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Ep. 233 How to Optimize Your Hormones & Metabolism For Vitality with Kyle Gilett


I am excited to interview Dr. Kyle Gillett today! He is an integrative and precision medicine physician who focuses on bio-individuality. He is active in obesity medicine and hormonal methodologies. His approach is evidence-based, and it involves shared decision-making.


As a physician, Dr. Gillett wanted to treat people holistically. Hormone pathologies, menopause, and metabolic syndrome are common, so he decided to become proficient in those areas to serve his patients in the best way possible. 


Dr. Gillett and I dive into his background, his six pillars of health, the value of evidence-based medicine, how our modern-day lifestyles impact our hormonal health, nutritional dogma, and the importance of sleep. We discuss adrenopause, perimenopause, menopause, changes in body composition, and broken metabolisms. We also talk about weight loss resistance, lab work, muscle-centric medicine, and valuable supplements.


I’ve waited months to interview Dr. Kyle Gillett! I hope you enjoy listening to today’s conversation with him! Stay tuned to learn about hormones, weight-loss resistance, and more!


IN THIS EPISODE YOU WILL LEARN:

  • Dr. Gillett dives into his 6 pillars of health. 

  • How our modern-day lifestyles impact our hormonal health.

  • What is food intelligence?

  • Dr. Gillett unpacks the concept of evidence-based medicine.

  • How providers can prevent a breakdown of the patient-provider relationship.

  • The challenges women tend to face in menopause.

  • How Dr. Gillett helps women cope with changes in their body composition.

  • What happens in our bodies when we are stressed or lack sleep?

  • What is adrenopause?

  • The benefits and effects of using melatonin.

  • Dr. Gillett’s take on oral contraceptives and HRT.

  • How Dr. Gillett addresses a broken metabolism.


Bio:

Kyle Gillett MD: 

University of Kansas School of Medicine. 

Dual board Certified Obesity Medicine and Family Medicine. 

An undergraduate dual major in Critical Thinking and Biology. 

Dr. Gillett enjoys providing holistic individualized care to his patients. His practice includes preventative medicine, aesthetics, sports medicine, hormone optimization, obstetrics and infertility, integrative medicine, and precision medicine including genomics. He believes that each human is a unique creation that requires attention to their body, mind, and soul. He uses shared decision-making and an evidence-based approach. He firmly believes “food is medicine” and “exercise is medicine”. Dr. Gillett describes the “7 pillars of health”: exercise, diet, sleep, stress, social, sunlight, and spirit. These are more powerful than any medication or supplement. He enjoys spending time outdoors on the farm with his wife, two sons, and two wolfhounds.

 

"If you look at the chart of the progression of aging, the sarcopenia, and the insulin resistance or the increased body composition often happen concurrently."

-Dr. Kyle Gillett

 

Connect with Cynthia Thurlow


Connect with Dr. Kyle Gillett

  • On Instagram 

  • On all social media platforms: Gillett Health


Transcript:

Cynthia Thurlow: 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 are 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 interviewing Dr. Kyle Gillett. He is an integrative medicine and precision medicine physician focused on bio-individuality as well as using shared decision-making and evidence-based patient-centered approach. He is active in obesity medicine as well as hormonal methodologies. Today, we dove deep into his background which set him up for a holistic focus, the role of six pillars of health, the value of evidence-based medicine, the impact of our modern-day lifestyles on hormonal health, nutritional dogma, the importance of sleep. We spent a great deal of time talking about adrenal pause as well as Perimenopause and menopause changes in body composition, broken metabolisms and weight loss resistance, lab work, the value of muscle centric medicine, as well as supplements that he finds valuable in this particular patient population. I hope you will enjoy our conversation as much as I did. I had been waiting months to interview him and I'm so glad that I did and that I can bring this information to the audience.

Well, thank you, Dr. Gillette. I'm so excited to have you here today diving deep into hormones and weight loss resistance and topics that I know you are very well familiarized with.


Kyle Gillett: Thanks. Yeah, a pleasure to be on.


Cynthia Thurlow: Now, I know that your training is actually very lifestyle medicine focused. And I would imagine, at least for those of us that trained in the 90s, before lifestyle medicine started to become a larger focus of traditional allopathic medicine and functional integrative medicine, was that a choice of yours? Were you looking for a medical program that had a unique lens or unique slant? Or is that just serendipitous?


