Understanding Weight Loss Resistance

Welcome to Everyday Wellness Podcast. I'm your host, nurse practitioner, Cynthia Thurlow. This podcast is designed to educate, empower and inspire you to achieve your health and wellness goals. My goal and intent is to provide you with the best content and conversations from leaders in the health and wellness industry each week and impact over a million lives. This is Bonus Monday , your most downloaded favorite podcast. I love that this community runs the gamut from medical professionals , research scientists, science writers, personal trainers, and more. These are your favorite , most loved podcast of the last five years. I could not be more proud of the diversification of guests that appeal to all of you. Thanks for tuning in. Today I had the honor of reconnecting with Dr. Deb Matthews. She joined me previously on episode two hundred ninety five . She is a remarkable best selling author , international speaker, devoted educator, and the happy hormone doctor. Today we dove deep into a conversation around cardiovascular disease , how cardiovascular disease causes one in three point two deaths in women each year in the U. S. and remains the number one killer. We spoke at length about benefits related to HRT, pertinent labs, testing, and medications , as well as focusing in on neurocognitive changes in perimenopause and menopause, the role of lifestyle, gut testing , and a fan favorite topic, weight loss resistance. I know you will enjoy this conversation as much as I did recording it. Dr. Matthew, it's such a pleasure to have you back on the podcast. Thanks again for joining us. I'm so excited to be back. Yeah. So in continuance to our last conversation, which was so impactful and so information savvy , today I thought we could shift and talk a little bit about the perimenopause menopause transition and how women's risk of cardiovascular disease increases significantly. I was just reading a statistic that I want to share with listeners. Cardiovascular disease causes one in three point two deaths in women each year in the US remains the number one killer of women accounting for approximately one death eighty seconds . Why are we not talking enough about the role of HRT and how this improves not only our all cause mortality but our cardiovascular risk reduction. I know that you're talking about it, but why are we not talking about it enough as clinicians. Well, you know , we as women are scared of breast cancer . You know, we worry about breast cancer. We lie awake at night being scared of breast cancer. Breast cancer takes women's lives relatively when they're younger sometimes. And so that is one of our big fears . We don't fear heart disease in quite the same way, do we? Like most of us, if we're in our forties and our fifties, we're not lying awake at night worrying about having a heart attack even though that is the way that most of us are ultimately going to meet our end. But heart disease as a general statement tends to take women's lives relatively when they're older, and so we're not so worried about that. But of course, heart disease is something that happens sort of very gradually over many years. And so we need to be worried about it now. We need to be doing the things that we can do to prevent . So I'm really glad that you that we're going to be talking about this today because this is so big and women need to know. Yeah, and it's interesting. When I started the trajectory of my P career in cardiology around two thousand one, preceding the WHI study coming out, I remember how many of my middle aged female patients that were taken off of HRT , and then if they had a known history of coronary artery disease, they're like, Oh, we absolutely positively can't have you on estrogen. We need you to talk to your primary care provider, your internist. We're so concerned about this , not realizing if we really look at the research that's being done now and over the last several years , that loss of estrogen in our bodies has such profound systemic effects . And so to me , the thing that I think is really interesting is this complex interrelationship with estradiol and how that actually protects our vasculature . It protects the internal lining of our blood vessels, the endothelial lining , and helping women understand as well as clinicians that we have this like ten year window and ideally some people will say a five year window of when we make this transition into menopause and when we start HRT , but in your clinical experience do you find and you mentioned this already, we're so worried about breast cancer. We're not thinking about coronary artery disease , but are you seeing an uptick or more awareness around this topic or do you feel like it's still kind of flat line? We think about men and men dying early of cardiovascular disease. And yet we think of this as like an old person 's problem, but it really isn't. It's a now, it's a now issue. It is. Well, I think there's so much to talk about. Like we need to talk about all the ways that estrogen is beneficial for women's hearts, but then we also need to think about why would the cardiologists, you know, that you were working with want women to stay away from estrogen? And if we sort of unpack that just a little bit , one of the things that we always used to do in the past when we were giving women hormone replacement therapy is we gave it as a pill . And what we learned is that when we give women estrogen orally , especially if we're not giving them the bioident form, which is estradile, which is what our ovaries naturally make. But there's many chemical forms of estrogen. There are estrogens that come from horse here, and there's different kinds of estrogen. When we give estrogen in a pill, it increases the risk for cardiac for blood clots and especially the synthetic estrogens. And we know this whether it's in birth control pills, whether it's in hormone replacement therapy . And so a blood clot in your heart would be a heart attack or a blood clot in your brain would be a stroke. So if we're trying to do something to reduce somebody's risk of heart disease, it wouldn't make sense to give them something that's going to increase their risk of a blood clot. So that was one part of it. Another part of it is that when women on HRT relatively when they're older, especially and when they take this oral estrogen , one of the things that it seems to do is it causes plaque in our arteries to become more unstable . So if you have plaque in your arteries and you were to start on the studies were done on it's called conjugated equine estrogen, which is the kind of estrogen