How to Navigate Menopause & Perimenopause for Maximum Health & Vitality | Dr. Mary Claire Haver

Andrew Huberman 0:00 (instrumental music) Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is Dr. Mary Claire Haver. Dr. Mary Claire Haver is a board-certified OB-GYN and an expert in perimenopause, menopause, and all aspects of female-specific health. During today's episode, Dr. Haver explains exactly what perimenopause and menopause represent in terms of their underlying psychology and biology and the specific actions that all women can and should take in order to navigate these stages in optimal health. She also describes the things that all women should know and do long before perimenopause arrives in order to best navigate perimenopause and menopause once they arrive. We discuss specific nutritional practices, supplementation practices, as well as conversations that you should have with your mother and with your physician, in particular your OB-GYN, not just as perimenopause and menopause approach, but at every developmental stage. A fair amount of our discussion centers around hormone replacement therapy, not just for estrogen, but for testosterone in women as well, and the many misconceptions and controversies that exist around hormone replacement therapy for menopause. Dr. Haver explains how the specific timing in which hormone therapy is initiated plays a key role in whether or not the hormone therapy is beneficial for women or not. And of course, today's discussion gets into ways to offset some of the more common difficulties associated with menopause, including sleep issues, hot flashes, inflammation, and more. By the end of today's episode, you will have a clear picture from Dr. Marie Claire Haver about what perimenopause and menopause actually represent, the best way to approach perimenopause and menopause, and the various considerations around hormone therapy and lifestyle choices that can allow any woman to approach the years of perimenopause and menopause and beyond with the utmost vitality and

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Andrew Huberman 6:30 to have you here and to learn about menopause and other aspects of women's health. There's a lot happening in this area right now-

Dr. Mary Claire Haver 6:39 Yeah.

Andrew Huberman 6:39 ... and you are at the center of what I understand is a new direction for the understanding and treatment of menopause-

Dr. Mary Claire Haver 6:47 That's what we hope.

Andrew Huberman 6:48 ... and related themes, like perimenopause-

Dr. Mary Claire Haver 6:50 Yeah.

Andrew Huberman 6:51 ... and the many important aspects of female health that stem from it, like cardiovascular disease, osteoporosis-

Dr. Mary Claire Haver 6:57 Right.

Andrew Huberman 6:57 ... and so on. So we will get into all of that today, but just to kick things off, how do we define menopause?

Dr. Mary Claire Haver 7:04 So the medical definition of menopause, which I have a huge problem with, is one year after the final menstrual period. And the reason why I have a problem with it is not everyone has a menstrual period. What if you've had a hysterectomy? What if you have an IUD? What if you've had an ablation or something that's suppressing your periods, PCOS? So for a lot of women, and even clinicians, they are struggling to, like, find that diagnosis because it doesn't fit everything. What it represents is something much bigger. Menopause is also one day of your life. It is that one day exactly one year after your last period. But it represents the end of your ovarian function. Some of us call it ovarian failure, ovarian senescence, but basically, what separates males and females is... Many things separate us, but in my world, um, we are born with all of our eggs. We have 1 to 2 million at birth. By the time we're 30, most of us are down to about 10%, maybe 120,000. By the time we're 40, we're down to 3% of our egg supply, and the quality is declining as well. So menopause is when you have no more eggs left and therefore no more sex hormone or very little sex hormone production from the ovaries. So estradiol levels will decline less than 1% of your reproductive years. Your progesterone levels will decline as well. Testosterone declines for sure, but we have other ways to produce it so it's somewhere 50% or less than your healthiest years.

Andrew Huberman 8:39 So is it fair to say that we need a redefinition of what menopause is?

Dr. Mary Claire Haver 8:44 I think so. I think defining it as the presence or absence of a period is a mistake.

Andrew Huberman 8:50 Is there any consensus about the, quote unquote, "typical" age of onset for menopause, and is it changing? You know, I hear a lot about how the onset of puberty is shifting earlier-

Dr. Mary Claire Haver 9:02 Mm-hmm.

Andrew Huberman 9:02 ... in females, and given that puberty, at least by some definitions, relates to the onset of menses, uh, one could imagine that menopause would be shifting earlier as well.

Dr. Mary Claire Haver 9:14 So the things that determine when we have puberty or not are different than the things that determine when we run out of eggs. Um, right now in the US, it's the average age of that one year after your cycle, so menopause, that one day, is about 51 to 52 years old. However, normal is still 45 to 55 and there's a big variation. You know, that curve's pretty wide.

Andrew Huberman 9:41 Mm-hmm.

Dr. Mary Claire Haver 9:42 Um, perimenopause begins 7 to 10 years before that last menstrual period.

Andrew Huberman 9:50 Wow. Okay. And I say wow because, um, it's the first time I've ever heard a, a specific number tacked to this word-

Dr. Mary Claire Haver 9:56 Mm-hmm.

Andrew Huberman 9:56 ... perimenopause. Maybe we could talk a little bit about perimenopause-

Dr. Mary Claire Haver 10:00 Sure.

Andrew Huberman 10:01 ... since it sounds like it represents a transition phase-

Dr. Mary Claire Haver 10:05 Yeah.

Andrew Huberman 10:05 ... into, uh, official menopause-

Dr. Mary Claire Haver 10:08 Right.

Andrew Huberman 10:09 ... um, however one chooses to define that. What are some of the, I don't know if I should call them symptoms-

Dr. Mary Claire Haver 10:14 Sure.

Andrew Huberman 10:15 ... or I should, uh, just-

Dr. Mary Claire Haver 10:16 Well, let me, let me do, let me walk you through the endocrinology-

Andrew Huberman 10:19 Mm-hmm.

Dr. Mary Claire Haver 10:19 ... and then we can go through symptoms so you understand.

Andrew Huberman 10:21 Great.

Dr. Mary Claire Haver 10:21 So in a normal, healthy menstrual cycle before menopause ever becomes an issue, the female hormone cycle is a very EKG-like reproducible monthly rise and fall of estrogen, progesterone, and then the brain hormones LH, FSH, and then GNRH. So the way it works is our brain in the hypothalamus, um, is sensing for, has a little sensor in the blood looking for estradiol levels, and when they get low, it sends GNRH down to the pituitary saying, "Hey, tell the ovaries to start trying to ovulate so we can get more estrogen on board." The process of ovulation is what drives up our estrogen levels, okay? So pituitary sends out this pulses of LH and FSH, which then lead to ovulation. When we reach, in perimenopause, the beginning of perimenopause, that critical level of egg supply, those signals don't work as well. We start becoming resistant to the LH and FSH pulsatile surges. So the brain's like, "Hey, I told you we need more estradiol." And the pituitary is like, "I sent the signal." And the brain's like, "Send more." So we get much higher pulses of FSH, and then finally the ovary kind of, ugh, is able to get that egg out, but sometimes it's delayed. So we have the timing of that monthly predictable cycle goes awry. Sometimes the periods are closer together, sometimes they're further apart, but also the estrogen and progesterone levels start changing dramatically. We see much higher surges of estradiol than we ever had in our preproductive years and then much lower levels underneath. So we end up with this very volatile curve and not predictable at all. We call it, in our world, the zone of chaos. So it is literal hormonal chaos. What used to look like this, you know, every month is now...... just, just insane and very, very, very unpredictable. That is why we don't have a good blood test in perimenopause to make the diagnosis. Those of us in the menar- menaverse use symptoms, usually, to make the diagnosis and we rule out other conditions that might overlap. So perimenopause, basically critical threshold. It's a downward trend overall of estradiol, but it is a very chaotic, you know, race till you flat line and bottom out.

Andrew Huberman 12:39 I see. So for those listening, um, your description of the, um, kind of the amplitude of the-

Dr. Mary Claire Haver 12:46 Mm-hmm.

Andrew Huberman 12:46 ... estrogen surge, it gets much greater-

Dr. Mary Claire Haver 12:48 Mm-hmm.

Andrew Huberman 12:48 ... in this perimenopause phase. You also mentioned that follicle stimulating hormone, which comes from the pituitary, has to be or somehow is upregulated in this phase because-

Dr. Mary Claire Haver 12:58 Mm-hmm.

Andrew Huberman 12:58 ... I don't know, is it that the receptors for FSH are somehow not responsive, or ... At the level of the ovary, do we know what's happening to the ovary? Is it obviously the signal's getting there, it's not effective, so then the brain is kicking out more FSH?

Dr. Mary Claire Haver 13:11 Mm-hmm.

Andrew Huberman 13:12 Is it that the ovary is some-

Dr. Mary Claire Haver 13:13 So the egg quality-

Andrew Huberman 13:13 Mm-hmm.

Dr. Mary Claire Haver 13:14 ... is poor, and then around each germ cell is the theca lutein cells, which is actually where the estradi- the, the whole pathway going from, you know, actually testosterone's converted to estradiol.

Andrew Huberman 13:24 Mm-hmm.

Dr. Mary Claire Haver 13:24 So that whole pathway, uh, you know, it still will respond, but the cells are just old, you know-

Andrew Huberman 13:31 Mm-hmm.

Dr. Mary Claire Haver 13:31 ... is the way that it's been explained to me and, and from what I've read. I think we need a lot more research in this area, because that is how we're going to help women, I think, longer term, is understanding that process better. But, you know, all I learned in school 25 years ago was it's the transition to menopause, the end. You know, the whole endocrinological process, I didn't learn till about two years ago.

Andrew Huberman 13:52 And my guess is, just based on my understanding of the only recent trend toward emphasizing studies of both female and male, even just mice in mouse models, which is where generally this stuff originates-

Dr. Mary Claire Haver 14:05 Mm-hmm.

Andrew Huberman 14:05 ... and then it shifts into humans once certain targets are identified. Um, only recently has the NIH insisted that there be, uh, female, uh, mice in the studies of mice. I mean, it's, it's been a few years now, but that's a, you know ... Sex as a biological variable is, is actually a requirement in most grant applications, unless of course there's a specific reason to study only one or the other, um, sex of mice. So you can imagine that, um, the dearth of research in this area is, uh, due to a, a long, um, desert of, um, absence of studies into what is perimenopause.

Dr. Mary Claire Haver 14:41 Right.

Andrew Huberman 14:41 So

Andrew Huberman 14:42 for women who are in the age range of perimenopause-

Dr. Mary Claire Haver 14:44 Mm-hmm.

Andrew Huberman 14:44 ... or, or who are thinking about this, are there things that they can do in order to either upregulate the sensitivity of the ovary to FSH or to somehow prolong this period of perimenopause? Um, and I should also say, what are some reasons why they would want to do that? Um, you know-

Dr. Mary Claire Haver 15:03 Right.

Andrew Huberman 15:03 ... obviously this is part of the, um, of the arc of maturation-

Dr. Mary Claire Haver 15:07 Mm-hmm.

Andrew Huberman 15:08 ... of the female reproductive axis, but of course, that alone is not a reason to not try and, um, I guess we say optimize it for one's wellbeing.

Dr. Mary Claire Haver 15:17 So we don't know. When you ... Uh, the best way I can highlight why we don't know or, or where the dollars are going for research, you know, we go to PubMed and you type in the word pregnancy, 1.1 million articles come up. Type in the word menopause, it's down to 97,000.

