Lisa Mosconi, PhD: The Upsides of Menopause
Neuroscientist, Lisa Mosconi, PhD, currently has 11 grants—including four from the NIH—to study Alzheimers, menopause, and the female brain. Dr. Mosconi is an Associate Professor of Neuroscience in Neurology and Radiology at Weill Cornell Medicine (WCM), and the Director of the Alzheimer’s Prevention Program at WCM/NewYork-Presbyterian Hospital. The program includes the Women’s Brain Initiative, the Alzheimer’s Prevention Clinic, and the Alzheimer’s Prevention Clinical Trials Unit.
There are many things to love about Dr. Mosconi and her work—one, that she’s focused on an underserved group, i.e. women, but also because her insights dramatically expand the way we’ve been conditioned to understand these hormonal shifts in our lives. The picture she paints of the female brain is not only fascinating, but it’s inspiring: As we age and move through stages, our brains continually remodel, becoming leaner, meaner, and more empathic. The female brain is…formidable. There are also many things we can do to make these turbulent transitions slightly smoother sailing, which we dive into throughout our conversation. Let’s turn to it now.
MORE FROM LISA MOSCONI, PhD:
Brain Food: The Surprising Science of Eating for Cognitive Power
Lisa’s Website
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TRANSCRIPT:
(Edited slightly for clarity.)
ELISE LOEHNEN: I'm excited to talk to you. I haven't, on this podcast at least, really done too much on hormones or specifically menopause, in part because I'm 44, so I'm not yet in paramenopause, though I recognize it's coming. And I appreciate that your book speaks to this, I'm thrilled that we're having more conversations about it culturally. But then I have this wall of resistance that rises in me both because I feel like so much of the conversation is pathologizing menopause and is entirely negative and is fully grounded in the body, instead of talking about some of the things that you mentioned in the book, that it's actually, could be one of the most compelling periods of a woman's life, increased happiness, vitality, opportunity to do things culturally that might not have been available through time. And so I wanted to see the conversation about menopause crack open to be both more positive and also less focused on the body and or a lot of things that you need to now buy. We're so good, right? at turning everything into an event of like, well, you need 80 bottles of things now. So I liked that you, it's obviously not the focus of the book, but speak into this cultural fear of menopause and explain why that might not be necessarily well placed and then I thought it was a great resource for Things to think about and things to do. So we'll talk about HRT and all of that, obviously, but I just wanted to start with that. How do you feel as someone who is a neuroscientist, which is fascinating, but are you excited that there's so much more conversation or do you have concerns or do you feel like now this HRT mess is finally being clarified? Talk to me about where you are.
LISA MOSCONI: So I started working in the field of menopause maybe 10 years ago by now when really no one was talking about it. I mean, obviously in gynecology, in the Obergine kingdom, there was a lot of conversations happening about menopause, but as a brain person, as a neuroscientist and a clinical research brain person, I really was never exposed to a lot of conversation around menopause and the neurological effects and psychiatric effects of menopause. So that was quite uncharted territory back then. There was work done mostly preclinically, animal models, molecular biology, system bio, but not so much, really on women. So that was fascinating and a little bit uncomfortable because as a scientist, you always want to build up on what's already been done. And it's quite difficult to have no precedence for your findings and I just like, I don't know what I'm doing right. I'm busy as a mouse, but it's not really the best, you know, it's complicated, it's more difficult, it's more challenging to do it right. So you're super conservative and just trying to do the least amount of harm, you know, figuratively speaking. And just in about 10 years or so, I would say, especially this past two years, so many people have started to talk about menopause more openly, which I find wonderful. And I'm hoping that my previous book helped a little bit. And I'm really hoping that the research helped because we're legitimizing and validating what women have been saying forever by showing Actual brain scans and real data and doing the groundwork in a way. At the same time, it is a little bit unsettling when anything goes mainstream, and then it becomes a marketing term, it becomes monetized, it becomes a business venture, and a lot of people now realize that menopause is having a moment. Especially on social media, right, and they're just jumping on it and there's this shirtless guys with a stethoscope around their necks talking about how they actually knew what it is, which is fine. I mean, if you know what you're doing and you're shirtless, no problem, but there's a lot of strange things being said, right? So I think it's becoming like diet a little bit where everyone has an opinion and it's all about opinion and we need to really stick with the facts because unlike lifestyle, here there is a clinical component that needs addressing sometimes, not for all women.
ELISE: Yep.
LISA: many, so, you know, good research is evolving, it's good that menopause is having a moment because The more people talk about it and demand information, the more research will be done on this topic, and funding agencies will hopefully change their priorities so there will be funding for research on menopause and brain health. So that's the plus. And then, of course, we need to be careful about balance of information to misinformation that can follow.
ELISE: Well, what's so interesting about you and your research, and you have a massive grant, right? Is it from the NIH or am I getting that wrong? Yeah.
