Women’s Heart Health with Dr. Felice Gersh: Rational Wellness Podcast 73

Dr. Felice Gersh talks about how to improve heart health in women with bioidentical hormone therapy with Dr. Ben Weitz. 

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Podcast Highlights

1:52  Prior to menopause, women tend to have a significantly lower risk of heart disease then men because estrogen is protective of the heart.  This is one reason why many doctors were prescribing estrogen and hormone replacement therapy (HRT) to women after menopause. But then in 2002 the Women’s Health Initiative Study was published that showed that HRT was dangerous and raised a woman’s risk of heart attack and stroke, as well as breast cancer, and many doctors stopped prescribing HRT. 

2:58  Dr. Gersh explains that this study was really disastrous for women’s health and amounted to a roadblock in the developing story of estrogen and women’s health. First of all, they did not study human estrogen. The compound studied is Prempro, which is derived from the urine of pregnant horses. It’s not even the estrogen that the horses wanted. It’s the estrogen that they excreted, which is why it is known as conjugated equine estrogen. And the form of progesterone used in this study is Provera, which is a synthetic form of progesterone known as progestin, or medroxyprogesterone acetate, which is actually an endocrine disruptor.  It’s a chemical that binds to progesterone receptors, but it has variable effects, and it turns out in the uterus, in the uterine lining, it acts as a big blocker of estrogen, but when you look at the other parts of the body, you look at the cardiovascular system, and the brain, and so forth, what you find, it actually is a progesterone blocker. The same in the breast, so it actually is like an anti-progesterone. And these were also women who were in their 60s, so most of them already had some pre-existing cardiovascular disease since they were often more than 10 years out from when they actually went through menopause, which we know is a big risk factor for cardiovascular disease.  It turns out that Premarin increases the risk of blood clots by 400%, so it is really disastrous for women’s health!

7:30  Estrogen is very protective for the heart, especially estradiol more so than estriol.  Estradiol protects our arteries through stimulation of the endothelial nitric oxide synthase, which produces nitric oxide, which maintains the dilation and the health of the endothelium (the lining) of our arteries. Without estrogen you get reduced levels of nitric oxide. There are estrogen receptors in the gut, which is why that after menopause you tend to get leaky gut. There are estrogen receptors on the immune cells, like macrophages, neutrophils, and mast cells, which are part of the gut-associated lymphoid tissue, so this sets up systemic inflammation, which is a major factor in arterial problems in heart disease. Also, estrogen reduces platelet aggregation and blood clotting. Without estrogen you have the perfect scene for trouble–platelet aggregation, reduced dilation of your blood vessels, leaky gut, and inflammation. You also get more oxidized LDL because estradiol maintains an enzyme system called the peroxidase 1, PAN1, which reduces the oxidation of LDL. Without estrogen you also get an increase in ADMA, which further reduces nitric oxide. All this is happening very rapidly as women proceed through menopause, which is why women have higher rates of stroke than men and women tend to die more commonly than men from their first heart attack and they actually start to surpass men in terms of percentages of women dying from cardiovascular compared to men, and none of this is recognized by our conventional medical world, and they fear estrogen.  Dr. Gersh said that she fears lack of estrogen and this is just the tip of the iceberg. There are also estrogen receptors in the mitochondria that keep the heart beating properly, so without estrogen you’re more likely to get arrhythmia, atrial fibrillation, and heart failure.  2-methoxyestradiol is an estrogen metabolite that helps to maintain heart function. Basically, the entire cardiovascular system is reliant on estradiol, not estriol. It is shocking that renowned cardiologists are denouncing estrogen and telling women to stay away from estrogen and they are equating issues with birth control pills, which are estrogen endocrine disruptors. They are the evil twin of estrogen. Everyone, unite to defend our hormones.

17:22  Many doctors, especially Functional Medicine doctors, who recommend bioidentical hormones to women tend to prescribe a combination of estradiol and estriol (Biest) in the belief that estriol is a weaker form of estrogen and that this will balance the stronger effects of estradiol and that this will reduce the risk of breast cancer and have other beneficial effects.  Dr. Gersh explained that these doctors are basing this on data that is 30 years old, but at that time, we didn’t know that there were alpha and beta receptors of estrogen and we didn’t know about membrane receptors.  For generally healthy women who are hitting menopause, estriol is really not a good tool. There can be some specific uses for estriol if you’re treating specific condition, maybe even breast cancer or autoimmune disease, like multiple sclerosis. But estriol, which is a very dominant estrogen in pregnancy, only works on the beta receptor.  The B cells of the immune system have primarily beta receptors, while the innate immune cells primarily have alpha receptors. During pregnancy, the estriol down-regulates the immune system so that you don’t reject the baby. This is why if a women has autoimmune disease, it will often go into remission during pregnancy. This is also why women who are pregnant are more likely to die if they get the flu or chickenpox. This is why it may be useful to use estriol in women with MS because it down-regulates the immune system, like a biologic drug like Humira.  Prior to menopause, women tend to survive septicemia at higher rates than men because they tend to have a stronger immune system than men.  If you give women estriol instead of estradiol, you will be down-regulating their immune system, which is generally not a good thing.  In addition, alpha receptors are in the brain in the hippocampus, and women already have three times the rate of Alzheimer’s as men, so if you give estriol you will not be stimulating the brain to function as well as estradiol does.  Also the beta-receptors tend to up-regulate the appetite center in women, which is good in pregnancy but not in menopause, so giving estriol may encourage women to gain weight. And if you give estradiol, the body will make some of it into estriol.

We also should consider the interplay of various hormones in the body and the importance of estrogen and progesterone for allowing the other hormones to work properly.  For example, when you have the normal surge of estrogen that occurs during part of the month up-regulates thyroid receptors, so thyroid hormone works properly.  That’s why so many women in menopause have symptoms of low thyroid. Low T3 is associated with heart failure. If you have no estrogen and no progesterone, then you will have worse thyroid receptor function. If we get estrogen, progesterone, and testosterone right, then thyroid, oxytocin, and growth hormone will all work better. 

