Menopause and the Female Brain
S2, E17
April 10, 2024

Dr. Lisa Mosconi is a neuroscientist and educator known for her work and research on Alzheimer’s Disease, and the author of The Menopause Brain(published March 2024). She joins Stacy for an informative and expansive conversation about menopause and the female brain. Through brain imaging studies, Dr. Mosconi found that women in midlife show red flags for Alzheimer's disease and have reduced brain energy levels. In this conversation, she explains how women can optimize brain health to prepare for and manage menopause. Stacy and Dr. Mosconi discuss what actually causes hot flashes, the lifestyle changes that can help alleviate menopause symptoms, and Dr. Mosconi explains how the brain rewires itself to our benefit as we age.
Hello Menopause is a podcast from the national nonprofit Let’s Talk Menopause. Produced in partnership with Studio Kairos. Supervising Producer: Kirsten Cluthe. Edited and mixed by Justin Thomas. Artwork by Stacey Geller.

Thank you to Always Discreet for sponsoring this episode of Hello Menopause. Always Discreet, because we deserve better. Available at Target. Please rate and review the show on Apple, Spotify, or wherever you get your podcasts.

Stacy London: Welcome to Hello Menopause, I'm Stacy London. Dr. Lisa Mosconi is a groundbreaking neuroscientist focused on Alzheimer's disease, particularly in women. And her research is focused on how genetics, hormones, environment, and lifestyle shape the female brain. She's also the author of the bestselling books, the XX brain and Brain Food. And her TED talk has been viewed over 2 million times. Her new book, The Menopause Brain is out now. Please welcome Dr. Lisa Mosconi to hello menopause.

I am so excited to finally virtually meet you, Dr. Mosconi. I have been following all of your work. I am so excited. I'm such a fan. I'm like, I feel like I'm fangirling out. Like some people love Taylor Swift and I love you.

I'm so grateful for all of the research that you're doing and, and I want to talk about your book and there are so many things, but I will say you are the only person I was actually nervous to interview. It's such an honor to meet you. And it really means a lot to me that you are participating in this season with us. I'm sure we could have you on like 15 times and we'd still have more to talk about. We hear so much now, um, about menopause and about a lot of the mental and cognitive, uh, you know, changes that can occur. But I think that people are confused by the fact that menopause does not just, you know, really focus on the ovaries, right? And you are a specialist in talking about menopause and the brain. Can you talk a little bit about how you started this research and why you made this connection so early?

Lisa Mosconi: I wouldn't say so early. Actually, it took a minute. Um, yeah, so I am a neuroscientist. I'm a brain scientist by training, but I specialize in nuclear medicine, which is a branch of radiology where We use tracers that go in the brain and then you can see those beautiful maps of the brain in different colors that most people are familiar with. So my approach to the brain is quite vertical. You know that we study neuroscience, we do brain imaging, we go deeper and deeper and deeper. And I actually specialize in Alzheimer's disease and the prevention of Alzheimer's disease and cognitive aging and more broadly neurodegenerative disorders. So for me, the idea that I would be here with you talking about menopause is very bizarre. Like just 10 years ago, I would have said just, there's no, but it's the research that really convinced me otherwise. So ever since I was probably in grade school, I wanted to study the brain and my parents are nuclear physicists. Both of them. Oh, wow. Yeah. It's very interesting. So my family almost completely split. Half of us have a PhD either in physics or biology or something like hard science, and the other half is in the army. Oh

Stacy London: That is a crazy combination, but you know, brains and brawn, right? I'm sort of into it. It's like as a family, you have everything you need. You've got like, you know, right? That's amazing. That's amazing. What a funny split.

Lisa Mosconi: Yes, it's very funny. It's like when one kid is born, the gods just toss the coin and it's like, all right, are you going to be a scientist or a soldier? And they really do not overlap. It's really interesting. It's family reunions and whatnot. But then the point is that I grew up with my parents because I'm an only child. And so my parents are really scientists, like 100 percent scientists. And they would grow up and dinner conversation was around positron decay and, you know, accelerators and gravity and bosons and stuff like that.

So I always wanted to use those techniques to do something that was interesting, more interesting to me personally, which was really brain health. And in part, that was because I have a family history of Alzheimer's disease. that affects the women in my family. So my question was always from the get go, is there something about being a woman that puts you at a higher risk for Alzheimer's disease, or is it just that women live longer than men, which is usually the pushback I get in my research, or are there any other factors at play?

So my whole research started from my PhD. And I started very early, even the PhD in a way. So I've been doing this forever. And every decade at this point, and my whole work was really focused on showing that Alzheimer's disease is not a disease of old age, so longevity doesn't quite matter, but rather it's a disease of midlife with symptoms that start in old age.

But the disease actually starts with negative changes in the brain years or decades before the symptoms become evident on clinical examination. So that completely changes the question to, okay, if Alzheimer's is a disease of midlife and women have a greater lifetime risk for Alzheimer's than men, then what happens to women?

In midlife, they could potentially explain the higher risk of dementia down the line. And we're doing all these brain imaging studies and we, we were comparing midlife women to men of the same age. We match them by age, right? If I have a 42 year old woman in the study, I try to find a 42 year old man and we keep going.

We have hundreds and hundreds of people in the study. Thank goodness. And, um, We really bless them for doing that and when you compare the brain scans you find that on average The women tend to show red flags for alzheimer's disease in their brains already midlife in their 40s and 50s

Stacy London: Talk about those red flags a little bit.

Lisa Mosconi: So the red flags are indicators of Alzheimer's risk. They're not a diagnosis of Alzheimer's, just a sign that your brain may be in danger of developing Alzheimer's later on in life because maybe the memory centers of the brain show a little bit less volume. The neurons aren't quite there. Right. Or maybe over time, maybe you lose neurons at a higher rate than a man of your age, of your same age.

What we find consistently is that brain energy levels are reduced. The brain seems to be under stress. And that results in a reduction in the rate at which the brain is able to burn glucose or other substrates to make energy. And that is very specifically found in the parts of the brain that are also impacted by Alzheimer's disease in the same exact way.

So if you compare the average woman's brain in midlife to that of a patient with Alzheimer's disease, you can see a little bit of the same pattern, just obviously not as strong. Red flags. are there. And this is obviously not universal. There are some women who show no changes whatsoever. Women who show more severe changes.It's more about connecting the two things and say, this looks a lot like that. Could it be a precursor? Could it be something that leads to the Alzheimer's pattern at some point in your life? We find more Alzheimer's plaques, for instance, in the brain of midlife women as compared to men of the same age.

So the question was why? Is it just that women are just like that? Or is there something that could explain? Because when we do a statistical analysis, we're always looking at the average difference, right? So this is the group of men, women, this is the group of men. On average, they're different. But there's also quite a bit of overlap.

