#1: Cracking the Code of Ovarian Aging - the Secret to Healthy Longevity? Insights from Dr. Jennifer Garrison

Jennifer Garrison is an Assistant Professor at the Buck Institute for Research on Aging in San Francisco. She is also the Co-founder and Director of the Global Consortium for Reproductive Longevity and Equality. Additionally, she contributed a chapter on female health in Tony Robbins' latest book, "Life Force."

In this episode, we explore the crucial topics of reproductive longevity and reproductive equality and examine why they matter to every woman, regardless of age or fertility plans. We also uncover valuable insights from research on these subjects that impact overall healthspan and lifespan for both men and women. Join us as we kick off our very first episode, and don't forget to tune in regularly for more engaging and informative discussions.

WHAT YOU WILL LEARN:
Understanding Reproductive Longevity: Gain insights into the importance of reproductive longevity and how it affects women's health across different stages of life.

Impact of Menopause on Healthspan and Lifespan: Learn about the effects of menopause on both healthspan and lifespan and why it's crucial to address these changes proactively.

Holistic View of Female Health: Understand why viewing the female body as a whole system, rather than isolating individual parts, is essential to improve overall health outcomes.

Hormone Replacement Therapy (HRT): Discover the different methods, benefits, and debates surrounding HRT, including synthetic vs. bioidentical hormones and the optimal duration for therapy.

Future Directions in Reproductive Health: Explore the potential for global solutions in reproductive health and the importance of staying informed about new research and advancements in this field.

01:15 What you need to know about The Buck Institute Research Lab

14:51 What are other animals' cycles?

19:10 What is menopause?

25:18 The grandmother theory

28:24 Why do ovaries go through a decline?

30:00 Why it is important to look at the female body as a whole system

31:50 How does the human system function at every adult life stage?

32:46 Menopause and lifespan versus menopause and Healthspan

35:32 How a fertility future test is done

40:25 All you need to know about Hormone Replacement Therapy (HRT)

48:18 How long is hormone therapy usually given if you start at the right time?

49:10 The synthetic vs bioidentical debate

51:54 How does hormone therapy work?

55:50 What are the different delivery methods of hormone therapy

57:17 Important topics that women should start reading up on

1:10:26 Will there ever be a global solution?

CONNECT WITH JENNIFER :

Twitter : https://x.com/jenngarrison

Resources mentioned in this episode

Book: "Lifespan" by David Sinclair

• Discusses aging, longevity, and practical tips for extending lifespan.

Book: "Lifeforce" by Tony Robbins

• Jennifer contributed to a chapter on women’s health, focusing on breakthroughs in health and energy.

Resource: National Menopause Foundation

• Support and community around menopause.

Book: "The Evolution of the Female Form" by Dina Amira

• Focuses on the evolutionary biology of women’s bodies, including menopause.

Organization: Global Consortium for Reproductive Longevity and Equality (GCRLE)

• Jennifer’s organ

Insta/TikTok: @BiohackingEve
Website: www.BiohackingEve.com

Transcript

Judith Mueller  00:12

Hello everyone. Welcome back to another episode today. We're speaking to Dr Jennifer Garrison, who's an assistant professor at the Buck Institute of Research on aging in San Francisco, and the co founder and director of the Global Consortium for reproductive longevity and equality. And you might already know her as the author of the chapter on FEMA health in Tony Robinson's latest book, life force. So today we're going to talk about all things reproductive longevity and reproductive equality and why they matter to every woman, no matter age or fertility plans. And we're also going to talk about the insights we can gain from research on these topics for over health span and lifespan for both men and women as well. So Jennifer, lovely to have you here. Hi, thank you for having me. Fantastic. So I'll leave the stage to you, and I think you're very good authority on the topic. Thanks