28:18   Progesterone, which is estradiol’s sidekick, also has receptors all over the body. The key is having the right amount of hormones in the right rhythm. We should not give a small static amount of estrogen and progesterone every day.  We want to try to mimic the rhythms of hormones that occur in a healthy 25 year old woman, though we to do need more research on this. Even pulsing the progesterone so that you do it 14 days a month is better, and there is some published data that that lowers the risk of breast cancer.  Progesterone is not just there to counteract estrogen’s effect on the uterus.  Progesterone has amazing effects all over the body and it’s very neuro-protective. It actually down-regulates estradiol receptors. It’s all a beautiful balance of proliferation and anti-proliferation. As far as the appropriate dosage, Big Pharma has recommended either 100 or 200 mg, but we don’t have enough data on what the optimal dosage should be. Dr. Gersh said that she is working with a nonprofit doing research to answer the question of what is the best dosage of progesterone to be used for each woman. 

35:50  For the 60 or 70 year old woman who decides that she would like to take hormones, we should start with a lower dosage because the receptors have been in hibernation and work our way up. 

39:40  Testing for women with cardiovascular disease is often different than men.  Coronary calcium scores are less important and have less predictive value for women.  Many women who die from heart attacks don’t have severe atherosclerosis. They tend to die from spasm.  Checking their blood pressure is very important. Echo stress tests have virtually no predictive value for women, though echo cardiograms can be helpful.  She will often see patients who return from the cardiologist with mild diastolic dysfunction, which they are told is normal. But this is not normal and it indicates that your heart is stiff and is deficient in energy.  This is a sign of mitochondrial dysfunction in the heart muscle and such women will have higher rates of conduction defects and will have higher rate of arrhthmias and Afib. For such women, having more estrogen can be very helpful.  Estrogen controls the enzyme matrix metalloproteinases, which are involved in tissue remodelling and hyperplasia of the heart muscle. It can result in heart valve problems.  Dr. Gersh prefers to look at carotid intima media thickness. It is important to look at labs for inflammation. 

44:43  Since women have so many mitochondrial problems with their hearts, then statin medications, which are known to negatively impact the mitochondria, probably are not a good medication for them. The two areas of the body that have the most energy needs are the brain and heart, which is why they both are so dense in mitochondria. One of the better supplements for managing lipids in women is citrus bergamot. We should remember that as women age, low cholesterol is more associated with higher mortality than high cholesterol. What you want is to do to reduce cardiovascular disease risk in women is to drive down oxidized LDL, which we know is controlled by the enzyme PAN1, which is controlled by estradiol.



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 http://www.felicelgershmd.com/ and she is available to see patients at 949-753-7475, she lectures around the world, and she will be releasing her first book on PCOS in November 2018, which is called PCOS SOS: A Gynecologist’s Lifeline to Restoring Your Rhythms, Hormones, and Happiness.

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, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111.


Podcast Transcripts

Dr. Weitz:            This is Dr. Ben Weitz with the Rational Wellness Podcast, bringing you the cutting-edge information on health and nutrition from the latest scientific research and by interviewing the top experts in the field. Please subscribe to Rational Wellness Podcast on iTunes and YouTube, and sign up for my free e-book on my website by going to drweitz.com. Let’s get started on your road to better health.  Hello, Rational Wellness Podcasters. Thank you so much for joining me again today. For those of you who enjoy listening to the Rational Wellness Podcast, please go to iTunes and give us a rating and review so more people can find out about the Rational Wellness Podcast. Normally, I introduce the topic first and then the speaker, but today, I’m going to introduce the speaker so I can tee up the first question for her when I do a short intro on the topic.

Our guest speaker today is Dr. Felice Gersh. She is a board-certified obstetrician and gynecologist. She’s fellowship-trained in integrative medicine. Dr. Gersh is the director of the Integrative Medical Group of Irvine where she sees patients. She also lectures around the world on various topics relevant to women, and her first book on PCOS will be released very soon. Hi, Dr. Gersh.

Today, our topic is heart disease in women. We all know that heart disease is the leading cause of death for men, but what about women? Well, you might be surprised to know that just as many women die of heart disease each year in the US. Prior to menopause, women tend to have significantly lower risk than men, and we have known for a long time that estrogen is protective for the heart.  However, after menopause, heart disease rates rise in women. This is one reason why prescribing hormone replacement therapy became popular to not only deal with the problematic complaints of menopause like hot flashes and night sweats, but to reduce cardiovascular disease risk.  And there were quite a number of studies showing reduced risk of heart disease in women taking hormone replacement.  But then, in 2002, poof, a bomb went off in the hormone replacement world when the Women’s Health Initiative was published. This large study showed unequivocally that women who took estrogen and progesterone replacement therapy after menopause had an increased risk of heart disease. Doctors stopped prescribing hormone replacement therapy for women in order to reduce their risk of heart disease. Is this the end of the story, Dr. Gersh?

Dr. Gersh:           Well, it actually is, what you might call, a deviation in the story. It’s a big bleep, and it’s been really disastrous for women’s health and really, for moving forward the whole conversation because of this … Well, I call it a gigantic roadblock. Right? We’ve got to really detour around this, and what they studied in the Women’s Health Initiative was not human hormones, and there’s so much more to it than even just that. But again, if you just start with what they actually studied, it was a compound called Prempro, and that was really what they mostly studied. They had in the women who’d had hysterectomies say, “Just use Premarin,” and they actually had somewhat of a better outcome, but Prempro itself has some really bad things about it.