that comes from horse here. And we know it is Primarin. It used to be the kind of estrogen that everybody took. So if we give women primarin and they have already have plaque in their arteries , in the first twelve months of being on Premerin, there was an increased chance that a little piece of cloth would or a little piece of plaque would break off from the inside lining of their arteries, become a clots, and therefore they could have a heart attack. Now, if that didn't happen within the first twelve months, the risk of heart disease started to go down and down and down . So the longer that they were on the estrogen, even this kind that increases the risk for blood clots , the risk for heart disease went down . But all that doctors need to hear is if you take the pill, there's an increase in the chance of a blood clot, an increase in the chance of a heart attack and they're going to write the whole thing off. And most of the time, if you're a woman going through menopause, you don't even know if you have plaque in your arteries. Nobody's even really started to check for that for the most part yet, unless you've got other risk factors. So that's it causes blood clots, it could cause blood clots. The blood clot issue is much more of an issue in older women than in younger women. But you know, hormones just get all painted with the same brush, right ? It could make plaque more unstable in the very beginning. And it's probably because the estrogen is doing good things to the plaque. It's changing it, it's helping except that maybe a little piece could break off and that's part of the downside. And then the third thing that went wrong is that we were also giving women a drug form of progesterone. So instead of giving progesterone like our ovaries make , we were giving women medroxy progesterone acetate, which is a chemical, a man made chemical that's meant to mimic progesterone. It was studied for what it does to our uter ine lining and it can protect our uterine lining from the effects of estrogen, but we didn't really study what it does everywhere else. And what it did in our heart is it caused something called coronary vasospas m, which means our coronary arteries would go into a spasm, they would squeeze down and then blood couldn't get through and it was causing essentially a heart attack. So if we give women a pill that makes their plaque unstable, increases the risk for a blood clot and squeezes their arteries, that's not the greatest way of going about preventing heart disease . And so in the study, the one that you talked about, that women's health initiative study, the main point of the study was supposed to prove once and for all that hormones were the greatest thing since sliced bread, and they were going to reduce heart disease in women. But it came out to be a wash. It's not that it made more heart disease in women. It just didn't reduce the heart disease the way that we were hoping it would . And it was also done in older women. So the average age of women in the study was, you know, quite a bit past menopause . So there were just so many things wrong with the analysis , but hormones just all got lumped into the same basket with the message that hormones are potentially bad and dangerous and they don't in fact decrease women's risk for heart disease. What does it feel like when your clothes really feel great ? This spring , Cozy Earth makes the case that what you wear at home matters just as much as what you wear out of it, maybe more. For a lot of us, it's not something we planned, it's just what we kept grabbing. Cozy Earth's jogger sets are the answer to that the thing you reach for first because it genuinely feels so good . What I love best about their jogger sets is they're made from vis as from bamboo, which means it's breathable and soft in a way that actually holds up. 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Born from a decade of longevity research, one skin's OS peptide is proven to target the visible signs of aging, helping you unlock your healthiest skin now as you age. For a limited time, try one skin with fifteen percent off using code Cynthia at oneSkin . CO slash cynthia . That's fifteen percent off one skin. CO with codecynthia. After you purchase, they'll ask you where you heard about them. Please support our show and tell them we sent you . Yeah, and it's really interesting because you did such a nice job cohesively explaining a very complicated situation that's gone over the last twenty years. So let's say a woman comes to you and again, this is an umbrella statement, not medical advice. She's coming to you. She's within five, ten years of transitioning into menopause. She's interested in the benefits of H RT, what are some of the preliminary tests or studies you like to run to ensure whatever next decision you're making is in her best interest and most safe for the patient . Generally , so first of all, we want to do a hormone panel because we only want to replace hormones that are deficient and women's hormone levels change as we go through menopause and our ovaries shut down , but not everybody has the same degree of estrogen deficiency . Women who are overweight tend to make more estrogen in our body fat, even when our ovaries are kind of lowering down. And so they may do fine without needing extra estrogen in their system . Some women make a fair amount of testosterone even when they go through menopause because half of our testosterone is made in our ovaries and the other half is made in our adrenal glands. So even if your ovaries go down, if your adrenal glands put out a lot of testosterone because testosterone is really important for women too. And one of my fav orite factoids is that we have ten times more testosterone than estrogen in our bodies. It's just that men have ten times more testosterone than women do. But if a woman makes a fair amount of testosterone that testosterone naturally gets converted into estrogen in all of us. That's just a natural thing that happens. So somebody who has a generous amount of testosterone and they make a fair amount of it into estrogen, they might be okay and they might not really need estrogen replacement therapy. So we shouldn't just automatically oh you're menopausal here's your estrogen. We want to look into it a little bit more and understand more about the different hormones. Another hormone that is really important for us to know about in my opinion for women is DHEA and that's another hormone that comes from our adrenal glands. Our body can use it to make a little bit of estrogen and testosterone . And in fact, that is where our estrogen comes from when