Ep. 484 AMA #13: Strength, Hormones & Muscle in Midlife

Today, I am excited to welcome you to AMA #13.

In this AMA episode, I cover a wide range of topics, including satellite stem cells and the importance of strength training as estrogen and testosterone levels decline. I also answer many questions about hormone replacement therapy, offering general explanations and resources rather than medical advice.

Join me for another information-packed AMA session.

IN THIS EPISODE, YOU WILL LEARN:

• Why strength training and sufficient protein intake are essential when your estrogen and testosterone levels drop

• Importance of HRT for women experiencing mood disorders

• What reverse dieting is, and how it is more challenging for middle-aged individuals than younger people

• Benefits of testosterone for muscle building and executive function

• How low estrogen levels impact the body

• When should you start taking estrogen?

• How reduced satellite cell activity during menopause can impair muscle repair and regeneration  

• The value of progesterone, beyond the uterus

• What are peptides, and why are they important?

• How GLP-1s can assist blood flow and immune regulation, and support tissue regeneration

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“I think it is much easier for young men and women to do a formal cut than it is for middle-aged people.”

– Cynthia Thurlow

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• Submit your questions to support@cynthiathurlow.com

Transcript:

Cynthia Thurlow: [00:00:01] 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. 

[00:00:29] Welcome to AMA #14. I have been delightfully appreciative, surprised and grateful that the AMA I did last month is the most downloaded podcast episode I've done in the past two months. So, I think this has reaffirmed for me and my team that you would like me to do more solo episodes. So, here we go. Today, we're going to talk about multiplicity of topics including things like satellite stem cells and why strength training is so important in the absence of premenopausal, estrogen and testosterone levels.

[00:01:08] We're going to hit on a variety of topics. A lot of it's going to be about HRT questions. Again, not medical advice. But I'm going to try to give everyone that has asked questions, resources and/or some generalized explanations. The other thing that I want to make sure we touch on, number one, a lot of questions about when plain creatine is going to be, well as Myo-Inositol, the answer is probably early August. There are powers that be that are beyond my control, namely tariffs didn't help with getting pricing in a timely manner and just other things that are happening. So, the goal was to have everything ready by mid-July. It's looking like late July, early August, but they are coming and they will be coming out in little containers. 

[00:01:51] So, plain creatine monohydrate just like I was doing before at 5 g per scoop. And then we have Myo-Inositol coming out or inositol starting with 1 g per scoop and you'll be able to adjust your dosing as needed. And the other thing that I'm really excited to share is that I've gotten very interested in peptide therapies. So, I think many of you are familiarized with GLP-1s. They are very popular right now for good reason. But there's a whole world of peptide therapy beyond that. And that is what I have been really interested in not just personally but also professionally. So, there may be opportunities to work with me. Yes, work with me directly if you are in the great state of Virginia. I'm not in a position right now where I am looking to be licensed outside of my state. 

[00:02:41] I do have quite a few NPs and PAs that have reached out wanting to partner with me. And so, we are in conversations about what that might look like. No promises, because I really stepped away from doing a lot of direct patient work beyond being in group programs. I do still have a group of private women that I work with, but it's a very small group and I may open up some opportunities to work with me directly. But it will be just for those that are in the great state of Virginia or are coming to Virginia and want to establish care here. So wanted to make sure I mentioned those things up front. Let's dive in. Let's talk a little bit about strength training. There were a lot of questions that came in from a variety of women.

[00:03:24] People are looking at what they call exercise snacks. Is it okay? This is a question that comes from Deanna. “Can I do individual strength training exercises throughout my day instead of one 25-minute session?” Yes, but-- the question is always yes, but you have to make sure that you are pushing yourself enough. And if you are new to strength training, please, please, please go back and listen to some of the podcasts I've done with Stacy Sims, Vonda Wright, Dr. Shannon Ritchey, Debra Atkinson, where we're talking about appropriate technique and why that's so important. But if you are an experienced strength training aficionado, yeah, I think you could probably get away with that. I mean, it's probably not particularly efficient and I'm all about efficiency. But as my cousin says to me, you do you. 

[00:04:08] If it is easier for you to take 5 or 10-minutes multiple times a day and that works for you and you are working hard enough, then I haven't read any research that suggests that would not beneficial. So, an exercise snack is probably not a bad idea. The other thing that I think is really important to mention here is that it's not just the strength training. It really has to be a concerted effort of ensuring that you are eating adequate amounts of protein. I'm getting ready to do a podcast with the head of Kion, Angelo Keely and we're going to talk about protein intake, protein needs, especially as we get older, especially in the setting of declining sex hormones. 

[00:04:48] And I'm going to do a little mini, mini, mini masterclass talking about what satellite cells are, why you should care about what this is. Those are stem cells, how they're impacted in a low estrogen state. So, as you're navigating perimenopause into menopause and I'll talk about some research and we'll include the research that I'm talking about in the show notes. So, if you are a nerd like me, you can go check that information out. But I think it's very hard when we have conversations about strength training without also having a concurrent conversation about the need for hormone replacement therapy. And I think there are still a lot of women that I say this lovingly that are still confused. They still have antiquated providers saying things like hormones cause cancer. And they're still very fixated on the post WHI, Women's Health Initiative. 

[00:05:35] Go back and listen to the podcast I did with doctors Avrum Bluming, Carol Tavris. Their book Estrogen Matters is a really important book. I think it should be on the desk or in the bookcase of every female and every provider in the United States and abroad. Like it is that impactful, that important. And I would actually argue that if your provider is still making that argument to you, that you should not consider HRT because it is it's causing cancer. Run, don't collect, go see someone else for a second opinion. Now, having said that, are there specific circumstances where someone may be listening, where they are not an appropriate candidate for hormone replacement therapy? 

[00:06:15] Yes. But it's important that each and every one of us be informed. We make informed consent. We have a mutually important conversation with our healthcare provider. You better believe my physician that I work with we have vibrant discussions. I will interject questions that I've been looking at. I follow a physician researcher who talks about how follicular stimulating hormone should be low in menopause if you're on enough hormone replacement therapy. I'm not sure I'm a hundred percent on board with that yet, but I'm still processing it. So, I think for everyone listening, I encourage you to have a conversation where it's a collaborative effort with your provider, whether it's a physician, whether it's an NP, a PA, a nurse, midwife, etc., etc., etc., make sure you're having those conversations. 

