Ep. 297 Dr. Felice Gersh: Estrogen, Immunity & Menopause Mysteries

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Ep. 221 Part 1- An Integrative Approach to PCOS and Menstrual Irregularities with Dr. Felice Gersh

Ep. 237 Perimenopause and Menopause: What You Didn’t Know with Dr. Felice Gersh

Transcript:

Cynthia Thurlow: Welcome to Everyday Wellness podcast. I’m your host, Nurse Practitioner, Cynthia Thurlow. This podcast is designed to educate, empower, and inspire you to achieve your health and wellness goals. My goal and intent, is to provide you with the best content and conversations from leaders in the health and wellness industry each week and impact over a million lives.

Today, I was joined again by the very popular Dr. Felice Gersh. She joined me on Episodes 237 and 221. She is an award-winning physician with dual board certification in obstetrics and gynecology, as well as integrative medicine. Today, we spoke at great length about the role of estrogen and immune function in the body, the impact of ovarian aging, menopause, loss of bone, ligamental challenges, sleep and mood, cognition, the gut microbiome and vascular system. Today, we spoke about different types of estrogens, different types of estrogen receptors, the role of inflammation, and the impact on the gut microbiome, as well as speaking quite extensively about the critical window for hormone replacement therapy and how she best serves women in perimenopause and menopause with regard to early versus late hormone replacement therapy. I know you will find this conversation with Dr. Gersh invaluable as I always do, and don’t be surprised if we have a fourth or fifth podcast together later this fall because she’s just such an incredible resource for women. I know you will find this conversation invaluable.

Welcome back, Dr. Gersh. It is such a pleasure to have you back on and I’m not sure if I’ve told you this in particular, but over the last three years I track information on the podcast metrics, analytics, and our second podcast together is the most downloaded of the past three years. So, it just goes to show how much your message resonates, how much my listeners know and appreciate the incredible resource that you are. So, I’m so very grateful to have you back on today to talk about a topic that I think for many listeners, we haven’t really explored at any great length on the podcast, but one that for every woman in perimenopause and menopause is really helpful for them to understand what is happening in our bodies as we are transitioning into menopause and the net impact on immune function. And for anyone that’s listening, that’s thinking that doesn’t sound like a particular sexy topic, I reassure you, after Dr. Gersh and I have this conversation, you’re going to be very vested and want to do everything you can to support immune function and hormonal balance in the body at this stage in our lives.

Dr. Felice Gersh: Absolutely. And it’s such a joy to be back with you. And I’m really excited about this topic because it certainly is not one that’s well discussed, [Cynthia laughs] it’s not widely recognized the critical role that immune function plays in all aspects of health and the changes, the dramatic changes that occur with the transition into the menopausal status.

Cynthia Thurlow: What’s interesting to me is even as someone that has traditional, both allopathic and functional integrative medicine training, I didn’t realize until I went into menopause the changes that were happening. They may not have been visible on the outside, but when I was looking at labs with my functional integrative medicine physician, I was like, “I cannot pretend that I’m not seeing changes in my lipids, in my insulin sensitivity, in a lot of different things that are going on.” So, for women that are listening that maybe perhaps are not on HRT yet or have not started that discussion with their providers, understanding that you don’t have to look unhealthy from the outside to have changes going on at a cellular level that are quite significant in this transitional period. 

Dr. Felice Gersh: Absolutely. In fact, I have really changed my own approach and over the last just very few years, I’ve really started supplementing hormones during the perimenopause, because the whole notion that menopause is crossing a finish line [chuckles] is so absurd. It’s a process and conventional medicine has looked at it as well. You’ve reached that point, 12 consecutive months without any bleeding. We don’t even know what that bleeding is. That’s why I can’t say without a period, because it could be just dysfunctional uterine bleeding from hormonal imbalances. Not necessarily that you ovulated. So, you go 12 months and there is no bleeding, and then suddenly you have that title, you are in menopause and the rest of your life will be postmenopausal years. And that is so incorrect in the whole view of what’s going on, because it’s a process of ovarian aging or ovarian senescence. And during that time there are hormonal fluctuations with a general trend downward. And we now know that long before that so called last period and last end of reproductive life, that there are changes like loss of bone, there’re changes in the ligaments, in your joints, there’re changes in sleep and mood, and cognition like word finding, especially nouns, people can’t remember names and such. And this is very, very, very prevalent.

There’re changes in the gut microbiome, there’re just loads of changes. There’re changes in the vascular system. Plaque starts to develop, blood pressure starts to rise, and plaque, of course, is the instigator to heart attacks and strokes. So those risks really start to accelerate. And none of this is really taken into account because it’s just viewed as aging as opposed to loss of these vital life hormones. So, I look at it, kind of like thyroid. No one waits till you have no thyroid function. Your thyroid gland has evaporated. No, when you have lower thyroid production, you get thyroid supplementation. Well, if you have reduced hormone production from your ovaries, you should have hormone supplementation. And when hormone production ceases in terms of no production of estradiol, the estrogen from the ovary or progesterone, then you have hormone replacement. So, before that it’s hormone supplementation. And this, I think, is really a new idea of viewing women’s transitional health years. And this can make a total major change in the future of women’s health and longevity, healthy longevity, not just surviving.

Cynthia Thurlow: And what’s interesting to me, as I certainly my training came about in the 90s and early 2000s and when I finished my nurse practitioner program in 2001 and I drifted off into cardiology, this preceded the Women’s Health Initiative. But I recall how many of my patients, all of their HRT, their hormone replacement therapy was stopped because of the results that came from the WHI which thankfully, we now understand was an improperly interpreted study, really not looking at a healthy population. And we’ve unpacked this on many other podcasts, so I don’t want to go down that rabbit hole. I think, from my perspective, looking at HRT, looking at this transitional period in women’s lives, helping them understand that the time to intervene is not to wait until you have your final menstrual cycle, as you’ve stated. It’s to really help women understand that if we are supplementing with hormones in that perimenopausal period, you probably will have less side effects.

You probably will make a less dramatic transition. And what I see on a daily basis across social media is how many women are suffering in silence. They’re being told, as an example, I was in a group the other day and they said, “Oh, my physician put me on oral contraceptives. That’s to help me transition into menopause.” And I know your feeling and mine are very similar on this and helping them understand, “Well, that’s not actually replacing your hormones, that is suppressing your natural production even further and actually introducing an endocrine disruptive chemical into your body.” And so, helping women be their own best advocates. And so that’s why I love and appreciate your work so much because you are the consummate women’s health advocate and physician. One thing that I think is really interesting when we’re talking about estrogen as an immune modulator is talking about these different types of receptors, the estrogen receptor alpha, the beta receptor. Can we start the conversation there? Because I think some of this physiology is actually quite interesting and I know my listeners would probably agree with that as well.

