Does Estrogen Cause Breast Cancer? Dr. Felice Gersh on Hormone Therapy, and Risk.

Welcome back, Senergy listeners. We are going to answer that question today: does estrogen cause breast cancer? For so many women, that question is not theoretical. The words estrogen and breast cancer can carry fear, confusion, and deeply personal meaning, especially for women navigating menopause, considering hormone therapy, or living with the, the history of breast cancer themselves. And this conversation is personal for us too. Lori is a breast cancer survivor. So today, this discussion is not only from healthcare professionals and educators, but with real understanding of how tender this complicated and important question can be. The one reason we're so grateful for Dr. Felice Gertz to join us today— Lori and I have had the privilege of learning from her through A4M with her lectures and mentorship. And we know firsthand the depth of thought, experience, and passion that she brings to women's health. Dr. Gersh is board certified, dually certified as an OB-GYN and in integrative medicine. She's the founder and medical director of the Integrative Medical Group of Irvine. She's an internationally recognized speaker and educator and a bestselling author. So long before integrative medicine was the thing, she was looking at women's health through a broader lens. Asking not only how do we treat disease, but how hormones, metabolism, inflammation, lifestyle, and so many of the female systems work together. So today we want to have a thoughtful and nuanced conversation about estrogen hormone therapy, breast cancer risk prevention, and the questions that women are often afraid to ask. We want to talk about actually estrogen and breast cancer and what happened in the wake of the Women's Health Initiative. Whether all forms of hormones carry the same risk and how the conversation changes for a woman with family history, genetic predisposition, or a personal history of breast cancer. And just as importantly, we want to talk about what women can do, because this conversation should not leave you feeling afraid. It should leave you feeling empowered and informed and better equipped to have meaningful conversations. So before we Welcome, Dr. Gersh, into the conversation. I want to thank you for being here, for listening. I want to thank Lori for showing up and sharing her story today, too. And I want to get into it with Lori, if she doesn't mind sharing where she is on her breast cancer journey relative to hormone replacement therapy for herself.

It is a sensitive topic, right? And I think, you know, I am so glad to be here and be a part of it because I think not only as practitioners in, you know, in our clinics, when it's personal to us, it just makes us louder about it. And we need to be loud about it collectively as a community, right? So, my journey is this. I was diagnosed with invasive ductal carcinoma in 2018. And in, of course, 2019, faced with decisions of what to do and the angst around, do it quickly because that's what you do, right? Just get it out. And even as a practitioner, just faced with a lot of anxiety around what is the best thing to do. And my background, simply put, is I am a metabolic mess. Background history of diabetes and cardiovascular disease in the family. I have all of the genes, right? I got the best of all of, you know, my parents. But faced with all of those decisions, I had surgery. And years now, fast forward to where we are now in the past year and a half, I decided that I was going to actually do as I felt needed to do, was to get back on hormone replacement therapy, bioidentical hormone replacement therapy. And I say that with— it was a lot of angst because my traditional doctor were very against it, and even I had a hard time having conversations with them feeling like I, even having all of the knowledge I had, feeling completely inequipped to stand proud and stand firm for making this decision. So I know there are a lot of people out there today that this conversation is very important for them, whether they have breast cancer, they have a history of it in their family, or they have been Scared or feared into making the decision to never be on hormones. You're here today for a reason, and we have the best here to talk to you about it.

Yeah, Dr. Gerst, we just so appreciate you being here. And like I said, when we heard you speak at A4M in, I guess, April of this year at West Palm, Lori and I were both like, we have got to have her on for a conversation because this is such an important and tender conversation to be had. So thank you for being here.

