I was just talking to my wife earlier and I told her, I'm doing this interview with you, so I promise to take lots of notes. I think out of all the things that I've done, the interviews that I do, I think she's the most interested in this one. And let me just start with this. Is is menopause a bad thing?

No more than you would consider puberty or pregnancy, but things.

That's Lisa Mosconi. She's an associate professor of neuroscience and the director of the Women's Brain Initiative at Weill Cornell Medicine. She published a groundbreaking study in 2021 about what really goes on in the brain during menopause. And it's far more fascinating than you probably realized. For starters, her team found that the brain actually gets remodeled during that specific time of life. There is this sort of rewiring that goes on. Different parts of the brain shrink, others grow. What she discovered was entirely new.

So when my research has shown and other people's research has shown, is that the brain does not age in a linear fashion. Not true at all, when it comes to women's brains. Women's brains go through phases, and these phases are really cued by biology, and especially by your hormones.

During menopause, your estrogen levels drop drastically. That affects the reproductive system, obviously. But it also leads to this remodeling of parts of the brain responsible for the connection between the brain and the ovaries, the neuroendocrine system. Other things happen as well due to that drop in estrogen, including an increase in cholesterol. A negative impact on your cardiovascular health and, yes, your brain function. It leads to many of the classic symptoms of menopause. Think: hot flashes, fatigue, trouble sleeping, brain fog. In fact, Mosconi hopes that her work on menopause could help us one day understand why women are at higher risk for Alzheimer's disease. Something that I should add is very personal for her.

'I was raised in good part by my grandmother, who developed dementia just as I was finishing university. And my grandmother was one of four siblings - three sisters and one brother. All three sisters developed dementia and died of it. And the brother did not, even though the brother lived exactly to the same age. So that for me was traumatizing.

But as I've now learned, menopause isn't all bad.

I think your wife may think that there is an upside to menopause that we don't really talk about very often, that people are not aware of and they think is fascinating. So a lot of my research is now looking at both the vulnerability that we need to address so that we can provide better solutions and better care for women in menopause. But I'm also looking at the resilience.

Look, there's still a lot we don't know about menopause, and there's a reason for that. In fact, part of the reason Mosconi wanted to study it, part of the reason my wife was so excited for this interview is that women's health often gets ignored. It's overlooked. it's underfunded. And that's been true throughout the history of medicine.

The fact that estrogen has an impact on the brain was only discovered in 1996. For context, men landed on the moon 30 years prior.

On today's episode, the menopausal brain: the good, the bad, and the unknown of a biological process natural to half the human population. How can you prepare for the stages of menopause and even the benefits of making the transition? I'm Dr. Sanjay Gupta, CNN's Chief Medical Correspondent. And this is Chasing Life.

I want to make sure I get the terms correct here. Perimenopause. Menopause, Post menopause. When are they and what's the differences between those things?

That's a really good question. And I think I find that there is so much confusion that even with our patients, we have hundreds and hundreds of women working with us at this point. And we ask, are you in menopause? The answer is, I have no clue what it actually means. I don't know. And it is a complicated system that can be simplified into three major phases. So pre menopause is when you have a regular menstrual cycle. You are in your reproductive life because it starts with puberty and it's your entire life span. For as long as you have a regular menstrual cycle. Now, if you never have a regular menstrual cycle, then we can talk about it. But let's say on average most women have a regular menstrual cycle for as long as it's regular and you don't skip periods. That's perimenopause.

'So after puberty, you're essentially in premenopausal for decades. That's kind of a strange way to define it. Now, you're in the pre-menopause phase for several decades of your life.

Yeah. You want to think ahead. You know?

Thinking ahead. Yeah. Okay. So pre menopause and then. And then?

