For many women, the shifting hormones of midlife bring troubling physical and mental health symptoms, hot flashes, disrupted sleep, mood changes, and even memory issues. But although half the world's population will probably experience menopause, for decades it received relatively little serious attention from doctors and researchers. Instead, it's been the subject of sitcom jokes and something that women were just expected to put up with. In recent years, though, researchers have focused new attention on women's health and learned more about the short and long-term health effects of menopause. They've even found links between menopause symptoms and cardiovascular and Alzheimer's risk. So what are the major mental and physical health effects of menopause? How common are experiences like hot flashes, mood changes, and memory changes? What are the implications for women's physical, mental, and cognitive health later in life? And what risks and benefits should women consider as they think about and talk to their doctors about treatments including hormone replacement therapy? Welcome to Speaking of Psychology, the flagship podcast of the American Psychological Association that examines the links between psychological science and everyday life. I'm Kim Mills, coming to you today from our annual convention, APA 2025 in Denver. My guest today is Dr. Rebecca Thurston, a clinical health psychologist and assistant dean for women's health research and director of the Center for Women's Biobahavioral Health Research at the University of Pittsburgh. She also holds appointments in the departments of psychiatry, epidemiology, psychology, and clinical and translational science. Dr. Thurston's research has looked at connections between menopause and cardiovascular disease and brain aging as well as how a history of trauma affects people's experience of menopause. So Dr. Thurston, when does menopause start for most women and how long does it typically last? For most women, the beginnings of the menopause will happen in the 40s. Late 40s, maybe early 50s, and that's marked by the perimenopause, which is a time of menstrual cycle irregularity and skipping. And after a woman have skipped 12 months of menstrual cycles, she enters into the post-menopause, where she stays the rest of her life. And the average age of the onset of post-menopause is 51. What hormonal and other changes happen to the body during menopause? There's multiple different hormonal changes. The most well-characterized hormone changes are declines in the ovarian estrogen estradiol. That's our most potent estrogen in the body. And in about those plus or minus two years before and after that onset of post-menopause is when you have the most dramatic declines in estradiol. And then you have steady increases in something called follicle-stimulating hormone. That's secreted by your pituitary trying to tell your ovary to excrete estradiol, the ovary system done. FSH keeps rising, trying to get that ovary to respond, and then eventually levels out at high levels. And that's the same. It's around those plus or minus two years around the onset of the post-menopause. But what's really important to keep in mind is that these hormones are bouncing around from month to month during the perimenopause. So one month will be very high, one month will be very low. So getting a single hormone test during the perimenopause, that time of menstrual cycle irregularity and skipping, is typically not so useful. It's when you enter into the post-menopause that you really can understand from getting your hormones tested where you are. And why would a woman want to have a test? Many women want to know what's going on. They're having a lot of symptoms. Things feel a little out of control, whether it's with the symptoms they're experiencing or their menstrual cycle changes. And they want answers. They want to know what's happening. So it's useful to be able to tell women where you are in the menopause transition. Unfortunately, that single blood test hormone assay is not going to do it if you're in the perimenopause. Hot flashes are one of the most well-known symptoms of menopause. How common are they? Why do they happen? What is the biological mechanism that's at work? Well, I've spent decades studying hot flashes specifically, so you've come to the right place. About 70, 75% of women will experience hot flashes. They typically start during the perimenopause and continue. So they last about seven to ten years for moderate to severe hot flashes and longer for less severe hot flashes. And there's pronounced racial ethnic differences in hot flashes. So upwards of 80% of black women will get hot flashes. We used to think Asian women didn't get hot flashes. That's not true. Upwards of 50% of women, Asian women will get hot flashes. And the white and the Latino women, at least in our swan study, were kind of in the middle. And for some women, they actually start when they're still menstruating in those late reproductive years. For other women, they go on and on and on well into their 60s and beyond sometimes. So if you still are having hot flashes, you're not alone. That's probably about 20% of women. It goes on for quite a long time. So the neurobiology of hot flashes. We've just recently, there's been recent breakthroughs in this. For a while, we didn't really know what caused them. And we knew it has something to do with the thermoregulatory system. And it went something like this. So our body keeps our core body temperature within a thermonutrile zone. When we go above the zone, we sweat. When we go below the zone, we shiver. And those are mechanisms that our body uses to bring our core body temperature within this thermonutrile zone. However, there was some evidence, early evidence in the 90s to show that these women who had a lot of hot flashes, they had a very narrowed thermonutrile zone. And so small changes in core body temperature were experienced as much too hot. You get this massive heat dissipation event in the form of