This is Your Brain on Menopause

Some of the more concerning (and bothersome) symptoms of menopause are brain symptoms. When it happens, brain fog can be totally terrifying. And, the older we get, the more we worry about things like Alzheimer’s Disease. We were recently lucky enough to have Dr. Lisa Mosconi as our Webinar guest to talk to us about brain health in menopause, along with our very own Anne Fulenwider and Dr. Sharon Malone!

Dr. Lisa Mosconi is an Associate Professor of Neuroscience in Neurology and Radiology at Weill Cornell Medicine (WCM), and the Director of the Women’s Brain Initiative and the Alzheimer’s Prevention Clinic at WCM/NewYork-Presbyterian Hospital. She is ranked in the top 1% of scientists of the past 20 years by official metrics, and was listed as one of the 17 most influential living female scientists by The Times. She is the author of the bestselling book The XX Brain and of the international bestseller Brain Food. Her latest book, The Menopause Brain, is available for purchase now!

Dr. Sharon Malone is a board-certified OB/GYN with decades of experience caring for women in menopause. She is the author of the just-released book Grown Woman Talk: Your Guide to Getting and Staying Healthy and, of course, is our Chief Medical Advisor here at Alloy.

We’re sharing highlights from the interview, which has been edited for length and clarity here. Watch the whole thing on our YouTube! As always, please note that this Webinar is for educational purposes only and is not meant to be used as personal medical advice.

Anne Fulenwider: Thank you both for being here. We have so much to cover. I’m going to start with Dr. Mosconi: Why did you enter the field you did? And, why this book? Why now?

Dr. Lisa Mosconi: Sure. So I literally grew into science. My parents are nuclear physicists and I was always a weird child, if you will. I was really interested in the brain and brain health and neurology and what not. So I was able to get into nuclear medicine, which is a branch of radiology that specifically looks at functionality and biochemistry in different organs including the brain. And as part of my PhD, I transferred to NYU Medical where I was then hired as a faculty member. I would say the major focus of my research has been on the early detection and prevention of Alzheimer's disease and neurodegenerative dementia. And more recently, I got kind of pulled into the menopause field in part because my research shows how important and impactful menopause is for women's brain health.

As far as the book, and why now, the research is new, and there is a lot more research being done on menopause and brain health than ever before, and it's so important to take the research out of the lab and make it not just accessible, but actionable. Menopause is having a moment, and there are a lot of things being said about menopause and about the brain. And so I wanted to make sure that women have access to this scientific information.

Anne Fulenwider:

Dr. Malone, how did you get here?

Dr. Sharon Malone: Thank you. I’m so delighted to be joined by my friend Dr. Lisa Mosconi. I’ve had a rather circuitous route to where I’m now, but it started when I was in college. I was a psychology major, but I was actually in psychobiology or physiological psychology because I was fascinated with all the things that were going on in the brain. And this was a long time ago. It was when we were figuring out it's the brain, not the mind, that is really the seed of a lot of the really the psychiatric disorders that we found. So I went to medical school thinking that I was going to be a neurologist and my advisor was this woman, this amazing woman, Dominique Toran. She was a neurologist and she did her research on the effects of estrogen on the development of neurons and how putting estrogen in a Petri dish actually changed how brain cells grew.

So that was where I kind of started. But it ended up being frustrating for me because we had so few treatment options for so many of the neurological conditions we were seeing. Ultimately I got into OB/GYN because more often than not, people were happy and healthy and you were going to get a good ending. So now I have come full circle to get into menopause. It’s not just an event you move on from. It is a distinct phase of women’s lives that we have not paid attention to. And thankfully that as we've come full circle, and we have people like the brilliant Dr. Lisa Mosconi who are trying to answer some of the questions that we had 40 years ago when I started in medicine. And that's why I think that ultimately our connection has been as strong as it is. We both are looking at menopause from different perspectives. But our goal is the same, which is to make women age more healthfully and more functionally.

Anne Fulenwider: Beautifully said. As we age, we go through menopause, if we’re lucky enough to live that long, and we all start to worry about our brains. But, let’s start from the beginning. Dr. Malone, from the OB/GYN perspective, just give us the baseline definition of menopause and talk a bit about how we treat it. 

