Hormones and Heart Disease: A Vital Conversation with Dr. Felice Gersh

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I'm JJ Virgin, PhD dropout. Sorry, Mom. Turned four time New York Times bestselling author. Yes, I'm a Certified Nutrition Specialist, Fitness hall of Famer and I speak at health conferences and trainings around the glob. But I'm driven by my insatiable curiosity and love of science to keep asking questions, digging for answers and sharing the information I uncover with as many people as I can. And that's why I created the well Beyond 40 podcast to synthesize and simplify the science of health into actionable strategies to help you thrive. In each episode, we'll talk about what's working in the world of wellness, from personalized nutrition and healing your metabolism to to healthy aging and prescriptive fitness. Join me on the journey to better health so you can love how you.

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Women seem to focus a lot on breast cancer and not much on heart disease. And it's always been perplexing to me because when you look at the statistics, we are at far more risk for heart disease than we are for breast cancer. And so I was thrilled when Dr. Felice Gersh sent me her recent article that got published in Science about women and heart disease and really dove into hormone replacement therapy and its impact on heart disease. So I was like, you have to be on the show.

You have to come back.

Because she's been on the show before. In fact, I'm going to link to that in the show Notes because that was one of the most shared episodes of all time. And I'm going to put the show notes, by the way, @jjvirgin.com Gersh G E R S H for Dr. Felice Gersh. And the reason is is because Dr. Felice is really, I call her the goat of hormones and hormone replacement therapy. She has been working in this field for decades and continuing to learn, evolve, et cetera. She has her degrees from Princeton and the University of Southern California School of Medicine. She's fellowship trained in integrative medicine from the University of Arizona School of medicine. She is a multi award winning physician with dual board certifications in ob Gyn and Integrative Medicine and she is the founder and Director of Integrated Medical Group of Irvine. That's where I first met her years and years ago and it is such a cool place because she combines therapies from conventional, naturopathic, holistic so you go in there, she's got all these different things going on. Practitioners. She's very open minded. She's taught obstetrics and gynecology at Keck USC School of Medicine for 12 years. She now serves as the affiliate faculty membership member at the Fellowship in Integrative Medicine through the University of Arizona School of Medicine where she lectures and grades can't believe she wants to grade grades final exams. She's Also written PCOS SOS and PCOS fertility facts Track and Menopause 50 Things yous Need to Know and has published a lot of articles in peer reviewed medical journals which I'm going to link to the latest one that I talked about here at JJ virgin.com forward/gersh she has been in a ton of different podcasts and films and documentary series including the Real Skinny, I'm Fat and Fasting with Valter Longo and the Business of Birth Control. And she is my go to when I speak, especially around these questions which we're going to get into. Some of the tough questions today like can you take HRT if you have had breast cancer? Can you take HRT if it's been 10 years or 15 or even longer since you went through menopause? And why are women at such risk for heart disease and what else does estrogen do? And honestly, this was pearl after pearl after pearl in this interview, so I am thrilled to share this one with you. We're going to dig into heart disease and its risk for women, but we're going to go a lot further with than that with everything estrogen related. So I will be right back with Dr. Felice Gersh. Stay with me. Hey jj, Virgin here.

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Dr. Felice Gersh, welcome back to well Beyond 40.

Well, it's my pleasure. And I'm so excited because we were just talking about what an important topic we're going to be covering today.

Yes, yes. Well, the last interview we did, I literally got stopped in the street by people thanking me for it.

Well, I hope I can outdo that one.

I know.

So the bar is very high here, Felice, but I have total confidence in you, especially since we're going to be talking about an article that you wrote that was published. So here's what we're talking about today. And I think this is so important because I feel like breast cancer gets so much publicity and yet you look at it and go, heart disease is the number one killer of women. Why isn't there more out there about this? So could we start with just painting the picture of heart disease and why women need to be paying attention to this?

Well, absolutely. Well, you started out with exactly the right intro. It is number one as the killer of women. And in fact, by age 65, 75% of women will have hypertension. And by age 65, women outdo men in terms of the incidence of strokes and ruptured aneurysms. They die more from their first heart attacks. And yet, because prior to the onset of menopause, women have a substantially lower incidence of cardiovascular events than men. It's sort of forgotten. It's like they don't see the difference. And when they've done studies of cardiovascular issues, up until just not even 10 years ago, they didn't even have to include women in any of the studies, and they therefore left them out. Even rat studies left out female rats. So we had, like, no data. There was no, like, observation of what was happening. And it was just like, mum's the word. It was really completely ignored. And that's why I'm just trying so hard, along with you now, to get the word out that cardiovascular issues are really a big deal for women. And I'm trying so hard to get men, mainstream medical societies to actually embrace the differences between men and women and the roles that hormones play in terms of protection. And then what happens when you lose them with menopause and all of this for women's healthy longevity, it's essential.

So when you started to describe that and started talking, I didn't know those statistics. Those are absolutely, like, jaw dropping about the risk of stroke and hypertension. But it sounds like you hear that and you go, okay, 60, 65, what happened? Well, we went through menopause, so I'm assuming that hormones play a big role here. So can we, like, break that open and talk about what is this role? Why is this now with 65, all of these things start to happen. Is it hormones?