LISA: have 11.
ELISE: Eleven. Okay, sorry.
LISA: Not all from NIH, but yes, we have four from the NIH and then foundations and then we have major gifts. So you need to have a lot of funding to do this kind of research, It's expensive. It takes a big team of people between internal and external collaborators and our like full time team, we work with almost 80 people on different projects.
ELISE: Yeah.
LISA: And also what we do is very expensive, like the brain scans are complicated.
ELISE: Complicated and fascinating and so that too I think is just worth pausing on, which is that you're a neuroscientist and typically the way that women, you know, you might get a hearing right from your OBGYN in terms of how you're feeling, but there's this general idea that it just sort of starts and ends with your uterus, right? But meanwhile, you're making the point that this is More of a brain phase, maybe not more, but certainly like a significant factor in terms of hormones. So can you talk a little bit about why these two things need to be talked about together?
LISA: Well, the reason is genetic and biological and physiological, so that from the moment we're born, we're born with a system, the neuroendocrine system that connects our brains with our ovaries in women and the brain with the testes in men. And this is a major neuroendocrine system that we carry with us for life that nobody's aware of, that nobody talks about. It's a little bit like an invisible pathway that is so massive and so powerful, but doesn't always manifest itself to goodness in some.
ELISE: Mm hmm.
LISA: They were born with this system that connects the neurological system, the brain with the endocrine system. So the hormonal system that ends in the ovaries and the system is basically silent until we hit puberty, at which point is activated and turned on, prompting all the bodily changes that every woman is aware of, right? But at the same time, it prompts of remodeling and rewiring inside your brain, because your brain now needs to really start working with your ovaries every day of your life until menopause, basically, even just to cue menstruation and to make sure that you're able to sustain a pregnancy. But at the same time, there's so much more that goes into a woman's romantic and reproductive life that is not just purely, Oh, I see a man, that's it. Let's have a kid, right? There's so much that needs to happen that this system has evolved to involve the entire brain. So Throughout every productive life, every time we go through a menstrual cycle, our brain goes through a micro cycle. And we have constantly the micro cycles where the architecture of the brain is gently changing. Consistent with the changing hormones that take place in the rest of the body and inside the brain.
So the same hormones that the ovaries make go all the way inside your brain, telling the brain what to do, how to feel, you know, what the rest of the body is doing. And the brain sends hormones right back. So it's a constant loop. It's a constant exchange of information that is then upregulated during pregnancy. And every time a woman becomes pregnant, the brain goes again through a massive remodeling that can cause some glitches, like the baby blues, the postpartum depression, the brain fog, the sleep changes. But also it's a wonderful experience because your brain gets stronger and you are neurologically equipped to be a mother, which is. Obviously, one of the biggest accomplishments, I think anyone can put in their resume, even we do not. I would say I have a child and she's alive and everything is a big deal. But then what happens is that we hit menopause. And the same exact system gets switched off. And then, in combination with the fact that we're a little bit older at that point in time, can cause symptoms that feel alien, because we don't think about this continuity between puberty, pregnancy, and perimenopause, or the transition to menopause. And many women really suffer because, number one, they have no idea what hit them, and number two, they don't really know how to feel better. And this leads to over medicalizing menopause in some ways, or fearing menopause, or dreading menopause, and not seeing the upside of this transition that I know you're interested in discussing.
ELISE: and that all of these events are turbulent, potentially, maybe less so for some, more so for others. But then there's a recalibration or a balancing of the brain. So it feels, I think you call it growing pains, and that was so, I didn't realize, I didn't quite understand that with menopause that we have so many receptors in our brains for various types of estrogen and that those receptors are hungry, right? That we're sort of having to recalibrate or rebalance and there's that pruning, I guess. Is that accurate?
LISA: Yeah.
ELISE: Okay. Yeah.
LISA: Yeah. So what happens at all the three P's, I call them the three P's, so puberty, pregnancy, perimenopause, what happens during these transition stages is that the brain changes in response to changes in estrogen levels and other hormones, right? And all three P's are linked with pruning. which is a neurological phenomenon by which the brain discards neurons. So you're effectively losing gray matter, which may sound really frightening, but actually is a smart move. Why? Because the brain is the most metabolically active organ in the body. It constantly requires nutrients and oxygen and blood flow and glucose, and it requires so much energy just to have a big brain.
So if you don't need certain neurons, It makes so much more sense to just get rid of them and focus on the ones that you really need to keep and make them stronger. So during puberty and pregnancy, and in my opinion, also during menopause, there's a pruning event that takes place, so let's take puberty as an example, right? At that point, you're a little bit older, you know how to ride a bike, you know how to tie up your shoelaces, you know how to do a two plus two. Those neurons that were needed to power every single step, put your foot on the pedal, push forward, don't fall, all these neurons can go because you don't need them anymore. There are so many things that are now going on autopilot. So it's best to get rid of the fluff.
