Male and Female Immune Differences with Dr. Felice Gersh: Rational Wellness Podcast 283

Dr. Felice Gersh discusses Female and Male Differences in Immune Function with Dr. Ben Weitz at the Functional Medicine Discussion Group meeting on October 27, 2022.

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Podcast Highlights

9:51  The Prime Directive of Life is the creation of new life.  Everything in the female body is designed for successful reproduction and this involves fertility, a successful pregnancy, birthing the baby, having the baby nurse, and raising that child to its sexual maturity, so that it can carry on the process of new life creation.  In general, women have a more responsive and robust immune system compared to males. But during pregnancy the immune system has to have very significant moderation and modulation and alterations so that it does not kill this little foreign creature growing in her, that little fetus and this is accomplished through estradiol, which is decreased during pregnancy.  Before and after pregnancy, estradiol stimulates the immune system, which is why women have a stronger immune function and can better fight off infections than men, but also have a higher rate of autoimmune disease.

17:43  Women have a more robust and powerful immune system than men and this is why the mortality rate from COVID in New York City was 60% for males versus 38% for females.

19:03  Women are also more likely to have Long COVID because we believe that it involves an autoimmune component and 80% of those with autoimmune diseases are women.  When you have an infection, the body makes antibodies and because women have more B-cells, they tend to make more antibodies. When you make antibodies against bacteria and viruses they can cross react and attack cells and tissues in our body that have a similar amino acid structure. Having leaky gut and leaky brains and leaky vagina increase the risk of autoimmune diseases because this means that the barriers that prevent pathogens from entering these organs.  The dendrites are the immune cells that facilitate this cross reactivity.

25:48  Women are born with two X chromosomes and this extra X chromosome is instrumental in women having a stronger immune system.  It is believed that one of the X chromosomes is randomly silenced during the time of being an embryo, but what really happens is both X chromosomes are functioning for several weeks. And during that time, before the one random one is quieted down, they actually are changing how genes express themselves within the immune system. And even when that X chromosome is silenced, it turns out that 15% of the genes are not silenced and they keep functioning. And this is why it is critically important not have fetuses and babies exposed to endocrine disruptors and other toxic chemicals, since this can make them more prone to childhood cancers like acute lymphocytic leukemia.

28:41  There are a number of genes that have immunological functions on the X chromosome, including pattern recognition genes, cytokine receptor genes, transcriptional factor genes, noncoding DNA regions, and even immune cells themselves. 

29:37  When you look at where estradiol receptors are, they are everywhere and this affects the immune system in various ways.  Dr. Gersh published a paper on the estradiol and the renin-angiotensin-aldosterone system, Gersh FL, O’Keefe JH, Lavie CJ, Henry BM. The Renin-Angiotensin-Aldosterone System in Postmenopausal Women: The Promise of Hormone Therapy. Mayo Clin Proc. 2021 Dec;96(12):3130-3141. Estradiol is the switch that can turn on and turn off inflammation as needed. 



Dr. Felice Gersh is a board certified OBGYN and she is also fellowship-trained in Integrative Medicine. Dr. Gersh is the Director of the Integrative Medical Group of Irvine and she specializes in hormonal management. Her website is IntegrativeMGI.com, and she is available to see patients at 949-753-7475.  Dr. Gersh lectures around the world, and she has just written her third book, Menopause: 50 things you need to know: What to expect during the three stages of menopause.  Her other two books are PCOS SOS: A Gynecologist’s Lifeline to Restoring Your Rhythms, Hormones, and Happiness and PCOS Fertility Fast Track and she has also published a very influential paper in the prestigious journal Heart, which is part of the British Medical Journal family of journals: Postmenopausal Hormone Therapy for Cardiovascular Health: the Evolving Data.

Dr. Ben Weitz is available for Functional Nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss and also athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111. Dr. Weitz is also available for video or phone consultations.


Podcast Transcript

Dr. Weitz:                            Hey, this is Dr. Ben Weitz host of the Rational Wellness Podcast. I talk to the leading health and nutrition experts and researchers in the field to bring you the latest in cutting edge health information. Subscribe to the Rational Wellness Podcast for weekly updates and to learn more, check out my website, drwweitz.com. Thanks for joining me and let’s jump into the podcast.

                                                All right, welcome everybody to the Functional Medicine Discussion Group meeting tonight on why males and females have different immune systems and why it matters, with Dr. Felice Gersh. I’m Dr. Ben Weitz and I’ll start by making some introductory remarks. Then I’ll introduce our sponsor for this evening, Integrative Therapeutics, and then I’ll introduce our speaker, Dr. Gersh. I encourage each of you to participate and ask questions by typing your question into the chat box. And then I’ll either call on you or I’ll ask Dr. Gersh your question when it’s appropriate.  So thank you for joining our Functional Medicine Discussion Group, monthly meeting, and I hope you consider attending some of our future events. And I look forward to meeting in person again, once the Santa Monica library goes back to their normal hours. I’m not sure when that will be. And so our future events, November 17th, Julia Zaslow will be speaking about the business of functional medicine. So we’ll go into a bit about marketing and how to run your practice. There’s going be no meeting in December, and then we’ll start up again in January. And if you are not aware, we have a closed Facebook page, the Functional Medicine Discussion Group of Santa Monica that you should join so we can continue the conversation when this evening is over.  I’m recording this event and I’ll include it in my weekly Rational Wellness podcast, which you can subscribe to on Apple Podcast, Spotify, or YouTube. And if you listen to the Rational Wellness Podcast, please, please, please give me a five star ratings and review on Apple Podcast. So I’m pleased that the sponsor for this evening is Integrative therapeutics, and Steve Snyder is going to tell us a bit about some of their products. Steve?

Steve Snyder:              Hello everyone. Just tonight, just a couple little updates, one not so little update. As most of you probably know, Cortisol Manager is by far our biggest selling product. It’s a formula to help people fall asleep when they’re elevated cortisol at night. The original product was compressed tablets. In about two years ago, we released a newer version, an allergen free version that was capsules, but a lot of people stayed with the tablets. And there’s a big update that if you’re using those tablets, or your patients are using those tablets, you’re going to hear about it. We took the titanium dioxide out of the product and basically all that was, was a cosmetic to make the tablets white. It kept the tablets looking uniform, and so that they were, from batch to batch, they looked the same.  We’ve gotten to the point where we’re consistent enough in our manufacturing that that’s not an issue anymore. And a lot of people, I think just because of the name titanium dioxide mostly, didn’t like that ingredient. And so it’s no longer in the product. It’s a big difference in looks. So if you have people taking that one, they’re going to say, “Hey, this isn’t the same thing I normally get.” And you can tell them that they can be sure it’s the same formula, just a different color. So we think it’s a good thing overall. We don’t really have a position on titanium dioxide itself, but there’s a perception out there. So we reacted to market concerns.

                                                The other one is just a really quick immune update. We have a product called V Clear, used to be called Vibra Clear. It’s a pelargonium extract that has been studied in over 20 clinical studies. It’s actually, technically a homeopathic product, although it’s really just an extract. But because it’s labeled as a homeopathic product, we’re able to make claims on it. And the claims we can make are that it treats the common cold and flu. There’s about 20 studies on it over 9000- Over 9,000 subjects so far, 3000 [inaudible 00:05:01] … And the most recent one basically compared V Clear to upper bacterial infections, lung infections, and showed V Clear to be more efficacious with less side effects. So it’s the real deal. We can make it because we’re a drug manufacturing facility, even though we don’t make drugs, we have the GMP practices in place to make a product like this. And as far as we know, so far, we’re the only drug GMP manufacturer of supplements. So it adds a lot of layers to the quality control and stuff. But anyway, remember V Clear, it’s the real deal in upper respiratory infections.

Dr. Weitz:                            Thank you, Steve. Dr. Felice Gersh is a board certified OBGYN, and she’s fellowship trained in integrative medicine. Dr. Gersh is the director of the integrative medical group of Irvine, and she specializes in hormonal management and care of patients for many chronic diseases. Her website is integrativemgi.com, and she’s available to see patients. Her phone number is (949) 753-7475. Dr. Gersh lectures around the world. She’s published three great books. Her most recent book is Menopause, 50 Things You Need To Know. She also has a book on PCOS, PCOS SOS and PCOS Fertility Fast Track, her third book. She’s also published a very influential paper in this prestigious journal HEART, which is part of the British Medical Journal family of journals on postmenopausal hormone therapy for cardiovascular health. And if estradiol were a corporation and were to a hire lobbyist, it would most surely be Dr. Felice Gersh. Dr. Gersh, welcome to our meeting.

Dr. Gersh:                           Well, thank you. It’s such a pleasure. It’s been too long. And I’m so happy that, even though we’re not in person, that we have this opportunity to get together. And I get to talk about some of my favorite topics, of course, involving estradiol. And I am going to share my screen here. So my topic for tonight is all about immune regulation, the relationship to hormones and what to do about it because hormones are so important and there are such differences between males and females.  Now notice I put flowers everywhere. You know this is a girly talk, right? Because I definitely love flowers. Now, these flowers that I have pictures of here, were taken by my youngest daughter because she loves taking pictures of flowers in her yard, in her garden, she got a new house. And flowers are very symbolic to me of all kinds of things, beauty and happiness and love. And it’s the reproductive organ of a plant, right? And a beautiful, healthy plant is going to have beautiful, healthy flowers. And of course, when you have an unhealthy plant, it’s not going to create gorgeous flowers. If you’ve ever tried to grow plants with flowers, you know that, right? So everything about the female is about beautiful reproduction and flowers and health and vitality, which of course, involve a healthy set of hormones and immune function.