Kyle Gillett: Yeah, I've known that I wanted to be a physician for a while, and I wanted to be able to treat people holistically. Common problems are common, and hormone pathologies happen to be common. Menopause is, of course, extremely common. And metabolic syndrome is extremely common. I figured I would become as good at those things as possible so that I could be of best service to my patients.


Cynthia Thurlow: I think that's really important. And certainly, for many of us that are more traditional allopathic trained, it took me quite a while in cardiology to recognize the significance of the lifestyle contributors, as opposed to just managing symptoms with medications. Now, you have these six pillars of health, which I think are really foundational to the work that you provide in your practice and things that are very aligned with my own recommendations. But let's start there, let's start the conversation so that the listeners have some context of your background and what you bring to your patient profile.


Kyle Gillett: Absolutely. I like to write prescriptions for lifestyle, I truly believe food is medicine and exercise is medicine. I do my best to practice what I preach as well. Obviously, nobody's perfect but I like to be prescriptive for things that are going to help the patient all in all. Sometimes, I make the analogy, that if pathology is at play, you're stuck in quicksand. So, you want to both teach the patient how to dig their way out, and also provide them for the correct tool to do so, if it applies.


Cynthia Thurlow: That's certainly helpful. And what is one of many ways that our modern-day lifestyles are actually contributing to hormonal health dysregulation and hormonal imbalances that are becoming so very, very common?


Kyle Gillett: Yeah, there is obviously many ways, I would say the big three are metabolic syndrome. And one of the reasons for metabolic syndrome is that for thousands of years, humans have done a lot of manual labor and lived outside. We haven't been in these artificial indoor environments, as I'm sitting here in the studio, where there's air conditioning, and where you don't have sun exposure, and where you're not moving. We also have invented wonderful technologies to help us move. If you look at areas like the Mediterranean, yes, they had the Mediterranean diet, but also, it's very common to walk places. So, one of my pet peeves is, I would say, pedestrian deserts. So, you have healthcare deserts, food deserts. And then also, even in many places, it's just literally difficult to get out for a walk.


Cynthia Thurlow: And then in terms of, meal frequency, this is something that I see being hugely problematic is the access to hyper-palatable, highly processed, nutrient-devoid foods as being a huge contributor to a lot of the metabolic syndrome metabolic imbalances that are becoming so common.


Kyle Gillett: Yeah, that is certainly true. Some people use the term called 'food intelligence' or 'nutrient intelligence' and regardless of the term that's used, I think the important distinction to make is the difference between caloric density and nutrient density. And also, not for the nutrients that are often left out. For example, different types of fiber, prebiotic fiber, even different types of prebiotic fibers, omega-3s, and then various things that specifically help your gut microbiome that might not even need to be bioavailable at all. I think those are some big three lists of commonly left-out food items, just like people can be uninsured or underinsured. People can also have little to no food intelligence and a little bit of food intelligence. So, there's a spectrum. And actually, at the opposite end of the spectrum, we're seeing a new form of disordered eating, some people call it orthorexia, or intellectualized eating, where you're most scared of eating things that are not perfectly healthy. So, finding a happy medium in there, where you're able to adhere to that new lifestyle, and hopefully getting some pleasure from it is what I like to prescribe.


Cynthia Thurlow: I think it's really important. And I think a great deal about the intellectual eating, as you mentioned, are orthorexia that are becoming more commonplace largely because they're, we now have these social media platforms where people's behaviors may be much more clear to those of us that are clinicians, I think, on a lot of levels. When I'm looking at the distinctions between food intelligence and metabolic syndrome and meal frequency. I also think about these, hyper-palatable ingredients, I think about the role of seed oils, I think about high fructose corn syrup, I was in Costco over the weekend, and I took a snapshot of the soda aisle. And because I don't drink soda, and we don't have soda in our house, I sometimes forget how proliferative this is, and how this is more than norm that people are consuming these, like largely rancid, highly inflammatory seed oils, along with high fructose corn syrup, which is processed very differently in the body. When you're having conversations with your patients. Are you getting down to the details about food ingredients along with these other parameters in which you're discussing with them? You said the prescriptive approach about lifestyle medicine.


