Hormone Replacement Therapy To Prevent Heart Disease: Rational Wellness Podcast 211
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Dr. Felice Gersh discusses Hormone Replacement Therapy to Prevent Heart Disease with Dr. Ben Weitz.
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3:27 As an OBGYN, Dr. Gersh was taught mainly about the benefits of estrogen for reproduction but she was not taught and what is not well understood is the role of estrogen in maintaining cardiometabolic homeostasis or metabolic health. Estrogen and the rhythmic secretion of estrogen helps keep women healthy up until menopause. Estrogen is the reason younger women have lower risk of heart disease than men. Women need to have adequate amounts of estrogen, and ideally the hormones should be a normal rhythm to really to optimally be healthy.
5:25 Nature made it that women’s bodies will functional optimally so that reproduction will be successful, which is the prime directive of life. But once reproduction ends, nature can be cruel and it winds women’s bodies down, with their hormones dropping and menopause is nature’s exit strategy for women. Nature winds women down by taking away her hormones.
9:00 Since we know that naturally women’s bodies are designed to wind down, we should be super smart and not wait for the body to have problems have to have stents and start replacing organs. In order for our cells to function optimally, they need the proper hormones, so Dr. Gersh believes in giving estrodial and progesterone to restore her vitality, since they are no longer being produced by the ovaries. There are receptors in virtually every organ and cell for estradiol, including in the arteries, the myocardial cells, and the mitochondria. If there is no estrogen, all those cells with estrogen receptors will not be getting the information they need to function. The goal of Hormone Replacement Therapy is not just to suppress symptoms like night sweats and hot flashes but to try to maintain the metabolic state as close as we can to a woman at her optimal health, which would be, for example, in the early 20s.
14:16 Estrogen is important for reducing a woman’s risk of heart attack. Women are more likely to die from their first heart attack than men and cardiovascular continues to be the number one killer for women. Unfortunately, most of the research on cardiovascular disease has been done with men, but women’s cardiovascular risks are different than mens’. Women’s hearts contain many mitochondria and without estrogen, the mitochondria in the heart become energy deficient and their hearts tend to become stiffer. Women’s hearts may continue to pump well, but may be unable to relax and fill normally. This is called mild diastolic dysfunction. When women have heart attacks, it’s usually related to blockages in the microvasculature rather than due to blockages of the major arteries supplying the heart. This difference has not generally been well appreciated by doctors and researchers.
20:41 Angiograms do not analyze these smaller vessels, the microvasculature. Levels of microalbumin might indicate that you have leaky arteries. You can also see decreased blood flow on functional testing of the heart, like stress echo or radionuclide stress testing. Even when women have large vessel blockage, the stents that have been developed for men, who have larger coronary arteries, in women can break off plaque and create heart problems. And even stenting for men is controversial, since prophylactic coronary artery stenting has not been shown to lengthen the lives of these patients. If a patient is found to have blocked arteries but does not have symptoms, this has not been shown to make people live longer, though if stenting is done because you are in the middle of a heart attack or have a coronary syndrome, stenting can be life saving.
23:38 One of the most popular blood pressure medications for men, the ACE inhibitors, that affect the renin-angiotensin-aldosterone system, which is also known as the RAAS. But women are better served with taking an ARB, an angiotensin receptor blocker, as opposed to an ACE inhibitor.
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 written two books, PCOS SOS: A Gynecologist’s Lifeline to Restoring Your Rhythms, Hormones, and Happiness and PCOS Fertility Fast Track and she has recently published a 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 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.
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 drweitz.com. Thanks for joining me and let’s jump into the podcast.
Hello, Rational Wellness podcasters. Today, our topic is the use of hormone replacement therapy in postmenopausal women to prevent heart disease with Dr. Felice Gersh. We all know that heart disease is the leading cause of death for men, but what about women? Well, prior to menopause, women do have a lower risk of cardiovascular disease. But after menopause, their risk go up dramatically.
Menopause, on average, occurs around age 54 and while there’s ample evidence that this increase in cardiovascular disease after menopause is likely due to the loss of estrogen, the American Heart Association website states, “A decline in the natural hormone estrogen may be a factor in heart disease increase among postmenopausal women. Estrogen is believed to have a positive effect on the inner layer of artery wall, helping to keep blood vessels flexible. That means, they can relax and expand to accommodate blood flow.” Despite the benefits of Estrogen, the American Heart Association recommends against using postmenopausal hormone therapy to reduce the risk of coronary heart disease or stroke because some studies have shown, it appears to not reduce the risk. A similar position is taken by the American College of Obstetricians and Gynecologists. This is why I’ve asked my friend, Dr. Felice Gersh, to join us, since he has recently published a paper in heart which is part of the very prestigious British Medical Journal, family of journals, entitled Postmenopausal hormone therapy for cardiovascular health: the evolving data.
Dr. Felice Gersh is a board-certified obstetrician and gynecologist and she’s also a fellowship-trained in integrative medicine. Dr. Gersh is the director of the Integrative Medical Group of Irvine where she continues to see patients. She also lectures and writes on various topics relevant to women and she is the bestselling author of two books, PCOS SOS and PCOS SOS Fertility Fast Track. Dr. Gersh, thank you so much for joining us.
