Hormone therapy — replacing estrogen, progesterone, and sometimes testosterone — in female bodies as they approach and enter menopause has been met with fear and warnings that these chemicals could harm long-term health, from increased risks of breast cancer to blood clots. Yet, that belief is founded in myth and misconception, says, Dr. Stephanie Kuku, Dr. Kara Goldman, Dr. Heather Hirsch, and Dr. Jennifer Garrison during “The Science of Women’s Health” session at DOC 2025 in Yountville, California.
“Hormone therapy for women right now, is really underutilized,” says Dr. Garrison. “It’s not perfect. It doesn’t work for everyone. But what we do know about hormone therapy is that it reduces all-cause mortality.”
Weeks after their talk, the panelists earned the highest level of validation when the Food and Drug Administration (FDA) removed the black box labeling on hormonal therapy that had kept women from pursuing these options for more than 20 years. With just 2 to 5% of women currently on hormone replacement therapy, the FDA’s decision opens the door to not just relief, but a potentially longer health span.
Women’s health, as the foundation of human health, underscored many conversations at DOC 2025, including the standing-room-only session moderated by Dr. Kuku. The thread throughout the morning’s talk sat anchored in the understanding that female bodies hold the kernel to helping everyone live longer, healthier lives — men included.
While bodies differ based on sex, one unifying truth holds: “women’s health is human health,” says Dr. Garrison and “a window into systemic health decline,” says Dr. Goldman. Ovaries in particular are far more important than directing fertility in women — they are critically promoting and directing the overall health of the female body, or as Dr. Garrison names them, “the pacemakers of aging.”
You can hear from this extraordinary panel of doctors and researchers about the research transforming our understanding of aging in the video, or read our transcript below.
TRANSCRIPT:
Dr. Stephanie Kuku
It’s wonderful to be back here. We have three amazing women here. The field of women’s health has so much to teach us about longevity, science and unless you’ve been living under a rock, I think everyone knows that the ovary is a critical driver of healthy living in women. We’re going to start with the science. Understanding the science is key to understanding the future and the opportunities that lie ahead for women’s health span.
We’re going to start with a pioneering new biologist whose research aims to identify novel markers of aging in women. She is a professor. She is an academic. She’s a founder, Until recently, the Co-director of the Institute of Healthy Aging and Women at the Buck Institute. But currently, on the faculty of UCSF’s Department of Cellular and Molecular Biology, amongst other things. She has a long list of awards. She is formidable. She’s a friend. Jennifer Garrison.
Dr. Jennifer Garrison
Thank you. I’m really excited to be here. And thank you to Jordan, to John, to Stephanie, to Julia, to the entire team. I think this is really exciting. I’m really actually pleased that you’re all listening to this because I think, you have the opportunity to take what I tell you right now, and what we all talk about here on this panel, and transmit it to a much larger audience.
I’m here to tell you, just to set the stage for what we’re talking about. Then, hopefully by the end of my eight minutes, you will agree with me that understanding female bodies will actually help everyone live longer and healthier, including men. So stick with me here. You don’t have to be a scientist or a doctor to understand that female and male bodies are different.
You can see it with your eyes, but that extends further down to the cellular, to the molecular level. There’s lots of diseases that manifest the same between the sexes, some that manifest differently, like heart disease and some that are only in one or the other, like endometriosis or prostate cancer. But it’s pretty clear that we know a lot more about male bodies than about female bodies.
We are not here today to rehash all the things that we can agree on, societal taboos, systemic sex bias and biomedical research, underfunding for research, and also a lack of funding for women’s health companies has led us to this point where the female body is like a puzzle that we have not yet solved.
I think most people actually don’t understand that at baseline, females have a shorter health span than males. So if you’re female and you’re lucky enough to live to old age, then you are going to spend a significant period of time at the end of your life in poor health, suffering from one or more age related disease, about 25% longer than if you were a man. So let that sink in for a second. In America, that means that for most women who live to old age, they will spend about 12.5 years on average at the end of their lives, suffering from one or more age related disease. Why is that? That was something that really, drove me kind of crazy.
It’s because we have these organs, ovaries that are aging faster than the rest of the tissues in our bodies. We call them the canary in the coal mine for aging. The fact that that’s happening is what setting up this disparity in health span. It has a profound impact on female health span.
I’m here to tell you that ovaries are not just egg factories. They are for more than baby making. I beg of you, if you don’t remember anything else that I say, please stop calling them reproductive organs. They are important for more than just fertility. And for menopause. They are sitting at the center of a really complex signaling network, a beautifully complex signaling network, and they are talking to almost every tissue in the female body.
They’re talking to your heart, to your bones, your brain, to your skin. I could go on and on. There’s the list. But what they’re doing is they’re promoting health. We do not understand with any resolution what those chemical conversations are. That’s the gap in the science. But what we do know is what happens when you take them away or when they’re not working properly.
One way to think about it is that they are promoting health throughout a woman’s life. And they are important for health at every age. So if ovaries are not working properly, that uncovers different risks for your health depending on your age. So if you’re ten and you’re female and your ovaries aren’t working properly, that means that you might have issues going through puberty.
If you’re 20 and your ovaries aren’t working properly, that might uncover risk for things like primary bone insufficiency or primary ovarian failure in your 30s. If your ovaries aren’t working properly, that uncovers health risks for things that we’re more familiar with, like miscarriage and infertility. And in a woman’s 40s, when her ovaries start to fluctuate and function, that uncovers all of the 135 symptoms that are associated with perimenopause risk for those symptoms. The reason that there’s so many is because if you believe what I told you about ovaries sitting at the center of this complex network, all of those different conversations can change in different ways. When ovarian function starts to fluctuate at perimenopause and so at an after menopause, it uncovers risk for things like increased risk for cardiovascular disease and a whole host of other things that we’ll get to in our panel.