Like I was saying, some women show no, no issues at all. Some women show more severe red flags for Alzheimer's. So what could it be? And we looked at, believe me, we looked at everything. We looked at genetics. We looked at family history. We looked at things that we know are not so great for your brain, like having high cholesterol levels, or high triglycerides, or insulin resistance, or having a poor diet, or having no exercise, right?

We looked at everything I could get my hands on, and that, yes, that helped a little bit, but couldn't quite tell the groups apart until one day, my students were doing cognitive testing on one of our participants, and she was having a really hard time. She was like, I really can't focus. Can you open the window?

And they were like, uh, open the window? Why? And I just say, because I'm having hot flashes and I can't think straight. Oh my gosh. And we don't Oh my gosh. You know, back then, we did not do menopause. So my students were like, you're having what? I don't know, these are like kids who are fresh out of college.

Maybe in their 20s. Wow. They had no clue what menopause was. No idea. And we didn't talk to them about it either. And she was like, yes, yes, I'm sweating and I'm having the brain fog. I need to come back. No, in the end they were like, absolutely take your time. We can just reschedule. Don't worry at all. And then they ran to me in a panic. She said something about sweating and the window and I don't know what's going on. And do we need to call the emergency room?

Stacy London: And did a lightbulb go off for you? Were you like, Oh my God, that is the one thing that we have not looked at?

Lisa Mosconi: Yes. And I said, huh, that's a good point because menopause, a lot of women with menopause come to us because of brain fog.

Stacy London: Absolutely. I mean, I couldn't remember my name.

Lisa Mosconi: That happens a lot. In our studies as well, but I always start that our work was more about reassuring them that it was not dementia, the brain fog. But then we were like, wait a minute, she was doing poorly on cognitive testing because of this. And so we went back and we worked with the OB GYN department and they were just as surprised as we were to be like, hey, I need you for neurology.

Stacy London: What year, what year, what year was this? I'm so curious.

Lisa Mosconi: 2014.

Wow, wow. So think about that. I mean, it's just like we're just over 10 years of this insane discovery that is so amazing. so important to understanding women's health overall.

Lisa Mosconi: And so then we went back and we were able to do menopausal assessments on almost all our participants. And then you've got it because you look at the brain scans and the data and before menopause when women have a regular menstrual cycle, their premenopausal, there's no difference with men's brains.

They're all fine men at the same age, but once we're looking at women who are perimenopausal as compared to the men of the same age, then we see a little bit of a difference. We see an emerging, the onset of a difference, the start of a difference. But then when we go to the postmenopausal stage, then there's a difference.

like a significant effect. So there seems to be something about the menopause transition that's like a little bit like a tipping point for the brain to become more sensitive, if you will, maybe more vulnerable to a medical risk that is now becoming a medical finding. Right. And that was the first study that we published was in 2017. And this is also interesting because they, as I said,I'm an Alzheimer's person. I'm not an OB GYN, you know, I'm not a menopause special. And so I was like, Oh, this is very important, I think. And this is interesting. There's also a lot of preclinical work showing menopause, basic science work showing that menopause is a trigger for Alzheimer's disease, at least for some women, obviously not for all women. So this makes sense in many more ways than just us stumbling upon something. What's been done? It's already been published. What do we know about this? What can we add to science? And guess what? There wasn't a single study that looked at the brain of women at different stages of menopause.

Stacy London: I mean, there was no research whatsoever.

Lisa Mosconi: No, we couldn't find any. And I believe that our study is widely recognized as being the first in the field, I think.

Stacy London: And Dr. Mosconi, I'm just curious if you think that the reason for that was that, you know, we weren't talking about menopause for so long and menopause gets conflated with aging and then you're talking about women. So it's almost like these three marginalized categories that nobody in medicine is paying attention to that much anyway, right? And that, you know, we're really, that was sort of the hurdle is that none of these things, women's health was not being studied before 1993, right? In. It wasn't required to be in any kind of physiological testing. And then age seems to be like, we get written off the older we get anyway, right? And then nobody knew anything about menopause. To me, to be able to get to that aha moment must have been so gratifying for you. I mean, just in terms of being a scientist and a researcher, to understand that you made a connection. I mean, I feel like you should win the Nobel Prize, like who makes a connection like that? Yeah. You know, it's so, to me, it's so exciting. These are aha moments.

Lisa Mosconi:. It was aha, yes. It was quite interesting for the reasons you mentioned that I, I was never taught anything about menopause and I have 23 years of formal education and not once did anyone mention menopause to me in a four month educational setting, which is insane. And also to the point you were making before about aging, the other issue is that very little research is done on women in midlife. There's research. on younger women, especially pregnancy, puberty, a female specific in quotes things.

And then there's research on individuals who are 65 and older, which is the Alzheimer's research in general starts at 60, 65. And so there's that window. or the menopause transition that's usually not captured when you do a brain study. And yeah, I mean, those are the effects. Also the other problem for me as a brain scientist, or as a brain specialist, I don't know if I mentioned that before, but I took over the Alzheimer's prevention clinic as well.

So I run the Alzheimer's prevention clinic at Weill Cornell Medicine and I'm in charge, I launched and I'm in charge of the entire Alzheimer's disease prevention program. of what could not medicine. So we also do clinical trials and Menopause is a strange factor to include in the research on Alzheimer's.There aren't that many people who were doing it until we started. So that was quite interesting. But the problem from a clinical perspective is that menopause is considered an issue with the ovaries, right? And it's been relegated, for lack of a better word, but it's been confined to the OBGYN territory, right? So the department, the OBGYN, and we, we don't usually work with them, but the problem is, as any woman can tell you, right? So what was interesting to me is that OBGYNs are not trained, obviously, to diagnose or manage brain health. It's just not in their curriculum. It's not something they should be doing, frankly.

But also, many OBGYNs are not even trained to manage menopause. It's one in five, I think, in the United States. And the problem on the other hand is that brain specialists really don't do menopause at all. And we don't, there's no framework that integrates these different disciplines so that we look at a woman as a woman, as an organism, rather than different organs that magically come together and make a person. So this is a big issue. So as soon as I said. Yes, I'm taking over the Alzheimer's Prevention Clinic. The first thing I did was to call, to call my colleagues in, you know, began the Midlife Clinic at Weill Cornell, the Reproductive Medicine at Weill Cornell, um, Obstetric, uh, Oncology and Gynecology at Weill Cornell.

So now we work together and they send their patients to us when there's a concern around brain health and brain fog, especially when we get a lot of that. And we send our patients to them to make sure that we have the right information about their patient's menopause and how best to address whatever symptoms together. So it's a super comprehensive approach that I think will be implemented in many centers in the future.

