Is Estrogen Replacement Safe? The Truth They Might Not Tell You | Dr. Felice Gersh

0:00Estrogen is not a hormone. It's a family of hormones. So there are three estrogens. E1 is estrone, E2 is estradiol, and E3 estriol. All of these are present in a reproductive age woman, but in different quantities, percentages, based on what the body needs. Estradiol controls the immune system for turning on inflammation and turning off inflammation. But when you end up with too much estrone, you end up with too much inflammation and simulation of cancers. A lot of people are afraid of hormone replacement therapy because of the cancer scare. Talk to us about that. Dr. Felice Gersh is a world-renowned OBGYN, integrative medicine pioneer, and best-selling author who's changing the way we talk about women's health.

0:55With over four decades of clinical experience and dual board certifications, she's leading a revolution that fuses cutting edge science with holistic healing. From PCOS to perimenopause, Dr. Gersh has become the go-to expert for women who want more than Band-Aid solutions. Estradiol is very key to why you have a lower risk of dying if you get breast cancer when you're on hormones, is that estradiol causes the cells to be more likely. When it comes to the conversation of cancer and hormone replacement therapy, how do you approach hormone replacement therapy in women? Well, I always say I'm a simple thinker, so I want to replicate.

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2:48As always, I'm bringing you the latest, most up-to-date information to help you take charge of your health and take back your hormones. If you enjoy this kind of information, I invite you to visit my website, drbrighton.com, where I have a ton of free resources for you, including a newsletter that brings you some of the best information, including updates on this podcast. Now, as always, this information is brought to you cost free. And because of that, I have to say thank you to my sponsors for making this possible. It's my aim to make sure that you can have all the tools and resources in your hands and that we end the gatekeeping.

3:25And in order to do that, I do have to get support for this podcast. Thank you so much for being here. I know your time is so valuable and so important, and it's not lost on me that you're sharing it with me right now. Don't forget to subscribe, leave a comment, or share this with a friend because it helps this podcast get out to everyone who needs it. All right, let's dive in. Dr. Felice Gersh, welcome to the podcast. Well, I'm so excited to be here and talk about my favorite hormone, estrogen. Oh, yeah, we're going to get in good with estrogen. But I want to make sure everybody is on the same page.

4:00So when we say estradiol, what are we talking about? Well, I'm glad you brought that up because the word estrogen is bantered around and people don't know what it is. So estrogen is not a hormone. It's a family of hormones, just like there is a family of B vitamins. You wouldn't interchange them. If you're deficient in B12, you can't solve the problem with B1. So there are three estrogens that are in the adult female, and they have a number and a letter, just like the B vitamins. So E1 is estrone. E2, which is the one made by the ovaries, is estradiol. And E3, estriol, is the dominant estrogen produced by the placenta during pregnancy.

4:45But all of these estrogens are present in a reproductive-aged woman. but in different quantities, percentages, based on what the body needs. Estradiol can be converted back and forth to estrone and a one-way street from estradiol into estriol. So it's all managed by the body to make everything right. And there's different estrogen receptors that bind differently to the different estrogens, creating different effects in different organs. So it's really important to understand that when you say the word estrogen, that means not that much, actually, if you're getting down to the nitty gritty of what is actually happening.

5:25Yeah. So you said estriol or E3. That's predominant in pregnancy because it's predominantly made by the placenta. When do we see estrone and estradiol in a woman's life? So you see a teeny bit of estriol in the reproductive age woman. And the estrogen from the ovary is estradiol. But there's plenty of estrone in the adult reproductive age female. And unfortunately, sometimes too much in the woman who is metabolically unhealthy, which usually involves having some excess abdominal fat, you know, with the visceral fat, the really hostile inflammatory fat. Yeah. And also in postmenopausal women. And so estradiol can convert appropriately to estrone when the body wants it to be into that form, and it can convert back.

