring to, you have to find out what works for that person in front of you because everybody is so different. I'm afraid you actually use the, the middle pause shift, the middle pause. I love that middle pause, you know, cuz this is a transitional phase, right? Yeah. So why don't you talk about that, this middle pause microbiome shift, this middle pause change that is over, like, is this over a month or is this over a year? Or how long is this?

It's, you know, 5, 10 years. And here's the thing, when I was writing the book, I got tired of writing the perimenopause to menopause transition. It was just such a mouthful. That we kind of came up with middle pause, because I was like, "Okay, this speaks to what's happening, and we don't have to keep saying this like a long phrase." So before we even talk about what changes in the absence or decline in hormones, it's important to kind of identify what the gut microbiome is, because people, they understand where their stomach is, hopefully. They understand where their brain is, their heart, but the microbiome, people are like, "Where is it?" It's 40 trillion bacteria, viruses, fungi, and protozoa that are contained in the large intestine or colon. And I would make the argument that this is the key longevity organ that no one is thinking about. It's kind of like the dark horse in the back, but it really should be at the forefront because it interfaces with every single organ system. There's a gut-ovarian axis, there's a gut-brain axis, there's a gut-bone axis, et cetera, et cetera, et cetera. And so, as we are seeing this decline in hormones, in particular estrogen, that's probably the hormone we know the most about, and really speaking to estradiol, our predominant form of estrogen that our bodies make prior to menopause. With this decline in hormones, we start seeing changes in diversity. So, the types of beneficial bacteria decline. We see an uptick in inflammation. We get changes in the immune system. We get an uptick in autoimmune cases. So, 80% of autoimmune cases are women. We get a 4 to 5 times exponential increase in menopause. So, there's over 100 autoimmune conditions now. And I always say, like, the two kind of new kids on the block are chronic Lyme, and long-haul COVID. But, you know, back when you and I trained, we probably thought there were 20 or 30, and now there just seems to be an explosion of autoimmune conditions. We get a reduction in short-chain fatty acids. And for anyone out there that thinks fiber's irrelevant, I'm going to make the argument today that fiber is really, really important as we have a decline in hormones. And that's just a starting point of things that are happening. I think for a lot of people, they think about the decline in hormones through the lens of bone health, brain health, heart health, and that is really important, or the physicality of the changes that are happening. We start seeing more wrinkles, our skin will age, or it might sag, all things that I think most women kind of get irritated about. But at a very fundamental level, that microbiome is changing so dynamically. The health of the microbiome impacts when we go into menopause, it impacts our bone health. I think a lot of people don't know that. It impacts our mood. It impacts whether or not we are able to fight off opportunistic infections. I mean, there's a lot that goes on, not to mention the fact, you know, when the immune system kind of starts to unwind, we use the term immunosenescence, which is the big fancy way of saying aging of the immune system. When that's happening, that has potentially really catastrophic effects on the body. When women will say to me, "I don't need HRT, I feel great." What they don't understand is if you were to look beneath the hood, if you were to look beneath the surface, there's so much inflammation that's starting to happen in the absence of key hormones, key neurotransmitters that, you know, long-term can have a huge impact on how we age. And aging well or not has a lot of impact on, you know, how we're going to feel moving forward.

Yeah, one thing I think is really key and important with this is talking about it. You know, my wife is, you know, you know my wife and, you know, I'm collecting this group of patients in this age range. And the recurrent theme I'm hearing over and over again is no one told me how much, how hard this was, how difficult this would be. And I, and I think, and I wanna come around this, this idea as you're transitioning. It's interesting how, like I, I say that women's estrogen is their, is their superpower. Estrogen allows you to have like 3 careers, raise a family, not sleep, like all this, you know, do it all right. And then you— but high cortisol, right? You get a little insulin resistance. The stress affects your gut microbiome. And then all of a sudden, you go— you lose your superpower, and it's almost like things fall apart. And it's this thing where, okay, if you're gonna keep on going at this rate or speed, which I usually encourage people to reassess their life, you know, to keep on being healthy and thriving for 30 or 40 more years, you can't just— you have to actually address the insufficiencies of some of these hormones. That are, that enabled you to do what you've done for the last 30 years, not make your levels like you were when you were 20, but at the same time, acknowledge that something has to happen, you know? And yes, you know, 30% of women in their 70s have a normal testosterone level. Yes, there are some women who might not need it, but you know, it's probably a, a majority. What are your thoughts about that?