[00:07:02] So, let me get back to the strength training piece. We answered Deanna's conversation. I do want to answer a couple more strength training questions. Then we're going to talk about the research. Then we'll answer more questions that have come in.

[00:07:13] Jen Strope asked, “How do you do a cut?” So, this is someone who is interested in probably changing body composition. I'm not an expert in body composition specific to someone that is in a fitness competition or is doing bodybuilding competitions. But what I have learned from friends and colleagues who have done those kinds of things. A cut is something that you are typically doing where you're having a reduction in calories in an effort to shift body composition. 

[00:07:43] Now, I think it is much easier for young men and young women than it is for middle-aged people to do a formal cut. I think it gets a little more complicated because we're dealing with shifts in sex hormones. We're dealing with a little less stress resiliency, which means if we put too much stress on our body and our cortisol goes up, guess what? You're not going to be in a position where you're going to easily be able to lose weight. So, I'm not per se interested in the cut, but I think what you're probably speaking to is reverse dieting. And I think we touched on this in the last podcast AMA that I did. This is when someone is trying to add back some macronutrients because they've been in a caloric deficit for too long.

[00:08:25] And certainly many of you in the intermittent fasting community that have gotten stuck at 600, 900, 1200 calories a day, you understand this because you can't just go from 600 calories a day and try to get up to 2,000. You have to do it slowly. Generally, I'm encouraging women to add in protein, another 100 g of protein, tracking not only body composition, whether it's with bioimpedance readings, Bod Pod, etc. Not obsessively weighing yourself, because that is not healthy for any of us. I do not weigh myself. I go by how my clothes feel and I get regular interval body composition readings usually every quarter. And that's my tell.

[00:09:04] And I was very transparent in my last AMA, I talked about how I had gained three pounds of muscle, lost a pound of body fat. And so, we're still endeavoring to work on that. So, when we talk about reverse dieting, we're really speaking to a specific time period. Whether it's 10 or 12 weeks, where you are reintroducing maybe 100 additional calories in the form of protein typically, and you are staying on top of body composition shifts, you're probably weighing yourself not obsessively, and you are tracking your macros, which is not a sexy thing to do. But if you are trying to figure out what your macronutrient ratio needs to be, for some people, that can be very helpful. I hate tracking macros, but I do it on occasion. There is utility to it. But we don't want to be obsessive. 

[00:09:47] Obsessiveness leads to unhealthy maladaptive patterns. And I do see quite a bit of body dysmorphia. My team and I do, quite frankly, and I say that lovingly, I think that the toxic diet culture that my generation grew up in has certainly contributed to this obsessiveness with weight. Filters on social media don't help. There's actually a funny account that I follow on Instagram and he was commenting about how a celebrity who's an actress who is doing a video, I think in conjunction with a very recognizable brand. He was demonstrating how much body contouring had been done, meaning that the video had been augmented. And this is already a very thin woman. And so, I think these kinds of images can be very challenging because women see that, they think this person is as tiny as she looks on video and she's probably still very small. 

[00:10:41] But whoever augmented the video made her look even thinner. And she looks quite sarcopenic. She looks very thin with very little muscle tone. And I would imagine this individual is probably in late perimenopause, if not in menopause. But the intent is not to shame that person. I'm just saying that I think many of us are influenced by things we see on social media which are not exactly helpful or beneficial. So, let's focus a little bit on the strength training piece. Then we're going to talk about these satellite cells. Someone asked here, what are my thoughts on testosterone for helping to build muscle? I think it's a test. Don't guess. About 25% of us still continue to make healthy, robust testosterone levels. Yay you. If you're one of these people. I'm not one of them.

[00:11:25] Even with mild PCOS, thin phenotype PCOS, I do not have testosterone levels that are. They're almost nonexistent unless I take testosterone. So, I'm a huge fan for testosterone. Not just for helping to build muscle mass, but also for executive function. It's the “get off your ass and go to the gym.” It's the “get off your butt and finish your work.” It's the “engage with your friends.” It's the executive function piece. I think so many people tie it in with libido and desire and interest in sex. And it's so much more than that. We know that testosterone plays a role in cognition, brain function, health of our bones, sexual wellness, a lot of different things. Just like there's not just one benefit of estrogen, there's not just one benefit of progesterone. These are systemic hormones. 

[00:12:13] And so, nuance is important here. I do like testosterone. I think I tend to be on the conservative side. And I think that for women, starting with transdermal applications can be very helpful. I do like to see testosterone or DHEA included intravaginal products. So, if someone is using vaginal estrogen, using also vaginal testosterone or DHEA, why do we do that? Because it helps with that muscular layer. The vagina is actually a big muscle, and it is very important to ensure that you've got some muscular inclusion. These things are compounded generally speaking. 

[00:12:50] Dr. Anna Cabeca is the person that really has been instrumental in helping me understand and appreciate why DHEA or testosterone is so helpful, especially intravaginally. So, just kind of there you go transdermally on the side skin. I apply it on my lower leg. Some people apply testosterone cream for systemic absorption to their inner thigh. Really depends on your personal preference. I just find it's easier for me to put it on my lower leg than my upper leg. 

[00:13:18] I've done a lot of laser hair removal, and I was aghast when I started getting like this patch of hair regrowth. I was like, “Oh, no, I don't want that.” So, after spending many years doing a lot of laser hair removal, but it's all about, like, what works for you. Are there companies where I see women using subcutaneous, which means you're superficially injecting testosterone? Yes, I have companies that other patients have worked with, and they've showed up on our doorstep and they've disclosed and shared sometimes they're getting very super therapeutic levels of testosterone. They're getting acne, they're getting angry. Their libido goes through the roof. Same thing can happen when you're utilizing pellets. Have I had guests on the podcast physicians in particular that use pellets? Few and far between. And I think they're probably being very conservative. 