It's quite a great introduction that you gave about the topic and how sensitive and how meaningful it is to every female. You know, every woman knows someone, is related to someone, has a best friend who's had breast cancer. I mean, it's like everywhere. Everyone knows someone. And now I know you, you know, and you have this history. And it is very frightening because there's been so much We'll say noise out there, bad noise about the role of hormones in breast cancer. So we'll start with what is a hormone's relationship to creating or initiating breast cancer as opposed to what if you've already had it? That would be like part B, like what do you do after you've had breast cancer? If we start with what causes breast cancer, What I can tell you is it's not human-identical estradiol, and it is not human-identical progesterone, and certainly not menstrual cycles, you know, having hormones that are aligned with what young women have. If we look at who has the highest incidence of breast cancer, women who are pre- or post-menopause, by far it's post-menopausal. Now, we do have an increase in younger women having breast cancer, but it's not because they have hormones. It's because of chemical endocrine disruptors that interfere with normal hormone function. And it includes, unfortunately, as a small increase in terms of its impact, things like oral contraceptives, Mirena IUDs. That's been shown that it has and impact, and this is all based on observational data. No one's doing a proactive, double-blinded, placebo-controlled study. So it's observational data, which always opens up a lot of Pandora's box kinds of stuff because there's a lot of variables, they're not controlled, and so on. So what is there about, say, hormonal contraception or the Women's Health Initiative, which did show a small, probably not significant statistically, increased risk of breast cancer in the women who were on what was called, still is, Prempro, a combination of conjugated equine estrogen called Premarin. And it's estrogen that a pregnant horse, a mare, is trying to exit its body through the urine. And it's gone through the liver to turn the estrogen product into a water-soluble You know molecule, so it could go out in the water, like which is urine. It's like water. So, and that's why it has the word conjugated. It went through the liver and went through this molecular biotransformation process called conjugation. And so the horse is trying to get rid of it. Okay, the horse says this is old yunky yucky old estrogen product. I want to get rid of it. And in addition to that. It's also including medroxyprogesterone acetate, we call MPA for short, which has the word progesterone in it, but it is not human progesterone. It's a completely different molecule that has very different effects in the body. You could call it a progesterone endocrine disruptor. So as an endocrine disruptor, it has alternate effects in the body than the real hormone, and it can actually act as an, like an agonist, like it turns on the receptor, or a blocker, an antagonist on the receptor. So it has different effects in different organs. It is not human-identical progesterone. And it turns out that in that horrible— I have to use the word horrible, I have no other word that I can put to it— Women's Health Initiative, which has been scaled into thinking that all hormones are the same, And that the products, the medroxyprogesterone acetate and the conjugated equine estrogens used in that study, their results with those molecules, which are never found ever, any time in any human female ever naturally in their lifetime, that somehow the effects caused by those molecules is the same as what human hormones cause in a healthy female. It's totally different. So The bottom line is from that study, it came out that there was a very small, like 24% increased risk of breast cancer. Now, the reality is that breast cancer typically takes quite a few years to develop. So if you go on something and a year later you're diagnosed with breast cancer, the odds are overwhelming that that breast cancer already was there and that it was just either initiated in terms of growing more or being found, but it didn't just initiate and grow and be found all within 1 year and so on, or even in 4 years. Okay? So probably the breast cancers that were found had already been there and maybe they were stimulated to grow, not initiated, but stimulated. But the bottom line is in that study, they did find a small statistically borderline, we'll say, increase in breast cancer. Now, in the arm of that study that did not include the medroxyprogesterone acetate, they only gave the Premarin or the conjugated equine estrogens. These were women who had a hysterectomy, and they believe that you only give progestins or progesterone to women if they have a uterus, 'cause they don't even understand the role of progesterone either. But in the women that were only on the estrogen product from the horse, They had, when they reworked the data, which has been reworked umpteen times, they found a statistical borderline reduction in breast cancer incidence in that group, which held. And then other studies have been looked at, which has also shown that estradiol, in fact, any estrogen that they used seems to reduce the risk of breast cancer, not increase it. And if you look at things like hormonal contraceptives, which do seem to have a mild increase, about the same as what they showed in the Women's Health Initiative, a small increased risk of breast cancer. It's because it seems the progestin, the fake, I'll call it fake progesterone product that's in it, because it turns out that another study was done more recently called the E3N study in France. And this study is groundbreaking in that it looked at biohuman identical estradiol and progesterone and found that when they gave the combination of the human identical estradiol and progesterone, they had no increased risk of breast cancer, zero in. It was neutral, like number one, it's equal, no increased risk. And further reworking, suggest a reduction in risk of breast cancer using these bioidentical human estradiol and progesterone. And when you give the hormones to be more human mimicking of a menstrual cycle, so you give the hormones in a cyclic manner as opposed to continuous, like you're not giving progesterone every day, you're giving it for 14 days or so out of the cycle, reduction in risk compared to if you give the progesterone daily and reduction compared to if you were on no hormones at all. So it's like completely upside down, 180-degree turn. But you can't convince doctors and you can't convince the public because the fear is now so ingrained that it can't— it's like I have to do like an exorcism or something to get this fear out of the brains of doctors and women alike. It's like, what will it take for them to understand that the Women's Health Initiative only represents in its conclusions what was studied, which was not human hormones? Nothing in that study is ever naturally found in a human. And the regimens, the doses, everything about it was unhuman. Unhuman. No human female has that. And it turns out, like they said, when they looked at the only estrogen arm that had the conjugated equine estrogens, the real culprit is that fake progesterone, medroxyprogesterone acetate, that in the breast tissue and maybe on the immune system as well, which is very not looked at enough because progesterone, human identical progesterone, is very anti-inflammatory. And when— but birth control pills are not anti-inflammatory. We know that. And it may be a lot of it is from the progestin, the fake progesterone. So in the breast tissue, the fake progesterone, medroxyprogesterone acetate, seems to be more an antagonist or like a blocker. It's like the antagonist to real progesterone. It blocks the real progesterone and its metabolites, how the body breaks it down and how enzymes in the body affected, totally different than human identical progesterone, completely dissimilar. So progesterone, human progesterone, is broken down into a whole variety of metabolites, you know, different molecules, by enzymes that are present in the brain, in the liver, and so on. None of those things happen when you take medroxyprogesterone acetate. So you don't get the metabolites. either that are proper. And when you take the wrong kind of hormone, it can also affect your gut microbiome. And there's some data that the gut, and this is also controversial now and it's been questioned, so not everything is so clearly understood, that the gut microbial population can impact on breast cancer risk through the creation of metabolites or breakdown products of estrogen through these different pathways that happen involving both the gut and the liver. Okay? And so these are like really important things that we're still trying to figure out. And some of these metabolites that are formed through the biotransformation, or you can call it detoxification process of estrogen, and they have the, what they call like 2-hydroxyestrone and 2-hydroxyestradiol and 16-alpha-hydroxyestrone. There's these different breakdown products that which ones are the preferentially made ones or not may, and this is, like I said, somewhat controversial. It was thought to be very sure. Now nothing is quite so sure, but may have some impact on breast cancer risk. So if you take the wrong chemicals, like these compounds like medroxyprogesterone acetate and the wrong kind of estrogen that never exists in a human, and you put them in the gut, we know that they can alter the gut microbiome in ways that may be actually pro-breast cancer inducing. So there's so many things that are still being worked on and being investigated, but more and more the data is supporting that human bioidentical hormones, which makes most sense because human beings didn't evolve to create cancer in ourselves when things are right. The idea that our human female life hormones made by the ovaries are designed to kill us is weird when you think about it, and there are mechanisms in play. Depending on what you think your audience would like to hear, I can talk about what is intrinsic to estradiol that actually can lower mortality if a woman gets breast cancer and she's on these hormones and actually works against metastatic disease. So we can go in all those directions, but I want everyone who hears this to know that the current data is that human identical hormones at least are neutral And maybe lowers the incidence of actual breast cancer. And that's the way I think it's trending.