ELISE: Mm hmm.
LISA: Really keep the neurons you need to transition to the next phase, which is becoming an adult, becoming a parent, potentially, and becoming a member of society. So the remodeling means that some neurons are lost, which can trigger all sorts of different things like reckless behavior that so many adolescents manifest, but also the depressive symptoms and the anxiety and the sleep changes or the changes in sleep patterns and the fact that a lot of kids that age just can't focus for more than five minutes, right? These are all symptoms that we don't necessarily worry about during puberty, though they're very common changes in body temperature, right? It's the same system that at the same time prepares the brain for adulthood and the way that it does it is that there are very specific parts of your brain called the theory of mind network that gets remodeled and activated and becomes really better connected and is that part of your brain that allows you to mentalize, to empathize with others, to put yourself in another person's shoes, to put other people's needs before yours, which is everything that we need to be effectively adults, like responsible grownups. So we feel, as scientists, that this pruning that happens during puberty has its dangers in a way, right? It can create symptoms, There's a lot of trouble during adolescence. I embrace it myself. My daughter is eight and she's already talking about puberty and, you know, going to parties and all that kind of stuff. It's like, oh, okay. It's a little earlier than I thought, but we know what's happening. The upside is that your brain is becoming mature and is allowing you to control the impulses and really become responsible, basically, and good to other people. And then a similar change takes place during pregnancy, every time a woman is pregnant. So the neurons are shed. And the architecture of the brain is changing in a way that strongly boosts the theory of mind networks again, because now we have a little bundle of joy who can't speak for a really long time. So you really need to learn to read minds. And that's something that the mommy brain can do, right? It's a very reactive, it's a very strong minded and highly focused and very specialized brain that is neurologically wired to take care of an infant. And then you may forget what time it is, or you may forget to buy the groceries or to pay the bills, or you may feel overwhelmed, or you may feel sad because it's the same brain regions that allow you to be very focused or very spacey.
ELISE: Right.
LISA: And then all these changes take place again during menopause, but we're only looking at the symptoms and the negatives and never celebrating the positives, which are many actually.
ELISE: Yeah. And I want to go into that. And I thought this part was fascinating, too, when you talk about so much of the way that we think about women is shaped by early science where, you know, it was the Charles Darwins of the world, you know, who found that men's brains are bigger, therefore they must be better and stronger. But women's brains, this was fascinating. Women's brains are more interconnected. And obviously we're typically not as large and don't need probably the same size brains. And I know that this is early and that there haven't been that many studies, you go into gender affirming therapies and care and you're talking about changes, primarily I think it's in the trans female brain that they also remodel, right, with gender and both sides and become either more interconnected or larger, which is fascinating. That's fascinating.
LISA: I know, it's
ELISE: amazing.
Yeah.
LISA: In the study of how hormones impact brain health are still scars that aren't that many, but those that we have, I think are really helpful in many ways that you mentioned gender affirming therapy where, yes, we are effectively supporting, I'm hoping, transgender individuals to change their body's embrains at the same time they would align more consistently with characteristics of the gender.
ELISE: Yeah.
LISA: And the neuroscience of this transition is showing that that's also happening a little bit inside the brain. Obviously, nobody wants to buy into gender stereotypes necessarily. But like you said, typically the brains of cisgender women are more highly interconnected relative to the brains of cisgender men. And it looks like feminizing therapy aligns the brain of transgender women in a way that it makes them, you know, more similar to the characteristics of the gender that they desire. So I think in the other way around for transgender men, which I also think is interesting. So bigger brains, less interconnected, you know, better sleep, more libido and yeah, less I guess, less mood fluctuations up to a certain point. So I think it's very interesting. Yeah, it's really a field still in its infancy, I would say, it's also important to acknowledge that there are changes. Right. And that hormone therapy has an impact.
ELISE: Yeah.
LISA: that has been really fully mapped out. And as a woman, I find it offensive because women have been put on hormones for over 50 years, right? Starting at puberty, we start birth control, I mean, not always puberty, but like birth control for many, many years. And then we switch you to hormone replacement therapy for menopause. And we use endocrine therapies for cancer treatment. We use hormones fairly freely in some ways without really knowing how these therapies impact brain. And that is my opinion. It's just not okay.
ELISE: And I'm glad you're going to catch us up. And we'll talk about HRT, cause I learned again, I learned so much from you. And I have two sons, seven and 10. So I'm right there with you. Although as you point out, girls tend to go through puberty three or four years ahead of boys, which is not surprising, I think, to most people who are listening and I don't want to conflate nature and culture, but I did love this part of your book where you're talking about some of the symptoms of menopause, brain fog, and how terrifying it can be because women do have an increased rate of Alzheimer's, which I want to talk to you about as well. But that your point is mostly forgetting where the keys are is not the equivalent of early onset dementia and you write as well, which I think should give every woman consolation not to put too fine a point on it, but even during this phase, women outperform men on those very same cognitive tests, measuring memory, fluency, and some forms of attention. That's true both before and after menopause. During the menopause transition, cognitive scores may take a dip, bringing women's performance effectively within men's range. In other words, the average menopausal woman performs just as well as the average man of the same age who is not, of course, in menopause. And then we recover, right? Then we go back to just killing it. But it's so refreshing when We have been told throughout history that we're the weaker sex, and the mentally inferior sex, and to know, actually, cognitively, sorry, fellows. We've been outperforming you for a long time.