                                                I do work with a number of companies as an educator. Now, it’s so important to know, that in order to be healthy, you have to have what? You have to have optimal immune function, optimal metabolic function, and optimal hormonal status. Now, unfortunately, for women, this is really problematic these days because of the ubiquitous endocrine disruptors, xenoestrogens that are everywhere, that interrupt our normal hormone production, receptor function, degradation, elimination. And of course, every woman universal, unavoidable, maybe deferrable, but not for very long, has to deal with menopause, ovarian senescence and loss of ovarian hormone production. Now, this creates a huge hit on immune function, metabolic function, because it’s one body.  It sinks and swims together as a whole because the prime directive of life is what? I knew this after I delivered just a few 100 babies and I’ve delivered 1000s. It is the creation of new life.  Now, humans are the only species on this planet that actually controls, hopefully we control it, when and if we have children. And I’m all for having timed kids when we want them, or not having them if you don’t want them. But we’re the only animal that tries to say, “Oh, this isn’t a good year.” You put a bunch of animals together like a herd of deer, and they’re not going to say, “Oh, this isn’t a good year to mate.” It doesn’t work that way. So they just do what comes naturally. And so they have the creation of new life.

                                                So it turns out that once you accept that the prime directive of life is in fact, the creation of new life, then you can see how everything in the female body is designed for successful reproduction. And that involves fertility, having a successful pregnancy, then having the baby born, having the baby nurse, raising that child to its sexual maturity. So it can carry on the process of new life creation. And doing this, as a human, multiple times in order to make sure that the species can survive. And that requires a wonderfully healthy body and a hugely important and very dynamic immune system because pregnancy is an incredibly unique state of being, when the immune system has to have very significant moderation and modulation and alterations in order to be successful. And of course, not have the immune system of the woman kill its little foreign creature growing in her, that little fetus.  So in order for that to be successful, for there to be a baby that’s born, that’s healthy, and then the mom is healthy, and then this happens over and over, a female has to have an incredibly responsive and robust immune system compared to males because males don’t go through this incredible process called pregnancy. Now, whether a woman wants to have a baby or not, her body is essentially designed for that purpose. And in order for that to happen, you need to have what I call the mother hormone, the hormone of life, estradiol. Now, I often in my slides, I use estrogen to be synonymous with estradiol, just because that’s the word that people use. But we’re going to talk a little bit about estrogen because there’s so much misuse and misunderstanding about estrogen, estrogens. And the thing about women, is that because they have this amazing, more responsive and robust immune system compared to males, when things go wrong, they go wrong in a bigger way.  And we’ll talk about the issue of autoimmune disease. Now, quite epidemic, as you probably know from your own practices, how many women are dealing with autoimmune disease and autoimmunity, right?  Because we, as functional medicine practitioners don’t just care about end stage disease. In fact, our goal is to prevent end stage disease by recognizing the early incipient signs like autoimmunity, like positive ANAs before the actual autoimmune disease is evolved. So estrogen, in order to maintain the immune system working properly, has receptor systems all through it, all aspects of the immune system are involved with estrogen.

                                                Now, I mentioned men and women are different. This comes up all the time in all my talks and the gut microbiome, which is talked about in everything now, as the center of the universe, who knew 15 years ago that we have this little control center in our gut that has these trillions of microbes that’s actually could sort of like pulling the strings around our bodies? Well, men and women, as they have very different immune systems, you may say what? They have all the same cells. Well, they actually work in somewhat different ways, and we have actually, different microbiomes in our gut. And this was found out when they did some fecal transplants, for example, and they gave male transplants of fecal material into females, and then the females started making a whole bunch of testosterone. And so it’s really interesting. We are different in so many ways.

                                                And when I was back as a younger woman, I was growing up during the age of feminism, when the word even evolved, the word feminist. Did you ever hear that? So I was an early feminist and I thought men and women should be the same, that we should wear those men’s suits as a female. Well, that’s not true. We are really different and we can accomplish all the same things, but we are different. And we need to, if we’re going to take care of women, we need to understand their physiologic differences from males, so we can optimize care. Did you know that it wasn’t until 2015, that’s not that ancient, that history, that it was not required by the National Institute of Health that females be incorporated into studies?  So we have actually, kind of limited data on a lot of female topics because nobody was studying women. Why was that? Well, because we’re more complicated because we have cycles. We could get pregnant, we could be on contraceptives, which are chemicals, and we could go through menopause and all these things complicate women as study subjects. So they just left us out. That was it. So who knows about women? Well, we’re trying, but I’m telling you, we need more data. Always. When people say to me, what about this, what about that? I say, well, I’ll give you my best guess based on the science. Because guess what? We have actually no data, but we do have information. We do have science. And we do know, as I mentioned, that females and males have a lot of differences within how their immune systems work. So it’s not just about how things look from the outside, it’s how they work from the inside.

                                                So males and females, their differences are driven by their chromosomes. Now I’m sure you know this, what’s a guy, male from birth? We won’t talk about what they choose to be later just from birth. So they were, say, an XY. So they’ve got this big X and this little bitty y, but you guys out there don’t think it’s inferior. It’s just different, that little y. And we have females born with two big X’s, and we’ll talk more about that. And of course, it’s not just having chromosomes and genes, it’s how they’re expressed. And hormones are very big on that, our gut microbiomes, our circadian rhythms. And then of course, females are more limited, in that they have a very defined time when they can be reproductively successful, whereas males potentially, could create new babies at any stage of their lives. It turns out this isn’t just a human kind of a situation because when you look at other animals, in fact looking at insects and lizards and birds and other mammals, they also show immunological differences between the male and the female.

                                                Now, females, as I mentioned, have a more robust, more dynamic, we’ll say more powerful immune system, and that allows greater survival in things like pandemics. And this became actually, very evident early on in the COVID pandemic in New York where things were really in disarray back at the time of March and April 2020. And looking at the mortality rate in New York City from COVID, males made up over 60% of the deaths versus females, 38%. That is, why is that? Because males do not do as well because their immune systems are a little bit weaker in terms of their ability to fight off infections and sepsis.  In fact, going way back into 1998, ancient times for many of you perhaps, when they looked at survival of males and females who suffered with sepsis, look at the difference in the survival rate. About three quarters of women survive versus only a little over 30% of males. Women just have a higher survival rate from pathogens because of their very robust immune systems.

Dr. Weitz:                            Dr. Gersh, do we know about the likelihood of having long COVID for women versus men?

Dr. Gersh:                           It seems that women are more subjected to, more likely to have long COVID than males. And that’s because when women are challenged and they’re having metabolic problems and they develop these, we’ll say long acting viruses, they have chronic viruses, they end up having more autoimmune. A lot of the long COVID is felt to be possibly, I mean we don’t even totally know, but it may be an autoimmune driven thing. And women, which we’re going to talk about, make up 80% of all the autoimmune sufferers. And we know that women are just more prone to having reactions. And we’ll talk about it, actually, I can talk about why does an infection even cause autoimmunity?  In fact, let me just tell you why, okay. So why is it that chronic infections and the common ones are all the different herpes viruses. So there’re a lot of chronic infections with herpes. And then of course, now we think that the SARS-CoV-2 can cause a chronic infection. There’s chronic infections with various hepatitis viruses, right? Hepatitis B, hepatitis C. HIV is obviously, sort of chronic and so can HPV.  So when you have an infection, an acute infection, the body makes antibodies by the adaptive immune system. Well, I’m going to cover this, but I can jump ahead because what, who says, we have to go in any specific order here? So this is very important. Women have more B cells. Women actually make, women have more immune cells than men. Women make antibodies in greater quantity and more robustly and more readily.  So every time you have an infection, the body will create antibodies. And that of course, applies to vaccines as well. That’s why every single vaccine has the potential to have an autoimmune reaction. This is a 100%. Every single infection has the ability to create an autoimmune response. Why is that? Because you always make antibodies with every infection. And it turns out that we and viruses and bacteria, come from the same primordial pool of nucleotides. The building blocks of RNA and DNA are the same throughout every life form on planet earth. They’re just rearranged differently. Like amino acids to create different proteins.  And so these nucleotides, RNA, DNA are similars. So when you make antibodies against a virus or a bacteria, there is always what we call molecular mimicry. These antibodies will always attack our own cells, always, a 100%, but it should be in an acute situation it’s short lived. So you make antibodies against whatever tissue in the body is most similar to that particular pathogen. And in fact, they even have charts showing different pathogens that are associated with different autoimmune diseases. Because if you have a chronic infection, and remember leaky gut is like a chronic infection because you’re having influx into the body of pathogens from the gut. But you can have leaky other things too. Women can have leaky vaginas, where they have any barrier between the outside world and the inner body can be leaky. So you can have leakiness in the sinuses, in the bronchial tree, but the gut is the biggest potential source of this leakiness.