Dr. Felice Gersh: Well, yes. And the first thing to just touch on is the word estrogen. Because like, you talk about estrogen receptors. But what is estrogen? Well, estrogen is not a hormone, it’s a family of hormones. And there’s basically in the adult female, human female, there’s three. There’s estradiol, which has a letter and a number so it’s E2 and that’s the estrogen made by the ovaries during all the reproductive lifespan of a woman. There’s E1, which is estrone, and that becomes the dominant estrogen, which is predominantly made in fat tissue, adipose tissue, in metabolically unhealthy women who have excessive amounts and a lot of inflammation and also in postmenopausal women. And there’s also a balance between estradiol and estrone in reproductive age women that the body directs so that it’s done appropriately. And then there’s E3, which is estriol which is the dominant estrogen produced by the placenta during pregnancy which also exists in reproductive women in smaller amounts and it’s a derivative of estradiol. So, there are these three. And then there’s another one which we won’t even go into, E4, which is a fetal estrogen although just to know that estetrol and that one is now being looked at to be marketed in products for adult females which makes no sense.

Just because you can make it doesn’t mean that you should be using a fetal estrogen. It’s like so absurd, even the thought of it. And then, of course, they use the word estrogen to apply to a whole host of chemical agents that exist either in other animals like horses or coming from manufactured products from factories that are really essentially endocrine disruptors, like you mentioned. So, they bind in various ways to estrogen receptors. They interfere with the production, degradation, distribution and so on, of real human produced estrogens. And they call them estrogens but they’re really endocrine disruptors, these chemicals. So, it’s just very weird how that word estrogen is thrown around. But if we look at estradiol E2, the dominant estrogen of the reproductive aged woman made by the ovaries, it has a balanced effect on the different estrogen receptors. So now we know that much of the action of hormones not 100%, but most of the action of hormones occurs through the binding of the hormone to its receptor. And sometimes people think of it as like a lock and a key and the receptor is the lock and the key is the hormone. But it would be more like a Jim Carrey mouth where it has like [Cynthia chuckles] a shape shifter because it’s not fixed.

The receptor isn’t in a fixed shape like a lock. It can actually open and close more like a mouth and it can be open a little bit. So, I think of a receptor also like a baby’s mouth. If the baby doesn’t like that food, you’re trying to get into him or her, it’ll just clench that little mouth closed and if you try to get it in that little tongue will just push it right out. So, receptors aren’t always so receptive. It depends on different things that are going on in the body. And these receptors for estrogen, estradiol in particular they have a different propensity, a different predominance in different organs. So, for example, in the brain and we’re still learning about this, there’s predominantly the beta that’s in the cerebellum and the cerebral cortex so it’s more about thinking. But in the hypothalamus which regulates a lot of metabolic and reproductive processes that’s more alpha. And in arteries, it’s more alpha. In the gut, it’s more beta. And on immune cells, it’s a blend. And they’re always a blend. It’s never 100% one or the other.

So, in immune cells, the innate immune cells, so they are like the, I call them like the first responders or the attack animals. They’re like landmines that are set up and they indiscriminately want to kill any invader. They don’t think about the type. They just say invader, invader, kill, kill. And that group is predominantly not exclusively alpha. And then the other immune cells that make antibodies, the B lymphocytes, they are predominantly beta, but not altogether. And this is also an evolving science. And then there are different types of receptors on the membranes, on the surface of different types of cells. But we now know that the other types, the alpha and the beta, which we thought were only nuclear receptors, so they only worked in the nucleus of the cell. They also have sites on the cell membrane as well, and they interact with one another. So, if you have a great deal of beta activation on the receptors, the beta receptors, it actually down regulates the alpha receptors. And so all of this is very, very intricate, very complicated, and it relies on the specific type of the estrogen.

So, the estradiol has the balanced effect on all the receptors. Estrone E1 is predominantly alpha and estriol is predominantly beta. And of course, the immune system has to be amazingly modified during pregnancy to allow a fetus, an alien, to actually exist in the mother and not be destroyed by the immune system saying attacking, “We’re going to attack this alien.” And of course, that does unfortunately happen. And that’s one of the causes that some women have recurrent miscarriages. So, the immune system is very dramatically modulated by the different estrogens that are present within the pregnant woman. And the thing that is so confusing to so many people is that when you take certain types of hormones, like for menopausal replacement, and you take them orally, even if it’s estradiol, but you swallow it, it goes through the digestive tract and the liver, and it’s converted predominantly into estrone. So it goes into the body, into the bloodstream as a different form of estrogen than what you swallowed. And it has a different effect because estrone is predominantly going to affect the alpha receptor.

And when you use the conjugated equine estrogens that you mentioned from the Women’s Health Initiative, that particular group of estrogens, which include this equine with horse estrogens that don’t even exist, and these are previously conjugated, they’ve gone through the liver so that the horse can now put them out through the urine to get rid of them. The horse doesn’t even want them anymore. And they have a lot of alien types of estrogens that would never exist in a human female. And now we know because inflammation is about blood clotting. That’s like a really important facet to understand about the immune response called inflammation. So, when you swallow the pill, the conjugated equine estrogen that was under the brand name Premarin, that was used in the Women’s Health Initiative, it increases the risk of blood clots fourfold. So that is now going to create problems. If you have a fourfold increase of blood clotting and then you’re giving it to older women who innately have a higher risk because they’re older and also, they’ve been estrogen deficient for many years. And when you swallow estradiol, that increases the risk of blood clotting about twofold. And when you use transdermal estradiol, it not only doesn’t increase the risk and I can’t prove this, but if you look at the mechanisms that occur in the body with estradiol, the one that the ovaries make, that you’re giving through the skin, whether through a gel, a patch, a cream. When you use that type of estrogen, I personally believe I can’t prove it yet, but it lowers your risk of blood clotting, not increasing because so many people are so mixed up.

That’s why bringing up estrogen receptors and different types of estrogen and they have different effects. So, another analogy I use now is fats. So, if you said, “Fat is evil,” well, we know that. I had to defend fat. You probably did too for a very long time because fat is a group of compounds and there’s trans fat, the evil fat that was manufactured, which we know that’s what kept Twinkies fresh [laughs] for 100 years, it would not go rancid, it would also destroy your body. But there’re monounsaturated fats, there’re polyunsaturated, there’re saturated fats. They have different effects in the body. There are different structures. And so, you can’t say fats do this, fats do that. You’ve got to say what kind of fat? The same thing with estrogens. Well, what type of estrogen are you even talking about? Is it a human estrogen? Is it a manufactured estrogen that isn’t ever found in a human female naturally and so on. So, by looking at the effects of the different types of estrogen on immune cells and the different types of receptors that are activated, we can really start to decipher and understand the global effects throughout the body of estrogens and the one made by the ovary, estradiol.