Andrew Huberman 15:32 Really?

Dr. Mary Claire Haver 15:33 You type in the word perimenopause, and I checked this, like, two weeks ago, and it was, like, 6,400 and something.

Andrew Huberman 15:39 Wow.

Dr. Mary Claire Haver 15:40 Yeah.

Andrew Huberman 15:40 That is surprising.

Dr. Mary Claire Haver 15:42 So-

Andrew Huberman 15:42 Or maybe it shouldn't be surprising given what we were just talking about in terms of, um-

Dr. Mary Claire Haver 15:46 So as far as, like, why those cells are becoming resistant and what's happening at the level of the receptor, I think we need a lot more research in this area. I think it's starting to happen because women are realizing there's a demand now, because the older you are when you go through menopause, the healthier you are for cardiometabolic disease. It's the loss of estrogen that accelerates our path to those diseases.

Andrew Huberman 16:11 So are there clinical signs of perimenopause-

Dr. Mary Claire Haver 16:14 Mm-hmm.

Andrew Huberman 16:15 ... that either directly or indirectly relate to these bigger surges in FSH-

Dr. Mary Claire Haver 16:20 Mm-hmm.

Andrew Huberman 16:21 ... and these larger amplitude, um, estrogen, uh, surges?

Dr. Mary Claire Haver 16:25 The, the two best documented and studied are mental health changes. Um, the brain does not like the chaos of ... And, and the neurotransmitters are very, very sensitive to estrogen and progesterone and even testosterone. And so we see aberrations in serotonin, in norepinephrine, and in dopamine as the levels start becoming chaotic. So we have at least a 40% increase of mental health disorders inc- no- and SSRI use doubles across the menopause transition, across perimenopause. And now the data is showing that women who are given hormone therapy in their perimenopause have a lower incidence of new onset depression. And now the neuroscientists are saying, "Hey, for these women who are developing depression in perimenopause, giving them estrogen is better than an SSRI. They're going to have a better outcome."

Andrew Huberman 17:20 Yeah, I think most people don't realize how rich the brain and rest of the nervous system are with hormone receptors, in particular estrogen receptors and, as you mentioned, testosterone receptors as well, androgen receptors.

Dr. Mary Claire Haver 17:35 Mm-hmm.

Andrew Huberman 17:35 Um, and the often direct relationship between estrogen and the neuromodulators such as serotonin, dopamine, epinephrine, acetylcholine.

Dr. Mary Claire Haver 17:44 And GABA for, for-

Andrew Huberman 17:46 Yeah.

Dr. Mary Claire Haver 17:46 ... um, progesterone.

Andrew Huberman 17:47 Mm-hmm. Yeah. It's, it's interesting during neural development, which is kind of where I started off, which was, um, neural embryonic development, the hormones exert, you know, these widespread roles in defining even which neurons will express certain neurotransmitters. And then somehow the field of neuroscience has only recently gotten on board the idea that, um, this intimate relationship between hormones and neurotransmitters is something to consider in essentially every aspect of, of brain health.

Dr. Mary Claire Haver 18:17 Right.

Andrew Huberman 18:18 Not just cognition, but maintenance of neurons and, um, offsetting neurodegeneration and so on. Um, I mention that only, um, so that people, uh, I think-... typically think of hormones as something, sure, there's a signal from the brain and, but that hormones are mostly of the body, when in fact hormones play an, an absolutely crucial role within the brain.

Dr. Mary Claire Haver 18:37 Yeah.

Andrew Huberman 18:38 Yeah. So, you mentioned that during perimenopause there, there are symptoms that are, I guess, it's per- are mainly reflected as shifts in mental health.

Dr. Mary Claire Haver 18:48 Yeah, so, that's-

Andrew Huberman 18:49 So is this women suddenly feeling, um, kind of, um, less, uh, optimistic? Is it, like what, what's the sort of, um, constellation of, of, of psychological shifts that can occur?

Dr. Mary Claire Haver 19:00 So we see, uh, increasing anxiety. We see definitely loss of executive functioning, so nuanced set of ADD-type symptoms. Um, we see, of course, the cognitive d- you know, the, what we call brain fog in, in lay terminology.

Andrew Huberman 19:15 Mm-hmm.

Dr. Mary Claire Haver 19:16 Which is cognitive, you know, so they lose their words. They're not able to do the calculations at work, like their executive functioning ability in their jobs is huge. Like one in five women will quit their jobs because of menopause symptoms. Um, yeah.

Andrew Huberman 19:30 Wow, that's an- that's an outrageous number.

Dr. Mary Claire Haver 19:32 Yeah, and the- the economic impact is huge, and so now companies are starting to get on board. And this is the time of our lives when the kids are grown for a lot of us, you know, and we're trying, we're r- ready to lean into our positions and really get into leadership and we have all this experience, and now we can't reme- you know, and now all of a sudden these ... And their confidence is just wrecked. So, and then the depression and they're not sleeping and like it's this horrible feedback cycle that they end up in.

Andrew Huberman 19:55 Yeah.

Dr. Mary Claire Haver 19:55 That we end up in.

Andrew Huberman 19:56 Yeah, I wasn't aware that one in five is, is-

Dr. Mary Claire Haver 19:59 Yeah.

Andrew Huberman 19:59 ... striking.

Dr. Mary Claire Haver 19:59 That came out of the UK.

Andrew Huberman 20:01 Mm-hmm.

Dr. Mary Claire Haver 20:01 But they're starting to, like, crunch the numbers here in the US and it's looking very

Dr. Mary Claire Haver 20:04 similar.

Andrew Huberman 20:05 I know we're going to get into actionable tools-

Dr. Mary Claire Haver 20:07 Mm-hmm.

Andrew Huberman 20:07 ... uh, later as it relates to menopause, but as long as we're discussing this phase of perimenopause-

Dr. Mary Claire Haver 20:11 Mm-hmm.

Andrew Huberman 20:11 ... uh, what are some of the basic things-

Dr. Mary Claire Haver 20:14 Sure.

Andrew Huberman 20:14 ... that women could, A, pay attention to?

Dr. Mary Claire Haver 20:16 Mm-hmm.

Andrew Huberman 20:17 We don't want to make people hypervigilant to the point of anxiety.

Dr. Mary Claire Haver 20:20 Right.

Andrew Huberman 20:20 But, but, um, certainly given the frequency and given the implications, um, s- it's important for them to pay attention to this phase. And then, some of the things that they can do to, you know, either behaviorally or perhaps through other tools offset, um, some of these changes.

Dr. Mary Claire Haver 20:35 Sure. Uh, dysfunctional uterine bleeding, um, which is abnormal periods. So, and again, nothing's off the table. It could be heavy periods, menorrhagia, too frequent, too few, skipping. It's really, really chaotic. And, but a lot of women are suffering horribly from really debilitating periods, either through the volume of blood loss or they're having, you know, cramps and, you know, really, and so 90% (laughs) of us will have that s- as a symptom. Um, fatigue is a huge one. A lot of them, the symptoms are kind of vague, you know, and can be attributed to a lot of other things. In our, in my what we call the Menopausy Chat Group, you know, we have a lot of theories about a lot of conditions like fibromyalgia and the irritable bladder syndromes and that probably just perimenopause and menopause, and doctors didn't know how to put th- you know, make that diagnosis. And so, you know, musculoskeletal system takes a huge hit through the transition, so all of a sudden you have no injury and you're having hip pain, joint pain, back pain, with, you know, you go to the doctor and you get an X-ray or you do whatever workup and they can't find anything wrong. Palpitations are huge. It is a vasomotor symptom. So along with hot flashes, palpitations, so a woman will walk into the emergency rooms sweating profusely, horrible palpitations, she's anxiety, and they'll tell her she's having a panic attack. You know, um, they'll work her up, you know, everything's negative, and just say, "Well, it's a panic attack. Go home." And no one knew to connect the dots and figure out that this woman was in her menopause transition and this is how her body was expressing it. It's complicated because we have sex hormone receptors, as you do, in every organ system of our body, and when these levels start going chaotic, it can present in so many different ways. And so when the patients come to me, I'm doing blood work, not a lot of hormone levels 'cause they're not super helpful, but I am doing thyroid workups and autoimmune workups and looking for r- um, nutritional deficiencies and anemia and different things because I don't want to miss those things and just pin everything on perimenopause.

Andrew Huberman 22:42 Are there lifestyle factors that can-

Dr. Mary Claire Haver 22:44 Yes.

Andrew Huberman 22:44 ... offset some of this?

Dr. Mary Claire Haver 22:45 It's not a perfect correlation-

Andrew Huberman 22:47 Mm-hmm.

Dr. Mary Claire Haver 22:47 ... but the healthier you are, so anti-inflammatory diet, you know, Mediterranean-esque, Alvesson diet-esque, you know, nutrition pattern, um, regular exercise, good sleep habits, you know, all the pillars of health, the healthier you are when you hit perimenopause, the better the course is going to be for you. They're looking at extending the life of the ovary with pharmacology. We know what can shut it down faster, so we have kind of a genetic predetermined age of when you're gonna lose all your eggs, but we can speed that up. So if you smoke, you're gonna go through menopause sooner than your twin would have if she didn't smoke, okay? If you don't have children and you ovulate regularly, then the more you ovulate, the faster you run through your egg supply. Okay?

Andrew Huberman 23:31 Interesting. I, I wasn't aware of those data. That's, uh, I don't know that most people are aware of those data.

Dr. Mary Claire Haver 23:36 No. If you have a hysterectomy and you leave your ovaries behind, I didn't kn- I didn't ever counsel my patients about this. You lose four years off the life of your ovaries. If you have a tubal ligation, you lose a- lose a year and a half. Huge genetic disparities, so African Americans tend to go through a year and a half sooner, and then there's Caucasians in the middle and then Asian fam- tend to go through later and they're not sure why. You know, a year or two years. So, there are, if you have chemotherapy, if you have surgery, if you have any inflammatory process in the abdomen, irritable bowel or endometriosis, you are going to lose some of the life of the ovary.

Andrew Huberman 24:10 You mentioned smoking. Are there any data on vaping?

Dr. Mary Claire Haver 24:13 Not yet. I haven't seen any. There might be out there, I just haven't seen it yet.

Andrew Huberman 24:16 No, I'm, I'm guessing, uh, if they're out there, they're not, um, prominent or you would've seen them. I'm curious about vaping because a lot of people are vaping instead of smoking.

Dr. Mary Claire Haver 24:24 Mm-hmm.

Andrew Huberman 24:24 And hopefully people are neither vaping nor smoking because it seems that, we had an expert on vaping on the podcast recently from Stanford and it seems that, um-There's nothing great about it.

Dr. Mary Claire Haver 24:35 Right.

Andrew Huberman 24:35 And there may be some things really bad about it, but was just curious, given that a number of young women, and men for that matter, are vaping nowadays-

Dr. Mary Claire Haver 24:44 I think we probably need-

Andrew Huberman 24:44 ... who, and where smoking rates have gone way, way down.

Dr. Mary Claire Haver 24:46 ... another 10 years before we'd be able to, you know, see when those women are going through menopause, you know, 'cause vaping, I think vaping is younger, the younger generation. Um, like my kids, their, their friends-

Andrew Huberman 24:59 People in their 20s and 30s.