Kyle Gillett: Yes, often I do. And often we do as well. I also work as a member of an interdisciplinary team, with dieticians, and with health coaches, and with many people that are basically on board in order to provide a different angle of foresight, I think that a diversity of thought and ideas is a wonderful thing within the healthcare team. And I learned a lot from my colleagues that I work with on a day-to-day basis. A lot of people ask me, and I'm sure they asked you the same thing, "How did you get into this?" And then, "How did you acquire this niche of evidence-based preventive medicine or health optimization?", whatever you want to call it. That's the same thing. And I suppose the answer to that question is, it's a bit of a snowball effect, where you just dip your toe in, and then it just keeps getting larger and larger and reaches critical mass.


Cynthia Thurlow: Absolutely, for those individuals that are perhaps listening and aren't familiar with the concept of evidence-based medicine, let's unpack that a little bit, because that guides a lot of treatment protocols and recommendations, and has a trickle-down effect. I mean, it can ultimately impact clinical practice quite significantly.


Kyle Gillett: Yeah. So, there's actually a pyramid of evidence-based medicine. And at the top of the pyramid, you have meta-analyses and systematic reviews. Of course, these are applied to populations of people, you also have randomized control trials, often they're double-blind or placebo controlled. So that's what you think of a trial when you have two or more groups. And then past that, you have cohort studies, prospective cohorts, where you look on the future retrospective cohorts look into the past. And then you have case-control studies, we're getting down toward the bottom of the pyramid. And then you have case studies. Just like a single case study, which can certainly be helpful. And then you have anecdotal evidence and expert opinion. And there's this odd dichotomy where a lot of the expert opinion is based on meta-analyses and systematic reviews, but often you don't have that to be based upon. So, in that case, practicing along the tip of the pyramid is evidence-based. That's where the practice of medicine comes in. To assess, does this specific patient, the end is one, so 100% or 0%? With that one single patient? Can I apply this on a population-based or is there another variable that would have perhaps excluded them from the study called confounders? Often reading the limitations can tell you a lot about a study including what they leave out of the limitations that they perhaps should have put in. Often in the functional medicine sphere, the question is functional medicine evidence-based medicine? And that's just like asking, is conventional medicine evidence-based medicine? Sometimes yes. And sometimes no, it's up to the provider to apply that literature to each individual.


Cynthia Thurlow: I think that's really important. That lens of bio-individuality really makes a huge difference. And I love that you were suggesting that both traditional allopathic and both functional medicines can use along this continuum can utilize information and apply it to their patient population. I know that this is one of the more common questions that came up. And there's a lot of nutritional dogma, there's a lot of confusion over, what bucket people want to identify themselves within, whether they're keto or carnivore or vegan, etc. But as a clinician, I would imagine that you are probably doing diagnostic testing, taking a really good history to determine which nutritional program you're going to make in terms of recommendations for your patients.


Kyle Gillett: Yes, certainly. There are two main types of things that healthcare providers take into account subjective evidence and objective evidence. And both are particularly important for working up any assessment and plan including a nutrition assessment and plan. Just like we take into account if there's a family history of a bunch of people in the family reacting to a medicine, perhaps having a seizure with that medicine, even if that patient is not at particular risk, perhaps we look for an alternative, it's the same way for a diet. So, if one person, the family or friend, or for whatever reason, they are less likely to adhere to a certain diet to a certain diet, I'm probably not going to prescribe it. For example, at a family of cattle farmers, even if they're a perfect candidate for an Ornish Diet, of which I don't think there are very many good candidates at all, by the way. But probably would not prescribe an orange diet, maybe that's a bad example. But that's the way that you look at it. You take that subjective information. And then you also take objective information that can be anything from labs to genetic predispositions, then you synthesize the two and come up with a plan, there are two terms that people like to throw out that I'll define quickly. One is motivational interviewing. And that basically just means shut up and listen to the patient, and don't try to plant ideas in their head, and then share decision making. And that just means making sure the patient is okay with the decision before prescribing it. The alternative to that, which is what used to be done typically years ago is called medical paternalism. Where is what you just tell a patient what to do. And some patients do like medical paternalism, they might be used to going to their doctor, and they just say, "Doc, just tell me what to do." Or they just want to be told what to do by their healthcare provider. And that's okay.