Jennifer  01:07

so much for having me. I'm really excited to talk to your audience about women's health. I am an academic scientist. I'm a neuroscientist by training, and I have a research lab at the Buck Institute, which is located just 20 miles north of San Francisco. It's an academic research institute like any other, and it's wholly devoted to studying mechanisms of aging. So it brings together a broad range of scientists who are all trying to understand what are the underlying causes of aging, and that the reason for that is that, of course, aging right now as a public health pandemic, it is the major risk factor for most chronic diseases of the modern world, things like cancer, heart disease, neurodegeneration and things like that. And of course, thanks to lots of research over the last few decades, we now know that biological aging is malleable, and so if we can understand what's driving it, what are those underlying mechanisms, then we can exploit that knowledge to reduce overall disease risk for all of these age related diseases at the same time. And so my lab is really focused on trying to understand how the mind, the brain, communicates with the rest of the body, and how that changes with age. I'm not going to talk about that today. I'm actually going to talk about something completely different, although in my lab, we do spend a lot of time thinking about the brain over a connection. But what I want to talk about more broadly is thinking about as we're trying to extend health span, which is really our goal. We're not interested in extending lifespan, at least not this at this moment, what we're more interested in doing is trying to understand how we can extend the number of years that someone's healthy. And when we think about human females, soon, women are going to be living more of their lives after menopause than before. And as we're making progress in extending healthy longevity, we really need to think about reproductive spam, meaning when ovaries start aging. If we don't address that, then we're going to increase the divide between men and women. And I think we're all familiar with the graph of organ function decline over time, and if you're lucky enough to live to old age, most of that decline across your organ systems is going to happen in the last few decades of life, in your 70s, 80s, 90s. But aging in the female reproductive system poses a paradox, because ovaries are aging prematurely. Now I want to be clear, aging also happens in the male reproductive system. No question about it. The difference between males and females is that in the male system, aging in the reproductive system is it's synced up with aging in the rest of the body, whereas in females, aging and ovaries falls off a cliff right in the middle of a woman's life. So ovaries are aging at about two and a half times the rate of the rest of the tissue in a woman's body. And we think about it kind of like the canary in the coal mine for human aging. So for every single female on the planet who is lucky enough to make it to midlife, she absolutely will go through menopause, her ovaries absolutely will stop functioning in the middle of her life. And so thinking about why that is and what's happening there something that I think is profoundly important. Now there's a lot of myths and misconceptions around women's health, and so I think it's always important to just level set and make sure that we're all talking about the same thing, even with an audience that's really literate in the space. So by the time I was born, I had about a million eggs in my ovaries. So human females are strange in the way that we've decided to approach reproductive biology. So around 26 weeks gestation, human fetus will have about. About 7 million eggs in the ovaries, that number drops to about a million by the time they're born, and then at puberty, that number has dropped to about 300,000 and these are all average numbers. To be clear, female physiology is one of the most complex signatures in all of human health, and so at the level of the individual, these numbers might be very different, but on average, around the time of puberty, there's about 300,000 eggs, and once a female starts cycling, she will lose about 1000 eggs per month. And so while there's just one egg that gets ovulated with each menstrual cycle, there's, on average, about 1000 that are recruited to grow and one of them wins, and the other 999 die through atresia. And that is true whether or not you're taking hormonal birth control. So a lot of women tell me that they are preserving their ovarian reserve because they're suppressing ovulation every month with their birth control, but actually it's just that one egg that you're saving the other 999, are still lost through atresia, and so once that number approaches zero, that is when a woman goes through menopause and ovaries stop working. So the science behind menopause is fascinating, but it is woefully incomplete. We do not understand number one, why women go through menopause, why ovaries are aging prematurely. We don't understand why in the animal kingdom, human females have this happen. So most animals can reproduce throughout their lives. It's us, some non human primates, a few species of whale and maybe giraffes that go through menopause were very strange in that sense. So understanding why it happens at all is actually really important. We also don't understand what the drivers are like. What is actually causing ovaries to start to age prematurely? What's pushing that forward? And then we don't understand why it's so variable the level of the individual so age at natural menopause can span 10 to 15 years and be considered normal. If you go through menopause before age 40, that's considered early, and if you go through menopause after age 54, that's considered late. But there's this 14 year window of quote, unquote, normal there's nothing else in all of biology that happens on such a hugely variable time scale. There is also this really interesting correlation, and I think it's important to point out that it's a correlation between the age at which a woman goes through menopause and her overall lifespan. So women who go through menopause later tend to live longer, and that also extends to male brothers. So there's a component here, some sort of a genetic component, that's important, not just for women, but also for men. So one of the goals that I have is to reframe the narrative around healthy aging and women. The consequences of ovarian aging are profound. Ovarian aging leads to issues like fertility problems, miscarriages, birth defects. It also can increase the risk of a whole host of different diseases. So in addition to being important and essential for fertility and baby making. Ovaries are also absolutely essential for overall health. They're endocrine organs, which means that they're making a cocktail of hormones, which are just basically signaling molecules that can signal to almost every tissue in a woman's body. So ovaries are signaling to brain, heart, bone, skin, the immune system, the breast, the fat, the vasculature, the liver. I could go on and on, but because they're they're signaling to all of these different tissues to promote health. When they stop working, when their function declines, that means that all of those signals go away, and that can lead to an increased risk for developing dementia, metabolic disorders, depression, osteoporosis, heart disease and lots of other things. And so from my perspective, you know, menopause, even in healthy females, it impacts health and quality of life, and I think about this as an issue of equality. So from the moment a woman goes through puberty, whether or not she wants to have biological children, every single decision that she makes will be overshadowed by the fact that she's going to undergo this decline in the middle of her life, decisions about family planning, about career, about health, and men don't have these concerns. Put bluntly, menopause can make a woman's body age faster, and so we've come to think about ovarian age. Teaching as a potential target for Jared protection and women, and one of the things that that we've done here at the Buck Institute is to start a global consortium whose goal is really just to build the research space around these questions, because there are a lot of a lot of things about women's health that are understudied, underfunded and just underappreciated. And we think that if we want to try to, you know, alter the societal balance towards equality for women, defining what leads to menopause, and trying to develop interventions that will slow it down, or that will hopefully try to mitigate some of those health risks, is really important. So in terms of reframing the narrative, one of the questions that I often get is, How is it that we are where we are? To put it bluntly, I think women's health in general, forget about aging, but just women's health in general, has been treated as a niche subcategory of medicine for forever in the US, it gets about 10% of the research dollars and less than 4% of biopharma investment. So we're talking about half the population, and yet the amount of funding that's gone towards trying to understand healthy aging in females, and the amount of money that's gone towards developing products and diagnostics with Therapeutics is paltry. So that's all changing. I think the dialog right now is really positive, and there's been a huge amount of movement in the space of the last few years. But before 2016 at least in the US, the National Institutes of Health, which is the major funder of biomedical research, did not require grantees to study both males and females. So what that means is that we have 80% of NIH funded studies only used male animals, and if you're only looking in males, it's really impossible to understand how female bodies are working. I think that one of the things that we need to do right now, one of the things that I'm really passionate about, is thinking about new language. So by calling them reproductive organs, I think we've allowed women's health to be pigeonholed through the lens of fertility solely, and by calling them reproductive organs, we leave out all of these other important things that ovaries do. They really are the architects of health and female bodies. And so we need a paradigm shift in how we think about them and how we talk about them, quite frankly. So I call them ovaries, as opposed to calling them reproductive organs. I hope everyone else will too, and if you have better ideas for language, I'm really open to hearing them. But in addition to a lack of funding, what that's really led to is a lack of data, right? The research we fund dictates what we know. And so right now, if, if I go to my doctor and I want to talk about, you know, perimenopause and what it means, how to measure it, how to mitigate any of the consequences that I'm experiencing, usually, the answer is going to be, we don't know. We don't know how to measure your hormones in a way that gives us data that will be interpretable. And that's not because there's not a signature there that's measurable. It's that we haven't measured it in enough women with enough time resolution and then analyzed what that data means to to make statements about what it means when your estrogen level is x and your progesterone level is y at this stage of your cycle. So what we need is, is a lot more research, a lot more data collected, just a lot more work on trying to understand what it is that drives these changes in female bodies. So

Judith Mueller  14:02

in terms of the research, I think one reason why we really have to look at that, that I think I've heard you mentioned previously, is women born today are expected to have a lifespan of almost 100 years now. So under current expectations, under the current conditions, basically, women will soon live more their lives after menopause than before. So I think that's definitely one reason why we need to look into that. I think people really need to understand, and you highlighted this, that this is also ovaries, reproductive system. This is all divorced from fertility. This is relevant to you no matter where you are in life, where you are in your cycle of life, and actually, whether you're man and a woman, and I found it really interesting because you mentioned other animals not going for menopause. Actually, menopause not being a biological imperative. It's out of curiosity. What are other animal cycles? Obviously, we as humans have a theoretical 28 day cycle plus or minus, etc, at the individual days. But what are normal cycles, or typical cycles out their nature? And do you have any idea what they're determined by?