LISA: Even after the diagnosis of dementia, if you can imagine, even among patients with a clinical diagnosis of Alzheimer's disease, women tend to still outperform men on cognitive testing, which is interesting in many ways. And it's a big shout out for women's cognitive performance, but also it's concerning in some ways because it may mask the detection of Alzheimer's and diagnoses. So yeah, pros and cons.
ELISE: But it's kind of perfect that a demented woman still outperforms a man when we love to talk about how crazy women are, right?
LISA: I think it's a good point because so many women in menopause really are scared of going crazy and losing their minds, especially those who experience brain fog, which is over 60 percent, almost two thirds of all women going through menopause experience brain fog. Clinically, we call it mental fatigue or cognitive fatigue, which I think describes this reality quite well. so when they come to us for evaluation, we do very thorough cognitive testing and we do all the brain scans, of course, but I think it's really helpful to have this cognitive test done, because then we can score them, you know, they're standardized scores. So we can compare you to everybody else your age and gender and educational level so that you can get a good sense of whether or not it's a subjective perception of cognitive decline or objective because in so many cases, you're actually fine, like you're not fine by your own standards by relative to all other women your age who are going through the same transition, you are within norms, and this is good to know because we also know that after menopause for many women, cognitive performance has a rebound, right? It may not go to fully premenopausal levels, but it still gets better for a lot of women. Sometimes it stabilizes. Sometimes it doesn't. And then we talk about Alzheimer's prevention and we do more brain scans and try to find out what's happening. But in general, yes, it's traumatic and it's scary because you are not performing the way that you used to. So not all women, obviously, the women who have this problem, which can be terrifying, can be terrifying. You end up not trusting yourself. And for those who have a family history of disorders like dementia or Alzheimer's disease or memory loss, that's even scarier.
ELISE: Right.
LISA: I think it's really good to have a good solid baseline in midlife so that let's say 10 years later you're having real serious, more serious trouble. Then we can compare back to your baseline and see, okay, is the change consistent with the aging process? Or is it more severe? And then let's see what we can do.
ELISE: Yeah. So you, you know, open the book talking about how women, it's two to one for Alzheimer's, right? And obviously autoimmune disorders are far more prevalent with women and so on. What are the leading theories? Is it about sleep disruption and deprivation or Specifically for Alzheimer's maybe, I know they're all very different, but what do you think is happening?
LISA: I think it's hormones, in part, At least in part. At least this is what we're chasing as a possibility then. So we call sex hormones like estrogen, progesterone, testosterone, have been actually mislabeled for almost a hundred years, because they're not just sex hormones, they're brain hormones as well, but they play different roles for brain health than for reproduction. So the same estrogen that is involved in having kids and whatnot is also really crucial to brain health. Estrogen in particular, estradiol, which is one type of estrogen, is referred to as the master regulator of women's brains, because it's like, it's basic estradiol is to your brain what fuel is to an engine. It keeps it running and supervise like an orchestra conductor that supervises a lot of different functionalities in the brain from growing neurons and keeping them plastic and active to improving blood flow to the brain to improving immunity. So it makes your brain stronger. It also gives energy to your brain. It's a very energizing hormone, but more or less we can say then estrogen is a neuroprotective hormone. It protects your brain from aging and from harm. And so the difference between men and women is that our brains as women are loaded with estrogen receptors and therefore are wired to run on estrogen, whereas for men, they have more androgen receptors that bind to testosterone, right?
So they respond preferentially to changes in testosterone levels, which don't really happen that much. So for women, estrogen basically plummets after menopause, but it starts fluctuating widely during the transition to menopause, which can be anything between two years and ten, sometimes even longer. The average is four to seven, a long time, but not such a long time. If you go from having a lot of estrogen in your brain, it's very happy and energized to having very little. So that creates a window of vulnerability for the brain. This is my theory, our theory, many people's theory, during which medical predispositions have a chance to manifest. Like think of estrogen as like an amazing bodyguard that keeps all the bad guys in jail, right? As the bodyguard retires, that's the best chance for anyone to break free. And so if you do have a predisposition to Alzheimer's disease, this is when we start seeing the plaques, the Alzheimer's plaques and the different lesions show up in the brain.