[00:14:04] With that being said, I think testosterone is very potent in our bodies. We want to be as conservative as possible. With that being said, let's talk about what satellite cells are. I promise this is really important. Satellite cells are actually stem cells, and they're really important for muscle repair and growth, and they actually decline in function and number as we make that menopausal transition, which can actually accelerate muscle loss. So, it's not in your head. If you feel like that transitional time in your life, you went from being able to build muscle fairly easily to now feeling like it is a second job to try to build muscle. I am right there with you. I feel like it is much more challenging. And that's even with hitting my protein macros, lifting heavily, and taking hormone replacement therapy. 

[00:14:55] We know that the acceleration of the loss of these satellite cells is actually related to estrogen. I think a lot of people assume it's all testosterone. It is estrogen too. And so, we know that estrogen plays this very unique role in maintaining these satellite cells and our ability to regenerate muscle. So, I'm going to talk a little bit about what these muscle stem cells are. They're dormant under normal conditions, but become activated when we have muscle damage or stress occur. So, like when you're lifting weights or when you are lifting heavy weight, heavy enough weight that it's creating a stimulus to tell your muscles to grow. 

[00:15:30] So, then the satellite cells, once they get the stimulus, they will grow, they will proliferate, and they differentiate into muscle cells which are called myoblasts, and they'll actually fuse with existing muscle cells and fibers to repair and rebuild damaged tissue. So, whether or not you realize this, when we're building muscle, we're actually creating little micro tears in the muscle. And we know that as we make this menopausal transition, the decline in estrogen goes hand in hand with a reduction in these satellite cells. And so, we have less of them around, so less satellite cells around. Studies have actually shown that the numbers of satellite cells are reduced in menopausal women. And this reduction correlates with lower estrogen levels. So as your estrogen's going down, you have less ability to build muscle. 

[00:16:16] And we know that the reduction in their function can actually accelerate this loss of muscle and weakness, which is the other part that we get really concerned about, is that when we lose muscle, we get weak. Weakness leads to frailty, frailty leads to fall. So, you can see this stepwise approach. We want to do everything we can to avoid getting weaker so that we become frail, so that we fall and either break our wrists, break our hips, hit our heads, all these things that are negative. We know that reduced satellite cell activity can impair muscle repair and regeneration, potentially leading to this decrease in strength and weakness. And we know that research in mice and human biopsies, so muscle biopsies, which are not pain free, have shown that estrogen efficiency leads to this reduction in satellite cell numbers. 

[00:17:02] And one study that I looked at found that satellite cell numbers declined by 15% on average during the menopause transition. And this decline also correlated with low estrogen levels. Inevitably, people will ask me, well, what levels do we want our estrogen to be at? And I think a lot of the research has been focused on what maintains bone and what confers cardiovascular protection. And typically, we're looking at levels that are greater than 60. So, personally, what I see is when we're looking at estrogen patches, as an example, when you look at a 0.025 patch, that'll get you to about 25, a 0.375 will get you to about 37, 0.05 will get you to around 50. So, for most people, they need to be on a decent patch size. 

[00:17:53] And the cool thing about patches, they can be totally, you can add and subtract, so you could take a 0.05 and a 0.025. You can put them together. Lately, we've been trending my estrogen patches up to hit that threshold. Dr. Amy Killen was a great recent podcast where we talked about the value of oral estrogen, and again, a very personal decision. And we're talking about oral estradiol, which is the predominant form of estrogen that our bodies make prior to going into menopause. So, what's interesting is when I was looking over all of these studies, there were two studies in particular. There was one from the University of Minnesota. It was a paper published in the journal Cell Reports that shows that muscle stem cells start to disappear when estrogen levels decline.

[00:18:35] So, again, this is consistent with what I stated earlier. The repair and rebuilding of skeletal muscles depends on the specific population found in muscle tissue and the researchers show these cells require estrogen to function optimally. So, another reason, like a lot of people focus on brain benefits, bone benefits, heart benefits. Well, if we want to build muscle, we have to be conscientious of about estrogen as well, not just testosterone, also estrogen. The Minnesota group shows that the hormone effects exert its effects through a protein called estrogen receptor alpha, which combines with incoming estrogen and glides it into the satellite cell nucleus. And this might be a little sciency for you, but I think it's interesting. There they found estrogen suppresses genes that would otherwise cause the cells to self-destruct. 

[00:19:21] So, estrogen is super protective, not just for brain, bone, heart, but also for muscle cells. And so, I think that's important. And so, what's interesting is when I was looking at this other piece of research. It is also making this connection. Lowered estrogen, lower affinity to utilize these muscle stem cells, less ability to build muscle. So, rah rah, yet another reason to utilize estrogen. And now I’m going to answer some of the estrogen questions that came in because I think it makes it really relevant. Will estrogen help sudden depression during perimenopause? Now I think that from everything I've read and I'm getting ready to interview an evolutionary biologist who talks a lot about women still in those peak fertile years and the role of follicular phase, luteal phase, progesterone, estrogen, etc. 

[00:20:12] You know I think people that have underlying propensities for depression and anxiety, this has been my clinical experience. Sometimes those things get worse as they make this transition. Especially, if someone's had PMDD which impacts a very small percentage of women. I think it was less than 5% if I am quoting Dr. Sarah Hill correctly. When I'm looking at patients that tell me like “Oh yeah, I had postpartum depression, I had like low-level depression throughout my life or it was worse in the luteal phase right before I got my cycle or I've had more anxiety and depressive symptoms and perimenopause.” I think these women are just much more sensitive to hormones. And this is not a criticism, this is just this bio-individual approach that I think is so important. 

[00:20:56] And so I think it goes without saying that can estrogen and progesterone hormone replacement therapy be helpful plus or minus testosterone for improving baseline depression/anxiety symptoms? Yes, but you need to be evaluated by your provider. I think that for every person that sees like the-- I used to have a patient that used to say it was like a veil was being lifted when she started hormone replacement therapy. Her mood improves so significantly. Because there are things that impact our mood that are beyond just our sex hormones. It can be neurotransmitter-mediated serotonin, dopamine, glutamate, GABA can all be heavily influenced by not only sex hormones but also lifestyle things. So, I think that the answer to that question Brenna is really yes, but I think this is a very much a bio-individual approach. 