Cynthia Thurlow: I think you bring up so many good points. Clearly it is more complicated than we realize. Number two, understanding that these systemic effects, different types of estrogens have different effects within the body. And very interesting about Premarin that’s the pregnant mare’s urine. And I think for many years there were a lot of prescribers that were using that understanding you get a greater increase in DVTs or deep vein thrombosis, probably pulmonary emboli as well. But with the more natural estradiol or transdermal estrogens, you’re going to have less likely exposure to those kinds of issues. Can we speak a little bit about mast cells and histamine and hives? Because a lot of women that I’m seeing in this transitional period of time and this loops into the immune system discussion, why do we see so many women at this stage of life that suddenly start getting activation of a histamine response? Because in this presence of probably fluctuating higher levels of estradiol in their bodies in this perimenopausal into menopausal transition. I have women that will tell me, “I’ve never had hives in my life. And now if I eat too many of the wrong types of foods, all of a sudden, I’ll break out in a systemic head-to-toe hives. And why is this happening?” I know there’s this interrelationship with mast cell degranulation and histamine response and estrogen as well.

Dr. Felice Gersh: Yes, and like everything, it’s on multilayers of how this is happening. So, mast cells are part of the innate immune cell group. So, what we call the first responders. And in fact, mast cells are the ultimate first responders. So, mast cells are located along interfaces between the outside world and the inner body. So, you see mast cells very heavily in the skin because that’s obviously an interface between the outside world and the inner body. But also in sinuses, in nasal passages, in the bronchial tree. You even see it in the so-called blood-brain barrier. So, mast cells are very, very key as first responders. They are the only immune cell of the body that has prepackaged all kinds of stuff like tumor necrosis factor alpha, these inflammatory cytokines. They have chemokines that call in the troops, the other immune cells, to come to the scene of the injury or the infection. It also has prepackaged histamine, like you said. So, it has a whole bunch of different things. It also has receptors on it, they call toll-like receptors. Receptors to bind with everything, parasites, every kind of bacteria, every kind of virus, all kinds of things. So, the mast cells are the ultimate first responder.

They are there like landmines to protect the body and they are appropriately activated if you have one of two things, damage, which could also include like dying cells, old cells and injury. Like a burn or a trauma of any kind to the body that will activate mast cells and that is to protect you. So that if you have an invading pathogen, like a virus or a bacteria trying to get in, this is like, okay, you’re going to throw everything at this invading pathogen. You’re going to create an inflammatory response, you’re going to call in the other immune cells to come to the scene. You’re going to try to create just a lot of putting out enzymes and histamine, which is going to create a lot of different change of blood flow to the area and so on. So, we know that these mass cells are going to save your life in the proper scenario. And as well, if you have other issues that activate the mast cells inappropriately, then you get these abnormal responses. Like you have allergic rhinitis, for example. You can have asthma responses and so on. So, when you have a dysregulation of the immune system, then you can have these abnormal activation of mast cells. Sometimes when people do it all the time, they call it mast cell activation syndrome. And since mast cells contain all of these proinflammatory products, which includes the histamine, it can really play havoc through the body.

Now, as well as being activated by estrogen and predominantly the alpha receptor, it also interconnects with the autonomic nervous system, which is the neurological system of the body, which controls everything that we don’t think about, including things like vasodilation or constriction of blood vessels, sweating, temperature of skin, your pulse so, your blood pressure, all secretion of digestive enzymes, motility of the gut all the things we don’t think about. And that includes a lot of effects on the immune system including mast cells. Well, it turns out that not only does estradiol, I call it modulate, like, regulate all of the immune cells so it turns on. This is like a really important concept. So, estradiol is the on and the off switch to the inflammatory response. So, inflammation is essential to save your life. Like we said, if you have an invading pathogen, bacteria, virus, fungi, anything, or you have trauma to your body, the proinflammatory response can save your life. So, we definitely want to have that and estradiol turns that on appropriately because there are receptors in every one of the immune cells of the body, every single one. So, it turns on the switch to create inflammation when you need it, but it also turns on the off switch. And what happens when you turn on the off switch? That promotes healing and resolution, creates growth factors so that you can heal injured tissue, replace tissue.

It creates growth factors for new blood vessels to provide blood supply. It also causes platelets when you need them, not only to create growth factors, but to also wall off infections. That’s how you get access cavities that can save a person’s life. It walls off the infection. So, it does all these things to promote healing, but it also creates the inflammatory response in an appropriate way. Well, when you’re in a perimenopausal state, all of these things are in a fluctuating status, and the hormones often go up and down inappropriately. So, the signals that are coming to the immune cells can become sort of jumbled. And on top of that, I mentioned the autonomic nervous system. So, the autonomic nervous system is actually also modulated by estradiol. So, there’re two arms of the autonomic nervous system, the parasympathetic, which is what should be the standard baseline status, which is like, calm, you have proper gut function, motility, your skin is warm, everything is right. Your immune cells are surveilling but quiescent. They’re not activated.

They’re just kind of like they’re guards, they’re watching out for you, and everything is quiet. But when you don’t have enough estrogen, the autonomic nervous system becomes quite dysregulated, and the parasympathetic gets sort of like taken over by the sympathetic, which is the stress response. And that changes everything, that activates your immune system often inappropriately, like if you’re feeling all stressed out and tense but there is no invading pathogen, you’re not really in danger, but you’re acting in your body as if there is. And the neurotransmitters for both of those types, the parasympathetic and the sympathetic, are controlled in large measure by estradiol. So, the one that activates the sympathetic is norepinephrine and epinephrine. And everyone’s heard of an EpiPen. So, if you inject someone that is having anaphylactic reaction from an allergic response, you inject them with an EpiPen. It actually dilates their bronchial tree so they breathe. And that’s part of the stress response.

So that if you’re running for your life, you get more oxygen into your lungs but it changes everything as well throughout the body in very different ways. And your heart beats faster, you change blood flow to your skin. Your immune system becomes hypervigilant and upregulated because you may be injured, because you’re in a stress situation. And the parasympathetic is controlled by a different type of neurotransmitter called acetylcholine and that is actually in the brain, helps to create memories. That’s another problem that we have when we lose our proper production of estradiol. But in the autonomic nervous system, it keeps you in that calm state and it keeps those mast cells from going wild. Okay, so you have the problem with the fluctuating estrogen. You have the autonomic nervous system becoming dysregulated. You have the receptors on the actual mast cells becoming on and off switch and so on. And in addition, you have, as you transfer your hormone production and it changes, your gut microbiome changes. And now we know that about 70, 80 plus percent of the gut is surrounded by the immune system called the GALT, the gut-associated lymphoid tissue. So that’s the majority of the immune system of the entire body.