6:16But it turns out that adipose tissue, a.k.a. fat, has the same enzyme, aromatase, that's present in ovaries that can actually make different conversions and can convert the androgens that are predominantly coming from the adrenal gland. A little testosterone, that's about 25 % of all the androgens is coming from the ovaries testosterone. And the rest is predominantly coming from the adrenal gland. But when you have a lot of inflammation, it upregulates this enzyme called aromatase and starts converting these androgens into estrone. And when you have a lot of inflammation, it downregulates the enzyme that can interchange to convert estrone back to estradiol.

7:07So you get stuck with estrone. And estrone isn't evil. It's all about proportions. Like you can die of water intoxication. You know, we always use those analogies. Because estrone isn't evil. It's just you don't want too much. You could have too much of a good thing. And estrone, differently than estradiol, binds pretty exclusively to the alpha receptor, which has different functions. So I like, it's kind of simplistic, but really it's easy to think this way. Estradiol controls the immune system, the on-off switch for turning on inflammation and turning off inflammation. Estrone is predominantly the on switch.

7:52And you can think of estriol as predominantly the off switch, but you need the balance. And that's estradiol. That's why that's like the master of the different estrogens for the typical reproductive age woman. When you end up with too much estrone, then you are turning the on switch to inflammation, to proliferation, like uncontrolled growth. One of the wonderful things about estradiol is that it controls growth factors, which are so important for rejuvenation, replacement of cells, and control of mitochondria, the energy factories of cells. All this is under the auspices of estradiol. But estrone has different effects.

8:38So you end up with too much inflammation, uncontrolled proliferation, and that can underlie stimulation, not causation, but stimulation of cancers that have estrogen receptor positivity. And so, unfortunately, a lot of the drugs that have been used as estrogens are oral estrogens, some of them from a horse's urine, conjugated equine estrogens, the ethanol estradiol, which is not a real human estrogen. That's the dominant one in birth control pills, which you've talked about so much. And they take in orally, they are converted predominantly into estrone, creating an abnormal balance of these hormones that are so important.

9:27And so it's really so important to understand the differences between the estrogens. And that's led to, unfortunately, a dislike and fear of estradiol because of the harms that can come from inflammation. It's the inflammation that underlies the problem and then the creation of too much estrone So I want to recap and say this back to people because I think it's just so important to underline what you said So estriol, E3, that's going to have an anti-inflammatory effect And that is, I think anyone who's been pregnant and has an autoimmune disease is like This is why I feel better in my pregnancy And like that's one of the contributors to having less inflammation and autoimmune disease progression during pregnancy.

10:16But once you enter menopause, we've got Estrone coming online. And there's a lot of changes that are happening with Estrone and with menopause altogether. And Estrone is the on switch. We're turning on inflammation, whereas Estradiol, it can be on or off. It's a regulator. So I just wanted to reintegrate all that. And that is so true that many autoimmune diseases, the one that has the most research is like multiple sclerosis. They go into remission because of the estriol down-regulating the innate immune response. And that's, of course, so important and part of pregnancy so that you don't actually kill your fetus with your immune system, which also involves progesterone.

11:03So it's really complicated. But learning about pregnancy is really amazingly significant for understanding the immune system and how these hormones interact and how they relate to immune function. Yeah. And so people know if they're like, what, why would my body kill my baby? Because your immune system is designed to attack anything that is non-self. That's not you. And baby is genetically distinct, different from you. So your immune system would identify that and say, we have a foreign invader, but the body wisdom, I mean, and the way it's orchestrates everything is so beautiful and how it builds that tolerance.

11:37I want to go back to the metabolic piece because you really underscored the issues with inflammation. Talk to us about the interplay between estrogen and our metabolic health. Oh, it's so key. So and it's like always is more complexity than first meets the eye. Yeah. When you have inflammation, the inflammation creates in part of inflammation is circulating inflammatory cytokines. These cytokines are produced by immune cells, and they're designed to signal and tell other immune cells to do things and to create reactions. And this is life-saving if you have trauma, injury, or you're infected with a pathogen like bacteria or virus.