Yeah, I would love some— I love some good news. And that is fabulous news for our female listeners, for sure. I want to go back to some conversation around the diagnosis of breast cancer and the information that women get, and how it can confuse them when they're thinking about estrogen replacement or hormone replacement in general. Like estrogen receptor positive and progesterone receptor positive tumors, right? Or negative. I think that can be a really difficult conversation for them to navigate because they don't understand the terminology, and it's just estrogen's bad, progesterone's bad, don't use either of them.

Well, the first thing to know before anything else, and we'll go over, is that if a woman gets a diagnosis of breast cancer, And it has strong, strong estrogen and progesterone receptor positivity. That's a good sign. Okay? That's a good sign. Now they say, "Oh no, that's bad." No, it's good. Now why is that good? Every breast cell, when it's born from a stem cell, right? All cells are like well not all. The vast majority of cells in your body are not the same cells you were born with. They live and they die. They have a life cycle and they're replaced by stem cells. That's why we have stem cells. That's the source of new replacement cells. So when a new breast cell is born, you know, there's different breast cells. We'll just say breast cells, okay? They innately have estrogen and progesterone receptor positivity. That's what breast cells are. They naturally have those receptors. They're supposed to have those receptors. So if you get a breast breast cancer and it actually has those receptors working, what it means is it's more like a normal breast cell. The worst kinds of cancers are ones that are really the most distant looking and functioning compared to the origin of organ cell that it came from. We call that poorly differentiated. Under a microscope, When the pathologist looks at the cancer cells, they usually put them into different grades. Like, it looks like low-grade, moderate, or like high-grade. Like, it looks like more normal-looking. It's cancer, but it looks more like a normal cell, or it looks like wild. Like, we don't even know what cell it came from. Like, we don't know what organ this came from. It's so wild. All we see is like— Cancer, it looks so abnormal, that would be poorly differentiated. And that happens sometimes. Somebody will have abdominal surgery and they have diffuse, like everywhere, metastatic, poorly differentiated cancer, and they can't even figure out what organ it came from because it's so unlike any tissue, natural tissue. So breast tissue that is converted into a cancer that looks and acts more like a normal breast cell, even though it's cancer, but it's more like a normal breast cell, is going to have a better prognosis. So the worst prognosis breast cancers are what they call triple negative, but it doesn't have functional receptors for— and we won't go into HER2 and HER— we won't go into that part. But in terms of estrogen and progesterone, when it's triple negative, that includes the 2 negatives, it has no receptor function for estradiol, estrogen of any kind, and progesterone. So there's no receptors that are working. Those are the worst prognosis cancers and they have the worst treatment available. So that's what you don't want to have the most. You don't want to have this receptor-negative cancer. So that's an important takeaway that the fact that you have a breast cancer that has positive receptors doesn't mean that the hormones cause the cancer. Every breast cell has those receptors naturally, and they should be strongly positive. That's what a normal breast cell would have. So if you have a breast cancer that looks and acts more like a normal breast cell than some wild, crazy abnormal cell, that's a good prognostic indicator. But it doesn't mean that hormones cause the cancer because the cell is acting more like a normal breast cell that has those receptors in it. So that's like a really important takeaway because I think that's what's really confused a lot of people. They think, well, if it has receptors, then it must be that the receptors somehow are related to the causation. No, that doesn't mean that at all. Not at all. Not even a tiny bit. So that's the first really important thing. And then if we look at like estradiol, what What are some of the things that nature gave as a function of estradiol that lowers the risk of dying from breast cancer? Well, there are genes that are actually modulated or controlled by estradiol. One is a gene that controls the cohesiveness of cells. So if you have a breast cancer, say, and, you know, no matter what you do in life, you can have the best hormones, you could eat the best diet, that doesn't mean you can't get breast cancer, right? Because we all live in— I hate to tell you, but I call it poison world. I mean, we live in a world where there's air pollution, water pollution. God knows what's in everybody's water. They don't test for everything. Like some of the forever chemicals, they haven't even been testing for them. So there's stuff in our air, there's stuff in our water. When there are fires, who knows all these chemicals from construction, You know, breakdown burning products and everything that gets into the air. And then of course, all the different plastics, the bisphenols and the phthalates and the pesticides and the herbicides. Even people who eat everything organic are still getting these chemicals because they blow in the wind and the water and they contaminate the organic foods as well. You know, it's less, it's best to eat organic, but it doesn't mean you're not going to get any pesticides. And who can always eat organic? Do you ever leave your house? You know, so And sometimes you buy organic and it says organic from a country. It's like, I don't know, is anybody actually testing it there? You know, so there's a lot of faith and trust. And sometimes you scratch your head and said, I'm not sure that I paid double the price and I even really got organic. Like sometimes you're not sure. So, and then we all live in a world with, we go outside and we don't know if they sprayed that building for ants or cockroaches yesterday. You know, we go in airplanes and they're full of flame retardants and they're always spraying so that bugs are not running around the floor when we're flying. From one country to another. Nobody wants to sit in their airplane seat and see cockroaches running up and down the hall, you know, of the middle area of the plane. So they spray them with all kinds of stuff and the flame retardants. So no matter what we do, we're exposed to chemicals. And these chemicals are very heavily endocrine disruptors. So they interfere. Many of them are what we call xenobiotics or xenoestrogens. They interfere with normal estrogen functioning in terms of blocking the receptor, the production, the degradation, the distribution. All kinds of ways that it can interfere. That's what endocrine disruptors do. And so you can do everything right, but you're still living your life and you're getting exposed to stuff, and you can get breast cancer because your genes may predispose you. Maybe you had childhood traumas and emotional things that happened that you can't control for. So there's a million things we can't control for in this world. So the bottom line is that You know, if you do get breast cancer, don't blame yourself. Don't blame— you know, there's nothing— there's no blame game here. But, you know, when you do get breast cancer, knowing that the estrogen that you have or had in your body did things like increase cohesiveness. So if you have breast cancer, what kills you? What kills people with breast cancer? It's not the breast cancer in the breast. Women don't die of breast cancer in their breast. What they die from is breast cancer that metastasized, left and traveled and implanted in other organs like their lungs, their brain, their liver, bone, which doesn't usually kill them but is miserable. But in the liver, in the pleura, and all these other organs, it can kill people. So what causes metastasis? It's the cohesiveness. So if you have a breast cancer and all the cells of that cancer, even though it's locally invasive, it's growing in the breast, it's invading in the breast, but the cells are very tightly glued together, like they're superglued together, then they're not going to break off, travel through the lymphatic system or the blood into distant organs to implant and grow. So That feature, cohesiveness, is controlled— that gene is controlled by estradiol, and higher levels of estradiol cause more cohesiveness. So that's why if a woman in menopause is diagnosed with breast cancer and she's been on hormones, her prognosis is better. She's less likely to have metastatic disease. Because her cells are more cohesive of that cancer. So may I say something?