Dr. Sharon Malone: Sure. Menopause is when you’ve had your last menstrual period, and it’s confirmed when you haven’t had one for 12 months. There’s also the transition, called perimenopause, which is a long process. It can take years, anywhere from four to ten years. For African-American women it’s closer to ten years. And it’s marked by all of the symptoms that we associate with menopause like hot flashes, mood swings, and brain fog. They don’t just happen when you’ve had your last menstrual period; they can start as early as a decade before. And what we’ve been figuring out is how to treat those symptoms, because they can be bothersome at best, and for some they can be quite devastating.

Menopause is a hormonal event. Perimenopause is really characterized by vast fluctuations in your hormones. They're up, they're down, and everywhere in between, and menopause is really defined as the moment at which your hormones, your ovaries have stopped functioning, stopped producing estrogen and progesterone on their own. Your levels remain low from that time forward. So it sort of makes sense that when we are looking at treatments and how to deal with a hormonal process, that hormones are part of that. So, hormone therapy, either in perimenopause or menopause, or both, is really the keystone. It is the most effective treatment for symptoms of menopause. And, as we’ll hear from Dr. Mosconi, it’s also important for preventing some of the long-term consequences of that estrogen deprivation as we age. 

Anne Fulenwider: Beautiful. I also want to talk about how these symptoms are more than bothersome. They’re not benign. They have long-term effects. So that brings us to Dr. Mosconi. How do you define menopause as a neurologist, and what have you learned about the connection between menopause and the brain? 

Dr. Lisa Mosconi: What I've learned is that in medicine we base the definition of menopause on the OB/GYN definition, which is very ovary-driven. And that makes sense if you’re an OB/GYN. But if we look at the entire woman’s body, it’s an organism. It’s not just a number of different organs that work independently from each other. 

From a neuroscientific perspective, menopause is defined as a neuroendocrine transition state. It impacts multiple organ systems. So, what does that mean? It means that as women, we were born with a neuroendocrine system that connects the brain to the ovaries and the rest of the endocrine system. 

That system is turned on in puberty, it’s overactivated during pregnancy, and it’s in a turbulent state postpartum. It’s partially deactivated after menopause. And what matters most for this transition is the perimenopausal period, which from the brain’s perspective is even longer than the four to ten years window. It starts earlier than that. And by doing brain imaging, which is what I do for a living at this point, you can see the very subtle changes in brain structure and function starting when women are basically in their early forties, and their periods are changing a bit, even if they’re still quite regular.  

Your brain is already getting signals from the ovaries that it’s time to prepare for this transition. Then, once the ovaries stop making estrogen and progesterone and run out of follicles, the brain is still not done. It takes the brain up to a decade to really settle down and find a new normal and carry on. And outcomes vary from person to person.

Brain symptoms of menopause include hot flashes, night sweats, insomnia, depression, anxiety, brain fog, memory lapses… Those are all neurological signs that the brain is undergoing a transformation along with the ovaries. But the timeline is different. 

Anne Fulenwider: Can you talk about how hot flashes are a brain symptom? 

Dr. Lisa Mosconi:

The brain is responsible for regulating body temperature. Body temperature comes from your brain. So, in part, it’s a neurological function. 

Anne Fulenwider:

You have some famous pictures of the brain before menopause and the brain after menopause. Can you give us an overview? Are our brains just declining rapidly once we hit menopause, and that’s it?

Dr. Lisa Mosconi: Well, I wouldn't say declining from a clinical perspective. But, basically, as Dr. Malone was saying before, menopause is kind of identified as the end of your menstrual cycle. And especially in brain imaging research, all the work had been done on women who were postmenopausal, and by a long shot. It was women who were in their seventies and eighties. So we really didn't have any information about how menopause directly impacts the brain and how the brain changes during the transition, which I think is much more interesting than what happens 30 years later if you want to understand menopause. And so we did brain scans on midlife women ages 40 to 65. And we have two sets of those brain scans. The original set, which Sharon has seen multiple times in this point, shows two different women, the premenopausal women in the postmenopausal woman. 

But now we also have longitudinal data so we can track brain changes in the same woman over time. And what we've learned is that menopause changes the structure of the brain. It changes metabolic activity in the brain, which means energy levels in the brain. It changes the connectivity of the brain, it changes blood flow to the brain and it changes the biochemistry of the brain as well. So it's really a bit like a renovation project on the brain–so many things change. The brain is rewiring to prepare women for a non reproductive stage of life, and that is associated with multiple changes that may be associated with the symptoms. And this is what we're studying now, brain fog, what are the actual brain correlate of brain fog? And yeah, I mean it's something that we need to better characterize for sure.