our ovaries quit after menopause . So depending on a woman's DHEA level, she may have relatively more or less estrogen inside her cells and that DHEA goes down with age , but it also goes down with stress. So if we have acute stress, it can go up, but over time it can go down. So looking at the lay of the land amongst these different hormones can help us to understand better , and also looking at cortisol, which is our main stress hormone because we've all got stress these days and when our bodies react by making more and more cortisol, cortisol does a lot of things that are not good for cardiovascular disease . High stress , high cortisol makes your heartbeat faster, it makes your blood pressure go up , it drives up your blood sugar . So all of those things are hard on your heart and just kind of where is your heart if this is going on year after year after year. And then there are some really interesting studies that look at the risks for cardiovascular disease and cortisol metabolism. Is it okay if I kind of explain that? Absolutely. I would love that. Okay , so there is a really interesting study that looked at what we call the circadian curve of cortisol. What naturally happens is in the wee hours of the morning our cortisol level starts to go up and cortisol is kind of like long acting adrenal ine. So it's like we get this little adrenaline surge in the wee hours of the morning so our eyes pop open and we leap from bed and we're ready to start our day. And then over the day cortisol levels start to go down so they're nice and low at night and we're relaxed and we can fall asleep and we sleep through the night. Now that's not what happens for a lot of people, right? For a lot of people it gets flipped around backwards. So in the morning they don't get that peak, so they're exhausted and they have to press the snooze button a few times and they drag themselves out of bed. It takes them a while to get going . And then at night, their cortisol is higher and now they can't sleep. They're wide awake they need an ambient, you know, so it gets flipped around backwards . But for some people , that up and down curve ends up being kind of like a flat line. So they don't they lose that circadian change, that circadian rhythm. And it turns out that that circadian rhythm is really, really important . So if cortisol levels are chronically elevated sort of throughout the day, we know that that's hard on our heart because higher blood pressure and higher heart rate and et cetera. So that's not a good thing . But what was actually worse if it was just a flat curve, there was no up and down , the flat level of cortisol over the day had the strongest associ ation with cardiovascular risk, stronger than high blood pressure, high cholesterol, high blood sugar , et cetera. And in fact they did a correlation . They showed that like how strong was the correlation between bad cholesterol and heart disease? How strong was the correlation between the systolic blood pressure, which is the top number on your blood pressure and heart disease and then the diastolic bottom number and your blood pressure. They looked at all the different numbers. And what they found was when they kind of crunched the numbers and put it all together , it actually looked like the flat cortisol was the most important one of all out of them, but that is not what cardiologists are looking at. Cardiologists A don't measure cortisol at all, but for a lot of doctors, if they were going to measure cortisol, they just do it on a blood test and you can't see the curve on a blood test or sometimes if they're looking for a tumor they'll do a twenty four hour urine , but you can't see the curve. The only way that we can see the curve is in a saliva test or a urine test where we do multiple samples over twenty four hours so that we can see what's going on. So that's something that I like to look at in my patients because we see so commonly that this is a problem. This is sort of part of our modern civilization . We lose all of our circadian rhythms. We're in bright lights all the time. We've got lots of stress. We've got TV and we've got our phones. Oh my gosh , we can scroll through Facebook twenty four seven. We're not going to bed at a decent hour. And so our circadian rhythms are all messed up, and that's not a good thing for heart disease risk. It's really interesting because I think about when I 've looked at flat cortisol patterns with saliva, dried urine and these are the people that are chronically stressed, wiped out. I mean, it could be for a variety of different reasons , but it would make sense kind of mechanistically that this is someone that's at greater risk. Now I'm curious and I'm not sure if you do this in your practice, but are you ordering cats? Are you doing coronary artery scans ? Yeah, kind of looking that's one thing that as I was d iving into this research to prep for our conversation was that women as their clinicians are considering using HRT who's appropriate who is not, that five year window is significant for plaque b urden plaque, you know, progression. And so I was curious, are you doing the CACs and the CIMT? And we're obviously we'll explain what these are. These are diagnostic tests that are generally inexpensive and non invasive, but can be very helpful navigating choices of using HRT or other modalities to address lipid abnormalities, et cetera. Yeah, I would say that I don't routinely kind of as the standard order these on everybody. If somebody has a strong family history of heart disease, if they've got risk factors, I mean, if there's real reasons that we need to be concerned about cardiovascular disease risk, that we absolutely do. The coronary calcium score is basically a cat scan of the chest and the cat scan can see if there's plaque in your arteries . And you know, there have been times when we've found people who were completely asymptomatic and they had no idea, but they actually had some pretty significant blockages in their blood vessels. And so now that we know that, you know, we can jump in and do the things that we need to do in order to help protect them so that they don't have a heart attack . Sometimes and frequently, we find people have no plaque showing in their arteries at all. And I think it's important to say it's not perfect because it can see the calcified kind of plaque. So there are some kinds of plaque that won't show, but generally speaking, if they don't see any plaque, if your score is zero , that's a really good sign because if your blood vessels are going to get , you know, if you have atherosclerosis and you've got plaqu e billing in your blood