Dr. Mary Claire Haver 25:00 ... tend to vape.

Andrew Huberman 25:00 Yeah.

Dr. Mary Claire Haver 25:00 So we're, you know, we're 20 years out from seeing how it's gonna affect them.

Andrew Huberman 25:04 Is there any evidence that alcohol can impact perimenopause?

Dr. Mary Claire Haver 25:08 I haven't seen any, but I can't-

Andrew Huberman 25:09 Mm-hmm.

Dr. Mary Claire Haver 25:09 ... imagine that, you know, heavy use of alcohol would prolong the life of the ovary in any way.

Andrew Huberman 25:14 Right.

Dr. Mary Claire Haver 25:14 So.

Andrew Huberman 25:15 Um, and we know that any use of alcohol has some potential role in disrupting sleep, and presumably-

Dr. Mary Claire Haver 25:21 Oh, 100%.

Andrew Huberman 25:21 ... like everything else, uh, if you disrupt sleep, you disrupt things for the-

Dr. Mary Claire Haver 25:24 Everything.

Andrew Huberman 25:24 ... for the worse, isn't it?

Dr. Mary Claire Haver 25:25 (laughs)

Andrew Huberman 25:25 Got

Andrew Huberman 25:26 it. So you mentioned, um, rough ages for onset of, uh, menopause, um, 51, but anywhere from 45 to 55.

Dr. Mary Claire Haver 25:35 Mm-hmm.

Andrew Huberman 25:35 And that perimenopause, uh, is defined as a period about seven years prior to that?

Dr. Mary Claire Haver 25:40 Seven to 10, yeah.

Andrew Huberman 25:42 Okay. Um, what's the earliest you've ever had a patient come in who entered menopause? What's the latest you've ever seen?

Dr. Mary Claire Haver 25:47 My personal-

Andrew Huberman 25:48 Yeah.

Dr. Mary Claire Haver 25:48 ... patient, 27, and she came in just a couple months ago. So she had a special condition we call premature ovarian failure.

Andrew Huberman 25:57 Okay.

Dr. Mary Claire Haver 25:57 And she had found me on social media and wanted to come just to make sure she was doing everything right. And so early menopause is defined as between the ages of 40 and 45, and then premature menopause, or pre- premature ovarian insufficiency, it's not a complete failure for most women, but it is very, very low, is any time before the age of 40. So this patient kind of got kicked around for two years, went to her doctor, no periods, horrible hot flashes. Again, she was 25, and it was not on his radar, and he never tested her for menopause, and it took her, you know, 18 months to get the diagnosis. And so the longer your body is away from estrogen, the higher the risk factor. And it's been all over the news this week, where we know that untreated premature ovarian insufficiency has a earlier death. So they have higher cardiovascular disease, diabetes, stroke, all because estrogen is so protective and they have to go so long without it. We can back, negate most of those risks by giving her aggressive hormone therapy early. So she came in to make sure she was on the right dose (laughs) because in premature ovarian failure, we don't want to give them menopause hormone therapy doses. They're too low. We want to get her more like she would have, which is three to four times the amount of estrogen as a reproductive-aged woman. And so, and she wanted to have a period so she would seem like her friends. You know, it was an emotional thing for her, which I totally respect. And so, um, so we were doing cyclical progesterone for her so that she would have a withdrawal bleed and feel like she was normal.

Andrew Huberman 27:35 Basic question, but I, I'm curious, so I'll ask. Um, given that levels of estrogen change so much-

Dr. Mary Claire Haver 27:42 Mm-hmm.

Andrew Huberman 27:42 ... naturally-

Dr. Mary Claire Haver 27:42 Mm-hmm.

Andrew Huberman 27:42 ... during the course of the, um, ovulation cycle, menstrual cycle, um, with estrogen therapy, is it a constant dose or it's modulated by-

Dr. Mary Claire Haver 27:51 Yeah.

Andrew Huberman 27:51 ... uh, week to week or day to day?

Dr. Mary Claire Haver 27:52 Good question. So there are some formula, so, and when we look at hormonal contraception, so the, the biggest difference between con- contraceptive doses and menopause hormone therapy doses, they're both based in estrogen and progesterone mostly, okay? The hormone therapy was developed to stop a hot flash. For decades, menopause was defined by the presence or absence of, you know, severe menopause was defined by hot flashes or not. They do, didn't, nothing else. And so they developed the formulations with enough estrogen to stop hot flashes. Birth control was developed to stop ovulation. You don't ovulate, you don't get pregnant. And it's, but the difference between low dose birth control pill and higher dose menopause hormone therapy is not that far away. And so, um, that, a lot of people don't understand. Now, the types of estrogen we use in birth control are a little bit different. Most birth control is ethinyl estradiol, which is one of the synthetics. We have literally millions and millions of womens' year data on it. We know its safety profile. I think we're not counseling patients adequately about birth control as far as what it does to their testosterone and what it can do to, you know, "Oh, it's fine. It's safe. I took it for years." But I think we need to do a better job as a specialty on counseling women. But I do think it's a good medication. And then on menopause hormone therapy, you know, it's much lower dose. It does not suppress ovulation. So in perimenopause, it's a little bit of the Wild West. Which one we're gonna use? How high do we want to go? Do we need to suppress our ovulation because she's got acne or horrible periods or cramps or something where I want to suppress that ovulation to help her? Or can I give her menopause hormone therapy doses, which, in effect, think of the hypothalamus. I'm giving her just enough estrogen to calm the brain down and tell them everything's okay. We're not gonna get those big peaks and drops, and if she still ovulates, that's okay too.

Andrew Huberman 29:42 As many of you know, I've been taking AG1 for more than 10 years now. So I'm delighted that they're sponsoring this podcast. To be clear, I don't take AG1 because they're a sponsor. Rather, they are a sponsor because I take AG1. In fact, I take AG1 once and often twice every single day, and I've done that since starting way back in 2012. There is so much conflicting information out there nowadays about what proper nutrition is. But here's where there seems to be a general consensus on. Whether you're an omnivore, a carnivore, a vegetarian, or a vegan, I think it's generally agreed that you should get most of your food from unprocessed or minimally processed sources, which allows you to eat enough, but not overeat, get plenty of vitamins and minerals, probiotics and micronutrients that we all need for physical and mental health. Now, I personally am an omnivore, and I strive to get most of my food from unprocessed or minimally processed sources.But the reason I still take AG1 once and often twice every day is that it ensures I get all of those vitamins, minerals, probiotics, et cetera, but it also has adaptogens to help me cope with stress. It's basically a nutritional insurance policy meant to augment, not replace, quality food. So by drinking a serving of AG1 in the morning and again in the afternoon or evening, I cover all of my foundational nutritional needs. And I, like so many other people that take AG1, report feeling much better in a number of important ways, such as energy levels, digestion, sleep, and more. So while many supplements out there are really directed towards obtaining one specific outcome, AG1 is foundational nutrition designed to support all aspects of wellbeing related to mental health and physical health. If you'd like to try AG1, you can go to drinkag1.com/huberman to claim a special offer. They'll give you five free travel packs with your order plus a year's supply of vitamin D3K2. Again, that's drinkag1.com/huberman.

Andrew Huberman 31:32 As long as we're on the topic of birth control, earlier you mentioned that the IUD, and presumably this is some form of the IUD, not necessarily copper IUD, can, um, disrupt or stop-

Dr. Mary Claire Haver 31:44 A period, mm-hmm.

Andrew Huberman 31:45 ... a, a period. Um, maybe we could talk a little bit about the different forms of birth control.

Dr. Mary Claire Haver 31:49 Mm-hmm.

Andrew Huberman 31:50 Um, IUD, um, as the pill, quote unquote-

Dr. Mary Claire Haver 31:53 Right.

Andrew Huberman 31:53 ... um, old term, but, um, uh, I think most people know what we're referring to when we say that. The ring-

Dr. Mary Claire Haver 32:00 Mm-hmm.

Andrew Huberman 32:01 ... um, and, and on and on.

Dr. Mary Claire Haver 32:02 Sure.

Andrew Huberman 32:02 Um, what is your stance on, on these different forms of birth control-

Dr. Mary Claire Haver 32:05 Mm-hmm.

Andrew Huberman 32:05 ... as it relates to their safety? Um, you know, uh, I guess about a year and a half ago, I hosted a, um, a female physician guest on, on this podcast, and both sides of the, uh, birth control issue were touched on. Uh, one, the relationship to, um, potential, um, inhibition of certain forms of cancers, but then also the potential for certain side effects, maybe even cancers. And so it, you know, it seems like it can play out both ways-

Dr. Mary Claire Haver 32:31 Mm-hmm.

Andrew Huberman 32:31 ... and this is a very heated topic.

Dr. Mary Claire Haver 32:32 Yeah.

Andrew Huberman 32:32 Um, in fact, so much so that I learned that if one is going to post a clip of any of this on social media-

Dr. Mary Claire Haver 32:39 (laughs)

Andrew Huberman 32:39 ... it, it almost makes sense to have them-

Dr. Mary Claire Haver 32:40 It's very-

Andrew Huberman 32:40 ... in the same post because we actually did both of them. We, we d- did a post where it was more about the, the pros of birth control and then the cons of birth control-

Dr. Mary Claire Haver 32:48 Right.

Andrew Huberman 32:48 ... as, as stated through, um, the words of this very same clinician. Um, so we will be sure to, uh... If, so for anyone listening-

Dr. Mary Claire Haver 32:56 (laughs)

Andrew Huberman 32:56 ... whichever answer comes first, stay tuned for the next answer (laughs) because, um, my understanding is that it's not a black and white issue.

Dr. Mary Claire Haver 33:05 I think the best form of birth control is a vasectomy, and so much of contraception is dumped in a female's lap, you know, in a committed relationship. And I can't tell you the comments I've heard when, uh, w- a patient comes to me and she wants to get X, Y, and Z simply for contraception. She's absolutely perfectly healthy. There's nothing wrong with her. She just doesn't want to be pregnant. And I'm like, "Okay, you're done ha-" you know, she's completed her family. She's out, you know? And I'm like, "Tell your partner to get a vasectomy," oh, he won't do that, you know?

Andrew Huberman 33:36 Mm.

Dr. Mary Claire Haver 33:36 So now all of the risk and the onus goes on her, and so we, we go through the options of surgical, like, you know, tubal ligation, um, which is basically blocking the tube. So when I, you know, talk to my teenagers, I'm like, "Here's how you not get pregnant. A, you don't have sex." Well, if that's not an option, then we have to either block the sperm, stop the egg from coming out, or stop the place where they communicate, which is the fallopian tube. And so when we look at the different forms of hormonal contraception, which are meant to stop ovulation, suppress ovulation, because they're telling the brain, "We have enough estrogen and progesterone onboard. Quiet down so it doesn't send those signals to the ovary," right? And so that can come in a pill form, a patch form, a ring form, and they each have their own pros, cons, risks, benefits. You know, transdermal has less risk of blood clots versus oral has a higher risk of blood clotting, any form of estrogen. So we talk about that. We look at their family history or if they have MTHFR, any of the clotting genes, you know, then we counsel directly versus the IUD. The IUDs create an, an inflammatory environment in the uterus that blocks and i- creates a plug in the cervix so that the sperm can't get through, and then if any do get through, it's a toxic environment in the uterine cavity for the sperm. So that's really how the I- those IUDs work.