[00:21:44] I think there are women that can be on hormone replacement therapy and see significant improvement in their mood disorders. I think there are also women who also then additionally need either changes in lifestyle because we know that ultra-processed foods will increase the likelihood that we will experience more anxiety, more depression, more mood disorders, more obsessive compulsiveness. And that's all related to the health of our gut microbiome. So, I think that this is a multifaceted response in that there's a lifestyle piece, there's a gut microbiome piece, there's a nutritional piece, stress piece, exercise. All these things are really, really important. So, working with a provider that's going to be able to look at this with a very multifaceted perspective is going to be very, very important. But do keep us posted. A lot of questions about peptides. 

[00:22:31] I will definitely talk about peptides on this podcast and I may devote an entire podcast just me talking about peptides. I do have Dr. Elizabeth Yurth coming on. I'm really excited about that. She is a permanent peptide expert and I feel like I'm just scratching the surface, but I'm really interested in peptides.

[00:22:50] This is a question from April. How will I know if menopause-- hormone replacement therapy is working, if you do not have menopause symptoms and are using it for heart and vascular benefits. This is a great question and we get this a lot. People will say, easy breezy, navigated through perimenopause, not a symptom. I sleep decently, I eat really well, I exercise. I don't want HRT or why would I want to take it? 

[00:23:12] I think what many people fail to realize is underneath the surface, in the absence of sex hormones, there's a lot of inflammation, oxidative stress. There's a lot of things changing and shifting even if you take really good care of yourself. And this is not to shame anyone, I think I've been very transparent that I had about six months where I was off of HRT trying to figure out next steps with my provider in conjunction with their agreement. Like, let's do a washout because I had been working with someone else and I can tell you I would not have believed had I not had a pre and a post looking at labs in particular, my lipids were like awful and I'd never had problems with bad lipids. And I'm speaking about my ApoB and Lp(a) I'm not referring to triglycerides. 

[00:23:54] My LDL did go up, my total cholesterol went up, but not-- in terms of a variance, it wasn't significant. But in the absence of adequate hormones we started to see this creep. I've never been insulin resistant, but did I see changes in my fasting insulin? No. But I think for the purposes of April's question. This is where I think testing can be helpful. Again, we've talked about this magic number of 50 to 60 being important. When we're looking at where do we see the benefits? I think we're looking at higher numbers of estrogen. We're not talking about like 25. We're not talking about 30. We want to avoid ever getting to a point where we have a lot of endothelial dysfunction. And that is really in the lining of our blood vessels. 

[00:24:39] That is where that inflammation, it's like lighting a match. I think the other thing is in the absence of estrogen, we have profound shifts in nitric oxide production. Why is nitric oxide very important? And we've talked about this on a lot of podcasts. I dedicated a whole podcast, Dr. Nathan Bryan, talking specifically about nitric oxide, why it's so important. But estrogen and nitric oxide are like peanut butter and jelly. They go together. So, in the absence of estrogen, you are going to have less nitric oxide, which means you get less vasodilation, which is a fancy way of saying that your blood vessels will dilate. It's very important that we have good vascular tone. What does that mean? It means that our blood vessels have the ability to expand and contract. We want that. We don't want them to be stiff. 

[00:25:23] Stiff blood vessels make our blood pressure go up. They impact our ability to properly regulate lots of processes in the body. So, getting back to April's question, even if you are without symptoms, please, please, please have a conversation with your treating provider. It doesn't mean that you have to be on high levels of hormones. I think you start low and slow. You monitor symptoms. The other thing that I think is important to just mention is that we know that progesterone tends to be an inhibitory hormone, so it tends to be a little more relaxing. Now, if you are someone that takes progesterone and it does the opposite, go listen to my podcast with Dr. Amy Killen where we talk about people who are progesterone sensitive and resistant. 

[00:26:02] So, I'm going to speak to the people that are not sensitive or resistant. It tends to be very relaxing. It tends to be not excitatory. So, if people are having trouble sleeping, sometimes we start with progesterone first before we think about adding a stimulating hormone like estrogen or testosterone. Everyone is a bio-individual, but that's typically kind of the methodology that we look at. Next question is from Amy regarding the estrogen patch. “Do you think that you should stay on the very lowest dosage in order to mitigate symptoms or safe to go to a higher dose if the patient feels even better on a higher dose.” Again, I go back to the you do you. I think each person has to be evaluated for how they feel. Some people feel better on higher doses of estrogen. 

[00:26:45] And by that, I mean maybe you do better on a higher dose patch. Maybe you're someone that just feels better. Maybe you have less vasomotor symptoms. We know that a lot of women experience years and years and years of having hot flashes, hot flushes, night sweats, just feeling like their body doesn't acclimate to temperature changes very easily. I know before I was on estrogen, if I walked into a hot room, I could feel my body not being able to properly regulate my temperature. And I'd never been someone that was like that. In fact, I remember we’re on a vacation together, my husband and I, it was a very hot country that were in. And I remember telling him, I thought I was going to pass out because I just couldn't regulate my temperature. Being on estrogen, it definitely helps with that.

[00:27:31] So, the point of what I'm saying is you want to have no symptoms. That's what you're aiming for. Symptoms are oftentimes a sign that multiple things may be problematic at once. You might have blood sugar regulation problems. You may be more sensitive to lower levels of estrogen. In fact, I remember the first time I had a hot flash I think it was like 2018. I was standing in my laundry room, I was folding clothes and I was like, “What just happened?” I feel tremendous empathy for individuals that will say to me, I get 10 or 20 hot flashes a day. That would be troubling, not just to help ensure that you can sleep at night, but just being in meetings or working or being outside the home or being in a situation where you have to show up and feel like your mental faculties are all there. 

[00:28:14] So, I think that it goes back to bio-individuality number one. Number two, are you having symptoms? Number three, how many women that I know need to be on patches, gels, compounded estrogen, and also need intravaginal products as well. I think it is a rarity for women not to need both. There is no shame in needing both. I think for some women, it's not a question of if, but when, you will eventually develop genitourinary syndrome of menopause. I think it is much easier to be in a position where you are using those products when you start to feel whether it's painful sex, itchiness, burning, friability of your skin, there is nothing more miserable than fixating on feeling uncomfortable in that part of your body. 

