Ep. 570 We’ve Been Wrong About Progesterone! – The Most Powerful Hormone for Heart, Brain & Longevity with Dr. Felice Gersh | Menopause & HRT

Welcome to Everyday Wellness Podcast. I'm your host, Nurse Practitioner, Cynthia Thurlow. This podcast is designed to educate, empower, and inspire you to achieve your health and wellness goals. My goal and intent is to provide you with the best content and conversations from leaders in the health and wellness industry each week and impact over a million lives. Today, I had the honor of connecting again with Dr. Felice Gersh, who is just such a prolific voice in the integrative gynecology space and truly a mentor and someone I respect enormously. We had a very lengthy conversation, which I have divided into two episodes. Today, we spoke at length about the value of progesterone and the systemic wide effects, the differences between synthetic bioidentical hormones and the women's health initiative, specifically the role of progesterone and cardiovascular disease health and the importance of nitric oxide production, ovarian senescence and aging and key ways that we can accelerate the aging of our ovaries, how the loss of nitric oxide production equates to aging, looking for ways to find optimal health and menopause, the impact of PCOS and fertility and longevity, and last but not least, the impact of estradiol and progesterone as they modulate neurotransmitters and impact brain and cognition in perimenopause and menopause. Stay tuned for my second conversation with Dr. Gersh. This is absolutely positively a conversation you want to listen to more than once. Dr. Gersh, such a pleasure to have you back on the podcast. We were so happy to have you here today. We're so happy to have you here today. We're so happy to have you here today. It's a pleasure to have you back on the podcast. We were speaking at A4M and we were speaking around particular topics that you were feeling emboldened to make sure that women were aware of. And progesterone came up and I think progesterone is really a misunderstood hormone. I still have patients and women in my DM saying things like, I don't have a uterus. My physician, my nurse practitioner, my PA told me, I don't need to take progesterone and perimenopause or menopause. And so I think it's just fodder for really important discussions like the ones that I have with you that help women understand that progesterone is more than just a hormone that protects our uterus. There is so much more to how it protects our brains and how it interacts with the microbiome and how it interacts with every system in the body. And so I'd really love to engage you in the conversation so that we can be even heart and bones. I mean, progesterone is a very important hormone that hormone, as we navigate the perimenopause to menopause transition, if we aren't replacing it, I think there are some significant health effects that many women may be unaware of. Absolutely. And it's also, I call it the beautiful dance between these hormones and another hormones. It's all like this beautiful web of life. And every time we think we're smarter than nature, we usually find out we weren't. I always say the biggest failed experiment in that we're smarter than nature is ultra-processed food. We'll make food that never spoils for 100 years or that tastes better than real food by adding more salt and more sugar. Where's that gotten us? Well, creating hormone regimens that are incompatible with physiology the way we evolved is also, I think, a very big failed experiment that really hasn't seen the light of day yet. I mean, it's just been accepted that, for example, like you mentioned that, well, you don't have a uterus, you don't need progesterone. Because after all, what does progesterone do anyway? You know, it just gives you periods. Well, you don't have a uterus, you don't have to worry about that, and you don't have to protect a uterus that doesn't exist in you any longer, right, from developing adenocarcinoma of the endometrium. So that's a faulty way of viewing the way the body and the female works and the way these hormones work. And so I'm glad to open up the dialogue about these vibrant hormones. I call them now life hormones, not sex hormones, because they are the hormones that give life and maintain life. Well, and I think that distinction is really important because for so many years, we just use them as sex hormones and we talk about bikini medicine and how, in many ways, people were thinking, oh, you know, whether it's testosterone, estrogen, progesterone, they're just for the genitourinary system. They're not for any or for pregnancy or for a menstrual cycle and now acknowledge that they are very important, very profound hormones. And there is an influence on, like, I think about the impact of progesterone on the cardiovascular system, which I know we've had conversations around this and how it's important for endothelial function, it's important for vascular health. And I think that a lot of women don't even understand that progesterone also moderates sympathetic tone in the body. And so when we lose progesterone as we're kind of navigating the beginning of perimenopause, women can get palpitations. And I think back to even when I was a new nurse practitioner, how I lost opportunities to help women understand that, you know, those palpitations may not be attributable to just your caffeine intake. It could very likely be where you are in your menstrual cycle, could very likely be the withdrawal of progesterone at the harkening of beginning of perimenopause and then also in menopause. And so I'm curious for you, when you're looking at cardiovascular health, metabolic health, where does progesterone play a role in your conversations with your patients right now? Well, very much so. And I'd like to just take one second to back up on how did we get into this problem of, well, no uterus, no progesterone? Because a very significant percentage of women do not have a uterus. A hysterectomy is one of the most common of all surgeries on women in general, just as all surgeries go. Well, back in the day, and the realities I remember these days, so they're not historical, they're my memories. And that's sort of one of the advantages to having been around for a while. And that is originally when estrogen started to be used, we didn't have the ability to create bioidentical hormones, like hormones that are identical to what the ovaries produced. So we did the best we could. Historically, the original estrogen that was produced was from grinding up cow's ovaries. Then we went to cow's placentas, then we went to the urine of pregnant horses. And that was what created what we call conjugated