Dr. Gersh: Well, it’s my pleasure and I just love your introduction. It shows the paradox in terms of the data versus the recommendations and that’s really my mission is to put those two together to actually create an evidence-based sensible way to deal with cardiovascular disease and all the other married issues that face women during their many years of life, during the menopause.
Dr. Weitz: Absolutely, you are the foremost supporter of the benefits of estrogen of anybody I’ve ever spoken to. So, before we get into some of the studies related to hormone replacement therapy after menopause, perhaps you can explain some of the benefits of estrogen.
Dr. Gersh: Sure.
Dr. Weitz: Especially with respect to improving cardiovascular health.
Dr. Gersh: Well, the fundamental takeaway always has to be recognizing that estrogen and the other hormones, I deal with a little bit. They’re like the secondary but the main focus is on the primary, we’ll say the top of the pyramid, which is the estradiol. So, reproduction, which every woman knows, involves estrogen, and that’s all I was taught about as an OB-GYN in training was the role of estrogen in reproduction. Well, it’s involved in having a menstrual cycle and you need to have it during pregnancy, and it’s made by the placenta in different forms. So, of course, everyone understands that there’s a role of estrogen in reproduction, but what is not well understood even by OB-GYNs and by cardiologist is the role of estrogen in maintaining cardiometabolic homeostasis, basically, metabolic health, which is about creating, maintaining, and use of energy in the body so that every cell can function and then the organs that are comprised of the cells can function and everything can work as a cohesive whole in the body to support reproductive success. You can’t have a reproductively successful woman who has an unhealthy body. And so, it turns out that you need to have adequate amounts of estrogen, and not just having estrogen, you have to have the rhythm to really to optimally be healthy, you have to have the rhythms of estrogen because we now know that everything in life is about beautiful rhythms. So that is the foundation of the health of the female body. So, nature made it so that estrogen, you can think of as the glue that glues together all the metabolic processes of the body with the reproductive processes, and many of the processes like the enzyme systems and so on, that people know of that are involved in metabolic and cardiovascular health and so on, are replicated within the reproductive tract. So all of these same systems and enzymes and peptides, they’re all existing and working in all the systems of the body to help a woman to be ultimately reproductively successful because that is, whether we like it or not, as a human species, the prime directive of life is successful reproduction and that brings up that nature is very wise. It makes it so that women will have all the hormones that they need to be reproductively successful and have a healthy body, but when reproduction ends, nature, although wise, can also be cruel because that is the nature of life on Earth, that we have reproductive cycles and then animals are not here anymore. That is how it is. Many species of animals, once their reproduction is over, like an octopus or a salmon, they may lay their eggs, and then they just die. So that’s where nature is wise. It does what it needs to reproduce the species and survival, but for the individual, nature can be cruel. So once you recognize that menopause is nature’s exit strategy for humans, for human females and it is what it is. So, nature winds us down. So, it takes it away.
Dr. Weitz: Essentially, what you’re saying is, is based on the whole concept of evolution and survival of the species, etc, after reproduction, essentially women are destined to just expire.
Dr. Gersh: Well, we’re one of the lucky species that we don’t immediately die when our reproductive capabilities end, but we become more metabolically dysregulated with the ultimate, of course, is death. It’s not a happy story, but here’s the thing, we are really clever. So, recognizing the naturalness, the universality of menopause, and what it means to every organ system of the female body and, of course, the cardiovascular system, which allows nutrients and oxygen to be distributed and toxins to be eliminated, and all of that, you can’t have a healthy functioning human without a really robust cardiovascular system as a foundation for health. So once you understand that menopause is not something that women benefit from. That’s just a foundational truth and then we can say, “Okay, so what are the bad things that happen, and what are they due to?” Well, most everything that we know as aging is really about deficiencies and the deficiency, including nutrient deficiencies, hormonal deficiencies, occur when you age and then you have the profound effects to many of the other organ systems that are even more profound deficiencies that add to the problems of the aging female. So, what we do is, okay, I hear that nature is what can also be cruel for the individual. So what am I going to do? I’m going to be super smart and not just wait to replace organs or have stents, all those things. What medicine has focused on is handling each individual problem as it arises. I want to be as proactive to prevent those problems in the first place by providing the body the foundational needs so that it can function. So every cell needs to function optimally. And in order to do that it needs to get the right information, is the hormones, is the information delivered.