But the key is that throughout adult life, ovaries are important for immune function, for metabolic function. If they’re not working properly, it can change your health risk profile. We call them the architects of health and female bodies, and they are also the pacemaker for aging. Again we don’t understand how they’re working. This is the gap. This is where the science needs to catch up. But what we can say is that the cost of not including female data in our knowledge base, it actually extends beyond adverse effects in women. It’s actually when we miss sex differences, we are missing opportunities for breakthroughs that would impact health in men as well.
One example out of dozens that I could tell you about if you catch me later, is that, you know, male and female immune systems are different. Female immune systems are much better at responding to viruses and dealing with vaccines. If you think about the Covid 19 pandemic, men died at twice the rate of women. We have absolutely no idea why. But differences in immune function, had we understood them better, might have helped us change that that stat. There’s a lot of things like that.
It’s a compelling shift that, that we’re looking at here. For every one of you in the room, whether you participate in terms of philanthropy, investment in women’s health companies, or whether you personally get involved in some way, you all have the opportunity to help us change this trajectory.
These are the statistics. Every $350 million invested in women’s health research, that’s not very much money, should generate around $14 billion for the economy. Now that’s a 40 X return on investment, which I think is better than most markets. That’s on the research side. On the investment side, we are talking about 4 billion people on the planet. There are female.
This is a huge market. I’m not going to go through all the numbers. But we’re talking about tens if not hundreds of billions of dollars in terms of market opportunity. There’s literally no reason not to think about this as a place to get involved. When we talk about these puzzles, solving them is a plus for everybody.
We’re going to talk on this panel. You’re about to hear from two amazing physicians who are going to dive into the clinical aspects of ovarian aging, and also some of the more practical things that we can do. But what I would say is that while we’re waiting for the science to catch up, there are a lot of things that are available right now in modern medicine that are not being applied to women.
There’s a huge opportunity for women to take control of their own health care trajectories. We’ll talk about that. But thinking about cardiovascular health, thinking about understanding your normal approaching menstrual cycles as a superpower that you should leverage instead of something that you have to deal with. Thinking about preventative health. For women’s health, female physiology is complex, and we need to actually acknowledge it and treat it that way. That means that personalized medicine, personalization of approaches like hormone therapy, these are going to become really important as we move forward.
I just want to set the stage for some of the conversations we’re going to be having. Hormone therapy for women right now, is really underutilized. It’s a bandaid. It’s not perfect. It doesn’t work for everyone. What we do know about hormone therapy is that it reduces all cause mortality if it started within ten years of menopause by 30%. We need to turn the conversation around, and certainly it’s a conversation between a woman and her doctor about risk and benefit.
It’s not perfect and it’s not right for everyone. But it should be that we start with hormone therapy, and then we discuss whether there are reasons you shouldn’t take it. We have 50 years of data to show that estrogen is going to reduce your risk of cardiovascular disease, osteoporosis, cognitive decline, and a whole host of other things.
I’ll just end by saying that, for centuries now, female bodies have been underserved, understudied and underfunded. And I think we’re all here to demand better. We can do better. We as a group, you as a group can help with this directly. I’m asking you to do that. I think we want to choose knowledge over ignorance. We want to invest in understanding all human bodies. Because at the end of the day, women’s health is human health. So thank you.
Kuku
Thank you. Jennifer. Our next speaker, is going to move on into the clinical implications of ovarian biology. She is a professor of reproductive endocrinology at the Northwestern University Feinberg School of Medicine. She’s also Medical Director of its Fertility Preservation program. Your research is looking to uncover the gateway of preventative health in women. I’m super excited to hear your talk.
Dr. Kara Goldman
Thank you very much. Transport yourself for a moment to a fertility center at a major academic medical center in Chicago. We meet a 30-year-old woman. She’s smart, she’s proactive. She’s health conscious. She has done everything right. She and her partner have been trying for a year to get pregnant, unsuccessfully. We talk about her biology, and she realizes she knows nothing except how not to get pregnant.
We review her lab results. We discuss her AMH level anti-Müllerian hormone. It’s the best marker we have of ovarian reserve. It’s the quantity of eggs remaining. It is not a perfect test, but the best we have. She learns in that moment that her number is exceptionally low. Not only does this predict, a poor response to medications that we use in in-vitro fertilization, there is a clear correlation between AMH and time to menopause. She is aghast that the first time she is hearing this is in the context of inability to conceive, and not years earlier. Because you see the ovary is a window into systemic health, and we are only looking through it at the time of infertility. But we should be looking so much earlier. Think about all of these earlier opportunities. Here we are meeting the patient at 30 years old. But what about six years earlier when she had severe pelvic pain? She was started on a birth control pill to control her pain. But maybe that pain represented endometriosis and endometriosis. There is a 7- to 9-year diagnostic delay. It’s no surprise it wasn’t diagnosed immediately, but there is an association with accelerated ovarian aging.