Perimenopause. And then next year, menopause. So perimenopause is is divided into two phases. There's an early perimenopausal phase when you start skipping your period, but you still have fairly regular. So maybe you skip one month, but then you have a period or two months and then you have a few so up to three months that the early perimenopausal phase. Once you start skipping your period for more than three months at a time, there's the later perimenopausal phase and it's getting closer to your final menstrual period, which is the last period you will ever have in your life. In that moment in time, it's called menopause. To think it's.

That moment in time.

'That that time like your last menstrual period. For at least 12 consecutive months. That's when you're diagnosed with menopause, which is very confusing for so many women because it's a bit of a guessing game, if you have to wait every month to be sure that this is actually your last menstrual period and you only really it's only confirmed after one year of not having any periods. So then they'll be like, okay, now you're officially menopause. Let's say then then you have a period. You're back in menopause and you have to start counting again, which is a very strange way of doing things. However, let's say that you no longer have a menstrual cycle. You're period free for at least 12 months. You are in menopause now. You begin your post-menopausal life.

Is there post menopause? Is that is a thing, post menopause?

'Post-menopausal phase and is divided again into two sub phases, sub stages. There's the early plus menopausal phase, which is about six years since the last menstrual period when you still have most of the symptoms. And then does the late post-menopausal phase, which is more than six years after your last menstrual period, and usually the symptoms dissipate. Usually the half flashes go away, you start sleeping a little bit better, their mood stabilizes and usually the brain fog goes away. It's not universal. For many women, the symptoms last longer than that. But on average, that's when there's this relief, just palpable relief.

And can you give us some rough ages here? I realize it's different. But what ages are we talking about?

So the average age to perimenopause is 47. But the transition can last anything between two and ten years. So you can be in perimenopause with an irregular cycle for usually a minimum of two years and the max of 10 to 14 years. So it could be a really long journey. The average is about seven between five and seven years, which is no picnic. It's a long time. 5 to 7 years with possible symptoms and disturbances and whatnot. Then the final message, the final menstrual period, usually, of course, around age 51, 52 in Western society. If we look at the entire world, it's actually 49. The average age of menopause is 49, which really defies the stereotype of menopause being a thing that happens to you when you're old.

We have this perception of menopause. Obviously, there's the physical symptoms, hot flashes and things like that. My wife said, great, You know, that sounds just fantastic. That's something to really, really look forward to. But but, you know, is she is she right? Is it is it sort of a four letter word, menopause? And when it comes to, you know, when you how you talk about it?

No, not necessarily. And no more than you would consider puberty or pregnancy. But think and where they were, they try to always explain. It's that biology really operates on a continuum. And we tend to see these life events has been separate and unrelated to each other. But that is not the case. Menopause is the third of the three piece. There's three phases that the female brain goes through in life, which are puberty, pregnancy and perimenopause, which is the transition to menopause. And those three phases are seen very differently culturally and in society. But from a neurological perspective, from a brain perspective, they have a lot in common in all three phases come with vulnerability. Like yous said, there are a lot of unpleasant symptoms that can arise during menopause, but also with resilience. And I think the resilience aspect has been completely overlooked in medicine, in science and certainly in culture. I think that mindset is extremely important for the experience of menopause. So then the reaction is not like, Oh my God, I wish I could avoid it, but more like, Oh, let's see what I can learn from this life event. How can I embrace it? How can I live it without pain, without suffering and with knowledge and with confidence?

You know, I imagine that with as with most things in life, there are upsides and downsides. Just about everything. There's goods and bads. But what is the upside of menopause with that?

You want to start with the upside? Usually everybody wants to talk about the downsides.

I'm an optimistic guy. I want to know what the upsides are.