Yeah, no, I, I think that perimenopause is a litmus test. And when I say a litmus test, the adaptive patterns that we learned as teens, 20s, and 30s. Suddenly become maladaptive with those decline in hormones. Because I know plenty of very successful women that got to perimenopause, and literally the wheels fall off the bus. They no longer can cope. They struggle with mood. They don't have the same energy. They don't have the safety net that those hormones created for them. And so, the way they perceive the world changes dynamically. I was certainly one of them. I think for a lot of women, especially women that experience quite a bit of adverse childhood events, which I'm sure your listeners are very familiarized with, I feel like the veil of perimenopause is lifted. And all of a sudden, the people pleasing needs to go away. With the changes in estrogen, women become a little less agreeable, and that's a good thing. And on the other side of that, it's— if you have stuff you have to deal with, you legitimately have to deal with it. Because with those declining hormones, even if you're on HRT, the way you view the world has changed forever. There was a, a Substack that I did earlier this year that went viral, really picked up a lot on social media. And I was sharing some very private things in that Substack, but I was also saying we have to find this reframe in middle age because a lot of those adaptive patterns that we used when we were younger, you know, the being able to push through, being able to focus, being able to get away with less sleep, not really managing our stress, 'cause I certainly thought I did, but I really didn't. You know, getting away with, you know, sometimes more processed foods, maybe you're drinking alcohol, maybe you're doing too much of intensity of exercise, you know, maybe having some toxic people in your life. All of a sudden, perimenopause forces you to deal with a lot. And I think that's what makes, they call it the zone of chaos. I think that's what makes perimenopause challenging, because for a lot of people, everything that they used to do is no longer really working for them. And it can be very hard to not only change, you know, at a very basic level, your lifestyle choices, but also like your relationships. I mean, I think 70% is the statistic I read, 70% of women initiate divorce. And I suspect there are a lot of divorces that happen in perimenopause and menopause. Let me be clear, I think there are some people who don't have healthy, happy relationships and need to end them. But I think there are equally amount of people that just don't have the communication skills or don't have the ability to articulate what they're experiencing. Plus, maybe they have a partner who's trying desperately to figure out what's happening. And there's this kind of mismatch of communication that then leads to more kind of interpersonal challenges. And so I think it really is a time in a woman's life where it gives them an opportunity to change a lot of things, maybe not the things you want to initially, but allows you to live a life very differently than maybe you did in your 20s or 30s. I know for me, in the past 10 years, I don't recognize the person I was 10 years ago. And I mean, that is a good thing. Like, I think I'm a much healthier person now than I was back then. But that's also, you know, you rip away the hormones and you change the neurotransmitters. And everything that you look at, whether it's physically, spiritually, psychologically, everything changes dynamically.

I love that statement. You said first on the litmus test, I'm gonna start using that actually. I'm going to, okay. I'm going to, I'm not going to ask for, I'm going to ask for forgiveness, not permission. I'll quote you. So you watch the podcast, but it really is a litmus test. It's like, if you're doing everything right and you go through menopause, then it's going to be a change, but it's not going to be catastrophic. And if your, your gut's not quite squared away, your cortisol is not quite where it needs to be. Your sleep's not great. You're not exercising at all. Then all of a sudden it's like a litmus test for what's really under the hood. I like that because I think that reframes it, not like, I need— oh, the patch is not working, I need a cream. The cream's not working, I need a pellet. I'm not working with the right provider, I need to get the super special person. I need to get the program in the box. It's like, oh, another phrase I love, because that's what people look for. They look for the magic fix.

And I mean, and it's— I'll be honest, I mean, if you were to ask my husband, because he knows me probably better than anyone, uh, how much has changed about my life in 10 or 12 years, I mean, it is a radical, and it wasn't that I was super unhealthy before, it's just, as your physiology is changing, you have to adjust your lifestyle, you must. I think I was someone that got away with many years of not enough sleep. I had a super stressful job. You can imagine clinical cardiology, I'm dealing with emergencies, and our NP service that worked within this very large practice in Northern Virginia, we had a lot of autonomy. So we had, you know, the physicians treated us more like residents, and so, and I say that respectfully, They really gave us a lot of autonomy and that was great, but it also meant with a lot of autonomy, you have a lot of responsibility. And so add that, little kids, husband who traveled a lot, and it was like the perfect storm for a bit of chaos in early— well, maybe I was not even early perimenopause, maybe that was mid-perimenopause. But for me, I think for so many women, they're like, "Wait a minute, you mean I have to sleep more? I don't want to do that. What do you mean I can't have my alcohol anymore? I don't want to do that." Or, you know, all of a sudden, like, no, you can't have 5 cups of rice with your dinner. What?

What?

What do you mean? So it's like, I think we have to find the reframe, Aaron, because if we don't, we will look at these changes as negatives. And I see them as positives. I think we really become the people we are meant to be in middle age because we are stripped of a lot of the people-pleasing tendencies that women— think about estrogen as a people-pleasing hormone. Like, why was I such a good NP in this practice of mostly men? Because I was such a people pleaser. Whereas now I'd be, I'd probably be arguing with them all the time, not arguing, but I'd be disagreeing with them. I'd be less agreeable.

So you're dropping tons of cool nuggets and I love that menopause transitioning, like you're the idea that the person you need to be, but at the same time, like you have to adapt and this is your body's natural time when you are supposed to adapt. Do you take advantage of it to prepare you for the next 30, 40, 50 years? If you don't, you might not have 30 to 40 or 50 good years. And I wanna use that as a transition to this whole idea of the gut microbiome diversity. For people who don't quite know what that is, it's just literally your gut bacteria are an organ. The bacteria in your gut are as metabolically active as your liver. And we've known for years in research that when you take animals and, and sterilize their gut, they get more cancer, they die younger. And so now one of the newer things is realizing that ultimately your gut microbiome connects to like everything, you know? And so, and you're taking that angle and saying, this is how it has an, you know, yes, it affects brain. Yes, it affects heart. Yes, it affects bone. Yes, it's an organ. Yes, for detoxification. Yes, 30% of all drugs are detoxified through your, you know, your gut microbiome, et cetera, et cetera, et cetera. Talk to us about the loss of diversity, which does, which speeds up during this thing. And how that can play into dysregulation or chaos with your hormones.