First of all, there’s no human Prempro. It doesn’t exist in any female anywhere on this planet. Premarin is actually derived from the pregnant horse’s urine, which has the actual … sort of the unwanted parts of estrogen. It’s actually metabolized estrogen. It’s really what it wanted to get rid of. It’s not the actual good estrogen that the pregnant horse even wants. It’s after it’s metabolized and it’s gone through conjugation. It’s all out. That’s why they call it conjugated estrogen. It’s actually altered to get rid of by the lovely pregnant horse. Of course, there has been some concerns about mistreatment of horses as well, which is a separate topic.

Then, the progestin. Progestin is a man-made-up word for a chemical endocrine disruptor for progesterone, the real human hormone, so medroxyprogesterone acetate, which is what is Provera, is really an endocrine disruptor. It’s a chemical that binds to progesterone receptors, but it has variable effects, and it turns out in the uterus, in the uterine lining, it acts as a big blocker of estrogen, but when you look at the other parts of the body, you look at the cardiovascular system, and the brain, and so forth, what you find, it actually is a progesterone blocker. The same in the breast, so it actually is like an anti-progesterone, and that’s why they call them endocrine disruptors.

Depending on where they are, they can be agonist or antagonist, and so we have a completely foreign substance that’s being put into women’s bodies, and these were generally speaking a little bit older women. They were in their early 60’s was the median age, and they already had some pre-existing cardiovascular disease because after all, they were … Many of them, at least 10 years or they were more than 10 years out from when they actually went through menopause, which we know is a big risk factor for developing cardiovascular disease, and it turns out that Premarin increases the risk of blood clots about 400%. Then, of course, what is a heart attack or a stroke? It’s really a piece of blood clot that breaks off of a ruptured piece of plaque, so you’re going to have dramatically increased blood clotting.

In fact, thrombophilia, when you have increased clotting, which happens as women age and men as well, is a very bad thing, and a lot of people look at cardiovascular risk as directly reflective for heart attacks and strokes of how clottability, the clottability factor of the blood. Here, you’re taking a drug that increases it four times, so it’s a big problem. Prempro is disastrous for women’s health, and even then, it actually didn’t kill as many women as you might think. Over time, women seem to adjust to it, so as you move further out, like more than a year out, it seemed like you knocked off the women that were going to get knocked off, and then it kind of seemed to adjust, but it was really disastrous for moving the whole conversation of women and cardiovascular health forward.

Dr. Weitz:            What is the answer about when and … What is the appropriate type of hormone replacement that women should consider using if they choose to do it after menopause?

Dr. Gersh:           Well, it’s a personal decision, but as many of you know, I love estrogen. I defend estrogen and progesterone too, when it’s needed. Progesterone doesn’t get quite as maligned as estrogen does.

Dr. Weitz:            By the way, can you explain how estrogen is protective for the heart?

Dr. Gersh:           Oh, yeah. Estrogen actually mediates most every function in the entire body. It’s really quite phenomenal as you learn more and more about estrogen, and the estrogen we’re talking about really is estradiol, and that’s really important because a lot of people are using estriol.  And estriol has very beneficial effects, particularly when you’re pregnant, but it’s really not … It’s going to create some problems if you use a lot of estriol in menopausal women, which I can explain if we have time, but …

Dr. Weitz:            Yeah. Well, I think a lot of the Functional Medicine doctors and people who prescribe estrogen bioidentical hormones tend to use estriol in the belief that it has a lower risk of cancer, of breast cancer.

Dr. Gersh:           Well, we definitely want to touch on that, for sure.

Dr. Weitz:            Okay.

Dr. Gersh:           If we jump on estradiol, so it turns out that estradiol is very key if we just start with the blood vessels. Okay? Arteries. There’s this magical substance. It’s a redox signaling agent called nitric oxide, and nitric oxide is made in various places all over the body. One of the ways that it’s made is through an enzyme system, nitric oxide synthase, and one form of that is endothelial, which obviously suggests it’s in the endothelium of arteries, which it is, and estrogen is very key to making that enzyme work.  Okay. You need estrogen. You need estradiol, and without that, you tend to get reduced levels, and nitric oxide really maintains the health of the artery and all the different layers of the artery. It maintains dilatation, health of the endothelium, so loss of nitric oxide occurs, dramatic decreases when you lose your estradiol production from your ovary, so that’s very important.

Then, estradiol has … It’s so complex because estradiol has receptors in the gut, and we all know now in functional medicine how key the gut is in every aspect of health, and without estrogen after menopause, leaky gut actually happens. We know that there’s a change in the microbial environment, the microbiome changes, and you get dysbiosis. You lose that protective mucus coating, and you lose the tight junctions, and you end up getting leaky gut.

The other thing that’s very key to this is that estrogen has receptors on every one of the immune cells, including the innate immune cells like macrophages, neutrophils, mast cells, which we know are in heavy numbers lining the gut and the gut-associated lymphoid tissue. Now, you have the perfect setup for systemic inflammation. You have leaky gut and you have powder kegs because I call them like weapons of mass destruction with no control like you have all these mast cells that contain tumor necrosis factor alpha and histamine. All this, which is designed to attack randomly any invader, right? Only now, you’re having … The least little thing is triggering them because they’re not controlled.

Women in menopause are inherently inflamed, so you have the perfect situation for arterial problems. You have loss of your nitric oxide that’s declining. You have leaky gut. You have inflammation, systemic inflammation, which we know is the trigger to most bad things that happen in the body, including cardiovascular events, and then it turns out that estrogen maintains blood … reduce blood clotting, so through these different enzymes and like the precursor of prostaglandins, the enzyme prostacyclin, which actually maintains reduced blood clot ability. It maintains healthy platelets and reduces the aggregation of platelets.  Estrogen controls platelets, so now you have the perfect scene for trouble. You have platelets that are becoming more aggregating. You have more clottability. You have more inflammation. You have reduced dilation of your blood vessels. You have inflammation rampant everywhere, so of course, that’s the perfect recipe for developing cardiovascular disease, and then on top of that, we have oxidized LDL. We have more inflamed or rancid LDL because estrogen maintains another enzyme system called the peroxidase 1, PAN1, which reduces the oxidation of LDL.