vessels, it doesn't start on Thursday. You know, this has been something that's brewing for decades and continues to get worse. So if we already see some and it's a small amount, that wouldn't pre clude me from prescribing hormones, but it tells us the problem has started. We need to jump in and make sure that we can do all that we do to not make it any worse. And if it was really if it looked worrisome on the test, then definitely we would want to think about what we were doing, both with hormones and everything else in order to minimize the risk. And the coronary intomedia thickness is looking at the lining of the blood vessels leading to the brain . And so that's a predictor for are you at risk for stroke because do you have plaque in the blood vessels leading to the brain? So I would say that we generally reserve them for people who are, for whatever reason, we're worried about them , but you know, anybody who would like one, I would be more than happy to order it. And like you said, they're inexpensive . So if you have, I don't know, some breathing problem, for some reason, you need a cat scan of your chest then you can go have a cat scan of your chest, they'll bill it to your insurance company, they'll charge you. I don't even know how much they cost now, a thousand dollars, however much they're going to bill . But here, insurance doesn't pay for these. So you just have to pay cash . Locally here, we can get them for about one hundred and twenty five dollars . It's the same cat scan. Go figure, right? No, and it's amazing. So for full transparency and I've been talking more about this on social media, I have some genetic lipid issues , which now that I know as much as I do, I'm like, okay, I'm a hyper absorber. I absorb too much cholesterol. So I have a high APOB, I've got a high LDL, I've high HDL. I mean, it's kind of like this constellation of lipid issues, but it's genetically mediated . And so I had a CAC, I had a CIMT, I had to pay out a pocket. I think between the two tests , it was two hundred and fifty dollars . But to your point, if I go to have a regular CAT scan, my insurance company is going to get charged probably several thousand dollars and I'll have a high deductible . And so it's fascinating to me how the way that our insurance industry works and how they arbitrarily choose to cover some tests and not others. I'm sure that's probably a conversation for another day. So as you're kind of navigating cardiovas cular risks, people sharing about their family history or personal history. Are you looking at advanced lipid markers? Are there other labs that you're looking at to help risk stratify your patients? Absolutely. So yes, so just a regular old lipid panel is just not enough to get the information that we need. So we want the advanced lipid panel. And what that tells us is what kind of bad cholesterol do you have and what kind of good cholesterol do you have? And the analogy for bad cholesterol that I like is you can have small particles or big particles . And if you think of the lining of your blood vessel like a tennis net, if you have small dense particles, they're kind of like a golf ball. And if you throw the golf ball at a tennis net, it's going to go right through. So the golf balls can get into the lining of your blood vessels and start to form plaque . If you have big fat , fluffy particles, they're like a beach ball. So if you were to throw a beach ball against a tennis net, it's just gonna bounce off. So these just bounce on through your blood vessels and they really don't cause plaque. So you can have a high LDL or high bad cholesterol number on your blood test, but if it's all these beach balls, it doesn't really significantly increase your risk for heart disease . But if you have, even if your bad cholesterol number isn't so bad , but it's really made up of mostly all of these dense golf balls. That's much more worrisome . And the same kind of thing is true for good cholesterol , then knowing your number of good cholesterol is not enough, because if you think of good cholesterol, the analogy is like a vacuum cleaner. So if you have big fat good cholesterol particles or like a big old shop vac that's sucking plaque out of your arteries, it's not exactly how it works. But for the analogy, you get the picture. So you can have the big fat shot vac sucking lots of stuff out or you can have like a little hand held dust buster that's barely sucking any out. So you can have little wimpy good cholesterol particles that aren't very protective . So if we know more about the size of your cholesterol particles , that can give us more information about just how worried do we need to be? Because if you've got all the wrong sized particles , even if your cholesterol is only mildly elevated, we might need to be really worried about it. And maybe one more thing about cholesterol that I think people really need to know is the number of your total cholesterol is somewhat irrelev ant. I mean, unless it's five hundred , but generally speaking, the total cholesterol number really doesn't mean anything . Roughly, it's the good cholesterol plus the bad cholesterol added together gives you your total . The math doesn't quite work , but if you have a generous amount of good cholesterol, that can drive your total cholesterol number up, but that doesn't necessarily increase your risk for cardiovascular disease. So there's just a lot more that has to go into the analysis of cholesterol besides just what your total cholesterol number is. And at the end of the day , fifty percent of people who have a heart attack have completely normal cholesterol , and fifty percent of people who have high cholesterol never have a heart attack. So cholesterol is really actually not one of the greatest risk markers or predictors of cardiovascular disease . And so some of the other things that we look at is LP Little A or Lipoprotein A , which I like to describe as like there's good cholesterol and there's bad cholesterol, right? LDLMH . So this is like nasty bad cholesterol. So this is like bad cholesterol that's been inflamed and oxidized. It does tend to be genetic . So it's a little bit harder for us to control with diet and exerc ise and whatever . But one of the things that can help to lower that lipoprotein A is estrogen. So I wouldn't prescribe estrogen for the sole purpose of lowering that lipoprotein A, but we don't like that one and that is one that we look for. Another thing that we look for is C reactive protein or CRP. It's just a marker of inflammation and it doesn't tell us where the inflammation is exactly. It's not like when you twist your ankle