equine estrogens. The brand name was premren. Okay, so premren was the only real form of estrogen that was given. And it was like, I think I got FDA approved around 1942. So we're talking, I wasn't like in medicine in 1942, I didn't exist in 1942. That's when, so my memory just didn't go back that far. But that's when premren came on the scene. And then it became more and more popular. And around the mid 1960s was when there was this sort of like big like epiphany of hormones are in estrogen was the hormone of that was talked about. That was the hormone that everyone wanted. And because it was recognized that it had many functions in the body and that it was really important for women's health and it became very popular. And so premren alone was prescribed. Uh-oh, then in the 1970s, it was found that there was an increase, something like seven times increase, but it's still in terms of absolute numbers, actually very small, just so you know. But you know, you can multiply something by any number, but if the number you're multiplying it against is actually low, then even multiplying it by like a number of seven is still going to be quite low. But there was this increase and it's statistically significant, of course, increase in the incidence of the creation or instigation of adenocarcinoma of the uterine lining, the endometrium. So it was like, oh, that's terrible. So the use of premren dropped a lot. And then it was found that you could use a synthetic progestin. Okay, so they made up the word progestin. Okay, and that was what became used in birth control pills. Another story for another day, you know, why did they use progestins in birth control pills? And then that's actually the foundation of how they work. So, but why did they use progestins? We didn't even have progesterone. Remember, this is back when we did not have the ability to create human identical hormones in a laboratory. So they then found that one of the progestins that's called medroxyprogesterone acetate. So it has to word progesterone in it, but it's not progesterone at all. Okay, it's a synthetic, it's technically an endocrine disruptor for progesterone. It binds and acts on the cells in the uterine lining very profoundly. So it acts as a progesterone mimic, even more powerfully than real progesterone does, on the uterine lining to convert it to what's called secretory transformation stage. So it converts the uterine lining to be like prepared for like a pregnancy for an embryo to implant, or it prepares it for what you might call the perfect period, so that's what was used because it countered the proliferative or growth effects of estradiol, which are really important to know that growth is really important for life. So when we talk about growth, we're not just talking about growing things, like in the uterine lining, it's proliferation, it's literally growing the uterine lining, but elsewhere in the body, growth factors, which are very key to one of among the many attributes of estradiol and estrogen, is that it creates growth factors that restore, rejuvenate, maintain all the different tissues of the body, and of course, activate stem cells to work so that you can create new cells when old cells become either very bad, senescent cells to get rid of them, or they die, right? Because all cells, except a few in the body, do live and die and get replaced. So we added then medroxyprogesterone, and that became the standard. And then you had Prem Pro that came about, that was a combination of premrin and progesterone mimic the progestin, medroxyprogesterone acetate in a single pill. Originally, they gave the premrin, and then they would give typically 10 to 12 days of the medroxyprogesterone acetate, brand name provera, to create a cycle or a period. And then they found that they could give a lower dose of the premrin with a continuous dose of the medroxyprogesterone acetate for the purpose solely of alleviating symptoms of night sweats and hot flashes, okay? Not for any other purpose like for health at that point, but we hope that it would do more, okay? That like, oh, it definitely was approved by the FDA quite early on for prevention of osteoporosis. Okay, so then we had the HER study, which I won't get into, that was testing women who had known cardiovascular disease, and it found that when you use Prem Pro, it increased the incidence of cardiovascular death in the first year of use. And then they did the Women's Health Initiative also using Prem Pro, and they found that there was some increase in risk of things like stroke and blood clots, and there was a misinterpretation, and we'll go into all that. I bet you've had plenty of that on your podcast, talking about that, but this all leads into the whole progesterone story. So anyway, after the Women's Health Initiative, and also the whole thing with the whole point of adding medroxyprogesterone acetate, the whole and sole point was to prevent the increase incidence of the development of uterine cancer of the anemitrium. So since it was also then seen that medroxyprogesterone acetate wasn't a health pill, it had some significant side effects that were undesirable, and then it also, in the Women's Health Initiative, was shown to probably, and like was, the culprit for a lot of the harms that were actually found. So the bottom line is the whole issue with the synthetic, not human, endocrine disruptor, MPA, medroxyprogesterone acetate, sort of spoiled the whole landscape for progesterone. So it was never looked at, like why is progesterone even here, other than to counter the effects on the endometrium of the proliferation, the growth factors of the estrogen? And so when you don't have a uterus, you just stopped using medroxyprogesterone acetate, and then when that fell out of use and progesterone, human progesterone became standardized as a much better superior replacement, it still was, go away if you don't have a uterus, and it still is that way. That is the standard of care. If you don't have a uterus, you don't use progesterone, forget medroxyprogesterone acetate, no one should you be using that as part of their hormone replacement regimen. But progesterone, that's why this happened in the first place. Okay, it all was because of the badness of medroxyprogesterone acetate, and it's only used being to counter the effects of growth on the uterine lining and the potential increase of cancer. So it turns out that nothing in the body that is made by the body is a single purpose. There's no enzyme, there's no peptide, there's no hormone, there's no neurotransmitter. There's nothing that does one thing in one place. I mean, so that sort of is a universal role that I want everyone to take away