Yeah, so I think it's interesting. There's a very important part of the microbiome. I didn't name it. I'll just preemptively say this. It's called the estrobolome. I was being interviewed by someone the other day and they called it the estrobolomi. And so every time I go to say this word now, I have to catch myself because that is such a beautiful way of saying the estrobolomi. The estrobolome is this estrogen processing center of the microbiome, it is heavily influenced by lifestyle choices. And by that, I mean, if you were eating a nutrient-dense diet, you manage your stress, you exercise, that Goldilocks effect, not too much, not too little, you're sleeping, your microbiome is going to be imprinted a little differently than the standard American diet patient who's sedentary, doesn't manage their stress, maybe drinks too much alcohol, maybe they also smoke. And they're obese. But it's important to understand the estrobolome is designed to be able to, you know, through the liver and then the gut, break down things that we're exposed to into water-soluble compounds so that in, you know, the next step in the detoxification process is the estrobolome. So, where we would package up estrogen, I'm going to oversimplify it, it's like we're packaging up a present and then our body, we want to eliminate it, we want to poop it out of our bodies. But what can happen in the setting of toxins, stress, garbage diets, like most processed foods, exposure to endocrine-mimicking chemicals, it can make it harder to get rid of the excess estrogen, and it can get recirculated. It goes back into the enterohepatic circulation, gets recirculated. And here's the key, I would make the argument that a lot of symptoms women experience in perimenopause and menopause are a reflection of the health of the microbiome, because if your microbiome is not optimal, if that estrobolome is not functioning properly, if you can't package up the extra estrogen and poop it out, it gets recirculated. Brain fog, breast tenderness, weight loss resistance, skin manifestations, mood disorders, all of which can be magnified. So, I look at it as another little another ability to show me like how well is your microbiome, how well is it functioning? And we can look at lab work to get a sense of that. But I always say symptoms will drive, will drive most of the direction in which we go based on what they share with me. But I think for a lot of people who are really, really struggling, it's a sign that detoxification patterns are not optimal. and that estrobolome, the health of the estrobolome may not be optimal. The other thing that I think is interesting is that with the changes in diversity that you mentioned, and I mentioned, we tend to see a rise in dysbiotic organisms, which is just a fancy way of saying weeds in the garden. So we plant beautiful fruits and vegetables, and what grows up in between, sometimes inflammatory dysbiotic organisms that can lead to more symptoms, worsening of the symptoms I just mentioned, vasomotor symptoms, hot flashes, And we know based on research, the women having the worst vasomotor symptoms, hot flashes, are also at higher risk for cardiovascular disease. So I don't look at that as being benign. I'm not saying, you know, you go through the transition or you're in that time and you have some hot flashes, but if it's persistent, that is a sign that there's probably more to what's going on than just, oh, your hype, your hippocampus and hypothalamus are trying to send signals to your body in the absence of estrogen. And that is what's driving— that's the working hypothesis of why you're having these symptoms. I think it speaks to larger issues like loss of insulin sensitivity, etc., inflammation.

Yeah. And with, you know, inflammation, you know, inflammaging, the idea that as you get older, you get more inflamed. You can actually, in women particularly, watch their sed rates creep up every decade from the 40s and 50s on. You can watch D-dimers. Which is a marker for increased clotting, which skyrocketed with COVID Actually, every decade after 50, the new normal goes up. And one of the things that's really interesting is that the effect of the gut health, the microbiome on actually controlling this, and then how hormones, if you, they aren't balanced or adequate, it just drives that whole thing forward. And what we learned with the whole Women's Health Initiative, which we misinterpreted and undertreated women horribly for 20, was 23. Years is that taking these things by mouth, the wrong kind, actually makes all of that worse. So could you talk about that a little briefly? Like, because we got that kind of wrong in the wrong way where we— let's use, you know, Prempro.

Oh yeah, pregnant mare's urine for anyone who doesn't know.

Yeah. Yeah. By mouth. Yeah. By mouth. And oops. But that was actually a big part of that was the gut microbiome and liver detox stuff that drove metabolites. That was the, the elephant in the room. This is why hormone replacement is bad with this stuff versus now we know, you know, the exact opposite. If you use hormone replacement accurately, lowering the risk of heart disease, 50%, lowering the risk for dementia, 35%. So like, and the, and the key is like the type, the gut, the mouth, the liver. So could you just talk about that nuance? Cause I feel like that's something that's was lost in the whole fray of the FDA changing back November and. No one's really talking about why was it that one thing was horrible and now one thing is amazing.