It absolutely is. And then compounding that, of course, are all the influences of lifestyle choices. But foundationally, the change is the hormonal shift that occurs with the onset of ovarian aging, the perimenopause into the menopause. And it's really a natural event. 100% of women will go through this transition of ovarian aging, Loss of these vital organizations previously called, by me, sex hormones, but now I changed it to life hormones, understanding what they really mean for the entire body, and that this transition, though natural, is really a cataclysmic transformation, metabolically speaking. I did thousands of deliveries back in the heyday of my doing obstetrics, and I figured pretty early on in my career, although it wasn't talked about, that hormones are really important for every organ system. And that's why they now talk about pregnancy finally, which was, like, so obvious as the ultimate stress test for women of reproductive ages, and that when they have complications, it portends of problems later on. That's because the whole female body needs to be healthy to support fertility and reproductive success. And therefore, these vital life hormones, the primary is estradiol and its sidekick, progesterone, have receptors in every organ system, including everything involving the cardiovascular system and all of the support system, the metabolic systems, and so on, in order to optimize fertility and reproductive success. So in order to be successful with Pregnancy.

The.

The heart, for example, has to pump 50% more blood volume through the body, so you need a highly energetic heart. And how does that happen? It's actually through the role of estradiol and the mitochondrial function in the heart. So when women transition into menopause, they often have a problem with their hearts that isn't really recognized very much or even really acknowledged where they have an energy deficient heart. And that's just one area. So when you lose these vital life hormones that are there for the support of reproductive success, you basically have sort of a chaos occurring throughout the body. And we could go organ system by organ system, because everything ultimately links into the cardiovascular health. Whether we're talking about musculoskeletal functions or the gut issues or the immune system, everything links into cardiovascular health. And so there really is this metabolic shift that occurs when you lose these vital life hormones. And reproductive loss is equivalent to cardiovascular decline. And it's so obvious when you really realize how all the body systems link together to support reproductive success, and that all of these systems start to disintegrate essentially when you lose these vital hormones. And we just have to get the word out that this is something that is preventable. A lot of these problems, not forever. I mean, what we're really doing is trying to kick the can down the road. So what may happen at age 65 instead? Maybe it'll happen at age 95. You know, eventually we're all mortal, but if we could have 30 extra years of total healthy living without all these chronic diseases coming into play, that is my goal for everyone. But it won't happen unless we embrace the importance of these hormones and what it means as the levels start to decline and eventually are completely gone in terms of their production from the ovaries.

Okay. The obvious thing we want to know is how to kick the can down the road. I'm like. Because 65 is right around the corner, Felice. However, before that, you said something I've never heard before, and I'm wondering if there's a way to know if you have this. And you talked about having an energy deficient heart.

Oh, absolutely. In fact, we do this in my office. But I even see echocardiograms. That's what we're talking about. An ultrasound of the heart. Completely non invasive, no radiation involved, no invasive dyes or anything. Just a simple ultrasound of the heart. And what this is, it's really fascinating. It can lead to a condition called heart failure with preserved ejection fraction. Ejection fraction is how the heart pumps the blood out into the arteries, like into the aorta and dispersing the blood throughout the body. And that's the ejection fraction. So when most men have heart failure, the majority, it's congestive heart failure. It's about the problem with the pushing of the blood out of the heart. But in women it is the majority of heart failure is actually different. It's called diastolic heart failure with preserved ejection fraction. And what that part is not the heart is, in simple terms, it's a pump. And so it gets the blood out and then it fills, and then it pumps it out and then it fills the filling phase, which is called the diastolic phase, which is the time, that would be the time when if you did a blood pressure, the blood pressure is lower because there's no blood coming out. And so the pressure in the artery will go down. That's the diastolic. Like if you have 120 over 80, 120 is systolic and the 80 is diastolic. It's the lower of the pressures. And that is when the heart is relaxing and refilling with blood. And it's a stiffer heart and you can actually see it on an ultrasound that it's not relaxing properly. And that can be just as deadly as the other type. And it's really a problem of energy deficiency. And on an ultrasound you can actually see it's a visible change in how the heart is moving, the movement of the muscle of the heart. And so this is like a really, really big deal. And it is totally related to the mitochondria, the energy producing factories of cells which are very interesting and unique, especially in the heart, which have like special types of functions. In fact, estradiol is so critical that in the heart there are receptors not just in the mitochondria for estradiol, but for its metabolites, like 1, 2 methoxyestradiol, which is a metabolite made through the conversion of estradiol in the liver into a byproduct. There's actually special receptors in the heart for this metabolic byproduct of estradiol. And there are other receptors called ester, estrogen related receptors. Whereas what binds to the receptor isn't the estrogen, it's something else. We don't even know what it is, but it won't work and help to create energy unless estradiol is there in the vicinity. So that's why they call them estrogen related receptors. So estradiol is so critical to the heart. And this is just for the pumping. And then if we look at the electrical conducting system of the heart, that is another really key thing. And that's why it's so common for women to get tachyarrhythmias like palpitations and ultimately atrial fibrillation. This is all estrogen related. And the whole neurological system that serves the heart, that's called the autonomic nervous system, the neurotransmitters of this neurological system depend on estradiol for the proper modulation or regulation of these neurotransmitters so that you have proper heart rate and conduction of the electrical system in the heart. And that's just the heart itself, not even talking about the arteries and the veins that are also involved with these vital hormones in order for them to be optimally healthy and functioning.

Wow. I did not know any of this.

And don't worry because most cardiologists don't know it either. That's like the shocker thing of it.