So my goal is even in menopause to produce from the natural source obviously, we’re adding it into the body because the body is not producing it from the ovaries, the hormones that maintain metabolic homeostasis, and like I said, the top of the pyramid, the most important of all, is estradiol, the dominant estrogen. So there are receptors in virtually every organ and cell for estradiol. That was a profound understanding that I acquired quite a number of years ago because I was not taught that. I didn’t know that the American Heart Association references that the arteries have estrogen receptors, the myocardial cells have estrogen receptors, the mitochondria are filled with receptors for estrogen. So, when you don’t have enough estrogen, not one cell involved with estrogen receptors, which is virtually every cell, maybe not blood cells, but just about every cell in the body, so that cell is not going to be able to get the information than it needs to then produce the desired effect. I recognize and we should all recognize, we’re not going to have yet, maybe this will come, the ability to create the health in a 60-year-old woman or a 55 year old to that of a 25-year-old woman, because were not really replacing her ovaries. That would be really, yeah, I wouldn’t mind a new fresh pair. But what we are trying to do is basically, often the blow of not having any hormones like estrogen and progesterone bumming them in doses at aren’t just like teeny, [inaudible 00:11:39] of hormones, to try to suppress a couple of obvious symptoms like night sweats and hot flashes, which don’t require as level two as we take, for example, or maintain the vascular system. So that’s not the goal. The goal isn’t just to suppress a few symptoms, but actually to try to maintain the metabolic state as close as we can to a woman at her optimal health, which would be, for example, in the early 20s. So the theory behind hormone replacement therapy, the conventional doctors are not using those words anymore because those have been tainted by the Women’s Health Initiative. But now they use menopausal hormone therapy. I don’t like those words, either because it’s also implying that you’re just giving some hormones to try to treat some symptoms, because that’s really predominantly how it’s used. So, I would just rather call hormones. I know, semantics are always an end game plus, they imply certain kinds of uses. So I just really would, even if I could, go back to the original, which is hormone replacement therapy.
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Dr. Weitz: Part of what you’re pointing to is that, in general, our current medical system is designed to treat symptoms. It’s just not designed set up to say optimize a person’s health and so, therefore, for things to go through the medical system, to get approved by insurance, etc, etc, you have to be treating a symptom instead of trying to optimize your health.
Dr. Gersh: Absolutely. My goal isn’t just to suppress a few symptoms. I really want women through their menopausal years to live optimally, to have robust zest and energy, and so on. And that really requires having optimal hormones. Optimal hormones are just downright essential for the health of every system with a key focus on cardiovascular. As you implied instead, in the very beginning, hormone problems are really the foundation of what is the number one killer of women, that is cardiovascular events. And so, women are very prone to dying from a heart attack, they’re more likely to die from their first heart attack than are men. And this always drove me crazy because the conventional medical world has always referred to the symptoms that women experience when they have heart attacks as atypical, it’s like, “Get out.” It’s not atypical for women, they’re typical for women, there may be more atypical for men. And that has also been a huge problem because most of the research that has been done on, for example, medications for hypertension, have been done in males until 2015, it wasn’t even required to have women in studies. And so, therefore, they didn’t have them. And even when they were included, they didn’t break it out. So, you didn’t know what works for women, what doesn’t work for women. And now that I’ve been doing a lot more research into it, there really is a difference, even with blood pressure medications as to which ones may be better suited to which gender.
So, that’s actually a big deal. And understanding women and heart failure is quite a very important thing because women have a totally different onset of issues involving heart failure than men. Even cardiologists don’t realize this, and they ignore very key findings on echocardiograms. They just say, “Well, that’s just typical for women.” It’s like, “This is a sign that the heart is energy deficient.” And what I’m talking about is what’s called mild diastolic dysfunction. This is a very common problem for women’s hearts after menopause. And it’s not even appreciated by most of the cardiologists, they don’t even call it out or pointed out.
And what it means is that in a woman’s heart, there are, of course, many mitochondria. And because the heart is one of the most energy needing of all the organs. There’s the brain and the heart, and they both need enormous amounts of energy produced in the mitochondria. The energy in the mitochondria to be produced properly requires estrogen. Now, in a male heart, they have estrogen, they make it on-site, they transform it from testosterone, they can make it on-site. Well, women have very low levels of testosterone. So, after the ovaries no longer are making estrogen, then the mitochondria in the heart become energy deficient. So the heart as a whole becomes energy deficient. And this is a really key thing. So when you have an energy-deficient heart, the heart actually becomes stiffer.
And so they can actually see on an echocardiogram that when the heart is relaxing and filling that it doesn’t relax in a smooth appropriate way. It’s like a stiffer heart as it opens up to allow the blood to flow in. And that is what they call mild diastolic dysfunction. It’s a key indicator of a heart that is energy deficient. And it’s so important, and they always talk about that, well, these hearts are still pumping well. So, it’s a different kind of a heart problem because the contracting is fine. It’s the relaxing, that’s the problem.
And so, it’s really a different category of heart failure. But ultimately, it goes from the stiffness that is involved in the diastolic phase or the relaxing filling phase, and ultimately, it involves the systolic or contracting phase, and then it becomes more of a conventional look like the passage into heart failure for women is quite different than from males. And for females, the heart attacks are quite different as well. For males, their heart attacks are in the main coronary arteries that end up having the blockage. Whereas in female hearts, it’s usually involved with what they call the microvascular system, the very small vessels of the heart become dysfunctional and women have a very sensitive autonomic nervous system. And estrogen is key to relating the autonomic nervous system which involves having blood vessels contract, it’s about the stress response. It’s about maintaining blood pressure and pulse and temperature and so on. And so, emotional changes or stressors of any kind are much more likely in women to cause a vasoconstriction and a very significant number of women’s heart attacks, if they die and they do an autopsy, they don’t even find significant amounts of plaque. But they had vasoconstriction with small vessel disease. And estrogen maintains the vascular system and the small vessels are very key. So with loss of estrogen from the ovaries, the small vessels, and this is throughout the whole body, they become less functional, and you have smaller amounts of these very critical small theater vessels that go to the organs. And so you have this microvascular disease. So, women are quite different than men and this hasn’t been well appreciated. And the good news is-
Dr. Weitz: How do those microvessels even get analyzed? Because I don’t think the conventional testing we have really looks at those.