And of course, they contain many mast cells. And of course, there are many drugs that are trying to modulate mast cells. Like people take Pepcid, that is a modulator of mast cells because this can affect your digestive tract in all kinds of ways. So, what happens is when you now have an altered gut microbiome you have what is called impaired gut barrier because you don’t have the right gut microbes to create this protective mucous coating. And then the lining cells of the gut become inflamed and the little fibers that hold them in close proximity, they start to degrade and the cells start to separate, like drift apart. And then toxins and bad bacteria and such in the gut can actually get into the body proper where the immune system resides and it activates the immune system. That’s what we call leaky gut. Now it turns out that when you don’t have enough estradiol, you lower the threshold to activating the inflammatory response. So, the same amount of toxic stuff, we call like endotoxins or lipopolysaccharides that get into the body through the gut, it takes less to activate the immune system to go into a proinflammatory state. So, it’s like the total perfect storm that’s happening in women. You’re having this dysregulation of your autonomic nervous system. You’re having altered actual receptor function on the immune cells themselves. You’re having this dysbiotic gut microbial population and leaky gut. And you have lower sensitivity of the immune cells so that they become sort of like we’ll say, lower resistance to inflammatory stimuli. So, they react with a greater response of inflammation to a lower degree of stimulation. So, it’s the perfect storm for having immune system dysregulation. And in many women, it will manifest as well, like you mentioned with hives. And we know that the brain is the ultimate regulator of a lot of functions in the body. And women, as they transition into menopause, have more anxiety, poorer sleep, a lower threshold to becoming very stressed. And the brain itself, through the autonomic nervous system, can trigger hives.

Many people have hives and they’re not even perimenopausal, especially women, because women are more sensitive to all of these things and they can have an emotional response and they break out in hives or they feel emotional and their face turns all red. That’s part of this response system. And so, it’s really a problem. And there’s been so little research on it. The traditional approach, of course, is to give antihistamines and that can help for a lot of people. So, I’m not against giving pharmaceuticals when you need to. And of course, there’re also herbal things that can help stabilize mast cells as well, like quercetin and stinging nettle and so on. So, there’re a variety of other natural products that can help stabilize mast cells. But the ultimate stabilizer is proper levels of estradiol.

Cynthia Thurlow: Well, and I think that connection is not made. I think there’s so much focus on appropriately so brain health, heart health, bone health. But when I started to understand the gut microbiome and the role of the estrobolome and all of these factors, I realized, why aren’t we talking enough about this? Because women are wondering why they’re suddenly more susceptible to parasitic infections or they’re having quite a bit of dysbiosis, whether that’s done by stool testing. And it makes so much sense about how there’s this protective role of estradiol in terms of down to a cellular level in the gut microbiome and immune function as a whole. Now, when we talk about how estrogen impacts these endotoxins, so lipopolysaccharides and for anyone that’s listening, I know that seems intangible, but I’ll provide an example. Everyone knows I like to travel. I went to Morocco and picked up the worst food poisoning I’d ever had and very clear that I had been impacted by this lipopolysaccharide, this endotoxin, which I think kind of preceded me developing a ruptured appendix.

But I think for so many people understanding the role of inflammation and these changes in estradiol levels that are impacting how well we can fight off infections. I think that’s certainly important. But can we speak a little bit to the estrobolome or the estrobiome depending on the individual that’s talking about it, understanding how our body in the setting of estrogen is able to properly or improperly break down and deconjugate estrogen so that we can get rid of what does not belong. I know that that seems to be a huge issue for many women as well. They get this recirculation of estrogen. The liver is designed to help break down these estrogen compounds. And in some people, whether it’s through genetics like poor methylation or other SNPs or contribute genetic propensities that make it a little harder for them. But I think the estrobolome is one area of the gut that I find really fascinating and I think for a lot of people they’re probably not as familiarized with it. It seems very strange. It’s a funny name. And again, I don’t think there’s enough focus on the interrelationship between estrogen and the gut microbiome.

Dr. Felice Gersh: Well, absolutely. And I think the first sort of we’ll say primary area that needs to be just acknowledged, because it isn’t, is that estradiol is the hormone of life. And that’s like really key because it’s really thought of as just a reproductive, I mean, not that that’s little, but reproductive related hormone. Like it gives you menstrual periods and it’s involved in getting pregnant, but that’s kind of it. But it is so not just it because the prime directive of life and I figured this out many years ago as I delivered thousands of babies as an OB-GYN. It is the creation of new life. Now, that’s what the whole female body is designed to do successfully. Now, we as humans, and I think rightfully so, we want to determine when and if we have babies. But there’re no other species on this planet that is thinking, “Hey, this is a bad year, let’s not mate.” That doesn’t happen in nature, only in humans do we say let’s not have kids. Let’s do something about it. But once you accept that the prime directive of life of all evolutionary life is the creation of new life, then you have to acknowledge that in order to be successful with pregnancy and this is actually a growing problem now, you have to have a healthy body and, in all aspects, you have to have a healthy body.

The brain, the entire neurological system, the musculoskeletal system, the gastrointestinal, the cardiovascular, the genitourinary, every single system has to be functioning optimally and together you have to have everything working in the same time zone that’s your circadian rhythm which is modulated also by estradiol. So, once you realize that every organ system requires estradiol to function properly, then it helps you to understand what’s going on in the gut. Why do we have this special group of microbial life forms in the gut designed to address detoxification or what I prefer is the word biotransformation, because it’s not that estrogen is toxic. That word gives you the wrong idea. It’s really biotransformation because you’re transforming products in the body from one state to another for the ability to get it out of the body, so you can transform it so that it becomes either water soluble so it can go out through the kidney and the urine or it’s modified so that it can go down, I call it the trash chute, the bile duct into the intestine, and then you can poop it out, because everything gets old and you don’t have the same hormones that you had when you were 14, everything changes. So, because estradiol is so critical to the health of the female body and we won’t go into men, they really should love estradiol too, because they make tons of it. They transform their testosterone into estradiol.

All estradiol comes from testosterone, every drop of it, no exceptions. And men make tons of estradiol, but they make it in the specific organs themselves. It’s not circulating, we call that [unintelligible [00:37:08]. So, estradiol is essential for males and females, but just focusing on females, there’s a time in a women’s life that when we talk about reproduction, when women stop making estradiol. Now, I’m not talking about menopause, although that can be useful because evolution wasn’t designed to deal with menopause. That’s sort of like the afterthought that women can live quite a number of years in a postmenopausal state. But that’s really not nature’s primary concern, okay? So, it’s really what about during the reproductive life? Because that’s really essential if you’re going to have multiple babies, because human females to be successful in terms of reproducing the species, they have to have more than one because that’s not enough.