Stacy London: I want to talk a little bit about the neurological basis for what we see as some of the most common symptoms in menopause. I don't associate a hot flash with anything brain related, because I'm hot in my body and I just think I'm getting hot. I don't know how that's happening. What are some of the neurological basis for these kinds of issues, even, even brain fog? What, what is causing that? And what have you seen? You talked a little bit about, uh, the postmenopausal brain being significantly different and that it has gotten smaller or shrunk in certain parts. I'd be curious to know what your studies have found.

Lisa Mosconi: Yes. And I would love to just. Preempt that we're doing more studies and that research is always step by step. So the very first study we did had maybe 60 people on, you know, because it was such a weird thing to do. And then the second one had like a hundred and then the next one had 200. And now we're looking at hundreds and hundreds. So. I am refining my way of answering these questions as I update my own knowledge, because unfortunately there's nothing else. We've remained one of the very few teams for looking into this question, but now people have started replicating our finding, which is amazing.

There was a wonderful study, um, using data from the UK biobank that replicated this difference in gray matter volume and concentration. So as women get. Also older, but especially as women go through menopause, which can be really at any age, you know, there are women who are in full blown menopause in their 40s and women who don't hit menopause until their late 50s. So obviously it's just not chronological age. It's more like menopausal age. This seems to really drive the brain findings, which I think is very interesting. Um, and overall what we find is that menopause is a neurologically active state. Right, so it's a neuroendocrine transition where the brain is as involved as the ovaries are. And both are changing with the difference that the ovaries can stop making estrogen and progesterone, but the brain is to carry on for another 30 years.

Stacy London: And what are the roles, let's say, of estrogen and progesterone? Like we know that we start to lose them in menopause, right? Or, or, you know, there's a more drastic drop in estrogen, I guess, and progesterone is a little bit. slower if I understand that correctly. Um, but what does that mean for our brain having to go on for another 30 years without those hormones or at least those hormones in a much smaller, um, degree than we had them before?

Lisa Mosconi: Yeah, it means that the brain needs to adapt and needs to make adjustments to lead to the neurologically active state, which means that at least we believe that the brain is rewiring itself. in a way that is conducive to a non reproductive stage of life, which I find sublime. So I'll tell you what my personal interpretation is. So women or individuals with two X chromosomes and or, and a female in quotes, reproductive systems at the minimum with ovaries. Yes. Two X chromosomes and or ovaries are also born with a brain that is deeply connected with those ovaries and to the XX chromosomes and other genes obviously as well via a neuroendocrine system. So this is a whole system that connects specific parts of the brain, external parts of the hypothalamus. It's a very important part of the brain, and I'm going to go back to the half flashes because of the hypothalamus. But it connects the structure to the ovaries, to the system that is present at birth, but is effectively activated at puberty, then gets over activated at pregnancy, every time a woman is pregnant, and then is transcribed.At least partially turned off after menopause. So if you think about it in this way, that menopause is no longer some alien thing you've never seen before. It's not something weird that's happening to you, that's hijacking your brain. You've actually seen some of the symptoms and changes before in your life. In puberty, which may be a little while ago, but certainly, uh, Any woman who's ever been pregnant had a little bit of a preview of what men can be, right? So what happens in puberty and pregnancy is that even though you have a ton of hormones going all over your body, your brain actually shrinks and you lose neurons. And these lost neurons are supposed to be what triggers the symptoms that can happen in any of these transition states. I call the three P's, puberty, pregnancy, perimenopause. So you lose your brain, you lose your neurons. Why? For two good reasons. The first one is that you don't need to have all those neurons. Right? At some point, you have learned so much in your life, that certain things become automatic. You just do them on autopilot. So the brain doesn't need to hold all that stuff, because it's very metabolically expensive.

Stacy London: It's like taking out the trash, right? I mean, I'm thinking about it in terms of a computer when you go to empty the, the, the, the, the trash widget, not, not, not, uh, not that our brains are garbage, just to, just to be clear.

Lisa Mosconi: Yes, you do a cleanup, right? Makes sense. And you upgrade your operating system in a way that makes it leaner and meaner. You always want to go smaller, right? So that's a good way to do it. At the same time, this rewiring also improves your brain in many ways. That during puberty, there are very specific parts, and pregnancy as well, there are the same parts of your brain that are connected to your ovaries via the hypothalamus that get stronger and better connected together. So you have fewer neurons, but better connected with each other, which is what makes your brain resilient. from a neuroscience perspective. Now something similar seems to happen in menopause. Which could be another biological clue for your brain to get rid of stuff that it's not going to use anymore. Like all the neurons that are there to enable a pregnancy, right? You're not going to be pregnant anymore. So all these apparatus are no longer needed. And I think this is why there is a rewiring and a remodeling where these neurons are gone because you don't need them anymore. Your brain is very smart. You know, nature is really smart. And the importance that you're holding in your brain becomes a little bit stronger in certain parts of your brain that once again are involved in things like empathy, emotional regulation, social cognition, sustaining happiness. And this is the latest research on menopause. So the rewiring on one hand triggers some symptoms. Right? A hot flash with adenosine triggers this intense, the hot flashes, night sweats, sleep disturbances, changes in mood, the brain fog, the memory lapses. And that is challenging and needs to be addressed. But I think it's important for women to realize that it's probably a good thing in the long term. Right? It's what enables your brain to just get rid of stuff it no longer needs most likely and prepare you woman for the next stage of your life. That is no longer Reproductive, but it can be just as productive.

Stacy London: Productive exactly what I was going to say and I have to say Dr. Mosconi, that listening to you explain this It literally makes, it's like an aha moment. Just this theory makes so much sense to me. And as somebody who had a very, very difficult perimenopausal experience where I had every symptom that you can think of, I mean, beyond 34, I just, I really struggled with it. mood and um, I had food allergies all of a sudden and you know, I've just everything that you can think of. Muscle pain, brain fog. I, I, and I was terrified actually at one point that I had Alzheimer's. I could not understand, I couldn't sleep, I gained weight, I mean everything that you can think of. What I, you know, what doesn't make sense is to, I think that we, we panic when we don't know what's going on and nobody ever said the word menopause to me.

So I thought I was just losing my mind and didn't understand hot flashes and night sweats and didn't understand brain fog. And to me, this idea that the brain is rewiring itself to be productive for a different stage of life is also so optimistic that if we knew that going into this conversation about menopause, it's what I always say, if I knew a Mack truck was coming for me, I could have stepped out of the way instead of getting, you know, getting hit.

But this idea that, um, the brain is actually doing something productive for us, even if there's like a little bit of tumult on the way there also feels very exciting. And I remember from, uh, you did this incredible TED talk on menopause and the brain, and I'm pretty sure you said that it was the executive function of the brain that dissipates a little bit in menopause. Is that correct?