hot flashes and cools you down. And then sometimes you get shivering and overshooting. So that was kind of the heuristic model, so to speak. But we didn't really understand the biology. Naomi Rans came along in the mid-auts, and she actually helped elucidate what's the underlying neurobiology. So this is all happening in the brain and the hypothalamus. And there's these cute little neurons called these candy neurons that actually act as the relay station between the thermoregulatory centers of your body and the hormonal centers, the master control of your reproductive axis, both are in the hypothalamus, and the way that they talk to each other is through the scanning neurons. And we have a new class of agents that are very effective in treating hot flashes on neurokinin-3 receptor antagonists, neurokinin-1-3 receptor antagonists that go after that neurobiology, and they very effectively treat hot flashes. Do we have any idea what purpose hot flashes serve as a woman is going through menopause? We have no idea. There's been many hypotheses, many tales told, but no, we don't really understand any kind of evolutionary benefit that hot flashes may have, or even health benefit to women. In fact, we typically find quite the opposite. So it's not like a fever where it's trying to fight off an infection. It's just your temperature has gone a little haywire. Your thermostat has gone a little haywire. So it's like your body's internal thermostat doesn't quite know that these small changes in body temperature are not a reason to have these big heat dissipation events. That thermonutrile zone getting very narrow indicates that that thermostat's a little broken, and it seems to come back online for most women when they make it through the menopause transition. What are some of the other physical and mental health challenges that women might experience during menopause? So the most common symptoms, so we have our hot flashes, upwards of 70% of women, about 50% of women, if not more, experienced problems with sleep. Clinically, significant problems with sleep. This is a huge one. In fact, there's a two to three-fold increase likelihood of having sleep problems during the menopause transition relative to premenopause when we follow women and compare them to themselves. So sleep problems huge. We see the brain fog and memory issues as well as a distractibility difficulty with emotion regulation, which is sort of part of this clustering of cognitive symptoms. We also see increased risk for depression and anxiety. The SWAN study actually did clinical interviews to be able to diagnose depression. We found a two to four-fold increase likelihood of depression, clinical depression during the menopause transition as compared to the premenopause. So that's really important. Also increases in anxiety symptoms. Really common. I see this a lot clinically, in fact. And in terms of the biological side, we do see with midlife aging, waking, that's a midlife aging effect. The menopause effect is changes in body composition. So even if your weight's stable, there's increases in fat mass, decreases in bone and muscle, unfortunately. And that little bit of attire you get around your waist, very common standard menopause thing. So the weight changes, we see accelerations in vascular risk, even when we image women's vessels, even controlling for age. And then also, like I mentioned, pretty marked decreases in bone mineral density. Anything on the plus side? I mean, you know, I think you're not having a monthly period anymore. You're not having those symptoms and you don't have to worry about getting pregnant during sex. So, you know, are there some good things? Yes, yes, yes. There are good things. Now, this is unfortunately received a lot less empirical attention than the bad things. And I forgot to mention the urogenital changes that come as well, so the vaginal dryness. So that's a thing. Now, on the positive side, what I see clinically, and there's some data to support this. So, of course, you don't have that period anymore. You don't have to worry about pregnancy anymore. But from a psychological perspective, I see increased self-confidence, increased feelings of being yourself, not caring what people think about you quite as much. You know, people talk about that invisibility of midlife women. Sometimes that's a gift. You feel it is enhanced sense of freedom. And you just realize that, you know what? Life's too short. I'm just going to be who I am. And people are going to take it or leave it. And that's what I see a lot of. And I think that's fantastic. I take it you've seen that woman online who does the We Don't Care Club. Yeah, I love it. She's hysterical. Love it. It's the glasses. All the glasses. Yeah, all the glasses. Yeah, she's great. Yeah. Your research has found that more frequent or severe hot flashes are linked to early signs of heart disease in women. Can you tell us about that research? What did you find? Why would hot flashes be linked to cardiovascular risk? Well, we started asking this question because we saw that there was two different analyses of our, these big hormone therapy trials. The Women's Health Initiative and the HER studies. Both studies looked at the effects of hormone therapy as a prevention for cardiovascular disease, whether primary or secondary prevention. Both studies showed that hormone therapy did not prevent heart disease, particularly for the older women, and may actually increase risk. Little known are several post-hoc analyses of those trials that showed that the women at the greatest cardiovascular disease risk with hormone therapy, the older women in the Women's Health Initiative, were women with hot flashes. So it made me ask, what is it about the underlying vascular that's different about these women with hot flashes? They are called vasomotor events, after all. So what role does the vasocator have? And I began by asking, is there something about the vascular endothelium that is different among women with hot flashes? And that's