Jennifer  15:06

Um, sure. I mean, the menstrual cycle is, is determined by a whole suite of hormones. So it's basically, I mean, I think of it like a symphony. So there's lots of different hormones that I know. The word hormone, just to be clear, it just means a signaling molecule can be peptide, can be steroid, can be small molecule can be lots of different things. It's just a signaling molecule that essentially transmits a message across a long distance. So it's a very imprecise term, but we typically, when we say hormone and we're talking about women's health, people automatically think of steroid hormones, so the big three, estrogen, progesterone, testosterone, and those are definitely players in this, in the symphony, but there's lots of other players as well, and what's happening is across the course of a cycle. And so in humans, I think it's important to say that the 28 day cycle is a myth. Something like 12% of cycles are exactly 28 days. Most women have cycles that are either shorter than that or slightly longer than that. And so it's important to say that you know what's normal for you is going to be different from what's normal for me, and that is true across every bit of female physiology. So this is a place where I think personalized medicine has a very large role to play. But whatever your cycle is, your normal cycle, however long it is, what's happening during your cycle is that there's all these hormones that are changing in different ways. So they're not all changing together, changing in different ways across the cycle, to do two things right to essentially, to make your uterus receptive, so to build up the uterine lining so that if there is a pregnancy, it can thrive and flourish. But then there's also, you know, basically, setting up ovulation, so getting your ovaries to release an egg, and all of those things happen in lots of different mammals, mice, for example, which are a really important model for biomedical research, have a four day cycle, and also the way that their hormones change, and the hormones that are involved are different from humans. So it's not exactly the same across all animal species. But you know, in general, yeah, we're all, we're all going through these, these cycles that are symphonies, symphonies. I wonder

Judith Mueller  17:30

if myself, PMS as well. That'd be an interesting one to find out.

Jennifer  17:34

Well, it's a four, it's four days, and it's not quite a it's not a menstrual cycle. It's not quite the same. They don't shed the uterine lining the way that we do, but they definitely do go through an estrus cycle where they ovulate, and it's only four days, so gosh,

Judith Mueller  17:52

it's a lot shorter, barely in and out of PMS, basically. Yeah, lots

Jennifer  17:56

of, lots of different strategies. And I think that's an important thing to point out that we don't have really great models for for the process of menopause, because there's not very many species that go through a true menopause, and because whales are not exactly amenable to research in the lab, it's, you know, it's one of The challenges, actually, that that we're facing right now in trying to build out the research is finding good models, and certainly we've funded a lot of grants to try to establish better models. And I think

Judith Mueller  18:31

especially the fact, because we're coming back to the sort of, you know, 80 to potentially 100 year lifespan that we're talking about, any changes that we're making now, we're not going to see any reliable data, 20, 3040, 5060, years down the line, basically. So really is guessing into the future. Okay, coming back to menopause, my understanding is menopause is when a woman runs out of eggs. Is it the absence of the egg that triggers an absence of the relevant hormones, or vice versa. Do we know any of that at all? Yeah, so

Jennifer  19:04

I guess this is the beginning of me saying, well, we need to do more science. So menopause is actually defined as a single day in in a woman's life. So menopause is the day just defined as the day on which a woman has not had a period for 12 months, that's it, full stop. And so the the period of time leading up to that would be called perimenopause, and the period of time after that would be called post menopause. Um, so I think a lot of times when people say I'm in menopause, what they really mean is I'm post menopause, because menopause is just a single day, and amazing, if you've got that on your calendar, but generally speaking, or thinking about the period before the period after, and I think it's important to say that we don't know what's causing ovaries. Start to age prematurely. So what's true is there is a correlation between not just the number of follicles or eggs, but also the quality, right? So over time, on average, the number and the quality declines with age. And when that number gets low, that tends to be when menopause happens. And so there's no question that fertility, that menstruation and that menopause are all intricately linked. But how you know exactly how they're related to each other, exactly what's causal there, I would say we still don't really understand that. It really is an open question, what sets it in motion, why it varies so much between individuals, and why it happens so early in humans? We don't know the answers to those questions, and that is what we're trying to solve. So

Judith Mueller  20:53

yeah, because the interesting thought, I mean, the for me, a logical thought, would have been, if the number of eggs decline, then the corresponding hormone should decline. Or is it at the point, again, we don't know. This just a conjecture. Is it basically the month where, okay, we've got less than 1000 eggs? This is it? This is where menopause are starting. So why is it a cliff, a complete cliff, rather than sort of a phasing out of a cycle? I guess it's my question.

Jennifer  21:19

Oh, we don't know. Like, why? Why you're asking? Why don't we just start with more eggs, then that that might take care of it? That

Judith Mueller  21:25

would be another logical conclusion we need to send up there or somewhere else.

Jennifer  21:29

Why, instead of 1000 why can't we just recruit the 500 to grow and that would certainly take care of things don't know. We don't know the answers to those questions. And I will also say we don't know. We don't know because we don't know what we don't know. It's not clear what the right strategy would be to try if your goal is to, you know, there's lots of different ways you can frame this problem. If your goal is to extend the number of healthy eggs a woman has when she's 50 or 45 there's lots of different strategies that I can draw on my whiteboard to try to do that, but whether or not any of them would actually work, we don't know. And I think it's really important to say that at the level of the individual, what's happening in that period leading up to perimenopause, right? So the number of eggs this and the quality of eggs is going down with time, but that period of perimenopause is characterized by fluctuations in the levels of the hormones that don't follow any stereotypical path. So perimenopause is is a period of time where hormone levels can fluctuate dramatically, up and down, and not in any way that we fully understand. So it's just a period of time where things are fluctuating, like I said, can go up or down. It's not like just because the number and quality of eggs is going down, that your hormones are also just going down. It goes like this and and it goes like this for, you know, a dozen different things in different directions, and that's part of the reason that perimenopause is characterized by such a huge range of severity of symptoms, and also just the breadth of symptoms that can occur, and it's so different between individuals. And again, this comes back to this question of why. Why is this so variable at the level of the individual? Can we understand, you know, how things are changing, why things are changing in a way that would even just allow us to predict what's going to happen, that would allow us to give women some sort of a guidepost about where they are in their own reproductive span trajectory, and also what those numbers mean at this stage, we don't really know, and that's why, you know, I think there's been a lot of news articles and also scientific articles about whether or not we should be measuring hormone levels in women during the perimenopausal transition. And the guidance right now from most of the professional societies is, no we shouldn't be measuring them. And the reason that they give that guidance, it's super frustrating. I know the reason that that guidance exists is because we literally don't know how to interpret that information. So, you know, from from a physician standpoint, and to be clear, I'm not an MD, I'm not a medical doctor, I am a PhD scientist, so I'm not giving medical advice. But from the perspective of a medical doctor, like, if we don't know what the data means, why measure it? Right? That's, that's kind of the mindset right now. And from my perspective as a scientist, I just I want to collect the data so that we can understand what it means exactly

