Menopause & Hypertension: Key Insights

Felice Gersh, MD

Well, I’m great, and I’m so excited to discuss with you a topic that is so important, all about hypertension and women.

Laurie Marbas, MD, MBA

Yes. We were speaking before we started the discussion, all about perimenopause and menopause. I think not only is this the typical age that we see in general populations, hypertension increasing, but there’s a lot that could be occurring just because of the menopause entering the puzzle. I think we should start there. Go ahead. 

Felice Gersh, MD

I say this. Because so often the discussion is about aging. They say, Well, with aging, you’re more likely to have changes in your cardiovascular system that can predispose you to hypertension. But I don’t think of it as aging per se. I think of it as the accumulation of deficiencies that lead to vascular disease. Of course, hypertension falls under that heading. When you look at women, 100% of them will go through menopause. It’s not that you can exercise or meditate your way out of it. You may delay it a little bit if you eat the diet, but it’s not going to stop it. It’s coming. It’s a huge metabolic shift. Now, by metabolism, we mean the creation, distribution, and utilization of energy, and of course, the cardiovascular system is an essential requirement for being healthy and needs a lot of energy to stay optimally functional.

Estradiol. The estrogen that’s produced by reproductive-aged ovaries is underappreciated for its extremely important role in maintaining cardiovascular health. By the time a woman is suffering from high blood pressure, that’s not an early sign. That’s a significant event in the decline of the cardiovascular system. When you lose your estradiol, and of course it goes through this process that we call perimenopause, which we can discuss into menopause, which are all just definitions that were created in terms of talking about the process of ovarian aging or senescence of the ovaries and the eventual loss of the production of these vital life hormones. Estradiol and its sidekick progesterone, and the impact that it ultimately has on creating not only the loss of those hormones but also other deficiencies through its effects on, for example, gut health and how the GI tract works.It’s a snowball effect that leads to more and more problems relating to cardiovascular function and health. It’s such a big deal that that’s why I am so excited that we can go over this so that everyone who is watching, whether you’re a woman or not, knows someone who’s going through the transition into menopause or already they’re in menopause. Every single person needs to know the value and significance of hormones and what happens when their decline happens. It changes everything.

Laurie Marbas, MD, MBA

No, I appreciate that. Being someone in my mid-50s, now that the perimenopause-menopause transition is a surprise thing, I think the study was misreported, and I think we’ve done a lot of disservice to a lot of women when it comes to understanding the importance of estrogen and progesterone. Maybe we can explain the symptoms that can occur with perimenopause with us because I think a lot of those will affect hypertension, which is a complex situation. There might be other things: stress, and lack of sleep—they all impact hypertension. Can you explain what those transitions are? The definition. But what’s going on in our bodies is that we’re trying to figure out: am I another person since last year? What’s going on?

Felice Gersh, MD

Well, It’s, as you were just saying, it’s the perfect storm. Every single organ system is affected. It’s important to know that I consider, and then everyone else will hopefully know by the end of this little interview, that estradiol is the master of metabolic homeostasis. It keeps everything humming along properly, and there are receptors in every single organ system. When you lose your estradiol, every single organ system is impacted. One of the first signs and classic signs of estrogen deficiency is the famous night sweats and hot flashes. Now, how is that even happening? What’s going on? Well, it turns out that we have these centers in the hypothalamus that regulate all kinds of metabolic functions, one of which is temperature.

We have it. We call it the Thermal Regulatory Center. When you don’t have proper estradiol, it doesn’t work properly. That is partially related to the fact that the immune system is embedded in the brain. Of course, the hypothalamus and the thermal regulatory center are part of the brain. You have what is called neuroinflammation. The immune system of the brain is not properly controlled. When you don’t have enough estradiol and you get this inflammatory state, in addition, you have a low level of inflammation throughout the body because the immune system is managed, or, you might say, modulated, by estradiol, and without estradiol, you don’t have the proper regulation of inflammation. Estradiol is what I call the master of the switch. It turns on inflammation when you need it. For example, you’re being invaded by a pathogen, a bacteria, or a virus; you’re injured; you have trauma; you have burnt or broken tissue; you have infected tissue; and you have damaged tissue. Those are the things that create the onset of inflammation appropriately, and that’s all managed by estrogen. Then estrogen turns the switch to the off mode so that it causes resolution of inflammation and healing. When you don’t have optimal amounts of estrogen produced by the ovaries, then this whole system of on-and-off switches where inflammation is not properly managed gets stuck in the default, which is inflammation. 