If you have a predisposition to depression, you may have, you may develop clinical depression during menopause, even if it's your first time. If you have a disposition to anxiety, that's when you get it. If you have a predisposition to brain tumors, they may start growing at that time. Menopause, for some women, it's like an activator for medical risks. And then, of course, there are other things. Women can't sleep, don't sleep as well as men do, like you mentioned, we don't exercise nearly as much as other demographics do, especially midlife women. You know, we're sandwiched in between responsibilities and whatnot, and it's hard to find me time. There's a lot of stress and stress is really bad for brain health. There's a lot of other things that can play a role. Genetics, of course, play a role. But we're looking specifically at hormones as one possible trigger, right, for Alzheimer's or other neurological disorders, because There's ways to intervene and either supplement the hormones they were no longer making, or maybe there are other ways to sustain hormonal health for longer that are more lifestyle based and medically based and behavioral, rather than pharmaceutical. So we're looking at all of them.
ELISE: Yeah. Well, let's talk about HRT and why it was deeply maligned, which is unfortunate. And then also in addition to sort of the resurrection of the reputation of HRT in general, some of the other innovations, I know it's early, but was it the phytosurf? But the hormones that might even go so far as to just skip our reproductive organs and our breasts and go straight to the brain.
LISA: Hormone replacement therapy is one of the possibly most controversial topics in medicine. And it's been like that for decades, ever since the women's health initiative failed like epically. So this is, this is what happened from my perspective, from a brain scientist perspective, hormones were discovered in the thirties. And they were put into use and commercialized heavily soon afterwards, so much so that estrogen therapy was the number one selling drug in the United States in the 60s and 70s. Like billions and billions of prescriptions every year. So every woman who was going through menopause was put on hormones, a very high doses of hormones and left on hormones almost for life. Now, the NIH, the National Institute on Health said, well, you know, we've never done an actual clinical trial of hormone therapy, like a big one. So why don't we start one? So in the 1990s, they launched the Women's Health Initiative, which is to this day, the largest clinical trial of hormone replacement therapy for everything from prevention of cardiovascular disease to relief of hot flashes and night sweats, all the way to Alzheimer's and dementia prevention. In 1996, three years, After this enormous, gigantic clinical trial was launched, scientists realized that estrogen gets inside your brain and does a number of things in the brain that are time dependent, right? So you can't just put estrogen inside a brain anytime because that won't work. You have to time therapy based on what the brain wants, and the brain wants estrogen during menopause, during the transition, not decades later. Now, the Women's Health Initiative investigators did not know that because the trial was planned years and years prior. And so they went for very high doses of hormones in women who were decades post menopausal.
So the women's studies were in their 70s and 80s. But hormones work when you're in your 40s and 50s, if you start them, then you keep taking them. But if you start in your 40s and 50s, that's when they really work. So what happened with this Women's Health Initiative, at least for brain health, is that they found an increased risk of cardiovascular disease, of stroke, blood clots, but also dementia. And there was also an increased risk of breast cancer. Not a hugely increased risk, but a little bit of an increased risk that was picked on by the media and overemphasized, which led to So many women just going cold turkey and just stopping taking hormones pretty much overnight. Bunch of lawsuits, of course, against pharmaceutical companies. And they also backed off and said, Oh, okay, if you don't want it, don't take it. And then research came to a halt as well, because the hormones harm you, then I'm not going to study them. And we remain in that horrendous situation for decades. The Women's Health Initiative was stopped in 2002, we're in 2023, and only last year, 2022, did the North American Menopause Society issue fully revised guidelines on the best use of HRT in clinical practice, where they say, actually, If you are an eligible woman, ages 40 to 60 or within 10 years of the final menstrual period, taking hormones is actually beneficial and has a really good benefits to risk, risk to benefits ratio, provided that you do the right thing, take the right hormones at the right dose for a decent amount, for the right amount of time, for a reasonable amount of time.
And Dr. Manson, who was head of the WHI, the Women's Health Initiative, also said that previous recommendations may actually have harmed some women because women were discouraged. Right? It was, the guidelines said, don't take hormones unless you really need them and stop taking them as soon as you can. So now the pendulum has swung finally and we are in a position when, where we can actually discuss hormone replacement therapy as a valuable option for many women. It's not the only option, but it is at least on the table for a lot of women who can really benefit from it, especially women who go through surgical menopause, when they have their ovaries removed or the uterus and ovaries removed. In that case, professional societies advise to start taking hormones as close as possible to surgery and keep taking hormones until the average age of menopause, which is 51, 52 in America. It's a complete change, right?
ELISE: Yeah.
LISA: The big plot twist, thankfully.
ELISE: I mean, this is obviously the focus of your study, of the hopefully long term benefits, but then there are also, I think you call them designer estrogen, right? That can bypass...