                                                And when you have an infection that is coming from, not from the gut say, with these other bacteria, people can have chronic strep infections where they have in the crypts of their tonsils, they can have the strep just kind of hiding out there. And that can create all kinds of problems. And of course, we know that strep infections, before we had antibiotics, the penicillins, they could sometimes give you things like scarlet fever, rheumatic heart disease, that’s autoimmune based. And if any of you’ve read Little Women, there was a little death in that family from a young girl who had the autoimmune response to a strep infection. And those are tragic things.  But autoimmune diseases are ongoing and we have so many disruptors to our immune system, so many more chronic infections that we’re having this autoimmune. And of course the leaky gut is a big source of these chronic pathogens entering into the body. So we have this molecular mimicry issue, where you make antibodies against the pathogen, but it cross reacts with ourselves and women because they make more antibodies than men, make them more readily and have more B cells that make and the antibodies and women have more of the dendritic cells. These are the ones that are the passers onners of the antigen. So they communicate with the other immune cells like neutrophils and mass cells, and they then have their little arms that stick out and then they connect with the B lymphocytes that make the antibodies.   So the females have a better, we’ll say, directional system of communicating the antigen being there to the cells that make the antibodies. And so this is going to apply to COVID as well. And so this is a huge problem for long COVID is more female, just like autoimmune. And so women have the advantage in survival for acute infections, but for long term chronic infections, it’s a problem because autoimmune disease can definitely ensue.  And over time there can be other things that sort of take over and almost get a life of its own, where the antibodies continue and sometimes you can never find what the original pathogen was that initiated this whole sequence of events. And if we go back here to COVID and we look, we can see that deaths and hospitalizations were also varied by gender as well.

                                                So I mentioned the X chromosome is different. This is actually not a small matter because this is huge, now you see hormones are a big part, but it’s never just one thing, right? Everything is always complex. So it turns out that extra X chromosome that females have…  So it turns out that that extra X chromosome that females have is very instrumental in creating this more robust immune system. So the estrogen sort of perpetuates it, but the X chromosomes actually initiate it. So when you are made as a female, you have two X chromosomes. Now, it’s belief that one of those X chromosomes is randomly silenced during the time of being an embryo. But what really happens is both X chromosomes are functioning for several weeks. And during that time, before the one random one is quieted down, they actually are changing how genes express themselves within the immune system.   So during those first beginning weeks of life, both X chromosomes in a female are acting, they’re functional, and it’s changing how genes are being programmed to behave and in terms of how immune cells will react. And then when that X chromosome is silenced, it’s actually not completely silenced.  It turns out that about 15% of the genes are not silenced. They keep functioning. And it turns out that most of those ongoing functioning genes of the extra X chromosome, they’re actually related to immune function.

So women are so programmed to have different immune systems from the earliest state of embryological life. And of course this is why it’s so important to not have endocrine disruptors and chemicals and things on board right from the get go because things are critically happening right from the beginning of life. And when things are not right, and we have improperly programmed receptors and these systems that are coming on board that makes women much more prone to diseases and cancers and so on.  They’ve now identified for example, that early age like little bitty kids, like two year olds and such who get acute lymphocytic leukemia in these really early childhood years that they were exposed in utero to things like high levels of pesticides. It changes how the immune system is working in utero. That’s why I’m so big on preconceptual planning and maintaining the cleanest possible environment and food intake and water intake during every stage of pregnancy including the very, very beginning.  So once you recognize that these genes that are involved in so many of the immunological functions are located on the X chromosome then you can see how the… Look at these different types of genes that are all X chromosomes, the pattern recognition genes, cytokine receptor genes, transcriptional factor genes, noncoding DNA regions, immune cells themselves. These are unbelievable. Even when you get rid of the hormones, okay? Females are going to function differently than males. And even in an environment where you take away the sex hormones, the X chromosome, the double X chromosome females, and this is in mice because sometimes remember we don’t have everything in humans, but we have a lot of data, they also had more of the mouse equivalent of lupus and MS.  So genes are not insignificant.

When we look at where estradiol receptors are, it’s everywhere and it affects the immune system in a whole host of ways. Now, you mentioned that I had a paper that was published in Heart last December. I had a paper that was on estradiol and the renin-angiotensin-aldosterone system, which is very related to survival and the immune system as well.  And basically the basic tenet of that is that estradiol, when you have the right balance of estradiol in the body, it actually operates the switch. The switch that turns on inflammation and turns off inflammation. That’s why sometimes it’s very tricky that people say, “Well, it’s proinflammatory. Well, it’s anti-inflammatory. Well, guess what? It’s all of the above because estradiol is a modulator regulator of the immune system.  So when you have an immune system that’s activated because of appropriately, it’s because a pathogen of some kind is trying to get into the body or there’s trauma. So the PAMs and the DAMs, right? so the immune cells are activated by pathogens and by damage. And so when this happens, it’s estradiol into action. It activates the immune system. It actually turns on monocytes, neutrophils, mass cells, all of that to get going to create the inflammatory response to save that woman’s life.  That’s why women have higher survival and infections and sepsis. But you don’t want unending inflammation. That’s a killer, right? Chronic inflammation is the last thing anybody wants. Estradiol also turns off the switch from pro-inflammatory into anti-inflammation and pro-healing. So this is really important that estradiol modulates every aspect of the immune system, which includes every immune cell and the platelets.

                                                So platelets are very involved in immune function and the way that’s involved with the renal angiotensin aldosterone system is that’s a system for survival. So if you’re infected or you’re traumatized, you’re bleeding, you want to activate the pro-inflammatory arm of the RAS system so that you have increased aldosterone. You have fluid retention to maintain volume in your vascular system.

                                                So you don’t go into shock. You want to actually create leakiness in arteries. You want leakiness because when you have immune cells circulating, if they can’t get out of the blood vessels, how are they going to get to the extracellular sites of infection? So you create a leakiness in the vascular system to allow platelets and to allow the immune cells to exit the conduit, the artery and the capillary so it can get out into the tissues.

                                                And then it activates the immune cells so that cells like macrophages, neutrophils, they put out all of their toxic products to destroy the invading pathogen and it activates… Estradiol, activates phagocytosis so that you can actually gobble up and then get rid of dead damage tissue, get rid of the pathogens. All of this is modulated by estradiol. And a lot of this is not as active of course in males because look at here what I put in a little, I don’t know what color that is, sort of RNG.

                                                I wrote testosterone suppresses immune cell activity. Sorry, guys. You have many other skill sets, but you are not as good at creating the pro-inflammatory state to deal with trauma, to deal with sepsis, to deal with infection. And I’ll tell you why in a minute. In case, you’re wondering, why is this? Well, why women have to have this dynamic immune system, it’s so that it can mod be modulated during pregnancy, but also because… Okay, I’m going to give it to you straight. If you had a pandemic and you had 10 men survive to every female, that’s not going to get you where you need to go as a species.

                                                But if you have 10 women survive to every male, well, you can repopulate the planet. Right? So nature wants survival of the species. So women have to raise the children. Women have to procreate and make new kids. So you need to have more women survive than men. If you have trauma, if you have infections, it’s just the way it is. Who’s better at surviving a famine? Who holds onto their fat more? Oh, it’s us. So it’s just what it is.  But you guys, you are bigger, stronger. You have more muscle mess and that’s where a lot of your energy goes. Where else does your energy go? Making all those sperm? Oh my gosh. It takes a lot of energy from the body to keep making sperm. It takes a lot of energy in the female to keep that immune system going. So it’s a division of labor and energy.   So there’s only so much energy that you can create in the body. The female puts an enormous amount of her energy into maintaining that robust immune system with all those cells, those extra cells, all that extra activity. And males put it their extra energy into maintaining a larger structure, more lean body mass, more volume, more mass. And the energy it takes to keep making all those sperm. So it’s just how nature divided up. Everything in life is about successful reproduction and survival for that purpose.

                                                And then indirectly, the hormones are going to be involved in microbiomes and circadian rhythms. There’s differences in every single part of the immune system between males and females. So women, as I mentioned have higher numbers of cells that are immune cells. Women have higher white counts. Women have more immune cells and they are more active. So you can see, I mean, we can go through everything. Women have more of this, they have more of that.

                                                By the way, anyone can have my slides. I share everything. Estradiol is so important that half of all the activated genes in the T-cell have estrogen response elements. Estrogen is involved in immune function. Now, men do have a lot of activity involving their immune system through estradiol as well. Because you know all estradiol is derived from what, a hundred percent, no exceptions, testosterone. The precursor of estradiol is testosterone, is converted by the enzyme aromatase.   And many, many tissues have the enzyme aromatase in them, many, including arteries, including the heart, including the brain, including the skin, including the gut. And that enzyme helps convert testosterone for the male into estradiol so that it can have… A lot of the benefits and functions of testosterone don’t come directly from testosterone receptors, but rather from its conversion into estradiol. So men have plenty of estradiol, but it’s not circulating.  It better not be, okay? So they shouldn’t have high circulating. It’s locally produced [inaudible 00:37:24] production and stays in those tissues. So I mean, I just put a lot of things here, but it’s really repetitious because I already told you women have more B cells. Women have more T helper cells. They have more T helper 1, they have more T helper 2. They make more antibodies. They have more immunoglobulin. we just have more of everything that has to do with immune function.   As I mentioned, it’s all about ultimate survival. Women have a bigger response to vaccines. And this drives me crazy. We don’t make sex specific vaccines. This is wrong because women have a greater reaction to them than men do. So they’re going to get more antibodies produced. So I mean they’re more effective in women, so that’s a good thing. But if they get an autoimmune response, then it’s going to be greater. So women are more likely to develop, for example, Guillain-Barré or Bell’s palsy from a vaccine than a male because we have a bigger response. But they don’t diagnose the vaccine for women because nobody cares. But we care. It’s doesn’t seem right.