And you’re going to have some unfortunate issues with child mortality and so on. So, nature wanted human females to have multiple pregnancies and bear multiple children and raise them. So, what happens in a woman’s life if she has a baby and then after the baby is born and the placenta, which is the primary endocrine organ of pregnancy making all of that estriol and also estradiol, and it also makes testosterone, which is a precursor for all of the estrogen, then what happens is the placenta is delivered. Oh, boy, no more placenta, no more hormones coming from that organ and the ovaries go into a quiet state. So, you make prolactin okay and that helps the woman so that she can lactate. She makes breast milk and that acts as natural contraceptive and it shuts down the ovaries. In fact, this is a problem in endocrinology.

If a woman has a prolactinoma in her pituitary gland she’s making, she has this little benign tumor, but it’s making too much prolactin. That’s the source of it. It will shut down her periods. So that’s what prolactin does and nature makes it intentionally. So, you have this little built in birth control. How great is that? Nature doesn’t want a woman who just had a baby to immediately become pregnant again. That would not be very useful, so prolactin shuts down the ovaries. Uh-oh, now the ovaries aren’t making any estradiol, but estradiol is essential for every organ system in the body. What’s going to happen? What are we going to do? Well, it turns out that the adrenal gland is still making its androgens and androgens can be converted through this enzyme called aromatase, which exists in many organs including in the gut. There are these special areas that are called Peyer’s patches that actually can make estradiol from precursors that come from the adrenal gland.

Okay. So, you can actually make some, but very small amounts, okay. But and you make it in the organs themselves so it’s not circulating. So, if you did a blood level, it would be very low. But it’s made in the organs themselves. So, you do make– that’s how women, when they’re nursing their babies, they still have some estrogen in their body because they’re making it from these androgens that come from the adrenal gland. Well, it’s so important to have estradiol in the body, but not to have fertility. So, the ovaries have to be shut down so you’re not ovulating and so that’s all quiet. So, nature made this special group of bacteria in the gut that can recycle estrogen that’s made in these other organs, like in the gut itself. And that’s like I’m never even sure how to totally pronounce it, estrobolome. But in any case, so that’s how I say it, which may be incorrect, but the estrobolome, so it’s just special bacteria that actually work on the estrogens to recycle them. So, in a healthy woman, this is nature’s best gift to give back estradiol into the circulation. But what happens now?

Well, we live in this crazy world where people are eating weirdo food, the standard American diet, and without realizing it, they’ve done everything possible to destroy their good gut microbiome. So, we have tortured them, we’ve poisoned them, we’ve starved them. So, the poor estrobolome, the bacterial group that is designed to help properly recycle estrogen so that women who are in the postpartum time have enough estrogen to maintain proper function of their organs. Uh-oh, now things are all messed up in so many ways. So, you end up with the wrong microbial population in the wrong ratios, and suddenly you can have poor metabolic transformation. This biotransformation isn’t happening correctly at any stage. So, the transformation of estrogens so that it can be removed from the body is a multistage process and it includes the intestinal tract and different stages in the liver. And then the final stage is back into the colon and involving these special microbes that are addressing estrogen types of issues in terms of eliminating estrogen.

So, when everything is wrong, which is what’s happening now, and then, not to mention it, but that unfortunately so many people are exposed to antibiotics which kill off a lot of what we call the commensals, the good guys. And then nature will never allow a vacuum. So bad dudes replace the good guys, so you have the wrong microbiome population. So now suddenly you may inappropriately create recycled estrogen when you don’t want it. So, it’s like too much of a good thing. You can have always too much of a good thing or too little of a good thing. Everything should be just the right amount at just the right time. So, when you have the wrong microbiome in the gut, you also probably have messed up problems going on in the liver and in the small intestine as well. So many people have small intestinal bacterial overgrowth. So, phase 2 detoxification isn’t going to happen properly either. And you need to have some degree of fasting, your expertise as well, in order to fasting in different forms can also upregulate the phase 2 detoxification pathways which are really sort of underrecognized and underappreciated.

So, the bottom line is that we often have an overpopulation of the wrong microbes that put out enzymes like beta glucuronidase and they end up creating too much recycled estrogens or the wrong types of recycled estrogens. Because remember, estrogen is a family of hormones and estrogen metabolites, like these downstream products of biodegradation of estrogens can have good or bad effects. Like there are some that are metabolites of estrogen that are so critical. There are even receptors, for example, in the heart to certain types of estrogen metabolites because they help create energy in the heart. So, they’re so important. But then there are other types that can actually be procarcinogens. They can maybe even promote breast cancer. There’s a link there. So, it’s so important to have a healthy gut microbiome and also to put the whole area of the estrobolome in perspective that it’s not abnormal. We want it, it’s actually lifesaving and I think critical during the time of life postpartum when women’s ovaries are not working, so that you get the adequate amounts of estrogen made and recycled. But when things go awry, as we know, then everything goes down the tubes and that’s unfortunately how estrogen often gets a bad rap.

So, the problem isn’t estrogen, the problem is the gut microbiome and the diet and the stress and all the other lifestyle issues that come into play that alter the gut microbiome and make it dysbiotic or abnormal. So, it’s a very crucial part of being a healthy woman is having this healthy group of specialized microbes that address estrogen. But it’s so important to keep it healthy. And what’s interesting is in menopausal women and I don’t think this was really nature’s intent because I don’t think nature had a grand plan for menopausal women because there’s no evolution in the menopause. So, I don’t know how a grand plan could exist. But women can utilize these specialized microbes for recycling estrogen appropriately. And there’s actually some published data that when women have a healthy gut microbiome, they can get some naturally produced, through the recycling process of estradiol that actually has been shown to help maintain vaginal health.

So, there’s a group of women that somehow even as they go through menopause, they don’t seem to have a lot of problems. Like they don’t have vaginal dryness. That’s actually a very small minority. They don’t have night sweats; they don’t have hot flashes. What’s so special about them? How are they doing this? And it may because they’re the ones who live the great lifestyle. They have maybe lucky genes too. And they maintain this healthy gut microbial population that they are able to actually use these specialized microbes and they’re recycling in a very good way. Their estradiol is coming back and it’s actually helping to maintain a healthy body in the menopausal years without even taking supplemental estrogen.

Cynthia Thurlow: That’s really interesting. And I would imagine individuals that are listening to the podcast, they’re probably wondering what are some of the common signs and we’ve touched on some of these, but what are some of the common signs that the gut microbiome is not optimized in these middle-aged years in perimenopause and menopause? What are some of the more common things that you’re seeing clinically with your patients?

Dr. Felice Gersh: Well, the most obvious one is change in bowel habits. So, I mentioned the autonomic nervous system is controlled through estrogens, estradiol in particular. And what happens is there’s this huge group of neurons. That’s why someone coined the gut as the second brain. Because the neurons in the gut are so complex, there’re so many of them. There’re a lot of similarities to the brain in terms of they have the embedded microglia, there’re the specialized immune cells and it regulates the gut motility. Okay, so after menopause there’s often a greater– and women tend towards having gut problems the most anyway because of their sensitivity. Women are just more sensitive. Their autonomic nervous system is much more reactive. Like it’s sensitive to emotions much more so than in men. That’s why 80% of irritable bowel syndrome occur in women okay.