Judith Mueller  24:47

start somewhere, and I think it's also curious. I know you've mentioned in other contexts that they're unexplained bouts of infertility in younger women and then unexplained bouts of fertility in older women. So it's not really the typical you know, you get to 35 and you sort of very rapidly fall off the cliff until, whatever it is, 42 basically. And then you even out until menopause, whenever that happens to happen for you. So again, another interesting factor to look into. Tell us about the grandmother theory. Oh,

Jennifer  25:19

coming back to the evolutionary question of, why does this happen at all? And I should say this is not my area of expertise. I am not an evolutionary biologist, but I definitely do talk to some I think you know, there's many different theories out there about why human females go through menopause, and one of them is this idea that having individuals who are past their reproductive phase, so from an evolutionary perspective, evolution doesn't care about you at all. Once you lose the ability to reproduce, right, right? You don't matter anymore to evolution. But perhaps there's a an additional benefit beyond reproduction to having older females around who can either help take care of offspring of younger women, or who have, you know, wisdom, knowledge about you know, if you're thinking about it from a hunter gatherer point of view, like where to find the food, or how to avoid predators or things like that. What I will say is that that is unlikely to be the explanation based on discussions that I've had with evolutionary biologists. It's much more likely to be a combination of factors. And I will go ahead and say, put in a plug for Dina Amira, who is one of my colleagues, who is a spectacularly talented evolutionary geneticist, who just wrote a book, actually, for the general public, not for scientific audience, about the evolution of the female forum, and she's looking at the evolution of female bodies as a whole. So there's a chapter on menopause, and it's a really great read, but it's an open question. Again, we haven't done enough research to understand what the evolutionary basis is of this accelerated reproductive decline in human females, but if we could figure that out, that would give us a lot of clues about what's driving

Judith Mueller  27:20

it? Because, again, there wouldn't be a grandfather theory, as men are in theory, at least able to reproduce until the very high age. So interesting theory. I look forward to having a look at that book. I think we've also had some some theory that was discussed previously when we said, if we could increase the number of eggs by, say, 1% in a women's 40s that could potentially delay the onset of menopause. Again, that's very, you know, statistically varied, as aware by, I think something like five to 10 years. I mean, let's do the maths on that. I think we said, what is that 1% based on? Is that based on at puberty? I think the 300,000 that was, so there will be about 3000 eggs. Oh, 1%

Jennifer  28:04

I think, yeah, would would be based on the the initial numbers of six or 7 million, you know? So, okay, so quite a few. Yeah, it's all very hand wavy, though, right? Like, I think it's important to to talk about this in concrete terms. The question is, how and why do ovaries go through this decline? And we don't know, and maybe, maybe increasing the number of quality eggs that a woman has at age 40 is one strategy to improve health span. But what I what I think is important to point out is that we don't know where along a woman's lifespan those causal driving things happen. It might be that there's some cue or timer or constellation of cues and timers that happen at different points that drive this forward. And so understanding the research needs to look at all of adult life like so what needs to understand what's happening at puberty. Needs to understand what's happening in young women, right? Because I think if you stop thinking about ovarian function through the lens of fertility, like set aside baby making for a moment and just think about it as an endocrine organ that's promoting general health. Then puberty is an interesting period of time in a woman's life, because, you know, there's a lot of hormonal fluctuations that are happening there that set up. You know, what's going to happen for the rest of a woman's adult life. What's happening in young women and their 20s is really interesting as well. You know, if there's underlying dysfunction in the reproductive system, so if a woman, for example, has PCOS or fibroids or or something else going on there that's pathologic, then there are more. Likely to have things like metabolic disorders later in life. So there's, there's a real need to think about the female body as a whole system, right, that it's a functioning whole, and that every part of the system needs to be working properly for everything else to work, right? So instead of looking at a woman's body through the lens of like one organ system at a time, we need to think about optimizing every part of the system. So having the reproductive system working properly is important for metabolism, right? And, and probably vice versa, but, but these are the kinds of, you know, these kinds of like, paradigm shifts in our thinking that we need to embrace going forward if we really want to make an impact. Here, I will also say, if you think about menopause and puberty as periods of time when, like, the endocrine function, you know the signaling function of ovaries is really changing a lot, right, in different directions and in different ways, but changing a lot. And when that happens, you know, when ovaries aren't totally working the way that we expect them to, it kind of uncovers, it sort of unmasks these underlying health risks, right? And so that's kind of, that's how I like to think about it, because then it's not about menopause, it's not about fertility, it's really just thinking about how ovaries are functioning through throughout a woman's life. And this is kind of how we're framing, you know, the way that we think about the science. Does that make sense? If you turn that around and you think like, Okay, if our goal is to extend health span, then what we want to know is, is how, how the system is functioning at every stage of adult life, and then the answers, or the the interventions, the things that we can do to impact healthspan will be different for women at different ages, right? So the the strategy that we might adopt to impact health span in a woman in her 20s will be wildly different from something that we would do for a woman in her 40s, which would also be wildly different from what we might do for a woman who's in her, like late 60s, who's already gone through menopause, right? But in order to think about how to how to tune those interventions, we have to understand how the system works. At the end of the day, what we're talking about is just understanding how female bodies work, full stop, that

Judith Mueller  32:37

big head start. Um, in terms of, I think this is less about the underlying causes, which in I think we agree on that there's a lot that we don't know. But in terms of observing that correlation between menopause and lifespan on one hand, and menopause and health span on the other, do you have any data on how strong that correlation is?

Jennifer  33:00

I personally don't, but there's, there's literature out there, and there's something like nine studies that have shown some sort of a correlation there, and I can't speak to the depth or the quality of those studies, and it is a correlation. So you know, it's interesting to think about what it might mean, but it certainly doesn't imply causation. So I think that's a really important thing to say. And again, we're talking about averages here. So it's also really important to say that if you go through menopause early, that does not mean that you're going to die young, like, that's not what that's not what this means at all. It just means that, you know, there's again, coming back to this idea of a woman's body as like a system that you know, if your ovaries stop working sooner than some other people's, and that you know that has an impact on how how your overall health is, then it's not surprising that that could impact your lifespan. But again, these are just like so early these studies, and I hesitate sometimes to even bring up that data. But the reason that I bring it up is because a lot of times when I'm talking to an audience that includes mostly men, they tune out the second you start to talk about women's health, the second you start to you say the word ovary. They're simply cells. You know, I don't have those organs. Maybe they're not interested enough for the females in their lives that they care about but I think it's important to say that ovaries are an amazing model for accelerated human aging, right? If we want to understand aging in general, understanding what's causing ovaries to age prematurely will give us clues about aging in the rest of the body, and that's important, not just for females, but also for males. And so it's something that you know, funding this research, doing these studies, it's going to impact everyone, not just women.