                                                And so I mention, I call estrogen, I named this. There’s no book that says this is me. I said it’s the mother hormone. It’s the hormone of life itself. It’s the master of all metabolic functions, metabolic homeostasis and immune function. And what is metabolic anyway? It’s the creation, distribution, utilization, storage of energy. So estrogen, and I say estrogen, but I’m talking estradiol, the ovarian produced estrogen. It’s involved in everything that has to do with energy.

                                                Now, why does energy matter? Because energy is the driver of everything. You need to have energy, it’s life itself. And in order to have proper energy, you need to have a regulation in the brain that says eat more, eat less. That’s regulated. Actually the nutrient sensors in the brain all have estrogen receptors and that’s a problem when you have a body full of endocrine disruptors, these diabetogens or you don’t have enough hormones or if you’re on chemicals like hormonal contraceptives where it can dysregulate your appetites.

                                                So your energy needs become mismatched to your energy consumption. This is a highly regulated system through estrogen because it’s so important for humans and every animal species to have the right amount of intake of food, AKA energy to match the energy needs of the body. You don’t want under and you certainly don’t want over. But the default is when things are not right, it’s over as you well know from all of your patient population.

                                                So just what is this hormone thing? A hormone is an information delivery system. It gets to the cell. It binds to receptors. They could be in the nucleus. They could be on the cell membrane and information is delivered. It’s like having a pony express and then when finally, the messenger gets there and he says, “I forgot to bring the message,” then it’s like, “What do we do? We don’t have the message?” That’s like, “What does the cell do if it doesn’t get the message or worse yet you have endocrine disruptors, it gets the wrong message.”

                                                Well, that cell is not going to behave properly. And that’s another competing problem for why we have such dysregulation of our immune system. I know when I was back in training back in the day and residency, I didn’t learn anything useful about hormones other than they had something to do with reproduction. But it’s really about survival and life itself because we now know that many creatures have estrogen receptors that do not have reproduction that’s anything like humans.

                                                For example, animals that predated clams. They actually have estrogen receptors. In fact, it’s believed that the first steroid receptor that existed in any life form was actually estrogen receptors. So that’s why it’s the preeminent hormone of life. And here I put down that invertebrates had no sexual production we have, and yet they had ancestral estrogen receptors.  This is really amazing when you think about it that estrogen, which we think in our current medical system as all about reproduction, really had its first entry into life forms as a metabolic regulator. Of course you can’t have successful reproduction without optimal metabolism. That’s like an essential. We know that estrogen, and I talk estradiol, it does a million things in the body. I go on and on, it’s like you already know I’m the lobbyist for estrogen as was said, right?   It’s like somebody’s got to stand up for the underdog here. Estradiol regulates everything. You name it because it’s about maintaining life. And there are these receptors. We now know alpha, beta.

Dr. Weitz:                            Now in your last slide you had estrogen increases lean body mass. Isn’t that what testosterone does?

Dr. Gersh:                           Well, testosterone does that too. That’s right. In fact, one of the biggest problems in menopause is actually sarcopenia. Estradiol is very big on maintaining lean body mass and muscle mass. That’s correct. Estradiol doesn’t get its place in the sun. I have whole lectures. Maybe another tale I’ll come back about how sexual functions, sex drive and everything relies on estradiol and the relationship to peptides and vasoactive intestinal peptide and oxytocin. A lot of the male stuff, it does rely on conversion into estradiol.  So yes, absolutely. One of the big problems after menopause is loss of lean body mass and the production of really toxic inflammatory adipose tissue, especially in the belly and the visceral fat is so horrible. So, oh my goodness, I am going to write a book. I have to get to it on the wonders of estrogen, but I don’t know who’ll buy that book.   But I’ll just give out copies because I want people to know how wonderful this hormone is that has been so maligned so terribly. And this is a little piece of important information that I always want to share. The estrogen receptors, which are more predominant in different organs, like the alpha receptor, is heavily in the hypothalamus and regulates a lot of the metabolic processes like appetite regulation, reproduction, like the menstrual cycle and so on, the circadian rhythm. The master clock is in the hypothalamus, which is heavily modulated by estradiol.

                                                In the gut, the intestinal tract is predominantly beta. The cerebral cortex is predominantly beta. Arteries are predominantly alpha. That’s why you don’t want one or the other. You want the balance of both. And when you have the… And these receptors are up and down regulating each other. Nothing is as simple as you may ever think. The more you learn, the more complex things become. And these receptors interact with one another.  High beta like estriol. Estriol works on the beta receptor. Estriol on the alpha estradiol is balanced. And high stimulation of the beta receptor actually downregulates the alpha receptor. And this is very key in pregnancy when you have lots of estriol because estriol is beta and it downregulates alpha and where is alpha? It’s on the innate immune cells. The innate immune cells. But it’s also on the arteries. That’s why pregnancy is the ultimate stress test for women because you have vascular challenges. You have changes in gut microbiome, which I’ll talk about.

                                                You have instantly dysbiotic gut microbiome very shortly, not instantly, but shortly after pregnancy occurs and it progresses and that’s designed to do what? To create a small degree of insulin resistance. Inflammation causes insulin resistance. And so every woman who’s pregnant is sort of on the fringe on thin ice between having just a little bit of insulin resistance and crossing the line into gestational diabetes.

                                                If you’re going like, “Why do women who are pregnant get these diseases like gestational hypertension, gestational diabetes, preeclampsia?” It’s because they become pro-inflammatory but for a purpose to increase insulin resistance, but just enough to increase fat storage and production in the pregnant woman because women have to store a bunch of fat. That’s why women who are pregnant gain weight even if they don’t eat more because they are insulin resistant. And insulin drives fat storage in production that also creates more blood sugar, enough to cross into the placenta into the baby to help grow that baby.

                                                Remember humans evolved during times of food deficiency. We didn’t have food on every corner so we had to be very capable of putting on fat and of growing that baby. And that’s why women who are pregnant become insulin resistant and their immune systems are altered because the alpha is on the innate immune cells.

                                                And you want to down-regulate them so that they are the attack animals, so they don’t go and attack and put out their inflammatory cytokines to kill the baby. That’s why women who are pregnant will often go into remission for many autoimmune diseases because they produce fewer inflammatory cytokines.

                                                They also are less capable of fending off pathogens, COVID, the flu, chicken pox and such because their innate immune cells are not going to be as functional. This is all part of the strategy of surviving during pregnancy for the baby to survive. So the mom’s immune system doesn’t kill off the baby. But we do not want to take a post-menopausal woman and try to recreate the scenario of a pregnancy because estrogen receptor alpha down beta, the beta receptor when it’s highly bound, it will actually down regulate alpha.

                                                And you need alpha. You’re not trying to get rid of alpha. The only time you’d want to get rid of alpha is if you’re treating someone specifically with breast cancer because breast cancer positive is always when it has receptor positive for estrogen breast cancer, it’s the alpha receptor. Okay? But that doesn’t mean that you don’t need alpha, okay? So you want everything balanced. That’s why for postmenopausal women please give estradiol not estriol because we don’t want to alter the immune status of women who are postmenopausal, so their innate immune cells are less functional. We’re not trying to do that.

                                                Pregnancy is a very unique state, so don’t try to replicate it because you’re not, and it’s not going to be beneficial. Don’t try to recreate human females in a way that they never exist on this planet. So understanding this dynamic between the receptors and how the immune system is working. So we’ll show you some other things here. I already went over a lot of this stuff, the different forms of estrogen and how they react differently with different receptors. And that there are estrogen receptors throughout the entire human body, as I mentioned, and on every single immune cell.

                                                So just getting to basics, why do we even have an immune system? Well, it’s just amazing. I mean I didn’t learn enough about the immune system back in the day when I was in medical school. I can tell you I didn’t realize all the things that it does, but it’s a tremendous information system. The inflammatory cytokines, and there are antiinflammatory cytokines as well. They’re also communication systems that really tell different cells what to do.

                                                So it’s amazing what the immune system does and we need to do everything we can to maintain it. In this busy looking slide, it’s just looking at some of the different peptides and enzymes that are all modulated by estrogen, estradiol. And I highlighted in yellow a lot of the ones that are specific for the immune system. But basically everything interacts with the immune system, but it involves all the issues with lipid metabolism, coagulation.

                                                So remember, estradiol does not cause blood clotting. When you have a regulated immune system. It causes blood clotting when you need blood clotting like when? If you have hemorrhaging, okay? Or as well platelets are activated if you have an infection. Why would platelets be activated if you have an infection? Because platelets help to create the encapsulation of… If you wonder, how the heck do you make an encapsulation of an abscess? How does that happen in the body? That’s through the action of platelets.