Cynthia Thurlow: Absolutely. And it's interesting that medical paternalism, I saw quite a bit in the World War II generation very respectful, came in, really wanted the plan to be laid out for them and presented to them and they would just take it and run with it. And then I've come to find out that younger generations want to be much more actively involved in the decision-making process. And I think a lot of it is just understanding what is your patient looking for. And leaning into what's going to be most, I don't want to say compliance because I think compliance is judgmental, but what is going to be the easiest next step for that patient to allow them to have small successes, so they can then go on to make more substantial changes over time?


Kyle Gillett: Yeah, that's a really good way to look at it. You never want to have a breakdown of the patient, provider report or relationship. When that breaks down. A lot of times, it's just time for a new provider. And perhaps they weren't a good fit, to begin with. But a lot can be done, two good examples of that is, one of my grandparents came to me years ago, and they had just gotten a new doctor, theirs had retired. And they were puzzled because they were given two different options. And then they had this chart that said pros and cons. And I thought that was fantastic. But they just didn't really understand that because they had never been introduced to it, so we had that conversation. But it was a bit of a breakdown. And that was also their first visit with that provider, there was a lack of trust. Another good example, which we see often is people going to the doctor, often for hormone pathologies, PCOS is a good example. And they're just told no dietitian referral, by the way, and they're just told to eat less and move more. And that can lead to a pretty big breakdown too.


Cynthia Thurlow: Absolutely, how many of us-- I can speak for myself, I may be at a position where you might have never done this, but that was the traditional prevailing wisdom when I was first in healthcare in the late 1990s, that we would just say to patients is as simple as eat less food move more frequently, and we now recognize that this concept is woefully ineffective. And in many ways, I think it can be detrimental, especially for individuals that have got significant hormonal imbalances. They may follow exactly what you're telling them to do, and they may not have the results. that they're looking for.


Kyle Gillett: Yeah, that's a good way to put it. It's like you find a new coach for your sport and then you get into an argument the first day. That's just not going to go well.


Cynthia Thurlow: Absolutely not. Now, I would imagine that you have quite a few women that are north of 35, and north of 40, that are starting to see the beginning stages of perimenopause and menopause. And I'd really love to focus the conversation on this because in a lot of ways, I think that a lot of middle-aged women feel underrepresented and underappreciated because a lot of the traditional focus is on contraception, fertility child, pregnancy, postpartum. And then there's this nebulous-- the woman is now going out to pasture. She's not as fertile or now she's no longer fertile. What are some of the common challenges you see in women in perimenopause and menopause, in your practice?


Kyle Gillett: One of the biggest challenges just right off the bat is that there isn't a huge supply of need a huge demand, I suppose. And not a lot of supply within the healthcare system. Often, by the time they see providers such as yourself and myself, they have seen many others, maybe not even healthcare providers, health coaches, or trainers, they've sought out help at a lot of different places. And they're already somewhat tired of trying, and they've lost some of that drive and motivation. And then often, there is other hormonal issues at play, for example, low testosterone, which gives them even less motivation and effort feels not as good, which is a bad combination of being mentally tired, and also having less hormonal motivation and effort does not feel good. And a lot of times, that just starts to spiral of the body mind soul treatment. It's not uncommon to see, sometimes people come and they just want to check everything and get a good baseline panel. So many people come in, they have 10 years of inside tracker results put into an Excel spreadsheet. So no, each individual is unique. But it is common, I would say probably 60 to 70% of my practice is females over the age of 35.


Cynthia Thurlow: Yeah, well, I'm laughing because I used to be able to pick out the engineers, whether they were male or female very easily and effortlessly because they came in with a lot of data. And if they didn't have a spreadsheet that everything perfectly aligned, I would say, are you an engineer, and they would always ask well, how do you know? Well, I know because you're just this quantitative-focused, it makes it a whole lot easier for me to understand the way that your brain thinks, you mentioned low testosterone. And one of the other things that I think is particularly frustrating for women as they are, having fluctuating amounts of progesterone and estradiol, which is the predominant form of estrogen prior to going through menopause. One thing that women become very frustrated with is this change in body composition, the relative insulin resistance that they start experiencing, even if everything they did before, now, all of a sudden, their normal eating pattern exercise program, not enough sleep, too much exercise no longer is working for them. And I'm curious where your starting point is, with individuals like that, because one big question that I got for you was talking about weight loss resistance, which I'm sure we are going to touch on. But, from my perspective, it's these changes going on physiologically in the body that we're not talking to our patients enough about proactively. So they're suddenly shocked when their progesterone levels are lower, and they're not sleeping well. And their periods get really heavy, and they're just weight loss resistant and frustrated. And as you said, by the time they get to you, they're incredibly just tired and burned out.