Well, I'm thinking about this Felice because I have a girlfriend. She is, gosh, I'm thinking she's 65 or 70. And literally we just sat down the other day, we were at an event and she said, I've been having afib all morning. This is been going off and on. I know, I just made a note, get her to heal off and on for the past couple months. They cannot figure it out. And I'm thinking, oh my gosh, I know she's not on hormones. I know she's not.

It is, it's really painful when, when you see so much that has a really strong potential for prevention and that the steps aren't taken. And, and this is a whole big area that is still under investigation because no one has done enough data collection or research. And that is, you know, because you're like talking about your friend. What about starting hormones late because. And that was really. Yeah, that's a very big question. And so what it appears, and this is still in debate and research, is that as you age, you will have more inflammation. In fact, the entire immune system is regulated by estradiol. In fact, I had some other articles I published that got, well, they published in the Mayo Clinic Proceedings, that was about a year and a half ago, on the renin angiotensin aldosterone system. That's a system that regulates fluid volume in the body and also vascular contraction or relaxation. In fact, many of the blood pressure drugs are involved in this system that are called ACE inhibitors. Like lisinopril and the angiotensin receptor blockers like losartan. They're all dealing with this system. This system is completely modulated or regulated by estradiol. And there's two pathways, a pro inflammatory and an anti inflammatory. And that's true for the entire immune system. There's the anti inflammatory, which should be the status quo when nothing is happening. There's no trauma, there's no pathogens trying to invade your body aggressively. And then there's the pro inflammatory, which should only be triggered in response to a real need, like injury, damaged tissue or infection, type of situation. But estradiol modulates, turns on and off, regulates the on and off switch for inflammation for these other systems, like the renin, angiotensin, aldosterone system. But when you don't have enough estradiol, it goes into the default, which is the on switch for inflammation. And somebody clever came up a number of years ago called it inflammaging the inflammation associated with aging. But I see it as the inflammation associated with estradiol insufficiency or deficiency. And what happens, though, in terms of aging is that as you have a lot of inflammation, you have damage to every organ system. And included are, of course, the mitochondria, so you don't make energy properly. And also estrogen receptors, these incredible structures that are vital in terms of creating the effect that the hormone is trying to create. The hormone has to fit into a receptor. It's not really the ideal analogy, but kind of like a key in a lock. The key is the hormone, and the lock is the receptor. But unlike a lock, which is in a fixed state, a receptor is more like a mouth. It can be like open or closed. It could be smiling or frowning, like a shape shifter. And it can also undergo damage. One of the things that, for example, damages the receptors or endocrine disruptors, those ubiquitous chemicals that we live with, which are, of course, creating metabolic havoc in our systems. And they even call them diabeciens and so on. So when you don't have the right hormones being produced in the body and entering into those receptors, it sets them up for both endocrine disruptors. Getting into those receptors and creating the wrong effect is it's like trying to shove a puzzle into the wrong slot, you know, but you shove it in anyway because it sort of is close, you know, but. Or you end up with this inflammating, this chronic inflammation that creates damage to these receptors. And so having estradiol on board, like if we started like Right. During the perimenopause. So you barely miss a beat. Of course, we can't replace the ovaries. And there are people researching that, like even looking at taking a little piece of ovary when you're young and then storing it and then putting it back in for an extra 20 years of normal ovarian production from the hormones, the ovaries, that you actually have a piece of ovary saved. But that's hypothetical right now. But there's actually research on that. But if we could have it, that would be ideal. But even though we can't do that right now and we can't be exactly the same, we can do a lot of good if we start the hormones before they really go into that decline. Because there is concern that as time goes by and you have damage to these receptors, how much can be repaired? Now, there's no exact answer, but I'll tell you what I think. I think a tremendous amount of repair can be done. And this is a whole new area that I'm really fascinated with, because I call it the lost generation of women. This whole group of women who lived through their menopause transformation, so to speak, during the years of the Women's Health Initiative negativity, this huge study that completely transformed, in a negative way, the perception of how these hormones from the ovaries actually work in the body. Because they used the wrong product and they did the study incorrectly, they interpreted the data incorrectly, and. And it really poisons as well.

And by the way, I'll interrupt for one second because you did an amazing discussion of that on our last podcast, and we will link to that. So, because, Felice, I still hear people afraid of hormone replacement because of the Women's Health Initiative. So we will make sure we link to that so that if you are one of those people who's still going, ah, you went through and refused the entire thing. So we'll put that in the show notes, okay?