Dr. Gersh: Well, when we do things like an angiogram, no, they’re not looking at those small vessels. Exactly.
Dr. Weitz: That’s what I mean they’re looking at the major vessels.
Dr. Gersh: That’s right. Most of this data has come from more like autopsy data when you can actually look at that. Some of the different tests that may be more useful in women might be looking at levels of microalbumin, which look at the essentially leaky arteries, which show vascular disease on a smaller scale. And all very understandable when you understand what is involved in…
Dr. Weitz: Can you see this small vessel disease on an MRI?
Dr. Gersh: Well, what you can see is when you have loss of blood flow. So, once you get to a point where the blood flow is impaired, then you can see that. And you might see it on functional testing where the heart may not be contracting as well. But you can easily see the changes in terms of-
Dr. Weitz: Like functional testing would be like a stress echo?
Dr. Gersh: Well, sometimes the stress echo and maybe more like some of the radionucleotide type of testing as well. So, it’s very important, actually, you bring up a good point because these tests that have been developed, were all developed for looking at male hearts. That is true. And even when you talk about stenting. So, stenting has been a big issue even for males because doing prophylactic coronary artery stenting has not been shown to lengthen lives, it’s really can be life-saving, if you do it in the middle of a heart attack, or maybe a coronary syndrome, like when you’re impending heart attack. But if it’s just done for like, “Oh, we’re just testing and we found that you have 80%, 90% blockage, but you’re functioning, there’s nothing really happening.” And you just put stents in, that actually has not been shown to lengthen the lives of those people. But in women, because most of the problems are these microvessels, these very small vessels of the heart, obviously, those can’t be stented. And when they stent women, a lot of the stents that were made were made for the larger coronary arteries of men, and then they put them in the smaller coronary arteries of women. And they actually can break off plaque. They actually can create heart attacks and problems and damage the vessels by putting in stents that weren’t even designed for women’s arteries, which are considerably smaller.
So, there’s just been a real, we’ll say insufficiency of research and data and treatments for women. Like I said, for example, one of the most popular forms of blood pressure medication are the ACE inhibitors. And then there’s the other group that are called the angiotensin receptor blockers. These are all involving blocking key areas involved in what’s called the renin-angiotensin-aldosterone system, which is also known as the RAAS. I’m very excited, this is a preview that I didn’t have another.
Dr. Weitz: We all know about ACE now because the ACE receptors are how the Coronavirus gets into our bodies.
Dr. Gersh: That’s right, the ACE2, part of the RAAS, and the ACE2 receptor part of the branch of the RAAS that is actually anti-inflammatory. So it’s like everything in the body is the Yin Yang so it’s the pro and the anti, and the pro-inflammatory branch of the RAAS is the target of many of these blood pressure medications. And just as a preview, I just had a paper on estrogen and the RAAS that was accepted by Mayo Clinic proceedings. So, I’m very excited about that. But in terms of the RAAS and blocking it as far as blood pressure meds, there’s data that shows that women are better off, better served when they have an ARB, an angiotensin receptor blocker as opposed to an angiotensin-converting enzyme inhibitor, an ACE inhibitor. And very few doctors are aware of that. And there’s actually some published data showing good news, if you give estradiol and you give an ARB, you get an even better effect. So, there is research out there, and we need to get so much more. And that’s why I have done some programs with the American Heart Association on educating the public and doctors on the importance of screening and recognizing the importance of the cardiovascular system in women, and how it differs from men. I’m really hoping to get more understanding that giving hormones in a… I’ve actually changed the wording. So, a lot of times the words that we use are bio-identical hormones. And that is also been maligned a lot and because people think bio-identical means that it’s coming from a compounding pharmacy, and it’s uncontrolled, it’s unreliable. Now, that is not true because compounding pharmacies can be incredibly reliable and most hospitals, their pharmacies are actually like compounding pharmacies, they do a lot of mixing and special kinds of formulations.
But when it comes to the hormones, I gave up the bio-identical because that also comes with too much baggage and I’ve recoined it as human identical because we got to get people thinking freshly about this. So I don’t want them bringing their old conceptions into the mix here because we got to put the old studies like Women’s Health Initiative, we got to put that in the drawer and close the drawer and lock it and just say historical interest only because they used all the wrong products in all the wrong patient.