[00:29:02] And for anyone listening that's experienced that you understand what I'm saying, whether it's an itchy anus, whether it's itchy external, vulva, vaginal tissue, painful friability, all these things can be a sign of low sex hormones. So, to get back to that bio-individuality, find a provider that's going to work with you until all your symptoms have improved and make sure that your brain, bone, heart muscle are protected.

[00:29:28] Next question is about cancer. With cancer history in my family, this is Luciana. She does not identify which cancer, what type of cancer, which family member this is. Is it still possible to be on HRT? Number one, yes, but you have to talk to your provider. They need to do a thorough evaluation. The book Estrogen Matters I recommend not just for you but also for your provider. It is a very important book I've had Dr.-- I always think about her little tagline. I think about there's an amazing female physician, Dr. Corinne Menn, who is both a breast cancer thriver and also a physician. She herself is a breast cancer thriver. She is more than 20 years, I believe, since her initial diagnosis. She is now on HRT. But again, it has to be used in conjunction with informed consent. Going through all these things. The other part of Luciana's question is “Is still time to have HRT as I'm 55?” Yes, but ideally you want to get HRT started earlier rather than later. Remember what I said, the longer we go without sex hormones, the more inflammation, oxidative stress can occur. Do I see women in their 60s that have been able to start HRT? Yes, with informed consent. 

[00:30:44] But also the older you are, the longer you go without hormones, probably the larger the workup that needs to be done up front to make sure that there's not underlying cardiovascular disease, etc. Average age of menopause here in the United States is 51-52. At 55, you're well within probably that five-year window, just based on statistics. But have a conversation with your provider and definitely check out those resources.

[00:31:10] Okay, next question is from Nikki. “Two months ago, I started an estradiol patch. She's on to 25 mg per day and I take 200 mg of progesterone, which I feel has improved my sleep quality. Over the last two months, I've gained a couple pounds and I often feel bloated by day's end. I also had a stool study that showed dysbiosis, H. Pylori and low secretory IgA. I will be starting a purification program next week, but my question is, would the hormones contribute to those symptoms? I'm also trying to dial in the correct dose of thyroid medications. I feel like there's so much going on with me in the last few months. I really put great effort into my health and I feel defeated.

[00:31:45] So, this is the gift that keeps on giving of perimenopause. So, this is someone who's not yet fully menopausal. This is an individual who's starting to get some bloating side effects. It's probably multiple things coming together. It is probably an underactive thyroid. It is probably some changes and shifts in the gut microbiome. It is probably not fully being at therapeutic doses of her hormones.

[00:32:08] And so, I think this is where working with someone that really is going to take the time to tease out all of your symptoms and do it in a way where they're going to, it's like peeling an onion. You peel back one layer. I think thyroid is grossly undertreated. Obviously. I just did a podcast with McCall McPherson. She's coming back to do an AMA this month. I'm not sure when we're going to publish it, but that was another super popular podcast. People really, really liked what McCall had to say and she is a thyroid expert. I think most people are not properly treated for an underactive thyroid. They're allowed to languish, they don't feel good, they're really tired, their hair is falling out, they're gaining weight, they're miserable. 

[00:32:44] So, I always say, like thyroid, there's a thyroid receptor on every cell in the body. So, it's really important that we are actively addressing thyroid function concurrently with addressing HRT and also gut health. Those things can all be gently addressed simultaneously in a stepwise approach. But, Nikki, I'd be interested in getting an update, seeing how you are feeling now, because I'm not sure when this question came in.

[00:33:07] Okay, this is a question from Ann “55 years old, I'm on bioidentical hormone replacement therapy, estrogen and progesterone and testosterone for five years. I just had excision surgery for endometriosis and a total hysterectomy with oophorectomy. So, this is a total abdominal hysterectomy. My doctor will not continue my micronized progesterone because I have no uterus. I've heard from many doctors and researchers discuss the importance of progesterone, many body systems. 

[00:33:33] I eat clean, high protein, supplement, strength train, no personal family cancers. I'm BRCA negative. It seems like many doctors are not yet aware of the importance of progesterone beyond the uterus. What are your thoughts? Thank you for all you do.” Not medical advice, but please get a second opinion. We know that we have progesterone receptors throughout our body. It is not just about our uterus. I think about the calming effect. There's a byproduct of progesterone called allopregnanolone that is the really calming neurosteroid that really helps with sleep induction, helps reduce anxiety, depression. We have progesterone receptors on our bones. 

[00:34:08] There is osteoblastic activity, so blasts mean build. So, progesterone helps with bone building. So, I think you need a second opinion. There are absolutely providers out there that will prescribe progesterone. You do not need to languish and suffer. And I hope if you have not already done so, we have a provider list certainly if you live in the state of Virginia. I have lots and lots of friends that are taking patients. So, please let us know how we can help you. 

[00:34:32] Next question is from Kevin. Kevin is a physician's assistant. He said “Thank you for all you do. You've helped me to begin to help a lot of women. That's awesome. And we do have male listeners and I think this really speaks to the fact that this podcast is designed to help everyone. We are focused myopically in women in middle age. But there are providers and there are loved ones of the women that listen to this podcast who want to help and want to be able to improve the quality of life of women. You've helped me begin to help a lot of women. I've noticed some patients getting worsening ADHD. So, ADHD when starting HRT, vasomotor symptoms, sleep. I'll improve it more squirrely three to four days into starting treatment. Can you discuss your experience with this, if any? Again, I appreciate you very much and can only hope to have an impact like you someday. You're helping a lot of people.” Thank you, Kevin.

[00:35:18] Well, just think about it. What I was saying earlier is that, if we're starting HRT, sometimes people need to get progesterone on board first, especially if they're feeling like they are overstimulated to begin with. Because we know estrogen, testosterone have these stimulatory effects. And sometimes if someone's more prone to feeling stimulated than we get progesterone on board first before adding estrogen or testosterone. I feel like sometimes even if you're starting them, a week or two out, that can make a big difference. The other thing is for some people, they're just again more prone to-- they are more sensitive to hormones. So, maybe starting a lower dose of estrogen, maybe starting progesterone first, seeing how the patient does, especially if they're only three to four days in and they're already feeling like they're just very stimulated, it could very well be that it's just too many things changing at once. This is where I will sometimes say, “If a patient tells me that they're sensitive, I take that seriously.” Sometimes we have to back off on the estrogen or the testosterone and get progesterone on board for a couple weeks before we add something else in.