and your ankle gets all swollen, we know the inflammation is in your ankle. Here it's just inflammation that's going through your bloodstream. But when you really heart diseases, inflammation is the root cause of heart disease. So if you have a lot of inf lammation, it's an important risk factor. And of course, there's so many things that we can do in order to reduce your risk. And generally speaking, hormones are anti inflammatory . And if I can go back to cholesterol, I'll take a breath after this , I promise. But cholesterol is really not the terrible thing that we've been led to believe because not only do, you know, just because you have high cholesterol doesn't mean you're going to have a heart attack, but cholesterol is really, really important as a building block for your brain . And so when people have low cholesterol , they actually have greater risks for dementia. So we're putting lots of people on cholesterol medicines and driving their cholesterol way down . And of course, if you're at high risk for having a heart disease and you could drop dead next Thursday, we're not going to spend as much time worrying about dementia when you're ninety because we just need you to get there, right? So but low cholesterol is not really the goal because you need cholesterol for your brain, you need cholesterol to make vitamin D, which is really a hormone, even though we call it a vitamin, it behaves like a hormone and estrogen, progesterone, test osterone, cortisol, DHA, all these hormones we're talking about today, they're all made out of cholesterol. And so if your body is deficient in these hormones, one of the mechanisms is to make more cholesterol because it's the building block to make your hormones. And if we can give you balanced hormones, the natural form of hormones just kind of normalize things, sometimes we see the cholesterol go down. It's such an important distinction because I feel that cholesterol has really gotten a bad rap. And just in putting questions out across social media in the past few weeks specific to lipids because I've been interviewing several lipid experts . It's interesting how many people have said my total cholesterol is X , my HDL LDL look good according to them . My physician, my MP, my PA, they'd like to put me on a statin and I'm like, I was like, this is not medical advice, but high cholesterol is not an indication per se. It's just a mechanism for transporting things in your body these lipoproteins. And so it's interesting being in cardiology for so many years, I started to back down on statins when I watched my patient's total cholesterol go down , especially because low total cholesterol can be a marker for morbidity and mortality. And how many of my patients would have total cholesterols around one hundred twenty five or one hundred ? And I would say to them , my goodness, you're having all these cognitive effects. You're having all these other things that are going on. Yes, if we look at the literature and we look at evidence based medicine, because you have vascular disease, a statin is indicated , but I think this dose is way too much. And so we would start backing down. And so with that being said , I think that there's more to the lipid analysis and all those little nuances that you kind of alluded to that can be very important . Now, when you're navigating perimenopausal, menopausal women, looking at these lipids, looking at risk stratification, considerations to HRT , are you prescribing lip and lowering agents or do you refer on to someone else to help with those kinds of selections? Or is that something that you're doing in your practice? I would say that we refer people on only if they're sort of like the worst case scenario . Like if we did, you know, the calcium score and we found a high score, like they're at very high risk for actually having a heart attack any day now, definitely we refer those kinds of people on. If really it's just that they're and I suppose to if their cholesterol was sky high, like five hundred, you know, like crazy off the charts, probably we would refer on because that's more than just poor lifestyle habits or whatever. So but otherwise we, really work hard to manage it ourselves because what we find is if we can get at the root cause for why the cholesterol is up in the first place, we can really help for it to come down. So if we can help balance your hormones with ormone replacement therapy, if we can get your thyroid managed because one of the important causes of high cholesterol is low thyroid . So we see this all the time. If we can if somebody is mildly hypothyroid and their cholesterol is up and we optimize their thyroid hormone, their cholesterol will come down. But it should just be knee jerk. If somebody has high cholesterol, we should be checking their thyroids to make sure that's not the cause of it . But instead we got all these women going into their doctor to say, I can't sleep, I don't feel good. I'm exhausted, I'm gaining weight, I'm cold, I'm constipated, I got dry skin, all the symptoms of low thyroid , and they're told your TS H is normal. That's the thyroid test. Oh, but your cholesterol is high. Here's your statin. And so that just makes no sense. So we want to optimize hormones. We also need to optimize blood sugar because insulin resistance is a really, really important cause, not just of high cholesterol, but having the wrong type, like having the golf balls instead of the beach balls or the little shop vac wimpy, good cholesterol particles. So if you have the wrong kind of cholesterol particles and we put you on a statin medicine, we can lower overall how much, but it doesn't really change what type you have. But if we can improve your blood sugar metabolism, that can help the bad cholesterol particles get bigger, the good cholesterol particles get bigger , so it improves your risk stratosphere in a much better way. So there are also some natural things that we can do to help lower cholesterol . So berberine , reggies rice , you know, there are things that we can do besides statin medications or other prescription medic ations and, you know, if cardiovascular disease is a long term thing, so if we just never can get it right, the medicines will still be there at the end of the day if we need to turn to them someday. Yeah, and I think it's so important to talk about those clinical pearls was. always That the first thing I would say to patients is if your lipids are not within a normal limit, you know, do you have latent insulin resistance? Are you pre diabetic? Are you dealing with an underactive thyroid which we saw so much, and certainly perimenopausal