Well, and it's interesting. So, let's talk about synthetic versus body-identical bioidentical hormones. So, Premarin is pregnant mare's urine. So, it's conjugated equine estrogen. And yes, years ago, that's all we had. So, I'll just put it to you that way. And when we say Prempro, we're talking about not just conjugated equine estrogen, we're also talking about MPA. So, it's a progestin. It is not body-identical progesterone. It is not body-identical estradiol, versus oral estradiol therapy or transdermal estradiol, very, very different. And, it's interesting when we looked at the arm with conjugated equine estrogen, that was very different than the arm that was looking at Prempro, which was the combination. They actually think it was the combination, the progestin, that was driving a lot of the negative side effects that we were seeing. But, anytime you take a drug, and whether it's synthetic or otherwise, it goes first pass. We use the term first pass. So it goes to the liver where it has to be broken down. And it's interesting that when you look at whether it's oral contraceptives, which are dosed at higher doses than hormone replacement therapy, synthetic hormones, and certainly I learned a lot of this from Dr. Felice Gersh, who I know we both hold in high regard. She was the one that first told me that when we're looking at synthetic hormones, and by synthetic, I'm talking about the non-body identical, they can change the landscape of the gut microbiome. So, they go to the liver, they're broken down, and then the microbiome, and we just talked about the estrobolome, the microbiome is expected to utilize this medication and either send it to wherever site it's meant to go to. So, obviously, depending on the individual, and we're talking about conjugated equine estrogen versus estradiol, we know that estradiol can be better for some individuals for lowering cardiovascular disease risk. It's a weak PCSK9 inhibitor, which I learned from our wonderful friend, Dr. Tom Dayspring. So, for some people that have elevated LP(a), that can be better. But we know that taking body-identical hormones is going to have a favorable net effect on the microbiome. And the research definitely demonstrates, if we look at a pre-perimenopausal woman, perimenopause, and menopause, the early— the younger women, and the menopausal women or postmenopause women, if they're given HRT, body-identical HRT, their microbiomes resemble one another. So, it's really understanding that when we're using estradiol and progesterone, which our bodies can utilize and effectively use properly in the microbiome, it can reestablish diversity, reduce inflammation, help with the immune system, and estrogen and the immune system go together. And I hate this analogy, but I'm going to use it. They go together like peanut butter and jelly. When we're thinking about the small intestinal lining, and I just want to dovetail this into this conversation, if you're looking at the small intestinal lining, it's one cell layer thick. So you can imagine it gets damaged pretty easily. Chronic stress, alcohol, antibiotic use, et cetera, et cetera. But as estrogen's declining, all of a sudden this brick and mortar lattice system, the estrogen is the mortar, And as the, uh, the estrogen's declining, all of a sudden it opens up these tight junctions. And so this is when we see this provoked immune response, underlying food sensitivities get worsened. And so when I'm thinking about the microbiome and helping people understand the net impact of the Women's Health Initiative, these two separate arms looking at non-body identical hormones versus what we're using now, the research is certainly suggesting that hormone replacement therapy will be as beneficial to the microbiome, we're just not there yet. Like we don't have this, you know, primary prevention, but we don't— but everything that I looked at as I was writing the book, it just reaffirms that this is another area of medicine where we're going to see significant benefits. Now, do I know what that level of estradiol needs to be in your blood? I don't. Just like we don't have 100% certainty about for brain protection. But I think for a lot of people, we're going to see improvements, less autoimmune conditions, less leaky gut, less inflammation, less inflammaging, restoration of these short-chain fatty acids, which are really important and why fiber is so important. So, to answer your question, our body, when we didn't have options before, conjugated equine estrogen was what was given to everybody. That's Premarin. Prempro is different, certainly based on research. And that's why I think these body-identical, bioidentical options are superior and we're going see improvements in changes in the gut microbiome that are going to be quite substantial enough that we're going to have— I think that in my lifetime, we'll have like a primary prevention of, you know, for gut restoration, we're going to say that you need, you know, estradiol levels to be X in order to confer the benefits, just like we know with bone health now, it's like 60 to 100 picograms for bone protection. I know I went off on a little bit of a tangent, but hopefully I answered your question adequately. But something that's really important because I think there's still a lot of misunderstanding about the WHI. I think there's still a lot of women that get confused. They're like, oh, I met someone the other day, actually it was a realtor, and she said, "Yeah, my doctor has me on Premarin." And I said, "A what?" "Just Premarin." I said, "Do you have a uterus?" And she said, "Yep." And I said, "You need progesterone." Like, what?

That's malpractice. Correct.

I just said, "Oh goodness, we need to get you connected with someone." ASAP.

Whoa. That's, that's literally, that's literally malpractice.

I was, I was kind of like, are you sure? Are you sure they don't have you on like Prempro? Nope. Premarin. I was like, oh wow.

Um, so in, in our world and in this integrative functional medicine, cutting edge, whatever you want to call this world, like we're starting to realize this idea of leaky gut, endotoxins, like we've known about in the autistic world for, you know, 20 years now, you know, now we've learned about in the post-concussive syndrome world, you get a concussion. It gives you leaky gut, these things called endotoxins, which are basically the toxins around bacteria in your gut are released and it just causes immune chaos. Um, you actually talk about in the book, and this is actually something that, um, I, you know, you read so many things and you, after a while you forget what you read or what you forgot. Right. But this is the first time I feel like I've read this 100% makes sense. I mean, makes 100% biological plausibility, but it's the first time I feel like I've seen it written. Like the leaky gut, worst thing in menopause, and the part of like the microbial translocation, like the idea, the bacteria coming, more of this inflammation, bad stuff, endotoxins that can drive dementia, that can drive heart disease, that can drive emotional things. Now we're realizing inflammation and depression, anxiety are big things. Maybe, just maybe hormones. And I'm just thinking out loud here with this thing. Maybe this is one of the reasons why women will feel so much better. All this, but could you just talk about that? Because this is the first time I've actually seen that written somewhere that I recall. And this is a really huge— I don't think people realize how big of a concept this is. Like, this is in some ways a game changer for a lot of women.