But basically, you know, and it's still ongoing, the lost generation for these women who are still embedded in the old ideas and their doctors may be still, you know, believing these wrong ideas and conclusions, but there's this whole group of women, it's huge, that we're told, don't take hormones, don't take hormones because they're bad for you. They'll give you all this, you know, they'll give you breast cancer, they'll give you dementia, all these bad things. And that group of women, now they're saying, but wait a minute, now there's more data that says good. And so what is happening is that these women are being told, now it's too late for you, you missed the boat, you're now over 60 or you've been 10 years or more out, and now we're not going to start it for you. And so now you're on this, this voyage through aging where it's medical, I call it medical whack a mole. As every new problem comes up, you then get a new drug or a procedure. Now you have osteoarthritis, you're going to have joint replacement. Now you have problems with your arteries, you're going to be on four blood pressure drugs for hypertension and then you end up having these problems with heart failure or heart attack or you have afib and you know, you go through all the different organ systems, you have prolapse of your vaginal tissues. That's a mega industry, incontinence. And you know, descensis, cystoceles, rectoceles. There are doctors, that's all they do is do surgical repairs. All of this is in large measure preventable. But you know, this is what's happening. And these women just have to go through life with one problem after another after another and they're not allowed to go on hormones. And, and I really believe, and this is an area that I'm researching actively, is how can we use lifestyle plus hormones to rejuvenate the receptors. Everything in the body has a potential for repair or at least some improvement. There could be a point of no return. Just like with end stage renal failure, end stage heart failure, no one knows how to treat. Turn that around and suddenly you have a well functioning set of kidneys or a heart. But short of total end stage disease state like with the receptors, I think there's a lot we can do. We know that the power of healing is so strong in us that if we do exercise, if we take appropriate supplements, if we activate every lifestyle pathway, we can fasting, all the different training tools and then we give estradiol at physiologic levels that we can reverse this. We know we can reverse early diabetes, which is resistance of the insulin, right? So insulin receptor resistance. If we can reverse other hormonal resistance problems where we have receptor malfunction, why is that impossible that they're just writing women off? It's like first they wrote them off at menopause, now they're writing them off if they're 60 plus. And this is like, once we hit that age, we don't want to be written off if you're like in that age group and you are told you missed the boat. So you know, this is like really important because these women have such high risk for cardiovascular events. It's really amazing when you look at the actual data. And almost everyone has family members who've had problems with their cardiovascular system. And of course now we also call it cardiometabolic because it's all about metabolism, the production, utilization, storage, distribution of energy, the spark of life, which involves, of course, all the issues involved in energy transport and like glucose transport and into the brain, which is so crucial. The vascular system is what isn't just for the heart, it's for the brain. In fact, much dementia that occurs in women is because of vascular problems. They call it vascular dementia, which is really common in women. So I don't want anyone to suffer unnecessarily. So I think that we can really approach aging from a whole new dynamic, a new approach, but starting early. But even if it's late, I don't believe it's too late. For the vast majority, the holidays are all about family.

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So this is such great information. The first thing I'd love to see, and I'm sure it's not probably out there, seeing how little research is done on women in the first place. I highly doubt this one's out there. But boy, wouldn't it be interesting to see the incidence of dementia and Alzheimer's, the incidence of hypertension, of stroke, of a heart attack and HRT versus non. Because everything that I'm looking at in terms of risk factors for heart disease, risk factors for Alzheimer's, it all points back to estrogen. It would be so great to be able to look at those retrospectively, you know, and say, were they on HRT or not? You made such a great point about the fact that we can reverse insulin resistance, that insulin resistance is damaged insulin receptors. However, we know that we can reverse it. And again, if we could reverse insulin resistance, why couldn't we reverse the receptor damage for I'm going To call it estrogen resistance. It just makes sense. And all these things you're talking about where they're now having to give polypharmacy all these medications where if they just went back and actually gave them hormone replacement therapy, they probably wouldn't need any of these things. So I just wonder, what have you seen so far? Because I know that you are really a pioneer here in terms of being able to put someone on hormones. Like what's the oldest age now that you've started someone on hormone replacement? And my. It would seem to me that someone would become more receptor resistant with a poorer lifestyle. Like, you know, someone who exercises, eats healthy, you know, does the different things that really help keep things more sensitive would probably have a better time of it at 65 than someone who.

They're spot on with that. In fact, one of the newest theories about receptor malfunction is exactly what you said. It's not about years lived, it's about damage from lifestyle and the environmental effects. So you can actually have a younger woman who has malfunctioning receptors because she is not cardiometabolically healthy, because she has what is now called metaflam aging metabolic dysfunction that's creating an accelerated type of aging in a younger woman. So you can be younger and have malfunction just like you can now have young aged onset of type 2 diabetes. Right. It's like ridiculous. Even in children, they're now seeing stuff like that. And you can have young aged women who have vascular dysfunctional function and their receptors are not right. In fact, we see that a lot in polycystic ovary syndrome. And the reality is that 100% having what I call your health savings account, that's what you bring into your health status when you hit this menopausal transition has a huge impact on the rest of your life. And so if that's why you're never too young to, to start preparing for the future, like they say, start saving early for retirement or whatever, you gotta build your health.

Well, also habits, you know, it's the habits that you do now, right? I mean, you look at it and go, I'm all about making sure you have as much muscle. To me, that's your real health savings account. But if you started that habit in your 20s, you would never have to think about it. So it's all of these things are the health habits. Sure, you can get away with stuff in your 20s and 30s. I used to be able to stay out late and get up early. That ship sailed. But the reality is the better those habits are now, the better off you'll be. And I just kind of looked at this list and thought all of these things that we know to be true for basically quality of life are also the things that we know to be true to help insulin receptor sensitivity are also likely the same things. And I would assume that, you know, this damage to the receptors can happen at any age. It's not just waiting.