LISA: yes. I'm very excited about that. So, you know, the concern around breast cancer was definitely inflated, as I mentioned by the media, because they reported like, Oh my God, there's almost a 30 percent increase in breast cancer, which is frightening. If they give you a percentage. Percentages are scary. So to our listeners, whenever you see a percentage, the right question is a percentage of what? You know, if it's 30 percent of 10, it's a lot less scary than 30 percent of a million. Like, how many women are we actually talking about? Because if you look at the numbers, and not just the Women's Health Initiative, but I can send you the link if you want. There's a wonderful meta analysis that was just published in The Lancet, it's a wonderful journal, that looked at over 30, I believe, studies associated linking HRT use with breast cancer also depending on formulation. And they show that with some formulations like, bioidentical progesterone, the increased risk in breast cancer is two cases per 10,000 women. The highest possible risk that we saw with the Women's Health Initiative is factored in is about 30 more cases per every 10, 000 women who take hormones. You know, so there is a little bit of an increase in risk, and it's important to know your family history and your own risk factors for breast cancer, but if you take the newest formulations of estrogens, like micronized, bioidentical, it's called micronized estrogen, and micronized or bioidentical progesterone, then the increased risk is low, and it's very similar to, for instance, drinking two glasses of wine per day. If we did it in context, are you worried about two glasses of wine? Maybe not. I don't drink any alcohol, so I don't know, but most people I know would be comfortable with that, maybe. Or, it's less, actually, the increase in risk is lower than being severely overweight. And nobody thinks that that is a risk factor.
Yes, it is significantly lower as compared to being a flight attendant, you know, so you, you put it in context and then it's up to you and everybody has a different risk tolerance. Nonetheless, I'm circling back to your point, there are concerns, you know, with medicines, there are always some concerns. What we're using in clinical practice now is the second generation of hormones. There's a third generation that's just been developed and is based off of an interesting concept that is the SERMs, Selective Estrogen Receptor Modulators. They're selective in that you can engineer hormones to target specific tissues in the body. So we have SERMs for cancer. Like tamoxifen, the very specifically blocks estrogen action in breast tissue, but some say it supports estrogen activity in the bones, right? So different tissues are modulated differently. So we need SERMs for the brain. And my mentor, Dr. Roberta Diaz Brinton at the University of Arizona, developed a NeuroSERM. So it's a selective estrogen or a designer estrogen for the brain to be used in menopause. And the way the SERM works, she calls it a phytocerm because it comes from plants. Everybody wants plant based stuff. So this one comes from plants, like bioidentical estrogen. Anyways, you know, similar plants. The way it works is that you take it by mouth. It's a little tablet. Take one a day, one pill a day, and it dissolves, you just metabolize it, and it goes directly inside your brain and has boosting effects for brain health. So it supports metabolic activity in the brain, it supports blood flow in the brain, it supports cellular energy production in the brain, but has inhibitory or neutral effects in reproductive tissue, which means that it does not increase the risk of cancer to the breast or the endometrium of the uterus or the ovaries.
So I think it's a genius formulation and we are testing it now in clinical trials at wild connect medicine on the upper east side where I work. If anybody's interested, if anybody's having half flashes or brain fog or sleep issues due to menopause, this formulation seems to help. with these symptoms, and we're also testing it for Alzheimer's prevention. So we do brain scans, we work with women who are perimenopausal, which has never been done. There are many clinical trials of perimenopausal women in brain fog and brain health as far as I know. At least not for Alzheimer's prevention, definitely. So, yeah, that's what we're doing.
ELISE: It's like very exciting. And so the Holy Grail really is both symptom amelioration, hot flashes, sleep disturbance and also health protective activity, protecting the brain, mitigating risk of cancer, et cetera, bone health. And then once you're through this transition. And you're stabilized on the other side, your growing pains are over, and then is the idea that you stop HRT and you just get to be a fully realized menopausal woman who, I want to talk about the way that people are like, why would we have menopausal women if they can't have babies, why don't they just die and go away? This general distaste, I know, right?
LISA: the world would just fall apart completely we didn't have older women, I think. No?
ELISE: It would.
LISA: Yeah.
ELISE: But that's the idea, is that you do it during that transitory phase, and then you are..
LISA: Some people just don't want to get off of HRT because they feel wonderful. And sometimes what happens is that the symptoms of menopause last for a really long, can last for a really long time. So there are different patterns of menopausal symptoms. There are some women who don't really have any, and that's amazing. So about 10 percent of women do not really have any severe discomfort, let's put it that way. So for those women, there's no particular indication that they would benefit from taking any exogenous or estrogenic preparation. Who knows? The research hasn't been done, but at least in theory, you know, those women would not require hormonal replacement. And then we'll see what happens once we have more information. But then there's women who start experiencing the symptoms really close to the final menstrual period, and then the symptoms just go away on their own within six years of the final menstrual period, and those are late onset flashers.