So basically what you're suggesting is what we shouldn't do is immediately take them off their hormones at the point at which they're diagnosed, but yet we see that all the time.

We have limited data on this. This is like, because it seems intuitive, but nothing is intuitive. You have to prove it. It seems intuitive that if you have a breast cancer, that is positive for receptor function for, say, estradiol and progesterone, but we'll just say focus on estradiol, and it has positive receptors, even if you take out of the philosophy that the estrogen caused the breast cancer, because we know it doesn't, but then you say, but now you have breast cancer and it does have estrogen receptor positivity, if you give estrogen, Will it stimulate the growth of that breast cancer? The bottom line is that we have data looking in both directions. Okay? There is some data that suggests that it can stimulate the growth, and there is other studies that suggest it does not. And nobody's doing a placebo-controlled double-blind study. So once again, these are observational studies because who's doing this study? Like nobody is doing this study properly. It's not being done. So Most of the couple of studies that suggest that if you give estradiol, we'll say estradiol or other form of estrogen, to someone who has estrogen-positive receptor breast cancer, those studies, which are observational, there are many flaws in them. So when they've been analyzed, it's like, well, there's these flaws. It wasn't controlled for this or that. And so the bottom line is that There is some suggestion it may promote the growth. And then there are other studies that show it doesn't, that it does not. And there were some studies that were also observational years ago looking at women who became pregnant. This is a long time ago, who became pregnant after a breast cancer diagnosis. And as a general statement, they did better. They did better than women who didn't become pregnant. And of course, the hormones of pregnancy are not the same. As what you have in your body when you're not pregnant. But if anything, it seemed beneficial, not harmful. So it's just interesting. And yes, we do need to have controlled studies, and I don't think they'll ever be done. Okay? I don't think anyone's ever going to do them. So we have observational data that is conflicting. So what I personally am recommending is that, and I'm just being, you know, I live in the regular world too, you know, so I can't be so deviating from everything, but I give informed consent. I think if you have a woman who has what isn't really truly, it's not invasive breast cancer like you had, it's ductal carcinoma in situ. Now, fully one quarter of diagnosed breast cancers And they call it breast cancer, but it's not invasive. So it's like a little different creature. In situ means it hasn't been— it hasn't broken below the basement membrane and spread. But the cells themselves don't look normal. So they call it ductal if it's coming from the ducts, if it's from the lobules, which is where you make milk. So there's the 2 basic— there's some rare things, but the 2 basic types of breast cancer are ductal, which is coming from the ducts. They're like the little tubes that take the milk and feed it to the nipple so the baby can suck the nipple and get the milk out for breastfeeding. And ductal carcinoma is the most common. And then lobular, that's where the milk is made. That also happens, but it's less common. But you can have in situ cancers where it hasn't broken through and invaded the tissue, but it looks like cancer cells. Of either lobular or ductal, but ductal more common. But a quarter of breast cancers diagnosed are called ductal carcinoma in situ. And about 20% of those diagnoses will progress to invasive cancer, maybe 30%, but the majority will never turn into life-threatening invasive cancers. And that has been a big challenge, like, because why should those women be deprived hormones? Why should— They don't have invasive disease. Well, they're trying to figure out which of those types of cancers, so to call, we'll call them cancer, ductal carcinoma in situ, will progress to invasive and which ones won't. Because then maybe we could treat women appropriately, not treat everyone the same. There's some ongoing studies where if they have grade 1 or 2, so that's not like wild-looking cells, that they have been observed. Instead of doing surgery, no surgery at all, no treatment, just watching, like watchful waiting. At the end of 2 years, the study only went for 2 years, what did they find? In terms of invasive cancer, statistically, they were identical between the women who were treated with surgery and the women who just were watched, they actually had the same incidence of invasive cancer. Isn't that amazing? So that may turn out to be a way of dealing with these things. But unfortunately, in terms of the emotional impact, it was the same. So whether they had surgery or they were watched, the horrible emotional impact, the PTSD, that's for— it was the same in both groups. But understanding that a quarter of all so-called breast cancers are not invasive is an important takeaway too. If you treat, as I look at it, women uniquely for each type of cancer and what's happening with it, if it is low-grade, so it doesn't look too wild, or it's ductal carcinoma in situ, doesn't look too wild, It's excised. Let's say it's not being observed, so they do a lumpectomy. They may or may not even need or feel the need to do lymph nodes in the axilla under the arm. Sometimes they don't do them anymore for cases where they know the odds are overwhelming there's not going to be any cancer in the lymph nodes. But say they even do lymph nodes and it's negative. Okay, so there's no evidence of spread. That looks like the margins are clear, they got all the cancer, plus minus if they had radiation. Radiation is only about recurrence of breast cancer in that breast. It is not a life-saving treatment doing the radiation of the breast in the vast majority of cases. It is just about lowering the incidence, not eliminating it, but lowering the incidence of recurring breast cancer in that breast. But when, you know, if you look at those women, the women that by all appearances are cured, they have had the breast cancer or the ductal carcinoma in situ excised. There is no evidence of any residual cancer. There is no lymph node positivity. The chance of metastatic disease is never zero, but it is really low. I personally think those women should be entitled to go on hormone therapy knowing that hormones don't cause breast cancer. Could they grow breast cancer? Maybe, maybe not. We don't have a definitive answer, but if you