[00:36:21] Okay. This is from Kim. “I recently read Estrogen Matters.” Great. See, this is a book I talk about a lot. “And was surprised by a few of their findings, such as oral estrogen is mildly more beneficial than the patch for preventing cardiovascular disease and stroke.” Yes. Dr. Amy Killen and I talked about this in a recent podcast. Really depends on the individual. And if we're really just looking at research, it's looking at serum levels that confer the most benefits. Does this mean that oral estradiol is right for everyone? Probably not. I think it's all about bio-individuality. Can you get your estrogen levels sufficiently elevated with transdermal applications? There's a lot of ongoing research looking at that.

[00:36:58] But oral estrogen tends to be. They're very visceral responses. There are a lot of people like absolutely no oral estrogen. We're talking about oral estradiol, which is very different than synthetic estrogens, Premarin, etc. It is not the same as oral estrogens used-- oral contraceptives is another example. Kim also mentions vitamin D is ineffective in preventing menopausal osteoporosis or fractures because they do not affect bone resilience. I would agree with that. Do I think vitamin D levels are important? Vitamin D is a pro hormone. Vitamin D is very important for insulin sensitivity, very important for immune health. But when I'm looking at what is going to prevent fractures and address osteopenia, which is kind of this precursor less strong and resilient bone, we're really looking at formal hormone replacement therapy. 

[00:37:48] This seems contrary to so many others in the field. Makes me question my use of the patch and supplemental use of vitamin D. I think you have to think about what is vitamin D. It's a pre pro hormone. It does a lot of things I think when we're looking at bone health. So, getting those DEXAs and if anyone's listening, please don't wait till you're 65 to get a DEXA. I started getting them in my 30s because they used to do screenings at one of the hospitals I worked at. And that's the only way that I watched this waxing and waning osteopenia in me personally. I would go from breastfeeding two kids being osteopenic and then two years later I was not osteopenic. Now I'm osteopenic again because I'm in menopause. So, I think for everyone listening, it's finding what works best for you, having that full conversation with your provider and figuring out what makes the most sense for you.

[00:38:35] Okay, next question is from Kavs. “I'm 45. I’ve trouble with sleep only during the luteal phase of my cycle, very likely relevant to drops in progesterone. Anything to help with this other than HRT? Yeah, I think being mindful of your nutrition, we know that you need about 7 to 11% more calories which turns out to be like 100 calories. We're not talking about voluminous amounts. Making sure you're getting high quality nutrition, you're managing your stress. I think that when I'm looking at supplements that I think can be helpful. I just think progesterone has so many benefits that once people start that they're very reluctant. Even if you're just using it for one week out of the month as a starting point, there are other supplements like things like Vitex or Chasteberry, not medical advice. Myo-Inositol can be helpful doing things that are reducing stress prior to bed. Really good sleep hygiene may beneficial, but there's no shame in taking HRT. I don't want that to be the message. I think it's really, really helpful for people to just consider that replacing what we're bodies are naturally making less of may improve our sleep metrics significantly.

[00:39:41] I wish I had known 10 years ago what I know now. I know so much more now. I really suffered in the beginning of my 40s. For those that have PCOS, you're already in a progesterone deficient state. You already have a luteal phase defect. You're already low in progesterone to begin with. So, my early perimenopause was wild, really wild. So, if you're one of those people, please don't tough it out. Progesterone is both inexpensive, very well tolerated, and for some of you can get away with a week or two of it in your cycles till you need it more frequently.

[00:40:16] Okay, this is a question from C. Johnson. “Good morning. I have the Mirena IUD and was put on a 100 mg of progesterone daily. I was wondering why they told me not to cycle it just the last two weeks of my cycle. I think it depends on the provider preference. Some providers will just tell you to use progesterone if you're in-- And you didn't give me your age, I'm not sure your age. But if you're in early perimenopause, you may just need it in that vulnerable stage in your cycle, the last two weeks or the week before your cycle. Seven to 10 days, 14 days before your cycle. 

[00:40:47] It's really a great question for your provider. But more often than not, you're probably in an earlier stage of perimenopause and they just want to give you a buffer to help get you through in that lowered progesterone state. Okay, I want to make sure that we make plenty of time to talk about peptides, because this is something I'm really super interested in.

[00:41:07] This is from Emily K. “Hi, Cynthia. Thanks for all you do. I would love to hear your take on how many days per week or month women taking HRT should pause from progesterone, estrogen and/or testosterone.” Okay. I did a podcast with Dr. Anna Cabeca, who is a dear friend and she was the physician that actually introduced me to the concept of giving your receptors a break three to four days a month.

[00:41:28] Anyone that's listening to this podcast, this is not medical advice. Talk to your licensed healthcare provider. But I will tell you what I do. I skip progesterone one night a week. I do it on Friday night because generally on Saturday I don't have to get up as early. I take estrogen. I have two patches a week. I don't stop estrogen. I do take a break with my intravaginal estrogen, testosterone, DHEA one day a week, usually the same day, just to make it easy. And that's what I do. That is what's worked. And the thought process is that you're keeping those receptors sharp. I do not take a break from thyroid replacement. And I probably would be the first person to tell you that I love the experimentation of the N of 1. My sleep is not terrible on the night I don't take oral progesterone. I'm sure if I didn't take it for two nights, I would probably feel it. But I tend to increase my Myo-Inositol on that night. So, I will take more adaptogenic products. I will ensure that I'm doing all the things on Friday night to decompress my body, but I usually will take more Myo-Inositol. And that's my trick, for me personally, that is what I do. But definitely discuss with your internist or your GYN. Okay. 