And then there's the early onset category where the symptoms starts early in life and they stay with you for many, many years. And then there's the super flashers who are not very lucky, it's one in four women or 1 in 5 who have really severe symptoms for many, many years that do not really fully go away after the final menstrual period. So for some women taking hormones for a long period of time is probably beneficial. In theory, at some point you stop, right? But there's some friends of mine who will say that they will just never take out their patch. They'll just spend the life, I'll die with my patch on. I've heard that. I've heard that many times. I think at some point women have been able to navigate menopause effectively for centuries without the menopausal therapy, not always smoothly. Right? But it is doable and that's how we learned a few things about the ways that menopause impacts brain health in the long term. Because we need to study women who are not taking hormones, otherwise there's a confounding factor.
So that research has shown that menopause is a neurologically active state that much alike the former two Ps, puberty and pregnancy, changes the brain in ways that, yes, can lead to the symptoms. They have flashes, the night sweats, depression, anxiety, insomnia, low libido, brain fog, memory lapses, just no picnic and should take seriously, managed as needed. But at the same time, rewire your brain by once again, boosting your theory of mind networks, to the point that a few things happen once the transition is completed. So number one, postmenopausal women have the highest levels of empathy, cognitive and emotional empathy, than any other age and gender group on this planet.
So your empathy is off the charts. Why? There's a whole evolutionary explanation for that, that if you want, we can talk about. But the point is that it does help society to have individuals who are so empathic and generous and able to support others basically for life. Number two, happiness or life contentment, which I was surprised to hear because all our patients come to us and they're basically suicidal. And I just not do, I'm not laughing about it just that the contrast is striking. During the transition, a lot of people are having a really, really hard time. But what data shows across the lifespan is that, yes, during the transition to menopause, there is a dip in happiness and life contentment. But then, the scores go back up after menopause, usually in the late post menopausal phase, which is more than five years after your final menstrual period.
And then they keep increasing to the point that post menopausal women who are really done, you know, with menopause are actually happier than younger premenopausal women, but also they report being happier than they themselves were before they went through menopause, which I found really spectacular and is consistent with some reports. The happiness in life shows a U shaped curve, right? So there's like a midlife slump for a lot of people, but then happiness usually tends to rebound and increase over time as we get older, which brings us to the next gift that we get from menopause, at least some women experience this, which is emotional mastering or transcendence, or as many women would say, including many of our patients and many friends also say, it's like giving fewer...
ELISE: fs. Fucks. Yes.
LISA: yes. That comes up. Every time. I just couldn't care less about this and that. I'm done with this. I'm over that. I have no time for this nonsense. So something that happens neurologically is that a very specific region of the brain called the amygdala is being rewired in menopause. And the amygdala is the emotional center of the brain. And what happens with menopause is that It gets turned down towards negative things. So it becomes less reactive to things that would have been upsetting before menopause. So your brain is still perfectly fine rejoicing for happy things, but it's less affected and you're less affected by things that would be upsetting otherwise, and that leads to emotional control and better emotional mastery and just being more kind of like going with the flow. You have a renewed sense of peace in nothing else. It's less reactive to things that were catching up a wall just a little bit to them. So these are some of the things that can happen after menopause that I think are very interesting and certainly worth looking forward to, right?
ELISE: Yeah. And you dive into this in the book, but one of the things that's so Distressing, I think, about this Western idea of old women and the fact that we have no venerating terms for them. It's, you know, crone and hag and witch and on and on. Is that, you know, when you look at early, this is more Barbara Walker's work, who's not a neuroscientist, but she talks about how in our earlier history, even up until I think the 16th century or the 17th century, there was this idea, even in Christian cultures, that women, when we retained our monthly blood were creating life, right? So there was, that happened with pregnancy and that with menopausal women, that there was an accrual of magic or power by the retention of this blood, and so these women became sort of magical, wise elders, clearly we're not doing that these days, but in some parts of the world, you write about how, like in Japan, there's a totally different perception of menopause and fewer symptoms, and that there's this anthropological reason that old women ensure the survival of our species, if we could see it, I don't know, I feel like acutely that we are in such dire straits environmentally and culturally and socially because we do not venerate older women and appoint them into positions of leading us as wise elders. But can you talk a little bit, I know it's slightly outside of your remit, but what you think, I mean, it affects our brain, right? The perception of older women.
LISA: Yes, of course. I mean, here in Western societies, usually we associate menopause with a lot of use, unwanted, unattractive, useless, you know, you served your purpose, now just go die somewhere else. We don't want to hear your story. And this is really a bit of a reflection of a very strong patriarchal society that's always, but certainly diminished women in every way, shape, and form, right? And this kind of stigma and bias has carried through to medicine. With menopause is, honestly, it's one of the very few situations I've ever encountered where suffering in silence is not only accepted, but is encouraged, widely encourage, just get on with it, you know, your mom went through it, so you can do it too, pat on the back. And that is just completely unacceptable. Especially if you think that in other parts of the world, older women, like you said, gain status after menopause, they gain something. There's something to look forward to. If nothing else, recognition and respect, right? They've done so much in life and now they are the wise elder women, you know, the chiefs of some cultures and societies and communities.