So, it turns out that a lot of women after menopause have a lot of gut problems in terms of acid reflux, the incidence of gastroesophageal reflux, you know GERD. GERD is higher in men up until women go through menopause. And then women have a higher incidence of GERD after menopause, women have more gut problems with constipation and so on. They’ll have change in their stool consistency and so on. So, look at changes in gut function, both upper like with heartburn and reflux disease and also with having regular bowel movements and the consistency of the stool, so that is really common. Those are the ways to really really tell. It’s so important to have at least one bowel movement a day. More is even better and there’re all these rating systems for a stool. But the most important thing is that you don’t have little rabbit pellets coming out of you, that is not good. And what do we know now, we didn’t know this in the past. What is the biggest component of stool? It’s bacteria. Okay, so if you have hardly any stool and they’re very tiny and they’re very hard, then you don’t have the right microbes. I can tell you that. That’s like the poor man’s way of getting a good gut microbiome test. Just look, if there’s very little stool, then you don’t have a lot of good microbes because it turns out that the microbial population, the bacteria actually make up the bulk of what stool is.

Okay, it’s not just leftover food. [laughter] Its really microbes coming out of you, the old microbes. So, having proper motility, having good these big sausage-shaped type poops coming out of you regularly, because elimination is not like an optional function of health. You’ve got to be able to have that happen properly. And of course, women, unfortunately, after menopause, have very high rates of developing non-alcoholic fatty liver disease. And of course, the liver is the powerhouse of detoxification and of course it’s a mega factory in terms of what it makes and different kinds of proteins and so on. So having a healthy gut is going to translate into a healthy liver and vice versa. So, when you have an abnormal gut microbiome, it creates a lot of inflammation and there’s what they call the enterohepatic circulation. The connection between the gut and the liver is very, very complicated and very important. So, when you have the wrong gut microbiome, that will impact directly on the liver’s health. So, I recommend that most women, if they are like, overweight, if they’re not feeling healthy, things are just not right as they’re transitioning to menopause get an ultrasound of your liver. That’s the only way to actually at this point, to diagnose this non-alcoholic fatty liver status. And that is not going to be found just by having abnormal liver enzymes. That’s a late stage finding. So, you’ve got to know this and that will be another very, very easily detectable way of knowing that your gut microbiome is off because they go together hand in hand health or poor health, the liver and the gut. So, these are really important.

The other ways that you can know is that the gut itself is also an endocrine organ, okay. So, there’s been a whole lot of emphasis on this little gut hormone, GLP-1. And that’s with all the weight loss drugs that are coming out, like Wegovy and Mounjaro, which also has GIP, another different little hormone-type product. Well, it turns out, most people don’t know this, but estrogen, estradiol in particular is very key to the production of this little hormone that is very key to regulating metabolic functions and appetite regulation and so on. So, when women are transitioning to menopause, if they notice that they have dysregulation of their appetite like they have the night munchies, they start binging. All of these things can actually be treated. In fact, there’s published articles showing that binge-eating disorder can be treated with an estrogen patch because low estrogen is key to regulating or dysregulation of proper appetite and fat burning the little peptides like AMP kinase. These are really regulated by estrogen.

So, without adequate estrogen, your appetite becomes dysregulated, you will gain weight, particularly visceral fat and you’re going to just not know when you should eat. Like you don’t know, “Am I hungry, am I not hungry?” I could eat at any time. You may start binging. That’s a clear cut also indicator that you have abnormal gut microbiome and that’s why one of the other things that can help to increase your own natural production of GLP-1 is fiber because fiber nurtures the gut microbiome as well. And also, I call it the magic of food, the phytoestrogen. So many of the so-called superfoods are actually containing phytoestrogens. They’re not estrogens, but they’re plant based components, molecules that actually combine to estrogen receptors creating a very beneficial effect and these have been shown to help restore gut microbiome, they help restore appetite and they do a lot of amazing things.

There’re studies that even show they can suppress night sweats and hot flashes and they’re not real estrogens, they’re plant based, these amazing products, I call it the magic of plants but they’re not replacing giving estrogen in menopause. But no matter how hard we try; we’re not going to replace hormones like by giving a new set of 21-year-old ovaries. So, we need all the help we can get to restore the gut microbiome, to maintain a healthy immune system so that we don’t get cancer. Like when people talk about cancer, who has the most cancer? Older women, postmenopausal women, not healthy women who have beautiful regular cycles, when they get cancer, which is horrible, it’s usually because of chemical endocrine disruptors these toxic chemicals that we’re unfortunately bathed in in our societies now that interfere with proper hormone functioning. So, it’s really essential that we stop putting the blame on the blameless that estrogen is the cause of all of these things.

It’s loss of estrogen and then loss of our healthy gut microbiome and loss of control of our immune system because it’s chronic inflammation which underlies every bad thing in the body, including cancer, cardiovascular disease, dementia, osteoporosis, osteoarthritis, these are all inflammatory processes. And once it’s recognized and hopefully everyone out there now will understand this, that estradiol is actually the regulator of the immune system, it turns on and it turns off inflammation. When you don’t have enough estradiol, you go into a chronic state of low-grade inflammation and that’s what happens in postmenopausal women. They have the abnormal gut microbiome, their immune cells are dysregulated, and they go into this proinflammatory state, and different estrogens have different effects. So, it turns out, you can think of it this way. It’s a little simplistic, but estrone turns on the innate immune cells. It turns on inflammation okay. And estriol turns off the innate immune cells through the beta, okay. And estradiol takes care of everything. It turns it on when it should. It turns it off when it should. So, after menopause, when you have a lot of inflammation, what does that inflammation do? It actually upregulates the enzyme aromatase that converts androgens into estrogens.

Well, the dominant estrogen that’s made is estrone, and it’s made from the adrenal androgens and it turns out when you have a lot of chronic inflammation, it actually blocks the action of the enzyme that can interconvert between estrone and estradiol. So, you make estrone and then you get stuck as estrone. So, you get stuck with the on switch for inflammation. I mean, that’s really important, so it’s not estradiol from the ovary, it’s not estradiol that we would give women through the skin as a postmenopausal hormone therapy, it’s estrone made from proinflammatory fat due to a proinflammatory state of the body with the upregulation of this enzyme aromatase that’s causing the production of estrone. Now, why would that be like, why is it that inflammation would turn on this enzyme?