Lisa Mosconi: Well, there are cognitive changes that, that, that can take place. Um, this is an interesting conversation actually, because the reason that women come to us is brain fog. Yes. Now, brain fog is not a clinical term. Right? The clinical term is cognitive fatigue or mental fatigue, and it's very, yeah, yes, I hear that a lot, and a lot of women have it during pregnancy as well. They feel foggy and have a hard time just staying focused. They just feel tired, like their brains are tired. And they think if you have it during pregnancy, there's a strong chance you have it worse during menopause. So there's something just good to consider. It's the same brain, you know, it's the same network that changes in that is impacted by this process.

Stacy London: I, again, this is why I think the continuum that you're talking about in terms of having an XX chromosome and ovaries is so important because that communication is happening at every one of these Stages. If we knew that, if we were aware of that, I think that it would make these conversations a lot less scary for a lot of people. Yes. That, you know, there are so many people even asking me, I, I don't know what's happening. I've never felt this way before. I can't control my emotions. Things that are, are even bigger than brain fog that we don't necessarily associate with cognitive health.

Lisa Mosconi: Exactly. Anxiety. You know, some women are suicidal. I think one thing that is completely missing from the conversation is the range of menopausal symptoms because we have vocabulary for, let's say for pregnancy. There's an understanding that there are mood changes that can occur with pregnancy. For some women are mild, like the baby blues, whereas some women are severely depressed for a certain amount of time, postpartum depression. Some women develop postpartum psychosis. It was only in 1994 that these words came to reality in a medical textbook.

Stacy London: Isn't that amazing? Because ‘93 is when women started to be included in clinical trials or testing. A year later and we understand that there's something called postpartum depression or psychosis. I mean, that's, that's pretty telling.

Lisa Mosconi: The concept that hormones would drive a woman crazy was deleted from medical textbooks in 1984. 84! I was born! This is insane! Anyway, going back to menopause, the point is, with pregnancy, now we do have a vocabulary that formalizes these different expressions of mood changes with pregnancy and other, you know, the mommy brain isn't quite a thing yet, but it will be, I think, soon. But we don't have the same framework for menopause. Menopause is menopause. There's no understanding that number one does not happen when you're old. It actually happens when you're younger, by every standard.

Stacy London: I thought it happened in your seventies. That was my, that was my impression. Never occurred to me that it would start for me at 47.

Lisa Mosconi: And you know, the other, so everybody says the average age of menopause is 51, 52. But then if you look at women globally, it's actually 49. So it's going to be younger than that if you don't just look at white women. You know, high socioeconomic standards, this is actually 49 years old, which is even younger. Number two, it does not happen overnight. It's actually a process. The end of your menstrual period is probably the least important thing in the entire transition because the actual trouble is before, in the two to 10 years transitional phase that's now called menopause transition or perimenopause depending on who names it. And that's when your body's changing the most and your brain at least is changing the most during that time. And number three, that this process is not uniform and it's not linear and does not impact all women the same way. So there are women who breeze through menopause, which is amazing. There are women who have discomfort. There are women who have moderate discomfort. There are women who are severely impacted, and there are women who are really close to suicide, and this diversity and range is not recognized. It's not formalized. Therefore, there are no treatments that are tailored towards every woman's experience of menopause.

We just have one, two standardized doses of hormones or, you know, but there's not much of a range in therapeutic options. And I think that's a, it's a huge missed opportunity because You know, uh, by 2030, 1 billion women will be in menopause or close to menopause. And menopausal women are the largest growing segment of the population, at least in the United States, but I think globally as well. And most women spend over a third of their lives in menopause. And we don't embrace it, we don't celebrate it, we don't even acknowledge it most of the time. And whatever support we have, it's sad, it's miserable, it's really just not much.

Stacy London: Well, what I wanted to say that I think is so interesting, and we'll get back to the hot flash questions and how things are related to the brain, sorry, because this is all so important. Because I think what you're. What I'm talking about here is the fact that there is no nuance to understanding the menopause experience. It's why we talk in these generalities. There are 34 common symptoms. You may experience them. You may, some may be severe. Some may not be severe because we don't know. We don't know enough about the mechanisms that are causing menopause for us to be able to say, well, if you're having, experiencing light symptoms, here's, you know, the recommended therapy. Or, you know, if you're suicidal, here's, Here's another recommended therapy. They might be completely different if we understood the nuances, um, because there's no such thing as individualized medicine for one billion people, right? But we don't, we're doing it so, um, generally that I think a lot of people feel like they're being miserved or it's a disservice. It's one of the things that I talk about all the time is sort of advocacy as a patient. Really, you know, coming in with as much information, as informed questions as you can ask. Otherwise, you're probably not going to be able to get information the way that, that you're, it makes sense to you or that you're able to understand it. Because most doctors, as you said, one out of five really understands the menopause transition.

Lisa Mosconi: You know, I was talking to a number of colleagues of mine, you know, began, I was like, okay, you are trained in menopause, but what does that mean? Because I am trained in brain health and that means like eight hours a day for five years and longer. They're like, no, I mean, it was like maybe 10 years, 12 years in total. I, I, and I want to really know everything about anything.

Stacy London: So exactly. And I'm wondering if it's gynecologic, if it's neurologic, if you need, you know, cardiac, uh, like somebody, you know, working on heart health for the menopause transition and bone health for the menopause transition. And, um, you know, I keep going back to this idea that if you have an XX chromosomes and, uh, ovaries, we just don't understand how much more complicated our physiological states may be or how they're connected because we've just seen it through this kind of patriarchal lens of, of an XY chromosome body, right? Which is not the same.

Lisa Mosconi: No, it's not the same. And also, I think our biology has been downplayed and overlooked forever, because we even think of aging as somewhat of a linear process, right? I hear it all the time that people are aware of something like, as soon as you hit 30, 35, you start losing a little bit of neurons over time. That's if you're a man. If you're a woman, the process looks a little bit like an up and down more wavy, up and down. You know, they're kind of that because you start puberty with a massive remodeling that activates your ovaries. And at that point, on a weekly or bi weekly basis, your body's changing just a little bit, but so is your brain. Every time your ovaries go through a menstrual cycle, your brain goes through a microcycle as well.

Stacy London: I've been thinking about that straight line versus the wavy line when it comes to aging or menopause or the physiological effects on our body. Do you think that we Think of aging as something linear because that's what happens to men or people with an XY chromosome.That's the only lens we've really seen it through. I just wonder if people with an XX chromosome have never had a straight line. It has never been a linear process and we've just never studied it.

Lisa Mosconi: No, because we don't know all the brain, the vast majority of brain imaging or brain studies either use. Male mice or male animals are different, right? Or they lump men and women together. Together. And then they use statistical procedures to remove the effects of gender.

Stacy London: I mean, it just sounds outrageous to hear it out loud.