with, that there's nothing that is only doing one thing in one place. In fact, the more you study all of the different systems, you see the replications of the different systems in terms of how they work and how they intervene in the reproductive system. Everything works in the reproductive system in some way. But then in other systems, like in terms of the neurological system, the cardiovascular system, the musculoskeletal system, genital urinary system, everything. And there's nothing that isn't involved in all these systems. And progesterone as well. So progesterone has functions and receptors in many systems of the body. And of course, there's a lot we don't even know yet, because it hasn't been the subject of enough study. And that's one of my main goals is, of course, to get more studies on everything, including progesterone. But in terms of the cardiovascular system, we know that progesterone is very important. And there's always direct and indirect. So if we just talk direct on the vascular system, there's a very important gas called nitric oxide. And the enzyme endothelial nitric oxide is very key and involved with estradiol. But most people don't know it's also very involved with progesterone as well. So progesterone also increases this vital gas. Now, what does nitric oxide do? Well, it blocks the aggregation of platelets so that you don't have inappropriate blood clotting. The opposite of madroxyprogesterone acetate and pretty much all the other progestins, the fake, we'll call them fake progesterones that are out there. They not only don't do what progesterone does to create more of this amazing gas, nitric oxide, which I'll tell you more about what it does, but they actually block its production. So it's the opposite of good, also called bad. So it does very bad things for the vascular system. So nitric oxide helps maintain the integrity of the lining, the intima, and maintains vascular dilation so that you don't have constriction of your arteries. So it's maintaining nitric oxide, which is like you can think of it almost as a hormone in itself. It's a signaling agent. Some people even consider the decline of nitric oxide as the basic definition of aging. There's many, what's the definition of aging? There's the mitochondrial and there's the telomeres. Some, but there are experts in the world of anti-aging and age management and all of this, and that think of the loss of nitric oxide as the definition of aging itself. So everything that we can do to maintain optimal nitric oxide is very, very critical. And it's involved in neurological functions. So there's every nerve has what's called a myelin sheath. It's like the insulation for the nerve. Now there's a disease state that's really terrible that is of 80% in women. It's one of the autoimmune diseases called multiple sclerosis. And in multiple sclerosis, what happens is we make antibodies that destroy our own myelin sheath. And that has repercussions that are severe and significant in terms of motor function of nerves, sensory, like so how you move, how you feel, and also the brain, okay? Because the brain obviously has neurons as well. And most people have no clue. I mean, even doctors, I mean, I would say generally speaking, that includes doctors, that progesterone is critical for the maintaining the health and function and structure of the myelin sheath. Now you mentioned the heart. Well, the heart is part of, you know, is interconnected with the autonomic nervous system. That's the key neurological system that is doing everything we don't think about. Like, can you imagine if you had to tell your body when to sweat, when your eyes to tear, when you should make saliva, you know, how your blood vessels should dilate and constrict, or when your heart should be, I mean, come on, of course we can. So that's all part of the autonomic. I think of it as automatic. So it's easy to remember automatic, autonomic. And in order for the heart to work correctly, in fact, every organ system to work correctly, you have to have healthy functioning neurons. And that means, you know, when you don't have enough progesterone, you're not going to have such healthy neurons because you're not going to have a proper maintenance of the myelin sheath. And that can affect conductivity. They're like the heart beating, right? So it can have a variety of repercussions, much of which has yet to be actually thoroughly investigated. And we know that estrogen, of course, is also critically important for the issues here of the autonomic nervous system because the main neurotransmitter of the parasympathetic nervous system is acetylcholine. That's the neurological signal, the neurotransmitter for the vagus nerve that maintains calmness and so on. But it's all interconnected with estrogen and progesterone are interconnected. So we'll deal with that in more depth. But just as an overview, you can already see just in these few words, these few minutes, how progesterone is not just about the uterine lining. You know, it's like about maintaining the health of the vascular system, the neurological system. And it gets even more in detail. Like for example, we'll talk more about neurotransmitters in the brain, like, you know, the GABA and so on. But in terms of seizures, and we'll talk why that is, there's actually a condition that's called senior seizures. That's also not talked about enough, but neurologists see it. And that is also dampened down the incidence of seizures as people age. And that is very important because obviously, how are you going to have a quality life if you're having seizure problems, right? And seizures damage the brain as well. So it turns out that without adequate progesterone, you're more likely to develop these senior seizures. And there's quite a bit of data, and there definitely needs to be more research done on the role of progesterone in terms of healing the brain in post-traumatic brain injuries. So it turns out after people have traumatic brain injuries, that having high doses of progesterone can help to prevent inflammation, swelling, and further damage, and helps to promote healing and reduce that post-trauma inflammation. And we'll get into that, so I don't give a two-hour lecture just on the role of progesterone and the immune system. So I'll see where you'd like to go with all of this. It's a big topic, and it's so poorly understood, all the interconnectedness of progesterone and all the systems on the body. And then we'll touch on how progesterone and estrogen affect each other's receptors too, if we have time. If you're in perimenopause or menopause and are feeling more fatigued, dizzy, lightheaded, struggling with headaches, or noticing your workouts feel harder than they used to, electrolytes may be part of the missing piece. As estrogen declines, we lose some of the fluid regulating and vascular protective effects that hormones once provided. 