What if she will go through menopause early, and what could we have done differently? And what about when she was ten years old? Her mom went through menopause at the age of 40. But our patient didn’t know that because they never had that conversation. And it was only until we had a visit. And I said, when did your mom go through menopause, and she texted her mother, and this happens in every single consult, and that’s when she found out. Why is this conversation not happening earlier? When we know that that relationship between a mom’s age of menopause and a daughter’s is really clear. And if that same patient had gone through chemotherapy for cancer or had a genetic predisposition to low ovarian reserve like a BRCA1 mutation, Fragile X mutation, Turner syndrome, these are all opportunities that we could have intervened.
And in utero, we know that the majority of egg cells are lost in utero. There are 6 to 7 million eggshells at 20 weeks of gestation. By birth, 1 million remain. By puberty, 300,000 remain. By menopause, 1000. The vast majority is follicles, serve an endocrine function, not a fertility function, and we are only watching as that decline has already happened, rather than prospectively.
What I’m really worried about with this patient, she’s worried about her fertility. I’m particularly worried about what’s going to happen when she completes her family, and we then have decades remaining. She, if she goes through menopause early, will have an earlier risk of cognitive decline. So significantly greater risk of Alzheimer’s and vascular dementia. If she goes through menopause early every one year earlier of menopause is going to correlate to a 3% greater risk of incident cardiovascular disease. Every one year earlier of menopause increases her risk of fracture by 2%. And if she goes through menopause before the age of 45, she has a 50 to 100% greater risk of hip fracture, with significant morbidity and increased risk of mortality, and all cause mortality is greater with early menopause. For every one year earlier of menopause, there’s a one year shortening of lifespan.
So let’s dive into the biology of the ovary to understand what we can be targeting here. So the ovary has all of the egg cells it will have at birth. They sit in little primordial follicles that surround the edge of the ovary. This is where there’s dormant egg cells that are dormant at prophase of meiosis 1, Follicles activated to become a growing follicle. Once that follicle is activated it is lost. This activation is critical. And this is the key to maintaining follicles in this dormant pool.
Let’s take ourselves to Easter Island for a second. Everyone in this room is very familiar with rapamycin and mTOR. We know that mTOR activation is associated with age-related diseases, and it’s a very attractive target to promote longevity. But it also plays a critical role in the ovary. And mTOR is critically involved in that activation from primordial follicle to primary follicle.
This is an opportunity to harness that ovary and harness the potential that of those follicles. We return to our clinical console room. We have in front of us our patient. Let’s think about the different ways that we can utilize the biology of the ovary to potentially protect the ovary and protect her future health span.
So first, the acute consult. I have a young patient in front of me who has a new diagnosis of breast cancer. She will be faced with significantly anatoxic chemotherapy that will either render her ovaries completely dysfunctional post-treatment or, severely, suboptimal. But there’s a higher risk of ovarian insufficiency after chemotherapy. The only option that we can offer her right now is we can freeze eggs and we can freeze embryos. That is certainly only viewing her ovary through the lens of fertility. But we can do nothing to protect her ovaries from the long-term risks and consequences of ovarian insufficiency. In a mouse model, my question was can we look at mTOR inhibitors to protect those primordial follicles and maintain follicles in that state to protect ovarian function. In mice it was absolutely effective. So we administered cyclophosphamide, a very toxic agent, to the ovary alongside mTOR inhibitors everolimus, INK128, and primordial follicles were protected and fertility was protected.
What we didn’t expect to find is that even without treatment, and we were just looking at mTOR inhibitors alone, there was a significantly greater pool of primordial follicles. So these follicles were protected, and, and potentially this has an implication for ovarian, reserve, long term and reproductive longevity and ovarian function long term. What we did was we mated mice at a young age, after exposing them to mTOR inhibitors and looked at their reproductive function over the course of many months. At a very, advanced age, saw that the mice that were exposed to these drugs had significantly improved reproductive function, which, of course, looking at fertility, it’s just a proxy for the ovarian function. But improved ovarian function over time. We are now translating this in other and other models. I’m partnering with Oregon Primate Center, who have treated rhesus macaques with rapamycin and caloric restriction. We’re studying their ovaries, and what we really need to do is if we are going to translate this to humans, we need to understand how these drugs interface with the ovary in humans.
There’s a population of patients who take these medications, takes relevance for lymphoma angio mitosis. We’re studying the ovaries of these women. They are young, they have ovaries. They are on single agent treatment, and evaluating what do these drugs do to these patients’ ovarian reserve, and what could this mean for other patients if we were to consider this as an intervention.
In my clinical space, I take care of women who are going through infertility, egg freezing. In the embryology laboratory, we have access to a tremendous rich opportunity to study ovaries. In young women who are freezing eggs, we can remove the cells from the outside of the egg that would otherwise be discarded and study markers that may be promoting aging. And the same for our older patients who are 44 years old going through IVF, we can study those cells. In fact, the heat map that you see, it’s a representative heat map. The red indicates upregulation of kinases. These are proteins that modify other proteins. We’re seeing this upregulation in these older patients potentially targets that we can look at that are associated with aging in the ovary and thus would have implications for the health of the ovary and health span.
Ultimately, if we are going to think about translating this to humans, we need to understand dose, duration, timing. How would this actually work in practice? Would we take care of women at 30 and administer a medication and try to protect their ovaries, not just from a fertility standpoint, but from an ovarian health and longevity standpoint? My area of focus is on follicle activation. But there are so many other targets within the ovary. We focus on the cells surrounding the ovary, and we can focus on the vasculature within the ovary. We know that vascular decline is of course a critical part of aging. Systemically, we don’t understand what that looks like in the ovary. We have so many opportunities, and we need to harness these opportunities to protect women. Because the ovary is so much more than fertility. The ovary is heart, brain, bone, and every other organ system.