the single cell layer lining the vessel, very important to vascular tone and health, and it is one of the first things to go in the atherosclerotic process, the development of cardiovascular disease. You see changes relatively early in life. And indeed, our first analysis showed in one of our big cohort studies that women with hot flashes had poor endothelial function than women without hot flashes. Later, we conducted something called the Ms. Heart Study, where we had women wearing objective hot flash monitors so we get markers of their hot flashes, these wearable monitors, and indeed, among the women with hot flashes, the more they had, the greater their underlying atherosclerosis when we imaged their vessels. And then, in our large longitudinal cohort study called SWAN, we were able to ask, if you have lots of hot flashes in your 40s and 50s, what happens to your heart disease risk later in life? We actually had hard clinical events, heart attack strokes, and we found that women with lots of hot flashes during the peri and post-menopause, particularly if they persisted for many years, those women had a 70% increased risk of heart attacks and strokes later in life after controlling for things like smoking or obesity or blood pressure, etc. And this was not explained by your levels of estrogen in your body. Are there genetic links? So if your mother went through those kinds of hot flashes, that you might be more likely as well to perhaps be at risk of cardiovascular disease? So whether there's a genetic underpinning to hot flashes is still an active area of investigation. I don't think we have a great answer to that. However, I will tell you colloquially that women tell me all the time that their hot flashes are similar to their mothers, their mother had lots of hot flashes, they have lots of hot flashes. Now how that plays in the intergenerational sort of clustering of cardiovascular disease, that part we still don't know. You've also found connections between hot flashes and increased risk of Alzheimer's disease. Can you walk us through that research? Sure. So it's an interesting story. So as I was doing the work around hot flashes and cardiovascular disease, my dear friend and colleague, Pauline Mackey, was showing that these motor symptoms or hot flashes were associated with poor cognition. So one of the major things that happens to women during the menopause transition, they talk to me about it all the time, women started having cognitive symptoms. They're feeling brain fog, they're feeling fuzzy, they're having a harder time remembering why they walked into the room, what's that word I can't remember, you know, it's very common. And when you measure women using objective neuropsychological tests, you see declines in what we call verbal memory performance during the menopause transition. That's memory for words on verbal material. She was showing that the women with the poorest verbal memory performance during the menopause transition were women who had lots of overnight hot flashes, objectively measured overnight hot flashes, from these monitors. And I was showing that women with lots of hot flashes had poor cardiovascular health. And so we teamed up and we established the Ms. Brain Study. And this is a study that looked at whether hot flashes, objectively measured hot flashes, were associated with poor brain health. And indeed, what we found is that women with a lot of hot flashes, particularly overnight, these women had greater white matter hyperintensities in their brain. So cerebrovascular risk, stroke risk, markers in their brain that indicate cerebral small vessel disease. We also found that women with more sleep hot flashes had lower A beta 4240. That is a blood circulating marker of amyloid, which is important to the pathophysiology of Alzheimer's disease. They don't have clinical Alzheimer's disease. These are women typically in their 50s. But it's a marker of increased risk for Alzheimer's disease later in life. And this was not explained by hormones levels. It was not explained by sleep, by mood, or any other risk factor that we could think of. We're going to take a short break. When we return, we'll talk with Dr. Thurston about the treatments available for menopause symptoms, including hormone replacement therapy, new medications, and behavioral interventions. What about treatment? Let's talk about treatment for a minute. What are the treatments that are available? I mean, hormone replacement therapy has a long and complicated history. It swung back and forth between being recommended for almost everyone and then being shunned for contributing to increased cancer risk. So where's the research now? So the history of hormone therapy is really interesting, and the pendulum has just kept swinging on this one. So way back in the 90s, 80s and 90s, we started to see hormone therapy as kind of like the panacea for all that algae. We thought that it could do everything, whether it was make your skin look better, hair loss, weight maintenance, prevention of heart disease, prevention of dementia, treat your hot flashes, help your bones, all the things. No one medication can do all of those things. And what we learned from big studies like the Women's Health Initiative, for example, that looked at whether hormone therapy can be used for disease prevention, things like cardiovascular disease or bone loss or dementia prevention. And the bottom line was that hormone therapy was not necessarily effective for preventing things like heart disease or dementia. And in fact, for women who began hormone therapy when they were a bit older in their 60s, it may actually increase your risk for heart disease and possibly stroke and dementia. Now, this was not necessarily everybody, and hormone therapy is still a very useful tool for the management of menopausal symptoms, like hot flashes. We also found that women, or that study also found that women who used hormone therapy or randomized to hormone therapy had less bone loss during the menopause