                                                So they’re activated in infections as well. But if you have a really severe chronic infection, this has happened with COVID, right? That you can end up having uncontrolled inflammation and then you can have abnormal blood clotting that of course can kill people. So it’s a fine line. Just like pregnancy is a fine line. SO2 is navigating an infection so that you can control the proinflammation and the anti-inflammation. And in order for that to happen properly, you need to have the right amount of hormones and elderly people don’t, that’s why who tends to die the most from COVID? The elderly… That’s why, who tends to die the most from COVID? The elderly people. By the way, right at the beginning of COVID, I said we need to do a study with estrogen to see if estrogen is going, like menopausal women who are on estrogen, they’re going to have better survival. But I couldn’t get any of my friends who actually do studies, because I’m a clinician. I couldn’t get anyone to be interested in it. Well, there were some studies and there were some published data that yes, indeed, estradiol helps to prevent COVID deaths. Because duh, it modulates the immune system. And of course, pregnant women, now papers have come out that has been significant excess female maternal mortality related to COVID, because pregnant women are not as able because of their innate immune cells being down-regulated by estriol. And we don’t want to do that to our postmenopausal women. So understand that in the end, estradiol modulates all of these systems.

Dr. Weitz:                           Well, essentially you’re saying no Biest cream recommended.

Dr. Gersh:                           I am. I am saying that. I’m begging you to stop using that. And then if you are using it, then say, why? Where did you get this data? What is it based on? Somebody who said something 35 years ago who didn’t even know, not through any fault of his own.

Dr. Weitz:                           So there’s no decreased breast cancer risk.

Dr. Gersh:                           No. Where’s the data on that? If you’re treating breast cancer there, why do they give tamoxifen? Okay, Tamoxifen is a chemical version, to some degree, of estriol. So I’m not saying also, there is some published data that estriol can help modulate the immune system. Think of it as an immune modulator. So it will down-regulate the production of inflammatory cytokines just like Remicade and Humira, and all these drugs that are now so prevalent all over the place that are blocking, this one blocks tumor necrosis factor alpha. This one blocks interferon, this blocks some interleukin and so on. Well, guess what? Estriol decreases the production of all of them. So there’s some data that it can help with MS. So I’m not saying there can’t be potentially. Now of course, we have pharmaceuticals that are doing all these things. So they never used a natural product because no money in that, right?

                                                But understanding the mechanisms, yes, there may be some benefit. If you have breast cancer, there may be some benefit if you have MS. But to give it to just the typical average woman who’s in menopause, what the heck are you doing? You’re not treating breast cancer. And by the way, estradiol helps prevent breast cancer. That even came out in that stupid Women’s Health Initiative study. So how does this happen? Let me just step back a minute, because breast cancer always comes up. When you don’t have enough estradiol, who gets the most breast cancer? Postmenopausal women. Postmenopausal, not premenopausal. When you have enough estradiol, you’re modulating the immune system. So you’re preventing runaway inflammation. Okay? You’re maintaining a healthy gut microbiome, you’re controlling your immune cells, right? It’s the controller. You’re controlling all this. When you don’t have enough estradiol, you end up in this pro-inflammatory state.

                                                You have gut dysbiosis, you have leaky gut, and you end up in this default system where the anti-inflammatory pathways can’t be activated. It turns out that the anti-inflammatory pathways are probably more beta-driven and the pro-inflammatory more alpha. Well, after menopause, what do you make if you’re a female? You make estrone. Now, estrone is made through the conversion of androgens, predominantly coming from the adrenal gland, which makes huge amounts. That’s where the biggest steroid hormone is what? It’s DHEAS. So that can be converted into estrone. Now, when you have chronic inflammation and postmenopausal women like inflammation, they become low-grade chronic inflammatory people. And inflammation up-regulates the enzyme aromatase. So now you’re converting these androgens to estrone. Inflammation blocks to a significant degree the enzyme that converts estrone to estradiol, because it should be back and forth. But the enzyme to convert estrone to estradiol is now largely blocked.

                                                So you end up stuck with estrone, the alpha receptor agonist. Now when you have that, you’re ending up feeding the inflammatory state, you’re activating the innate immune cells even more. And when you have chronic inflammation, it’s everywhere in the body, including in the breast tissue. Then chronic inflammation drives DNA instability and breakage. You get cancer. Now, estradiol and estrone, they’re all growth hormones. Now they promote growth. Now growth is evil if it’s uncontrolled, but it’s essential for life, because growth isn’t about just getting bigger, like the uterine lining gets bigger. Growth is about repair, rejuvenation. That’s why everyone loves stem cells. And you know, can’t replace old dead cells, senescent cells, regenerate healed wounds or anything if you don’t have estradiol. So it’s like the growth hormone of rejuvenation, okay? That’s why you can put it on your skin. And guess what? Wrinkles go away. I’m not kidding.      There’s data on that. Okay? So the thing is, you don’t want uncontrolled growth, because uncontrolled growth can grow cancer cells that have those estrogen receptors. I told you breast cancer is alpha-receptor positive. So now you have the perfect scenario, you have chronic inflammation that’s driving DNA instability and breakage, and then you have breast cells exposed to estrone. Now, estrone is made wherever there’s adipose tissue in an inflamed person. Now, where is breast tissue? What is breast tissue composed of in postmenopausal women? Largely fat. So estrone is made in the breast. So when you talk about where’s the estrogen coming from, it’s coming from in the breast tissue itself. And so that’s driving the growth of that breast cancer, which is estrogen receptor-positive for alpha receptor. But if you had estradiol present in the first place, then you modulate the immune system to keep that inflammation, to keep the gut microbiome healthy and proper, so that you don’t become elderly in the sense that you have this inflammaging process.

                                                So by starting your women patients on bioidentical estradiol and progesterone in a physiologic way, you can help to maintain them in a premenopausal health status to a large degree. It’s not like getting 25-year-old ovaries, but it’s sure better than the opposite. And estriol is not designed for that. And remember, estriol is beta, so it’s not on the arteries, it’s not the same. Please stop trying to create some new dynamic that doesn’t exist. So just give the body what it does best on during the reproductive years, and that’s estradiol. And you will make estriol, by the way, from estradiol, when it’s needed in the right amounts. So please, please think about why are you giving Biest, and who told you to do that? I’m evidence-driven. There’s no good data on that. It’s only negative when you understand the science and when you look at what estradiol does, look, it’s helps prevent people dying from influenza and more.   These are just articles that have been published. You can read this. The content, it’s so interesting. Estrogen receptors regulate innate immune cells in signaling pathways. I mean, the takeaway from tonight is estradiol is wonderful, and you can’t have a functional immune system if you don’t have it. Okay, got it, everybody? And look at the different pathways. It’s like, so 17 beta estradiol, that’s made in the ovary upregulates, the, I call it NERF2. I don’t know what you say, but this is not optional. This is so important. Everybody wants to increase NERF2, right? Well, estradiol does it. Estradiol does everything that you think you want to do. Where do you think you get NAD to activate? Okay, that’s a co-enzyme with the sirtuins. Guess what? Estradiol promotes NAD function. What else? How about the sirtuins that you want from fasting?

                                                That’s a bidirectional effect between estradiol and the sirtuins. So all of you antiaging fanatics, you can’t have any of these whole enzymes and enzymes work properly in an absence of estradiol. Okay? And look, I look for articles everywhere. So everything is science, evidence-based. You want to control inflammation, you get estradiol on board. And look at all what estradiol is regulating through the innate adaptive immune cells. I mean, all the neutrophils, all of these cytokines, everything is regulated by estradiol, Th1, Th2, the Tregs. If you don’t have enough estradiol, guess what happens? You don’t have proper functioning of your T regulatory cells, which help to control things in the body. So definitely need that. So I think you know why we have inflammation, well, inflammation needs to be tightly regulated by the toll-like receptors, which are circadian. And of course, estradiol helps regulate the circadian block, as I mentioned.

                                                Now I have a whole bunch of slides here that just to, oh, and I mentioned that estradiol is essential for phagocytosis. And what’s a cousin of phagocytosis? Autophagy. Okay, estradiol. You always want autophagy, right? You never want continuous autophagy, but you want autophagy so that you can have cellular renewal. I call it house cleaning. You get rid of the junk and you turn it into fresh. Well, you need estradiol for that. And if you don’t believe me, go on PubMed. There’s a ton of articles on that. Now I put this here to show you this is actually a mass cell. And look what’s smack in the middle there. ER alpha, oh, estrogen receptor alpha. I told you, it’s on all the innate immune cells. And there’s the toll-like receptors, and it’s being activated in this case by the damage. This is actually endometriosis that they’re talking about here.

                                                But this could be a mass cell with any kind of injury. And then it de-granulates and releases all of its toxic products in order to deal with an invading pathogen, or damaged tissue and trauma. And then the mass cell then calls in the troops through its chemokines and activates all the other immune cells. And if you don’t have proper estrogen receptor alpha function, oh, remember, estriol doesn’t work on it and actually downregulates it. You’re not going to have proper immune response. Now this is just showing this is a mass cell, all the millions of things that mass cells do. And you see how it links to pain? Who has more pain? Men or women? Women. Women experience greater pain. Who frequents cannabis dispensaries if you went to their cannabis dispensary? It’s two groups of people in general. Young males looking for recreational cannabis, and postmenopausal women looking for something to help them to deal with pain and insomnia and menopausal symptoms and such. Because women are more sensitive, and mood problems, to all of these things.

                                                A lot of these things are actually driven through the inflammation that becomes uncontrolled after menopause. So menopausal women are frequently visiting the cannabis dispensaries. And they need you to guide them so that they don’t feel they’re on their own, nobody cares about them. And then I just go through all the different immune cells. So you can look at this later, how estrogen works through all of these different immune cells. And you need to know at some point, I think, you know what these different immune cells do. It’s really fascinating. So I just put down a lot of the things that neutrophils do and macrophages. And of course, what are specialized macrophages? The microglia in the brain are specialized macrophages, microglia in the gut are specialized macrophages, osteoclast in bone are specialized macrophages. And after menopause, they all go wild without control. They’re like weapons of mass destruction without control, damaging the brain, damaging the gut, and of course, causing more osteoporosis.