Kyle Gillett: I think that's where a holistic approach comes in, and an individualized approach. That's why I call what I do like individualized medicine rather than algorithmic medicine. There's a checklist of what to do, especially when it comes to finding a new body weight and body composition setpoint. And that checklist includes looking at your household, family, and friends, especially people that you're around on a daily basis. This would include people that you work with coworkers and seeing if their habits have changed as well. And then next would be "Are you mentally in a good place? Is there any other pathology at play a touch of disordered eating, perhaps not even enough to diagnose, but just the touch that needs address maybe with counseling or therapy, maybe with just realizing it and doing some mindfulness and meditation, controlling stress and then looking at your other lifestyle pillars? I recently added a seventh one which is social, because I thought that it was just too important to include with stress and then looking at sleep, often there's a bit of disordered sleep. And that can be optimized as well, and that sometimes does go along with low estrogen and progesterone and vasomotor symptoms. So, it's like you're getting hit or kicked from all these different points, and you have to block all of them. And you don't necessarily have to block them at the same time. But just knowing that if you blocked the punch to your shoulder, then it's not your fault that you're still getting kicked in the shin.


Cynthia Thurlow: I think that's such a great explanation and for many women that come to me, they're coming to me, because they want to talk about intermittent fasting. And I remind them, it is a great strategy. But it's one of many strategies, and sometimes it's not the one that is going to make all the difference. It's all the other things that we have to be doing concurrently, the sleep stress, anti-inflammatory nutrition. You mentioned, the spiritual and social and I think if we've learned nothing else over the past two years, is that we are social creatures, whether we realize it or not, and it how challenging it can be to live your life and feel like you are isolated from your loved ones.


Kyle Gillett: Yeah, that's very true. And I feel that's perhaps the one that affects me personally, the most, as well, between starting a business and having very young children, a toddler and a baby. And trying to do both of those things concurrently, there's just always going to be things that are difficult, it's going to affect your sleep, it certainly affects my sleep still, but it's definitely hard. And it's one of the ones that are least in your control, as well. So, it has a trickle-down effect on all the other ones. I was chatting with Rich Roll. I was on his podcast, and I was talking about the six lifestyle pillars, and he said that there really needs to be a seventh. So, I guess he came up with the seventh one. But it's like you're trying to get into a club or sorority, I suppose. You're not just becoming best friends with one of those pillars, you want to have at least 80% or 90% so that you don't get blackballed. I suppose you want to have all those fairly well. The law of diminishing returns does apply when it comes to health.


Cynthia Thurlow: It makes a lot of sense. And I would say that one of the things that I think many women find surprising is that chronic stress, like maybe the things you tolerate in your 20s and 30s are no longer tolerating-- you're not tolerating quite as well, and your 40s, 50s, 60s and beyond. And so, when we're not getting proper sleep, when we are not getting restful, deep sleep, REM sleep, what are some of the things that can happen? So, I'm kind of leading you to a leading question because I want to lead into what happens in our bodies with chronic stress. Because it's not benign, I think quite a bit about women that are going through a divorce, where they've had a bad hospitalization, or they lost their job or a big move. We don't weather stress quite as effectively at this stage of life. And so, we may start seeing other issues cropping up in our bodies in response to those.