It's great. It's a wonderful way to start. So we really need to think about this life events, these hormonal life events as from an evolutionary perspective. So puberty, all these brain changes that take place during puberty are deemed necessary for the brain to mature so these children can finally master impulse control. The prefrontal cortex, which is that part of the brain in charge of multitasking, of language, attention and focus and managing your instincts. It's finally mature enough that it has control over the rest of the brain. And at the same time, your brain regions that are responsible for empathy, in theory, your mind, which is mentalizing putting yourself in another person's shoes, have developed enough that you can actually become a proper member of society. Pregnancy. All these changes that are very severe are not too different from what happens during puberty shape your brain in such a way that the limbic part of your brain, the primitive part of your brain comes back in the front. Why? Because you have to protect your kids. You have to turn into the mama bear. There was bought the little toddler in a sandbox full of toddlers and can come to the rescue in a microsecond. You had to be able to to understand nonverbal clues for basically ears. That brings us to menopause. It's the same brain regions that are changing again. But this time the change brings up perhaps more symptoms. Maybe because we're a little bit older as well. So there's the hot flashes, the anxiety, these depressive symptoms, this brain fog, this memory lapses. But there's more empathy. And that is considered to be very important for the next phase of your life, where you're no longer reproductive. But you're very much supposed to be still active and productive. You have more empathy because that's your time in your life in theory, when you can really help others grow, develop, evolve, you turn into the elder woman, the wise woman. There's so many cultures around the world celebrate, whereas a Western society basically says you're useless. I'm sure you know about the grandmother hypothesis of menopause.

What's that? What's the grandmother hypothesis?

Oh, okay, good. So there are two hypotheses, major hypotheses or theories about menopause. There's one school of thought that says menopause is a fluke. It's a complete accidents, a freak of nature, Women we're all supposed to die after menopause. That's Darwin. Right? But the idea was that menopause is very strange. So there are very few animal species all over the world that go through menopause and outlive it.

Fascinating.

'So we can say there's something special about human menopause and there is some parallels for instance, with orcas, the killer whales, because they live in matriarchal society. So the children stay with the mother for life. The father goes about his business, but the kids actually live with the mothers and then the grandmothers. And the grandmothers when they once they're no longer reproductive, because they're post-menopause. They really become the main source of sustenance for the grandchildren. They find all the good salmon, they lead them to the safest places. They really kind of lead the pack. And people think that something similar happened in human societies. This is the grandmother hypothesis, which is the opposite view. It either says evolution is not as misogynistic as those who conceived it, right? Maybe there's something maybe nature actually likes women and found the way to keep us alive because we're actually helpful, even if we're not bearing kids every minute. That is the grandmother hypothesis that says post-menopausal women are actually helpful and there's a reason that they are on the planet. And so that if you interpret that from a neurological perspective, it makes perfect sense that the brain would adapt and change in a way that would support this new role in society that post-menopausal women developed that really had the survival of the species.

I had not heard that before, the grandma hypothesis. But you know what it makes sense. And despite what society tells us, I think there is a case to be made that there are upsides to menopause. It doesn't have to be a dirty word. And in other cultures, even other species, it's an honor, a rite of passage. I really love that. After the break, tips and tricks for a more manageable menopause.

We're back with Chasing Life. So far in this episode, we've learned about the stages of menopause, when it typically occurs, how it's fairly unique in nature. Women's brains undergo serious changes during this period, some of which may contribute to a higher risk for Alzheimer's disease. Mosconi's 2021 study involves scanning the brains of 161 women between the ages of 40 and 65. All were in premenopause, perimenopause or postmenopause.

You've alluded to this a couple of times, but how challenging, Dr. Mosconi, is it to do this research? To look at I mean, to look at menopause and the menopausal brain? How hard is it to to publish and get this research done?

It's very challenging. It's really demanding. I'll tell you a couple of reasons for that. The first one is the funding. Funding is just not quite there. I was looking at the federal budget at the NIH, the federal budget for the past reporting period, and of the entire $20 billion do you know how much was given to menopause research? 16 million.

Out of 20 billion though. Wow.

Yeah. And that is for everything. No brains, anything related to menopause, including brains and including therapies. The majority of it is actually allocated towards testing hormone replacement for different things that had nothing to do with the brain. And then there were like three grants given to Alzheimer's disease research.