You have this low level of inflammation in the body. It affects the gut as well. You have altered gut microbial populations that we call the gut microbiome, which leads to an impaired gut barrier and a leaky gut. It’s very involved and complex and involves all the organ systems, but you ultimately end up with some degree of inflammation in the brain. Then, to compound it, there’s a system in the body called the autonomic nervous system. That’s what controls all the things we don’t think about our temperature, our pulse, whether we’re sweating, motility of the gut, digestion,  and all of those things. Thank goodness. But they’re controlled through this autonomic nervous system. Now, the neurotransmitter pairs of the autonomic nervous system are controlled by estrogen. When you don’t have enough estrogen, you don’t have the proper production.

For example, the neurotransmitter that keeps things humming and quiet and calm is the default system that should be in place, which is peace in the body. That’s called the parasympathetic part of the autonomic nervous system, and its neurotransmitter is acetylcholine. Without adequate estrogen, you don’t make enough of that neurotransmitter. You end up in a more sympathetic or stressed state. That’s the other side—the other half of the autonomic nervous system. That’s why you get this dysregulation and end up with temperature problems, and you have the night sweats and the hot flashes. You can also have other parallel things like palpitations, which are also controlled through the autonomic nervous system and their effect on the heart. You can have problems with your bladder, and you can have problems with digestion. All of these things are under autonomic control through parts of the neurological system that we don’t think about. All of these become somewhat dysregulated when you don’t have enough estrogen. Now we know women who suffer from the worst night sweats and hot flashes have a higher risk of ultimately having strokes and heart attacks.

It’s not just miserable in itself. It’s foretelling potential added risk. Of course, there’s nothing that can be worse for the total body’s health than lack of sleep. When you have night sweats and you have to change your sheets and your pajamas and everything because they’re soaking wet at night and you’re waking up and you’re not getting any of the proper phases of sleep happening, then that leads to everything else going awry. We know that sleep deficiency and deprivation will increase the risk of depression, anxiety, diabetes, hypertension, heart attack, stroke, and weight gain. Then, when you have a lack of estrogen and a deficiency of sleep, you’re more likely to have weight gain. virtually every woman, even women that say, I’m doing everything I can, eating great food and exercising, why am I getting all this belly fat? Well, it’s because estrogen not only helps regulate sleep but also how fat tissue functions. The hormones that fat makes are called added proteins, which regulate appetite. That’s leptin and also adiponectin, which regulate fat burning. All these things go off-line. You end up once again in the default position, where you start to accumulate visceral fat, that inflammatory fat that’s within you, in your organs, and in the belly. You can see that you’re truly bringing up the perfect storm of things that happen when you have this decline in estrogen. It’s just not well recognized. 

That Women’s Health Initiative, which was a study that was done over 20 years ago using hormones, I wish we didn’t even have to use that word for them, because technically for a human, they’re endocrine disruptors, which are chemicals that don’t belong in a human body, that disrupt any potential aspects of how hormones work. It didn’t have the most optimal outcome, although, interestingly, for younger women, it was still better than nothing. It still did better than the placebo group. But the bottom line is that we can’t replace real food with processed food, and we can’t replace real human hormones with fake stuff. It’s the same as a parallel. It doesn’t work. We have to stop mixing apples and oranges. If we had done a study that was all processed food, we would have concluded that we should never eat food. That would be insane. But if you do a study, we’re using phony baloney hormones that would never be found in a human body. Then the conclusion is: never give humans bioidentical hormones. When you put it that way, it’s insane. We need to embrace and love our hormones and recognize that even though menopause is natural, it is not beneficial just because it’s natural. Remember, earthquakes can be natural, tornadoes, and tsunamis it doesn’t make our lives better. Everything natural isn’t beneficial. We need to take hold of the concept that menopause, though natural, is not beneficial. 