That's right. It's not just about age at all. It could be just due to that inflammatory process that sort of causes a degradation of every structure in the body. But no matter what we do, without adding on exogenous hormone supplementation, every woman is going to lose that vital life force of her vital estrogen and estradiol that comes from the ovaries, along with her progesterone. And so it's then a question of, this is how I look at it. When you hit perimenopause, it's like you're in a two propeller, two engine plane and one engine goes out and then you hit menopause and then both engines go out. So if you've been very healthy and you have this great health savings account and all, and then you hit that point, your plane turns into a glider and you can actually stay drifting high. Eventually you're going to go down, but you can stay high and have a smooth ride for a long time. Your plane doesn't have any engines, but now you're a glider. But if you have no health status that's really robust or anything close to it, when you hit this menopausal transition and your plane turns into just dead weight, it just goes straight down. And so that's why it is so critical. In fact, they've shown, for example, that doing the right things with diet and exercise can dramatically postpone by at least 13 to 15 years the onset of osteoporotic fractures by doing bone building in the bone building years, which are not, most people don't know this. It's like from the mid teens to the very early 20s, that's when you build. The vast majority, over 90% of your bone mass is built during those years. Often when women have a lot of eating disorders and they're not doing the right things, it's so painful. And bone is actually not just involved in being upright and not being a little crumbled mess on the floor, but bone is actually an endocrine organ. It actually makes a hormone, osteocalcin, that's critical for glucose regulation. A whole big part of metabolism Glucose regulation and also cognitive function. So bone and muscle are not just about locomotion. It's really part of your whole cardiometabolic and brain conglomerate. You know, it's really part of everything. So that's why it is so important. That's why. And this is a fascinating thing. I was just reading this. You're like the real muscle expert that when even in menopause, when you don't have the estrogen on board, muscle, like many other organ systems in the body, has the enzyme aromatase that allows the conversion of androgens. Most of them are coming from the adrenal gland to convert them into estrogen in the tissue locally. It's not circulating. You won't measure it in the blood. It's in that tissue. And with exercise, muscle actually makes its own little estrogen supply to feed the muscle.

Really?

I just read that. It's like, wow, talk about nature, like, being a little kind here. You know that if you exercise, even if you're not on hormones, you will make estrogen in your muscle. I thought that is so amazing.

Did they talk about specific. Any type of exercise whatsoever, or is it really. If we were really focused on more resistance training.

Yay.

I know, it's great. So every little bit of help. The other thing that's like a little bit of help is eating phytoestrogen foods. I call that nature's gift to women. These fascinating polyphenols that actually are not estrogen, they're not estrogen, but they can bind to our estrogen receptors and actually have some dramatic beneficial effects. In fact, almost everything that's called a superfood. And it has its little polyphenol. These like, I call it the magic sauce of plants, of vegetables, beans, legumes, nuts, seeds, fruits and so on. They're actually all phytoestrogens. Every time I hear about a new polyphenol, I look it up and it's, yep, it's a phytoestrogen. It's like amazing. Almost everything is.

So I'd love to hear some because we hear so often. You know, it used to be all you heard about was soy. And then a shout out to Dr. Lisa Moscone when she wrote the XX Brain. And she talked a lot about the different phytoestrogenic foods. What are some of the ones that are your favorites here?

Well, apples, onions, garlic, have the quercetin. And quercetin helps to stabilize immune cells, particularly mast cells, to keep them from rupturing, creating like a cascade of inflammation. So it's really amazing how beneficial those foods are. And they have that. Now, pomegranates have ellagic acid, which is a polyphenol that can convert to urolithin A, which has been shown to be a big muscle booster and mitochondrial supporter. And not everyone has the proper gut microbiome. The same thing with soy. You have to convert the isoflavones into equal. And not everyone has the right gut microbiome. This is part of why we focus a lot on gut microbiome repair as much as we can as well. So I love pomegranates and I love apples, onions and garlic and red grapes as a source of that still bean. A still bean is a type of phytoestrogen, and the specific one is the resveratrol, which has tremendous benefits. Resveratrol is like a fasting mimetic. It's like a mimic for fasting. And we know that different types of fasting can trigger autophagy. Internal cellular renewal can trigger the right cells to die, those zombie cells, those senescent cells that are killer cells. And so that is really helpful. I try to eat food, red grapes, all the time. They talk about, you know, you have to eat truckloads, but the reality is that you don't get a reasonable benefit when you're putting it as part of an overall healthy diet.

And I love. Yeah, these things work in combination. There's two things when you just said that, like, do you take timelines might appear.

I do use. I actually. I'm not taking it myself right now. I actually am thinking about it. And I do recommend it to many of my patients, especially my sarcopenic patients. You know the one I'll get you.

Hooked up with Timeline. Because that, like, ever since I've been on it and I remember looking at the research and saying to them, you know, this. This is kind of like exercise in a bottle. But I don't ever want to say that. I don't want someone to think they can just take this. But it is because most of us aren't eating pomegranates. And even if we were, we couldn't go convert to the urolithin A. And what it can do for the mitochondria is amazing. And then the other one I've been taking is through Qualia Neurohacker. They have a product you take twice a month called senolytic, and it's got resveratrol, quercetin, fisetin, and a bunch of different phytoestrogens.

I'll bet you. I mean, 100%, you know, you were.

Saying that and I'm like, ooh, they do it to help get rid of.

The zombie cell, of course. And that's what we want. And so by the way, the fact that urolithin A, you know, from, you know, the mitopur, seems to be beneficial in all ages. And it. What is, what is the phytoestrogen urolithin A, what does it work on? Predominantly estrogen receptor alpha. So if. And the alpha receptor is very largely the receptor in the arteries and the vascular system that is so critical for maintaining proper production of nitric oxide, maintaining the lining, the endothelial health and so on. And it's the degradation of the alpha receptor that is felt to be a problem for developing vascular disease, that loss of that vital estrogen receptor alpha. And that's the estrogen receptor that is the dominant one that urolithin A binds to, acting as a phytoestrogen. And so if it can work, then why can't. I was actually thinking that, I mean, we have to talk together because what if we looked at using something like Urolithin 8 to help revitalize and maybe bring back the estrogen receptor alpha. Maybe there's like a synergy here between the phytoestrogen and then the real estrogen. I mean, we have to think out of the box. That's the way.