It is it is kind of amazing. And, you know, all kidding aside, know, obviously I'm married. I have three teenage daughters as well. And it is it is kind of amazing just even talking about this podcast with them and in telling them I was going to interview you, just even the basic terms, what is menopause? When does it occur? How long does it last? What is really going on? Let alone, what is the impact on the brain? There's there seems like there's so little that's that's known about it. So I really applaud your work. So so when you when you think about this, is estrogen really at the heart of what is happening with the symptoms that women have during menopause, as well as these brain changes?

'The vast majority of studies has focused on estrogen, and they have shown consistently that one type of estrogen called estradiol is the master regulator of female brain health. And master regulator means that it's basically like the orchestra conductor is this one key player that knows every aspect of the business and is able to help the leader beat everybody else. So it is like the social butterfly inside your little brain then is able to make sure that everybody is doing their job and do it well. So, for instance, estradiol, or estrogen, in general, is really for the age of neuroplasticity, which is the brain's ability to adjust and evolve to the experience from the outside into internal changes in stressors. So it's the brain's ability to remains resilient and to whatever the life brings to your table. Then it's really important for neurogenesis, which is the growth in birth and neurons. And we're older it is important for the way the neurons branch out. So all the different connections between different neurons are much stronger when estradiol is high and then it's really important for blood flow. It stimulates blood flow and circulation to the brain, which means that the brain gets more oxygen and nutrients so it can work better. And it's key for immune function inside the brain. It is neuroprotective, I would say, if nothing else. If there's one take home message is that estrogen for women and testosterone for men are not just hormones that are involved in reproduction. They're not only important for fertility. They're also extremely important for brain health and brain function. They keep your brain active. They keep your brain energized. They keep your brain young because they also have an anti-aging effect.

Why is it that women are more likely to develop Alzheimer's? And what is the connection to menopause?

So when I was doing my PhD, I decided to focus exactly on that question. And what people would say to me was, "Well, you know, sweetheart, women live longer than men, and that Alzheimer's disease is a disease of old age. So unfortunately, more women than men end up developing dementia." Nearly two out of every three patients with Alzheimer's disease are women. For many, many years we had no explanation other than women lived longer than men. It's just longevity. The biggest turning point in this sense was work that we and others were doing, showing that Alzheimer's disease is not a disease of old age, but rather it starts with negative changes in the brain years, if not decades, before the clinical symptoms of Alzheimer disease become evident. So that changed my entire question. The question was, if Alzheimer's disease is a disease of midlife, what happens to women and not to men in midlife? It could potentially explain the higher prevalence of Alzheimer disease down the line. And for a long time I had no clue. We looked at genetics, we look at family history, we looked at risk factors for Alzheimer's we looked at cholesterol, we looked at triglycerides or the blood pressure. We looked at diet, exercise. We looked at everything. And the explanation, yeah, there was a trend. There was always a trend, but they could never find one thing that could really split up the data. And then what happened is it's not me but my study coordinators who were testing a person, a woman, 50 year old, a young, young woman who was doing cognitive testing with us, and she had to stop. And she said, "I am sorry. I just cannot continue. I'm having hot flashes one after the next." And they were like "hot flashes menopause." And so we went back and we asked every woman in the study about their menopausal status, and we classified them as having a regular cycle, no longer having a cycle, being in menopause and being in the transition in the cycle is kind of irregular and you're having half flushes, night sweats and all this stuff, 100% separation.

Wow.

Very clear. Very clear.

Okay, let's pause there for a second. Mosconi and her team were studying Alzheimer's when they stumbled onto the idea that a potential midlife trigger of the disease could be related to the transition to menopause. As estrogen declined during perimenopause, the production of certain proteins linked to Alzheimer's began to pop up, at least in some women. Now, this may be a big step toward understanding why women are at higher risk for Alzheimer's. But the truth is, there's still a lot that we don't know about the disease or exactly how the menopausal transition factors into all of this. Which is why Mosconi, who told me she's in her forties and premenopausal, is now taking things into her own hands.