have no breast cancer, then you're not going to grow breast cancer. The fear is that there's some microscopic spread somewhere And going on the hormones is going to trigger its growth. But here's some important information on that: What typically causes breast cancer? Say you have a little metastatic disease in the lung or in the liver. What would cause that metastatic breast cancer to grow? Well, yes, it can be estrone. It can be estrogen because estrogen. Causes the creation of growth factors, which can grow everything. I mean, which is essential for how you repair when you have injured tissue, how you replace cells that die. I mean, you have to have growth factors or you can't be alive. You know, that's how you repair, replace, and maintain and everything else. But if you create growth factors that can grow breast cancer, that's the fear. But what is really the cause of those growth factors? Breast cancer itself is extraordinarily inflammatory, and inflammation triggers the activation of the enzyme that's present in surrounding tissue that we call the stroma. It activates an enzyme that's been just kind of like dormant. That enzyme is called aromatase, and that enzyme causes the conversion of Androgens, mostly coming from the adrenal gland, into estrone, E1. It's a different estrogen than what we give for hormone therapy. It's not the hormone that's made in the estrogen family by the ovaries. So estrogen is not a hormone, it's a family of hormones. The hormone estrogen made by the ovary is called estradiol, and it has a name. And it has a letter and a symbol and numbers. It's E2. Estrone can be made from estradiol, but it also is made from androgens coming from the adrenal gland, which is the vast majority of androgens in the body. And when you have inflammation, it blocks the enzyme to convert it from estrone into estradiol. So you get stuck with estrone. Estrone is a weaker estrogen. It binds to the receptor much weaker than estradiol, but it binds to create growth factors. It's the alpha receptor that it activates, which is the receptor that's positive on breast cancer that creates growth factors. So the breast cancer itself creates its own estrone supply in the tissue surrounding it by upregulating the enzyme aromatase through its inflammatory processes and creates its own supply of growth factors. But here's the thing, estradiol downregulates the enzyme aromatase and it downregulates inflammation. So you could be reducing the ability of breast cancer to create its own growth factor factory. And that is probably one of the main reasons why estrogen given in menopause lowers the risk of breast cancer, not increases, lower, by lowering lowering the function of breast cancer to create its own growth factor factory, and also by reducing inflammation. Inflammation in cells creates old cells, damaged mitochondria, and mitochondria that are damaged is the main source of damaged signals that create a systemic like feed-forward inflammatory process. And inflammation causes misfolded proteins and DNA damage that can lead to altered chromosomes, DNA damage, and the production of cancer. So also estradiol controls the health and function of mitochondria. Mitochondria are known as the powerhouse of the cell. They create energy, but they also control what's called the cell cycle. It tells old cells that we call senescent cells that it's time for them to die, to commit programmed cell suicide or apoptosis. So cells in the body get old and then they kill themselves. Like, it's amazing, right? That it— and then they get replaced with new cells. But what happens if the old cells just keep living and they don't die when they should? And they create all this damage and inflammation response. Those are sometimes called zombie cells, and they create more and more systemic body-wide inflammation. And those cells are not good cells at all, and they can get the misfolded proteins, the damaged DNA, and develop into cancer cells. Estradiol, the estrogen from the ovary, controls all of that so that you are less likely to create these zombie cells, these old senescent cells that create cancer. So estradiol has multiple mechanisms to lower the risk of breast cancer in the first place, but also to potentially lower the risk of activating and growing metastatic disease by lowering the inflammatory process in the first place to reduce that enzyme aromatase, creating the estrone that creates the growth factors to grow the localized breast cancer in the liver, in the lungs, or wherever it may have metastasized to keep it from growing. But of course we need more studies, we need more data, but we understand a lot of the mechanisms that make it logical, at least from a scientific perspective, to allow women who have these early-stage breast cancers, no evidence of metastatic disease, to go on even if, 'cause we don't know for sure if estrogen will grow metastatic disease, but it may reduce metastatic disease from actually growing. But at least if women have no evidence of metastatic disease, it looks like they're cured, they didn't have wildly aggressive cancer, for them to be enabled to actually go on hormones. The problem is the mainstream medicine world does not see hormone therapy in women in menopause as anything more than for reducing night sweats and hot flashes. I see it as a very important, viable tool for healthy longevity. We have a completely different outlook on what hormones can do for females. If all you see is reduction of night sweats and hot flashes and you don't see healthy longevity as a huge aspect of what hormones do in the female body in menopause to maintain the health and function optimization of every organ system for many more years than you would have if you didn't have the hormones on board, you have a whole different viewpoint of what the point of hormones are. So the mainstream medicine still only looks at hormones for treatment of night sweats and hot flashes. And so if that's the only point, then why would you give hormones in women in menopause who've had breast cancer when you have other drugs available that can help to reduce night sweats and hot flashes reasonably. But if you're like me and you see hormones as a critically important tool for healthy longevity, for optimization of cardiovascular health, musculoskeletal health, neurological health, skin health, you name it, right? Then you view the whole point of why you would want hormones in menopause after a breast cancer diagnosis completely differently. And that's that huge divide between how I see hormones and how they see hormones in menopausal women. If we don't agree on what the point is, of course we're not going to agree on what the next step is.