We return to our clinical setting with our patient in front of us. She has completed her family. Hopefully she has been successful with in vitro fertilization or whatever tools we have. She wants to know how can she support her ovaries moving forward. We need better biomarkers, we need earlier intervention, and we need to view the ovary as not just a window into systemic health decline, but a therapeutic opportunity to promote health span. Thank you.
Kuku
I’m looking forward to seeing a lot of your work being translated into practice, and new drugs and therapeutics and biomarkers for women. Our next and final speaker is going to take us into menopause prevention, longevity and how you can help us live better for longer once we reach perimenopause and menopause. Heather is a board-certified clinician. She set up the menopause clinic at the Brigham Women’s. She’s on the faculty at Harvard Medical School. Heather is she’s not quite a doctor, an influencer, but she’s a celebrity of sorts. She doesn’t try and sell you supplements. She shared the stage with Oprah and Drew Barrymore, but her superpower is that she’s an educator.
She’s passionate about educating health care professionals, and the wider audience about menopause and how we can help women. So educating people to help other women. I witnessed today seeing one of the members of DOC go up to her and say, “Can you come and teach us in our clinic how to look after women better?” Which made me so happy. Heather Hirsch.
Dr. Heather Hirsch
Thank you, everyone, for, inviting me. It’s such a privilege to be at this conference. So I never thought I was going to grow up and be a menopause doctor in fact, that was not really on my radar. I always wanted to take care of women. After I did my internal medicine residency, I did fellowship at Cleveland Clinic, I was really interested in long-acting contraception. I wanted to help women know more about their bodies, peri-, partum-, postpartum. But when I saw my mentor treat women who came to what we called, “the Mistake on the Lake,” Cleveland, for all these crazy symptoms that they didn’t know what was happening to them. They thought they had dementia. They thought they were never going to sleep again. They lost interest in things like sex and even decorating for the holidays. When she treated them with menopausal hormone therapy, I thought to myself, what is going on? Because they would come back full of life and reborn. I knew that that’s what I wanted to dedicate my career to, and that’s what I’ve been doing. That’s what I just love doing, teaching because I didn’t get any education on this when I was in training.
I want to ask you because this is important. So I need to ask a question. So I need a show of hands. Who here does know this recent study? 70,000 women were in a randomized, double-blind, placebo-controlled study that showed an intervention that increased women’s health span by 3.2 years.
Who knows that study? We’re going to talk about the forgotten longevity date. Nobody knows what study I’m referring to. Come on somebody. All right. The Women’s Health initiative. Great. So I want to start by talking about the forgotten longevity data.
In the 1980s, in the 1990s, in fact, the American College of Physicians in 1992 strongly advocated that women use hormone replacement therapy. Most women in menopause, early in menopause were given Premarin, a conjugated equine estrogen, and the clinician saw that it was increasing their lifespan, reducing heart disease and reducing fractures. Then they came up with a randomized control study called the Women’s Health Initiative. The Women’s Health Initiative changed the game in a good way. But unfortunately, we’re stuck somewhere deep in myths and misconceptions about what the science actually showed.
This study was 70,000 women randomized to placebo or menopausal hormone therapy. They found that women who took the menopausal hormone therapy lived on average 3.2 years longer. Name one medication that we know of that already does that. They also had less cardiovascular disease, the leading cause of death in women. They lived longer, they had less fractures, and they had amazing quality of life.
Now before we go any further, let me define what’s menopausal hormone therapy. We use this blanket statement. But it can mean so many things. Menopausal hormone therapy for most women is an estrogen replacement either in the form of patch pill, spray or gel. FDA-approved is what I strongly recommend, because it has the safety data to go along with this.
I have an ice cream cone theory about hormone therapy, where estrogen is the ice cream, it’s really the main ingredient. That’s what actually helped women have less heart disease. Live longer. If you have a uterus and you’re taking estrogen, you need to take some progesterone with it, and then some women will add some low dose transdermal testosterone. Some women will add low-dose vaginal estrogen. But it’s very personalized. That’s important because some women may be on just progesterone and testosterone. Some women may be on vaginal estrogen and progesterone. Some women may be on all four.
We have a medication that has improved health span for women in many different organs. The fact that we are not speaking about this every single day and helping women understand menopausal hormone therapy is absolutely wild to me, is the reason I get up every single day and do what I do, whether it’s teaching students, whether it’s seeing patients, and whether it’s going on social media, because this information is pure gold.
While I know all the science behind this, and I only have a few seconds for this slide, hormone therapy-reduced osteoporotic fractures, of which one and two women will suffer from, of which more women will have an osteoporotic fracture than heart disease, breast cancer and strokes combined, costing trillions in health care. Women’s leading cause of death is cardiovascular disease. In the Women’s Health study, the women who took hormone therapy also had less cardiovascular incidences, MI’s and lived longer. They had less diabetes. Can you believe that? Women who took menopausal hormone therapy, this is science, this is not opinion, had less progression to the development or diagnosis of diabetes. They also had better brain function and improved their quality of life significantly.
How many women take menopausal hormone therapy knowing that? Two percent. The 2024 menopause position statement or menopause guide that came out said about 2%. Sometimes you hear 5%. Imagine if 80% of women were on hormone therapy. You may say, how many women are good candidates for hormone therapy? I would say the vast majority of women are good candidates for hormone therapy, especially when you’re thinking about the fact that menopausal hormone therapy could mean different things for different women.