Judith Mueller  34:58

I agree with you, into. Terms of, have a look at, let's call them action items, what we can actually do. So there's a couple of things I like to address. But for example, one question is diagnostics testing actually see where we are on Let's take, for example, the fertility curve I remember seeing. This was in London some 10 years ago, and one of the clinics that offered a fertility future test, it was something like 800 pounds, I guess would have been like $1,200 something like that. Do you have any idea what they might have done? I guess they would have determined, AMH, so anti immuno hormone, which is supposedly a good indicator of ovarian reserves, egg reserve. Are there any other useful indicators that you're aware of.

Jennifer  35:42

I mean, a lot of the tools that we use are pretty rudimentary. We do things like take temperature. That's not to say that there aren't things coming down the pipeline. I think, right now, I think that the most promising things that are likely to lead to products and diagnostics for women are coming down the pipeline. I am not aware of any comprehensive test that will tell you where you are in your reproductive span trajectory. There are a collection of imperfect markers that you can look at, but at this moment, what you need, I think what we all would like, is to be able to sample a lot of different markers at very high time resolution across one or two cycles, right in an ideal world, when I was young and healthy and in my 20s, I would have had available to me some tests that would have allowed me to establish what was my normal, right coming back to this idea that women's physiology is variable at the level of the individual, and that it would have been great if I could have established what my normal Was that doesn't exist. We can't sample those hormones at the time resolution that you would want across a couple of cycles, and we don't even know what all of the players are in the symphony. And so that's where we are right now. I think that there's technology being developed to allow you to sample at a higher time resolution, and certainly there's a lot of very deep phenotyping that's available. It's expensive, but that's available. And I think what needs to happen, in addition to the technology development, is that then there has to be a large scale data collection and analysis of that data so that we can understand what all those numbers mean. Because right now, even if I had the technology available to me to be able to measure every single day, 20 different hormones, what that data means is still an open question. And so until we collect the data and analyze it and repeat it across large populations of people we won't know, but that everything I just described is very doable. So that's the that's a positive message here is that that is all within our grasp. Like this is not rocket science. We just need to literally do the work. And so I think in the next few years, we will see things like that coming out, and then I hope that we have a reproductive health diagnostic panel available to all of us. Beyond that, I think actionable things that I personally try to do aging in your ovaries is absolutely reflective of aging in the rest of your body. And so things that we know that impact healthspan overall, those things are also going to be important for maintaining ovarian function. And so everyone wants a magic pill, but at the end of the day, the best, the absolute best interventions that we know about for healthspan are exercise, and in women, particularly around midlife, that means strength training and maintaining muscle mass. Because, you know, one of the major risk factors for women after menopause is osteoporosis, and we know that muscle function and mass declines with age, and so maintaining a healthy amount of muscle also helps us maintain healthy bone. So, you know, strength training exercise and then paying attention to what you put into your body. So thinking about, you know, what you eat, those are the things that are the most robustly tested interventions that we know are beneficial. So there's no magic bullet at this point,

Judith Mueller  39:49

not yet. I mean, you know, we both know that Peter Tia, for example, has done great work on that to really break that down to doable level. What does that mean for individuals? Dual really put in plain terms. So a big fan of that. Um, coming back to what we can actually do. So this is, this is great, and this applies to men and women alike, in terms of women and in terms of menopause, for example. And then the hope that menopause is going to help us not just understand the human body better and sort of develop diagnostics, treatments, preventions from there, but also in terms of what we can actually do while we're still figuring that out, tell us about HRT. HRT

Jennifer  40:25

hormone replacement therapy. I would say, let's not call it replacement. Let's just call it hormone therapy. A hormone therapy is essentially, at this moment, replacing or adding back estrogen and progesterone, sometimes low dose testosterone, but typically it just includes estrogen and progesterone and hormone therapy is something that has been really controversial, mostly because of a study that was published in the early 2000s that was Based on a data set from the Women's Health Initiative, which is a large scale longitudinal data monitoring project, which you know in terms of of data, this is one of the very few data sets we have out there, and it's a spectacular resource. Unfortunately, the very first study that was published using that data way back in the early 2000s it essentially sounded the alarm that hormone therapy wasn't beneficial to women, that it didn't have any protective benefits for heart disease, and that It increased breast cancer risk. Now to be clear, there were major design flaws and analysis flaws in that study, and none of the results that were broadcast widely in the media were statistically significant. So full stop, none of that information is relevant. However, unfortunately, it was picked up by the press, and that message was broadcast, and it really translated into a whole generation of women being deprived of the opportunity to have hormone therapy. Now, again, I'm not a medical doctrine, so it's really important to say that I am not giving medical advice, and any discussion about hormone therapy or anything else related to your health should be made in conversation with your doctor. But it's, you know, there was just a lot of misinformation out there, and it it translated into a huge number of women suffering unnecessarily. So hormone therapy is prescribed, at least in the US. It's prescribed to mitigate some of the symptoms of the menopausal transition. So we touched really briefly on perimenopause. There are over 135 it changes every day, but lots and lots and lots and lots and lots of potential symptoms of perimenopause, and every woman is going to experience those symptoms differently. So the actual the universe of symptoms that I will experience is going to be different than the universe of symptoms you will experience. And if we happen to experience the same symptom, almost certainly we'll experience it to different levels, right? So some people experience symptoms far more severely than others, and so you know, hormone therapy can help to mitigate some of those symptoms, particularly things like hot flushes and brain fog, which are some of the major things that people complain about. But hormone therapy is also prescribed to reduce the risk of osteoporosis. So I think there's always a lot of questions about hormone therapy, and it's not for every woman. It's one of again, one of these situations where an individualized approach is absolutely, absolutely required. And because of all the negative press around hormone therapy for the last 20 plus years, since its inception, since it was first brought onto the scene in the 70s, until now, there has been very little innovation, very little change to how hormone therapy is administered over that huge period of time. And that's really unfortunate, because this is an opportunity. You know, while it's a band aid, it's not it's not going to change things in any dramatic way. It is one of the important band aids that we have in our arsenal right now to help women as they're navigating menopausal transition. So you know, when I when I get this question from friends and family, I tell them to go talk to their doctors whether or not hormone therapy is right for. Individual really depends on a whole host of things that are specific to you, your environmental exposures, your genetic background, all sorts of things. And so for women who are able to take hormone therapy, generally speaking, it tends to have a positive impact on a lot of different measures.

Judith Mueller  45:21

So this is interesting in terms of contraindication. I mean, obviously this wouldn't be an exhaustive list, and this needs to be discussed with the doctor, but what would be something specific examples where you say, Okay, this is where you really should have it, or this is where you really shouldn't have it.