[00:42:35] This is a question from Bridget. What would cause a 42-year-old not in perimenopause? You probably are, though. Number one, when a young person. Young as in 42. Probably in early perimenopause has low testosterone, could it be genetic? Sure. More than likely it's stress and chronic stress. Like more often than not, it's women who have unrelenting chronic stress. Could be trauma that they've experienced that they just haven't processed or they just don't even acknowledge what they've gone through. We've talked a lot about these subjects, high ACE scores, but more often than not, I think that when someone has low testosterone, it is related to some degree of insulin resistance, chronic stress, chronic trauma, dysregulation of the autonomic nervous system, etc., etc. 

[00:43:21] You can have some SNPs or some genetic polymorphisms that can make you more likely to have low testosterone. I have had some Asian patients in particular that just have low testosterone and that's normal for them. I don't love pellets because I think they can be wildly unpredictable. She also mentions how do I feel about testosterone pellets? I feel amazing on them but my hair is falling out. Yeah, that can be common. What should I do instead? Well, again, Bridget, talk to your provider because they are treating you. But I would say that if your hair is falling out, it's a sign that there is a metabolism byproduct of that testosterone being really high that is probably contributing to the hair loss. Could also be iron deficiency. There's a lot of different things that can contribute. 

[00:43:59] I did a great podcast with Dr. Omar talking-- He's a dermatologist, but hair loss is his thing. That would be a really great resource for you as well, but definitely keep us posted. I just don't love pellets because I feel like they're unpredictable and you get so super physiologic dosing, not a steady state, predictable dose you generally feel really good for a couple weeks and then you feel like crap. And you have to wait till you get to that 12-week mark to get a new pellet. 

[00:44:27] This is from Amanda. “Is it beneficial to start low-dose estradiol in oral or patch form? As I know my estradiol is declining. I'm on oral progesterone and compounded testosterone. My FSH levels are getting higher and estradiol levels are low. I've not cycled in four months. I just want to be proactive.” Yeah, I think that if you're starting to see a trend of low estrogen, you're at 48, so you're probably in mid to late stages of perimenopause. I think that's the time when you start feeling symptomatic to consider the utilization. I'll tell you why personally, why I like patch. It's a set it and forget it. 

[00:45:00] I've had guests on here that are physicians that feel like, they prefer other ways to take hormones. I'm someone between oral progesterone, oral thyroid replacement, transdermal testosterone, intravaginal hormones. I don't want to rub one more thing into my body. So, I love the patch, but it's a really easy way to get a fairly predictable dose. Again, bio-individuality rules, there are some people that just don't absorb enough. I'm absorbing great. I did better on a patch than I did on a compounded version. It's also incredibly inexpensive. I think I pay $5 a month for my box of patches when I was paying over $100 for 60 days-worth of compounded estrogen. So, talk to your provider for sure and see what they're willing to prescribe for you and when is the best time to start estrogen. So that was the other part of her questions. 

[00:45:56] I think you start in perimenopause. I think all the research is identifying that you don't wait until you're in menopause. The thought process is that you have a more concentrated dose heading into your body not making as much hormones. And I think that there's value in that because you're not likely to have as much dips and ebbs and flows, you know, peaks and troughs like high and then low. And so, I think for a lot of people, if you have the ability to have that conversation, do it earlier rather than later. And don't suffer. Like I tell everyone, 10 years ago, I didn't know what I didn't know. I know better now. I try to encourage people like, “Do not suffer, start them early, feel better. Don't experience all the highs and lows that many of us did.”

[00:46:38] Okay, I want to make sure we make time. I still have tons and tons of questions, but I want to make sure we talk about peptides because I think that there will be opportunities for me to do a whole masterclass on peptides. Maybe will do that before my podcast with Dr. Yurth, who is an expert in this area. Like, very savvy. Very, very savvy. So, what are peptides? Why are they important? I think nearly everyone listening to this podcast has heard of GLP-1s. Those are a type of peptide, right? Peptides are short chains of amino acids that function as signaling molecules. So, it's like they're little conductors in our bodies. They've gotten much more popular over the last several years. So, there's many, many options for peptides. 

[00:47:18] Please don't go out and buy something on Amazon. That is not what I'm talking about. I think the way to go is a really high-quality peptide, either something that is prescribed and is available through pharma or is compounded for you. And there are compounded things that we'll talk about. We know that there are peptides that can help with muscle mass and fat loss and metabolism. Obviously, the most popular ones that we're talking about right now are the GLP-1s. There are peptides for sleep. There are peptides for neuroprotection. There are peptides for immune function. There are peptides for gut health, joint pain, tissue healing. And I think that-- there's research on each one of these focusing on three, obviously, GLP-1s, because everyone's familiarized with them. BPC157 and something called thymosin alpha. 

[00:48:08] There are other peptides out there, but these are the three that I feel like for the benefit of the listening community, are things that we can all wrap our heads around. They're not too crazy because there are some crazy peptides. There is some crazy peptides that I'm learning about, but I'm like, I'm not so ready to talk about this because I feel like I don't know enough yet. So, let's talk about thymosin alpha. Now, my youngest son got mono in January, and every time he started to feel better and go back to school and start becoming more physically active, he would feel poorly again. So, my functional medicine doc and I agreed in conjunction with Liam because this is what Liam wanted to do. He was like, “I need to feel better. I'm in a very demanding high school. It's my junior year.”

[00:48:54] I think he had seven AP classes. No, six AP classes and one dual enrollment. All his choice. He's just an intense kid. So, thymosin alpha was what we started for him. And it was pretty miraculous. This is compounded. This is through a compounding pharmacy, a very high-quality compounding pharmacy. You don't just roll up and, it's not like taking a capsule. So, it's injectable, subcutaneously teeny tiny insulin needles. But we know that thymosin alpha is important for immune modulation. So, in someone who has viral activation of mono, which is Epstein Barr virus, working to help his body support, enhancing his immune system. And also, T cell activation, which is part of our adaptive immune system and antiviral defense. So, for him, total game changer. He was on it for about six to eight weeks, made an enormous difference, along with some other things that we're doing.