Here’s a couple of myths that I’m going to debunk in about 40 seconds. We now use different formulations of FDA-approved hormone therapy than we did in the Women’s Health Initiative. So in the Women’s Health Initiative, it’s conjugated equine estrogen and progesterone acetate. Now we use FDA-approved estradiol and typically Prometrium. When we use Prometrium with an estradiol, we see no increased risk of breast cancer above a woman’s baseline. The biggest fear that women still have is that hormone therapy increases breast cancer risk. That’s because when the Women’s Health Study came out, training became extinct and physicians and women threw their hormone therapy in the garbage because they said there was a 26% increased risk of breast cancer. That is the big reason why we’re here, why only 2% of women take hormone therapy, not 80%.
It’s still this fear of breast cancer, and it’s the extinction of training. So clinicians have not learned how to prescribe menopausal hormone therapy. I said that the biggest fear that women have about breast cancer is actually debunked. We know that transdermal estrogen does not increase the risks of clots. We know that if women start within ten years, that’s when they get the most benefits. Although I believe all women should be counseled about menopausal hormone therapy, they can start in perimenopause. And there’s so many positives here. Not to mention the economic increase in women who are feeling well, not missing work, not seeing multiple clinicians as well as how much we would save in health care.
I believe in personalized hormone replacement therapy. What does this mean? Well, I’ve been doing this for the last 12 years, and I’ve found that not all women are going to need the same formula. It is really hard to protocolize hormone replacement therapy, which makes it hard to scale because it must be individualized. So we also want to think about not only do women need estrogen, progesterone and maybe a testosterone and maybe vaginal estrogen, but what order do they do this? That is something I call hormone stacking, which is really actually my way of thinking about precision medicine. Now I have to do this blindly. I don’t have enough data to know what are the genetics or epigenetics of someone who’s going to tolerate progesterone or not tolerate progesterone. Need a gel versus a patch of the patchwork stick? I don’t know yet, but what I know is a pattern that I see.
Metabolic monitoring is also really important in this menopause manual, which is that not all women must take hormone therapy. I want to make it clear there’s not one right answer, but all women and all clinicians should know the benefits of hormone therapy. We should be monitoring for their A1 C’s, for their lipids, as well as for brain markers, as well as for autoimmune and inflammatory conditions that start alongside menopause and lifestyle is
really important. We all know lifestyle. I’m not going to harp here for too long. But women who are in supportive communities also have improved health beyond 5 to 7 years longer than women who are not in supportive communities. I believe you have to start with personalization, which we’re going to use AI to help with.
Everything that I’ve either done, taught or recognized as a pattern, we’ve turned into a closed loop LLM, to help us be able to scale while also personalizing it. Because when you get it wrong, women do not like that. They’ve already had periods for a lot of years endometriosis, chronic pain, infertility, C-sections they didn’t want to happen. Then you get the hormone therapy wrong and the clinician and the women throw it in the garbage. It has to be personalized and we have to scale it.
Teaching is critical. We have a decade or two of clinicians who have never seen a clinician counsel and prescribe hormone replacement therapy. So this is really important. So what is the future here? I want all everyone here to know that menopausal hormone therapy is only used by 2% of women. It is something that 80%, if not more women are good candidates for.
It is the only thing that has shown to increase health span in women. We have the solution. We have to train clinicians, we have to be able to scale, but we also have to personalize. We have to use artificial intelligence for that. Thank you guys.
Kuku
I’m looking forward to questions from the audience. But we’re going to start off I’d like Jennifer to kick us off, I know for Kara [Goldman] you had some interesting overlaps. So I’d love to start off by, seeing if you have any questions for Kara. I have a lot of questions for both of you.
Dr. Garrison
As a woman, I think I’m very curious, and probably everyone in the audience is, hopefully the men are curious because they have partners or friends or sisters or mothers or other people in their lives who are female. What do you tell women right now that they should be doing to preserve ovarian function, while we wait for the science to catch up?
Dr. Goldman
It’s a great question. I think about this all the time because I have three daughters and I want to know how to protect them and their ovaries. I have patients who ask me this every day. I think the first thing is we you know, there are things that we know. We know that your mom’s age at menopause matters and can predict yours. Having that conversation and understanding that and the implications and self-advocacy matters. Digging a little deeper if you have that severe pelvic pain, getting answers.
I do think that there’s a role, the biomarkers we have are poor. AMH is not a great marker. However it is really the only one we have. I would compel women to at least know that information because, you know, yes, it’s, you know, there will be some people who will, check your AMH and potentially then try to kind of push you to freeze eggs. That’s certainly not the direction that I think everyone needs to go. I think if you have that lower number, you need to ask some questions about why, like is there some predisposition, should we check a karyotype? Should we check adrenal antibodies? Is there something going on that is driving that. And then how could we intervene differently. And so when she is 38 and she’s starting to have hot flashes, she doesn’t get dismissed, you’re too young. Maybe that’s an opportunity to intervene, so she knows that information.
Dr. Kuku
What is a guidebook. Give me a quick what I do at 20, 30. 40, to increase my health span.
Dr. Goldman
If you’re 21, and you’re having your first pap smear, we need to teach doctors to have that conversation about ovaries. I think it’s fair in your 20s, see, reproductive neurologist.
Dr. Kuku
What test do you do?
Dr. Goldman
AMH and follicle count.
Dr. Kuku
You repeat them every year? And what else can I do to know?