Lisa Mosconi: There's a reason for that. And the reasons are rooted in biology because neuroscience was born back with Darwin, right? The father and mother of biology who. number one was a profound misogynist, and number two did not believe the women were worth studying. And afterwards, neuroscience kind of embraced this doctrine that the only difference between men and women is the way that the reproductive organs function, and that these differences are not important for brain health, except there's some over exaggeration in there and that increased volatility, which is what led to men being studied because men do not have this kind of hormonal changes or fluctuations. So, and it also sort of led to the cultural bias that women are hysterical or that, you know, that's because, because we don't have this. Same kind of, um, straightforward, linear approach to help.

Stacy London: I mean, it's, it's heartbreaking to hear it, but it's also, um, amazing that we're talking about this in 2024 and that it's just now that, you know, doctors like you are, are, are not only making this distinction, but make, recognizing that there are different mechanisms at work.

Lisa Mosconi: You know, it's hard for a scientist to - look, women have been different from men because that means that you effectively need double the sample size and twice as much money. So it's not necessarily up to a scientist to decide.

Stacy London: It always comes down to money.

Lisa Mosconi: It really comes down to money. And until very recently, sex medicine was not a priority for funding agencies. It's still not really a priority, but it's becoming more of a priority. And I think that the fact that so many women are now really interested in menopause and brain health and just overall women's health done right and remedies for menopause, I think it's opening up where more and more women are realizing that research has not been done. What research we have was flawed, like the Women's Health Initiative, which is to this day, that the media don't, didn't help that much, actually made things worse, like 20 years ago. And we're still suffering because of the media misrepresentation of research findings. And I feel like this generation of women really is used to fighting. And, you know, they don't want to be silenced. They want to fight for their rights and they want a solution and they refuse to suffer in silence because look, pause is, oddly enough, it's, it's a very unique scenario in medicine. We're suffering in silence. It's not only accepted. It's actually encouraged. Yes. And it is so bizarre because of culture, because of medical misogyny, because of bikini medicine, women have been made to believe. We have been made to fear our hormones and distrust their brains. It's really in our culture like you're having a bad day.You must be hormonal. You're upset with me. Oh, you must be PMS. It's not something I did. Of course, it's you. It's all in your head. It's your hormones. So there's a lot that needs to happen. We need to fight the stigma. We need to realize that a lot of things are really sexism and ageism rather than biology or hormones. And, and then we need to start asking for solutions and for science, for all the things that we never had.

Stacy London: This is sort of, it's amazing to have this conversation with you having done, some prior episodes, that this is the resounding opinion of all the doctors, right?

Lisa Mosconi: Yeah, what's really interesting to me is that when I wrote The XX Brain, it came out in 2020.

Stacy London: Yes.

Lisa Mosconi: It was about Alzheimer's prevention, but it was one chapter about menopause. And all everyone wanted to talk about was menopause and how menopause affects the brain. Because back then it was interesting that when people wrote about it or talked about it, they would quote me. They would say, Oh, she says this, or menopause impacts the brain as much as the ovaries according to her. And now it's actually a fact. It's like 40 years later and they don't feel the need to say somebody said it, not me. I'm not sure. It's more like, no, now it's recognized. It's understood. And we're actually trying to learn more about it. So I feel really happy about that.

Stacy London: So I just want to go back to some of the, kind of, you know, nuts and bolts of this because we, you know, we've been talking about this in generalities, how you got to, um, this, you know, area of study, all of the things that, that, that sort of feel like, you know, just inequality and iniquity around, um, female health. But, you know, I'm curious if you can talk a little bit about, um, what are the key areas of cognitive function that are most affected by the changes that are, we're experiencing in menopause? Um, I, you know, I know we say brain fog, but what does that actually mean scientifically?

Lisa Mosconi: You know, it's a really good question. It means different things to different people and it depends on what is causing the brain fog. So brain fog is found in a number of conditions besides menopause and it's been formalized only in very few conditions like fibromyalgia and for COVID, long COVID. Now there is a sort of attempt at least to quantify this brain fog and describe it. We're actually doing this for menopause right now. Which I'm very excited about. We're trying to come up with a formal, yeah, with a formal definition of brain fog, quantitative measurement of brain fog, because obviously there's no fog in your brain that I can measure, but there's a lot of parameters that are impacted. And we're using a combination of cognitive testing and questionnaires. And obviously brain measures to come up with a brain fog score or index.

Stacy London: Yes.

Lisa Mosconi: That can be really helpful for research. So from a cognitive perspective, brain fog typically manifests in two ways. There's a self awareness that your level of cognitive performance has declined relative to your typical standard. So that, in my field, is called a subjective cognitive complaint. SCC or subjective memory complaint, but brain fog is more than just memory. So there's this self awareness or self reported change in cognitive performance that is very upsetting and very unsettling to many, many women. However, When we try to objectify, when we try, when we do cognitive testing and we measure those cognitive domains that we measure memory, we measure executive function, we measure perceptive speed, we measure fluency.

You were saying [you] had a hard time with wording. That's very common. We measure, we measure so many different things, um, with memory. Lots of different aspects of memory, like, um, short term memory, long term memory, free recall, queued recall, retracted memory, recognition, verbal memory, visual memory, you know, all these different aspects. And what happens here, which I think is very interesting, is that they don't match. a woman's self report. In that, this is what happens. This is, at least in my hands, this is what happens. Let's say we're using a test, like it's called the MOCA, the Montreal Cognitive Assessment Scale, that looks at global cognitive function.

Let's say that before menopause, you were 30. which is the highest score. As you go through menopause, there's a chance that your score may go down to 29 or 28. So it's a two point decline. It's not for all women. I'm just saying it's an example, right? So let's say there is a two point decline. Now for you going down from 30 to 28 means that you can't going down to zero. It means that you don't remember where you put your keys. You can't come up with words. You're feeling all tired. You can't just do mental arithmetics, but 28 is normal. is within normal cognition relative to all other women your age and educational level. So yes, there is a little bit of a change. However, the change does not put you in the impaired range, which starts 26 and times below 24 is more. It's more concerning.

Stacy London: So I think that it's really that when, when you're talking about that, that, that, um, self diagnosis, I'm just going to call it for a second, or, you know, that self reflection that, um, things, you know, if we're so used to being quick on our feet, if we're so used to being, you know, I mean, there were times where I was like, Oh my God, I can't remember the noun for that, for a bottle or a pencil or, you know, something like that.

And, I thought it was the end of the world. And to, to, to feel that, like, you know, that my cognitive functioning wasn't at the level that I was used to is very different because that obviously your, your personal standards are going to be different from what you see scientifically and globally. But what, how reassuring to hear that this is, this is natural.