Jennifer  45:36

I can speak to what the data says. So the data that's out there is pretty clear that in order to be beneficial, woman needs to start hormone therapy within a certain window of time of menopause. So that day, you know, that single day in your life when you haven't had a period for 12 months. So there, there is like a sweet spot of timing. And that's because, if you think about how the biology is working, right, those hormones, estrogen and progesterone, they're released from your ovaries, right? And then they circulate through through your blood, and they reach whatever target tissue they're going to signal to you. But there's two components to the system, there's the hormone itself, so the estrogen, let's say, for example, but then there's like, when it gets to the tissue that is trying to signal to nothing will happen unless there's a receptor there to to catch the estrogen, right? And so what happens is, cells on your tissues have these receptors kind of sitting out on their surface. And so when estrogen binds, actually, in this case, it's inside, but doesn't really matter. When estrogen binds to its receptor, what it does is it turns on and off a whole bunch of different genes. So it has this huge pleiotropic effect, and it's different in every tissue what it affects, but you need to have that receptor there. If you don't have the estrogen receptor present, then you can have as much estrogen as you want. Nothing's going to happen. And what's clear is that after menopause, when there's no or very little estrogen around, your cells stop making the receptor and it doesn't come back. And so there's a sweet spot of timing to reintroduce those hormones, and after a certain period of time when all of those receptors have have been depleted, they're not going to come back. And so the guidance, I think, is somewhere around, definitely within 10 years. But most of the benefit, I think, is if you start within six years of menopause. It's also an open question, and we need more research to understand whether it might be worth starting hormone therapy before menopause, during perimenopause. It's an open question, and again, we just need to collect the data to figure out whether or not that's something that would be beneficial, because

Judith Mueller  48:02

it sounds like some an obvious win to actually start doing perimenopause, ie, between month zero and 12 of not having had your periods. I think after, you know, a couple months, it's fairly obvious you are entering menopause. Okay, again, we need more data on that. How long is hormone therapy normally given for if you start at the right, quote, unquote time. So

Jennifer  48:24

in the US, for reasons that are unclear to me, the guidance is to have it to do hormone therapy for five years. There's nothing that I know of in the data that suggests there is a good reason to stop after five years. So that's always puzzled me. So you know, if I personally were going to take hormone therapy, I would continue taking it, unless there was a reason, you know, a reason specific to me that would contraindicate me, me doing that, and again, that would be a conversation between me and my doctor,

Judith Mueller  49:01

okay, and I think part of the controversy my understanding regarding hormone therapy is the synthetic versus bioidentical debate. Tell us more about that.

Jennifer  49:15

This has always puzzled me. Bioidentical sounds to me like a marketing tool women like the words natural and bioidentical sounds like very, I don't know, very sci fi, and very absolutely what I want you know. But to be clear, hormones, estrogen and progesterone in particular, they're chemicals. They have a very specific chemical structure. And if you monkey around with that structure in any way, shape or form, even if you just change one atom, then it is no longer that hormone. It's called something else. So it doesn't make any sense to me at all. The difference between bioidentical and synthetic is just a question. Of where you're getting it from, whether you're making it in a lab, or you're isolating it from, you know, from scratch, or whether you're isolating it from a particular source. So there are rich sources of estrogen and progesterone out there, in plants and also in for a long time, actually, we isolated hormones from horse urine, because horses make a lot of urine, and it turns out that there's, there's a lot of of these chemicals in horse urine. And so you can take horse urine and purify out these things. But the key piece of information that is so important to understand is that the chemical structure of estrogen is the same. No matter where you get it from, it is the same. So you can try to parse out whether it makes more sense or whether the source that you're getting it from has you know, there's going to be different. Getting a 100% pure chemical of any kind is very difficult. There's always going to be little impurities, whether you make it in a lab or you isolate it from a natural source, you'll always get some some impurities coming through. So I think the only difference between them is what impurities are coming through and how much of them are there. And that's not something you know, that's not something that's easy to make sweeping generalizations about. I think that you know, again, I would strongly recommend conversations with your doctor. And for me, I like pharmaceutical grade when I put things into my body. I like to know that they were approved by the FDA and and that they were made in a facility that may or isolated in a facility that that the FDA has scrutinized, but that's just me. I'm

Judith Mueller  51:45

with you on that one regarding how hormone therapy. I keep I keep thinking hormone replacement therapy, but I'm trying to be corrected on that one. How does it work? In terms of, does it replace a cycle, or does it stabilize hormones as an Are you mimicking a cycle, estrogen, progesterone, etc, or is it literally, get a dose of this, get a dose of this. Everything's the same every day.

Jennifer  52:07

It's the latter. So again, we don't know enough about I think it would be quite challenging to try to use hormones to reinstate or prolong the menstrual cycle. That's that would be tricky. I'm not saying it's not doable, but that would be a much more complicated problem to solve than just to provide steady levels of these hormones that then, at least in some sense, hopefully mimic the endocrine function of ovaries, right so the signaling to tissues to promote general health. Now, again, we haven't done much work to try to optimize or to try to innovate. What's in hormone therapy, right? And what the what the relative amounts are and what the overall amounts are. So hormone therapy as it exists right now is a blunt tool. There's only a few different doses that are available, and it's administered kind of like a sledgehammer. I think there's a huge amount of opportunity, and there are a lot, there's a lot of work going on right now to try to optimize it, to try to think outside the box and to innovate so that, you know, we can, there's a there's so much knowledge that we have around how these how these hormones work, and so thinking about personalizing it to an individual is something that I think is on the horizon. I don't, I don't think we're there yet, but it's something that is hopefully around the corner. A lot of women try hormone therapy and experience negative side effects because it's the wrong dose, or because, you know, because there's something about it that's not quite optimized for them, and then they stop taking it, which is really a shame. And so, you know, being able to have more options, like a larger menu of options available, I think will be quite revolutionary. I

Judith Mueller  54:06

think having, because we said it's the latter, the option so hormone levels are being stabilized if we were able to reproduce a cycle. And again, we don't have the data on that, but what is it got? Finn and do you think that would be desirable. That would be superior, or would it just be the whole annoyance of you having to bleed another, you know, whatever it is, X number of years,

Jennifer  54:27

I genuinely don't know. I'd like I said I think that we have a very clear picture of what is happening across a menstrual cycle for about a dozen different hormones. We absolutely know the main players, right? We call it the HPG axis, the hypothalamic pituitary gonadal axis, and that part of the symphony we understand with great detail. And that is, I think today, if we were to try to would be complicated, but if we were to try to mimic. What's happening with what we know. I don't know if that would actually work, because I personally think that there's a lot of things that we have yet to discover that are that are part of that symphony, and I don't know why you would want to do that. That's the other thing. I'm not sure. I'm not sure what that would accomplish. You know, in terms of thinking about health span, even in terms of thinking about fertility, it's hard for me to imagine why you would want to do that. Yeah, that's