Hypertension, for example, by the age of 65, 75% of women have some degree of hypertension. That is terrible. By age 65, women surpass men in the incidence of strokes and ruptured aneurysms. These are not little things. Cardiovascular events remain the number one cause of female death, and much of this is preventable through proper hormone replacement during menopause supplementation during the declining years of hormones, the perimenopause, combined with essential lifestyle choices. It’s not one or the other. It’s the combination of hormones, which I call foundational to health. But just as you build a foundation for your house, you can’t move into the foundation. You need a house. You need the structure, the walls, the ceiling, the roof, and everything else. Hormones are foundational to health, but they’re not sufficient. They’re necessary, but not sufficient. You still have to do all the other lifestyle things to bring about optimal health and optimal health span, which I’m sure you’ve talked about—just living long, but living well. We have to embrace the role of hormones in women’s health. By the way, this is now being translated into male health and testosterone. There are more and more articles. I just had one published that talked about testosterone as having cardiovascular benefits. I just have another article that was accepted. I’m so excited because I keep trying to convince mainstream doctors that hormones are good. They’re good. They’re not bad; they don’t turn on us. I’m so excited when I can get my articles published in mainstream, prestigious journals to try to impact the mainstream of medicine that we have to rethink everything from that women’s health initiative, turn it on its head, and start seeing the benefits of hormone therapy along with all of the other lifestyle choices and sometimes pharmaceuticals.

When someone comes into my office and they have a blood pressure of 170 over 110, believe me, I’m not going to just say, Go home and eat vegetables and take your hormones. Those people need medical, pharmaceutical therapy, and maybe a lot more, and everyone needs to have. I love data. I’m sure you’ve talked about lots and lots of testing. How can you assess your risk and how can you look at your current status so that you can make personalized precision medicine decisions? But all of that should come into play. But the foundation is at least understanding that the loss of hormones is not about aging. The consequences of aging are the loss of hormones, the loss of sleep, the loss of proper nutrients, and so on.

Laurie Marbas, MD, MBA

I love that. Can you speak a little bit about the emotional, brain fog, fatigue, joint pain, and some other maybe less recognized symptoms of the perimenopause and menopause transition and how therapy or an integrative approach could help something like that? Because I think that’s what, besides the hot flashes, I call them internal solutions. Well, that was intense, but could you speak to that? Because I think those are the things that women will come, at least the ones I’ve seen, and I feel like I’m going crazy. It’s that you’re not going crazy. But could you share your approach to that?

Felice Gersh, MD

Absolutely. Just a small, little plug. My most recent book that I wrote is called Menopause: 50 Things You Need to Know Going Through the Three Phases of Menopause: Perimenopause, the First Decade, and All the Subsequent Years, where I itemize all the different myriad symptoms. It’s amazing, you said, all the different symptoms and problems that women can face that are related to menopausal hormonal deficiencies, and they’re not recognized. A mood disorder is certainly a huge one. When women go through this menopausal transition, the risk of anxiety and depression doubles. It doubles. It, for any woman, has a prior history. For example, she had postpartum depression, she had PMS, or she just had generalized anxiety or depression problems. Her risk goes up fourfold. This is a huge thing. For women in their 40s who are into perimenopause, the incidence of prescriptions being given to them is huge for anti-depressants and treatment for anxiety. Fully 25% of women in their 40s are now on an antidepressant. What is going on here? Well, it turns out that these hormones are very neuroprotective. It’s critical to understand. I had touched on, for example, one neurotransmitter, acetylcholine, which is important for the autonomic nervous system, for the vagal tone, what we call the parasympathetic. But in the brain, acetylcholine is about memory. You’re going to have brain fog, as you mentioned because you don’t make enough acetylcholine. Your memories are not being properly sealed. 