Lisa Mosconi: So there is this dip in cognitive function. What happens post menopause if there has been a dip? So, and this also, just to draw a parallel to the brain scans, the brain scans have not been used to show what happens to menopause. So that is one person, right? So we see something very similar as with the cognitive testing, especially with brain energy levels, that there is a little bit of a dip during the menopause transition. Then what happens after it's been explored, but at least with us, we find three possible outcomes. The most common outcome is diesel. This is before menopause. You're high up here. It goes down a bit during menopause, but then it stabilizes and that's your new baseline. That's very common. Then for some women, they may never show a change. But let's say that you do show a little bit of a change. So you start here, you go down and then there's a rebound. For some women, cognitive performance goes back to premenopausal levels or a little bit somewhere in between. Right. And this is the other outcome. It's a great outcome, frankly. Then there's one that is not as good, which is that you start here, you go down, you keep going down. And this is not easy, obviously, but it's important to be aware and have, I think, an objective measurement of this change, because then it's when we start talking about Alzheimer's prevention and potentially you know, some medications or lifestyle adjustments or things that are important, I think to support your brain health. If there's evidence that cognitive performance is not stopping, but keeps going down, it's time to intervene. You know, you do brain scans, you find out if something else is happening and do something similar with the brain scans. There's some parts of the brain, maybe showing a little bit of a recoup for some women. For most women, they stabilize over time, which seems to correlate with the easing or the symptoms of menopause as well. Right. Eventually the symptoms get better or go away for most women, not all women, but most women. And that is a sign. We think it's a sign of brain adaptation to menopause. But for some women that doesn't happen, they keep declining.

Stacy London: Is that, is that just all symptoms of perimenopause, not just brain fog? Like, let's go back to the hot flashes for a second. Yeah. So hot flashes start in the brain, right? Is it that they get, you know, really hot? Some women may get severe ones like I did, but they were severe in quality and they were frequent. And that's not everybody's experience. But what does that mean that there was something specifically happening in my brain in terms of a dip? Was that a dip of estrogen, or is there something in the brain that causes hot flashes to happen?

Lisa Mosconi: So, there's, there's a few things that converge up to a certain point, they're complicated because there isn't a lot of research that's been done. So I'm just being cautious, you know, maybe perhaps we don't know we need to replicate. What we do know is that this structure in the brain that I mentioned before, it's called the hypothalamus that is directly connected with the ovaries is also this structure. Or one of the key structures that regulates body temperature or thermal regulation. And it's actually the node of activity where all the estrogens are right to the brain. And it's therefore very easily impacted by the fluctuations in estrogen concentration. So what we believe may happen is. a misfiring hypothalamus that is activated by estrogen in bursts rather than consistently because the concentration is jagged, right?

And these bursts activate the immune system as well. That starts, you know how it works in the brain, the immune system? So there's very little structure. They're called activated microglia. Those are, um, the first line of attack that the brain has against any issues or pathogens or things that the brain feels like shouldn't be there.

So this little thing that the migrate towards the side that has issues, they move inside the brain and they can go straight to the hypothalamus that is behaving weirdly. Thinking, oh my goodness, is there an issue? Let me just shoot you with cytokines. That's what the hypothalamus can do. And this is very new research. This is something we're testing. This is what we believe may be happening. It is a convergence of factors. The estrogen is fluctuating, it's acting weird, so the hypothalamus already can't quite Keep it together, in a way, in the brain all the time, regulating your body temperature.

Stacy London: The hypothalamus is being hysterical. Exactly, right? It's like, but are there, and are there different parts of the brain that are affected or different symptoms that are, um, that derive from different parts of the brain. So we know the hypothalamus is about thermoregulation. Um, you know, brain fog in particular, is that coming from a specific part of the brain?

Lisa Mosconi: It's hard to tell when we believe that brain fog, because it's such a nonspecific term. In a way that includes a combination of things is more likely to be multifactorial and yes, all be different parts of the brain. But once you break it down into separate components, there's an executive function that is a little bit different, you know, not working so great. There's forgetfulness and there's attention and there's language and, and so just those, these functions are related to specific parts of the brain. So there's one part of the brain called medial temporal lobes that are in charge of memory and learning and like direction. You know, when, when you get confused, you don't remember where exactly you are in the supermarket. That's your Hippocampus and parts of the brain related to it. Then there's the frontal cortex. I think it's probably a big site because it's the integrated part of your brain that also really helps you with thinking and reasoning and multitasking and also language. It's in the left, um, frontal part of your head. So it's a combination in different regions that gives you a little bit of the anatomy, the brain aspect. Yes. Menopause, if you will. And then of course it's more complicated in that, but at least it's right, because if you're like, oh, so the hippocampus is in charge of memory and is very sensitive to estrogen. And estrogen is now kind of hidden. randomly, and it may be misfiring.

Stacy London: That makes sense then to have the memory lapses because you're, it's effectively under attack in some ways, right?

Lisa Mosconi: The frontal cortex doesn't get all the estrogen it needs to work consistently. Estrogen is an activator. It's like estrogen is to your brain what fuel is to a car.

Stacy London: That's actually a great way to put it. I love the idea of just measuring your own cognitive function against your past cognitive function is also just a good way to talk to your doctor about what you're experiencing so that you can be tested. I want to go back to what you said about estrogen being like fuel for a car. Estrogen is fuel for our body. What are your feelings and what is your opinion about, um, hormonal therapy because it was villainized? Yes. It was villainized for so long and it's only now that we're talking again about hormone therapy as the gold standard for menopausal care. And you know, in the WHI study, we destroyed that and we're still bouncing back from that. I mean, it could have been one of the most detrimental things to happen to XX chromosomes and ovaries ever. I'm curious, you know, It would make sense to me that we would continue to need estrogen postmenopause.

Lisa Mosconi: See, now you're activating all my neurons.

Stacy London: Okay, that was, my whole goal was to activate your neurons. Just, just go for it.

Lisa Mosconi: I think there's two, two different things, right? Actually, there's more than two, but let's say three. When I talk about estrogen, it's being neuroprotective, it's being good for your brain. I'm talking about the estrogen that your body makes. And I want to be very clear about this, that hormones can be endogenous or exogenous. Endogenous hormones are the hormones that you, yourself, your body makes because the system is calling for it. There's a biological reason to be making those hormones. There's a biological reason to stop making those hormones as well, which I think is important to acknowledge.

Exogenous hormones are hormones that we introduce from the outside, right? With birth control, with hormone replacement therapy, with xenoestrogens, you know, in a number of different ways. Those Hormones are not nearly as well studied as one would hope. So, of course. But it's an important distinction, especially for me, because whenever I post something saying that estrogen is so important for brain health, I keep getting all these questions. Well, I have breast cancer. I can't take hormones. estrogen and my do, but I never mentioned taking hormones, right? I'm just explaining how the brain works. I'm saying physiology, but I also understand why we are going two steps forward. So that's my point. Number two. Which is that, yes, the Women's Health Initiative really did a lot of damage to hormone therapy. And I think we're still not quite past the bed wrap that HRT or MHT has. And I think it's really important that Professional societies have revised their guidelines in 2022 saying, okay, with all the data that we have and the knowledge that we have so far, we can actually say that the previous recommendations were incorrect.