Well, once again, it goes back to reproductive success and survival of the species. So once again, in a postpartum woman who is breastfeeding, she is not making her own estrogen from her ovaries. So, what happens? Well, what if she gets a breast infection? She’s breastfeeding? Well, estrogen turns on and turns off the whole inflammatory process so that you can deal with invading pathogens, like in the breast. So, the breast has a lot of fat tissue and that’s not an accident. So, the fat tissue in breast can actually make its own estrogen locally in the breast to control the inflammatory response of the breast to an invading pathogen. So that if you get a breast infection in a breastfeeding mom, you have the capability of modulating or regulating the immune system in the breast to actually properly fight off that infection. But that’s a temporary thing. And when the infection is gone, then what happens is the production of estrogen in the breast goes down. Well, what about in a postmenopausal woman?

Well, her whole body is in a proinflammatory state including her breasts. So, the fat in breast tissue has the ability to make estrogen at every stage of life, including in the postmenopausal women. So now you have the perfect storm for creating breast cancer. You have an inflammatory environment and inflammation causes potential DNA instability and DNA breakage and the production of cancer cells. Now you have fat tissue in the breast that’s in an inflamed environment and the enzyme aromatase is upregulated. So now the breast tissue in a postmenopausal woman is making estrone. But it can’t get converted into the proper estradiol because of inflammation downregulating the conversion enzyme. So now you have the perfect storm. Like I said, you have inflammation, you have production of estrone and estrone works only the alpha receptor. Well, it turns out that breast cancer, when it has estrogen receptor positivity, it’s always the alpha receptor. So here you have it. You have inflammation promoting the production of cancer through DNA instability and breakage. And now you have estrone. And estrone, like all estrogens, can promote growth factors. And so now it’s actually promoting the growth of this cancer, which has estrogen receptor positive alpha receptors. But why is this even happening? Is this because the woman was getting estradiol as a replacement hormone in menopause? Absolutely not.

It’s most likely because she wasn’t. Because without estradiol, you get this proinflammatory state. You have the dysbiotic gut microbiome, the leaky gut, the dysregulation of the immune cells so they become more hyperreactive, more proinflammatory, and you can’t turn the inflammation process off because you don’t have the estradiol. So, there’s really a logical reason why postmenopausal women and particularly women who are obese. I have obesity, because we know that the most high-risk factor for postmenopausal breast cancer is weight gain, actually. And of course, weight gain is associated with more proinflammatory status. So, it’s inflammation that’s out of control in the breast that’s causing the production of damaged tissue and the proinflammatory production of estrone that then feeds and nurtures this cancer that has nothing to do with estradiol. And when you get estradiol into a woman right at the get go during the perimenopausal years, you can hopefully and we need more data, but when from a scientific perspective, it seems obvious to me that you will maintain the environment of a healthy premenopausal woman. If you can maintain that, then you won’t get into this chronic state of systemic inflammation and particularly in the breast tissue you’re not going to have all this estrone produced which is proinflammatory. You’re going to have the proper estradiol, which is the balance effect on the immune system. So, you’ll be able to reduce your incidence of cancer.

Remember, cancers increase with aging like colon cancer is much more common in postmenopausal women than premenopausal women just as is breast cancer and other cancers like pancreatic cancer, brain cancer, liver cancer all of these are much more common in postmenopausal women because the immune system is now not regulated properly to do its job optimally. And also, like sepsis, women who are premenopausal have much higher success rates in survival with sepsis, like infections, systemic injuries from bacteria, and even like brain trauma. Brain trauma is much better controlled in premenopausal women than in postmenopausal women because estradiol is key to regulating the healing process in the brain as well, so that’s very key. So, estradiol is the modulator of the immune system. It keeps everything humming just right. Without it, everything goes into this disarray, and you end up with things like these cancers and you get overproduction of estrone from this proinflammatory adipose tissue. But once again, because people don’t distinguish this estrogen from that estrogen and the underlying mechanisms, it all gets jumbled together, and then estrogen becomes the evil enemy, and they think it’s estradiol, so we just have to stop this. [laughs] You know that’s why estradiol is a woman’s best friend. That’s why I’ve changed it from being called a sex hormone to a life hormone. It’s about life itself, about the functionality of every organ system. And key to every organ system functioning properly is a properly regulated immune system.

Cynthia Thurlow: No, so beautifully stated. And I think there are probably listeners that are wondering, if they are in menopause, is there a magic window? Because I’ve heard five years. Five years is the magic window. Five years into menopause, if you start taking hormone replacement therapy, there’ll be more benefits conferred. I’ve heard as far into menopause as 10 years for prevention and support against coronary artery disease. If we’re speaking about generalities, again, not giving medical advice, for you, if you are starting to work with someone who’s already in menopause and they’re within that five-year window or that 10-year window, what are the conversations that you’re having with them? Because I think for so many of us, there was this long period where most women where they were thinking, and many clinicians as well, that hormones are going to give people cancer. And that’s not the message we know that’s actually not correct, but helping people understand to be thinking about these things as you’re in perimenopause. But if you are already in menopause, what are some of the conversations that you have with your patients?

Dr. Felice Gersh: Well, certainly early is better than late when it comes to starting, because it’s much better in everything, to be preventative than to try to be reactive. So early is better, but I say it’s never too late. Now, what do I base that on? Well, the whole thing about which is now the general trend in the conventional medical world is that hormones should be stopped arbitrarily at age 60. Because once you’re over 60, 59, okay, but 60, no way okay. Once you hit 60, you’re too old to be in hormones because suddenly they become dangerous. Although what the heck that mechanism would be, nobody cares to elaborate upon. And if you’re out 10 or more years from the onset of your last period, okay, from the last period, that’s another arbitrary thing anyway. But so, if it’s 10 or more years, it’s too late for you. You’ve missed that window of opportunity, which is the words that they use. So, first of all, all of that is based on the Women’s Health Initiative, which to me is irrelevant to everything except to itself. Like, it means, “Okay, if you use those products, that’s the advice you should follow.” But I never use them so that’s not the advice I would give.

Now, how do I know or what do I base that it’s never too late. Well, it turns out that all of the organizations like the North American Menopause Society, they’re huge now in advocating for vaginal estrogen. Oh, my gosh. They changed the name from vaginal atrophy to genitourinary syndrome of the menopause. Okay, because, oh, by the way, there are some committees, their whole job is to change the names of things, . [Cynthia laughs] so important. So that’s big focus now, is genitourinary syndrome of the menopause for better urological health, for better vaginal health. And they’ll give vaginal estrogen, estradiol, occasionally they’ll give vaginal Premarin, but usually estradiol. And they will give it at any age. It doesn’t matter if a woman is 20,30 years out in menopause, there’s no maximum time that you’ve crossed the line. You’re too late. No, there is never a too late. Now guess what happens when you give the vagina estrogen? It gets better. Does it turn like a 70-year-old vagina into a 19-year-old vagina? No, [Cynthia laughs] but it gets healthier. There’s no question it gets healthier. So why would I think that only vaginal estrogen receptors can wake up? That doesn’t make any logical sense whatsoever.