Andrew Huberman 34:55 Mm-hmm.

Dr. Mary Claire Haver 34:55 Some IUDs are coated with progesterone or progestin, not progesterone, a progestogen, and those end up decidualizing the endometrium so thinning that lining from that constant progesterone to the point where you stop bleeding. So a lot of my patients really loved that option of being amenorrheic, no periods, just for the convenience of it. But they were still ovulating in the background, so we're not suppressing their natural cycles, just their periods.

Andrew Huberman 35:19 I see. And is there any evidence that the use of any form of birth control can disrupt the, um, timing-

Dr. Mary Claire Haver 35:26 Yes.

Andrew Huberman 35:26 ... or the, um, availability-

Dr. Mary Claire Haver 35:29 Good question.

Andrew Huberman 35:29 ... of, I, I realize availability of eggs is a very, um, uh, clinically naive-

Dr. Mary Claire Haver 35:33 So when-

Andrew Huberman 35:33 ... biologically naive statement.

Dr. Mary Claire Haver 35:34 (laughs)

Andrew Huberman 35:34 But basically what I'm saying, can it, can any of them accelerate the onset of perimenopause? Can they delay the onset of perimenopause?

Dr. Mary Claire Haver 35:41 They will delay the onset a little bit, you know?

Andrew Huberman 35:43 Mm-hmm.

Dr. Mary Claire Haver 35:43 It's, it's maybe a year if you use it for a long time from what the data shows. So women who suppress ovulation, we lose about 11,000 eggs each month with the ovulation process to get one out, 11,000 race to the finish line, and only one makes it, but we lose about 11,000 in the process. So women who are constantly, you know, for a long time suppressing ovulation will have, um, a slightly older age of menopause had they not done that.

Andrew Huberman 36:11 When you say slightly older, what's the longest extension of, of sort of-

Dr. Mary Claire Haver 36:15 The best I could see in the data was maybe nine months.

Andrew Huberman 36:18 Okay, from nine months use of-

Dr. Mary Claire Haver 36:20 No, no, no.

Andrew Huberman 36:21 ... birth control?

Dr. Mary Claire Haver 36:21 So, so maybe, like, five to ten year use. I have to look at the data again to be, you know, I, I'd have to look that one up, but it was several years.

Andrew Huberman 36:28 Got it. Um...

Dr. Mary Claire Haver 36:30 To, to gain an extra maybe nine months, maybe a year of-

Andrew Huberman 36:34 Nice.

Dr. Mary Claire Haver 36:34 ... ovarian life.

Andrew Huberman 36:35 I see. And, um, nowadays, uh, at least if people have the means, there's some, um-... trend, if you will, toward, um, freezing one's eggs.

Dr. Mary Claire Haver 36:46 Mm-hmm.

Andrew Huberman 36:46 Um, this might be a good opportunity to just state-

Dr. Mary Claire Haver 36:48 (laughs)

Andrew Huberman 36:48 ... something that came up before when we had, uh, Dr. Natalie Crawford-

Dr. Mary Claire Haver 36:51 Mm-hmm.

Andrew Huberman 36:52 ... on the podcast to talk about female fertility. Um, I think surprising to many people was her statement that, not because it's controversial but because we just don't hear this, uh, often enough, that harvesting eggs for freezing or for IVF does not diminish the pool of eggs that one would have, meaning you're losing them each month-

Dr. Mary Claire Haver 37:17 Right.

Andrew Huberman 37:17 ... anyway.

Dr. Mary Claire Haver 37:18 Yeah, and so they're only pulling out, I don't know, 10, 12 maybe in a cycle, and, and when you're losing 11,000 with an ovulation, so it really isn't going to affect when you go through menopause.

Andrew Huberman 37:30 Such a crucial thing for people to hear.

Dr. Mary Claire Haver 37:32 Yeah.

Andrew Huberman 37:32 Um, I think, uh, there were a number of comments when we posted that clip on social media and people, uh, women saying, "Wow, I didn't realize that harvesting eggs would not, um, somehow, uh, shift the onset of menopause earlier." And so for the record, we are not saying that. We're saying that-

Dr. Mary Claire Haver 37:51 (laughs)

Andrew Huberman 37:51 ... um, it does not. And, um, and very interesting that the use of, uh, birth control, but I'm guessing only forms of birth control that suppress ovulation-

Dr. Mary Claire Haver 37:59 Ovulation, yeah.

Andrew Huberman 38:00 ... can delay the onset of perimenopause, menopause by about nine months-

Dr. Mary Claire Haver 38:04 Yeah.

Andrew Huberman 38:04 ... maximum.

Dr. Mary Claire Haver 38:04 Maximum.

Andrew Huberman 38:05 Um, so things like the copper IUD which-

Dr. Mary Claire Haver 38:07 That won't affect it.

Andrew Huberman 38:08 Right, which, um, prevent pregnancy by creating a unfavorable environment for the sperm rather than disrupting o- ovulation in any way-

Dr. Mary Claire Haver 38:15 Right.

Andrew Huberman 38:15 ... will not presumably extend, um, perimenopause, menopause.

Dr. Mary Claire Haver 38:17 Mm-hmm.

Andrew Huberman 38:18 Okay, just wanna make sure we're crystal clear for people.

Dr. Mary Claire Haver 38:20 (laughs)

Andrew Huberman 38:20 You're being very clear, but I, I wanna make sure that I'm clear on it and then reiterate because this can be, um, uh, kind of tricky territory. I think there, there are a lot of assumptions about this stuff, and there's a lot of lore out there. What, why do you think that is? Is that because of the lack of solid research and communication in this area?

Dr. Mary Claire Haver 38:35 I think so.

Andrew Huberman 38:36 Or, or is it something else? You know, I, I, I think that these are, um, tricky topics for, for, uh, discussion often because, uh, w- we hear all this stuff, like birth control pills disrupt one's ability to get pregnant when they come off or, or it, we just learned that it can delay the onset of perimenopause, which, by extension, means there's a greater window for pregnancy if one, um, thinks about it that way. But, uh, why do you think it's, it's so, um, such a tangled discussion out there?

Dr. Mary Claire Haver 39:05 I think just the way that society views pregnancy and female health, and you know, at least, you know, I live on the internet now. You know, this new life has brought me life on the internet and this, what the algorithms-

Andrew Huberman 39:21 Welcome.

Dr. Mary Claire Haver 39:21 ... are showing me. (laughs) Yeah.

Andrew Huberman 39:23 (laughs) It's a very friendly... They... Everyone's super... No, it's-

Dr. Mary Claire Haver 39:25 Everyone loves you, every, yeah. (laughs)

Andrew Huberman 39:26 It's a, it's a great... Listen, it's... What you're doing, um, is so important.

Dr. Mary Claire Haver 39:31 Yeah.

Andrew Huberman 39:32 And, uh, I understand the, the statement behind that statement, I, I think. Um, but it's so important because it, people are getting the opportunity to learn about really critical public health-

Dr. Mary Claire Haver 39:42 Right.

Andrew Huberman 39:42 ... and female health issues, um, in a way that just was inaccessible before.

Dr. Mary Claire Haver 39:47 Yeah, it is. And I, I... It's good and bad. You know, there's a lot of lore and misinformation that's getting propagated, and I feel like as a specialty, you know, as a women's health specialist, we did this to ourselves. You know, we have not properly educated ourselves. We have not spent the money, the research, really, you know, championed women after reproduction. When you look at the dollars and, and the research and where it goes in women's health, I mean, women's health just gets a little sliver of all the NIH funding. When you look at all NIH funding and what goes to menopause, it's 0.03%.

Andrew Huberman 40:21 Unbelievable.

Dr. Mary Claire Haver 40:21 Less than half a percent, and this is one-third of a woman's life. And when you look at... God, McKinsey & Company just, just published, um, a report where they pulled 680 studies on, like chronic diseases, diabetes, hypertension, cardiovascular disease, and they looked at how... They had... There were women included in the studies, but how many presented the data for the different sexes, like what happened in men versus what happened in women. It was only 50%-

Andrew Huberman 40:48 Hmm.

Dr. Mary Claire Haver 40:49 ... of the articles actually did sex-specific differences in how this medication affected this process or whatever. And then of the ones that did, 30% of women had poorer outcomes. And, and the other, and on the flip side, 10% of men had poorer outcomes. And these things aren't just being brought to light. So the, the lack of recognition of sex-specific differences in chronic disease and how menopause kind of plays into all that I think is where the future needs to go. So we deserve as much good health as everyone else, 'cause yes, we're living longer than men, but 20 to 25% of that life is in poorer health.

Andrew Huberman 41:24 Wow, that's a, a really significant statement. I mean, I think that the National Institutes of Health has been terrific in establishing new institutes-

Dr. Mary Claire Haver 41:32 Yes.

Andrew Huberman 41:32 ... within it. Um, they even have a complementary health institute now.

Dr. Mary Claire Haver 41:37 Mm-hmm.

Andrew Huberman 41:37 There's the, the National Eye Institute. There's the, you know, cancer, urology. Um, is there a plan or one would hope for a dedicated institute for-

Dr. Mary Claire Haver 41:47 There's a-

Andrew Huberman 41:47 ... women's health?

Dr. Mary Claire Haver 41:48 ... push.

Andrew Huberman 41:48 Mm-hmm.

Dr. Mary Claire Haver 41:49 Um, so there was one piece of legislation that got pushed through. The Bidens signed it, and it was $100 million for women's health, and that got chopped up very quickly. Menopause did get a little piece of it because we're also really struggling with endometriosis and, you know, a lot of the female-specific uterine diseases and, and PCOS and things. And so we need more funding there as well. Um, and then there's another bill that just got... That's the one Halle Berry was, like, um, on TV talking about, another bill for $250 million. That bill includes language for education of providers. So we have a whole generation of providers... Like I graduated my residency training the year the WHI came out. So all... We had very little, like real clinically significant menopause education, and then we knew about HRT, and we were giving it in clinic, um, if she was coming in with severe hot flashes. But-... that got taken off the table after the WHI, and then we have a whole gener- like, all menopause education basically stopped after that.

Andrew Huberman 42:51 So the- so WHI, Women's Health Initiative-

Dr. Mary Claire Haver 42:53 Sorry.

Andrew Huberman 42:54 ... HRT. Uh, no, that's fi- that's okay-

Dr. Mary Claire Haver 42:55 Yeah.

Andrew Huberman 42:55 ... just so that people are on board, uh, hormone replacement therapy.

Dr. Mary Claire Haver 42:57 Mm-hmm.

Andrew Huberman 42:58 Um, yeah. It's, um, it's a- well, we, uh, can encourage the, uh, expansion of, of, uh, research in these areas and, uh, with this discussion. And, um, certainly, uh, I was on NIH panels for years, um, as a regular member in the Eye Institute, and what I've noticed with, um, NIH is that they are very responsive, uh, to the public call for growth of research in particular areas. You know, it can take time.