Without estrogen, you’re going to have more oxidized LDL, and when you have more oxidized LDL and you have more inflammation, you increase this product called ADMA. Okay? ADMA then blocks even further the production of nitric oxide, and without estrogen there to come to the rescue, you have this perfect recipe for a cardiovascular disaster, and all of this is happening very rapidly as women proceed through the menopause. We know that in menopause, women have higher rates of stroke than men do. They tend to die more commonly from their first heart attack, and they actually start to surpass men in terms of percentages of women dying from cardiovascular compared to men, and none of this is recognized by our conventional medical world, and they fear estrogen.

I fear lack of estrogen, not having estrogen, and you can see, and this is just the tip of the iceberg. I didn’t even touch on … We can go into that that there are estrogen receptors in mitochondria that keep the heart beating properly. Without estrogen, you’re more likely to get arrhythmia as an atrial fibrillation and heart failure. The myocytes, the heart muscle themselves have estrogen, and even more than that, they have receptors for what they call estrogen-related receptors, which are all about creating energy. Even the metabolites of estrogen, one that’s called 2-methoxyestradiol has its own receptors. It’s so important. It’s an estrogen metabolite that helps to maintain heart function itself.

Basically, the entire cardiovascular system is reliant on estradiol. These are all estradiol, not estriol, mediated events, and that’s like another important take-home message, and then we’ll get into estriol whenever you’re ready, but I just am … Obviously, I’m exploding. I’m a powder keg. I am trying to get the word out, and it is shocking that even “renowned,” we’ll put that in quotation marks, “renowned” cardiologists all over the world are denouncing estradiol and saying women should stay away from estrogen, and they’re equating issues with estrogen and, for example, oral contraceptives, which of course are not healthy for a heart.  We wouldn’t give someone who just had a heart attack a birth control pill, and then they … So, they’d maligned estrogen because of the evil twin, right?  Estrogen endocrine disruptors are being called estrogen, and progesterone endocrine disruptors are being called progesterone, and we have to defend this.  Everyone, unite to defend our hormones.

Dr. Weitz:            Great, so I want to get into estriol in a second, but you mentioned 2-methoxyestradiol, and I just interviewed Dr. Berkson, and she talked about taking 2-methoxyestradiol.

Dr. Gersh:           Wow, how funny.

Dr. Weitz:            What do you think about using that particular compound?

Dr. Gersh:           I am very simple. I say do what nature designed us to do. We are not smart enough to micro-manage much of anything. That’s why we can’t micro-manage receptors. We can’t micro-manage estrogen metabolites.  Give estradiol. Okay? Let the body make … Do everything to have a healthy gut, and that, of course, includes a liver, right, because it’s all part of the same process.  Try to have the systems working as best we can make them work so do as … I like to use like a 25-year-old as my goal.  If I can do things to try to mimic what goes on in a healthy 25-year-old, and some of them are not healthy at 25, but if you get the healthy 25-year-old woman, that’s my gold standard for what I’m trying to mimic, so I’m not going to give anyone metabolites.  I don’t want to give pieces of anything.  I want to give the whole.  Right?  It’s like the whole food, right?  I try not to … I love to use supplements, but I see them for what they are.  They’re pieces of the whole, right?  If I give a polyphenol, that can be helpful, but what if I give the whole food, right, and it has not only the polyphenol magic, but it has the fiber magic, and it has the other antioxidant magic?  Right?  I give estradiol magic and let the body make its own metabolites and so forth, and work the magic that it does in the female body, but you have to have the systems working, of course, or else you’re not going to get the right metabolites. That’s why the estrobolome exists. That’s why livers exist, but we have to nurture them so that the body will do its thing. We are not smart enough to try to break it into little pieces. Start with the whole and let the body do its thing. Oh, I’m not smart enough anyway.

Dr. Weitz:            That’s great. We mentioned estriol, and it’s common among doctors who prescribe bioidentical hormones to give a compounded product that contains a combination of estriol and estradiol with the belief that estriol has a lower risk of breast cancer.

Dr. Gersh:           Right, and I understand that that is data that goes back maybe 30 years, and in its time, it was very … No, extremely forward-looking, recognizing that there were different forms of estrogen, but it missed a lot because they didn’t know a lot. You can’t blame anyone for coming up with something without knowing. At that time that that idea came out, we didn’t even know there were alpha and beta receptors of estrogen. We didn’t know about membrane receptors. All they knew is that if you gave estriol, it seemed to reduce breast cancer, but now, we know that it really is not a good tool, and I’ll explain why, for generally healthy women who are hitting menopause. There can be some unique uses of estriol if you’re treating a specific condition. Maybe even breast cancer. Maybe things like autoimmune disease like multiple sclerosis, but that’s not replacement. That’s different. That’s treatment.

It turns out that estriol, which is a very dominant estrogen in pregnancy has only beta receptive functions, so it only works on the beta receptor. Now, there’s alpha and there’s beta receptors, and they’re both very critical, and then we won’t even get into membrane receptors, which actually trigger kinesis, I mean, and it turns out that alpha and beta, which we used to think were purely nuclear receptors are not. Everything is much more complicated than we ever thought. It turns out that they also have membrane receptor function, and they also up and down regulate each other, so everything … That’s why I say we can’t micro-manage because everything turns out to be more complex than we ever thought.

Beta receptors tend to cluster in certain areas. Nothing is exclusive. They tend to be in the lining of the gut, in the enterocytes. They’re in the lining of arteries. They tend to be in certain other areas like in the vagina, and if you think about pregnancy, you’re going to have a lot of beta, and that would want to be in the vagina so that you have this incredibly stretchy vagina. For example, if you were suddenly magically a woman … Not you. If a woman were magically pregnant and she had no estriol, normal amounts, but not the amounts that you’d have in pregnancy, and suddenly, she had to deliver a baby, she just rip apart because she wouldn’t be stretchy. I always think of it like a snake swallowing a big pig or something.