There’s nothing that evolved unique for the vagina that only the vagina can actually benefit, no matter how long it’s been. So, here’s my thing, when you don’t use receptors for a long time, they do become sort of like the equivalent of rusty. They may never become the same. So, I’m not going to say it’ll be the same. That’s why you don’t want to have a gap when you don’t have estrogen, the proper estrogen [laughs] in those receptors. And you don’t want them filled with endocrine disruptors either. They stretch them out of shape, so to speak. So, you always want to have estrogen, the estradiol in the receptors doing their job, but say you don’t. Well, the receptors may never be quite optimal, but that doesn’t mean they’re useless because the vagina has proven that. Now what else has proven that?

Especially back in the 1990s, but it’s coming back again now, they did quite a lot of studies applying estradiol cream to skin. And what did they find in women who were out in menopause a long, long time? If they put it on the skin in just two weeks, there was a reduction in visible wrinkles. Two weeks and you could see reduced wrinkling of the skin. Of course, the skin has estrogen receptors throughout every single layer. Every single part of skin has estrogen receptors. So, if the skin and the vagina, of course the vagina is like a type of skin. But if skin, no matter where it is on the body, can actually benefit. Why would I think that arteries can’t or the brain can’t or that your bones can’t? In fact, we know from the Women’s Health Initiative that giving the Premarin that the bones benefited and also the gut benefited. So come on, of course, it’s not going to be the same. It’s not going to be as good as if you were on full, proper replacement therapy and supplemental therapy from the very beginning of perimenopause. But it’s still good. Good is better than bad [laughs] so let’s go for it. Now, the whole risk, all of the risk that they say, “don’t give it to older women” comes from this excessive clotting propensity of the conjugated equine estrogens. I mentioned it increases the risk of blood clotting fourfold.

Well, if you take an older woman who already has vascular disease, and then you put in a product that increases blood clotting, she may end up having ruptured plaque, and then she may have problems with vascular flow, and they could be like little micro vessels. So, then she increases her risk of vascular dementia, which is what they saw, and increases risk of hypertension, coronary artery disease, can lead to heart attacks and strokes and so on. So, what did they see in the Women’s Health Initiative? Well, they saw an increase in dementia in much older women and probably it’s due to vascular dementia because of the alteration in the blood clotting factors from the conjugated equine estrogen, and there was an increase in stroke. Well, that’s a blood clotting problem. They actually didn’t end up finding that there was an increase in heart attacks, surprisingly. And they did have an increase in DVTs, like you said, deep vein thromboses. So, it’s all about the clotting problem. Uh-oh, that only applies to that product. It doesn’t apply to real estrogen. That’s estradiol that is exactly a clone of what’s made by the ovary.

Now, it’s really important to understand blood clotting is part of the inflammatory response, and its lifesaving, because remember inflammation is triggered by trauma, damage, or by pathogens. And if you have trauma, you want to have blood clotting so you don’t bleed to death if you have a laceration right, that can be lifesaving. And the clotting mechanism is the same mechanism that creates walling off an abscess cavity. So that’s part of survival from an infection as well. Oh, my gosh. That story about your ruptured appendix. Well, in ancient times, some people actually survived a ruptured appendix without surgery because their immune system walled it off. They actually–
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Cynthia Thurlow: Yeah, that’s actually what happened–

Dr. Felice Gersh: Oh, my gosh.

Cynthia Thurlow: –during my 13-day hospitalization, and my surgeon sent me home, and then they did surgery six weeks later. But when she went in to remove it laparoscopically, she took all these photos, and she said, “Cynthia, there’s no question in my mind that this is what saved your life, was that your body walled this off.” But at some point, in the future, there would have been a recurrent issue. So, to your point, before people had the ability to intervene and remove appendixes when they were inflamed and sick, there were those of us that by virtue of probably a healthy robust immune response, we’re able to wall the infection off. But how important that is to understand that distinction of that inflammatory response when it’s working optimally.

Dr. Felice Gersh: And that required estradiol for that. [laughs] That’s why older people will often have no response from a symptom point of view if they have a ruptured appendix because they don’t actually have the proper immune response and then they just die. And look at the whole experience with COVID who tended to die, the older people, obviously. And also, there was even published data. I said this from the get go, as soon as COVID came out as a pandemic, it’s like, “We should do a study. Women with estrogen are going to do better.” Well, I couldn’t get anyone interested in doing that study with me.

Cynthia Thurlow: Really.

Dr. Felice Gersh: The others did it and it showed women who are properly provided with systemic estrogen, estradiol in their bodies, they did better. Like, big surprise to me. Of course not, because the immune system works better in every aspect, including, of course, fighting off pathogens when you have that proper amount. And a lot of the problem that happened with COVID was people went into what they called like a cytokine storm. And that’s the case when you don’t have the proper hormones. And estrogen is made in men as well because we said that it comes from testosterone. So, older men tend to have low testosterone, so what you have is the proper on and off switch. So those people could turn on inflammation in a chaotic sort of way, but they couldn’t turn it off. You need estradiol to turn off the inflammation response too, which is what’s not happening in postmenopausal women. So, I mean, you can thank your estradiol for saving your life. [laughs]

Cynthia Thurlow: Well, you want to know what’s interesting is that I never had a period again after that, but I lost 15 pounds. And kind of the working hypothesis was because I lost so much weight, not being able to eat for 13 days, that stress probably pushed me over the edge. I know that average age of menopause in the United States is 51, as all of us know. But in my late 40s, getting that sick and being hospitalized, I think that kind of just shoved me. Maybe I would have had a couple more years before I went into menopause, but that kind of pushed me off the cliff.

Dr. Felice Gersh: Wow. Well, that’s quite a story in itself, but I’m sure glad it had such an happy ending.

Cynthia Thurlow: Yes, absolutely. Well, I could talk to you for hours. I’m hopeful I can persuade you to come back for a fourth podcast so we can talk about brain and bone health, because these are, again, very important topics for women. Please let my listeners know how to connect with you, how to get your books. I always say that your resources and your messaging is so vital and so needed in a space where there are sometimes a lot of polarity. You’re always a kind of bright shining light of advocacy for women, and for that, I’m very grateful.

Dr. Felice Gersh: Well, I appreciate it, because sometimes it is an uphill battle. [laughter] That is true. So, I have an old-fashioned brick and mortar medical practice in Irvine that’s Southern California, in Irvine, California, where I see patients every day, and I will be seeing them shortly. And so, it’s called the Integrative Medical Group of Irvine. And I do have three books out so far. And in terms of menopause, the most recent one is called Menopause: 50 Things You Need to Know. And then I have two books in the PCOS SOS series for women who suffer from polycystic ovary syndrome, which is a very high percentage of women these days. And those are easily obtainable on Amazon.

Cynthia Thurlow: Well, thank you again, Dr. Gersh. Always a pleasure.

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