12:23So we do not want to have no functional immune system with the creation of inflammation. It's out of control inflammation that is key to all the diseases known as the degenerative diseases of aging, which plague women in menopause even more than men. So estradiol, because when you don't have it, which 100 % of women are going to lose it with their ovarian senescence. And so you end up in this state of inflammation. It also relates to the gut microbiome. You get leaky gut. You get alteration. So it's multiple levels that you get this systemic level of inflammation. These inflammatory cytokines damage directly the mitochondria.

13:09So mitochondria are essential for the creation of energy and control of the cell cycle. Part of the cell cycle is when a cell should die. We call that apoptosis or programmed cell suicide. So when a cell gets old and yucky, and sometimes we call them senescent cells or even zombie cells. I do love that word. I know. I wish I had coined it. I know. Because they are insidiously harmful to the body, like they're invading our civilization. So they create this ongoing inflammation because they just won't die. It's like the grade B movie where the monster won't die. Like, didn't that monster die already?

13:55No, it's back. It's back. These zombie senescent cells create ongoing inflammation, which is so harmful and, you know, damages the lining of arteries. It creates neuroinflammation, which can trigger all the diseases of the brain, including Parkinson's, Alzheimer's, vascular dementia. It's just horrible stuff that happens in joints and bones and everything. So we do not want zombie cells. And you need to have this mechanism, which is controlled by mitochondria, to say, now cell die. Now, also, these zombie cells, because they're ongoing, old, yucky cells, they can have damaged mitochondria. I mean, they can have damaged DNA, which can lead to the formation of cancer.

14:44So these zombie cells have multiple levels of harm. So promoting cancer, we all know, I hope everybody knows, that which demographic has the most cancer, young people or old people? It happens to be old people by a lot. Young people, unfortunately, get cancer for other reasons, endocrine disruptors, antibiotics, gut dysbiosis and things like that. But old people get it because of this mitochondrial problem that doesn't allow these old yucky cells to die. In addition, mitochondria create energy. And estradiol, it turns out, has a role in all the different aspects of mitochondrial function. To maintain mitophagy, which is like cellular renewal when it's called autophagy.

15:33mitophagy is renewal like within the mitochondria itself it's like rejuvenating the mitochondria and when it's time for them to die it allows them to die to then be replaced with mitogenesis under the control of estradiol if your adhd feels different across your cycle postpartum or in perimenopause adhd in women explains why hormones can change your brain and what you can do about it Pre-order now and for a limited time, get the first chapter audio read by me, Dr. Jolene Brighton, for free. Plus a bunch of other bonuses like a free recipe guide and a PMDD workshop. Claim your bonuses at drbrighton.com slash ADHD and women.

16:17That's D-R-B-R-I-G-H-T-E-N dot com slash A-D-H-D and women. The creation of energy with the electron transport chain that makes ATP. People have heard of that. We want plenty of that so that we can do everything we want and have all the organs work optimally. That requires estradiol. Now, in the process of making ATP, you have a metabolic byproduct that is very toxic called superoxide. It's two oxygen molecules. Now, we need to get that out of the mitochondria, but it can't. It doesn't have any mechanism to exit and then get out of the mitochondria, but it's poison to the mitochondria. So there's an enzyme that's in the mitochondria called manganese superoxide dismutase, which converts this toxic superoxide to another poison, hydrogen peroxide.

17:13But unlike superoxide, hydrogen peroxide can diffuse out of the mitochondria into the cell where other enzymes convert it to harmless water. So we have O2 to H2O2 out of the mitochondria to H2O, water. Under the auspices, the control of estradiol to have this enzyme work. So when you lose your estradiol with menopause, there are so many things that are going wrong in that mitochondria. You have the promotion of inflammation that damages it. You can't make energy with the electron transport chain. You can't do the renewal and the proper elimination of mitochondria with mitophagy. And you can't get rid of the superoxide byproduct of creation of energy.

17:59So what happens? Everything deteriorates in the body. Energy, which is what metabolism is. And everyone knows, I want a really good metabolism, right? I don't want a slow metabolism. Well, you've got to have mitochondrial function, metabolism, the production, distribution, storage of energy. Energy is what differentiates life from death. You know, when we look at energy in the brain, we look at an EEG, right? It's energy. In the heart, an EKG. That's the little, you know, when you see it. And everyone knows from watching movies, TV, that when you see the EKG monitor in the person in the hospital room and then it goes.