In addition, another neuron transmitter that’s very heavily impacted by estrogen is serotonin. That’s the happy-feel-good neurotransmitter that is hopefully, supposedly, increased in amount when you take an SSRI, these antidepressant drugs Prozac and Lexapro, and so on. Well, there are serotonin neurons in the brain that require estrogen for the proper production of serotonin. From serotonin comes the hormone melatonin, which facilitates sleep. Without proper estrogen in the brain, guess what? You’re not going to have proper production of these vital neurotransmitters for memory, feeling good, and then dopamine. I can’t leave that one off the list. That neurotransmitter, which is important for feeling good as well as having good mental health, is also impacted by estrogen. Tremendously so. 

These neurotransmitters, which we take for granted, require estrogen. What about oxytocin? That’s considered a neuropeptide or hormone. The difference is just the length of the amino acid chain. But oxytocin, which is essential for what? Well, appetite, regulation, and also the love and bonding hormone, as it’s often called. For having a proper orgasmic response, it’s involved in having a proper sexual response and having orgasms. Guess what? Their receptors for oxytocin are not functioning properly, and a hormone cannot have an effect if it does not work properly on the receptor. The receptors become more welcoming to oxytocin and more receptive to the presence of estrogen. Without estrogen, oxytocin doesn’t work properly, and it’s also not even made properly in adequate quantities. You’re not going to have that peace, love, and bonding. You may become what I call a victim of road rage. Without the road, you want to bite everybody’s head off. Then what? Why am I yelling at my kids? Why do I want to kill everybody? They didn’t do anything that bad because you had to talk about a short fuse. All of this is because you don’t have enough oxytocin. Estrogen is critical for brain function, cognition, and mood. They’re intertwined.

Women have at least two and a half times the incidence of Alzheimer’s disease as men at every matched age. At age 75, you’ll have two-thirds of all the people suffering from Alzheimer’s disease who are female. This is all hormonally based. This is not a little thing. This is a big thing. I’m so glad that you brought it up, because what is life without good health and brain function? You can’t be happy if you don’t have estrogen. Another very important function that estrogen has that is almost completely unrecognized is its role in the end-doe cannabinoid system. Now everyone’s heard of cannabis. Well, the endocannabinoid system is what cannabis works on. We have receptors in our brains and elsewhere in the body, but I will say in the brain for now, for talking about the brain that can bind these plants. Just we have fatal estrogens, estrogens, but they’re not estrogens. They’re molecules that combine with our estrogen receptors. You have cannabis that combines with our endocannabinoid receptors. Well, estradiol is responsible for increasing the product of the feel-good endocannabinoid called Anandamide. That is what helps reduce anxiety by the way THC, which is in cannabis from marijuana, for example, binds to the same receptor that our own produces anandamide, which is an endocannabinoid. These are lipid signaling agents that are derived from the fatty acid called omega-6. These lipid signals make our brain feel happy and reduce anxiety. That’s what THC in marijuana works on. I am not advocating for that. I am advocating for estrogen because it increases our production of anandamide, which lowers anxiety and makes us feel happy and peaceful. It’s amazing. By the way, this whole system is replicated in the reproductive organs. 

That’s why if you, for example, smoke marijuana, you increase the risk of miscarriages because there are receptors for the endocannabinoid system throughout the female reproductive tract. Everything is replicated everywhere throughout the body, and everything is related to estrogen. When I give talks, I often say I’m going to give spot quizzes here. You have to be ready, but I’m giving you the answer. The answer is always estrogen because estrogen is involved in every single function in the body. That’s why I just can’t stop saying enough good things about estrogen and trying to counteract all the negativity that has become so pervasive and so embedded in our medical system and the population at large.