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Dr. Weitz: In one of your talks I heard you talk about how estrogen reduces oxidized LDL and that’s through its inflammatory effect on the PON1 receptor and interestingly, I just had a discussion with Dr. Mark Houston and there’s been… some of the latest research on HDL is that the key factor now is HDL functionality and one of its functions is its effect on PON1 and its antioxidant and the anti-inflammatory effects when he’s working, he just developed a nutritional product to help increase the HDL functionality by positively affecting PON1 and I heard you say that estrogen also affects PON1.
Dr. Gersh: So, there are many nutrients that can be helpful and beneficial. When you actually get down to the nitty-gritty which I actually look into them, almost all of them are phytoestrogens. Like a lot. So, it’s amazing. Every time I look for the link, I find it’s a phytoestrogen in some fashion. So I’m not against that at all but I say give the primary, give the estrogen, and then you can give because no matter what we do, we’re not giving back the ovary. So we need all these other adjunctive helpers. So I’m all for it. It’s really their phytoestrogens and estrogen has so many effects. So I love that you brought that up. So yes, estrogen maintains the viability of the antioxidant status of LDL. And that’s really the foundation because it’s only oxidized LDL that gets into artery walls. So, the only way you get plaque is you need to have oxidized LDL, and you need to have damage to the [inaudible 00:30:20]. So you need to have a damaged lining of the artery. So, estrogen is involved in maintaining the health of both of those. So when you have adequate estrogen, you not only reduce oxidized LDL, estrogen also maintains the LDL receptor functionality on the liver so that you can then have the docking of the transporters that have the LDL cholesterol to dock with the receptors on the liver for it to then be taken back into the liver for disposal or recycling whatever the body needs.
Dr. Weitz: It sounds like estrogen is going to promote HDL functionality because that’s what [crosstalk 00:30:58]-
Dr. Gersh: Yes, absolutely.
Dr. Weitz: … LDL back to the liver. Yeah.
Dr. Gersh: So this is really important. Estradiol, we can do just on estrogen, why I love it. Because estrogen maintains the apolipoprotein A1, which is a part of the HDL complex. And apolipoprotein A1 is also known as reverse cholesterol. So it’s the little carrier particle that takes cholesterol and brings it back from the arteries, walls, and other places, brings it back to the liver for disposal. Without adequate estrogen, you’re not going to have adequate functionality and levels of the Apolipoprotein A1 which is all about the functionality. So, estrogen is key for that. And then the other thing estrogen maintains the function of and health of the artery lining, as you mentioned in the beginning by maintaining adequate levels of nitric oxide.
So, estrogen is key to the functionality of the enzyme endothelial nitric oxide synthase, which is what produces adequate amounts of nitric oxide as well estrogen reduces the inflammatory cytokines because it controls the immune cells in it. And it modulates inflammation, prevents chronic inflammation. And it turns out that elevated levels of inflammatory cytokines like tumor necrosis factor alpha also interfere with the production by interfering with the way that the whole ADMA is made. And it then acts as a blocker.
So, it controls the inflammation, which actually then is an interference to the production of nitric oxide. So there’s a few both direct and indirect ways that it maintains nitric oxide levels which are so critical for vascular dilation and health of the lining of the arteries. It actually is key to the production of what are called prostacyclins, which are also promoting, their anti-inflammatory promote the health of the vascular system, and suppresses endothelin-1, which is a very potent vasoconstrictor.
So, we know how estrogen maintains the health and function of the heart, how it maintains the health and function of the arteries. So that’s why it’s so ludicrous to me to think that all of these things that happen in women in the menopause, which are due clearly to a deficiency state of estrogen being not produced any longer from the ovaries, and the solution is not to give estrogen [crosstalk 00:33:38].
Dr. Weitz: So when we’re getting to the next part of the talk, I want to set it up with a question, Felice didn’t the Women’s Health Initiative study first published in 2001 and show unequivocally that taking hormone replacement therapy after menopause increases the risk of heart attack and stroke.
Dr. Gersh: Well, it proved unequivocally that you shouldn’t give Prempro. And in fact, they even had that in their article, they said, “The results of this study apply only to the product that was studied.” But somehow that totally got lost in everything that followed. So, it turns out that there are [crosstalk 00:34:20]-
Dr. Weitz: In other words, Prempro-
Dr. Gersh: No.
Dr. Weitz: … for listeners who are not aware is estrogen meds excreted in a horses’ urine, combined with synthetic progestins.
Dr. Gersh: That’s right. So, it’s a combination of what are called conjugated estrogens. And what happens is when estrogen is to be eliminated-
Dr. Weitz: Conjugated equine estrogen.
Dr. Gersh: That’s right. Equine because from a pregnant horse, so what it is, is when estrogen is going to be eliminated in the body, that’s right. So, a girl has her first period and she’s 13, those hormones that are in her body at that age, they’re not there when she’s 40, they get eliminated and replaced. So the way that the body gets rid of the old estrogen is by going through the liver and there’s a process that sometimes people refer to as detoxification. But it’s a process that goes through different phases and ends up with conjugation. So, it’s altered. So it’s a chemically altered now product.