What was very interesting to me is to also realize that in countries where women look favorably towards menopause. At least there's no fear of menopause or no negative anticipation, the symptoms are much milder. And that's interesting because if menopause was just a reproductive event or a hormonal event, which is what Western medicine tells you, you lose your hormones, you're hormone deficient, which is a word I absolutely detest. And that's it. That's all there is to menopause, which is obviously not true. In other countries, like you mentioned, Japan, in some parts of Asia, women do not fear menopause as much. The symptoms are milder and they don't even have hot flashes that much. You know, they tend to have frozen shoulders or pains and aches, but certainly not these devastating symptoms, as some women in Western societies report. In some parts of India, where, again, older women are celebrated, then the most common complaint is lost vision or eyesight.
ELISE: Interesting.
LISA: Yes, it is interesting. In some rural male societies, women have no symptoms at all. although their estrogen drops just as much as, you know, as ours do. So there is a mindset component that I think has been a little bit maybe overlooked, but that is really well known in medicine. Everybody knows the placebo effect, right? If you think that a medicine is going to help you, you will feel better. Even if you're just having a sugar pill instead of your medication. But there's also nocebo effect, which is the opposite of the placebo effect, which is done if you're scared that something will harm you. Chances are you will have symptoms. Chances are you will be harmed by something that is completely harmless. So I think this is important to realize because our expectations, our minds are way more powerful than we give them credit to. And really what you think shapes many of your physiological reactions. So it's important to realize that yes, menopause can come with symptoms, but the symptoms are not alien symptoms. We've seen them before. We've seen them at puberty. We've seen them at pregnancy, if you've been pregnant. We've been there before. And I like to say that menopause is just another tune that we learn to dance to, right? We can do it. We will navigate it. The point is let's make sure that we have the right information, that we understand how it works and that we're aware of the solutions because there are so many women who decide how to navigate menopause based on information that is not unfortunately accurate, it is not up to date. So a lot of decisions are really based on fear rather than facts and then there's regret. I hear this constantly. I wish I had known. I wish somebody had told me. I wish there was public information. I wish there was better education. I wish my doctor knew, right? Now that menopause is having a moment, I think it's important to really push for education. Right? Because once we go through puberty and we gather periods, we all get the talk. At least we know what to expect, what to do, whether it's tampons or something, but you have a sense of being part of a team of women who's been there before, whereas menopause is completely covered in secret and there's absolutely no reason for it. So I think that this is a good time to prepare.
ELISE: Well, thank you for your work. Congrats on everything and I'm excited to follow this space and people like you make me want to engage with it rather than just run out of the room.
There’s so much that we didn’t get to. She has comprehensive sections about chemo and the brain, about gender affirming therapies, about exercise, diet, nutraceuticals, sleep, etc. So it’s a really great resource and as I was saying to her after we ended, I had felt so much resistance in myself to even engaging with this next phase of life as a pathologized state and I found her book to be incredibly affirming, positive and aligned with how I wanted to see it.
We talked a bit at the end, obviously, about some of the cultural differences and she writes about how in Japan, the word—it’s funny, you think of the word menopause as this massive transitional zone in our life and the way that that’s describes, which literally means “monthly pause.” And again, as women, I think we’re tired of being described, conceived, and delimited to our reproductive status, right? No thank you, we don’t do the same thing to men at all and it’s strange. We’re so much more than our ability to birth children or not. And she writes about the Japanese word for menopause, which is konenki, which “Literally translated, ko means renewal and regeneration, nen means year or years, and ki means season or energy. The Japanese define the same event we dread—menopause—as a much lengthier and spiritual transition where the end of periods is just one element.” And I love that, this idea of season or energy as a transitional phase. And as she points out “only about 25 percent of Japanese women reportedly experience hot flashes, a considerably lower rate than in the United States.”
And I have more conversations coming about older women and what we do to them and the way that we should think about this stage—coming in 2024. But, I feel a certain desperation around re-centering the elder women in our culture, particularly in light of these very turbulent times we find ourselves in. To me, it feels like the missing piece. Going back to what Barbara Crone had said about how there was this perception of older women as being magical because of their retention of lunar blood, that of course, then turned on older women as they became the primary targets of the witch hunts, particularly the witch craze across Europe, where we’ll never quite know the number, but the idea or general consensus that it was about 80,000 people, some men, some younger women, but certainly the older women were the targets, I think out of this fear, right? Of this older women who know longer gave a fuck, as Lisa explained, this feeling of extreme maturation which I think can be terrifying to behold. And also these older women, particularly if they were widowed owned property that was disinherited from them as soon as they were hunted—a whole other conversation which I’m hoping to have. In the interim, thank you for listening. I’ll see you next time.