Dr. Weitz:            Yeah.

Dr. Gersh:           It’s like, “How does it do that?” But because of all the estriol. Okay, and the estriol helps block some of the estradiol effect in the breast or women would probably be size quadruple Z or something. Right? It would be impossible, so there is this beautiful balance between estriol and estradiol in pregnancy, but it turns out that it gets more complex because if you think of pregnancy, it’s a very special immune state. Right? You do not want to reject the fetus. It is a foreign tissue, so it turns out that the beta receptor is the receptor that’s primarily on the B cells, and the alpha receptor is the primary receptor on the innate immune cells, like I mentioned, like mast cells, and the macrophages, neutrophils, macrocytes, and so on.

Those are primarily alpha, and B cells are beta, so it turns out that in order to basically dismantle the innate immune system to down-regulate it, you have a lot of beta. It turns out that beta down-regulates alpha, so in pregnancy and a lot of people know this that if a woman is pregnant often and she has autoimmune disease, she goes into a remission only to flare afterwards, but why is it? Has anyone ever thought about like why is it that in pregnancy, women often have a remission?

Also, women who are pregnant are more likely to die if they get the flu, if they get chickenpox. I’m sure a lot of people know that. They are more at risk if they get an infection that they may die, but they’re less likely to have flares of their autoimmune conditions than they often go into very dramatic remissions. It’s because the beta, which is estriol, is down-regulating the alpha receptors, so basically, it’s like an immune modulator that you’re getting. This big dose of estriol is like an immune modulator. That’s why I do some research on using it, for example, in MS. It’s down-regulating just like a biologic, just like an immune modulator like ramicade and humira. It’s down-regulating your innate immune system, but it’s …

Dr. Weitz:            That’s good because women have such a high risk of autoimmune, and in fact, depending upon how you look at it, heart disease is an autoimmune disease.

Dr. Gersh:           But the problem is that women, for example, pre-menopause have dramatically higher survival rates if they become septic and they … Women have higher survival rates than men across all ages when especially though the difference is very dramatic pre and post-menopausal. There are some innate benefits that’s actually built into the X chromosome. That’s why even girl children tend to outsurvive boy children if they get an infection, but it’s dramatically increased with the reproductive years when they have estradiol on board, so it really … Women have a very robust immune system. Much, much more powerful than males at fighting off sepsis.

Women survive septicemia much higher rates, but not after menopause, so this is the problem just like if a woman is on an immune modulator like humira, ramicade, and so on. It says on the fine print you may die like of an infection, right? “Do not take this if you have a fever. Blah, blah, blah.” Right? What you’re doing to women in the menopause, if you keep them like in this pregnancy state where their immune system is down-regulated. You’re making them much more susceptible to die if they get pneumonia, if they get the flu. I don’t think that’s a really good idea, so the alpha is part … You’re taking out your immune system, your innate immune system, so that …

Dr. Weitz:            Right, and that’s going to put you at higher risk of cancer as well.

Dr. Gersh:           That’s right. You need an innate immune system. If you have estradiol, you will make estriol, and they’ve actually shown that you do … Of course, it’s part of the equilibrium, so you will make the right amount that your body needs. In addition, alpha isn’t just on the immune cells. Alpha is in the brain big time in the hypothalamus, in the hippocampus. You’re down-regulating your memory centers when you take just estriol, and women who are pregnant, often they say they have pregnancy brain. Oh, why is that? Because they’re down-regulating their alpha. It’s affecting the hippocampus. You’re affecting memory.

Women already have three times the amount of Alzheimer’s as men. Please stop doing us in. Okay? Don’t do that to us, and it also regulates the appetite center. Nature did this on purpose. Women who are pregnant are supposed to want to eat more, right? Especially think about ancient times when food was scarce, right? Women’s appetite is up-regulated so that they can gain weight, so you want to do this to your post-menopausal women. You’re down-regulating their appetite control centers. Don’t do it, so stop playing like you’re in charge. Stop being in charge. Give the body what it’s designed to have and stop micro-managing this. You’re micro-managing receptors. You have no clue what you’re doing, and that’s just the tip of the iceberg, I’m sure, of what we’re doing here, so we don’t want to give all this estriol and down-regulate all your alpha receptors. You’re doing harm.

If your patient dies of an infection, you may be responsible. If your patient gains weight, you may be responsible. That’s really not what we want to do, and I used to use bias too because I didn’t understand, but now we understand. I would never touch it because it’s really … It’s not what nature wants us to have, and we want to protect our women from infections, and that’s a big cause. Pneumonia is a big cause of death. We want to keep women on hormones for their lives. I mean, I don’t see any reason to stop it. I’m never going to stop mine unless they claw it out of my hands or something, but I think we should recognize our limitations, and there’s so much we can do just to help women to be healthy and have healthy cardiovascular systems without trying to be super clever. Just give the body what it would have when it’s a healthy 25-year-old.

Remember, think about a heart muscle. The heart turns over, and you get a new heart about every four years. Right? Every heart muscle in a woman’s body and yours as well is somewhere between just born and four years old on average. Those heart muscle cells don’t know how old you are. They’re born with the same set of genes that when you’re 20, or when you’re 50, or when you’re 70, every heart cell that’s created has the same genetic programming. If you give it what it needs to do its job, it will perform the same at any age, so that’s my goal. It’s recognizing that every heart muscle, every cell in the body is not the same age as you. Right? It was born later, and it doesn’t know how old you are, so give it what it needs, and it will behave the same as it did when you were young.