And what it does is it takes something that’s fat-soluble and turns it into water-soluble, so then it can be excreted in the urine, and some of it gets excreted in the poop, and so on. And so the part that gets excreted in the urine is now conjugated, and when it’s a horse, it’s equine. So, these are the hormones that the horse doesn’t even want anymore. This is their old yucky old estrogen, they’re trying to get rid of it. And it comes out in the urine, but it comes out with a whole bunch of other stuff too.
So it’s not like just pure anything. It’s like there’s at least a dozen different compounds. Androgens are thrown in. And then what they did, they dried it and they made it into a tablet. And that’s the best they could come up with many, many decades ago, before they could synthesize human identical estradiol. But that’s what they gave to women to try to relieve their hot flashes. And it actually did work.
But here’s a very important point, estrogen has three types of receptors. Well, it’s now known that estradiol, the estrogen produced by the ovary has a balanced effect on all the different receptors. And these receptors have similarities and very major differences. They have different concentrations in different organs, they actually can up and down-regulate each other. So there’s interactions between these receptors, and estrogen from the ovary, the estradiol is a balanced approach and it does exactly what is needed in each organ at the right time.
Well, when you take the Premarin which was named after the pregnant mare Premarin, and so the conjugated equine estrogens, when you give that orally, and it gets into the bloodstream, it gets in predominantly overwhelmingly as a variety of these different course estrogens and also as estrone. There’s actually four but we’ll say there’s three main types of estrogen in the female body. There’s the estradiol, there’s estrone, and there’s estriol.
So estradiol, the dominant estrogen produced is a balanced effector on the different receptors. Estrone, which is the more dominant estrogen of the menopause, which is made in peripheral tissues like fat tissue is predominantly effective on the receptor alpha, and estriol, which is made in the placenta in very large amounts in pregnancy is predominantly effective on the beta receptor. And they create very different effects. So, compared to having the balanced one, which is estradiol, so when you take an oral estrogen, it goes to the liver, and it comes out into the bloodstream as predominantly estrone, which has very different effects throughout the body.
So it’s like a totally different chemical that you’re giving. And as well, when it goes through the liver, it up-regulates some of the liver production of coagulants, procoagulant. So, clotting factors like thrombin. So, it actually is a promoter of blood clotting. So, it’s a totally different product. It’s really like night and day. And so, my analogy is if you did a study with strawberry flavored jelly beans, and then the results were that it gives you cavities and diabetes and obesity, then you draw the conclusion, you should never eat organic strawberries, you’d say, “Well, that’s crazy.” But that’s what they did with this study. And they didn’t give progesterone, they gave a progestin which is a man-made word for an endocrine disruptor for progesterone.
So it turns out that the endocrine disruptor that they gave medroxyprogesterone acetate can bind to progesterone receptors, but depending on the organ, because it’s like a pro and an anti, that’s what they call an endocrine disruptor, it has different effects. It’s either a promoter, so it’s like an agonist or it’s an antagonist. So it either blocks the progesterone receptor, or it actually activates the progesterone receptor. So it has different effects in different organs. And it’s been shown now to increase bad things like breast cancer, like heart disease. So, it actually has a negative effect in like the breast tissue.
So, we have all kinds of problems and the other thing is that when you have in the breast, it’s predominantly the alpha receptor. So when you give predominantly something like an alpha receptor agonist like estrone, that comes from Premarin, you’re going to have a greater impact on the breast tissue. You don’t have the balance because you’re not getting any of the beta effect. So, you’re just giving the wrong thing. Something that increases blood clots, something that then, of course, was shown to, well, it increases dementia.
Well, how can estrogen in the form of estradiol increase dementia when the brain loves estradiol? It monitors the immune system of the brain. It regulates the [crosstalk 00:40:38]
Dr. Weitz: Let me just stop you for a second right here on the breast cancer, estrone, and the estradiol thing. I wanted to ask you about the best form. I know we’re not done with critiquing the Women’s Health Initiative, but in terms of the best form of estrogen to be prescribing to women say, I wanted to point out that we have the three forms of estrogen. We have the E1 estrone, we have the E2 estradiol, we have the E3 estriol.
And because estriol, as you just pointed out, works more through the beta receptor, it’s believed to be safer in having less risk of breast cancer. And so, this has led, especially doctors in the integrated world, who recommend hormones to postmenopausal women to recommend estriol or a combination of estradiol and estriol often in a cream that has a higher percentage of estriol. And that’s because estriol is a weaker estrogen, and because it works. The beta receptor, we think it’s going to have less risk of breast cancer, but you think that E2 really should be your preferred form of estrogen?
Dr. Gersh: Well, I think that this is a really well-intentioned but very misguided approach to hormone therapy for menopausal women. So, estriol is the dominant estrogen of pregnancy. So people think, “Oh, well, why don’t we create a more pregnancy-like effect?” Well, that is actually the exact opposite that we want. So, most people don’t understand pregnancy. Remember, I’m OB-GYN so I’ve dealt with pregnancy my whole career.
So, pregnancy is actually a pro-inflammatory state. So, with this is like the opposite of what we would want to create for a menopausal woman. So what happens in pregnancy? As soon as a woman becomes pregnant, and she starts having higher levels of estriol, her gut microbiome changes immediately and it becomes more dysbiotic, it actually becomes more pro-inflammatory and pregnant women develop a leaky gut, and then they end up having more inflammation, as you have the endotoxins, the lipopolysaccharides are leaking through.