Laurie Marbas, MD, MBA

I know. It’s a very complicated system. The more I dived into it, the more I saw the disservice in which I was training during the time that it was concluded. I was at the forefront of the newly minted doctors—no HRT, no MHD, none of that. It’s interesting. Now I take it upon myself to educate myself, but also, for example, I’ve mentioned my daughters, who are physicians, I’m like, Are you aware? No. Well, I’m going to make sure that you get this too with your friends. It’s fascinating. But, yes, it’s a good point here. I think I just want to say thank you to everyone for joining us today. But I hope you find this conversation insightful and engaging. If you’re a summit purchaser, you can stay right here because we’re about to dive in a little bit deeper I want to ask how you determine who and what is prescribed. We’re going to get into a little bit more nuanced discussion about it. If you’re not, you can go ahead and click on the button below to the side and get access to the rest of the conversation. Now, if you’re watching this, thank you for being a valuable member of our community, and let’s continue our conversation. Dr. Gersh, can you speak to us a little bit about having someone in their offices symptomatic of menopause or perimenopause? How do you determine if someone is a safe candidate for any type of hormone replacement therapy or hormonal therapy at all? Is there anyone who isn’t? How do we approach that? What questions should they be asking their doctor to maybe broach that subject?

Felice Gersh, MD

Well, happily, the vast majority of women are excellent candidates for hormone therapy. There are just a few groups—very few. For example, if they have breast cancer. Now, I just have to say that hormones don’t cause breast cancer. They do not. Inflammation underlies cancer because it creates DNA instability. Estrogen helps prevent breast cancer because it promotes what we call autophagy, or cellular renewal. It also promotes what’s called appropriate apoptosis, or what we call programmed cell suicide. When you have senescent cells, they’re old, they’re yucky; they have what we call misfolded proteins. It causes those cells to self-destruct. You get rid of those potentially pre-cancerous cells and estrogen in the form of estradiol. That’s what triggers these things to happen. When we have a lot of benefits from, for example, fasting, which is so trendy now, but appropriately so, fasting can trigger a lot of these mechanisms as well, but they don’t work properly if you don’t have any estrogen. It’s important to know that breast cancer is not caused by estrogen. But if someone has active breast cancer, they’re undergoing treatment or may be metastatic. Those are not candidates for hormone therapy because of the potential of their hormonally receptive positive that taking hormones may stimulate their growth. It’s because everything becomes hijacked when you have cancer; that’s a whole complex conversation. But other than that, as long as you give the estrogen transdermally, that means through the skin. 

There are very few other absolutes, and you can’t get out of them, contraindications. Only oral estrogen, for example, increases the risk of blood clotting. That’s an important takeaway. There have been many studies and a lot of data—observational data as well—that show that when you give estradiol through the skin, it does not in any way increase blood clotting mechanisms. Estradiol lowers blood clotting because it increases the production of nitric oxide, which is an antioxidant gas that also prevents the aggregation of platelets, clumping together platelets inappropriately, which can result in abnormal, inappropriate clotting. It increases what is called prostacyclin, which similarly prevents abnormal, inappropriate clumping and clotting of platelets. There are mechanisms in play when you have a proper hormonal balance that prevents just random blood clotting because blood clotting is part of the inflammatory response, and it’s very critical and lifesaving under the proper scenario. 

Estrogen, as I mentioned earlier, regulates and modulates the on-off switch for inflammation when you don’t have the right estrogen estradiol, or if you don’t have enough. Then you get into this proinflammatory status, which includes blood clotting. Okay. That’s part of the inflammatory response. Most women can take hormone therapy. When do you start it? Well, I started now. I didn’t always do this. I started in the perimenopause because once we understand that this whole process is over time, it’s that they define menopause as 12 consecutive months without an arbitrary period. You could have said 13 months. You could have said eight months. It’s just made up. But it’s a process. Instead of thinking you’re hitting a finish line and now you’re in menopause, it’s a process of ovarian aging, and it can go over many years. At this time, bad things are already happening. We know that when you look at the vascular system for ultrasounds, for example, you’ll see changes in the lining; what we call the intima will become thickened and inflamed. You’ll see plaque formation developing during perimenopause, and you can lose a significant amount of bone before that official menopause because it’s a time of estrogen in irregular production. But ultimately, decline. You’re changing your bones, you’re changing your joints, you’re losing collagen, and you’re losing elastin. Everything is less flexible, and almost every woman has problems with word-finding, particularly nouns. We’re very good at adjectives and verbs, but not very good at nouns. We can’t. What was the name of that thing? I can’t remember. I now give hormones; I call it hormone supplementation. During perimenopause and then hormone replacement, When you have no estrogen, no progesterone, that’s full of hormone replacement in the menopause. How long should this go for? Forever. For the life of the person. It’s irrational to think that you should stop it. 