Dr. Mary Claire Haver 43:26 Mm-hmm.

Andrew Huberman 43:26 It's government after all, and they need funding. There's a finite amount-

Dr. Mary Claire Haver 43:29 Yeah.

Andrew Huberman 43:29 ... of funding. But, but I think that, um, ra- rarely do I ever get into legislature-based things.

Dr. Mary Claire Haver 43:34 (laughs)

Andrew Huberman 43:34 But if you are somebody who cares about, um, more funding in a given area of research, it's actually very straightforward what to do. You call your congressman-

Dr. Mary Claire Haver 43:41 Mm-hmm.

Andrew Huberman 43:42 ... or senator, and you tell them, literally you leave a message. I find this kind of interesting, and so it's kind of like what we learned in, um, social studies and, uh, in elementary school, but you call your-

Dr. Mary Claire Haver 43:54 SchoolHouse Rocks.

Andrew Huberman 43:54 ... you call your, um, senator or your governor, and you leave a message, and you say, "Hey, you know, there's this issue that impacts a ton of people, and it's really important. And, um, the next time it comes up, uh, when budgeting, uh, comes up in Washington, it's really important." And if you hear about a bill, you can call and support a bill. And believe it or not, some of that stuff actually translates to more funding in a given area. In fact, the, the Brain Initiative, which unfortunately had its budget cut significantly recently, maybe put that funding back.

Dr. Mary Claire Haver 44:25 (laughs)

Andrew Huberman 44:25 Um, but, you know, arose from the, um, I believe it was the child of two neuroscience professors up at University of Wisconsin. I'm probably gonna get some details wrong, but I, um ... so the Khalils are the, are the professors, as I recall, and their son overheard all these conversations growing up about the importance of brain science and then eventually pushed through government channels for more money for brain research. And then we had a, a long phase of, of, um, pretty, pretty substantial research, and then it was cut. So these things, um, but it persists. And so these things really matter.

Dr. Mary Claire Haver 44:56 They do.

Andrew Huberman 44:56 They can impact it. So and, um, maybe we should send them a clip of, of, uh, your statements on this podcast.

Dr. Mary Claire Haver 45:01 (laughs)

Andrew Huberman 45:01 Getting back to, um, kind of things that people can control-

Dr. Mary Claire Haver 45:04 Mm-hmm.

Andrew Huberman 45:05 ... so for people who are heading into perimenopause-

Dr. Mary Claire Haver 45:07 Mm-hmm.

Andrew Huberman 45:07 ... or who are in the perimenopause phase, um, aside from the, the typical things that we hear about, fortunately, a lot these days, like getting adequate sleep-

Dr. Mary Claire Haver 45:16 Mm-hmm.

Andrew Huberman 45:16 ... um, getting exercise-

Dr. Mary Claire Haver 45:17 Mm-hmm.

Andrew Huberman 45:18 ... um, nutrition, maybe we could touch a little bit on nutrition in a moment.

Dr. Mary Claire Haver 45:21 Mm-hmm.

Andrew Huberman 45:21 You mentioned Mediterranean diet, Galveston diet, um, things that are going to promote overall health.

Dr. Mary Claire Haver 45:26 Right.

Andrew Huberman 45:27 Um, are there any things that people can do, maybe even take, that would improve, uh, their outcomes in this phase? Like I, I've heard of people, and b- I have no bias here or even knowledge-

Dr. Mary Claire Haver 45:38 Mm-hmm.

Andrew Huberman 45:38 ... of the research on this, if there is any, of people taking, for instance, grape seed extract or people trying to do a number of things to reduce inflammation, kind of general themes around, um, self-care and wellness these days. But what are sort of the five or six that come to mind, um, perhaps as, like, the things that can move the levers in the right direction?

Dr. Mary Claire Haver 45:56 What I would tell my 35-year-old self, you know, who just kind of went into this obliviously and what I know now is, your diet is probably one of the most important things that determines your level of inflammation. And then estrogen is a really powerful anti-inflammatory hormone, and we lose that protection when we go th- we start losing it through the transition. So whatever you can do in the other areas, especially with nutrition, sleep, stress reduction, we need to do it. So fiber, we are not getting enough fiber in our diet. In the Western diet, I think it's most women are getting 10 to 12 grams per day, and we need at least 25. And the health benefits tend to max out around 30, 32 grams per day. So focusing on foods that are rich in fiber. Fiber's feeding the gut microbiome, slowing down glucose absorption, you know, glucose levels, uh, sugar absorption into the bloodstream. It is slowing down the rate of, you know, certain parts of transit and pulling more water into the gut, and, like, there's nothing bad about it, right? The foods that are rich in fiber have a lot of other stuff that's good for you too, cofactors, vitamins, minerals, nutrient- you know, just, they're just so healthful. Um, and then anthocyanins, you know, just find things that crunch, that are g- and get as many colors as you can, you know, green, red, purple, yellow. Every color represents a phytochemical that is going to be good for you in, uh, different areas of your body and try to keep it as varied as possible. Um, we're not getting enough protein, and I have to thank Dr. Gabrielle Lyon, you know, really helping me focus in on that. You know, when I first wrote Galveston Diet, to be honest and transparent, it was for weight loss. And, you know, I was frustrated with my weight gain, and I- that was the pain point my patients had, and that was my pain point. But I didn't realize it represented something much more sinister than, than just the way I looked, you know, the visceral fat gain. And so, uh, learning about visceral fat and what it really means, and that is, for your listeners, the fat that wraps around our internal organs. It's a very different fat than the subcutaneous fat. And, you know, a premenopausal woman, so we age matched and looked at visceral fat levels, measuring it with the, uh, um, DEXA scanners. You have a- about 8% of your fat is visceral as a premenopausal person, and then when you go through the transition, it's 23%-

Andrew Huberman 48:04 Wow.

Dr. Mary Claire Haver 48:05 ... with no changes in diet and exercise.

Andrew Huberman 48:07 The, uh, visceral fat is not something that gets enough attention.

Dr. Mary Claire Haver 48:10 No.

Andrew Huberman 48:10 I think everyone thinks about subcutaneous fat-

Dr. Mary Claire Haver 48:12 Mm-hmm.

Andrew Huberman 48:12 ... because of its relationship to aesthetics.

Dr. Mary Claire Haver 48:13 It's cosmetically distressing, but really, yeah. Like ... (laughs)

Andrew Huberman 48:16 Um, and one doesn't want too much of it for health reasons eith- either, but the-

Dr. Mary Claire Haver 48:20 Right.

Andrew Huberman 48:20 ... it's the, um, intraviseral fat that, at least by my understanding, is, is really, uh, the most problematic for-

Dr. Mary Claire Haver 48:26 Yes.

Andrew Huberman 48:26 ... for our, for our health.

Dr. Mary Claire Haver 48:27 It's a h- harbinger of, of chronic disease, so

Dr. Mary Claire Haver 48:31 ...

Andrew Huberman 48:31 I read that weight gain is one of the primary symptoms of menopause itself.

Dr. Mary Claire Haver 48:37 Yeah. So it's- you have to be careful how you think about that. When we, when we plot weight gain versus age, it's a very straightforward linear curve, and menopause does not seem to affect that. What is happening is a body composition change. We are losing muscle, and we are gaining...... visceral fat. And so, and you might be gaining some c- subcutaneous fat, but those are kind of the key things that are happening. And so that's really, when I'm counseling patients, what I'm focusing on. 'Cause I have a body scanner in my office where I can tell them what their level of visceral fat is and their muscle mass. And so we, bone and muscle, that musculoskeletal unit works together. And so we see this acceleration of muscle loss, which controls our basal metabolic rate, which determines our resistance to insulin, which, you know... So it's just, that's the l- eh, the organ of longevity. That's what I've learned from Dr. Lyon, you know, and everything we can do to hang onto it and build is so important. So protein, going back to the original point, protein intake is key. And women, by and large, are getting 50 to 60 grams of protein per day, and we really probably need 80, 100, 120 depending on our body composition.

Andrew Huberman 49:46 Yeah, thanks for mentioning Dr. Gabrielle Lyon. She's doing what I view as just, just-

Dr. Mary Claire Haver 49:50 Beautiful work in the world.

Andrew Huberman 49:51 Yeah, terrific work, really promoting women's health and health generally. I know she's now, I believe, is exploring, um, advanced training in, uh, in urology-

Dr. Mary Claire Haver 50:01 Mm-hmm.

Andrew Huberman 50:01 ... for males as well.

Dr. Mary Claire Haver 50:03 Mm-hmm.

Andrew Huberman 50:03 And, um, so, you know, it's, um, it's, it's only fair to, to credit her with, with really expanding into these different areas, but especially this idea that we need, and women perhaps in particular, from what I understand of, um, she'll be on the podcast soon, so we'll get more of a, uh, of an understanding, at least one gram of quality protein per pound of lean body mass, maybe even per pound of body weight per day in order to optimize their, their health.

Dr. Mary Claire Haver 50:31 Yeah. She's, she's definitely on the higher end. You know, the WHI, the Women's Health Initiative, some of the, my favorite data, you know, it's not all bad, it's data, and was looking at frailty scores and protein intake in women. And what they found was women who were having 1.5 to 1.7, so basically it was the higher their protein intake, the less likely they were to be frail. The end. And it was, you know, they were reaching, it was kind of peaking out somewhere around 1.5 to 1.7 grams for kilogram of lean body mass. And most women are getting around, you know, the FDA recommends .8.

Andrew Huberman 51:07 Wow. And source of protein, also important, high quality.

Dr. Mary Claire Haver 51:11 Right, right.

Andrew Huberman 51:11 Yeah, yeah, yeah.

Dr. Mary Claire Haver 51:11 You need all the amino acids. Yeah.

Andrew Huberman 51:13 Very interesting. Um, now that's in menopause, but presumably also-

Dr. Mary Claire Haver 51:19 So starting those habits in peri-

Andrew Huberman 51:21 Mm-hmm.

Dr. Mary Claire Haver 51:22 ... just getting that laid down and getting those habits laid down are gonna set you up for a much better post-menopause, a much healthier post-menopause. And we have to stop defining menopause by your hot flashes, you know? It may or may not make your hot flashes better, and we have great medications for that if it's disruptive. But I'm talking about your, your cardiometabolic disease risk.

Andrew Huberman 51:43 I meant to ask this earlier, so forgive me for, for leaping back briefly, but is there any value in knowing the age at which your mother-

Dr. Mary Claire Haver 51:50 Yes.

Andrew Huberman 51:51 ... went into menopause-

Dr. Mary Claire Haver 51:52 Tremendous genetic-

Andrew Huberman 51:52 ... as a metric-

Dr. Mary Claire Haver 51:53 Mm-hmm.

Andrew Huberman 51:53 ... uh, or a sensor rather, uh, for, or a, as a window into whether or not you will go into menopause at more or less the same age?

Dr. Mary Claire Haver 52:01 Yes. There is a, of course it's not one-to-one. We get half of our DNA from our fathers. So, but I always ask, and there is a d- you know, acc- the latest data that looked at it, genetics is the biggest factor that determines when you're gonna go through menopause. So knowing when your mothers, your aunts, you know, went through and if there were any medical conditions associated with that is huge.