                                                That’s why the best thing for bone is what? Estradiol. I do whole lectures on bone health. And of course, everyone out there who deals with the musculoskeletal system needs to appreciate that, because women have 80% of osteoporotic fractures. This is preventable. Over 50% of women have osteoporotic fractures. And bone is amazing tissue. It not only is structural, but it also is an endocrine organ as well. So the dendritic cells I’ve mentioned, they are the messengers between the innate and adaptive immune systems. Women have more of them and are better able to transmit the information to the adaptive immune cells, the lymphocytes that make the antibodies. And all of the T cells are up-regulated and functional with estradiol, the T lymphocytes of all the B1s. And so all of these things you have to think about when you’re giving chemical endocrine disruptors like oral contraceptives.

                                                I mean, this is really important when you understand the importance of how hormones work in the female body. What the heck are we doing when we give chemicals that prevent ovarian function during the reproductive years? I don’t think this should be ignored. We know, for example, that young women, because we don’t have data on women over 20, but girls in their teens who start on birth control pills have higher lifetime risk of cardiovascular events. They never reach optimal potential for bone density and muscle growth. So these are big deals. And then think about all the endocrine disruptors. And then once again, think about what hormones do you want to give women in menopause? The lymphocytes, of course, and they’re all involved with the function of the immune system and regulated by estradiol. It’s important to know estradiol is essential for proper phagocytosis. I mean, most people don’t know that.

                                                So antibodies lock onto the antigen, but they don’t kill it. Antibodies alone do not kill. It’s the phagocytosis that actually does the killing. It’s the one-two punch. And all of that involves estradiol for optimal function. And estradiol, its effects are variable depending on levels. That’s why the whole concept that came out after the Women’s Health Initiative of give the lowest dose. That’s insane. What you want to do is give the most physiologic efficacious dose. Because women who have very low estrogen are more pro-inflammatory. What’s a pro-inflammatory state of a woman in a natural cycle? It’s when she’s having her period, that’s when estradiol is the lowest of the menstrual cycle. And why is that? Because having a period is actually a pro-inflammatory state. Because your body is contracting the uterus, getting rid of the lining, and it produces pro-inflammatory prostaglandin. And of course, when you don’t have proper regulation, you end up with what?

                                                Heavy periods and terrible cramps. That’s a red flag that this person is not properly regulated. They have too much inflammation. They may be stressed, they may have nutrient deficiencies, hormonal imbalances, endocrine disruptors. So remember, the menstrual cycle is a vital sign of female health status. So when you have a messed-up menstrual period, it means they have something wrong with the owner of that menstrual period. The solution isn’t to give her chemical endocrine disruptors. The solution, that’s smoke and mirrors. The solution is find out what’s wrong and fix it like we always do in functional medicine, right? And so also, it affects Th1, Th2. Who has more allergies? Oh, women, did you know that? And that’s Th2-driven in pregnancy. Progesterone pushes towards Th2. Okay? And down regulates Th1, because you don’t want to have so much cell-mediated immunity, you go more to humoral immunity.

                                                And I would love to give a whole course on immune system if you don’t know what I’m talking about. But these are things that you should look up if you don’t, because this is really important to understand. I think foundational to understanding how to treat anyone is understanding the basics of the immune system. And I mentioned progesterone is actually innately anti-inflammatory. Because remember, everything’s about survival. And pregnancy is about reproduction and survival of the fetus and the mother. So you don’t want to have the immune system killing that fetus. Progesterone is innately anti-inflammatory. And that’s really important, because some people don’t give progesterone to women who don’t have a uterus if they’re going in menopause. This is so important. It has all the functions of down-regulating muscle. So that’s why women in pregnancy are often more constipated. They have more laxity, I’m sure, dealing with people in their joints. That pregnant women are more likely to have more laxity in their joints because everything is a little bit looser.

                                                And so everything, when you think about it, it’s all about survival. And just to let you know how important estradiol is in modulating the immune system and inflammation, here is looking at ERR alpha. ERR stands for estrogen-related receptor. Estrogen works not only directly estradiol on its receptors, but also through other ligands that are binding to receptors. We don’t even know what those ligands are that are binding, but they don’t work properly in an absence of estradiol, and see how it helps to regulate or modulate a block, NF-kappaB. And it helps improve mitochondrial function and biogenesis. This is all through secondary actions of estradiol. And I mentioned about autoimmune disease, but now I think you already know, because women have more robust immune systems, they are going to make more antibodies more robustly. They’ve delivered the information to their immune cells more aggressively.

                                                And it’s just a big problem for women now. And we know that, I’ve already talked about sepsis is definitely works better. So here when you took out the ovaries in rats and then you didn’t give them estrogen, they died. If you gave them estrogen, they didn’t die. That’s pretty good. And in terms of the microbiome, estradiol is very key to regulating the microbiome. Women in menopause have an altered gut microbiome. It’s dysbiotic. Women in pregnancy have an altered gut microbiome, but that’s intentional to create a low-level controlled fire, low-level inflammation and low-level leaky gut. But so many women now, pregnancy-related complications are through the roof. Horrible, through the roof. So it’s important to understand that every woman going through pregnancy needs to be optimally healthy first, because this is such a stress test for women. So I know we don’t want to be here forever, but if I’m let alone, I probably will keep you here. So I’m going to-

Dr. Weitz:                            Can I just ask a question? Speaking for men, who don’t have a lot of estrogen, but-

Dr. Gersh:                           They make it. Remember, they make it.

Dr. Weitz:                           Yes. I know we have some estrogen, but are there strategies that can allow men to get some of the benefits that women get from this estrogen?

Dr. Gersh:                           Absolutely. Because once you know that men, okay, so it’s changing a bit now because of all the endocrine disruptors. But traditionally, men had much higher rates of non-reproductive cancers. Way back in the day when I was being taught in medical school, men were the ones who had most lung cancer, bladder cancer, pancreatic cancer. Like I said, it’s not the same as it used to be, because of all the endocrine disruptors that are present. But men do have more deaths from immune-related issues. So what they have to do is maintain a high intake of antioxidants and polyphenols to help to deal with that, and take targeted supplements. A new article just came out, shocker alert, that low vitamin D is associated with increased mortality. I mean, how many people got in line because we said in COVID, “Take vitamin D.” It’s like, oh no, you can’t say that.

                                                It’s like, “Oh, get out.” So make sure that if you’re a male, of course females too, that you don’t have deficiency states. And make sure you have plenty of testosterone. Males have dramatically reduced testosterone levels, even young males, because a pro-inflammatory male is not going to make adequate testosterone. It’s a huge problem. I’ve seen young males, I don’t even see very many males in my practice. They’re usually someone’s relative who gets brought in. And I’ve seen young males with testosterone levels in the low 200s, and they’re 24 years old. What do you think their immune system is going to work like? But men, for example, in their brains during the reproductive years, they’re manufacturing from their testosterone six to eight times more estradiol. Remember, all the testosterone turns into estradiol when it’s converted. But women do fine if they have functioning ovaries, because they get plenty of estradiol from their ovaries.

                                                Well, what happens if they don’t have functioning ovaries because they’re being suppressed through contraceptive methods, or through anorexia or whatever? Then their brains are not going to work right. And their brains are the control centers too. So men, you have to do all the lifestyle stuff to keep at a low level of inflammation. So that what you do have, those little tiny quantities of immune cells that you have, they’re going to work optimally, right? Nature doesn’t want you men to die. It just, if you have a pandemic, it picks women to survive more. But nobody should die. Everyone should stay healthy. Take your vitamin D, make sure you get all your antioxidants in, and don’t eat a processed food. I mean, when’s the last time you ate a bunch of processed food? I bet then you don’t eat it.

Dr. Weitz:                           I just don’t do it. Yeah.

Dr. Gersh:                           Me either. To me, it’s-

Dr. Weitz:                           Haven’t for decades. Yeah.

Dr. Gersh:                           I never eat that stuff. Why was any, I look in the grocery store and I say, “Why is anyone buying that poisonous garbage? Real food tastes so much better.”

Dr. Weitz:                           Right. But one reason why is for $5, you can get all this stuff. And I won’t call it food.

Dr. Gersh:                           I get organic dried beans, I make the best bean soup, lentil. This stuff is really inexpensive. Eat your beans, guys. Okay?

Dr. Weitz:                           Can I ask one more question right now?

Dr. Gersh:                           Yes. And in fact, if this is too many slides, we can stop anytime. I don’t want to be here forever.

Dr. Weitz:                           No, it’s okay. We can go on a little longer. But since we’re talking about breast cancer risk, and I mentioned using estriol as one of the strategies, another strategy that is utilized is to follow estrogen metabolites. And then if estrogen is going down the wrong pathway, then we can use perhaps nutrients, [inaudible 01:17:16], calcium, D-Glucarate, et cetera, et cetera. Do you follow estrogen metabolites? And if so, what testing do you like to use?