I love that. You have said so much. And right now I'm going to have to tell you that I have brain envy because you have just spoken out so much biochemistry and so many pathways. That is just incredible. And I love it. You know, for our listeners, you've teased some things about metabolic health when you talked about aromatase and how that all happens at the breast tissue. We think about visceral fat and we think about inflammation and how that drives that aromatase activity. There's so much power that our listeners have in preventing all chronic disease states, even breast cancer.

Absolutely. So estradiol— and they've actually shown it's predominantly the alpha receptor— so estrogens activate more than one type of receptor. It's complicated. There's alpha and there's beta. We love Greek letters. And then there's the G-protein-coupled receptor. Alpha and beta predominantly work through the nucleus of the cell to create proteins, but they also work on the cell membrane to create very rapid effects. The G-protein-coupled receptor works exclusively, we think, on the cell membrane. And these receptors interact with one another, they talk to one another, so it's very complex. Well, it turns out that the alpha receptor, which is the one that's on breast cancer, by the way, but the alpha receptor is very critical in adipose tissue, fat tissue, for creating important metabolic effects and the production of even hormones called adipokines, like adiponectin, which is critical for creating the stimulus for AMP kinase, which is how we burn fat. Like, the fat-burning signal actually interestingly comes from fat, you know. So, and it's all modulated, regulated by the alpha receptor from estradiol. So when you don't have enough estradiol present, You don't make enough adiponectin. You don't have proper functioning of adipose tissue, so you don't burn fat properly. And so the default is you store and create more fat. And the default is visceral fat, belly fat, and fat around the organs and in the organs, like in the liver, in the pancreas, even in the heart and bone marrow. And that's why women after menopause have significantly increased incidence of what is called hepatic steatosis or fatty liver. Okay? They keep changing the name, but we'll just call it what it always was called, fatty liver. And it doesn't mean you're fat. You could be thin as a rail and have fatty liver. I mean, so it's not an insult to say you have fatty liver. It doesn't mean you're fat. Not that that's an insult either, right? It doesn't mean anything except you're probably in menopause, right? Okay. So it's a very big problem. And if you don't have enough estradiol and you don't have the activation of that alpha receptor in adipose tissue, you're going to get what so many women I hear from all the time. They come in and they say, I don't know what's happening to my body. It's morphing. I'm doing nothing differently. In fact, I'm eating less and exercising more and I lost my waistline. My body is transforming into some SpongeBob kind of character. I have all this belly fat. I have a muffin top. I don't know what to do. I'm gaining weight and I feel awful. I don't understand. I can't fit into my clothes. I want to wear muumuus. That's all I want to wear is a muumuu. I feel terrible. And it's not their fault. If you don't have estrogen in the right amount, in the right type, you don't activate alpha receptor in adipose tissue, you can't properly burn fat and you collect it and it collects in the viscera and in the belly. So these are like why the optimal time to start hormone therapy is in the perimenopause, because it's really hard to reverse a lot of these things. I mean, I, you know, this is where you get into fasting-mimicking diets and time-restricted eating and high-intensity exercise, all these things. And of course, GLP-1 receptor agonist drugs to try to find ways to get rid of this accumulated belly fat and visceral fat. But the reality is that if you start hormones and if you've led a pretty healthy life up to that point, I mean, you could be unhealthy, very unhealthy, and be 21. We know that, right? But if you've led a good, lucky, you know, lucky you, you came from enough money that you could buy good food. You know, you weren't living in a desert, a food desert where you had nothing but, you know, fast food places to eat at and couldn't get any fresh organic vegetables or anything. So you were lucky enough to have the funds and the education to know how to properly feed yourself, and/or you had parents that gave you healthy food, you had clean air, you had clean water, reasonably so, you exercised. So by the time you got to perimenopause, you were actually been pretty healthy. I call that your health savings account. You get to perimenopause and you actually are in good health. Not everybody does, but you're in good health when you reach perimenopause. You need to start on hormones then. To wait until you're a year out of having no periods—that's late in the game. That's late-stage ovarian aging. We want to get started early because stuff is happening a few years before that final period during the perimenopause, and some of those things that are happening are obvious. We call them overt. Some of them are invisible to you. They're covert, but they're happening whether you know it or not, and they're bad for you. So it's much easier to prevent than to reverse. They have now plenty of studies showing that women who go on the GLP-1 receptor agonist drugs, they do much better in the menopause if they're on hormone therapy. Estradiol modulates how almost everything in the body works, including the vast majority of the peptides The hormones, the neurotransmitters, most all, and with progesterone you add in as well, most, not all, but most are under the control of these vital life hormones. I don't call them sex hormones anymore. They're life hormones, the givers and maintainers of life itself. And these hormones control so many things, including GLP-1 receptor function and production. So, you know, if— but if you go on these hormones and you exercise and you eat the right food, then you don't need these drugs. Because guess what? You actually make your own GLP-1s the way you're supposed to all your life. You don't need to take a drug. You can actually be healthy. And estradiol controls— and this is a little off topic, but you talked about you open the door for metabolic health in terms of like cholesterol. And all of these things, metabolic health, in fact, people talk about cancer is a metabolic disease.