transition. So there's really this kind of risk-benefit equation that we need to be thinking about when we're thinking about hormone therapy. We also found the hormone therapy trial was stopped because of increased breast cancer risk. So that can be an issue for some women. So again, balancing risks and benefits, we typically don't recommend hormone therapy for primary disease prevention for things like heart disease or dementia. However, very effective for the management of menopausal symptoms provided that you don't have contraindications. And that is very important to talk to your healthcare provider to really tailor whether hormone therapy is right for you, as well as what kind of formulation you should be taking. There's a whole different ways to take hormone therapy, and that is something to really work with a provider around. But hormone therapy is not the only tool in our toolbox. So we also have this new class of drugs called NK3 receptor antagonist. Vazoa is one of these, otherwise known as pheasant linotant. That is from that neurobiology that I talked about. That is a non-hormonal medication. It is also FDA approved for the management of hot flashes. Other drugs that are FDA approved for hot flashes, the only other one is Paxil, essentially, peroxatine. But SSRIs and SNRIs are also used in an off-label fashion. They're not quite as effective as these other medications, but they're oftentimes used as is gabapentin and some other non-hormonals. Now that's hot flashes, right? That's only one of our menopausal symptoms. And if there's any message that you take home from this, is that if you're trying to seek treatment for your menopausal symptoms, the treatment needs to be tailored to the specific symptom you're having. So if it's hot flashes, if it's sleep problems, if it's weight, one drug or one pharmacologic approach is not going to do everything. Now we can't forget about our behavioral approaches, too. So for sleep, cognitive behavioral therapy for insomnia has been shown to be effective for sleep problems during the menopause transition. Cognitive behavioral therapy for the management of menopausal symptoms can help manage those vasomotor symptoms that won't necessarily make them go away, but can help you cope with them. And then we don't, when we look at women's brain fog, we tend to first look at their sleep and their mood to make sure we treat those things first. And then the mood symptoms, whether it's depression or anxiety, many of our standard psychotherapies are still what we would recommend on the behavioral side, whether it's CBT, IPT, mindfulness-based therapies, et cetera. You've looked at how women's life experiences, especially sexual abuse or trauma, can shape how they experience menopause. Can you talk about that work? Absolutely. So this just really sprung up from our menopause studies. We just kept noticing that things looked a little different among these women who had trauma histories. And what we found, whether it's childhood abuse or adult trauma exposure, that these women had more vasomotor symptoms. So we started this with a SWAN study, and we found that women with a history of child abuse or neglect had an odds ratio of 1.8. So in 1.8-fold increased likelihood of having hot flashes or night sweats during the menopause transition. Later, in our Ms. Hart studies, where we actually had measured these hot flashes objectively, we also found that the women with a history of childhood abuse, these women had more objectively assessed hot flashes, particularly nocturnally. So that was really interesting. And then my junior faculty member working with me, Karen Jakobowski, has shown that women with trauma histories, whether it's adult or childhood, have an increased likelihood of persistent sleep problems over the course of the menopause transition. So more symptoms. So we have more vasomotor symptoms, more sleep problems. And we also show that women with a history of trauma have an increased likelihood of cardiovascular disease. So accelerations in their underlying vascular risk over the menopause transition, when we measure their vessels using ultrasound, we see this accumulation of plaque, particularly among the women with a sexual assault history. We find that women with a sexual workplace sexual harassment history have the doubling of the odds of hypertension. And women with a history of intimate partner violence have the doubling of the likelihood of heart attacks and strokes later in life. And that was driven by emotional intimate partner violence, not physical intimate partner violence. Because we didn't have a lot of women with a physical intimate partner violence in that study. So even that non-contact sexual and interpersonal violence has implications for the heart. And then finally we found that women with a history of sexual assault had more white matter hyperintensities in the brain. So that's that marker of cerebral small vessel disease in your brain that places you at risk for dementia and stroke later in life. But all of this is correlational, right? I mean we don't really know an underlying cause, whether it's like a lifetime of anxiety or underlying anxiety because of what had happened to you when you were younger or it's happening to you chronically. The mechanisms are probably multiple. So you probably have that those classic stress pathways, whether it's activation of the HPA axis or the autonomic nervous system. Actually that's one additional thing we found is that women who had a history of trauma, whether it's childhood abuse or adult trauma exposure, those women had lower high frequency heart rate variability during wake and particularly during sleep. And that's a marker of autonomic dysregulation. And that's one way that you can get from that exposure to stress to cardiovascular disease. And in the case of the intimate partner violence finding, that was explained by the elevated hypertension risk among women with that intimate partner violence history. So there's probably multiple different