We wouldn’t necessarily repeat every year. You get a one time test, and if it’s low. I think that’s when we intervene and say why is it low? And then you follow that. I think if you’re in your 30s, you in the same way that we screened for cervical cancer and we screened for breast cancer, and we’re really good about screening for certain things. We’re not screening for ovarian decline, which ultimately correlates with cardiovascular disease, which is the number one killer of women. Why are we not thinking about the ovaries in the same way?
Dr. Kuku
So we use the test that is available now. But do we do other things. More hormone tests there.
Dr. Goldman
Don’t smoke.
Dr. Kuku
40s. What do I do to increase my span. What is the guide the test or scans?
Dr. Goldman
We need the data. We need data. We need biomarkers. We don’t have that data. We don’t. There’s a relationship between, diabetes and diminished ovarian reserve BRCA1 mutations. There are these isolated findings that will correlate with diminished ovarian reserve. But the problem is we need to connect the dots for patients. And it’s not currently happening in that way.
Dr. Garrison
Can I clarify just for people in the audience? What you just said is that if you have a BRCA1 mutation that you are at increased risk of what?
Dr. Goldman
Diminished ovarian reserve. So you know, this is an opportunity we have young women who are getting screened because their mom has breast cancer. They find out they have a BRCA1 mutation and they might be counseled about prophylactic mastectomy. Maybe at 35, they’re sent to see me to talk about IVF, the genetic testing of their embryos before they have their prophylactic overactivity and have their ovaries removed. That person should have been sent at 22 years old when she had the test done, because we could at that point intervene. She has a significantly greater risk of diminished reserve infertility, diminished health span all of those things, we have opportunities to intervene earlier.
Dr. Garrison
But that comes back to this idea that metabolic health and ovarian function are intricately linked. We don’t understand how they’re related, but they’re clearly very intricately linked and immune function as well.
Dr. Hirsch
I know that breast cancer patient should also who has BRCA1 should also be counseled that she should take hormone therapy after her ovaries are removed. If she’s going to have a bilateral ectomy, she’s going to take those ovaries out. But a lot of women think if they have a BRCA1 mutation, they can’t take hormone therapy, which is a huge myth
Dr. Kuku
For the non-scientists in the room, are you saying that I could do a genetic test that could find out if I have a risk of cancer and infertility and potentially early menopause? I can do something about it and hence increase my health span.
Dr. Goldman
Yes. And for the oncologists in the room, the current model, of course, is that when someone’s diagnosed, then this testing is done and you look for a link and maybe you do cascade testing to look for affected family members. But the current model is such that you often are only diagnosed with these mutations once you’ve gotten that disease. We could prospectively look. What’s interesting is when you, you know, do preconception carrier screening, you’re trying to get pregnant. You screened for 200 mutations to see what you could pass on to a child. We’re not screening for BRCA. We’re not screening for CHEK2. We’re not screening for all these mutations that have cancer risks, and we should be.
Dr. Kuku
In that vein, then how do you see menopause? What are the questions you have for, for Heather [Hirsch] around the future of menopause and increasing health span?
Dr. Goldman
Yes, I mean, so many. What’s fascinating from our training. You were internal medicine-trained? I was OB/GYN-trained. And as an OB/GYN in residency, you got no menopause training. Maybe lectures. It’s minuscule. It’s such a missed opportunity. And so, you know, certainly I think that’s part of why we’re seeing this gap. People aren’t comfortable. But what else do you see as the gaps, the patient gaps and why patients aren’t getting the care they need?
Dr. Hirsch
When the Women’s Health Initiative came out in 2002, there became this deeply-rooted idea that estrogen is dangerous and harmful. That idea has persisted despite a plethora of evidence showing how important estrogen is. That caused a lot of biases. One, clinicians didn’t want to touch it anymore. Patients were scared of it. Training became literally extinct. We need to retrain our clinicians. We need to actually start to work to like work through those biases. But clinicians ourselves have because clinicians are human too. We got the same message. Estrogen is dangerous and harmful. How do you do that?
What I’ve learned in retraining clinicians is I have, this incredible community where we trained thousands of clinicians. What it takes is not only learning how to prescribe menopausal hormone therapy, but a community of like-minded clinicians and health care professionals, that you can work through some of these biases with they’ll say things in this message boards like, “Okay, I know it’s safe, but someone just like someone, just tell me to do it.”
It’ll be like, “Should I prescribe vaginal estrogen four times a week instead of two?” And if you know anything about medicine, that’s very safe. It’s a lot of working through your old biases yourself around prescribing hormone therapy. We also have this really interesting. What’s happening right now is that women lay women are watching all this on social media, which is a big part of why we’re here. They’re going to clinicians and actually feeling like they know more than their clinicians. This is a weird situation because you want to be able to trust your doctor. You want to be able to help them. We call this the blind leading the blind. Sometimes the clinicians will kind of blindly start prescribing things, which is which is better than where we were even 5 to 10 years ago, which was it was just Kryptonite, and you couldn’t prescribe it. It will kill you.
That retraining of clinicians as well as women in society at large, like we all have to be using the same message about hormone therapy, because you could also scroll and find 3 or 10 different clinicians or other health care professionals talking differently I think it’s retraining, retraining with the community where we can work through these biases that were created in the early 2000. It’s practicing. It’s practicing prescribing hormone therapy, because if you are a physician and you’ve never prescribed a new medication before, especially one that’s kind of scary, you’re not just going to start whipping out your prescription pad, you’re going to really want people to help you prescribe this medication. Hopefully also too, we could use AI to be able to help clinicians like type in a complicated case and maybe get some suggestions and resources on how they could help.
Training both for clinicians and women is great.