Absolutely. Well, you've always been an out of the box thinker, which I love, because someone, let's face it, medicine's kind of notorious for not doing that. And you're out there pushing the envelope on this and asking the right questions. And so going back to the question I realized we never tied a bow on right now, what would you like? Where would you not give estrogen? If you had someone coming in, maybe they're 65, maybe they're 70. Is there an age where you'd go, eh, I think the ship sailed because it still feels like it's not just age, it's lifestyle. Like, what would you do with someone who, you know, clearly. Well, I was gonna say it's kinda. I look at every woman, I go, clearly, every woman should be on estrogen. Unless there's some reason in terms of cancer. But what would you do?

Well, here's what I have to support what I do. Number one is the elite study. The elite study was done probably now about six years ago. It's not that new, maybe even a bit more. And in the elite study, it was looking at the what's called the timing hypothesis, looking at the time of initiation of hormone therapy and whether it will be cardio protective or cardio damaging. And in that group, they took a group of women who were recently menopausal, they had to be within six years, years. And then they took another group that had to be more than 10 years post menopause. And so menopause is defined as 12 consecutive months without any vaginal bleeding. And what did they find in the younger group? They found, by the way, they used the wrong products too. But it is what it is. But in that they used oral estradiol. But in, I know it's put together by cardiologists. But in the younger group, despite that, despite that they used the wrong form of estrogen, they actually showed that that group compared to the control group, the group that had, that were, you know, controlled match, but they did not get the hormone therapy, that the group that did receive the hormone therapy, they had better vascular health. They looked at the arteries and they saw that there was less of a development of any kind of damage to the arteries or plaque formation. When they looked at the older women, 10 plus years out from menopause, and they compared them to the control group that didn't receive the hormones, they saw no difference. But once again, they were using the wrong product. But here's the thing that supports what I do. They found no harm. There was no harm. And these were all women over at least 10 years out. So I feel that's a green light to me. It showed no harm, you know, so that is great. And we know that there's benefits even if they're not optimal compared to a younger woman. So I have no age restriction on the initiation of hormones. But for women, particularly 60 plus, I am pretty demanding. I want them to have vascular ultrasounds. I want to know the status of their heart. I want to know the status of their key arteries, the carotid, the aorta, the leg arteries. I want to know their coronary calcium score. So I want a lot of data on these women. I want to know what their risks are going in, not from going on hormones, but just being who they are. And then I want to add in all the different lifestyle things like put them on an exercise program, give them appropriate supplementation, add in everything that's necessary to optimize their health, work on stress and sleep, you know, you name it, the whole array of lifestyle things. Because I want to make sure, because I take my Hippocratic oath very seriously of do no harm. There's no way I'm going to have any of my patients suffer because, you know, I did some kind of treatment. But I have a study that was well controlled, well designed, even though they used the wrong estrogen, that showed no harm in starting hormones in women. Just, you know, random sort of women who were at least 10 years out from menopause. But all of my patients who are older, I mean, I like to do it more as well on the younger, but I'm not as strict about it. But on the ones that are older, I want to know all of their cardiometabolic health status. I want to get lots of labs, I order all the high end inflammation markers and lipid, you know, advanced links, lipid markers and so on. So I want to know all about what's going on in them. I assume they all have leaky gut, so we're going to work on their gut, you know, gut microbiome and so on. But I have no age limits and I know, like, once again, I'm an outlier and I always totally. Everyone gets all the information. It's informed consent. Nothing is done without total, you know, transparency of what we do know and we don't know. But here's the problem for this, like, lost generation of women, they don't get any more chances. This is, we know that if they get to truly end stage, any end stage disease, no one is going to reverse that. So they don't, they can't, like, wait for the additional studies. They're not being done. They're not even being designed. They're not coming, like, no one's coming to rescue you. You know, like you're in the boat with no paddle. You better start like just using your arms because no one is coming to rescue you. So I don't, I accept that there are limitations. There are limitations in so much we do in medicine. But we have to make decisions. Doing nothing is a decision. And we know where that leads to. In most women with aging. If you've ever been in a nursing home, you do not want to take that path. That's not the path you want to take for aging. I want all of my patients to have the opportunity to become one. What I call superagers. A superager means that in your 90s, you can do pretty much everything you did. I mean, not perfectly, that you did in your 30s. You want to travel the world, you can do it. You don't need a wheelchair to get through even the most challenging airport. You can follow complex plots. You can learn new anything. You can learn New games. You can learn how to play marjan or bridge or you can take up a foreign language. You can do whatever you want that you did at 35, you can do at 95 plus. But it's not going to happen statistically speaking. I deal in medical probabilities. I know there are outliers that live to be 100 with no problem, but that's an outlier. I deal with medical probabilities. I want to increase the medical probability that my patients can be superagers.

The oral estrogen. I have a couple other questions I would love to ask just on what you just talked about, but I would love just so people hear this because Felice, I still talk to people who are on oral estrogen. I know, I'm like, what? So would you just please explain why this is problematic?