And now we believe that women who are younger than 60 or more broadly within 10 years of the final menstrual period can safely take hormones, estrogen alone or estrogen and progesterone, and that the benefits outweigh the risks. And this is for women who are eligible. Of course, there's contraindications. They also add that the previous recommendations that we had to endure for 20 years potentially were harmful to some women, right? Which is not so great to hear. However, it's great that now we have updated recommendations that say it's totally fine to take hormones to support your menopause and that hormones are indeed on the table for men and women.

Stacy London: And as you said before, I mean, science is always changing. It's part of the reason we can say now that WHI study was actually not true. Great data, right? Um, but I, but I appreciate what you're saying about the, uh, the estrogen our body makes versus introducing estrogen post menopause. That, to me, is very fascinating.

And also that you said that there is not a ton of research. That there still needs to be more research to really understand the risk benefits of hormone treatment or menopause hormone therapy. In order to really better serve the patient. Um, you know, I, I, I think it's so interesting that you said before, we have to use the words maybe and perhaps, and we're not sure yet because we just haven't had that research funding that is really necessary to really understand that.

You are actually studying the most complicated part of the menopause piece, right? I mean this is, this is what is, it's like you're in charge of the engine of the race car and there are so many things that can go wrong in an engine and so many things that can go wrong and, and I don't mean wrong as in, um, Uh, not natural, but like, you know, we don't know how these things dip and ebb and flow in terms of hormones and how they affect all the parts of the brain.

Lisa Mosconi: Can I say one more thing? I just don't want to lose my train of thought. There was my third point. It's that estrogen does not matter. Estrogen alone does not matter. The thing that matters is the unit, that is a combination of two parts, the hormone and something called the receptor. Hormones alone don't do anything for you. The only thing that has either a good effect or a bad effect in your body is the way that the hormone latches on the receptors, like a key and a lock, right? You can have a door with a lock that you can't open because the key isn't there. You can have a key that doesn't open anything because the lock isn't in the door. You need to have both. And it's the binding of the estrogen to the receptor. That activates all these wonderful things that happen in your body, right? So just putting hormones in your body May not be helpful because maybe the receptor isn't there to take them or maybe with that there, but doesn't want it And with that, with that receptor, I mean, that's one reason that hormone replacement therapy has variable effects for different women and unfortunately, we have not studied that at all when it comes to brain health. We're trying to measure that.

Stacy London: I'm so curious if, you know, part of menopause and part of aging is losing receptors in the brain or, or somewhere else, if that's just natural. I mean, there are so many questions.

Lisa Mosconi: My theory is actually that the brain makes more receptors when we go through menopause. So if our brains are compensating, we should be seeing an increase or an overexpression of receptors. They're either more receptors. The brain makes the receptors. You know that, right? It's not like we have receptors. You just happen to be there. It's a constant process of making and using, making and using, and I'm thinking what I'm trying to test right now is if the brain is actually making more receptors during the menopause transition and beyond, and for how long, or do we just have the same amount of receptors, but they're overexpressed? It's just their date. grab the estrogen really sticks to it for longer. We don't know. And how does hormone therapy play in the mix? No idea because nobody's ever done it. So I have so many questions about hormone therapy for brain health. But what I wanted to say is that there are very specific indications.

So there are, um, FDA approved indications for using hormones, which I'll summarize super quickly. They're for hot flashes and night sweats, no matter your age or menopausal status. So you may be postmenopausal, but if you still have hot flashes and night sweats, it means your brain is still transitioning, and you should be eligible for hormone therapy provided no contraindications. Then we have prevention of osteoporosis, and we have relief of genital urinary symptoms, vaginal dryness, vaginal atrophy, UTIs, and low sex, uh, low libido. And then there are off label indications, like for some women it works, but some people were not sure, which is sleep dystrophy. Disturbances in peri and postmenopause, especially as related to, um, night sweats or other things that wake you up at night that are menopausal symptoms, so hormonal, and then there's relief for mild depressive symptoms during perimenopause, and we're, we're trying to figure out when it actually works with brain fog.

We see an improvement. However, there are basically hardly any clinical trials. So we need more clinical trials to be clearer on what HRT can and cannot do. And then I'm sure there's a lot of clinicians who will tell you, Oh, I love it. It works so great. And other clinicians were like, Well, there's no clinical trials. I'm not so sure or not enough. Trials. Right. So we're looking into that too. We have a meta analysis that I'm hoping will be published

Stacy London: I'm so excited. I can't wait to hear more about this. But I guess the big thing is that, you know, what can we do to protect our cognitive function? As we age, as we enter perimenopause and postmenopause. So, if we're saying that there may be a dip in our, you know, uh, hormones that produce what I'm just, you know, brain fog, whatever that term means, right? Um, it may, you know, our brains may come back up a little bit and we'll have the same cognitive function or slightly less. But, you know, When we're fearful that we are actually losing cognitive function, is that, is that when we should get a brain scan or are there things that we can do ahead of that time, even ahead of perimenopause that will strengthen our, our cognitive skills as we go through this?

Lisa Mosconi: Yes to both. The first is testing. If you are concerned that your cognitive performance is deteriorating, then I think testing is a really good thing to do. It's hard to get it done with regular insurance. Unfortunately, you need to go to a specialized, um, either clinic like ours. the Alzheimer's prevention clinic or to a clinical research center like ours, where you get all these tests done for free. And in return, you support the research by letting us use your data, which I think is a pretty good trade off. There aren't too many, but there are some places where that can happen depending on your age. I strongly support cognitive testing because Especially if you don't yet have an issue, but you're concerned that you might, maybe because you have a family history of Alzheimer's, or maybe because you were pregnant and you had brain fog for a long time, or you had a hard time after giving birth with a mommy brain. You know, those are good indicators that something may bother you during menopause as well. So if you have time and resources, do come get tested. Because it's every, every doctor's call dream is to have your baseline when you are fine. So then when you come back and you have an issue, I can compare you to you. And the same for brain scans. I love brain imaging. I think it's so helpful. And there are so many things that can happen to the brain that we never even know about until there are symptoms that are not only something you can intervene on right away, but often preventable.

And they could really be ameliorated by just doing the right thing at the right time. So when people come to us, we do brain scans on everyone. And it's not uncommon to find things inside the brain. Some people have brain tumors, they're more common than we probably know about. Some people have risk factors for aneurysms, some people have malformations, some people have demyelination, there's gliosis, there are a lot of things that, um, can be found that could be made better right away that could also impact your experience of brain fog, you know, and in terms of being proactive, uh, lifestyle, I believe there's enough evidence that leading a healthy lifestyle is brain protective. I have a lot of colleagues in this space who not only believe in it, but really take a proactive approach. Like my lifestyle has changed radically. My husband thinks I'm nuts.