I make the analogy with the thyroid. When we give thyroid hormone, we’re not giving it to people who typically have no thyroid. That does happen. Sometimes we have to take out the thyroid surgically or destroy it with radioactive iodine. However, the majority of people who are on thyroid medication have a functioning thyroid. It’s just suboptimal functioning. It’s thyroid supplementation. then we would give it if, for life, we don’t say, now you’re so old, we’ll just stop it when the irrational why would we not treat a hormone from the ovaries the way we would treat hormone from the thyroid? It’s part of the endocrine system. If you’re deficient in a hormone, replenish the hormone. That’s what I’m going to do starting when this hormone is in an insufficient state, which is the perimenopause, which is years before, and how do I determine it? Combination of testing and symptoms. If a woman is having symptoms that are completely aligned with perimenopause and I rule out that they have a thyroid problem, an infection, or something else as the cause, then that’s what it is.

We don’t have a definitive perimenopausal test, but we can do one. I do this all the time. It’s a test called menstrual mapping that involves multiple collections of urine during a cycle. This could be a woman who’s still having regular cycles. But what I can do is measure her progesterone, her estradiol, and the LH luteinizing hormone that comes from the pituitary, and it maps out as a whole menstrual cycle. I see multiple hormone levels for a whole cycle, and I can see maybe she is not producing enough estrogen, maybe she’s not producing enough progesterone or both. That’s why women, for example, who are 45 and are still having regular cycles, have fertility that is not the same as that of 25, yet they’re having regular cycles because their eggs are old, they don’t have good-quality eggs, and they’re not producing hormones in the same way. I’m going to supplement those women, and they feel better and are healthier. It’s a combination of everything. Everything gets better. 

Then in menopause, as I give virtually all women except those in that small group that have absolute contraindications, or, unless they don’t want to, I don’t force anyone. I just try to tell them the facts, and then they decide. I give virtually all the hormones; of course, patients tend to see me because they want hormones. I give them hormones, and I try to give them physiologic levels. I want to recreate hormones to be at the levels that a healthy woman would have when she’s in her early 20s. Why am I trying to replicate the hormones of a 45-year-old? I don’t want to replicate it, but I can’t. Okay. I’m just saying I’m going to do the best I can. That’s why it’s a lot better than not having hormones. But what I can’t do, not yet, is give a new set of 21-year-old ovaries. We do the best we can, which is pretty darn good. I want the hormones to be cyclic. I want to continue women having periods and have them embrace their periods because that is just how we’re made. That’s how we’re healthy. That’s another whole long discussion we don’t have time for. What happens when you have rhythmic hormones versus just static hormones? 

But here’s the goal. We don’t want to recreate something that never existed. We’re trying to recreate when you were healthiest. We’re not trying to create a whole new paradigm for how women should have hormones. Nature knows best. We want the hormones to be similar to what a healthy 21-year-old female would have. That means cycling. It’s just how it is. Progesterone downregulates estrogen receptors. We don’t want to give progesterone all the time. We’re turning off the estrogen. If we try not to have any periods, it means we have to give estrogen at such a low level that we’re not creating growth in the uterine lining. Well, guess what? The growth of the uterine lining is reflective of more than just growth; we could also call it rejuvenation, repair, and regeneration of other tissues in the body. It is what it is. We are cyclic creatures. We need to be optimally healthy to recreate the cycle we keep going back to. We don’t want to create fake food. We don’t want to create faux hormone regimens. We want our hormones to be as close to nature’s best as we can. When we do this, we can slow the aging process. We don’t stop it, but we slow all the things that are associated with aging, which of course includes hypertension.

Laurie Marbas, MD, MBA

Now, I think that’s a wonderful way to conclude our discussion, that you’re providing longevity through the appropriate use of hormones, lifestyle interventions, and everything else in an integrative manner. This is fantastic. Thank you so much, Dr. Gersh, for sharing your wisdom and information with us today.

Felice Gersh, MD

My pleasure.