Oh, my goodness. I've been thinking so much about it, and I have changed my whole routine to prepare for menopause. I have changed my diet. I have changed my exercise. I sleep. I prioritize sleep hygiene in a very very specific way. I do stress reduction. I get rid of all sources of environmental toxins in the house as best I can. And I just do a lot of things that are more lifestyle based. And I'm also tracking, you know, hormones and cycles and preparing mentally. And kind of trying to decide whether or not I would take hormones. The problem is the transition. Is when all the symptoms can take place, is when you can have hot flashes, sleep disturbances. I'm worried about that. The brain fog, the memory lapses. I can't afford to have any of that. I need to to be, you know, sharp.

'Well, it seems like you'd want to get the benefits of the post-menopausal brain, which, again, is this brain that is strengthened by that pruning and and then strengthening that goes on, that gives you the resilience, gives you the empathy. You'd want to get all that without having some of these very tough symptoms in between: the brain fog, the memory problems, depression, anxiety. To say nothing of the physical symptoms, the hot flashes. So you want both. You want the benefit of a post-menopausal brain without the high price to pay?

Absolutely. I used to exercise for different reasons, and then I now actually focus on exercises that are known to support mental health and brain health both. Which is aerobic exercise. It's not my thing. I'm more of the yoga and Pilates type of person. But aerobic exercise is when you get the most bang for your buck. It just, it's true. And it's the one type of physical activity that's been more consistently shown to reduce hot flashes and to alleviate the intensity of hot flashes. Prevention is important in addressing the symptoms as you have them is important. And taking care of your brain after menopause is also really important. So these are all the things they want to do. And lifestyle is important, medical care is important, and sometimes hormones can be helpful. They say for women who are younger than 60 without an existing risk of breast cancer, so women who are free of cancer. Healthy women up to age 60 can safely take hormones. Estrogen and estrogen and progesterone, depending on what kind of regimen you need, without fear of adverse outcomes.

Do women's brains still change through menopause if they are taking these hormone replacements?

There's hardly any research that's been done to really confirm that. But research has shown, and I think everybody agrees on this, that there is a window of opportunity for estrogen action in the body and brain. Which means you need to take it as you transition to menopause or when you are in early post menopause, which is the 1 to 6 years window after your last menstrual period. That's a great time to take hormones if you choose to do so. If you take them much later in life, they actually don't seem to have much of a good impact, at least not on brain health. And I just want to say one more thing. I do not mean to say that the risk of breast cancer is not real. It's just that we need to put it in context. It's not as high or as absolute as we were led to believe. When you contextualize, it is a similar risk as drinking two glasses of wine per day.

Lisa Mosconi is an associate professor of neuroscience and director of the Women's Brain Initiative at Weill Cornell Medicine. Her book, "The Menopause Brain," comes out in March 2024 and goes much deeper into this phase of life and how women can make it work for them. I have to tell you, this particular conversation was fascinating. It was enlightening not just as a doctor, but as a husband and as a father of three daughters. Most of us have loved ones who have or will go through menopause, so it's a topic all of us would do well to learn more about.

That's it for this episode of Chasing Life. Next week on the podcast, kid's brains, sports and concussions.

I know there's always this push that you want to get back as soon as possible from any injury as an athlete. But this is your brain and you only get one.

Thanks for listening. Chasing Life is a production of CNN Audio. Our podcast is produced by Eryn Matthewson, Madeleine Thompson, David Rind and Grace Walker. Our senior producer and showrunner is Felicia Patinkin. Andrea Kane is our medical writer and Tommy Bazarian is our engineer. Dan Dzula is our technical director and the executive producer of CNN Audio is Steve Lickteig. Special thanks to Ben Tinker, Amanda Sealy, and Nadia Kounang of CNN Health.