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You'll learn why the same diet that worked in your 30s may not work now, how your gut influences hot flashes, mood, and weight, the truth about fiber, protein, and blood sugar in midlife, and the daily habits that help your body feel safe, stable, and resilient again. If you're tired of blaming yourself for changes that are actually biological, this book will help you understand what's really happening and what to do about it. You can pre-order The Menopause Gut wherever books are sold, and when you do, be sure to check out the special pre-order bonuses I've put together for you. Again, you can go to www.CynthiaTherlo.com. You'll click on the banner. It'll take you to multiple options for where you can order The Menopause Gut in pre-sale. Yeah, and I think it's so interesting, and obviously listeners can appreciate why you've been a guest five times. I learn just as much as I know that listeners learn about all this interconnectedness. And from the perspective of you've been a gynecologist obstetrician for many, many years, in the wake of the Women's Health Initiative, which we have talked about quite a bit on the podcast, where most of your peers, did they go from prescribing both estradiol or estrogen and progesterone to no longer prescribing these medications? Were you someone that was questioning some of the information that was coming out post-WHI? Were you, I would imagine because you're an incredibly intelligent astute person, or were you someone that fell into that mindset of there are concerns about this interconnection between utilizing conjugated equine estrogen and MPA on the long-term effects for women in looking at the longevity and risk for other types of comorbidities. And for listeners, the term comorbidities is just looking at disease progression to these disease development. Well, I didn't know then, because now we're talking getting close to 25 years ago, right? I didn't know as much then as I know now about how these hormones work, the different receptors and so on. But I knew enough, and I'd been dealing with patients on hormones for a while at that point, that women felt so much better when they were on hormones. They lived better lives, they felt better, and they looked better. I mean, you could just see how it slowed what you might call visible aging from the outside. And they also didn't develop the same, well, visceral fat development, growing belly fat and losing their waistline. They maintained a much more normal body composition. They seemed stronger. They just looked healthier and behaved in a healthier way and had better markers when I tested them with their blood. And it made no sense knowing, of course, as a gynecologist, the variations that are so significant and when women go into menopause. And how could it be since the so-called normal menopause is from 45 to 55? And it's an arbitrary definition. Even back then, I knew like, what the heck? Saying that 12 months without any vaginal bleeding is the arbitrary definition of now you've arrived at menopause, like you're crossing a finish line. That made no sense because it's a process. I mean, it was so obvious to me 25 years ago that this isn't something that you're fine, you're fine. Then one day, you just stop ovulating. Then a year later, you're officially in menopause. It's not how it worked. It was obvious that there were women having symptoms in the years preceding that final period as well. And why is it that if a woman is 45 and she goes into menopause, which is called normal, or 55, which is also called normal, that the one who goes into menopause at 55 gets to have her hormones for 10 years more than the one at 45. And the one who gets at 45 shouldn't even have any hormones because they're so dangerous. But yet not for the one who goes into menopause at 55. So how can this make sense? And so I had been a very active member up until that point of some of the organizations like the American College of OB-GYN and what was called then the North American Menopause Society. I quit my memberships. I said, you are not supporting women. What your attitude, which was they went right along with the conclusions that became widespread at the time, which weren't even supported by the study itself. The study even said, this only applies to what we're testing. And back at that time, I mentioned, well, in the beginning, we didn't have bioidentical estradiol. We didn't have bioidentical progesterone. By the time the Women's Health Initiative was out and even before it was out, while it was underway, we already were transitioning. I had totally transitioned my patients off of Prem Pro by that point. And I was using bioidentical estradiol and bioidentical progesterone. So this was already being used. It wasn't like it was, oh, well, we had no other options. And this other option really was dangerous or bad. No, we had other options. And they chose to use Prem Pro in that study. They didn't have to. They just did because it was common and it was sort of supported by the company that was making Prem Pro at the time, I guess still does. And the bottom line is that most of us who knew anything were transitioned off of that Prem Pro onto bioidentical, human identical hormones by the time the Women's Health Initiative was even begun, let alone by the time it ended. So it wasn't an issue for me. It's like, of course, I'm going to keep my patients on hormones. I beg them. I said, please don't go off these hormones. You will live to regret it. Hormones are the life of women. Even then, it's like their life hormones, they give you life, they work not just on your bones. I mean, it was already recognized because it was FDA approved long before that for the prevention of osteoporosis. And even then, before I knew what I know now about so many things, that nothing works in just one place or two places. Like, why would estrogen, we'll just say estrogen, we'll use the generic global estrogen, why would estrogen only be good for having fertility and bones? I mean, it's like nature would do that. You have this whole hormone system and it's only good for fertility related stuff, reproduction and bones. It's like, that's impossible. It's got to be doing things even when I didn't know all the things that was doing. It's not just working on bones. It's working. Just look at the women on hormones, look what happens when they go off. Like, do you have eyes? How about the power of observation? Anyone who knew any woman