Judith Mueller  55:27

I was just saying, if there's some hidden benefits to having, you know, for example, when you have supplements and you have to cycle them three weeks on three weeks after, if there's any sort of potential benefit, the same way, you've got estrogen three weeks on three weeks off or whatever. But I guess studies would have to with some brave participants who are willing to do that. Will have to find out, speaking of of sort of methods, what are the different delivery methods for hormone therapy? Yeah, that's

Jennifer  55:55

an important thing to to talk about. Well, you can take them orally, or you can have them delivered through a transdermal patch. And those are the two methods that I think are the most well studied. There are also, you know, you talked about bioidentical hormones. There are sources of hormone therapy that are made in compounding pharmacies that are like little pellets that you put under your skin. I personally don't think that's a great idea. I think that, well, what the data says is that oral estrogen can be metabolized by the liver into clotting factors, and so there is a risk, there's an increased risk of stroke and other things that are related to increased clotting factors with oral estrogen, I think that the recommendations that I've seen are that you should take transdermal patches. But again, I'm not a physician, so it's important to follow all this with your doctor.

Judith Mueller  56:58

Okay, and I know you've touched on a couple of things in life force, both regarding hormone therapy, as well as other things. And I really highly recommend everyone go and read that. Are there any other topics that you really wish that women out there would really know about, would start reading up on? I wish that women

Jennifer  57:18

would, and this isn't their fault, honestly, but I really wish that women would make sure they understand their bodies, and that starts with like basic biology, right? We get a little bit of basic biology about our bodies, usually in junior high, when we have sex ed, right? But when we're learning about puberty, and we're learning about the changes our bodies are going through, and we're also learning about how not to get pregnant, right? All of the information about female bodies is channeled to very young women through the lens of how not to get pregnant. So I think it's important that women sort of take back the power in a way, and learn about how their bodies work outside of fertility, right? That they understand, like, what all these organs are, that we have, that men don't have, why we have them, how they work, and then thinking about what to expect at different stages of your adult life, right? So, like, what's your normal? If you know what your normal is across a menstrual cycle, if you know what your normal is when you're in your 20s, you can actually leverage that information, right? I think when I was young, I viewed my menstrual cycle as like the enemy. You know, I had cramps. It made me irritable. Sometimes it made it so that I couldn't focus sometimes, and so I was constantly looking at it as like a negative. But actually, if you understand, if you really understand your body, and you are in tune, if you really understand what's happening in your body across the cycle, you can, you can leverage that right. You can actually use that to your advantage, and you can also plan your life in a way that makes it so that if you know, if you know, you're gonna be extraordinarily irritable on a particular day, then you can avoid having important meetings, or, you know, being around people who especially irritate you. So I think I would just encourage women to really learn about their bodies. And like I said, it's not their fault that that there's no point in our adult lives when we're given any education about this, not by our doctors, not by anyone, but that information is available like it's out there if you want to find it, and it's becoming more and more accessible, and we're learning more and more every single day. And so understanding what's normal for you, paying attention to your body, you know, and and understanding when something changes, whether or not it's something that you should go see a doctor about, right? I think. So a lot of women go through, go through health issues and ignore them, right? Because we're sort of trained to expect that there's going to be some kind of, like, low level of dysfunction in our reproductive systems. And so, you know, if we have a little pain, or if there's something that's a little off, like, that's, you know, just like, well, that's just what happens, as opposed to, you know, knowing what your normal is, and then recognizing when something is not right and going and getting it addressed, as opposed to just like, powering through. That's something that I think requires a real mind shift.

Judith Mueller  1:00:39

Are there any good resources you would send people to, gosh,

Jennifer  1:00:43

if you're interested in there are more and more lots of really great resources. We're trying to actually collect them on our website. We call them trusted partners if you, if you're looking for information about menopause, the National menopause Foundation has a great site. They've done an excellent job of creating a forum for women to talk to each other, which I think is really powerful. There are the professional societies in each country that deal with women's health, so they'll also have lots of great resources on their website at in the US, the NIH has an office for women's health, and so you can go there to see what the what the current research is that's happening. And our website, gcrly.org, which we're actually in the middle of retooling, we're putting together a Knowledge Hub, which we hope will be a place that women can go for information that is vetted by scientists and doctors and that is not trying to sell you anything. One of the really like double edged sword pieces of of the huge interest that's that's happening right now in women's health is that there are a lot of companies that are popping up selling products. And so if you do a Google search for PCOS, you're going to come up with a whole list of things that are cute little factoids that when you click on them, will take you to a product website, which I think is a little counterproductive, and we are also in the middle of a rebrand. So I said, I don't think we should call them reproductive organs. Well, we have reproductive in the name of our global Consortium, and so trying to get away from that. I think calling them reproductive organs really does limit the conversation. So we're rebranding as productivehealth.org where the word reproductive has the R E crossed out to make it clear that we're talking about all of women's health that we're talking about every woman who has gone like from puberty through death, and that, you know, we're expanding this conversation to be a lot bigger than just fertility. Fertility is an important piece of it, no question. But it's not the only piece. And

Judith Mueller  1:02:52

I think that's the key takeaway for me, at least final curveball of the conversation. So I have heard through the great wine, apparently, there's a paper. Haven't found it yet, where part of women's ovaries were frozen at some young point, whatever there was, 20s, early 30s, probably to later be implanted back at, I guess, around menopause. I don't know if that's been done yet. If that's a theory, if there's actually paper on that, have you heard anything on that? Oh,