100%.

Cancer is happening in people who are metabolically unhealthy. The biggest risk for breast cancer in postmenopausal women is weight gain and obesity. And of course, that goes along with insulin resistance, diabetes, vascular disease, You know, all these hypertension, all these things. So estradiol is the master. It's I call it the master of metabolic homeostasis. It keeps everything on track. So if you want to have good metabolic health, you want to control your appetite, energy burning to match your energy intake. That's like really critical, and it's all messed up as we age and. You know, so that your appetite should actually regulate how much you eat to actually give you what you need instead of giving you more than you need, right? So we have controlled appetite. You control the production of nitric oxide that keeps arteries healthy. You maintain the proper gut microbiome. You maintain your immune system so it doesn't go into an activated pro-inflammatory situation, which is what happens after you lose your estradiol, is that your immune system becomes more innately pro-inflammatory. There are immune cells— every immune cell in the body has estrogen receptors on them, and many have like progesterone receptors. When you lose these hormones, you lose control of your immune system, and it becomes more like a weapon of mass destruction, I think of, without control. Because these weapons, these immune cells, instead of saving you, can harm you. That's what they talked about in COVID when people had— they called it a cytokine storm. Your immune system became so pro-inflammatory that it actually destroyed you. You know, that we don't need. But it's kind of happening on a low-level basis in menopausal women. And so that's what happens in our bones, our embedded Immune cells called osteoclasts—they're a special form of immune cell, a macrophage that's embedded in bone—they become like weapons of mass destruction, and without estradiol to control them, they start gobbling up and destroying good, healthy bone. Like, and this is what's happening in the brain too—that can increase the risk of Alzheimer's disease. There too, in the brain, are these embedded immune cells called microglia. That are designed to help us if we have an infection in our brain, injury to our brain, but instead, without estradiol, they become like totally dysregulated, activated, and can actually destroy good, healthy neurons. This is what happens when you don't have estradiol. And the immune system, which acts as a surveillance system to essentially gobble up bad cells that could turn into cancer cells, they don't do that. They're not gonna do their job properly. So that's why older people, Who's more likely to get pneumonia and die? Old people, right? They always—you always hear that. Who's more likely to die from the flu? Old people and very young people because their immune systems are still evolving. Old people, their immune systems are de-evolving, right? They're working backwards. They're not working properly. And so older people are more likely to get cancer because their immune systems are not properly surveilling. They're more likely to get. Sepsis and die, infections and die, and immunosenescence— that's what we call it, aging inappropriately, you know, functioning, but aging of the immune system— we call immunosenescence is definitely going to happen younger and more severely if you don't have enough hormones. So, and yeah.

Dr. Gersh, I want to go back because you, you painted the picture of the female that lands in perimenopause in reasonably good health. And you said start hormones, right? Start them early and follow yourself through menopause. What about the female that lands there and maybe she doesn't have a chronic disease yet, but she knows her gas tank is completely empty? Like stress, lack of sleep, poor food quality most of the time. Maybe she's working out.

Yeah.

Maybe excessively.

Right? And that can be a stressor on the body too. So what is the advice in that category? Where do you go from there?

Every woman needs to optimize lifestyle. So I always say being healthy is like keeping a 1,000-piece jigsaw puzzle together. The hormones make up the 400 central pieces, but lifestyle make up the surrounding 700. Okay. Or actually 600. I could do the math. Okay. So it's 400 are the hormone pieces in the center, 600 are the surrounding. And we know that when we put a 1,000-piece jigsaw puzzle together, we always start with the rim, right? The straight edge. So the foundation of health is lifestyle. So if you are having a terrible lifestyle for all kinds of reasons, good, bad, whatever, you know, So you have to start there. The hormones are essential. I always say necessary, essential, but not sufficient. So if that's why— if you just give hormones, that's why I hate— I have to use the word hate— these hormone dispensaries online where all they're doing is throwing hormones at people and without even like knowing anything.