Now, people, they’re like, “What the heck, why would that be happening?” Well, this is nature’s way of helping women to actually survive and for the baby. So, if you think of it this way, what happens is when women become pregnant and they become a little inflamed, now, this should be like a controlled fire, it’s a little inflamed. And we know that when you have more inflammation, you develop insulin resistance. And that is intended in pregnancy to promote fat production, fat storage, and higher glucose levels so that you have more glucose being transported to the baby to help the baby to grow and then become fatter.
Most people know this, that pregnancy is now recognized as a stress test for women. pregnancy is a time when women who had no evidence of any cardiovascular or metabolic dysfunctions can develop gestational diabetes, pregnancy-induced hypertension, preeclampsia, these are all vascular conditions that are related to underlying inflammation. Women who are pregnant are more prone to blood clots.
So, that’s because nature creates this low level of inflammation in pregnant women to promote insulin resistance to enable women, remember, we evolved during millennia ago, when food was scarce, to allow pregnant women to put on more fat and to deliver more glucose to the baby to grow the baby. We don’t want to do that in not pregnant women.
Dr. Weitz: Isn’t it the case that women who have babies earlier have a lower risk of breast cancer because they have fewer periods?
Dr. Gersh: No, it’s not because they have fewer periods. It’s because there’s… Nature is amazing. So, if you have pregnancies starting at a young age, even women who have their first baby before the age of 19 have incredibly low risk of getting breast cancer their whole lives. It’s only endocrine disruptors that mess with this whole natural system because nature made it that way. There’s tremendous hormonal changes that occur that actually reprogram genes. So we have epigenetic modification during pregnancy. So, absolutely, I’m very pro pregnancy at the proper ages and nursing. Nursing as well is very protective, both cardiovascular protective and breast cancer. But this situation cannot be replicated in a 50-year-old woman, it’s not going to happen so that when you are pregnant, you are in a pro-inflammatory state. But the hormones do so many different things, and we’re talking about incredibly high levels of progesterone as well, which we’re not replicating in these postmenopausal women. So we’re creating a state that never exists. When you give Biest, this is not like how pregnant women have their hormones. It’s just giving us some extra estriol but estriol is not the same as estradiol. By the way, estriol does not help the brain. So it’s estradiol that the brain loves, not estrone, and not estriol. That’s why they sometimes talk about mommy brain. We don’t want that.
So, we have to recognize what nature is doing. So also, when women are pregnant, they have an altered immune status, which is very important so that the immune system of the body doesn’t attack the baby. We don’t want that happening. So that’s why women who are pregnant are more likely to have serious outcomes and mortality and morbidity from infections like the flu or if they got chickenpox or COVID. So, why is that? Because the innate immune cells of the body, the macrophages, the neutrophils, the mast cells, they all have estrogen receptors. Remember, everything has estrogen receptors, and they’re alpha, they’re the alpha receptor. Remember, estriol is all beta. And when you have high amounts of beta, it actually downregulates the alpha receptor. So what you’re doing when you have high amounts of estriol, this is all the beautiful wisdom of nature. Nature is wise when it comes to reproductive success.
It just is cool when it comes to getting old. But reproductive success. So the estriol with the high beta is now down-regulating the alpha. So the innate immune cells of the body are less active. That’s why a lot of women who have certain types of autoimmune diseases, they have remissions during pregnancy because you’re down-regulating the ability of these cells to make all these inflammatory cytokines, but the whole thing is very modulated and balanced so that you actually have this inflammatory state that promotes insulin resistance, but yet your immune cells are less capable of attacking. And that’s why women who are pregnant are living on the edge. That’s why it’s a really interesting stage.
Dr. Weitz: So, for all these reasons, you recommend transdermal estradiol not oral estrogen?
Dr. Gersh: Yes, because we don’t want to mess with the immune systems of postmenopausal women. We don’t want to create dysbiotic gut microbial populations, don’t do it.
Dr. Weitz: And one of the reasons why the Women’s Health Initiative was wrong was not only that they were using Prempro, but also because of the timing hypothesis, right?
Dr. Gersh: Well, I really am going to in the end, not now, because I have to take it stepwise. But the timing hypothesis is that you have this window of now they’re saying 10 years, 10 years that you can give hormones and after that, it’s too late. Now, I actually go along with that right now. But I’m telling you, I don’t, in my heart, totally believe that. But I have to go by steps.
So, in the Women’s Health Initiative, because they had certain caveats, they needed to use women who did not have hot flashes or any obvious symptoms of menopause because they were trying to make this a double-blinded study. I can tell you, every woman who got the active hormones figured it out right away because they all had immediate breast tenderness. And some of them had bleeding. They all figured it out. They couldn’t really blind it. Everybody figured out what they were taking.
But the idea was that they were not going to be giving something that suppress symptoms like night sweats and hot flashes to give it away. So, they had to use women who were not having any symptoms. And so the average age was 63. They went all the way up to starting women at the age of 79. And many of these women, they said healthy women, that was not true. So, some of the women had already, they’d been on a blood pressure medication, lipid-lowering drugs, they’d already had problems.