Jennifer  1:03:18

it's more than a paper and more than a theory, let me step back and just start from the beginning. So, so this, this goes back all the way to IVF, which was developed originally not as a fertility treatment to allow random women to have babies, but it was actually developed in situations where women were undergoing cancer treatment, right? So when a woman goes through chemotherapy or radiation treatment for cancers, that treatment will kill all of the follicles in your ovary like full stop. And so women who are undergoing cancer treatment are given the option of freezing their eggs before they go through chemotherapy or radiation, and that allows them options to preserve their fertility, and that's super important and really amazing that we can do that. But what do you do if you have a girl who is too young, if she hasn't gone through puberty yet, and she doesn't have any eggs to freeze, but she has cancer and you need to treat it. So what are the options there? So someone, a long time ago, decided to, rather than try to freeze eggs where there are none, to actually freeze a piece of ovarian tissue from those young women and they so, you know, it's an invasive surgical procedure to take out a piece of ovary. But there's lots of papers, actually, and lots of studies showing that if you freeze ovarian tissue, slice it up, freeze it and then take a piece of it later on, so decades later, in some cases, and put it back in the body. And it doesn't even have to be necessarily, anywhere near the ovaries, any place is vascular. Rise so back of the arm, but you put it back, and that is enough. So to be clear, there's no eggs there, right? There's primordial follicles, but there's no eggs in that tissue, but that that has been enough, in some cases, to restart the conversation between brain and ovaries, such that women can start to menstruate again, such that they can actually conceive and have children that way. So it doesn't work every time. But from my perspective, what that tells me as a scientist is that there's something, there's something in that ovarian tissue, some kind of a hormonal factor, or maybe it's a cocktail of things. There's something in that tissue that's not related to a fully developed follicle, but there's something in that tissue that can restart the conversation between brain and ovaries, and so a lot of the work in my lab is aimed at trying to discover what those factors are. Now there are clinics in some countries that advertise this as a menopause treatment. Now, as far as you know, what you can do to your body, crazy things you can do to your body at menopause, I would not recommend this. And it's not something that's, I think ever going to be some kind of, you know, a global solution, right? Because what you're talking about is a very invasive and risky surgery that you would have to do when you're young. We're talking about storing tissue and preserving it for decades, so paying for that, and then at some point later in life, having a second invasive, risky surgery for something that, you know, the statistics, I don't, I don't know what the current statistics are, but, you know, it doesn't work in every case. So it's not a generalizable solution, but it is a really important piece of data that that tells us that there are things that are yet to be discovered that can, hopefully, you know, help mediate that, that chemical conversation that that needs to happen in order for, in this case, for fertility to be reinstated.

Judith Mueller  1:07:09

So let me understand that so, so young woman not cycling yet, you're removing part of the ovary. So there's no eggs yet, but it has the Promote primordial follicles that would ripen into eggs down the line that

Jennifer  1:07:24

would become follicles. Yeah, it's important. You know, the terminology we threw around all these terms like egg, oocyte, follicle, really, what we're talking about is the follicle is the whole unit, so there's the egg inside, but then there's cells that surround the egg that actually help it develop, and then, you know, basically mature it to the point where it can be ovulated and competent to be fertilized. So there's a lot of steps between the primordial follicles that you have when you're born and getting to the, you know, the thing that can be ovulated. So in young women who haven't gone through puberty yet. Of course, they have all those primordial follicles, but they don't have any of this other stuff,

Judith Mueller  1:08:05

and the the other stuff, so they lose the other stuff, or potential other stuff, in chemotherapy, say, and then you're implanting this frozen part of ovary somewhere in the body. So, but it's not then to have her her cycling again, I guess you wouldn't be ovulating, though, because all the the follicles have died in chemo, and you're implanting part of the ovary somewhere in the body, so not necessarily next to the fallopian tubes, where you can actually have something reach the uterus. So which is she getting donor eggs at this point implanted? So we just recycling? No,

Jennifer  1:08:43

no, it's having that tissue put back. In some cases is enough to restore through mechanisms we don't understand, but it's enough to restore ovarian function. Some women do menstruate. Some women then can go on to ovulate and conceive and carry a pregnancy to term. So there have been babies born this way. So whatever damage was done to the ovaries, you know, decades before, from the chemotherapy of the radiation, it can be reversed. No idea how that works. So these

Judith Mueller  1:09:14

eggs that are then fertilized, they have ripened out of eggs that were in her body when she underwent chemotherapy that when viable, before the ovary that was removed, the partial ovary was re implanted. I

Jennifer  1:09:27

don't know that we have that information right, because here's the problem, like, here's the here's the problem with answering that question. How can you measure that? So how do we measure things in humans? We can't. It's not like it's it's not a mouse. We can't sack the mouse and take the ovary, right? Women like to hold on to their ovaries, as it turns out. So how can we measure that? Right? We can see using like ultrasound. We can measure these markers in the blood, like AMH, and we can see that there are now follicles there. How did they get there? No idea. Yeah, yeah. If we could just take the ovaries and then cut them up and dissect them and and look at them, that would tell us a lot, but, but, yeah, that that's not something we can do at humans. Okay,

Judith Mueller  1:10:10

so a long way ahead. You mentioned a global solution earlier. Do you think that hormone therapy could be potential global solution? Or do you think there's something in the works? There's, you know, a known, unknown, or even an unknown unknown that is going to become the global solution. Whenever that's going to happen, there will be

Jennifer  1:10:26

no global solution. I think it's really important to kill that idea. It just comes back to this idea that your physiology is complex and that it's it's dynamic, right? So there will be no global solution. I don't think, I mean maybe something that would be applicable to very young women that, you know, once we cycle through all of us old people who are too old for whatever that intervention is, maybe, you know, in a few decades, there will be something that's just universally applied. But what we're talking about is a menu of different potential intervention points that have a menu of different strategies to address healthspan at different ages.

Judith Mueller  1:11:09

So it's obviously socio economic impediment to some degree, but you think there's actually underlying biological impediment that we're not going to have a one size fits, hopefully everyone or sort of everyone's solution. I

Jennifer  1:11:22

don't think it's it's just it doesn't make any sense, right? If you think about how ovaries work, and if you think about what's happening in your body when you're 20 versus when you're 30 versus when you're 40 versus when you're 50 versus when you're 60 intervening, no, first we have to understand the biology at those different time points. And once we understand it, then we can think about ways to maintain it, right. But how you maintain health starting in your 20s versus how you maintain health starting in your 60s is very different, and it's a real logical fallacy to think that there's going to be some magic bullet that, or pill or thing. This is true for aging research, too. The idea that we're going to have one thing that will just work at any age, you know, across any sort of health background, is silly. It's just that's just not how your body works. We're not two dimensional. We are complicated machines. Tell

Judith Mueller  1:12:21

me about it. Fantastic. Jennifer, it's been an absolute pleasure. Where can people find you, follow your work, support you well

Jennifer  1:12:29

and certainly on LinkedIn. I'm also on Twitter or X right now, our website is G, C, R, L, e.org, a global Consortium for reproductive longevity and equality, we're a nonprofit. We give away grants to scientists, but we also building a lot of resources in this space, both for women and for physicians and for scientists. And when we rebrand that website, will redirect to our new website. But I would love to hear from people. I love getting questions. I'm happy to talk to anyone about this, my goal, truly is to just facilitate getting that research done and translate it as fast as possible. That is truly our goal. And so however we can accomplish that, that's our

Judith Mueller  1:13:11

mandate. Fantastic. Thank you so much for coming on.

Jennifer  1:13:14

Thank you for all your insights.