And that's why I wanted to ask that question, because so many people are going to hear this conversation and think, oh, I just need hormones. But if we do not optimize lifestyle, right, with what you mentioned before, detoxification—

if, if I had to choose, which I don't, between an optimized lifestyle or optimized hormones, I would choose optimized lifestyle. But I don't have to make that choice, not yet. I hope never. But the, the two together is what keeps your thousand-piece jigsaw puzzle together so you can see the picture of that puzzle, right? So If you don't eat the right foods, if you don't get enough sleep at the right time, if you have no fitness— fitness is a vital sign. Exercise is medicine. This is not like frivolous stuff. This is like critical, essential to health. So you need to have fitness, which involves having a good range of different types of exercise— aerobic, resistance training. You need to have Sleep. You need to deal with stress. Stress creates sympathetic overload, which is what women have without any reason other than going into menopause. They have reduced vagal tone. The vagus nerve controls—they call it rest and digest. It keeps your body, like your immune system, from going into a pro-inflammatory state. It keeps your organs working right. It keeps your intestine and like proper motility and digestion right. And that's why they sometimes call the vagus nerve rest and digest. And you don't have enough vagal tone when you go into menopause. The neurotransmitter for the vagus nerve is acetylcholine, of course modulated by estradiol. So if you don't have enough estradiol, you go into the default, which is the pro-inflammatory stress-induced sympathetic part of the autonomic nervous system. A component of that is called adrenergic activation of the adrenal gland. You make too much cortisol. Too much cortisol will affect your appetite. Your insulin resistance, your gut microbiome, leaky gut. So stress management of stress is not optional, and there you have to try to increase vagal tone through things like meditation of all sorts, guided meditation, you know, and there's you know nature meditation, prayer meditation, exercise is actually also good for the vagus nerve. And you know, working on like massage, essential oils, all these things are laughter yoga. They always say gargling cold cold plunges. Cold plunges and gargling are not my favorites. But you know, laughter, you know, I say laughing is the best medicine that increases vagal tone. So you got to work on stress. You got to work on improving your vagal tone. You have to manage sleep, which is a big problem. Estradiol. Creates and controls the neurotransmitter serotonin. And from serotonin comes melatonin, which is a potent antioxidant, also important for sleep, right? So if you don't have enough estradiol, 100%, you'll have disordered sleep in some— not only just from night sweats and hot flashes, but because you don't make enough melatonin. And you go— they've shown that even if you Give a drug that treats hot flashes, but you're not increasing estrogen. You're still going to have abnormal sleep patterns. Okay? Most women they wake up at two three in the morning. They can't fall back to sleep. So we have to work on optimizing sleep, and you can never underestimate the importance of love and purpose. So you have to have if you have toxic friends, maybe you have to make new friends. If you have toxic family members, you can't like divorce all your family. But you can create— I call it an imaginary force field around you. So when you have to be with toxic people in the workplace or family, just create this imaginary force field around you and say, your, your bad spirits can't hurt me. You know, I can just go through this day and, and it bounces off. It's like bounce, bounce, bounce. You know, can't get through my force field to harm me. I love the wisdom. I love that wisdom.

I know we've got to wrap up today. We could, we can We could stay here literally all day long. I know we could. But if we could ask you one question about your personal health, like what has been the biggest thing that has made the impact on your health for longevity, for vitality? I mean, you can tell you're young and vital. You're still out there actively seeing your patients, going and lecturing, spreading your wisdom. What, what has done that for you?

Well, this is almost like cliché already, but for me, it's actually the hormones. I went into early menopause, and I've been working out why that happened to me. But at age 43, I was completely in menopause. 43. That's early menopause. That is really bad. The earlier you lose your hormones, the worse off you are. And at that time, hormones were like Poison. That's how they were viewed. But I never viewed it that way. Even when the Women's Health Initiative, I begged my patients to stay on hormones. But I knew hormones were really important. I was really devastated that I was already in menopause at 43, but I knew I needed hormones. And now, so many years later, I think, where would I be? What would my body be like if I hadn't had optimized hormones, even when I went into such early menopause. Because, you know, I mentioned that lifestyle is— if I had to choose, I would pick lifestyle. Well, I was already trying to, except for, you know, like a little stress in life, you know, okay, so I have a stressful job. But for most things, like, I really— I was fortunate. I knew what to eat, and I ate lots of healthy plants. And, you know, I had a pretty good environment, you know, I had, you know, air purifiers. So I was very fortunate that my lifestyle choices were already very good. So, but my hormones were completely gone, like literally gone. So the best thing for me, for my healthy longevity, was that I replaced my hormones as optimally as I could to be more physiologically dosed and rhythmed so that I could withstand the loss of my hormones at such a young age, so that as I'm getting older and older I don't feel it. I know, I know I look in the mirror and I look at old photos, I show it some, but I don't feel it. And I feel that it's enabled me to have healthy longevity. There's no way to know if and how many years it could have cut off my life by going into early menopause. We know statistically women who lose their hormones earlier live less numbers of years, but I'm hopeful that by replacing my hormones, it has facilitated Healthy longevity. So for me, it's the hormones.

Well, thank you so much. Like Kelly said, we could stay here forever. Thank you for just your contribution to our lives, to the lives of those that we get a chance to treat. You carved out time in your schedule to be with us today, and we really appreciate that. But I just, you know, I'm just very grateful for the encouragement that you've given me as I have listened to your lectures to stand up for myself and actually have better conversations, not just on behalf of myself, but to be able to come alongside of patients and feel confident that we're making good decisions collectively together. So thanks for sharing all of that with us. Stay the course. We gotta have you around, so you gotta keep fighting.

I will.

That's all right.

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