who was transitioning through the whole menopausal transition saw that things were changing for her. Her skin was aging. Her bladder was changing. She was having more overactive bladder, more incontinence. Her blood pressure was going up. Her cholesterol was rising. This was a universal. She suddenly started having heartburn and suddenly she was getting gallstones. I mean, so many things were happening and of course, she was getting a lot of weight gain. Oh my gosh. Sleep problems, galore. Even the women who didn't have hot flashes had sleep disorder. I'd love to talk about sleep maybe another time because it's an under-recognized issue of menopause, really, not just unrelated to night sweats and hot flashes because sleep is not an optional thing. We now know that sleep is so critical for the brain clearing out the gunk. Another thing, we have two different systems in our body, the day system and the night system. The bottom line is that it was just obvious to me that there's so much going on with these hormones and we should be on them. In reality, which is really not the general statistics, by that point, fewer than after the women's health. When the women's health initiative came out up until that point, close to half of all women in menopause were on hormones, close to half. Now, after that, it was well under 4%. I don't know if it was 1%, 2%, but it was close to zero. It was just very, I know less than 4%, but very, very low. In my own practice, about 50% of my patients, virtually all of my patients were on hormones pretty much, not 100%. I would say 80%. And of course, there were some that had breast cancer. They had what seemed like legitimate reasons why they're not on soap. And then there were a few that just chose not to, or they came to me and they were 80 years old, not too many, but I wasn't starting them at age 80. So the bottom line is that of the users, which were the majority of my practice in that age group, about half of them stayed on hormones. So I felt really belly, but once I learned the statistics, it's like, well, that's better than by far most practices that went as close to zero. And I did have some patients come back a couple years later and say, this isn't working for me. I need to go back on hormones. You know, like I've suffered now. And because back after the Women's Health Initiative, the fear of hormones was so enormous that even women who had severe night sweats and hot flashes when they went off just struggled with them. You know, they just said, it's better to have night sweats and hot flashes. That's the lesser of the evils. Oh my gosh, I feel so awful for what those women went through and the harm that they suffered at the hands of the powers that be. These were mostly high level academics. And that's why I left those medical organizations because, you know, and I actually had, now I know, some people who stayed in them and they thought they would fight for women from within. And I, but they were not very successful. But I thought I would fight for women from without, you know, there's different approaches. I felt that I couldn't work within those systems. So I had to go on the outside to try to, you know, not be muzzled and to speak my thoughts. Well, and I'm so grateful that you care so much for your patients and don't subscribe to the degree of cognitive dissonance that I see that can be hugely problematic within the medical community. I say that lovingly as someone who has traditional training and then also integrative functional training. And I think that, you know, when I reflect on the patients that I had in the early 2000s in cardiology, that these women would be crying, talking to me either in the hospital or in the end clinic about how much they were suffering. And I was, of course, told by my colleagues to stay in my lane, but it left a really indelible impression on me. And I think for a lot of listeners, they have parents or loved ones that went through that, you know, early 2000s, post-WHI. I mean, really it came right at the time as I was finishing my training. And the impact that's left on my mother's generation is quite profound. And I think about not just these conversations, but other conversations I've had with you where we've talked about the influence of women going into menopause earlier than anticipated. And, you know, you mentioned this wide range of what is considered to be normal 45 to 55, but we recognize that stress and lack of sleep and even, you know, adverse childhood events can influence when women go into menopause. And I know that, and I hope that you're comfortable with me sharing your story. You had shared with me, you were up very late at night delivering babies for many, many years. And you said to me, I think this probably contributed to me going into menopause a bit earlier than I probably would have otherwise. And I reflect on me going in at 48, which to me seemed, although I'm on the spectrum of this is what's normal, certainly earlier than I had anticipated. And so I'm curious clinically, in your practice and given your extensive clinical experience, what are some of the things that can drive women into an earlier menopause that maybe some listeners may not be aware of? Well, think of the ovaries as very sensitive beings. And I do think this is really an important concept because we can really now, we talk about what is aging, right? And I said, well, nitric oxide, loss of nitric oxide, some view as aging, right? That's the epitome of aging. Well, I also am now looking at fertility and loss of fertility and ovarian aging as really aging itself for women. It really is. When women stop having ovarian function and producing those life hormones, that's really when the clock is really starting to tick. And it's almost like there's these two stages of women's life. And I really don't like to phrase it this way because I believe that since many women and myself would be one of them, I hope it will be, that will spend actually more than half their lives in the postmenopausal state, right? You too, right? You want to spend more than half your life in the, you didn't want to, but you will because you weren't even 50. And I was in my early 40s. So yeah, I definitely want to spend more than half my life given the early age I had menopause. And I don't want to think that, oh, these are like terrible years, you're going down the tubes, ladies and all that. But I think being honest about what's happening is the key to having resolution and to restore and maintain optimal health, you know, for optimal, healthy longevity. That's my goal, that's your goal, is that every woman can lead the healthiest and longest life and they go together, not just long