Well, and I think, you know, we really speak to how women feel like they are not themselves in perimenopause and, you know, eventually in menopause. And I think we're really speaking to these dynamic changes that are occurring in the microbiome itself The fact that we're so much more prone to leaky gut. And I think when people hear that term, it's like understanding like that small intestinal lining is one cell layer thick. It is so easily damaged. And it's damaged by like chronic stress. Like who doesn't have stress? Like I don't know anyone. Who hasn't had, you know, a round of antibiotics appropriately dosed? And I wanna be really clear, antibiotics saved my life. And so I always say like, I will bow at the temple, but we will acknowledge that more often than not, people are prescribed antibiotics inappropriately. But you think about, with this decline in hormones, and these alterations in diversity, and this kind of predilection and propensity for just being more inflamed, more provoked, more irritable, like everything about the digestive system just becomes irritable, it's cranky. It's kind of like, I have a dog that's 14, and we just say, "He was born cranky." It's kind of like, I think about the digestive system very similarly, that we are just more likely to deal with more alterations in neurotransmitters. And for anyone that's listening that's not familiar, the decline in progesterone will impact GABA. And GABA is this main inhibitory neurotransmitter. It's the neurotransmitter that makes us feel calm, makes us feel relaxed. And if we are a culture where most of us are not, you know, in a balanced autonomic nervous system, we tend to run a little Type A, we are more sympathetic dominant, I think it probably is a little harder for people, and I speak from personal experience, as progesterone is declining, you lose the ability to not feel quite as anxious, not feel quite as depressed, not have the issues with sleep. And we know that if you're not sleeping, that impacts your microbiome, that impacts your ability to make good food choices, that impacts your degree of irritability. On the other hand, we have progesterone, which— excuse me, we have estrogen, that impacts serotonin synthesis and impacts dopamine and other neurotransmitters. And as that's, you know, it can be 20 to 30% higher in perimenopause. And what's interesting is that can be both good and bad, but when it comes back down, women feel very irritable. They're like, "I'm irritable, I'm not agreeable." So, you add in the cumulative net effects of alterations in leaky gut and the provocation of leaking not just endotoxin or, you know, provoking cytokines, these inflammatory molecules, the interrelationship between the gut and the brain. So really understanding the vagus nerve, it's the wanderer, it's the longest nerve in the body, but it's constantly relaying information. So if your gut's inflamed and you're dealing with leaky gut, you're probably dealing with an inflamed brain, you're probably dealing with some degree of leaky brain, and it goes back and forth. So I think in many ways, we think about things very compartmentalized still, even in this kind of hormone space that I'm just going to prescribe the hormones, I'm going to replace the hormones, and that's going to fix everything else. And so what we're really speaking to is a more nuanced conversation that for everyone listening, it might mean different interventions to get people to feel like their brain's less inflamed, to, you know, be able to, you know, alter not only the terrain of the microbiome itself, but understanding that If the gut's inflamed, it's going to impact how your bones are. I think a lot of people don't realize that the quality of the gut microbiome impacts bone health because we, you know, it impacts osteoclastic activity, impacts when we go into menopause. I think that's another thing people don't think about. And so I think of it as a domino effect, Aaron Hartman, that it's never just one thing. It's many things kind of coming together that can worsen symptoms and do so in a way like Again, it's this nuanced conversation. I wish it was just as simple as I give you at least 2 hormones, maybe 3 or 4, depending on like what your thyroid's doing. But for a lot of women, it's the cumulative long-term effects of multiple things that will impact, you know, their perception, how they feel, and not just how— when I say when they— how they feel, how they feel physically in their body, but also how they feel emotionally.

I think also one of the things is just for women to listen to their body, to trust their intuition, to trust their gut. You know, one of the things I've learned from my patients, and it's one of these nuances I think plays into some of the stuff you said in the book here, and I didn't— this is something I learned from actually patients, is that, you know, progesterone, for example, I have some patients who they cannot tolerate any progesterone whatsoever at all. Like the smallest touch makes they feel horrible, they feel awful. And then you put it on topically and it's just like Wow, this is nice. And then you have to control the doses, but it's an interesting thing. Like, well, why is— and we're, we're, I was trained, you know, you do by mouth because it breaks down into pregnenolone and that helps you sleep and it breaks into metabolite that protects your breast. So this is the ideal way to do it, but there are a significant number of patients I've had and it tends to be my high stress, high producer, you know, women who've got, you know, lots of stuff going on, which everybody does. And they, it's interesting. What's the, what's the difference? What's, how the gut bacteria are interacting with that oral progesterone, which you need, versus the topical, which is bypassing that whole thing. What are your thoughts about that concept?

Yeah, no, I think there are definitely, I would say easily 20 to 30% of patients are sensitive or just intolerant. And it's interesting, there's existing research that's coming out about intravaginal progesterone, which is closer to the uterus versus intrarectal, which we know it has a greater, greater absorption. And that's a whole separate conversation. But I do think there are absolutely women that progesterone has the opposite effect, that they get stimulated, they don't feel sedated, it makes them feel irritable, they feel cranky. I had one woman who said she took 100mg of oral micronized progesterone, not even the Sustane release stuff, and she felt drunk. She said, "I don't know what happened. I took it before bed, I woke up the next morning, And it was like I couldn't open up my eyes. I was so sedated. So, I think there are definitely people that are much more symptomatic. And do I think that the microbiome plays a role? Absolutely, because that is kind of a main site for metabolism of hormones. We get that, again, the first-pass effect in the liver, and then it goes to the gut to be able to be broken down and absorbed. And I think that there are definitely people that— and this is that bio-individual approach. That, you know, maybe these people were gaslit years ago, and they don't realize that, you know, it's just their own bioindividual response to the hormone. And maybe when we optimize the gut microbiome, they may be more tolerant, or maybe that there's someone that needs like 25 milligrams or 50 milligrams, or we do a different route of administration to see how they feel.

So I'm gonna switch gears just a smidgen and talk about ovarian aging, because that's something as well you talk about in the book and them being like the time clock and then the whole idea of mitochondrial density and ovaries and which is getting super scientific. Like, I think I lost half my audience here. Oh, could you talk about that? Because you talk about the concept of your ovaries as being like literally the clock and you combine it with the idea that because of energy production mitochondria and how important that is. And then all of a sudden that's— now we're talking about environmental medicine and toxins and stuff. So could you take what I just said and unwrap that for us?