menopausal females, I want to say that in my clinical experience, I would say it's easily seventy five to eighty percent of women are dealing with an underactive thyroid and more often than not properly diagnosed so they're suffering with all those symptoms as you mentioned and that traditional allopathic lens will miss it, whereas a functional lens is much more narrow and it will say, okay, your TSH should be between here, your free T three should be between these numbers . And if you're also then also symptomatic , then there's probably some benefit. In addition to dealing with the lifestyle piece and co forsact, et cetera. So that is certainly very helpful. And I love that you touched on red yeast rice. That's one of my favorite supplements that can address lipid disorders that is not a statin but acts like a natural statin with that all the side effects. Yeah . Another area that I know is really important for women in middle aged is really navigating cognitive decline or cognition changes that I'm sure you're seeing. And it's interesting when I was looking at the research in prep for this how important both estrogen and progesterone and in some instances testosterone can be important for reducing our risk of dementia , neurocognitive disorders . And so when you're evaluating women and they're coming to you, maybe they're saying, I'm just forgetful, I have a lot of brain fog , how are you kind of differentiating or working them up to determine what is the primary reason that's driving these neurocognitive self reported changes that they're seeing. I think that is one of the most common symptoms that we see . And when women think about menopause, what they're kind of expecting to happen to them is they're expecting maybe they'll have hot flashes, they're expecting maybe they'll have vaginal dryness, they know their period is going to stop . But if that's all we had to deal with, like we would, make it through. I mean, sometimes the hot flashes are really annoying , but you know , when your brain doesn't work, that is way worse. And I hear this every single day . Women will say things like, I'm in the middle of a s entence and I just lose my train of thought or I just that word it's right on the tip of my tongue but I just can't think of it or I can't remember people's names or I got to write everything down and then I got to have sticky notes to remember where I put the lists and walk in the room and you can't remember why you're there. It just goes on and on and on and on and on . And because we don't think of that necessarily as a hormonal symptom , we just worry instead that this is the first sign of early Alzheimer's and it's really scary . And especially if you have somebody in your family that's had Alzheimer's, like, you know, it's terrifying . So So while we don't really spend an awful lot of time worrying about heart disease, we sure do worry about dementia, even though we think we don't have to worry about it for a long time, and then all of a sudden menopause comes along and we can't remember things and we're thinking, Oh my gosh , it's happening early. But there's a lot of things that we can do. So you're asking like how do we know what the problem is? And I think it's really hard. It's not like there's a test. We can't do like a brain MRI or there's no test that we can do that will exactly explain what's going on. So we just work through our list of things . And one of the things that I would say can make a big difference for people is what they're eating . So sugar , alcohol, if they're eating foods that they're sensitive to, they've developed food sensitivities, that just creates inflammation . Those are all things that can interfere with how your brain is functioning. Another really common thing that we see that causes brain fog is yeast overgrowth. So we all have Candida, which is a kind of yeast growing in our digestive tract. If we end up with too much yeast , the yeast release these little chemicals called aldehydes, they go through our bloodstream and they go to our brain and they cause really significant brain fog sometimes. And it can also go along with sugar cravings and bloating because you know we put yeast in the bread and it makes our bread rise, but it just makes our belly rise too. So we want to look at gut health because there's a huge connection between your gut and your brain . And then we want to think about the hormones. So the hormone that I would say is sort of the most connected most, closely connected would be estrogen . And I mean, I can tell you this personally , occasionally I forget I'm not a good patient and I forget about my estrogen and all of a sud den I'll catch myself not being able to think of what I want to say and I'm like, oh oops I forgot. So estrogen is really important for keeping our brain sharp. So is thyroid. If you are one of those many women who is under has an underactive thyroid , you can't remember things, it's hard to do math in your head. Like you just don't feel sharp. And if we can optimize thyroid function, your brain comes back online again. Progesterone is the calming hormone that helps you sleep. And if you can't sleep, your brain's not going to work. Cortisol is too much cortisol. High cortisol levels are toxic to your hippocampus, which is the part of your brain responsible for short term memory . And so what we commonly see in menopausal women or perimenopausal women is their estrogen is off and their thyroid is kind of off, and their cortisol is kind of off, and they've got too much cand ida and because they don't feel good, they're eating more comfort food, so they're eating more sugar and having the extra glass of wine just to deal with life . And so it just all spirals together. And the next thing you know, you got the brain fod. And then you go see your doctor to say, Listen, this is what's going on. I feel like this, this, this, this, this and this. And the doctor kind of rolls their eyes and hands me the Prozac prescription because they don't know what else to do. You know, this is not you're not sick , but you can be so much better . When we talk about perimenopause and menopause, the conversation often focuses on hormones. And let me be clear, hormones absolutely matter. But one thing I think we don't speak enough about is muscle . Women can lose significant muscle mass and strength during the perimenopause to menopause transition and that loss impacts far more than just our appearance. Muscle influences metabolic health, insulin sensitivity, mobility, healthy aging, and more. And the good news is there's so much we can do about it. Strength training and adequate