Dr. Gersh:                           So I don’t now. I used to. And the reason I don’t is that they’re pricey and I use, I can figure it out. I’m always right. Okay. I look at the person, I look at their other inflammatory markers that I can have covered, and I pretty much know who’s doing what. If you have a pro-inflammatory, inflamed, obese woman, I can guarantee you her liver is probably fatty liver. She’s not detoxifying well, she has the wrong, I have a whole bunch of slides here on the estrabolan alone that is so important that to make.  And the estrobolome that is so important to maintain to prevent reproductive diseases of women and cancer. So I just do everything to support, I give all those antioxidants, I use them, I do everything to support liver detoxification capability. I do everything to support restoration of a healthy gut microbiome. Recognizing, for example, the biggest risk factor for postmenopausal breast cancer is obesity. So we know the risk factors, so everyone should just treat them all as if they have bad metabolites. That’s the way I approach it. You can tell at a glance, all of us know you can walk down the street, and we do this in our heads, even if we don’t point at them and say, “You have diabetes,” but you look at someone, they’re going to have inflammation, insulin resistance, just by their body shape.

                                                And now I do body compositions in my office so I want to know, and can’t always judge what someone’s body composition is just by looking at them walking down the street, but you can get a pretty good idea. I bet you when you’re working with your patients and you see what their arms look like, their muscles or legs, you got a pretty good idea of what’s going on, and the skin by the way, is an excellent… I never understood how the Chinese could do it, “Stick out your tongue and then let me look at your hands,” and all that. I mean, they look at signs and things that we just ignore. But if you start actually using your amazing powers of observation, you will be able to judge a book by its cover in many cases.   Look at someone’s skin, and not just their face because maybe they had 20 peels and laser treatments, look at the other skin. When people have a lot of melasma, when people have a lot of aging spots, wrinkles, bruising, you know that the outside is the representative of the inside. So use all your powers of observation, if you feel comfortable, and assume the people who look unhealthy and have other unhealthy markers are probably unhealthy inside as far as their detoxification pathways. And save them the money so that they can save that money to buy the healthy food at the market, and not that garbage processed stuff.

Dr. Weitz:                            Do you use any-

Dr. Gersh:                           Unless all your patients are multimillionaires, then it doesn’t matter.

Dr. Weitz:                            Do you use any particular supplements when you recommend hormone replacement to make sure that they’re efficiently metabolizing their estrogen?

Dr. Gersh:                           Well, we have sort of a plan. We don’t enforce it, we don’t make people do anything, but we recommend that they do what we call the Anti-Inflammatory Gut Reset, that’s what we named it. We don’t actually use the word detox in my office, because in conventional medical circles they all roll their eyes. So we don’t want people rolling their eyes at us, because we don’t say we’re detoxing people, what we’re doing is supporting detoxification pathways and helping reduce inflammation. And if we use the word detox, you’re detoxing off of crap, processed food. It’s like people detoxing off of alcohol or heroin. You got to get rid of all that ridiculous sugar that you’re now addicted to.

                                                People go through sugar withdrawals, right? So it is kind of like a detox, but we go through, we do a lot of education about endocrine disruptors, how to live in a cleaner environment. We talk about time-restricted eating, then later on, we go into fasting possibilities. So basically, I start all my patients out doing everything I can to help them to optimize their detoxification pathways, and then we give the same stuff that I’m sure all of you give, some L-glutamine, we give some coating agents, sometimes I give butyrate and sometimes I give NAC and derivatives from milk thistle and selenium. All the usual stuff that all the nutraceuticals companies sell different packages for gut support and liver support, we use those kinds of things.

                                                And then we try to maintain all the lifestyle. We really incorporate a lot of lifestyle. We do the HeartMath for stress, which is so huge in women. Women have a dysregulated autonomic nervous system, particularly after menopause, but they’re more prone to it anyway. That’s why, who gets POTS Syndrome the most? It’s females. And so we work with that. We work with sleep, I work with body work for pains and aches and so on. That’s why I tried to recruit you here to my office. So I do, we try to cover it all. I hate, I hate, I hate with a passion hormone clinics, where they just, and this is now getting to be like a fad thing, where plastic surgery offices and cosmetic dermatologists are bringing someone in just to dispense hormones. But I don’t believe in that. I believe in looking at the total patient.

                                                Just like you were saying, I mean, we got to look at the total health, we got to look at supporting all the systems. Just giving hormones and leaving everything else on the table unattended to is not acceptable medicine in my book. So you got to look at the total person, you got to work on all these things, include all of this, and not just pass out hormones. That’s not good quality medicine. Hormones to me are like foundational, but building the foundation of the house isn’t the end. You got to do all the other stuff to make the house beautiful and inhabitable, and that’s how I feel about the human body.

Dr. Weitz:                            So, heal the gut, detox before you put hormones in, so you have a healthier body then going into it?

Dr. Gersh:                           All the way. All the way, a hundred percent. And we have a fitness specialist, happens to be my husband, but that’s convenient, so we do fitness assessments, exercise prescriptions, we have some small group classes for exercise, we do body compositions. So to me you’ve got to look at and you’ve got to deal with every lifestyle issue, as much as people will let you. Because, yes, just giving hormones in an absence of dealing with all these other things and looking at detoxification, even though I don’t get the metabolites, we cover it. I just assume, I make assumptions that everyone could do better. So that’s how I address it. But I don’t mind if anyone gets them, I’m just saying, I just assume that they could use all the stuff I’m giving them.

Dr. Weitz:                            And when you do recommend hormones, what’s your favorite combination of products that you like to use?

Dr. Gersh:                           Honestly, I’ll give whatever the patient is willing and can afford, because I actually don’t have all millionaires in my practice and we don’t price it that way. So, if something’s covered by insurance, as long as it’s bio human identical and I can measure levels and I get to physiologic levels, I’m happy. I will use all the gels, the patches that are commercial products, but I use compounded a lot too. The skin, it’s amazing. The skin was not evolved for delivery system for hormones. It’s supposed to be a barrier. It’s supposed to keep things out, and that’s why they developed the patch. It’s a special matrix dot to try to get the hormones through the skin, but sometimes it doesn’t get in.

                                                I’ve had patients where I give every dose of the highest doses of every commercial product and I can’t get levels up at all. So then I have to go to compounded, and then I have them place it around the inner labia minora, around the outer area of the vagina, because that area is very thin, the skin is thinner. It’s easier to penetrate and get it absorbed, because that’s when you say, “Okay, put it behind your knees, put it on your inner arm,” the thinnest areas of skin you can find to try to get it into the body. That’s why measuring levels is so important, unless the whole purpose is just symptom suppression.

Dr. Weitz:                            And you like to use serum levels for [inaudible 01:26:14], right?

Dr. Gersh:                           Yeah. I don’t, yeah, I don’t-

Dr. Weitz:                            But isn’t there an issue with when you use topical estrogen that maybe serum’s not the best way to measure it?

Dr. Gersh:                           No, it’s the best we’ve got, and we have the most data on that, and I’m waiting for the day that there’s some support for saliva. By the way, urinary is pretty good too. It’s just not very practical. But the saliva really has not held up. I know there are people out there who just adore-

Dr. Weitz:                            Why is urine not practical?

Dr. Gersh:                           Well, it’s expensive, it’s not covered by any insurances, so you have to send it out to specialty labs. But I do menstrual mapping with the urine when it’s appropriate. I am really, truly cost-conscious, because you can see all the things we ask our patients to do, right? Fitness and detox, what we call it reset, and buying these different supplements, and I tell them, “Please buy the best organic foods and things.” So I realize I can’t bankrupt every patient that comes through my door.

Dr. Weitz:                            Yeah, I guess as a chiropractor, I don’t ever expect any testing to be covered and we don’t even try to put it through insurance.

Dr. Gersh:                           Oh, well, since I can order tests that are covered by insurance, as much as I can, I try to get things covered by insurance. But if money is no object, then I will do other things, but you know?

Dr. Weitz:                            Yeah, you can get a-

Dr. Gersh:                           [inaudible 01:27:39] in my world.

Dr. Weitz:                            … female DUTCH panel for 150 bucks.

Dr. Gersh:                         Well, the DUTCH panel is fine, but not if you’re on hormones. I don’t actually think it’s as useful for someone who’s on hormones, but if they’re not on hormones, it’s fine. But I can get serum levels in someone who’s not on hormones and it’s usually close to zero or zero, but I’m totally fine with whatever people are willing to get or get. I just believe very strongly in monitoring. I don’t think that you should-

Dr. Weitz:                            Right.

Dr. Gersh:                           Yeah, I really believe that you got to measure and monitor and follow, unless your goal is nothing but suppressing night sweats and hot flashes. In that case, then you don’t have to measure anything. You just give the lowest dose, and when they say they feel better, you stop. But that’s not what I do. I’m going for healthy longevity. I’m not going for just suppression of the symptoms. But that’s what the conventional world is doing, though. We’re exceptions to the rule. We are, by looking at healthy longevity using hormones, because most, still even doesn’t matter what the data shows, the current mantra is use the smallest dose for the shortest time. It hasn’t changed. That’s why I’m out there trying to get it into people’s heads that if you want to have a long healthy life, you need to have hormones. It’s like foundational.  That’s why I say, you want to have metabolic health, you have to have hormones. You want to have immune function, you got to have hormones. You don’t want to be a status chronic inflammageing? Then get those hormones. But it’s necessary but not sufficient. You still need the nutrients. What’s the point, if you are deficient in half the antioxidants in your body and you have no healthy gut microbiome, just throwing hormones into someone? That’s why I don’t like hormone clinics where they just throw hormones at people. I think we’re all on the same page, because everyone who’s here, everyone who listens, we’re exceptions to the rule. We formed our own little club and we’re living in our own little cocoon because we know that this is the right thing to do. But that’s why I keep trying to break into that other gigantic cocoon, which is everybody else out there in the medical world, so that it’s not just us convincing us, but we learn from each other.