So, this was like standard Americana, women in their 60s and 70s. And they were not healthy group. The BMI was really high. So most of them were overweight and obese. I mean, it’s like, what kind of healthy population are you talking about? So they already had pre-existing conditions and now you’re giving them a drug that is going to increase their clotting propensity. So, yeah, that’s what actually happened.
So, in the very beginning, so the first year, and this happened in the [inaudible 00:50:09] study that came before this, so they had an increase of events in the first year because they took women who were on the edge of having some sort of a cardiovascular event, and then they pushed them into it. But once you got out by four years, you’ve already gotten rid of the ones that were living on the edge. And now you were actually starting to see some benefit.
So that’s like the most incredible thing is that even giving this really bad stuff, the actual incidence of problems was really statistically quite low. And in the group of women, which was only like 10% of the study population, that were in their 50s, they actually had overall lowered mortality of all causes, all-cause mortality was lowered by about 30 or so percent, which is amazing. So here you’re giving the wrong thing and you actually had really good outcome in women in their 50s.
Just think if you actually had done that study using the right stuff what you might have shown. But what it did is the study totally caused women to become scared to death, that they were going to get breast cancer and heart attacks and strokes and dementia and all this stuff. And they were all taken off of their hormones. There have been some estimates that as many as 90,000 women died unnecessarily because they were just taken off over the next few years because they were discontinued from using even the wrong stuff.
It also then poisoned the minds of researchers for future studies as well. All the studies shut down, there was no action, nothing, no further progress. And then even when study started creeping back in because this had affected everyone’s mentality, and so the dogma became, if you’re going to use hormones, use the tiniest dose for the shortest period of time. So that became the mantra, the smallest dose, the shortest time. So even when they created new studies, they followed that philosophy by using really low doses, obviously, for shorter periods of time, so it didn’t always show great results because you can’t use… it would be like doing a study of vegetables, and you eat one bite a month, and then you say, “What’s the point of eating vegetables? They obviously do nothing.” That’s the problem.
But then the conclusions that they drew from these studies in one, in the [inaudible 00:52:40] study, that they actually looked at the levels, the serum levels of estradiol, and they practically didn’t deviate from the levels of the women who were in the control group who didn’t get hormones. So, you get such low doses that there was almost no difference in the levels of estradiol in either group. And then it didn’t show great benefit. Well, duh. It’s like, drive me crazy.
Dr. Weitz: I have about 20 more questions, but neither you nor I have any more time because we both have patients. So, it’s the nine o’clock hour is [crosstalk 00:53:20]. So we’ll have to do a part two.
Dr. Gersh: Well, I would love that. If there’s interest, I am here. Because we’re both passionate about this, which I love it. I love how knowledgeable you are, and how interested you are in this. It’s not just academic. This is like real lives are at stake here, real lives. And we’re just touching barely the surface of what this really can mean for women. Once we accept that menopause is actually what it is, universal and universally harmful to women’s global health, it just is what it is. And that we can do a lot to change the outcome instead of just doing the whack a mole of trying to deal with each symptom as it arises and each complication, whether it’s with joints, or whether it’s with bones, or brain or heart or vessels. So we can do so much more if we just wake up to reality here and then sweep all this other bad stuff under the rug, close the door, and never go back and then look to the future.
Dr. Weitz: Great. So how can listeners, viewers find out about you? And also get your books and do you have any training courses for practitioners?
Dr. Gersh: Well, I’m thinking about that. If there’s demand, let me know.
Dr. Weitz: I’m sure there is.
Dr. Gersh: Well, I love to help both patients and practitioners. So my office, for people who want to either come or refer, I have a regular brick and mortar. I’m sitting on my examines right now in Irvine, California called the Integrative Medical Group of Irvine and I can do quite a bit with telemedicine as well. And I have an Instagram Live show at dr.felicegersh, which I try to do weekly. Every once in a while, I miss a week, but I’m trying. And I do have my two books on PCOS which have a lot of lifestyle advice, and I am almost finished with a book on menopause. And that will be coming out in the relatively near future, has to get cover and package and all that sort of stuff. So I am doing that. Honestly, if people are interested in courses and so on, let me know because I’m very open to helping in any way I can. And if some people have suggested shadowing, I’m open to ideas. I’m mostly what I do is try to educate and care for patients. I look forward to doing more with you.
Dr. Weitz: Sounds good.
Dr. Gersh: You’re a gem, by the way.
Dr. Weitz: Thank you, Felice. Thank you listeners for making it all the way through this episode of the Rational Wellness Podcast. Please take a few minutes and go to Apple Podcasts and give us a five-star ratings and review, that would really help us so more people can find us in their listing of health podcasts. I’d also like to let everybody know that I now have a few openings for new clients for nutritional consultations. If you’re interested, please call my office in Santa Monica at 310-395-3111. That’s 310-395-3111 and take one of the few openings we have now for a individual consultation for nutrition with Dr. Ben Weitz. Thank you and see you next week.
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