Now, of course, we can’t truly do that because it’s much too complex, but we can come a lot closer than we have been if we just do everything to feed those cells what it needs, the nutrients, the foundation, so it can run its machinery. Right? So it has the foundational tools, and then we give it the foundational hormones. It will do its job at any age, and that’s what we call health span. Right?

The thing that stops us from living forever is that at some point, our cells can no longer replicate, and then as they die, we can’t replace them, but until that point comes, there’s no reason we can’t be really healthy. I mean, not perfect because we can’t replicate a 25-year-old’s body, but we can come so much closer, and our society does not recognize it. Of course, we know that we’re always playing whack-a-mole. “This problem, we’re going to replace this joint. This problem, we’re going to do this surgery. We’re going to give this drug.” If we just give the cells what they need, they’ll keep performing for us, and that’s every cell in the cardiovascular system.

Dr. Weitz:            Great, and what about the progesterone part of the story?

Dr. Gersh:           Progesterone. I call it like estradiol’s sidekick. Progesterone has receptors all over the body as well. The thing about these hormones is that, and this really … We desperately need more research is that it’s not just having hormones. It’s having hormones in the right amount and in the right rhythm. We’re learning this with food. Right? Everybody is knowing that it’s not just what you eat, it’s how much of it and when you eat it. Right? You can’t just say, “I have one vegetable bite a month.” That’s not going to do it, so why is this whole idea of you have the smallest amount of estrogen possible to keep you alive? What is that all about?

You don’t want the smallest amount of anything. You want the right amount, and we are rhythmic. Women are so rhythmic. They have circadian rhythms, and lunar rhythms, and seasonal rhythms, and ultradian rhythms. That’s the rhythm through the day like the pulses, so we have just one giant rhythm, and when we give hormones the way we give them traditionally along with progesterone, we’re not recognizing the rhythms of progesterone. Let alone the rhythms of estrogen, but certainly, we’re not recognizing the rhythm of progesterone.

Progesterone is often given the same amount every day. Now, even if you don’t truly rhythmic hormones, which is probably really what we should do, whatever we should do, we want to, like I said, mimic a healthy 25-year-old. A woman who’s 25 not on birth control pills, thank goodness, a healthy 25-year-old woman has this incredible rhythm, the lunar rhythm of her hormones. She doesn’t have static dosing. Right? She doesn’t have a little bitty bit of estrogen and a little bitty bit of progesterone the same amount every day. That is not physiologic.

Even if we aren’t mimicking and menstrual cycle, which is where I think we should go, but we definitely need more research, but even pulsing the progesterone so that you do it 14 days a month is better, and there is some published data that that lowers the risk of breast cancer. We are not meant to have a little bit of progesterone every day. Progesterone is not just there to counteract estrogen’s effect on the uterus. We know that. Right? Progesterone is all over the body. It’s very neuro-protective. It has amazing effects all over, but it needs to be in a rhythm.

Progesterone is not supposed to be present every day, and we know that when progesterone in a normal luteal phase when progesterone is at its peak, it actually down-regulates estradiol receptors, so it helps to … It’s all a beautiful balance of proliferation and anti-proliferation. Right? We don’t have that balance when we just give the same thing every day. Also, receptors can get resistant. It’s just like, “Blah, blah, blah, blah,” you stop hearing. Right? The receptors stop listening after a while, and what’s not recognized is thyroid. A lot of women in menopause have symptoms of low thyroid, but they get to the doctor, and they test their levels, and they say, “They’re normal. You’re fine. You’re not a crazy lady.” Right? “You have all these imaginary symptoms. Go home and read a magazine or whatever.” They just brush them off.

It turns out that you can have plenty of thyroid hormone. It doesn’t matter if it isn’t working in the receptor. We all know that was insulin. Right? You’re getting high levels of insulin, but your blood sugar is sky high because it isn’t working. Well, the same can happen with thyroid. For thyroid hormone to work properly, you actually need the rhythm of estrogen and progesterone, so when estrogen spikes, which precedes ovulation, that estrogen spike opens up or up-regulates thyroid receptors, so the thyroid actually works. That’s why so many women in menopause have symptoms of low thyroid.

Now, is thyroid important for the cardiovascular system? You bet. Right? We know that low T3 is associated with heart failure and has a high mortality rate associated with it. That’s the last thing we want is low T3, but it doesn’t matter if you have it if it doesn’t work on the receptor, right, and you need this beautiful rhythm of hormones. If you have no estrogen produced by the ovaries and you have no progesterone, then you’re going to even have worse thyroid receptor function, so we need this. That’s why I like to look at the top tier: testosterone, progesterone, and of course, estrogen. If we can get them sort of right, then we get this, the downward cascade, so thyroid will work better. Oxytocin will work better. Growth hormone will work better. All the like next tier hormones will work better if we get the top tier working.

Dr. Weitz:            How do you determine how much progesterone to give?

Dr. Gersh:           That is the question of the year. There was no data. We have no data. That’s why I’m actually working now with a nonprofit that is going to be doing research in Mexico because it’s a lot cheaper to do human research in Mexico to look at those very questions. No one has looked at that. Big Pharma came out with these random doses, right? It’s like you can use 100 if you’re using oral, which of course, metabolized also, but if you use 100 or 200, oh, that’s only a double dose. I mean, like what is that?

Dr. Gersh:           The answer is we don’t know. That’s what’s so terrible. That’s why the Women’s Health Initiative set us back decades in terms of women’s research. We can use progesterone cream, but we don’t know what we’re doing. I mean, the bottom line is that we are all now, either ourselves or our patients, a little bit are guinea pigs because we don’t have published data on any of this. What we have to start with is just making it clear that women’s health matters and that we have to get more research on this. Otherwise, we’re just flying by the seat of our pants because we don’t have data on any of it.

Dr. Weitz:            What about trying to measure uterine lining thickness?

Dr. Gersh:           Well, that is something that can be done, but what’s interesting is how variable that response is in women.