Dr. Kuku
We need time for audience questions. So a quick, concise answer to a question I have for Jennifer [Garrison]. You’re looking into the future. In 20 years we are where we need to be in women’s health. I have so much at my disposal to improve my health spend in my daughters. Diagnostics, biomarkers, great biomarkers. We have novel therapeutics. We have next generation menopause replacement therapy, that makes me feel like 25. Fantastic. But we also have the investors who invested in these programs with their 40 X, I do an investment and I’m a billionaire like everyone wins. And how did we get that?
Dr. Garrison
How did we get there? Three things. First, all of you are going to go tell everyone you know, what you just learned. Immediately. That’s number one. Number two, if you are so blessed, you are going to invest either on the philanthropy side or on the company side. If you need ideas about how to do that, expert, Kara Goldman, there are other sciences here Frida Polli, machine learning, AI, women’s health, lots of companies as well. Happy to talk about that later.
I think the most important thing, though, is that if we’re really going to do this, and I hope you’re all listening because this is important, we got there because we had women in positions of power, at least 50% of the positions of power across every single sector. We need to have females in those leadership positions. I promise you, if we do that change, we’re going to solve this problem.
Dr. Kuku
Great. Questions. Yes, we have one.
Audience Member
One of the things that I found most interesting about the presentations today was the connection between metabolic health and menopause. I’m just wondering, given the environment where GLP’s are becoming much more prevalent and they have a positive impact on, blood sugar regulation have you found in your research? I’m just curious, your point of view about GLP’s and how they affect women going through perimenopause and menopause?
Dr. Goldman
I can speak to that. It is absolutely the next question. It makes so much sense in terms of the pathways that are being targeted in terms of the way that insulin signaling, the kind of activates the mTOR pathway, which activates follicle growth. We see in women with diabetes, who have activated insulin signaling, with severe obesity there’s diminished ovarian reserve. I absolutely think that this target will also preserve that primordial follicle and decrease AMH. We don’t have the data yet but we will.
Dr. Kuku
Stay tuned. I read on the way over Eric Topol’s Super Agers. There is an amazing chapter where he talks about GLP-1s and the potential in metabolic health. If you’re in women’s health, you can just see all the potential and the opportunity. It’s really exciting. Read that book. Eric Topol. Hello. Hi. Hi.
Roma Van der Walt (in audience)
I’m an entrepreneur in this and women’s longevity, and I’m also an exercise physiologist. We talk a lot about data, and we talk about AI. I think coming from the high performance space, we’ve obviously seen a really symbiotic and very close relationship between physiologists and clinicians. I think we’re starting to see that in the longevity space. A question to maybe Heather [Hirsch] and Kara [Goldman]. I talked to a lot of physicians, and we come to them with AI, and we come to them with the piece of lifestyle and the context around everything that cannot be captured adequately in the appointment, where even in a concierge setting, you see the person for longer, but they have to recall everything that happened in the past few months or weeks. What is the data you would like to see, and how do we get physicians to embrace this space?
Dr. Hirsch
I bet we both have different takes on this. For me, what would be really important is for women to start logging their symptoms. So last night when I was at dinner, the gentleman I was sitting next to said, “You must use bloodwork to decide what you’re going to prescribe for hormone therapy.” I said, actually, no, I use symptoms. Women can start logging their symptoms, whether it’s hot flashes, night sweats, brain fog or anxiety or insomnia. If they can really decide which symptom bothers them the most for how long they’re going on and what triggers them, we can better start them on menopausal hormone therapy. Because we have to do menopausal hormone therapy a little bit blind, we don’t know exactly yet based on a woman’s genetics or epigenetics, what formulation is going to be best for her?
The only way that we can tweak that HRT is to go by her symptoms. Women are busy. They don’t want to have menopause at the peak of their careers when their parents are aging, when their kids are going off to college, it’s just not the time for menopause to hit. It’s really hard to recall what night you didn’t sleep unless it was all of them. If they could log their symptoms really closely. What I could do along with me is actually work to create some predictive models. Maybe what needs to be tweaked before we have the kind of data to know exactly what someone is going to do?
Dr. Kuku
It’s tricky here because if the aura talk earlier he he talked about this and how you could almost use the Oura ring to track symptoms in response to treatment and tweak things. But, yes, it’s an interesting space.
Dr. Goldman
I’ll add we’re seeing signals so early, well before we expect perimenopause to happen, you know, cycle length gets shorter. Someone may have a 28-day cycle and an event, it starts to shrink to 27 days, 26 days, and then it starts lengthening. We see these things so early, and so we could be tracking that.
Tiffany Shlain
Tiffany Sloan Jordan, sister. This was a great panel, and I’m blown away that it’s just 2% of women on hormone replacement therapy. I know around three years ago, there was a New York Times extensive article that I sent to everybody and my brother about, that I really felt was like a renaissance in women’s self advocating. It blows me away how many doctors I see that still will not, and I have to pay Midi health. Everyone should have Midi Health, which will give HRT very inexpensively on top of what I’m paying. So is that 2% today or was it zero before that New York Times article came out?
Dr. Hirsch
Let me tell you what I know. We talked about how in the early 1990s, 65% of women were on hormone therapy. This is actually where the discrepancy lies. If you want to come to my table, talk and ask more, is that when they were doing prospective studies, women were taking HRT right around after menopause and t he timing at which you start really matters, and they were doing well. When you randomized, you had women who are older. So 65% of women, let’s say, give or take a little bit, were on hormone therapy. It was the ACC guideline to put women on estrogen after menopause, and they were doing fantastic. The guidelines come out and literally that number plummets to about 2%. Who are the 2% that stayed on it? The women who thought, this is bullshit, I’m going to say that anyways. And number two, the physicians wives who read the study, because when you read the study, you actually do see how safe it is. Those are the women who stayed on it. Then what happened? SSRI prescriptions shot through the roof. Everyone was prescribed SSRI instead.