Andrew Huberman 52:25 Okay, so now we're talking not so much about perimenopause, but also menopause itself.

Dr. Mary Claire Haver 52:31 Mm-hmm.

Andrew Huberman 52:31 What is the typical constellation of symptoms as one enters menopause? Like right at the beginning.

Dr. Mary Claire Haver 52:37 Mm-hmm.

Andrew Huberman 52:37 And then does that constellation of symptoms change as one is, you know, a year, two years, three years into menopause?

Dr. Mary Claire Haver 52:43 So it's almost 100% with body composition changes, like very, very close. You know, that visceral fat is tough to beat. It's beatable, but it takes a lot of work, you know?

Andrew Huberman 52:53 Do people know if they have visceral fat? I mean, there's, there are scanning approaches to-

Dr. Mary Claire Haver 52:56 So-

Andrew Huberman 52:57 ... to look at it.

Dr. Mary Claire Haver 52:57 ... gold, you know, of course the gold standard is a DEXA or even an MRI, but w- no one can afford that. So we have in, like what I have a- um, in my office is the InBody scanner. So it's electrical impedance scanner and it's, it's pretty good.

Andrew Huberman 53:09 So you stand on the scale, hold the handles.

Dr. Mary Claire Haver 53:11 And we hold, I have the medical-

Andrew Huberman 53:12 Okay.

Dr. Mary Claire Haver 53:12 ... I have the highest grade one-

Andrew Huberman 53:13 Mm-hmm.

Dr. Mary Claire Haver 53:13 ... for my patients. Um, and most people doing what I do, you know, utilizing a body scanner, use that one. Um, but you can use the waist-to-hip ratio. And so the waist-to-hip ratio is a better measure of your risk of metabolic health than your weight or your BMI. So it's so simple. You take a tape measure and a calculator, or you can do it in your head, but you measure the smallest part of your waist, and if you don't have a small waist, if it goes out, then just use your belly button. Just use something you can measure again.

Andrew Huberman 53:40 Are people sucking in or are they relaxed?

Dr. Mary Claire Haver 53:41 You should be relaxed.

Andrew Huberman 53:42 Okay.

Dr. Mary Claire Haver 53:42 And I tell my patients, you know, "Do it first thing in the morning when your bladder's empty and you're not bloated and, you know."

Andrew Huberman 53:47 Mm-hmm.

Dr. Mary Claire Haver 53:48 Um, and then the widest part of your hips. It's not perfect, but it's better than your weight or your BMI.

Andrew Huberman 53:53 So widest part of the hips with people with feet, feet parallel-

Dr. Mary Claire Haver 53:56 Yeah, just parallel.

Andrew Huberman 53:56 ... standing up. (laughs) I'm just, we're trying to get-

Dr. Mary Claire Haver 53:58 Standing up straight.

Andrew Huberman 53:58 ... for people, 'cause people are gonna go-

Dr. Mary Claire Haver 53:59 Right.

Andrew Huberman 53:59 ... try this, right?

Dr. Mary Claire Haver 54:00 And so, um, I only know the data for women, so forgive me, but, um, for a female, if it's less than 0.7, then your chance of having clinically significant aberrations in visceral fat are low. And then if it's greater than one, you likely have higher levels of visceral fat. And so in clinic or when I was coaching online for Galveston Diet, we were using the waist-to-hip ratio as one of the, you know, measures for their success.

Andrew Huberman 54:30 When measuring the waist, um, which point along the waist? Is it right at the-

Dr. Mary Claire Haver 54:34 So-

Andrew Huberman 54:34 ... navel? Is it-

Dr. Mary Claire Haver 54:35 It's just wherever you're smallest. So that's-

Andrew Huberman 54:37 Mm-hmm.

Dr. Mary Claire Haver 54:37 ... kind of different for different women. So I would just say look in the mirror, wherever your hourglass goes in is where you want to kind of stick to. But if you don't have that kind of a waist and you have a wider waist, just pick the belly button 'cause you always know you can go back to that level.

Andrew Huberman 54:50 Mm-hmm.

Dr. Mary Claire Haver 54:50 You know, that's m- 'cause we're tracking them over time.

Andrew Huberman 54:54 Great. Those are, um, very useful, um, recommendations.And how often should people do that?

Dr. Mary Claire Haver 55:00 Uh, you know, you should never weigh yourself every day. You shouldn't do this every day. We were having patients do it or, you know, our followers do it once a month.

Andrew Huberman 55:07 So changes in body composition-

Dr. Mary Claire Haver 55:09 Mm-hmm.

Andrew Huberman 55:09 ... as measured by DEXA or impedance or if you don't have access to that-

Dr. Mary Claire Haver 55:14 Or waist to hip ratio.

Andrew Huberman 55:15 ... uh, waist to hip ratio. Uh, what are some of the other symptoms of menopause?

Dr. Mary Claire Haver 55:18 Fatigue. Fatigue. Multiple causes for the fatigue. Um, a lot of sleep disruption. Um, sleep disruption is another huge thing. So s- all of a sudden you're struggling to go to sleep or you're having middle of the night awakenings and not able to go back to bed.

Andrew Huberman 55:32 That are new and different from previous-

Dr. Mary Claire Haver 55:33 New and different than before, right.

Andrew Huberman 55:35 I see.

Dr. Mary Claire Haver 55:36 There was a recent study that came out and most of my patients in hindsight say, "I knew something wasn't right." Or "Something was different, something had changed but I couldn't put my finger on it." And they'd just had a study come out saying some things, uh, th- when they looked at what that means, "What does 'I'm not feeling like myself' mean?" And it was psychological changes. So you lose resilience. You're suddenly more irritable. You're suddenly not able to, like, go with the punches or, or do, you know, you're, you're not adjusting as well to change that you used to. You're snapping at your kids more, or your partner, or you're, you know, you're, you're getting frustrated at work. You know, it's just very kind of subtle and it takes going through it and then looking back to say, "Yeah, I really say may- maybe about 47 that something was changing and I just thought I was just stressed out or whatever, and then now I can see that was the beginning of the pattern." So menstrual changes as we talked about. Um, you know, the big highlights, vertigo, tinnitus, ringing in the ears. Um, skin changes, so dry skin, itchy skin, feeling like you're having crawling under the skin. Big gut changes, so new-onset bloating. You're kind of eating all the same things and your gut's just not handling things like it used to. So the ZOE Nutrition Study took 1,100 women and, and did stool samples through menopause, through the peri-menopause, menopause transition, and saw the changes in the gut microbiome from the loss of the sex hormones. And basically we went from what a typical female microbiome to that of a male through the transition.

Andrew Huberman 57:08 Is there any direct evidence that, um, supplementing the gut microbiome, and here I don't necessarily mean pills and powders.

Dr. Mary Claire Haver 57:15 Right.

Andrew Huberman 57:15 I mean, um-

Dr. Mary Claire Haver 57:16 Just eating diets rich in-

Andrew Huberman 57:16 ... my understanding is that getting enough fiber-

Dr. Mary Claire Haver 57:19 Yeah.

Andrew Huberman 57:19 ... and low sugar fermented foods-

Dr. Mary Claire Haver 57:21 Mm-hmm.

Andrew Huberman 57:22 ... can also support the gut microbiome.

Dr. Mary Claire Haver 57:23 Yes.

Andrew Huberman 57:23 Things like, um, sauerkraut, kimchi-

Dr. Mary Claire Haver 57:26 Miso.

Andrew Huberman 57:26 ... kefir, miso.

Dr. Mary Claire Haver 57:27 Yeah.

Andrew Huberman 57:28 Um-

Dr. Mary Claire Haver 57:28 Plain yogurt, just-

Andrew Huberman 57:30 Mm-hmm.

Dr. Mary Claire Haver 57:30 ... straight up, nothing added.

Andrew Huberman 57:31 Yeah. So, uh, is there evidence that supporting the gut microbiome can, um, make this, uh-

Dr. Mary Claire Haver 57:36 So-

Andrew Huberman 57:36 ... stage of menopause more, I guess, um, reduce some of the symptoms of, of menopause?

Dr. Mary Claire Haver 57:41 So the best I could find was most of them are, are done with supplements 'cause those are easier to measure than handing someone a cup of yogurt.

Andrew Huberman 57:48 Right.

Dr. Mary Claire Haver 57:48 You know?

Andrew Huberman 57:48 And you know which bacteria you're providing.

Dr. Mary Claire Haver 57:50 Yeah.

Andrew Huberman 57:50 Right.

Dr. Mary Claire Haver 57:50 So, um, they did lactobacillus and looked, and bifidobacterium, I think, and saw that women who were obese and hypertensive and menopausal, and they had visceral fat decrease and blood pressure improvements versus placebo. Um, also it's hard to do placebo studies with food, you know, so-

Andrew Huberman 58:08 Right.

Dr. Mary Claire Haver 58:09 Um, but they do, and then in the retrospective studies they can look at dietary patterns and women who ate f- rich foods fermented and y- lots of yogurt, you know, Mediterranean-type diets, um, have better symptoms overall.

Andrew Huberman 58:22 What's the difference bet- between the Mediterranean diet and the Galveston diet?

Dr. Mary Claire Haver 58:26 So when I... So I w- got my culinary medicine certification. I was frus-

Andrew Huberman 58:32 Culinary medicine?

Dr. Mary Claire Haver 58:33 Yeah. So I was frustrated in, when I was working, because I didn't know anything about nutrition and suddenly, like, everything I was trying to tell my patients was based on, like, the one lecture I got in medical school and, you know, good nutrition was like porn. You know it when you see it, you know, the Supreme Court definition of pornography. And so, you know, the best I'd ever gotten was the gestational diabetic diet and it was this Xeroxed things with, you know, I was in the deep ... I was in Texas so it had, like, tortillas and stuff on it and, and it had been copied so many times you could barely read it anymore and that was the diet we would ha- that was the only nutrition I'd ever, like, handed to a patient. And so I'm like, "Eat healthy." And so I'm like, "I gotta do better than this. I don't know enough." And so we had a guest speaker for AO- uh, Alpha Omega Alpha, which is the honor society for medical school and I was one of the advisors so ... And it was this guy, Tim Harlan, who had started this culinary medicine movement and it was basically nutrition for doctors (laughs) . And he developed this, like, online program and I had to go to New Orleans for a lab, in San Antonio for a lab, and work in kitchens where you were learning how to counsel patients, how to cook, and also basically, like, getting a little minor in nutrition. Um, so it was the best thing I've ever done.

Andrew Huberman 59:40 Yeah. I was gonna say very cool what-

Dr. Mary Claire Haver 59:41 I mean, I learned about allergies and, like, all this stuff, you know, food allergies and things that I just didn't know and just basic nutritional principles like what it takes to build a healthy body and, and what ... You know, I knew about kwashiorkor and, like, severe deficiencies but not good basic nutrition.

Andrew Huberman 59:54 Mm-hmm.