18:43That means no energy in the heart. That's called death in the brain. It's brain death. Yeah. We need energy and we don't want a little. We want plenty. And women are unique. They're different from men because only women can do what? Make babies. So when a woman is pregnant, her heart has to pump at least 50 % more blood volume. So a woman's heart has to have extra energy. So the mitochondria that produce energy in the heart are extra special in women in their ability to make energy. And even not only estradiol has receptors, but metabolic byproducts that are created in the liver from estradiol, like 2-methoxy estradiol.

19:31It's a metabolic byproduct. It's made from estradiol, but it has its own unique receptors. And there are other things. We don't know what they are. They're called estrogen-related receptors. So what that means is we don't know what binds to the receptor. That's called the ligand. But we don't know what it is. But what we do know, if you don't have estradiol present, it won't bind. And that binding creates more energy in the heart. So women uniquely get what's called mild diastolic dysfunction. They have a low energy heart, a stiffer heart. And this can lead to a unique form of heart failure, most common in postmenopausal women, called heart failure with preserved ejection fraction.

20:20Ejection fraction is the blood coming out of the heart when you pump. That part's fine. That's the part that usually is what causes heart failure in men after they have like a heart attack. This is unique. This is truly a low-energy heart, which you can actually see on an echocardiogram, but it's not even usually looked at or talked about by most cardiologists. They simply say, oh, lots of women have this. Yeah, they do. That's a sign of a low-energy heart. And, of course, the brain needs so much energy. Women have two and a half times the incidence of Alzheimer's as men due to this low energy and the dysregulation of the immune system.

21:03And, of course, you know, having other problems like inflammation from systemic inflammation coming in, neuroinflammation. So there's a host of reasons. But mitochondria are also at the key, at the focus of having a low energy brain. And now it's been shown that just about all women at their transitioning into menopause have problems with word finding. It's always nouns. Like, so, oh, everyone can remember their adjectives and their verbs. So it's like a game of charades. You know, like, what was that thing that we saw? You know, what was the name of that restaurant? What was her name? She was wearing a red dress.

21:43Her hair was this way. They can describe, but they can't remember anybody's names. They can't remember places and they feel like they're losing their mind. And it's not totally not true. It is kind of true. They are having changes in cognition and that is not a good thing. So that's why I cheer Estradial every day, you know, because understanding is the first step to solving the problem. You've mentioned cancer a few times. a lot of people are afraid of hormone replacement therapy because of the cancer scare. Talk to us about that. That is so, so sad for me when I think back. I was only among the 20 % of doctors who were actually practicing medicine when the Women's Health Initiative came out in 22.

22:34That's like 2002. That's a long time ago now. And it turns out they did a survey. Only 20 % of actual practicing doctors today were in practice then. So like the lost wisdom of what happened prior was gone. And education went down the tubes as far as menopause and hormones. And the current practitioners, they weren't taught. And what happened was so devastating because this Women's Health Initiative, Actually, we knew before the study even started that this combination of medroxyprogesterone acetate, MPA, which is not progesterone. And actually, you can call it an endocrine disruptor for progesterone.

23:19and the conjugated equine estrogen. This is estrogen from a pregnant horse that it's trying to get rid of. It's already gone through the liver to be modified so it can be water soluble and go out the urine. And the horse is trying to get rid of it. And it contains estrogens, like equal line estrogens, equine estrogens. These are not even found ever in a human. This is a form that would never be in a human. And then they swallow it, which makes whatever is human turn into estrone. And then you have all these other unique horse estrogens going into a human female. Well, it turned out that a little bit, and actually not that much, because you know all about birth control pills, about the same degree as a birth control pill can increase breast cancer, happened with medroxyprogesterone acetate.