protein intake are critically . And increasingly, we're learning about the role mitochondrial health plays in maintaining muscle quality as we age. That's why I've been paying attention to the science behind Mitapure from Timeline. Mitopure contains Uralithin A, a clinically studied nutrient that supports mitochondrial renewal through a process called mitophagy. Think of it as support ing the energy systems that help keep your muscles functioning at their best. For women who want to remain strong, capable and resilient for decades to come, this is an essential area of research worth knowing about . Visit timeline dot com and use code cynthia for twenty percent off your order. Again, that's timeline dot com and use codecynthia for twenty percent off your order. This is one of my foundational supplements that I never miss. Yeah, and it's interesting because I think that reading the book X Brain was the book that changed my whole perspective not only on HRT, but just some of the neurocognitive changes that are occurring on our brains as we're getting older . And I remind myself and my husband that I have two teenage boys who I don't want to have to take care of me . And so I remind myself it's so important. Like I can deal with a lot of the changes that are happening in my body, but my brain not being as sharp is not one of them. And so to your point , this might be one of the common things that people come to see you for because you're like, something just isn't working right. And I've started sharing that when I first started HRT I was on way too much estrogen and testosterone and I was working with one clinician then switched to another and we had an abrupt kind of washout and I went to a mastermind event in Tampa and I got on the plane, got in the wrong seat, not once but twice . And then when I got off in the hotel got off on the wrong floor , and so I recognized pretty quickly, oh, you know, this is the effect of being super physiologic now not having enough. And my brain is trying to work effortlessly. So for me, I've had that scary experience of just being like, wow, like I knew something wasn't right , but it wasn't until I made the mistake that I was like, oh goodness , this is a byproduct of this low estrogen, low testosterone state in my brain. So perhaps we can kind of briefly touch on what is testosterone benefiting in our brain. Same thing with progesterone. You mentioned that like anti anxiety reduction, relaxation , but testosterone has an equally important component in brain and cognition and motivation . So, so much so. So we think of testosterone kind of as the male hormone, right? But it's so important for us too. It is important for sex drive and arousal and vaginal lubrication. So it's important , you know, for us and for our pelvic floor helps to decrease the risks for urinary leakage, for example . It's important because it helps us to keep our muscles and our bones strong, so that helps to prevent frailty . But it's kind of like our emotional shield , it gives us motivation and confidence and competitive drive and assertiveness and decisiveness . And that's a good thing, you know, at least up to a point. So when it starts to drop, you know, it naturally is going to drop as our ovaries are kind of kicking down towards menopause. It drops because of too much stress. If we got lots of cortisol, it shuts down testosterone. It drops because of birth control pills. Nobody ever tells you that when they put you on birth control pills, but birth control pills shut down testosterone. So women can have low testosterone levels really at any point. It's not just for menopausal women. Super common and we see it all the time in women in their forties. So you might be forty one. You're not thinking about menopause yet, but your testosterone level can be down . And how women describe themselves is just they feel kind of flat, you know, kind of bl ah . So you make your way through your day, you put one foot in front of the other, you do what you got to do. So, you know, if you got to put dinner on the table today or get that report filed or whatever you got to do, you'll make it happen. But if it doesn't have to be today , we tend to sort of procrastinate or just we're not really feeling like it. We don't feel like going to the gym or doing that project or going to meet our friends or just feel like too much trouble. So if somebody sort of asks for you to describe how you're feeling, it's really hard to put that into words. And so a lot of women will use the word like I feel a little depressed , but they don't mean they're like sobbing and hopeless and despairing , they just mean they're kind of just blah . And if you go to again, if you go to your doctor and say I don't feel like myself, I just I no longer enjoy things. Like it just like everything feels harder, you know, whatever, how have you try to put it into words ? They 've got prozac written all over it. And the problem is prozac works in a specific way. It recycles serotonin, which is a brain chemical in your brain. But if that's not the problem, it's not going to . And it shuts down libido and makes you gain weight and then you're even feeling more depressed. So testosterone transforms how women feel . It just gets us back to ourselves again . And you know, if you've got a career and you've got kids and you want to exercise, you've got stuff to do , then you need to have your testosterone going through your system. And it doesn't mean automatically that you need testosterone replacement therapy , there are ways that we can naturally boost testosterone. We can normalize your cortisol. Maybe we can help you find a different path besides birth control pills. We can make sure you have enough DHEA because that makes testosterone from your adrenal glands. So there's different things that we can do, but having enough testosterone makes a big difference. And so for our brain , all of these hormones are so important in maintaining all those connections between our brain cells so that we can think straight and do what we need to do. Yeah, and it's so important. And many questions came in about testosterone knowing that we were going to have a conversation again, not medical advice, but do you have a range that you like to see for total and free testosterone because if we look at the traditional allopathic ranges they're really wide and there's not a lot of there's so much dispar ity depending on who you talk to. I have female clients that will tell me I can get my total tested but not my free. I can get my free but not my total. When we're talking again in like broad terms, what is your comfort zone, your