So, when we're talking about ovarian senescence, and so it's this concept of our ovaries are the most mitochondrial dense organ in our bodies, and they are aging right along with us. You know, unlike men who replenish sperm, I think if memory serves me correctly, every 72 hours, we are born with a finite amount of eggs. There are definitely things that will age our ovaries faster, and these are probably not surprising. Smoking will decrease blood flow. Toxin exposure. So I don't think just about alcohol, I think about endocrine mimicking chemicals, I think of the impact of chronic stress. And so there's solid research talking about individuals that experience, you know, high ACE scores, how that influences when we go into menopause. And it's, it's interesting because the research is so solid about this gut-ovarian axis, the health of the microbiome heavily influences the health of those ovaries. And so it really just affirms for me that it is not just one thing that impacts when we go into menopause. Yes, there's some genetics, obviously, but I think for a lot of it, and, you know, there's some racial influences by far, like Southeast Asians tend to go into menopause a little bit earlier than African American and Hispanic women. But I think on a lot of different levels, there are things that we have control over. And so lifestyle choices, environment, toxin exposure, can all influence dynamically, not just the health of the microbiome, but also that kind of gut-ovarian interaction and interplay. And the thing that I found so fascinating when I wrote the book, I actually found it incredibly disturbing, was that when you look at the research of high ACE scores and how that impacts metabolic health and disorder relationships with food and, you know, autoimmune conditions, it also influences when we go into menopause. So it really speaks to how stress rewires the autonomic nervous system. And it also speaks to the fact that cortisol, which, you know, it's a good hormone, it's an important hormone, but just like most hormones, it's the Goldilocks effect. So too much cortisol over time is catabolic, leads to a leaky gut. We also know it can be caustic to those ovaries as well as the microbiome. And so I think that we're going to learn more about how these factors can influence ovarian aging and the microbiome vis-à-vis one another. And I think about how many women I know that went into menopause not at 50 or 51 or 52. The women that go in in their mid-40s, late 40s, a lot of them are thin, high-achieving women. A lot of them had very stressful careers. Like, I think of OB-GYN colleagues of mine, ER medicine colleagues of mine, people that do EMS work where they're up all night. You get a lot of circadian disruption. And so I find it fascinating that this is something— this research is evolving, but it's certainly really compelling. So ovarian aging can absolutely be influenced heavily by the health of the microbiome. So we have some control, maybe not control of everything, but a lot of these factors we do have under our control.

Yeah, but I think it's just important because, you know, we're seeing At least clinically, what I'm seeing, I've been doing this for 25 years now. It just seems to be a trend that women's cycles are starting younger. You know, I think mid-1800s average age of starting your cycles was 16. And when I was in high school, it was 14, and medical school was 12. And now in some ethnic groups, you know, 9 to 10. The American Pediatric Association is now saying, yeah, it's okay. African American young ladies, 10 years old, that's normal. And then, so we're seeing cycles starting earlier and then we're also seeing going to menopause earlier. And it's like, if the ovaries are this clock, so to speak, you know, what would be putting the clock back? And that's where all this environmental things. And it's really interesting as well when I was doing my OB training, just to see like how the, they, they've recognized that the vaginal microbiome has changed over the last 50 years from when colonizes the vagina that covers the baby, that the baby swallows. That passes on this microbiome. So this is something that's not just, you know, for menopause, but it's also for the next generation. It's, it's, it's actually a, a big deal. You literally pass on your microbiome to your progeny and it's gonna, it might be setting them up potentially for when they start their cycles or stop their cycles.

Yeah. I mean, it's interesting cuz you would look at, we get imprinted at birth, whether we're a vaginal delivery or a C-section, whether we're breastfed or bottle fed, formula fed. And then, you know, we get this next dynamic shift around puberty. Not surprisingly, I think everyone would not be surprised by that. The influence of rises in testosterone for men, influences of testosterone, estrogen, and progesterone, and whether or not a woman has a pregnancy, dynamic shifts. And then the next big kind of wave is perimenopause. What I find interesting is the research when I was learning about the microgenderome, which was a new term for me. It was speaking to the fact that in menopause, a woman's microbiome starts to resemble— so it's like life comes full circle. The woman's microbiome in menopause starts to resemble a male's, but that's not to our benefit to have those alterations. And so I think it's really interesting how these alterations in hormones— men, it's not nearly as dramatic. Andropause is a little like a slow, steady decline, whereas women, it's kind of like you get shoved off a cliff and then you're expected to acclimate. I think it's really fascinating how these hormones influence what we're doing. And what I find interesting, I'm getting ready to interview a fertility expert this afternoon. In her book, she was talking about how, you know, a lot of women are labeled that have infertility, that have luteal phase defects, or they may have some ovarian dysfunction. And she's talking about how even if they're in the absence of PCOS, how these women probably inherited that. That is probably something that was inherited. If people go back and talk to loved ones and their families, they may find, oh, oh yeah, there's a lot of people in our family who had infertility issues. It's just not talked about. Whereas I think our generation, younger generations are having those conversations because people are just much more open. There's not as much shame and secrecy, hopefully not as much shame and secrecy. So people will talk more openly about their experiences. But, you know, I find it all fascinating. And I think it's, it's fascinating and also disturbing that we have young women and young boys that are going into puberty so much earlier because that's a longer exposure of hormones. And, you know, let's be honest. I mean, do you think a 10-year-old or 11-year-old is equipped to deal with having a menstrual cycle every month? I think not. I think I was 14 when I had my first cycle, and I was like, "Oh, I can do— I don't need this. I can get rid of this for a couple more years. This is kind of a hassle." Um, for a lot of women. So a lot of responsibility when you start puberty at such a young age.