without health and not health without long. We want the combination of the two, you know, so that we truly thrive in all the different decades of life. And so, you know, I think that it's really important for us to look at ovarian aging as really aging. Now, what causes the ovaries to age anyway? And that brings up like, why do we even have to go through menopause? Like, what the heck? Why did nature do that to us? Men don't, they have like, they do have decline in testosterone production, but some men can actually have good testosterone, you know, into their 60s, 70s, even 80s, you know, but women, there's no chance they're going to have ovarian function, you know, as the age of 60 would be like beyond extreme, you know, so the vast majority of women have lost their ovarian function before their 55. So anyways, so what's happening? Well, we're born with a fixed number of eggs, right? And that can be, you know, variation, somewhat genetic, you know, so that there's some variation. So between different women and their family lines and so on. So there's something that's built in a little bit there with the number of eggs you're bestowed. But then what happens to these eggs? Well, it's important to know that you can't save them like by going on birth control pills. I mean, some people that, well, I won't ovulate, so I'll save my eggs. It doesn't work that way. They degrade anyway. Okay, so going on birth control pills is not something that will prolong. I think that's important to know that's not going to work for you. Now, what can work for you is optimizing ovarian health, which goes along with total body health. There's actually a tremendous link. That's why when they talk about what's the fertility diet, well, it's called the good health diet, you know, it's a plant focused diet. You want to have lots and lots of antioxidants, polyphenols, fibers, nutrients, micronutrients, macronutrients. So you need to have all the minerals, the vitamins, of course. And then you also want to have, you know, adequate protein. But, you know, most people overdo protein, especially before menopause, they like go a little overdosed on protein. So, well, that's an ulcer. Yes, more conversation for another day. But you don't want to like, there's like that old cliche, too much of a good thing is a bad thing, you know, so everything is like the right amount at the right time. So what ages ovaries, which is really aging itself is inflammation. So the ovaries of women can actually be screened for inflammation. You can actually, like in women who have a lot of obesity, they're very inflamed. They have other disease states. If you take the fluid from around the eggs, the follicular fluid out, you'll find that in these unhealthy inflamed women, there's actually a lot of the immune cells, the white cells that we call the polynucleus cells of, you know, like leukocytes of all kinds. You'll have neutrophils and macrophages and mast cells, and they're all right around the oocyte that pressures egg and they're damaging it. So that it gives you poor egg quality. Okay. So it's not just in terms of fertility, it's not just how many eggs, it's what's the egg quality. And the egg quality is influenced by the total body health status. And that is about not having systemic, uncontrolled inflammation and having proper nutrients and of course, not being poisoned. So another thing that can age ovaries would be like, if you're exposed to a lot of heavy metals, like lead and arsenic and strontium and cobalt and mercury, right? We do not want to poison our eggs. And then there's other things like how about all the plastics that we live in? You know, they're finding microplastics everywhere. I'll bet you they'll find it in the ovaries. We already know we can find talcum powder in the ovaries, in which has been associated with ovarian cancer, right? And so there's all these different things that can affect the health and quality of the eggs themselves. And one of the things that's also very important to know is that sleep, and I keep coming back to sleep and our circadian rhythm, it turns out that the ovaries have loads and loads of receptors for melatonin. Now melatonin is known for sleep, you know, it's a hormone. It is known for sleep, but it's also much more than that. Nothing is one thing, right? It's also very key as a potent renewable antioxidant, okay? So melatonin is one of the most powerful antioxidants in the entire body. And if you don't get enough sleep, you won't have enough melatonin, you're not going to get that big surge at two o'clock in the morning, which is actually very critical for ovarian health and function. And so one of the treatments to try to help prolong the life of the eggs and say women who are wanting to have fertility or just longer lasting eggs, you know, an ovarian function is giving small doses of melatonin, sometimes higher, you know, as women if they're trying to get pregnant, right? And there's data on melatonin in terms of fertility and ovarian function and health. So sleep is really key, avoiding toxicants. And of course, infections can affect the ovaries. So unfortunately, you know, sometimes we can't avoid infections, you know, there's been talk about like, did COVID affect the ovaries? Well, we don't even know a lot about what happened in some women who had infections with COVID and what we know for males that it definitely got into the male testes. There's some effect on the ovaries. I mean, just to limit how much research is always done in ovaries. It's like usually the last thought, you know, ovaries. Oh, I didn't think of that one. But so we know that ovaries are subject to infection, toxicants, and lack of nutrients, poisons, and just any cause of inflammation like chronic stress, to know that chronic stress, like a life of chronic stress, we know that chronic stress in childhood like childhood trauma can influence metabolic health for the rest of that person's life by sort of reprogramming genes, you know, epigenetic modification and make a person more prone to metabolic diseases, metabolic syndrome and so on. And so anything that causes inflammation, metabolic dysfunction, diabetes, smoking, these things can affect, of course, ovarian longevity. And it's been a sort of a misnomer, I think, and we need more data, but it's been talked about that the most common cause of infertility in women, polycystic ovaries syndrome, they said, well, it's associated with longer lasting ovarian function. But that makes absolutely no sense, because these are women who are chronically inflamed, 80% or overweight and sometimes morbidly obese, very commonly, unfortunately, they have now been proven to have gut dysbiosis. And there