[00:49:46] Why it can be important in menopause? We know that aging and estrogen both impact our immune system. I know I haven't unpacked what my new book is about, but I spent an entire chapter talking about immunosenescence, which is a fancy way of saying what happens to our immune system with aging. So, we know that in the presence of less estrogen, we have more inflammation. We've talked a lot about this. A lot of people call it inflammaging. I can call it immunosenescence. It means the same thing. Our bodies are aging from the inside out. And thymosin alpha can actually help this. It can actually counter balances and support the immune system.

[00:50:30] There was a double blind, randomized controlled trial, which is considered to be the gold standard, showed that we had accelerated recovery in women with- In this case, these are women that had HPV, so human papillomavirus, by enhancing their antiviral and immune signaling pathways. So, I've seen this used in many instances, but I'm speaking to number one, my son used this to heal for mono. I am currently using it because we're trying to get on top of my autoimmune stuff that is thankfully fairly quiet. But I do a lot of travel. And in light of the fact, we're trying to improve my immune system because of all the travel that I do. And so, I've been taking thymosin alpha for the last couple weeks. I will continue to give people updates. I feel fantastic. 

[00:51:16] I think that there's one of these burgeoning fields that I think for a lot of people, maybe it's a short-term thing for some, maybe it's a long-term thing for others, but it's helping support my immune system in conjunction with HRT and lifestyle. The other one that I want to talk about is called BPC-157, which is called [unintelligible 00:51:16] funny enough, clearly, I am tongue tied. This is called body protective compound and it's a synthetic peptide. So, again, made in a lab, derived from a gastric protein that supports healing in the gut lining, our joints and also our brains. BPC-157 I will probably be on forever. Why it matters in menopause or perimenopause for that matter. We know that low estrogen leads to leaky gut. There's a lot of emerging science talking about the role of the gut microbiome what's changing in the absence of these sex hormones.

[00:52:10] We know that estrogen is very important for fostering stability of our small intestinal lining. So, small intestine, it's kind of like all these interwoven connections that try to keep things out of our bloodstream and out of our bodies. But what starts to happen is in this low estrogen state, we're more prone to opportunistic infections and we're prone to underlying food sensitivities. And so, BPC-157 is going in there like mortar. It's going in there to help repair that gut lining. And so, we know leaky gut is more common in perimenopause and menopause. We know women tend to have more joint pain. I just did that great podcast with Dr. Jocelyn Wittstein talking about orthopedics and frozen shoulders, which is adhesive capsulitis for those of you that like the medical terminology. 

[00:52:58] And we know that we also just don't repair things as readily. So, BPC-157 can really help with that. And there's some good research. There was a 2021 double-blind, randomized controlled study and ulcerative colitis patients that found BPC-157 improved mucosal lining and healing and reduced inflammatory markers with no reported side effects. So, this is a pretty well-tolerated peptide. It's not a crazy one. Remember, I mentioned there's a lot of crazy stuff out there. This is again something that's compounded. My provider and I had a long conversation. He said sure, you could probably find BPC-157 on a website, but where is it made? Is it made in China? Then I don't know where it's made and whether or not it's going to meet his stringent needs and my own.

[00:53:42] So, with that being said, I think it always goes back to using stuff that's had some real research done on it. Being conscientious about sourcing. We're starting to see more BPC-157 used in women for gut dysfunction, autoimmune function flares or even connective tissue injuries in menopause we're just more prone to these things. And lastly, I would say I would be remiss if we don't talk about GLP-1s. I have a ton of content coming out around this but I'll just suffice it to say I think that, we think about these three that I'm specifically referring to number one, BPC-157, gut healing. We know that it regulates angiogenesis which means it helps with blood flow and new blood vessel connection, supports tissue regeneration, helps with gut lining.

[00:54:26] We know that thymosin alpha is again helping with immune regulation, has some antiviral properties. It enhances our adaptive immune system, so enhances T cell proliferation, reduces inflammatory cytokines. And then we're looking at GLP-1s and so probably the most popular ones, Ozempic or semaglutide, there's a second generation now. Tirzepatide is very popular. Predominantly used in weight loss but we're starting to see it used for reducing inflammation, reducing visceral fat, appetite suppression. We know that it actually mimics specific hormones in the body. These incretins can help with delay gastric emptying. McCall and I talk a lot about the use of these in a micro dosed approach. That may not be what your provider does but I think this is where this kind of off label utilization can be very interesting and can compelling and from my perspective, I think this is a whole other new world that's out there. 

[00:55:18] I think you're going to see people utilizing these drugs to help with taking the edge off on their appetite. They may not qualify for it being covered by their insurance. By that I mean, you know people that have to be a certain BMI, body mass index that have a concomitant risk factor like diabetes. Maybe their BMI is 27 and they already have diabetes or their BMI is 32 and they don't yet have diabetes and their insurance will cover it. Some of these microdosing efforts are being done and it's out of pocket. But I think for some people who don't want to be like on an example, they don't want to be on a statin and maybe this is going to help lower their cardiovascular risks. 

[00:55:58] I think there's a lot off label utilization of these drugs and certainly I'm very curious about them. So, of the three I mentioned, thymosin alpha is injectable subcutaneous teeny tiny insulin needle. Same thing with the GLP-1s. Typically, BPC-157 if compounded and high quality can be taken orally. I have seen some injectable utilization especially for people that are having joint issues. But I think it's like a case-by-case basis.

[00:56:29] So, I love this AMA. Keep your questions coming. Last time I mentioned this we got hundreds of questions. Keep your questions coming. I do endeavor to do a totally peptide-focused masterclass prior to interviewing Dr. Yurth because then everyone will be really ready for that information. Keep the questions coming. Just remember number one, plain Myo-Inositol, plain creatine are coming. 

[00:56:49] We're looking at like late July, probably early August at this point. Number two, I'm really, really, really interested in peptide therapy. So, if you're in the state of Virginia, I may be opening up a couple practice spots to help women, probably in conjunction with other providers that are less savvy to help augment some of the body composition changes, immune function changes that we are experiencing at this stage of life. I think these peptides in conjunction with HRT and targeted lifestyle are really like game changing and I'm really, really excited to be able to share the technology with my community. Always love chatting with you all. Have a great day. This is July 4th weekend. I'm moving on to my next thing I need to do and just really excited to spend this last hour plus with you all. 

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