Sure. Well, the estrogen. Well, first it's important to know estrogen is not a hormone. It's a family of hormones. And another way to understand it is that fat, which was maligned for a very long time, fat is not one thing. It's a family of different types of fats. Everybody knows there's saturated fat, there's omega 3, there's different polyunsaturated, there's trans fat, which is horrible manufactured fat. And estrogen is a family of hormones. There are four types that ever exist in humans and that would be the type that the ovaries make, which is called estradiol or the full name 17 beta estradiol. And like B vitamins, there's not one B vitamin. So estrogen has the big letter E and then a number. So estradiol, the ovarian produced estrogen, has a big E and a number two. Estrone is big E number one that is made predominantly as the estrogen of menopausal women converted from androgens, mostly coming from the adrenal gland, mostly converted with the enzyme aromatase in fat tissue into estrone, which only binds predominantly to one receptor, which is the alpha, which is a good receptor. But we don't want to just have that one being the one activated in pregnancy. E3 estriol is the dominant estrogen made by the placenta and it predominantly works on the beta receptor only. Estradiol has the balance effect on all three estrogen receptors and they're little modulations of different parts of those. The receptors are not even all identical in terms of they have different parts of even. Like alpha and beta are not all just exactly one. They have little subspecies. Two we now understand. And when you get the Balanced effect, you need E2 estradiol. When you swallow estradiol, it gets converted through the digestive tract and in the liver into E1 estrone. So you may swallow it as E2 estradiol, but it gets into your bloodstream primarily as E1 estrone. Now, as you age and you become more inflamed, it turns out that inflammation, systemic inflammation, impedes the enzyme that's in the body that allows conversion interconversion between E2 and E1 estradiol. And estrone can be converted back and forth between one and the other, depending on what the body needs. But it's not like a complete. If you overload the body with one, it's not going to turn into the other. It doesn't work that way. And when you have a lot of influence inflammation with aging, that enzyme is actually down regulated, so you do not have good conversion. So when you take estradiol orally, the dominant estrogen that you end up in your body with is estrone, which is not the balanced estrogen. Now it turns out that the dominant estrogen receptor on the innate immune cells, those are like the initial attack animals of the body. They include things like mast cells, neutrophils, macrophages, monocytes, they are predominantly the alpha receptor. So what happens is you're basically pushing down. Remember, estrogen modulates or regulates the on and the off switch for inflammation. When you have only or dominantly estrone, you're basically turning on the on switch for inflammation with your immune cells that activate this immune response of inflammation. So you go into a more pro inflammatory state. And this is why poor estrogen. But estradiol gets blamed for the deeds of estrone. You know, it's like the evil sister or somebody, it's not even a twin, but it's like a different relative who does bad deeds. Not because, you know, because they're like not trained properly or whatever, but the good guy gets all the blame. So poor estradiol gets the blame for estrone, which is now being overloaded in the body when you swallow an oral pill of estradiol. So you're not going to get the same outcome. It's that simple. You end up with a different product in your blood. And because it's a pro, a more pro inflammatory inflammatory scenario, part of the inflammatory response is activating platelets which aggregate or clump together and can increase blood clotting, inappropriate blood clots, and that can trigger bad things like strokes and heart attacks. Because you become more coagulable, you become a pro clotting state. So that's why we don't give it. It's really black and white and I don't know why anybody would use it. This is all common knowledge now in the medical world that when you give oral estradiol, you approximately double your risk of an inappropriate blood clot like a pulmonary embolism or a dvt, a deep vein thrombosis. Now, if you give the conjugated equine estrogens, that's the, the one that was used in the Women's Health Initiative, that is a unique one that comes from the urine of a pregnant horse, and that one actually increases inappropriate blood clotting fourfold. So the oral estradiol, it's twofold, and the conjugated equine estrogen is fourfold. If you give transdermal through the skin estradiol, it's zero. And in fact, there's a lot of data on how estradiol, when you have the right thing, because it's anti inflammatory, it actually lowers, through the production of these compounds called nitric oxide and prostacyclines, it actually lowers the risk of spontaneous blood clotting forming. So estradiol is not in our bodies to harm us. It's there to help us and to control all of these different functions of the immune system, which are not properly controlled. When you have the wrong form of estrogen in the body, don't take oral estrogens.

One final thing, and you got to come back again, clearly, because I got through about a third of the questions, but I know this one we have to cover as we're talking about all of this. And just to recap, what's been amazing is you really talked about all of the things that happen, you know, all of the challenges with our health that really happen when we lose estrogen, when our ovaries age, they age out, and everything from heart disease to inflammation to insulin resistance to dementia, every tissue being affected. Then you talked about the fact that, really, and there's a study to show it, that you can go on estrogen at any age. There's specific tests you're going to want to do, and there's the lifestyle stuff to help with estrogen receptor sensitivity and rehab, receptor rehab. There's one other piece here, and that is the piece. And I just think about some close friends of mine who have had breast cancer and of course, are not allowed to take estrogen. Is there a time when someone should not, you know, and whether someone's had breast cancer or not, are there people who Are not candidates for estrogen replacement therapy. And specifically, what about someone who's had breast cancer?