Dr. Mary Claire Haver 59:54 And so, you know, they talked heavily about Mediterranean and they talked a lot about the fad diets and stuff but, you know, the principles of the Mediterranean, I was like, "I want to teach this to my patients but they're not gonna eat a lot of, um, greek yogurt or they're probably not gonna eat a lot of feta." You know, like, "How can I kind of take these blocks and make it more Americanized?" So that was kind of like the brainchild for me around Galveston Diet was let me, like, create something and I really was into fasting at the time too so I was like, "Let me put this fasting thing together with, you know, good nutritional anti-inflammatory principles and talk about the things we know are probably you should, you know, not having a whole lot of, you know processed foods and high sugars and stuff and, and explain it in a way and how it's affecting their menopause and, like, how can she approach her nutrition?" And that's how Galveston Diet was born. It was for my patients and then I gave it to my girlfriends and then they started sharing it and I talked about it one day on Facebook and the world exploded.

Andrew Huberman 1:00:44 In the best way.

Dr. Mary Claire Haver 1:00:44 In the best way. (laughs) Yeah. It led me here.

Andrew Huberman 1:00:47 Right.

Dr. Mary Claire Haver 1:00:47 So-

Andrew Huberman 1:00:47 Right. Um, and we all benefit. W- what is the evidence that-... fasting can be beneficial or detrimental-

Dr. Mary Claire Haver 1:00:55 Mm-hmm.

Andrew Huberman 1:00:55 ... to, um, perimenopause and menopause.

Dr. Mary Claire Haver 1:00:57 Yeah. So, the jury's kind of still out on that one. I was a re- really liked the data that, you know, uh, I think it was Mark Mattson had done on neurodegenerative disease and, and using fasting as a tool there in lowering inflammation levels. So I was like, "This is amazing. This is great." Because so much about menopause is pro-inflammatory, you know?

Andrew Huberman 1:01:17 I- is this intermittent fasting?

Dr. Mary Claire Haver 1:01:18 Intermittent fasting, yeah.

Andrew Huberman 1:01:18 So time-restricted feeding?

Dr. Mary Claire Haver 1:01:19 So he was basically doing 16:8, you know?

Andrew Huberman 1:01:22 Mm-hmm.

Dr. Mary Claire Haver 1:01:22 And, uh, you know, very scheduled intermittent fasting. And so, that was something I was coaching my followers about. You know, "Consider this. Try this. This would- might be something to help lower inflammation." I pulled back on that because it's really hard to get enough protein in for a lot of, of women, especially if they came in at 60 and now I'm telling them to double their protein, you know, and then giving them an eight-hour window to do it. They're like, "I'm walking around gnawing on a chicken breast all day."

Andrew Huberman 1:01:46 Right.

Dr. Mary Claire Haver 1:01:47 You know?

Andrew Huberman 1:01:47 Right, right.

Dr. Mary Claire Haver 1:01:47 This is hard. And-

Andrew Huberman 1:01:48 Right. And m- metabolizing protein is its own work.

Dr. Mary Claire Haver 1:01:51 Right.

Andrew Huberman 1:01:51 Okay.

Dr. Mary Claire Haver 1:01:51 And so you have to spread it out throughout the day, you know, and a lot of that work was done at UTMB, where I did my undergr- I mean, my residency and where I taught for years. And so I was friendly with the nutrition department there. I was getting all excited about everything. And they were like, you know- I went to several of their conferences and, like, talking about breaking up protein intake into nuggets throughout the day, 'cause most women have very little protein with breakfast, maybe wheat gluten in their toast, and then have a little bit at lunch and then kind of stack their protein at night. And they're still not getting enough, but they're overdoing it in their evening meal. That's their big protein meal. And so, like, teaching them to kind of- you know, what I was teaching in Galveston Diet was you need to have a healthy fat, a, a good, healthy carb, and a protein with every meal and snack that you eat, you know?

Andrew Huberman 1:02:35 Why do you think that protein has not been emphasized, um, enough until recently?

Dr. Mary Claire Haver 1:02:42 I think because we didn't understand it. You know, we didn't understand how important muscle was. And I mean, we knew that protein intake was important for muscle, but muscle was for bodybuilders and not for women. I lived my whole life, up until about five years ago, eating to be thin and moving to be thin.

Andrew Huberman 1:03:01 Mm-hmm.

Dr. Mary Claire Haver 1:03:01 That thin was the only measurement of health that I needed to worry about. And what I did was chip away at my bone and muscle strength. And thank God I don't have osteopenia yet. You know, I've, I've hopefully have reversed whatever trend I was on, and I'm naturally low muscle. So now it's just a battle (laughs) to try to hang on to what little I have and build some. And so-

Andrew Huberman 1:03:19 A new, a new resistance train?

Dr. Mary Claire Haver 1:03:21 Yeah, yeah.

Andrew Huberman 1:03:21 Yeah, yeah. Yeah, th-

Dr. Mary Claire Haver 1:03:22 Now, now-

Andrew Huberman 1:03:23 Three days a week. Three days a week?

Dr. Mary Claire Haver 1:03:24 Three to four days a week, yeah, I'm resistance training, much less cardio. I was running marathons, I ... And it was a great social thing with my girlfriends, but, you know, everything I did was cardio. I taught step aerobics, you know? The only weights I did were maybe in Zumba, maybe one or two pounds, you know? So- and that was gr- better than being on the couch. I mean, I loved the community and doing that, but, you know, for me to, like, stay out of the nursing home, which was my ul- ultimate goal for as long as possible, I need to pick up some weights and heavy weights. And so that's where my focus has changed.

Andrew Huberman 1:03:53 Isn't it interesting that it wasn't until recently that, um, it was only bodybuilders and football players and people preparing for military or a specific sport would resistance train? And now we are told that everybody, male, female, young, old, should resistance train-

Dr. Mary Claire Haver 1:04:10 Absolutely.

Andrew Huberman 1:04:11 ... probably three times a week.

Dr. Mary Claire Haver 1:04:12 Yeah. And th- the- my generation is struggling because we don't know how to do it. And so I'm, you know ... And I'm not a personal trainer. I don't pretend, you know ... I hire one to help me develop a program so that I don't hurt myself and that I can get stronger, you know, progressive loads. So, you know ... And again, Dr. Lyon, such a huge-

Andrew Huberman 1:04:30 Mm-hmm.

Dr. Mary Claire Haver 1:04:30 ... proponent of that. And so what I try to do publicly is show my workouts so that people ... I normalize it, and people see me doing it and they're like, "Well, if she can do it, then I can do it."

Andrew Huberman 1:04:39 That's great. Super inspiring, and it really helps, uh, cross that threshold where people, as you said, they don't know how.

Dr. Mary Claire Haver 1:04:45 Mm-hmm.

Andrew Huberman 1:04:45 It's scary-

Dr. Mary Claire Haver 1:04:46 Right.

Andrew Huberman 1:04:46 ... uh, for people who've resistance trained for a long time. They go into a gym, they, they know how all that stuff works.

Dr. Mary Claire Haver 1:04:50 Yeah.

Andrew Huberman 1:04:50 But, uh, for those that don't, it's, it's-

Dr. Mary Claire Haver 1:04:52 You're wandering around. "What does this one do," you know? (laughs)

Andrew Huberman 1:04:54 Yeah. Yeah, it's intimidating for a whole bunch of reasons. Well, thank you for putting that content out, um, both the, uh, prescription, if you will, but also the example of that-

Dr. Mary Claire Haver 1:05:02 Mm-hmm.

Andrew Huberman 1:05:02 ... that one can go about it. So I'm guessing if you could go back 20 years, you would have started resistance training earlier-

Dr. Mary Claire Haver 1:05:08 Yeah.

Andrew Huberman 1:05:08 ... and eating more, like, quality protein.

Dr. Mary Claire Haver 1:05:08 Yeah. Strong over skinny, nutrition over calories, and, and stop looking, trying to look a certain way, you know? You're, you're undermining your future health by doing

Dr. Mary Claire Haver 1:05:18 that.

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Andrew Huberman 1:06:29 off. So, um, what are some other symptoms of menopause? You, you, you mentioned body composition changes.

Dr. Mary Claire Haver 1:06:35 Mm-hmm.

Andrew Huberman 1:06:36 Uh, the one that we hear about the most, for s- some reason, I don't know, is hot flashes.

Dr. Mary Claire Haver 1:06:40 Yeah, so, so I think-

Andrew Huberman 1:06:41 So, so maybe we could define-

Dr. Mary Claire Haver 1:06:42 ... hot flashes, um ... So in medicine, we call it a vasomotor symptom. So we have a, a dysregulation of the thermoregulatory center in the hypothalamus, and that, that g-... the, the way- the thermostat gets reset, basically. And so what happens is we have this vasodilation of, it starts in the core typically for most women, somewhere in the chest/neck area, and you feel this heat. You know (laughs) , I can probably trigger one just by talking about it. Um, and it, it goes up into the neck and out into the extremities, and then you just start profusely sweating from all the blood vessels dilating, and then it can last minutes to a second. But for some women, it's preceded by sometimes palpitations, sometimes by this intense feeling of, of dysphoria, you know, this intense sadness feeling, and then it, and then it just kind of passes. But, you know, say you're, you know, wherever you are in your life, whatever you're doing, all of a sudden you're just, like, sweating profusely in the middle of some important area of your life, work, you know, whatever your jobs are in your life, and it's disruptive. If it happens at night, you don't sleep. And for some women, it's severe where they're having multiple ones a day.

Andrew Huberman 1:07:48 And when, anytime you disrupt sleep, then daytime is far worse.

Dr. Mary Claire Haver 1:07:52 Yeah.

Andrew Huberman 1:07:52 It, regulation of everything. Yeah.

Dr. Mary Claire Haver 1:07:54 You eat differently. You, yeah, you stress differently.

Andrew Huberman 1:07:55 Yeah.

Dr. Mary Claire Haver 1:07:55 You, you know, everything changes, and so when my patients come in, the first questions we ask are sleep, and that's the first thing we work on is, is, you know, "What can we do to get your sleep better?"

Andrew Huberman 1:08:06 What can be done for hot flashes, aside from the things that you've already described, to offset menopause and bring menopause itself?

Dr. Mary Claire Haver 1:08:11 So the goal, absolute gold standard is hormone therapy, is, like, giving your body back the estrogen, which will readjuv- get your serotonin levels back to where they were and leave that thermoregulatory center (laughs) alone so it's back to where it used to be.

Andrew Huberman 1:08:24 Let's talk about hormone therapy.

Dr. Mary Claire Haver 1:08:26 Sure.

Andrew Huberman 1:08:26 It's a bit of a controversial topic.

Dr. Mary Claire Haver 1:08:28 For no reason.

Andrew Huberman 1:08:29 Yeah, I, I was gonna say, I don't know why. Um-

Dr. Mary Claire Haver 1:08:31 Yeah, it's demonized. It, it got such a bad rap, and we need to, to, it's just some of the, what was the worst misinformation campaign in the history of medicine.

Andrew Huberman 1:08:40 Well, that's a bold statement, but I believe you. The, um, the way I understand it is that there was this large-scale hormone therapy trial.

Dr. Mary Claire Haver 1:08:49 Mm-hmm, mm-hmm.

Andrew Huberman 1:08:50 Um, and the interpretation of that trial was something different than we now believe-

Dr. Mary Claire Haver 1:08:57 Right.

Andrew Huberman 1:08:57 ... um, as a medical community.