Dr. Weitz:            Okay.

Dr. Gersh:           You can give the same dose to women and get quite different responses. Certainly, if you get a level, a thickness that’s like three centimeters, you did something wrong. A lot of times, like if you’re doing rhythmic hormones, what you end up looking for is clinical results. You end up looking for a woman having a regular period like lead, and it’s about the same amount. It’s at the right time, so you’re almost using clinical guidelines more than any kind of blood, urine, or salivary measures because we really don’t know what we’re doing, and I have to be honest with my patients about that too that I can’t create data if it doesn’t exist.

A lot of times, we do end up treating clinically and saying … which is not optimal, but it’s what we have like, “How do you feel? Do you feel like you felt when you were 25? Are you having periods like when you were 25? Are they regular and so forth?” because we’re having to use human metrics rather than lab metrics for some of these because we don’t know what we’re doing. We don’t even know what the correct lab test is. It’s that bad.

Dr. Weitz:            What about the 60 or 70-year-old woman who avoided hormones and now wants to consider taking them? What advice to give then?

Dr. Gersh:           Well, number one, you have to always people that whatever you’re doing, you’re not standard of care, and so the standard of care is terrible care, but it’s very difficult when standard of care is women should have no care. It’s really how I see it. You have to be telling women that. Also, we do know that estrogen receptors do shrivel with time. The serotonin receptors, which are actually estrogen-dependent in the brain and also in the gut are very much going to shrivel. We don’t know how to bring things back when they’re too far gone, when they’re too off. They’re dead.  It’s like hair follicles. You can do so much to restore hair, right, with like PRP. If the hair follicle is dead, it’s not coming back. If you have some neurons that are really gone making serotonin, you have estrogen receptors that have really shriveled up and they’re gone, then we’re not going to bring them back to life, but we know from vaginal treatment. I use this as my beacon of hope. Okay? If you take a woman at any age and you give her vaginal estriol or vaginal estradiol, she’s going to have improvement.

What that tells me is that receptors are not dead, and you could do this in a woman who’s 70 or 80. You’ll still have some improvement. You won’t have a vagina that’s like a 25-year-old, but it’s not going to be maybe the 70 or 80-year-old one that it was before, so there is still hope. I tell women, “Is it optimal? No, but the receptors are not all shriveled up. Some of them are still there, and we can work if you want to and give it to them.”

We know that Dale Bredesen certainly at every age to try to do his Alzheimer’s reversal program has been giving estrogen to women at every stage in order to help their brains because there’s estrogen receptors all over their brain, every different part of the brain.  I felt that that was really encouraging for us because we’re less out on a limb. If we can say, “Well, you have some memory issues like who doesn’t, right?” and then you say, “Okay. Well, this has already been established by Dale Bredesen, and he has very big clinical status and so forth. He’s respected, and he’s giving estrogen to women at any age to help their brains, so now, I have at least a leg to stand on.” As long as my patients understand that, I will start, and because the receptors are pretty much in hibernation, we might say, I usually with an older population, I will start low and work my way up like we would do with thyroid, right?  If someone is severely hypothyroid, we don’t start them out on the physiologic final dose. We start them low and work our way up, and that’s what I do. Do I have any guidelines? Do I have clinical data? No. I have just my own experience for this, but for older women who’ve had a big gap, and certainly, that’s not what they did in the Women’s Health Initiative, of course, I would start them and try to build up their receptor function and work my way up rather than starting high. Whereas totally different if a woman is pre-menopausal or right at menopause. I’m not going to start them low. I’m going to start them at physiologic levels.  I mean, this whole idea of the smallest dose, that’s crazy.  We want the right dose, and the right dose is a physiological dose, so I’m going to go with higher dose. It’s not high, high. I mean, talking about this whole low dose notion is junk science.  That’s not … but I do different things in different age groups.  Certainly.  Older people, I’m going to be generally starting.

Dr. Weitz:            I know it’s a big topic, and I know we only have so much time, but what about testing for women with heart disease?  Should it be different than testing for men?

Dr. Gersh:           Well, I tend to not do so much in terms of calcium scores. I don’t think that they’re as useful in women as in men, and they just look at the calcium, and women as we know … Many women who die from heart attacks, they don’t even have severe amounts of atherosclerosis. They die from spasm. Right?  Sometimes, it’s called broken heart syndrome. I really want to know what their blood pressure is, how it responds.  I think that’s really, really important.

We know that by age 75, 85% of women, especially if they’re not on hormones, they are going to be hypertensive, and women have very, we’ll say, very powerful autonomic nervous systems, and emotions can cause spasm of their arteries, so just getting a calcium score doesn’t really have very much predictive value, and we know that doing echo stress tests has virtually no predictive value in women in particular. I like to do carotid intima media. I like to know what the status of their arterial health is and if they have inflammation in the intima and if they also have a lot of plaque, recognizing the limitations of that as well because plaque never kills anyone. It’s ruptured plaque, and it’s arterial spasm, and it’s having that extra clottability. That’s really where it’s at.

I definitely want to look at inflammation, so I use labs that look at inflammation because we know that without inflammation, you’re not likely to have ruptured plaque, and so for women, we want to work with their emotions. We want to have them have the tools so that when they feel stressed, they know what to do even if it’s simple yoga breathing because stress kills women. We know that, and so I want to know the status of their arteries, and I’d like to do echo cardiogram. This is something that isn’t really talked about.

Women have very different hearts because of all the estrogen receptors and the loss of estrogen, and it really changes the heart muscle dynamics. One of the earliest signs of cardiac problems, actual heart muscle problem, a deficiency of energy in the heart is what’s called mild diastolic dysfunction. It’s really a stiff heart. You can actually see it on an echo cardiogram. The heart has two basic functions, contract and relax.