Stacy London: What have you done to change your lifestyle? Because I'd be curious. Like I, I'll tell you, I, my, because of my menopause experience, my lifestyle changed significantly. I mean, I really went out of my way to start strength training and taking vitamin D and calcium and getting my heart tested and, and my bone, you know, my DEXA scan for bone health.

Like I became super proactive when I realized that menopause was actually. Maybe the last time that I could take preventative control of how I'm going to age. And so I changed a lot of things about the way that I behave in my life now. And I'm curious what, what, you know, the more you understand about the brain, what, how that's changed your lifestyle.

Lisa Mosconi: A lot. I use my brain like 12 hours a day. If nothing else, intellectual activity is a consistent part of my life. It's really, there isn't a single day that I'm not intellectually stimulated, but everything else I have optimized in part for brain health and in part to prepare for the menopause transition. I really am doing everything that I put in the book almost.

Stacy London: So let's end on that because I'm excited that your book, um, the menopause brain is coming out March 12th, but one of the things that we are talking about in this season of Let’s Talk Menopause is things that are actionable. And if you're talking about preventative changes, preventative lifestyle changes that we can make now, um, can you reference some of the ones that you talk about in the book? Because I do, I want people to walk away from this, not only as fascinated by the brain as I am, but really understand that there are things that preventative health can, can, you know,

Lisa Mosconi: Yes, so there are quite a few things that have been consistently linked with, um, having a better menopause and less severe symptoms that are lifestyle based and therefore actionable and fairly easy to implement. I would say the key word here is consistency, right? What needs to happen is that you choose a number of things, even just one thing that you can realistically do and do it for a long amount of time. They, you know, when you read those books that say, Oh, the brain reset, I'm going to change your brain in three weeks, or this is a complete plan is going to fix your menopause in two months. The brain does not work. The brain does not work like that. You can change. whatever you want from the neck down in a fairly short amount of time because your cells are always regenerating in the rest of your body. So you can see a change quickly. Your brain doesn't do that. Your neurons do not regenerate. So that's great. So that means that the brain is to protect them. So for any change to really occur, it means that that thing that you're doing has to be done consistently enough and frequently enough to actually have an impact. So slow and steady in a way wins the race and the, the pillars I would say are exercise. There's, I think the best evidence we have. for lifestyle is that specific types of exercise can really help with specific symptoms of menopause. You may know this already, but I found it interesting that cardiovascular activity seems to be best for hot flashes and brain fog and memory. Wow. I didn't know that specifically.

Strength training, not just for metabolism and bone strength, but also for mood. And mind body exercises, including yoga, Pilates, Tai Chi, you know, this kind of more meditative, um, kind of work, workouts, at least not as intense workouts, promote flexibility, obviously, and mobility, but also, um, stress reduction and sleep.

Stacy London: I've heard exercise can help reduce symptoms, but not that there were specific symptoms for specific activities.

Lisa Mosconi: I wouldn't say that this is, this is 100 percent the case all the time. It's just the research suggests this different pattern. So I would say, since we have the information, if somebody is having depressive symptoms and whatnot, I will start with strength training.

Especially with something that maybe can also be a little bit cardio at the same time. So you get all the benefits. And there's so many trainers out there, just so many apps, just so many YouTube videos that you can kind of get support quite easily and come up with a plan that works for you. That I think is very helpful. So I personally work out five times a week whenever I can.

Stacy London: Oh, wow. Okay I'm only at four, but I'm trying. I'm trying to get to that. I'm trying, well, I'm trying to get to you, but, but funnily enough, my trainer, if I like come three times a week or I have to miss one day, he said, you know, or even if I miss a week, if I go on vacation or something, he keeps saying to me, stop worrying about it. I don't care if you don't move that entire week, because you're going to come here every week. for the rest of your life. And if you're going to be that consistent, one week out, one month out, does not matter. Um, and, and it's a great way to think about it because I, I stopped worrying about the day to day and really work on that consistency that you're talking about. And I think that takes some of the emotional and mental pressure off of us. When we think about lifestyle changes, you. They don't have to be big, they have to be consistent, and that I think is a very helpful tip for people. Um, have you changed your diet at all?

Lisa Mosconi: I have, yes. So my diet has always been quite healthy, so I'm from Florence in Italy, and I've been eating, I've been following a Mediterranean diet my whole life, so that's not gonna change. I am adapting a greener version. or the Mediterranean diet. And I'm not saying that people should be vegan or vegetarian, I'm just saying that for me personally, I want to reach a certain goal when it comes to fiber, antioxidants, and anti-inflammatory nutrients, because those seem to be consistent, more consistently associated with brain health, um, for life. Really, especially in menopause and beyond. So for me, those are the three targets for myself personally, and I can only reach those targets if I'm focused on plant foods.

Stacy London: Plant foods. Where are we meant to find these things?

Lisa Mosconi: I think flexible diets and balanced diets and sustainable diets are really the best diets. That one thing I've never done in my life is eat processed foods. I just don't eat processed food. I don't eat fast food. I've had it once in my life, my entire life. Wow. Yeah. I'm a little strict.

Stacy London: But you're from Florence, right? I grew up in New York. Like McDonald's was a real treat when I was a kid. So, you know, it's, it's, it's a, I grew up in the seventies. It was like processed food. Food was like the best thing ever. Um, that's all we got was processed food and TV dinner. So it, you know, you understand, you start to see why America does have a problem with nutrition and with weight and how that would be something that would continue as we age. And then is sleep the other, is sleep the other pillar?

Lisa Mosconi: Stress reduction. Stress reduction is really important because people underestimate the connection between stress and sex, you know, with sex hormones. So stress hormones and sex hormones work in balance because the body makes them based on the same substrate, which is called pregnenolone.

So there's a hormone called pregnenolone that the body uses to make either cortisol and stress hormones. Or estrogen and sex hormones. So if you're under chronic stress and your body has to keep making cortisol just to keep you going, it will necessarily downregulate the production of estrogen and other sex hormones to make the cortisol. But if you can reduce your stress levels and bring down Cortisol production that's helpful to your body because it can just make your hormones normally. You know hormones are all related if one is out of balance. The other ones will be out of balance, too. So it's like they're going to compensate or overcompensate in some way, so stress reduction, meditation is helpful, exercise is.  I got a reformer pilates, a reformer, pilates, so I've been doing a lot of that and that helps me personally with stress. I have stress, I'm very intellectually stimulated, but I also have a ton of stress.

Stacy London: Oh, I can imagine. Oh, that's so exciting. I'm excited that you got a reformer. It's such great information because those are things that I think that people can take away from this and really put into action actionable and start doing.

Lisa Mosconi: And, antioxidants, antioxidants, antioxidants. The ovaries are very sensitive to oxidative stress and the only way to reduce oxidative stress is with your diet.

Stacy London: You kept us on track. I feel like this was just a goldmine of information for people in a way that makes them understand it. Thank you.