Anne Fulenwider: And Dr. Malone, you have mentioned multiple times in talks that I've seen you at recently, this idea that a hot flash is not just a pain in the neck. The more you hot flash, the more you have markers for things that will affect you later in life. Can you talk a little bit about that?

Dr. Sharon Malone: The reason why they are not benign is because we know that women who have very severe hot flashes, and hot flashes that last for a long time, are more likely to have cardiovascular disease and depression. When they do brain scans on women who have severe hot flashes, they have lesions on the brain that may be markers of Alzheimer’s disease down the road. Plus, if you have hot flashes, you can't sleep. If you can't sleep, that also is affecting your brain, your heart disease, all of this. So even though we laugh and people make fun of hot flashes and say, go get a fan and it'll be fine, they are not benign. They can be a harbinger of things that are problematic down the road. 

Anne Fulenwider: Dr. Mosconi, you’ve called estradiol the CEO of the female brain. I love that. Can you explain why? 

Dr. Lisa Mosconi: So, in neuroscience, estradiol has been named the master regulator of women's brains, and that's actually my mentor, Dr. Roberta Diaz Brinton, who came up with this definition. She’s been studying estradiol for brain health for about 40 years, and she was impressed at the range of functionalities that estradiol serves in women’s brains. That’s because estrogen alone is not nearly as important as the combination of estrogen with an estrogen receptor. The way the hormones work is that they're like keys to a lock where the hormone is the key and the receptor is the lock that you need to open for a million wonderful things to happen inside the brain and the rest of the body. And in the case of estradiol, women's brains are really full of estrogen receptors. Estradiol is the most bioactive and bioavailable hormone throughout a woman's reproductive life. What that means is that women's brains are extremely sensitive to fluctuations in estrogen levels. And when you do have estrogen in your brain, you can see in a Petri dish, you can see with brain imaging, your brain has more energy because estradiol is a neuroprotective hormone. It supports the immune system inside the brain. It's a neurotrophic hormone.. It also improves blood flow and circulation to the brain. It pushes your neurons to work harder and burn more sugar and more substrates to make energy. And it has a lot more functionality. It's involved in neuroplasticity, it's involved in immune control. So, it's like a conductor, or CEO. 

Anne Fulenwider: Dr. Mosconi, as you know very well, one of women's biggest fears at this age is Alzheimer's, Women are two thirds of Alzheimer's patients. So we are more likely to get it. We're terrified of it. We have brain fog symptoms in perimenopause and menopause that  make us think we’re getting it. And we want to prevent it. One thing we’re hearing a lot about recently is a fear about hormone therapy and Alzheimer’s. Can you unpack that for us?  

Dr. Lisa Mosconi: Every so often, there's a new headline–it feels like people are really determined to prove there’s something wrong with taking hormones. But when it comes to Alzheimer's disease, we and others have shown that menopause can be a risk factor for developing Alzheimer’s disease. 

When it comes to therapy, it makes sense that you would reduce the risk of Alzheimer’s disease by taking hormones and protecting your brain. The majority of scientists I work with would say that that makes a lot of sense. When you look at clinical trials, the evidence is mixed. And recently there’s been this group in Denmark who decided to terrify everyone by showing that in their cohort there was an increased risk of dementia, not of Alzheimer’s disease, but of all-cause dementia for those who were taking hormones before the Women’s Health Initiative.

So, in the early 2000s. And those women were taking high doses of conjugated equine estrogens, often with a synthetic progestin. So, it was a very specific type of hormone therapy, which is different from what is most widely used today. So it is not the same, and I think it's very important to realize that formulation seems to have an impact. What also seems to have an impact is timing, which Dr. Malone was talking about before. So what we had done, for peace of mind, is a meta analysis. So we have more than, I think it was more than 6 million women in the analysis at this point. And I can check, but there were a lot of studies. What we have shown is that for women who start hormone therapy in midlife, in response to the symptoms of menopause, then the risk of future Alzheimer's disease, but also all-cause dementia, but specifically Alzheimer's disease is actually reduced, especially for women with surgical menopause, which is exactly what Dr. Malone was saying. 

Dr. Sharon Malone: Can I make one quick plug before we go? 

We, as women, individually and collectively, need to advocate for more research. We’re still trying to answer questions that we’ve been asking for 30 years. We need to support researchers who are out there trying to answer them. Because the only questions that are going to be answered are the ones that are asked. It’s time for us to speak up. 

For more from Dr. Malone and Dr. Mosconi, including questions from our audience, watch the whole webinar on our YouTube!

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