happy zone for you to see a woman's total and free testosterone? Okay, so I'm just going to give you my opinion. This is very controversial . There's lots of doctors that have lots of different opinions. Every lab has a completely different normal range for testosterone . So lab or, the normal range, depending on your age is about four to forty . We use another lab sometimes called LabTech Diagnost ics, it just says anything less than seventy three. So you could be one and you wouldn't get flagged as too low and you can go all the way up to seventy three without being flagged as too high. So there's a huge range and there's no agreement even amongst the labs , let alone between the doctors. For me personally , I feel like if your total testosterone is less than twenty , I'm just going to tell you it's too low. Assuming you're coming to see me because you don't feel good. I mean, if you feel super fabulous, we'll just leave you alone. But less than twenty is when I would say it's slow. If you're between twenty and thirty, I'm going to sort of say, yeah, that's kind of borderline. If you're over thirty , you know, I'm probably going to tell you that we need to look elsewhere for the problem. And part of that comes from when we see women who have PCOS and these are women who they have side effects from too much producing too much testosterone. They often have testosterone levels, forties, the fifties, the sixties . So thirties , you know, is probably okay . So that's where I have landed. The free testosterone for women is actually a lot harder because when your testosterone level is kind of low, that free testosterone test is very inaccurate. It's very difficult for them to pick up those tiny little levels . So if you have PCOS and you have the higher your testosterone level is sixty five, we can look at the free testosterone number and we can sort of use that one more that one more reflects what kind of symptoms you're going to have because that's the active quantity. But when testosterone is low, the free testosterone almost certainly is also going to be low and it's sort of less helpful. So I don't exactly have for men, I definitely have what I think should be normal for women. It's harder. No, and that makes sense. I would imagine that most, again, there's always a percentage of women that are still producing vibrant testosterone levels. I know Dr. Pam Smith talks about the fact that she's a menopause and she still has a healthy testosterone level. And I was like, good for you , the magical unicorn for most of the rest of us, not so much. Now I would love to pivot and talk a little bit about weight loss resistance, which is a hot topic for every perimenopausal , menopausal female trying to figure it out . I know you've talked around a lot of subjects already, lifestyle , low hormones, et cetera. What are some of the less common reasons why some of your female patients may experience weight loss resistance at this stage of life. Okay, if we talk about perimenopause , the definition is that your hormones are changing, right? It's like puberty in reverse. And so progesterone levels are going down, and so women can end up with an imbalance where their estrogen is still where it was, but their progesterone is too low. And that can promote weight gain on the hips, thighs, and butt. When women actually go through menopause and the estrogen drops as well, that menopausal state, those low hormones actually create more insulin resistance . And meaning our insulin doesn't work well. And insulin is the hormone that's supposed to be keeping your blood sugar from going too high . And so if it's not working very well, your body is going to make more and more and more insulin in order to get your blood sugar normal. So at this stage of the game, when you go in for your an nual physical and they check your blood sugar, it looks fine. But the problem is it took all this extra insulin to get your blood sugar back down in the normal range and insulin is the fat storing hormone. So twenty four seven you've got this insulin going through your bloodstream constantly telling your body to store more fat. And so if you go walk around the block and do some exercise, you'll use some stored energy in your muscles and then you stop walking and you eat something and you put it right back again, completely bypassing all that stored energy in your fat cells. So insulin resistance is a huge , huge reason for weight loss resistance. And it just gets worse for women as our hormones change. And the toxins in the environment make it worse. And then our thyroid that's not working well, even though our doctor told us it was normal. Slow right thyroid is what sets your metabolic rate. So even if it's not like full blown off the deep end hypothyroid , if it's not really doing a good job, then your metabolism is kind of sputtering along. Testosterone maintains your muscle mass and your musc les are what drive your metabolic weight. They're the ones that burn a whole lot of the calories. So naturally as we age and our testosterone levels go down, we naturally lose muscle mass . And that means that your metabolic rate is going to go down over time. And so you can still weigh the same amount. You can generally kind of look about the same size, maybe even fit into the same size clothes, but now you have more body fat and less muscle. So you don't look the same. You know, your waist doesn't go in nicely. You're kind of straighter . Maybe you got that little belly fat that we get at menopause and everybody hates and you can kind of progress over time. So maintaining your muscles is something that's so so important for us as women . And Dr. Gabrielle Lyons has a new book out. She's all over right now talking about this. But so testosterone is an important piece, but you can't, I was just talking to somebody this morning. You can't just be on testosterone and have more muscles . You also need to eat protein and you need to do exercises resistance exercise. So you gotta have the whole picture. But these are all things that are changing. And then as we age , our cortisol level on the whole tends to go up and our DHCA level on the whole tend to go down. So those are the two from our adrenal glands. Cortisol is the one that ages you faster, it goes up. DHEA is the one that slows down aging, but it goes down. So now we just age at a more rapid weight and cortisol makes us gain weight, right? We all know cortisol is the one that puts on the belly fat. Cortisol makes insulin work worse. So now you have even more insulin resistance . And you can make a little bit of estrogen and progesterone and testosterone