Dr. Kuku
Antidepressants.
Dr. Hirsch
Antidepressants, yes. You would think, we had this renaissance around 2002, 2003 when The New York Times wrote this incredible article. It didn’t move very much. Now, in my view, because I think everyone’s on hormone therapy and I think everyone knows how safe it is. Of course, I know that that’s not true, but I also think that has to be more. I have read different reports, is probably a hard number to actually get, there’s probably women who are on unregulated, compounded non-FDA prescribed pellets and etc. that we do not know about. We may not be accounting for all the women who are actually taking some form of hormone therapy. But isn’t it crazy to think wait, you’re telling me we’re just where we are when this ended?
Dr. Reena Bhargava, Audience Member
Great discussion. Thank you guys, for bringing a really important topic for our audience, a mixed audience. I think there are more men than women here. I’m Reena Bhargava, I’m an internist, and, I’m building BioTrax, AI, a platform for physicians to practice longevity medicine, democratize the care. I think what we need to do is and I do remember when Women’s Health Initiative came out, and one fine day it was, “Oh, my gosh, what were we doing to our women patients?” Right until then, we thought we were doing great. We were protecting their hearts and everything else. But I think we need to translate this down to real numbers. Number needed to treat, number needed to harm. That’s the kind of medical statistics that really connect with our patients. Then if you say, and I don’t know the numbers for this, for each one of those factors, dementia, cardiovascular risk, menopausal symptoms, all of those that is so translatable. Then essentially at the lay person’s level, in community medicine, we can make a change. Because this has been dragging on long enough, and there is no good reason. We don’t need New York Times to give us the facts. We really need to change this and make a difference. Thanks so much.
Dr. Hirsch
I agree, I’ll tell you one one small statistic because that was the a point in and of itself is that when the WHI came out and they said there was a 26% increased risk of invasive breast cancer, that would freak out any woman, 1 in 4. Okay, of course, I’m not going to take hormone therapy. Estrogen is dangerous and harmful. That was the relative risk. What you’re talking about is turning that into absolute risk. If we actually took a little a little infographic and we actually kind of put the people who were diagnosed, they actually lived longer than the women who are on placebo and were diagnosed with breast cancer, that’s a whole other story. But it was 2 to 4 women out of a thousand over five years on Prem Pro. The women who took estrogen only had a statistically significant reduction in breast cancer. If we had an infographic on that, it would help tremendously.
Dr. Garrison
That’s the most important thing. All the drugs that were used in the study, we don’t use those anymore. It’s irrelevant. That’s all you need to know. It’s irrelevant.
Dr. Kuku
We have five minutes. Last question.
Frida Polli, Audience Member
That’s perfect. Hi. I’m Frida. I’m doing a Women’s Health initiative at MIT. Lovely to meet everyone. It’’s a two part thing. One is who up on stage is thinking about the link between PCOS [Polycyctic Ovary Syndrome] and natural age to menopause because genetically and otherwise, it’s pretty strong. And then, Kara, you should also know that a recent study came out showing that being a twin or a multiple compared to being a singleton is as bad as smoking, for age of natural menopause. So think about that in terms of the number of people that unfortunately, their mother’s age of natural menopause may not be, indicative.
Dr. Goldman
Yes, and to that point, there are also other ethnic groups where we see earlier age of menopause. This needs to be personalized. Patients need to know that there are unique attributes about them that need to be kind of identified and teased out to personalize their risk. That’s not currently happening. In terms of PCOS. Absolutely. We see a higher AMH level. Women with PCOS, often they respond very well to medications. They get a lot of eggs and embryos. If they’re going through IVF, they have poor quality eggs and embryos. But they do have prolonged endocrine function. Because they have this significantly greater pool of primordial follicles. They are actively a group that I’m studying as well, because they are so different than the other population with a normal ovarian reserve at the same age.
Dr. Kuku
We have three minutes. Any men want to ask any questions? Just one.
Audience Member
I’m going through a process with a strong-willed woman, this IVF process, in Madrid and I’m learning about the international regulations around moving eggs, all that stuff. I’m curious, where’s the best venue for research to be happening? Is it the United States? Because I agree with your comments, it’s going to be patient funded and I’m pretty motivated to get it right.
Dr. Goldman
Yeah, absolutely. You cannot you’re right. You cannot move eggs or embryos across international lines. If you’re looking at you know, where you could kind of do really powerful research with a lot of collaborations amongst a lot of different groups that the US probably there’s legislation in other countries that make it challenging.
In, Italy, for example, you can’t freeze a large number of fertilized embryos. We’re staying away from politics. I think that right now we are okay in most states in terms of what it means to create an embryo and freeze an embryo. There are concerns about personhood bills. We could talk offline about that. Right now, there’s so much work being done in the US. The problem is it’s just the funding situation.
Dr. Kuku
You mentioned, Madrid. Spain is the biggest IVF market because the restrictions on IVF are low. It’s a huge research center. Most of you would have heard of Carlos Simón who sold Igenomix for $1 billion. They have no restrictions. They have a huge number of clinics compared to the US. It’s where I would go if I wanted to do IVF. Certainly.
I think that’s it. Thank you.