Well, we always have focused on the contract part, right? That doesn’t pump out the blood. Well, it turns out the relax part, when it feels is really key, and that has been ignored, and it’s even … I see patients coming from cardiologists with echo cardiograms, and on it, it says, “Mild diastolic dysfunction.” I’ll say, “What did your cardiologist say about this?” He said, “Oh, it’s normal.” No, it is not normal. Your heart is deficient in energy. You have a stiff heart. This really matters, and it’s really a sign of mitochondrial dysfunction in the heart muscle itself and loss of energy.

Of course, this all relates to loss of estrogen, and we need to get some estrogen going into that heart muscle because women often with mild diastolic dysfunction, they’re going to have higher rates of conduction defects within the heart go into more arrhythmias, which we know that’s what kills people is the arrhythmias, and they’ll get Afib, which we know is now at epidemic levels. It’s like the whole world seems to be getting Afib, and they’re more likely to get heart failure itself, so we need to like look at these warning signs.

I believe that it’s really important and as well, looking at the echo cardiogram, you can look at the heart valves because one of the things that estrogen controls is what’s called the enzyme matrix metalloproteinases. These are about tissue remodeling, and the heart muscle actually can remodel and not in good ways. It’s not like remodeling your house. This is like bad, bad, and so you get this hyperplasia of the heart muscle. You get remodeling, and it can actually move the heart valves so that they don’t fit together properly, and you can start seeing that on echo cardiogram.

I think the echo cardiogram is the very underutilized tool, very non-invasive, completely non-invasive to get a really good view of what’s happening in the female heart in the menopausal years so that you can really gauge what’s going on, and then hopefully, do something about it, but at least you need to let people know what’s going on with their hearts, and this isn’t even happening in the cardiologist’s office. They’re ignoring all this stuff. They’ll say, “Oh, you have a little regurge. Oh, you have some mild diastolic dysfunction. That’s normal.” It’s normal to have problems. I guess you could say that, but normal is like having cataracts. Well, people don’t ignore cataracts, so having heart dysfunction and calling it normal doesn’t work for me.

Dr. Weitz:            If women have mitochondrial heart dysfunction, then probably, one of the worst things you could do would be to prescribe a statin which is going to block your Coenzyme Q10, which is necessary for the mitochondria. Right?

Dr. Gersh:           Oh, absolutely and this … The two areas of the body that have tremendous energy needs and lots of mitochondria, of course, the brain and the heart, and we know that both of them are impacted by statins, especially in women, and women are much more prone to develop diabetes as well. It’s just statins have no place probably in very much of anybody, but certainly, the data in women is really bad. I mean, the number needed to treat to do anything is ridiculous. The number needed to harm is not very high. You don’t need to treat very many women to harm women.

I see no benefit in giving statins, and we even went through these committees. It was almost a tie. I mean, it’s not like it was overwhelming, and they looked at the people who were on the committees. They were all … Almost all of them were on the payroll. If they weren’t then, they became afterwards. We now know that the committees that approve pharmaceuticals are very uncontrolled, and many of the participants … I’m not going to say all, but many of them receive humongous amounts of money after the fact. There isn’t even any law regulating what happens after they approve the drug. None, or the recommendation that they give for how it’s used.

There is no control, so they could say, “I have no ties to the industry,” now. But then, after they approve it or they make recommendations, like two months later, they could be on the payroll of the big pharma company that makes that drug, and actually, that’s considered completely legal. We have a crazy system, so there’s been a lot of problems, we’ll say, with statins.

In terms of herbals, while you’re trying to get things right by giving hormones and lifestyle, one of my favorites is bergamot. I’m sure you’ve probably heard of bergamot. It’s from a citrus fruit, and there’s actually published data on it that bergamot can help to regulate abnormal lipids, and so that’s good. Remember, as people age, which is more associated with a higher mortality, low or high cholesterol, it’s actually low cholesterol because low cholesterol … I defend estrogen. I also defend cholesterol. I defend the defenseless.

Cholesterol is essential for life. It’s driving down … LDL is crazy. What you want is to drive down oxidized LDL, which we know is controlled by the enzyme PAN1, which is controlled by estradiol, so it’s like … This is like a dying duck. If you have estradiol, you don’t need to have low LDL because you’re not going to have oxidized LDL, and that’s what harms people, not LDL. LDL, if without enough LDL, your immune system doesn’t work properly. I mean, excuse me. Cholesterol is not there for no reason. Cholesterol is so precious to the body that we have a recycling mechanism in the gut to pull it back in so that we save it. That’s how precious cholesterol is. We want to keep it. We’d like to have cell membrane’s brain and steroid hormones.

Dr. Weitz:            Well, it is an amazing conversation. Unfortunately, I have to bring it to a close because I have patients coming up. I love talking to you though.

Dr. Gersh:           Yeah, me too. We could go on all day, but probably other people have things to do as well.

Dr. Weitz:            How can listeners get a hold of you?

Dr. Gersh:           Well, if people want to be my patient, I’m an old-fashioned doctor. I have a brick-and-mortar practice in Irvine, California called the Integrative Medical Group of Irvine, and the practice website is integrativemgi.com. I also have a little personal website where I put out … I attach like things like this, and other articles, and blogs, and you can find out information about my PCOS book, and that is just my name. It’s felicelgershmd.com. It’s pretty easy to find my practice or to find my own website, and if anyone wants to follow me, I welcome it. I just love educating, and having fun chats, and trying to get the word out, and defending the defenseless.

Dr. Weitz:            You’re such a wealth of information, and when is your book going to be published?

Dr. Gersh:           Probably, it will be out in November.

Dr. Weitz:            Okay.

Dr. Gersh:           It’s called PCOS SOS: A Gynecologist’s Lifeline to Restoring Your Rhythms, Hormones, and Happiness.

Dr. Weitz:            Great, great. Talk to you soon, Felice.

Dr. Gersh:           Bye-bye. Have a wonderful day.

Dr. Weitz:            You too.

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