is, of course, a link between gut dysbiosis and ovarian health. And so they would have every indication of having shorter ovarian lives. The fact that they have high anti-mullerian hormone is not because they have better ovaries, it's because they have very dysfunctional ovaries. And, you know, we can talk about PCOS another day if you like, because it is a very big separate topic. But I believe, and there's like lots of scientific data to support my belief that PCOS is associated with shorter longevity as far as fertility goes. And so all those things are important. In terms of androgens, there's some data that DHEA can help prolong ovarian function, magnesium can help prolong ovarian function, I mentioned melatonin. And then there's some, like we'll say newer types of supplements that are really interesting that can potentially augment the longevity of ovaries. And that would be NAD. So I don't know if you've talked much about NAD, so like NAD plus. And you need to take a supplement as a precursor to NAD, because NAD can't actually get over cross the cell membrane and get into the cell. So you can use either NMN, nicotinamide mononucleotide, or NR nicotinamide ribonocyte, okay, as precursors to NAD. And they can get into the cell where the cell can then convert them into NAD. But here's an interesting thing. NAD will be destroyed by your own immune cells who produce, they produce an enzyme called CD38. And this enzyme will destroy the NAD as fast as it's made if you have a lot of chronic inflammation. So it's so important to have a very anti-inflammatory lifestyle with lots of antioxidants, anti-inflammatory foods, and so on, so that your immune system won't destroy your own NAD. The reason that we built this way, why we have this system in place, is that the immune cells are of course evolved to destroy pathogens. Well, every living cell, the whole system with NAD is what we call conserved ecologically. So they're like precursor organisms, even single-celled creatures like fungi or bacteria have NAD. And NAD is essential for life itself. It's a co-enzyme. That's another big lecture for another day too, would be talking about NAD. But NAD is essential for life of every living creature on planet Earth. And as part of the mechanism of the immune cell, to destroy the invading pathogen, they have an enzyme, this enzyme CD38, that can destroy the NAD. And it's designed to be activated when you have inflammation from an infection or injury to kill the invading pathogens. But when you have total body, you know, by killing the, by destroying the NAD of the invader. But when we have systemic inflammation, this life-saving mechanism becomes sort of aberrational and the immune cells create this enzyme that destroys our own NAD. Okay. So that's why you have to do all this anti-inflammatory lifestyle things. That's why there's no, you know, simple, you just take, you know, one supplement and it fixes everything. You know, it's not that way. I wish it were that easy. You know, it's like, it's hard work to be healthy in our world. That I'm just glad that you brought up that ovarian aging is really synonymous with aging itself in women. If you're a woman in midlife or beyond, you're probably noticed those changes in energy, strength and recovery just don't feel like they used to. And what's frustrating is that for many women, this happens even when you're eating well, lifting weights, prioritizing protein and doing all the right things. You're not lazy, you're not unmotivated and you're not doing anything wrong. A big part of what's changing actually starts inside your cells. As we age or mitochondria, the energy producing structures inside our cells become less efficient. And when mitochondrial function declines, it can show up as lower energy, slower recovery, reduced muscle strength and feeling less resilient overall. This is a normal part of aging physiology. And it's one of the reasons midlife can feel so different. And that's why I've added mytopure gummies from timeline nutrition into my daily routine. Mytopure is the only clinically proven form of urolithin A, a compound shown in human clinical trials to support mitochondrial renewal. In simple terms, it helps your cells do a better job of making energy. And when your cells have more energy, your body is able to support strength, endurance and recovery as you age. What I appreciate most about mytopure is that it's foundational, not flashy. This isn't a stimulant or a quick fix. 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AX3 has also generously offered a 20% discount on your very first order when you visit ax3.life and use promo code synthea20 at checkout. Again, that's ax3.life and use code synthea20 at checkout. My family and I are actually taking AstraXanthan to see if we can drop our LP little a stay tuned. Yeah, and I think it's really interesting as I was writing my new book, The Menopause Gut and I really dug into the whole ovarian senescence, which is a fancy way of saying ovarian aging. It was fascinating to me all the things that can impact how quickly we age, how slowly we age, and it really goes back to the basics that you very astutely stated like at the basis of acceleration of aging is inflammation. And so the lifestyle piece, the sleep, the stress, the nutrition, the exercise pieces all so important. And there's no supplement or pill that's going to fix all of that. We really do have to change our lifestyles and it's almost as if we have to go against the kind of prevailing conventional wisdom that we can not be physically active. We can stay up all night binging on Netflix. We don't have to manage our stress. We can eat all the ultra processed foods. We can become incredibly metabolically unhealthy and think that it doesn't have a long a long downturn effect on not only the aging process but our quality of life, which I think is even more important, irrespective of whatever life stage that we are in. We want to have the highest quality of life that we can have. And we know that women generally outlive men, but those last 10 years, I mean, of our lives can either be having a high quality of life or it could be this kind of, you know, I think Peter Atea astutely states it, that you have this last 10 years of your life, that if you are, you know, strength training and eating well and managing your stress and plus or minus some very targeted hormone replacement therapy and being really mindful about the people that you spend time with, because we know how important that is, you can decrease the likelihood that you are going to lose your independence as you're getting older, which I think for every one of us that is especially for health care providers, we