Dr. Mary Claire Haver 1:08:58 The initial... So it was really groundbreaking at the time. Aging women were finally being studied. We knew from observational data that women on hormone therapy, probably 40% of the population of females eligible were on HRT, okay? So very large amount. So the women who were given hormone therapy had lower incidents of cardiovascular disease, older ages of cardiovascular disease, lower death from cardiovascular disease. Some people argued that that was an artifact of healthier, wealthier women get HRT 'cause they go to the doctor, okay? So this is just because they're healthier that they have less cardiovascular disease, so let's prove it. What do you do that with? A randomized control trial. So flaws in the study, so they take, I think there were 11,000-ish women in the estrogen-only arm 'cause they'd had hysterectomy. So for your listeners, if you have a uterus and you're getting estrogen, you must have a progestogen with it to protect the lining of the uterus from endometrial cancer. As long as you give an adequate progestin, you're fine, okay? But if you don't have a uterus, progesterone is not mandatory. So the women who had had hysterectomy got estrogen only or placebo.

Andrew Huberman 1:10:04 All right.

Dr. Mary Claire Haver 1:10:05 And the estrogen at the time was Premarin, which was the number one prescription for HRT at the time, so nothing weird about that, okay?

Andrew Huberman 1:10:12 So it's just, um, synthetic estradiol?

Dr. Mary Claire Haver 1:10:14 Actually, no, uh, Premarin is, is... Premarin stands for pregnant mare urine. It is actually very natural. They take pregnant horses and extract the estrogens from their urine because they're pregnant and they're excreting a lot of it, and it was cheap and easy, and I have a lot of ethical issues about how they do that, but, and I don't prescribe it, but that's what was done at the time, so.

Andrew Huberman 1:10:34 I- I've seen horses-

Dr. Mary Claire Haver 1:10:36 So there's like-

Andrew Huberman 1:10:36 They urinate, they urinate a lot.

Dr. Mary Claire Haver 1:10:37 There are dozens-

Andrew Huberman 1:10:38 I didn't, I didn't realize there was a-

Dr. Mary Claire Haver 1:10:39 Sorry, sorry, sorry. (laughs)

Andrew Huberman 1:10:40 Yeah, yeah, yeah.

Dr. Mary Claire Haver 1:10:40 There's dozens of estrogens in that comp- but the main one is estradiol.

Andrew Huberman 1:10:44 Mm-hmm.

Dr. Mary Claire Haver 1:10:45 So, um, then they're, the other group who had uteruses were given Prempro, which is Premarin plus Provera-

Andrew Huberman 1:10:52 Mm-hmm.

Dr. Mary Claire Haver 1:10:53 ... and, or placebo. So off we go. They recruit 11,000 and then, I think, 15,000 in the other arm. Huge study. It was like a billion-dollar study. Like, we're so excited this is happening. This started when I was in med school, and then they start recruiting patients, and then, um, you know, everyone's taking their meds. They excluded women with hot flashes.

Andrew Huberman 1:11:13 What?

Dr. Mary Claire Haver 1:11:14 Because if your hot flashes go away, you know that you didn't get the placebo.

Andrew Huberman 1:11:19 Ah.

Dr. Mary Claire Haver 1:11:20 So they excluded women with hot flashes, problem number one. The-

Andrew Huberman 1:11:23 Yeah, that's a big problem.

Dr. Mary Claire Haver 1:11:24 Now-

Andrew Huberman 1:11:24 That's like, wha- (laughs)

Dr. Mary Claire Haver 1:11:24 ... the end outcome, the, what they were trying to measure was cardiovascular disease, so they started with an older population. The average age was 63.

Andrew Huberman 1:11:33 Whereas the typical onset of menopause is?

Dr. Mary Claire Haver 1:11:35 51.

Andrew Huberman 1:11:36 Wow.

Dr. Mary Claire Haver 1:11:37 So these women had been menopausal, you know, on average for 10, 12, 13 years. So time away from estrogen is when disease starts, accelerates, right? Okay, so put them on their meds, start measuring. In the estrogen plus progestin arm, they saw a non-statistically significant increased risk of breast cancer, and it was this. The relative risk, relative, now you know what this is but your, many of your listeners may not, was 25% and it, and I hope I get the numbers right. It was four out of 1,000 women per year to five out of 1,000 women per year.

Andrew Huberman 1:12:15 Okay.

Dr. Mary Claire Haver 1:12:15 Okay? So placebo arm was four. So we have breasts, we are females, we get breast cancer, about four out of 1,000 women per year, and that increased to five. In the estrogen-only arm, there was a 30% decreased risk of es- of breast cancer. So they kept-

Andrew Huberman 1:12:28 Regardless of the ons- of the average age?

Dr. Mary Claire Haver 1:12:31 Mm-hmm, and they kept that arm going, okay?

Andrew Huberman 1:12:33 Right, 'cause it's randomized, so presumably the average age for the other group is roughly 61 as well.

Dr. Mary Claire Haver 1:12:37 Yeah, they were matched.

Andrew Huberman 1:12:38 Okay, yep.

Dr. Mary Claire Haver 1:12:38 So in their 60s as well. So they call a press conference at the Watergate Hotel-

Andrew Huberman 1:12:44 The Watergate Hotel of all places.

Dr. Mary Claire Haver 1:12:45 ... to announce-

Andrew Huberman 1:12:46 Okay.

Dr. Mary Claire Haver 1:12:47 ... the findings. They hadn't even published the data yet. No one had had a chance to read it.

Andrew Huberman 1:12:52 Hmm.

Dr. Mary Claire Haver 1:12:53 And these, the head researchers call this press conference and say, "Estrogen causes breast cancer."

Andrew Huberman 1:12:59 Exogenous estrogen from these-

Dr. Mary Claire Haver 1:13:01 Yes. Yes.

Andrew Huberman 1:13:02 ... yeah.

Dr. Mary Claire Haver 1:13:02 And they said it's a 25% increased risk, but the absolute risk was, like, 0.8% per year. But that didn't get, that d- that's not a headline thing. So on every, like, ABC, NBC, CBS, all the morning shows, nightly news, every major n- magazine, it was the number one medical news story of 2002, that the estrogen was bad and it caused cancer and da da da. The estrogen-only arm kept going, and they found after a couple more years a slightly increased risk of stroke, so they stopped the study. The effects on cardiovascular disease were neutral, but there was lower qu- um, colon cancer in both groups. But no one talked about that. So American Heart Association in 2020 went and looked at, they looked at ages. So there were younger women who were given HRT.

Andrew Huberman 1:13:48 Mm-hmm.

Dr. Mary Claire Haver 1:13:48 And what they found was if you started hormone therapy between the ages of 50 to 59, you had a (laughs) 50% decreased risk of cardiovascular disease and death from cardiovascular disease and all cause of mortality.

Andrew Huberman 1:13:59 Wow, so age at which you start matters.

Dr. Mary Claire Haver 1:14:02 Matters. Estrogen, so that's where there's something called the healthy cell hypothesis or, and so basically estrogen is better at prevention than cure. And it's very protective, especially in the intima of the coronary arteries. So taking that estrogen away, we lose that protection. Once the disease builds up, there's some worry that adding estrogen once you've developed atherosclerosis or plaque might loosen the plaque, especially in that first year. So which led for some people maybe to have a slightly increased risk of stroke. So when my patients come in, we are talking about these differences. It doesn't mean that after 60 you might not have cardiovascular benefit. We start losing the benefit. So t- it's, the timing hypothesis is key, and it's the years away from estrogen that's the problem. There's a great study in the British Medical Journal. They looked at years of reproductive life plus HRT and looked at cognition scores and saw that the longer your body is exposed to estrogen in any form, like whether natural cycles or exogenous estrogen of any form, and it was estradiol in that study actually, then you had higher cognition scores, healthier brains. (laughs)

Andrew Huberman 1:15:18 Which at a just very, you know, top contour level makes total sense-

Dr. Mary Claire Haver 1:15:21 Mm-hmm.

Andrew Huberman 1:15:21 ... given that estrogen is neuroprotective. I realize it might not be neuroprotective in every instance and every neuron in the brain, but it's generally neuroprotective.

Dr. Mary Claire Haver 1:15:28 Generally neuroprotective, yeah.

Andrew Huberman 1:15:30 And decline in estrogen is correlated with neurodegeneration, which does not mean it's causal.

Andrew Huberman 1:15:36 I have to ask, when they announced this study at the Watergate Hotel of all places, um, and the conclusion that they put forth was that estrogen therapies can, um, increase rates of cancer-

Dr. Mary Claire Haver 1:15:48 Mm-hmm.

Andrew Huberman 1:15:50 ... um, I have to wonder if that had something to do with what I understand is the sort of party line around cancers and breast cancers in particular, which is that you want to quote unquote "block" the estrogen receptor.

Dr. Mary Claire Haver 1:16:02 Right.

Andrew Huberman 1:16:02 You want to get in there and put, give tamoxifen-

Dr. Mary Claire Haver 1:16:04 Mm-hmm.

Andrew Huberman 1:16:04 ... or nowadays I'm sure there are other drugs that are more effective to block the estrogen receptor. It all seems to, um, pile up on the side of a story that says, you know, estrogen and estrogen binding to the estrogen receptor is pro-cancerous-

Dr. Mary Claire Haver 1:16:16 Right.

Andrew Huberman 1:16:16 ... which obviously I think you're telling us, um, in a, in a indirect and direct way now and we'll go further into is simply not the case.

Dr. Mary Claire Haver 1:16:24 If you take a healthy breast cell and dump it in a Petri dish and then marinate it with some estrogen, it's not teratogen- I mean, it's not carcinogenic. Estrogen is not carcinogenic. We live with it our whole lives. If it was, in pregnancy, for those of us who are ever pregnant, when our estrogen levels skyrocket, we would see this in- uptick in breast cancer, and we don't.

Andrew Huberman 1:16:43 In fact, I think there's some evidence, uh, for the opposite, that getting pregnant prior to age 40, is- is it true that that's protective against certain forms of-

Dr. Mary Claire Haver 1:16:51 It seems to be somewhat protective-

Andrew Huberman 1:16:53 ... breast cancer?

Dr. Mary Claire Haver 1:16:53 ... for certain forms of breast cancer, yeah. So we have this whole generation of physicians who really weren't taught much about menopause, don't understand the protective benefits of estrogen and- and- and menopause's effect on metabolic disease, and they have this men- this mentality of estrogen is bad. And so a woman walks into her... Today, 2023, they looked at the data. She goes in to her doctor complaining of menopausal symptoms, which right now are still only recognized as general urinary syndrome menopause, hot flashes, night sweats, you know, the very cliché symptoms. Documents and the charts she's having, whatever. Only 10% are offered any therapy, and they're most likely four to one to be offered an antidepressant. That is where it stands today. That is what we are fighting against, is not every woman will choose HRT, but every woman deserves an informed conversation about it, and let her make her choice. You know, if you believe the WHI data, which there are some problems there, the risk is small, okay? But did you talk to her about cardiovascular disease and diabetes and insulin resistance and her cholesterol? Because those things go up through the menopause transition with no changes in diet and exercise, and those are all, you know, you're more... Even with a diagnosis of breast cancer, the most likely thing a woman is going to die from