Dr. Weitz:                            So, Lindel asked a question about studies to back up what you’re talking about, but every one of your slides is supported by references that you have on the slides.

Dr. Gersh:                           I’m very evidence based, and I show evidence-based research in my office to my patients. I want them to know that you can’t be more evidence based than me. I research everything. I’m like a PubMed, Google Scholar addict. I labeled myself a synthesizer. I’m not a researcher, I’m a clinician, and I have never published a single independent research paper. I wish I had, but that’s not who I decided to become. I was offered to be an MD PhD at NYU and I walked away from it. I just wanted to be a clinician. I didn’t want to be a researcher.  And so I’m a synthesizer. I look at everyone else’s research, everyone else’s published peer-reviewed reports, and I put it together to create a clinical message. Because what I hate is science that’s never applied clinically. That is crazy. You have all these amazing researchers, they figure all this stuff out and then it just languishes and doesn’t get applied in any clinical fashion to actually help people, unless a pharmaceutical company takes it over, and that’s not what we want. So that’s why my job is to research everything and put it together in some kind of cohesive whole and then apply it clinically.

Dr. Weitz:                            Okay. Maybe-

Dr. Gersh:                           So, yes, I can support everything I say.

Dr. Weitz:                            I’m sure you can, and-

Dr. Gersh:                           But sometimes I tell you it’s a rat study, and, “Sorry, there’s no human study.” I tell my patients all the time, “This is my best guess. There’s no data.” I’m always honest. When there’s no data, there’s no data. And I thought, well, what I can do is just make these slides available to people, because at the end I have my usual, which is, “Okay, what are you going to do? Well, you already know about hormones,” but then you incorporate all the lifestyle stuff, which I’m sure you’re all as expert as I am in it. I just emphasize over and over feed your gut and nurture your gut microbiome. And that’s really important for overall health of every organ system. Now the more we learn about these microbiomes, the more we know they’re precious material, precious cargo on board. We don’t want to torture them, kill them, or starve them. That’s not useful.

                                                So basically, I talk about how these hormones protect the brain from neuroinflammation, how the gut transmits signals to maintain, like here, it shows that you have the fermentation of the fibers and then you have the short-chain fatty acids and all of this information, there’s immune cells that line the gut, the gut-associated lymphoid tissue, and it communicates between the different cells, the immune cells that line the gut. And then you have the Peyer’s patches which have the lymphocytes and how all of this interacts to maintain proper function. And hormones have a huge impact on the gut microbiome. The gut microbiome is so important with estrogen that there’s a specific group of microbes called the estrobolome that are essential for the metabolism of estrogen, and this is so important to maintain. And we’ve talked about pregnancy a lot, and so-

Dr. Weitz:                            By the way, are there certain gut bacteria that you can point to that are important for the estrobolome?

Dr. Gersh:                           No, it’s like there’s trillions of bacteria, so we’re just breaking into it. But I tell people eat fermented foods. I’m a big fan of kimchi. My middle daughter married someone who’s half Korean, so we’re big on kimchi. My little granddaughter, her favorite food is kimchi soup. So that’s great. And I grew up with sauerkraut, fortunately I actually like this stuff, but it’s really essential. So I use a variety of probiotics. I think don’t use the same one over and over. We don’t want to push towards one species. We want to have diversity. If there’s one thing we know, it’s diversity of the gut microbiome is what really brings optimal health. And in this slide, I’d really love this slide because it shows when you have gut dysbiosis, you have estrobolome dysfunction. Look at all the things. It’s all interlinked. Increase of endometriosis, PCOS, obesity, metabolic syndrome, cancer and brain health goes down the tubes.

                                                That’s why focus on the gut. Focus on the gut. All of this stuff is interrelated. That’s why all of my women patients have to have gut restoration treatments. And this is like when you don’t have the right gut microbiome, you end up with autoimmune diseases and all these problems, and the circadian rhythm is regulated. When you eat matters as much as what you eat, so you have synchronization and you have metabolic health. And circadian rhythm is modulated by estrogen. Women who work night shifts have high rates of cancer, metabolic dysfunction, increased risk of dementia and mood problems, and I showed this, SCN stands for suprachiasmatic nucleus, the master clock, and here you see in the brain, this is the hypothalamus ER, ER, that stands for estrogen receptor. And see, it shows beta and alpha. That’s why you don’t want just one. You don’t want just any one. You want them all.

                                                See how they work together too, and they have, see these peptides? Everybody loves peptides. Well, you make them naturally when you give the right stuff, and see, VIP comes from the suprachiasmatic nucleus to the area, the neurons in the hypothalamus that then put out the little triggers that go to the pituitary to make the gonadotropins. The kisspeptins are peptides that feed, that recognize nutrient status, which is all regulated by estradiol. Without estradiol, you’re going to have massive problems in appetite regulation and circadian rhythm, and that translates into reproductive problems, but also metabolic problems. It’s all interrelated. So, this is about shift work. The immune system is incredibly circadian. When you have disruption, look what you get, low-grade inflammation, you have compromised adaptive immunity, autoimmunity, allergic responses, decreased tumor surveillance. That’s why it’s so important to get to sleep, to eat at the right times, and to have hormones, because it regulates.

                                                So, this is where I just go over my recommendations. Eat lots of healthy plants, eat at the right times, make sure you get some sleep, work on stress, sometimes do fasting, get exercise. And I have this whole section, which I’m not going to do because I love talking about more stuff, but I think I talked out. But HPV is an estrogen-modulated virus, and this is not well understood. So for example, estrogen is very important for, and metabolites of estrogen, that’s why DIM is often given to women who have HPV, chronic HPV. And this is important because oral contraceptives increase cervical cancer risk dramatically, dramatically. After 10 years of use, I have patients on 30 years of birth control pills, it increases the risk of cervical cancer 400%, four times. And so we’re giving all these women the vaccine for HPV, and at the same time that we’re giving them birth control pills, which dramatically increases the risk of cervical cancer. Why is this not talked about?

                                                The World Health Organization, WHO, this is back from 2002, published in the British Medical Journal, links long-term pill use to cervical cancer. This is not debatable. I put down from, I just copied a bunch of stuff from the article, because this is huge. And women who have babies, five full-term pregnancies and took the pill for more than five years, have increased risk of cervical cancer 12 fold. Come on, guys. Why is people not… And then what do you do nutritionally? Well, a lot of them have high homocysteine, you want to deal with that. So, who know high homocysteine increases cervical neoplasia? So we want to want to do all the things that we do. All the antioxidants, folate is always so important for protecting DNA. The fruits and the vegetables.

                                                So, you have patients who have chronic HPV, this is what I’m telling you to do to help them, that they need to recognize the birth control pill is increasing the risk of cervical cancer. Get off of it and do something else for prevention of unwanted pregnancies, and get all of these polyphenols and antioxidants from plants and such into the body. And soy isoflavones, eating organic whole soy and having green tea is very good for prevention of cervical cancer, and there’s studies to show that. And when you eat the wrong diet, guess what? It changes the vaginal microbiome. They’ve linked vaginal microbiomes to the Western diet. How is that? And then you have patients that come in with vaginitis, think about what they’re eating. Who’s thinking about that, right? Think about that. So, when you have the wrong vaginal microbiome, you increase your risk dramatically of getting cervical cancer. And they’ve shown the different, like you asked me about specific types of bacteria, we actually have that for the vagina. So you can look at this.

                                                So, the takeaway message, hormones matter. Females are better than men when it comes to immune function, but men are super great. We love them, okay? Just don’t get sick, please, because you’re less likely to survive. But if you eat all the right foods and you do everything, you will survive, okay? And maintain that testosterone and don’t have a lot of inflammation that lowers your testosterone. And in fact, inflammation lowers estrogen production. I deal with that with PCOS women. They have inflamed ovaries. Inflamed ovaries will cause earlier menopause. We do not want that. We need our ovaries to last as long as possible.  So, women are powerful with their immune systems. They’re more likely to get autoimmune diseases. When things go wrong, they go wrong bigger in those women who have smaller muscles, but great immune systems and lots of immune cells. So you want to do it all. Get sunlight, get love, exercise, eat, sometimes don’t eat, eat the right foods, keep your pathways going, work on your circadian rhythm, and you will live a happy life and so will your patients.



Dr. Weitz:                            Thank you, Dr. Gersh. Awesome presentation. Thank you for making it all the way through this episode of the Rational Wellness Podcast. And if you enjoyed this podcast, please go to Apple Podcasts and give us a five star rating and review. That way, more people will be able to find this Rational Wellness Podcast when they’re searching for health podcasts. And I wanted to let everybody know that I do now have a few openings for new nutritional consultations for patients at my Santa Monica Weitz Sports Chiropractic and Nutrition Clinic. So if you’re interested, please call my office, 310-395-3111, and sign up for one of the few remaining slots for a comprehensive nutritional consultation with Dr. Ben Weitz. Thank you, and see you next week.


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