see what happens when people are not thinking 10, 20, 30 years ahead. You know, I think about how many patients I took care of in the hospital that were maybe a few years, maybe 10 years older than me. And I would sometimes look at them and think, you know, would they have made different choices knowing what their quality of life is like now? And I'm sure you've seen that clinically as well. Oh, absolutely. And I want to bring one other thing back into the ovarian story, because it then leads back into the progesterone story. And that is, and I know you've talked about this many times as well, mitochondria. Okay. So it turns out the ovaries are just packed with mitochondria. Oh my goodness, because they need so much energy. Those little ovaries, they are just like people always talk about, well, you know, the brain needs so much energy and the heart needs like so my goodness, how about the ovaries? They are just jam packed with mitochondria to make energy. It's like really very energetically, you know, needing endeavor to ovulate to mature the eggs. It's like a really big deal what's going on in those ovaries. And so they do need a tremendous amount of energy. So anything that is a mitochondrial toxicant, of course, is going to have a big impact. And we know there's a lot of mitochondrial toxicants, you know, all the different poisons out there. And anything that supports mitochondria, of course, inflammation is a killer. And by the way, nitric oxide is really key for a mitochondrial function. And that gets also back to progesterone and estradiol as well. And, you know, in terms of supplements, urolithin A has some, which is a derivative of a lactic acid, which is a phytoestrogen phytonutrient polyphenol, which, you know, you can find in a variety of foods, but not everyone can actually have the right gut microbiome. You probably talk about that, you know, the gut microbiome to actually make the conversion of the original phytoestrogen phytonutrient, in this case, lactic acid, into its substrate byproduct, which is urolithin A and those urolithin B, but we're talking about urolithin A here, which is very important for mitochondrial function. And nitric oxide, as I mentioned, is also a key player. So what we need is to have, in addition, plenty of estradiol and progesterone. And in fact, we know that there are mitochondrial functions that are very, very incredibly important involving estradiol. And that's getting a little bit more recognized, not much considering what it should be, but this close to zero recognition that there are also mitochondrial receptors for progesterone. And that progesterone is also a key player in mitochondrial function. And we know, for example, women who have fewer ovulations and make less progesterone, and of course, that includes women with polycystic ovary syndrome, but other women, you know, who don't make enough progesterone, they could be having hypothalamic amenorrhea. So there's a variety of different reasons that women are not ovulating, not making progesterone. They tend to have shorter lives. They tend to have more metabolic dysfunctions and less healthy ovaries. So, you know, and everything else, because it all works together. So, and in terms of progesterone, so it's really important for people to understand all the people out there that are the mitochondrial convergence, you know, they believe that in the mitochondrial theory of aging, right, that as you're a mitochondrial, which it's all interconnected to the nitric oxide theory, because they're all completely intertwined here, you know, so an ovarian aging, you know, way of thinking of what is aging, because they're all interconnected, you know. So, but when you talk about, you know, mitochondrial aging is really aging itself, when you don't have enough mitochondria, they're not working and so on. Well, just think about progesterone is a key player in mitochondria, as is estradiol. And like I do whole lectures just on estradiol and mitochondria. So it's like really, really a key thing. And if beauty is your main interest, not you, you're already so beautiful, but you know, out there, we know that many drip, many women are driven by aging into cosmetic dermatology and plastic surgeons and cosmetic surgeons, because they visibly see the effects of aging. And, you know, so what's not really talked about enough is, you know, the role of estrogen, but even less so the whole of progesterone on skin. And we know that estradiol has effects on every single aspect of skin, every component of skin has estrogen receptors, everything from creating a healthy epidermis, having hyaluronic acid, having ceramides, having proper, you know, elastin and fibrinogen and, you know, fibrin rather, and having all these different structures in the skin working optimally, well, progesterone also has receptors in the skin as well. And in fact, there is some data that topical progesterone can also be an anti-aging for the skin approach. And many people, myself included, will prescribe progesterone and estrogen containing products for the skin as a sort of a supplement to trying to make women feel better about themselves and have healthier looking skin. So that's another thing. And you mentioned bones. Well, the osteocytes, they create the bone. Well, the osteocytes have receptors to progesterone and progesterone is very important for making bone. So, you know, now some people can consider musculoskeletal aging as aging, you know, because we know frailty syndrome where you have little muscle, which we call sarcopenia, and you have poor quality bones, which we call osteoporosis. And as well, you have poor joints, you know, and the joints are really where the two bones connect and then have mobility between the two bones and the ligaments, the tendons, all the structures, the cartilage, all of them are hormonally sensitive. And they all have receptors to estradiol and progesterone. So, you can consider the aging of the musculoskeletal system as the definition of aging, you know, because if you can't move and these structures are not just for movement and for stability and, you know, keeping people erect, they actually, everything is more complicated than you ever would have thought or I ever would have thought years ago, you know, the muscles make signaling agents, the myokines and bones make hormones, osteocalcin that are involved in glucose regulation and brain and cognitive function. So, you know, loss of optimal bone and muscle affects many systems in the body. So, I mean, and all of these are related to our vital life hormones coming from our ovaries. If you love this podcast episode, please leave a rating and review, subscribe and tell a friend.