Well, there are some exclusions to the use of hormones, as there is with probably every single type of therapy. So if you have an estrogen receptor and progesterone receptor, that's like progesterone for another day, but that's a very important hormone too. But if you have hormone receptor positivity, so all breast cells have receptors to estrogen and progesterone. And when you get a cancer, sometimes, in fact, in the majority of those cases, there is still receptor positivity. They're designed, they are developed from a cancer, they evolved from a cell that had those receptors. And as a cancer cell, they still have those receptors. And they can potentially. It's somewhat hypothetical that if you give exogenous hormones like estradiol and progesterone, that you may actually stimulate the growth of those cancer cells. Estradiol, among its many amazing functions, Is that it promotes different types of growth factors and growth factors in the brain can renew and create new neurons, and in the bone, new bone and rejuvenate and everything else. But in breast cancer, it can potentially grow breast cancer. Now, the biggest problem in terms of estrogen and breast cancer Is that breast cancer cancer creates its own estrogen source to actually feed itself. And estrogen receptor alpha is what all breast cancer is. So there is definitely a potential there that you might grow it. And estrogen is produced in the surrounding tissue around the breast cancer. It triggers the enzyme aromatase to create its own actual estrogen supply. It's amazing that cancer can do such things. So I would not use estradiol in someone who's being treated for breast cancer. Now, there's some interesting thing on the horizon. There is a fetal estrogen. I didn't mention this one. That's the E4, and that one has now been shown. It's not ever in a human adult, and I would not use it for hormone therapy. But in a woman who has breast cancer, it has been shown that, that I mentioned that breast cancer is always estrogen receptor alpha positive when it has the receptor positivity. Well, alpha actually has its own like variants. And it turns out that the variant of the alpha receptor that has the positivity in breast cancer Is not bound at all by this fetal estrogen estetol. So there is now research, and this form of estrogen will be coming out as an available form of estrogen on the market for menopausal women. And this might be the niche that it's actually appropriate for, for women who've had breast cancer or endometrial adenocarcinoma. That's uterine cancer, the lining of the uterus that also can have hormone positivity. And so for those, it may turn out that this fetal estrogen that does not activate the receptor for the breast cancer. And I don't know the research yet because it hasn't been done for the endometrial adenocarcinoma, but it probably will be. Okay, but I would have to see what the data shows. But for breast cancer, we do have the data that it does not bind to that particular form of the alpha receptor. But that group I would leave out. That's probably my only absolute exception to prescribing. And even then, there are some women that have ductal carcinoma in situ. They've been completely treated, it's definitely not a metastatic disease. And now they would like to think about hormones. And those women with adequate informed consent, of course, could be considered for hormone therapy, like after they've been through their treatment. And everything that we can possibly know says they do not have any residual cancer. Because if you don't have cancer, you're not going to stimulate something that doesn't exist. If you're treated and you're basically cured and it was an invasive cancer, so the risk of any kind of residual cancer lurking somewhere is pretty nil. Then those women could also be considered, but really that's the main group. Now, if you had someone who was end stage of life, probably I wouldn't be dealing with like someone who had end stage dementia. I know there's a lot of research and I totally agree that if you have mild cognitive impairment, maybe early stage dementia, that giving hormones has the potential to help revitalize the neurons. I'm totally for all of that. And we do have some data on that from Dale Bredesen and so on in his research. But once you have end stage disease, probably you've really missed the opportunity for any real substantial benefit. And maybe in those women there may be even some potential harm. So probably end stage life, end stage disease, probably not. But other than that, the field is wide open.

Well, that's really great information. Sadly, I don't think a lot of people know that information.

Now. They are learning.

You need to be out there teaching this, obviously. So hopefully this will get the word out some too, because I just hate the idea of someone suffering. And again, I feel so fortunate that I was surrounded. In fact, Felice, my 50th birthday party was Dr. Sarah Gottfried and Dr. Anna Kubeca and Dr. Jen Landa. It was like the estrogen was flowing. So I've never, from the time my periods got wonky, never not been on hormone replacement therapy and never intend to stop.

I applaud you for being on it from the get go and I am 100% for lifetime hormones. I say you decide to go off when you don't want to be healthy anymore. What kind of a thing is.

I'm like, I know what it felt like when my estrogen dropped. There was a little time in there when I wasn't aware and I couldn't recover from the gym. My gums bled. I'm like, what's going on? So no way. I'm not going through that. And my goal is to get this information out to as many women as possible so no one has to suffer. I know you created a Menopause 101 guide. We are going to make that available to everyone@jjvirgin.com Gersh G E R S H Every time I have you on I'm like, when am I getting you back on? I should just have blocked out an entire day.

Well, maybe we'll do a whole course sometime, unpack it.

Well, let's talk. Definitely. But again, I refer to you as the goat in this. You are the top, I mean the greatest of all time. I really do. When I just referred someone the other day, they're like, what should I do? I go, you need to go see Dr. Felice Gersh. That's it, go see her.

Well, I'm an old fashioned doctor. I still am in my brick and mortar practice and I see patients day in and day out and I just decided that I'm just going to do this forever. As long as that people come to me and I'm holding up, you know, my body is working. I just want to do what I can to help women one on one. But I also love like having platforms like yours because I'm definitely not going to see everybody. So this allows the word to get out because this is my mission, this is my legacy, is to try to change the trajectory of as many lives as I can. And I really appreciate you for having this platform and for inviting me.

Well, you have an open ongoing invitation. Again we'll put it@jjvirgin.com Gersh that will be the Menopause 101 guide. We'll link to this article that just came out that you wrote about hormones and heart disease. So we'll put all of that there and we'll get a date for the next one too. So thank you so much. Be sure to join me me next time for more tools, tips and techniques you can incorporate into everyday life to.

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