So our microbiomes are a wreck. It affects everything, hormones. Um, so what do we do? You know, what's the, what's the answer? You know, and you've mentioned fiber a couple times. We did, I didn't even go down the, the whole, the whole rabbit trail of short-chain fatty acids, which I had some notes on that. So talk about like, okay, so what's What's the fix for, or the answer or whatever, for a female who's in this middle pause, who's now going through these things, who's now just hearing, wasting my gut is a part of it. It's not just like, what are some things they can do to positively impact, um, their gut micro, their gut that would have a downstream effect on the hormones?

You probably won't be surprised that I'm going to talk about majoring in the majors because, you know, there's all these fun gadgets on social media and that people talk about, but I'm like, before we even get to the gadgets, I'm telling you, your sleep heavily influences not only your gut microbiome, but your degree of insulin sensitivity, your cortisol. So, high-quality sleep becomes critically important. And I would actually argue that is the most important thing to dial in on. If your sleep isn't good, you're not going to manage your stress, you're not going to, you know, not have gut issues. So, getting high-quality sleep consistently. Now, you and I travel quite a bit. I would say at any given time of the month, there's probably several days where I'm not getting 7 or 8 hours a night of sleep. I'm not talking about that. You want consistency over time. Next is stress management. And I think for a lot of women, they'll tell me they manage their stress, but they don't sleep well. So, I'm like, "Show me a woman who doesn't sleep well and show me a woman who doesn't manage her stress." So, stress management needs to be something you can do consistently. Find several strategies that you like and start with the basics, like sunlight exposure in the morning, grounding work. Breathwork. You don't necessarily have to be a meditation aficionado, but finding ways to stimulate your vagus nerve, gargling, humming, singing, all of which can do that. Vagus nerve's really important for getting out of that sympathetic state, getting into the parasympathetic rest and repose. We have to talk about nutrition. And I know it's not sexy, but it's true. Eat less processed foods, drink plenty of water, avoid alcohol, Eat plenty of protein. You know, we need more protein, not less, as we get older for a variety of reasons. We need, you know, that protein leverage hypothesis and the fact that we need more to stimulate muscle protein synthesis. Like, my teenagers who are very athletic and muscular, as are yours, they could probably sneeze and stimulate muscle protein synthesis. We need a larger bolus of protein. The other thing is fiber. And I know that fiber, everyone thinks back to Grandma's Metamucil. I'm not talking about that. I'm just talking about whether it's a tablespoon of fresh ground flax and chia seeds, whether it is artichoke hearts, whether it's cruciferous vegetables, fiber in our diets. And I always say, like, track and then adjust. So, if the average standard American diet patient is 5 to 10 grams, you definitely want to move the needle up. You don't want to go from 10 to 30 because your microbiome will not be ready. Be able to acclimate to the increase in fiber. And I'm sure we could probably have a long tangential conversation about fiber, but fiber really is important. So, you definitely want more than where you are. Next is exercise. And in each one of these interventions I'm talking about, there is scientific evidence to support the influence on the microbiome and the support of hormones. Exercise, so it has to be the right amount, it's the Goldilocks effect. 6 days a week of CrossFit or 6 days a week of Orange Theory Fitness. That's not the kind of exercise you should be doing 6 days a week. You need recovery, you need strength training, you need zone 2, you need some flexibility work. Once you've mastered those things, maybe some high-intensity interval training briefly. And then it's really looking beyond that, like dealing with your stuff. You know, when I mentioned stress management, it's also if you had significant adverse childhood events, you very likely have work that needs to be done underneath the hood because One of the few hormones that goes up in menopause and perimenopause is cortisol. And as I mentioned earlier, cortisol is an important hormone, but if it's elevated over time, if you're dealing with a lot of chronic stress, it's catabolic, so it breaks down the muscle that's so precious. It impacts your ability to fight infection, and the immune system really gets awry when cortisol is elevated over time. More leaky gut, as we already talked about, And cortisol tends to just make us irritable in and of itself. And it's probably because it's also interfacing with the immune system, which is impacting inflammatory cytokines. You know, the other things that I think about is, you know, really looking dynamically at gut health. And so fiber is helpful, sleep is helpful, stress management is helpful, getting granular about digestive fire. Now, that's not a medical term, but the lay public understands when I say that With age, a lot of things decline. Hydrochloric acid, which is a primary site for protein breakdown into amino acids so our body can actually absorb and assimilate it. Also digestive enzymes. A lot of my patients need digestive enzymes, and that can be helpful for breaking food down into usable concrete carbohydrates and fats and protein. The other thing that I think is fascinating is the role of estrogen and bile. So, a lot of women will say to me, "I don't feel so good when I eat a ribeye or if I eat a fatty piece of meat, like if I have duck or salmon." And a lot of it has to do with the decline in estrogen impacts how we break down and emulsify fat. So, it has a direct effect on bile acids. And interestingly enough, there's a supplement that I love that I know you're a fan of as well called Tudca. And Tudca is not just about biliary support, it's also important for mitochondria. And again, it's that estrogen piece that I found so interesting. The other thing that is very common that I see is women will say, "I feel like my food sits in my stomach longer." And it's helping them understand that progesterone is a smooth muscle relaxant. Estrogen has potent effects on nitric oxide signaling. So, when we're talking about gut innervation and things moving dynamically through the digestive system, in the absence of hormones, those things can change quite a bit. And I think sometimes we forget that. We're like, "Oh." Yeah, I know that the estrogen is important for the microbiome, as is progesterone plus or minus testosterone for immune function. I think sometimes we forget that these other pieces are really important. So, again, we go back to, you know, just simple things before we even get to gadgets, before we're even talking seriously about supplements or medications beyond things that we've kind of already alluded to. It's really understanding that those basic things become very, very important. In middle age.