24:08Not with the premarone. unbelievably even that horse urine stuff turned out to be breast cancer protective like who would have figured that because they've done now many studies have come out there's been big publications recently showing that any of those forms of estrogen are actually breast cancer protective and why would that be because it creates energy and energy keeps the cells alive so you don't get the senescent cells and all that stuff we talked about. And the medroxyprogesterone acetate turns out to be an agonist or like a similar to progesterone in some places, like in the uterine lining.

24:50But it turns out that it's actually an antiprogesterone in other places, uh-oh, like in the breast. And progesterone, and I talk about this more and more now, progesterone is anti-breast cancer. The real thing. The real thing. P4, not these pretend. And that's another problem. We talk about estrogen. People don't know what you're talking about. People use the word estrogen for endocrine disruptors and for xenoestrogens. It's like, I'm going to give you your estrogen today. Lick this plastic bowl. And you're like, what? You know, because it's a xenoestrogen. And progesterone is anti-breast cancer.

25:31It's anti-proliferative. It doesn't stimulate growth. It's the opposite. So I have a whole list of studies that show, it's pretty indisputable, that progesterone is anti-breast cancer. So estrogen and progesterone, both individually and separately, are anti-breast cancer. No one should think that nature gave females hormones to give them breast cancer. Who gets the most breast cancer? Women with their own bioidentical functioning hormones working around their body, doing all the things they're supposed to do, or old women who have no hormones in their body. It's the old women. In fact, the biggest trigger to postmenopausal breast cancer is obesity, which underlies inflammation and then all the stuff we talked about.

26:28And then breast cancer in the breast. This is where a lot of the misunderstanding came from too. When breast cancer develops in the breast, most of it, not all of it, there's the triple negative, but most of the breast cancer has positivity for estrogen receptors. It's alpha. Now, Now, what triggers only alpha, predominantly alpha? Estrone. So it turns out that, going back to what we talked about, when you have a lot of inflammation, it upregulates the enzyme aromatase. And in a postmenopausal woman or a woman that is quite obese and inflamed, it's going to trigger the conversion of androgens, mostly from the adrenal gland, into estrone.

27:15Well, breast cancer creates tremendous inflammation. Of course it does. All the mitochondria are not the same. Things are not the same. So you have inflammation right around the breast cancer in that tissue surrounding. The breast has fat and the breast has other connective tissue that contains the enzyme aromatase. Yeah. And that's actually for a purpose. Just think that when you have a woman who has, say, breastfeeding, her ovaries are not working. They're not making estradiol. And then she gets a breast infection, estrogen in the form of estradiol, which would be what would be made at that point, you know, because you don't have all that inflammation.

27:54You have a healthier young woman. So estradiol controls the immune system to help fight off a breast infection. Yeah. So everything that happens has a purpose. But when you have something go wrong, you're like misguided purpose. Like you're, you know, it's like it's, you know, just like sabotaged. So you have the aromatase turning on and converting these androgens into estrone, which creates growth factors, proliferation. And the breast cancers have positivity for the alpha receptor, which is what is activated by the estrone that's made by the breast cancer. So there's actually some issues because estradiol down regulates the immune system.

28:44It helps prevent that inflammation, controls all of this process. So there actually is some question that estradiol can actually help to calm down this inflammatory process of the breast cancer. And we know that women who are on estrogen, if they get breast cancer, being on the bioidentical types of hormone replacement lowers their risk. It doesn't mean you have no risk. It just lowers. So you can still get breast cancer. It's not because of, it's in spite of having hormones on board. But women who do get breast cancer, who are taking the hormone therapy for menopause with the bioidentical, they have a better prognosis.

29:29Wow. So we need to rethink everything. And I say there's plenty of things to be afraid of in this world. But bioidentical hormones should not be on the list ever. You know, what we should be afraid of is not having our hormones in our body. the foundations of creating information delivery. That's what hormones do. They tell the cells what to do. They're the instruction deliverers, you know? So it's like you're trying to create a complex dish, but you don't have a recipe and you've never made it. You tell a cell you're supposed to make proteins, you're supposed to make enzymes, and they're not told what to do, when to do it.