ways that you can get here and they all interact over the life course. Well, taking a step back, how much does all this affect women's mental health in midlife? I mean is this a generally less happy time of life or is it a happier time of life do we know? It really depends on the woman, right? So for some women, so that depression risk that I talked about earlier, so that two to four fold increased risk of a major depressive episode during the menopause transition that Swan found, the women at greatest risk were the ones who had depression history in the past. Our first onset depressive episode is typically late adolescence early adulthood, right? And then you go on to have recurrent episodes throughout life. And menopause is a time of vulnerability to a recurrent episode. There were a subset of women, however, in Swan, that they had their first onset depressive episode during menopause. They had never had one before is about 28% of the women who did not have a history. Those women were the ones with some health problems going on, anxiety, more vasomotor symptoms, and importantly, few close friends, not married, few close friends. That came up again and again and again in the Swan data. The important role that those friendships in your life can play to buffer against declines in mental health during midlife hormones did not predict. So that's for depression. Anxiety, I see a lot of this. I see a lot of rumination, a lot of anxiety. We're living in the age of anxiety. And indeed, the anxiety data is not as strong in terms of our longitudinal studies, but there is probably a 1.7 fold increased odds of having elevated anxiety during the menopause, particularly if you have lots of vasomotor symptoms. But, you know, those are older data. So I think we're in a different era now where anxiety is more prominent. And then we don't have a lot of data on other things like bipolar disorder or some increased risk for psychotic disorders. I pay attention to women's substance use. So a lot of people are trying to use various substances to help them manage this turbulent time, whether it's more alcohol to try to get yourself to sleep, which ultimately backfires. Or your doc has put you on benzos and then a stimulant. I see a lot of mixture of things that women are taking, and ultimately it can really backfire. So being really careful about your substance use is important. And then we see a lot of cannabis for the management of menopausal symptoms. There's not a lot of great data on whether that's efficacious or not. Now, so that's just when we talk about psychopathology. But this general sense of women's well-being, it's kind of a different thing, right? There's a sense of, do you just feel okay? One study found that about 63% of women reported that they just didn't quite feel like themselves during menopause. So is it time for people feeling just kind of off? However, at the same time, there's this increased sense of not caring, what people think, increased authenticity, potentially a feeling of some confidence and feeling more comfortable in your own skin, maybe, not everybody. But we do see that. And so I think as clinicians, our job is to help treat the negative sides and really build upon these strengths, this sort of deepening wisdom, this sense of, yeah, you know who you are and you know what you want a little bit more. Those things are really important aspects of midlife developmental maturation and aging that I think are great. You mentioned substance use, but I'm also wondering there are a lot of women who for many years, like perhaps their whole adult lifetime, have taken birth control pills. Any research into the impact of that on menopause? So birth control pills are essentially the same hormones, for the most part, that's in hormone therapy. Hormone therapy is just a lower dose. So some women will stay on their oral contraceptives or the birth control pills over the course of the perimenopause. But ultimately, that dose probably needs to be adjusted. So you need to talk to your doctor about where you are in the transition and when to revisit mixing up that hormone regimen as you age. So just to close, what are you working on now? What are the big questions you're still trying to answer? Oh, there's so many. I mean, we have some great data on menopause for sure from our large longitudinal studies like SWAN and others. However, there's so many more questions to be answered. I mean, I just named a bunch of things we don't know about increased risk for various types of psychological problems during menopause, whether it's anxiety or PTSD or substance use disorders or things like that. That we absolutely have to know. I'm very interested in these positive aspects and how do we do some really good empirical work around really understanding the role of menopause and midlife aging in women's psychological development and their feeling more positively about the world and about themselves. We need more interventions for helping women manage the menopause transition. Right now, so many women are kind of told and in this struggle, hormone therapy, yes, no. And menopause care is way more than hormone therapy. There's a huge, there's a wider range of tools in the toolbox that we have and we just women deserve more, whether they're pharmacologic approaches, behavioral approaches or both. And this is where we really need more research. Well, Dr. Thurston, I want to thank you for joining me today. It's really a lot of good information for our listeners. Thank you so much. This has been great. You can find previous episodes of Speaking of Psychology on our website at speakingofpsychology.org or on Apple, Spotify, YouTube or wherever you get your podcasts. And if you like what you've heard, please follow us and leave a review. If you have comments or ideas for future episodes, you can email us at speakingofpsychology.org. Speaking of psychology is produced by Lee Warnerman. Thank you for listening for the American Psychological Association. I'm Kim Mills. Thank you.