Yeah. And that's one of those things. I mean, I like the fact that you didn't go down this rabbit trail of, you know, do this thing that tracks your hormones or do this fancy test. You focused on the basics. Cause I feel like now with everything, you know, the, the gadget in the box kind of stuff or whatever that people, everybody wants a magic fix. Really the foundational things are foundational. You gotta perfect the basics just like a professional athlete. And all those things you mentioned are things we all should be working on. On a daily basis. And it just becomes— you can get away with it when you're 20 or 30, but when you're a female going through this middle pause, you really have to, you know, perfect the basics and really work on that stuff. And if you haven't been doing it for 20 or 30 years, now's the time to kind of reassess that and start working on that.

Yeah. And I think it's, it's interesting how we've been conditioned as a culture that it's the supplement or the intervention, like the gadget. And let me be clear, I, I'm I'm all about trying supplements out, and I have all the gadgets, and I have some preferences of some over others. But before you get the Oura Ring or the Whoop band, sorry to pick on those two, but I think most people know what they are. Before you even get to those devices, like, let's dial in on the basics because I find that most women are already overwhelmed. They're like, "I already don't feel like my brain works quite as well. I already feel overwhelmed with too much information." we make it as simple as possible. It's like major in the majors, get those dialed in, and then we can work on more complicated interventions. We can get really nuanced and, you know, helpful information. Like, you know, when people come to me and they're like, okay, I want to do all these integrative medicine tests. And I'm like, that's great, but we still have to deal with the basics first because you can spend thousands of dollars on these integrative medicine tests and they can be very beneficial. But if you haven't already done the basic things, they aren't going to be as effective. Like, I always use the example, you know, we've done the fatty acid test, fatty acid analysis, and not surprisingly, as someone who doesn't eat dairy, I was C15 deficient. And so, since I don't eat dairy, that's a supplement, but that makes sense because I'm not going to get it from food-based sources. But I think for a lot of patients, they go to functional integrative medicine and they come out with 50 supplements. And then they're like, wow, now I'm really overwhelmed because I have— well-meaning, well-meaning practitioners, let me interject that. But I think for a lot of women when they're dealing with this middle-aged piece, they're already overwhelmed. So, keeping things simple, I think, allows them to have greater success. And I always say, those little wins that you get up front, like, oh my gosh, I went to bed 30 minutes earlier and I feel like I'm a whole new person in the morning, or I'm doing breathwork before I go to bed, that makes, you know, I feel so much less stressed before I go to sleep, or eating more protein stabilizes my blood sugar so I can make better food choices throughout the day. Like those kinds of simple interventions can yield like big results. And then patients are interested in committing to other things beyond that. But those quick wins, I think, are important.

And then if you do the foundational things and you add on, a gut protocol or hormone replacement therapy, that's when you see magic. That's when you see them like, oh my gosh, I had no idea. It's just when people like slap a bandaid on a dysfunctional system, they feel better for a while and then they don't. Yeah. And then increase the hormone, they feel better for a while and they don't. And they do that for a couple years and all of a sudden they're coming to me and they're totally, um, just jacked up basically. And so that's where I, I love the fact you, focus on the foundational stuff, because that's what makes everything else work.

Yeah, no, and I think that, you know, unfortunately, I go back to hopefully well-meaning individuals that are out there that will promise it's like you need this one gadget, this one supplement that's going to fix everything. And I'm like, you may feel better short term, just like an estrogen patch may make you feel better in the short term. But if you haven't done the other work, it's not going to work quite as well. And I think most listeners to your podcast, certainly listeners to my podcast, they want to feel better long-term. Like, they don't want it to be a quick fix. And so, I always go back to, you have to change your lifestyle, and that's still very important. And, you know, in the interim, maybe we're layering in hormones, maybe we're layering in supplements, but being really intentional about what we are doing so that you get the best results long-term.

Yeah, absolutely. Well, Cynthia, I feel like we could keep on talking for more than an hour and just going, but I need to respect your time. If people want to learn more about you, find out about your book, where should they go to find out about your book? Is it out yet? Um, when's it coming out if it isn't yet? Oh, and if they want to learn more about you, where can they go to find out more?

Well, thank you, Aaron Hartman. Always a pleasure to connect with you. So probably easiest to go to my website. It's www.cynthiathurlow.com. At the top of the website is a banner which will take you to purchase the book. It is currently in presale. It goes on official sale April 28th, and it's going to be sold— it's in presale at any of the retailers you can imagine, Amazon, Barnes Noble, Target, et cetera. I do have a podcast called Everyday Wellness, and Aaron's been a guest multiple times. He's a fan favorite. I'm active across social media. I always say to people, I I have a free Facebook group called the Midlife Pause backslash my name. It is a group mostly of women, but there are some supportive significant others in there as well. I'm most active on Instagram, but I'm actively growing Substack. It's kind of become a really cool place to interface with my community and people that are new to some of the things that I explore and talk about, like subjects that we've talked about today.

Cool. Awesome. Well, Cynthia, thank you so much for your time. I really appreciate it. And we'll talk to you later.

Thank you.