Kyle Gillett: Yeah, a few things happen during stress and during poor sleep. I usually say the two things that are the best anti-agers. Specifically, the best to preserve quality and quantity of mitochondrial function is REM sleep and zone 2 cardio. And those two things can both be hard during times of stress, but they can also both be therapeutic during times of stress. So that can be a bit of a self-fulfilling prophecy. In addition, as age progresses, adrenal function decreases in general. So there's this little area of the adrenal gland known as the zona reticularis and it makes a lot of cholesterol-based hormones. So, stearyl. Cortisol is actually one of them. And DHEA or dehydroepiandrosterone is another one after menopause. By the way, Fernand Labrie was one of the first individuals that elucidated that pretty much all the postmenopausal androgens, for example, testosterone and DHT, come from DHEA and the adrenal because the theca cells in the ovary are no longer functioning. So, there's no ICD-10 code yet. I've said this several times, maybe there will be eventually for adrenal fatigue, but there is one for Addison's disease, which is like really severe adrenal fatigue, I guess. So, continuing Addison's disease, way up here is Cushing's disease. And just like you see a lot of cases of hyperthyroidism or Graves burnout and develop into hypothyroidism. We see the same thing in the adrenal gland. It's a fairly well-known phenomenon in endocrine glands like the thyroid and the adrenal. So, it's really a matter of time until you reach that point. And by the way, the term for the physiologic decline in adrenal function is adrenopause. So, you have menopause and then adrenopause. And yes, it is synergistically more difficult usually when you have both at the same time.


Cynthia Thurlow: Absolutely, and it makes a lot of sense. So, backing up to the sleep piece. If we're connecting with nature, if we are meditating, if we are doing a fair amount of exercise, and we're perhaps being really mindful about our diets, what kinds of sleep supports are you a proponent of? And the reason why I'm asking this is that I know when you were on with Huberman, you were both talking about melatonin and GABA. And so, these are obviously supplements that I do recommend in specific circumstances. But are there supplements that people can take like adaptogenic herbs or L theanine that you think are fairly benign to take every night versus things that should not be taken every evening?


Kyle Gillett: Yeah, definitely. It depends on the person, of course, but some good starting points is looking at your Inositol, In women, you want to look at Myo-Inositol, and D-chiro-Inositol. If you're taking lithium, even like a lithium supplement, like lithium orotate, that can deplete the levels of inositol in the brain. So, I put anybody that's on lithium, not necessarily lithium carbonate, which is the medication but there are supplements that are more mild if you will, I think all of those individuals should be on an inositol supplement, and it has other benefits as well. Apigenin is an interesting one, there are different types of Apigenin's and Apigenin Glycoside. They come from many different plants. Two of my favorite ones are vitexin and isovitexin. So, this can help with both monoamine oxidase I believe it's a weak monoamine oxidase B inhibitor. And it also helps with the synthesis of dopamine in the hypothalamus. There's an area called the basal ganglia and, in that substantia, nigra, and a lot of synthesis of dopamine occurs in this area. And as you age, it's similar to the function of the nephrons and the kidney, it decreases and even a normal healthy individual could have, 20% function left by age 80 or 90 and not have any noticeable pathology. As it decreases more and more. The next thing you see is REM sleep disorders. And by the way, REM sleep disorders, almost always precursors to Parkinson's disease or Lewy body dementia, which is a deficiency in dopamine.


Cynthia Thurlow: That's really interesting, I think, on a lot of levels. My experience with Myo-inositol has been around PCOS and certainly helping with insulin sensitivity, but some of those others that you mentioned, I'm not as familiarized with. What I do think is significant is the sleep peace and understanding that there's this interrelationship between not getting enough restorative REM sleep and making us more susceptible to certain types of neurocognitive issues. I mean certainly, Lewy body dementia is I believe what Robin Williams was suffering from or was diagnosed with at the time prior to his death. But certainly, dementia in neurocognition Is something the older I get, the more I get concerned about neurocognitive impact of not getting enough sleep, so certainly an area of focus. What are your thoughts about melatonin? I know that Dr. Huberman was saying he really only likes it to be utilized when people are dealing with jetlag, or with travel. Do you think low-dose melatonin in speaking in generalities, low-dose melatonin is reasonable considering we know we start producing less melatonin as we get older or do you feel like that is something we should just use very sparingly?


Kyle Gillett: It is reasonable, people metabolize melatonin at very different rates. There is salivary hormone testing where you can get melatonin along with cortisol that will just show unbound hormones, of course. So, if you have a really high SHBG, they'll look lower and then opposite, for low SHBG. But yes, melatonin is helpful. There are three main receptors. I think they're just called melatonin one, two and three. And there are different medicines. For example, ramelteon hits, I believe, the first and the second melatonin receptor. The third melatonin receptor is the most directly, hormonally active, I believe, on the pituitary, or perhaps it's the hypothalamus. It decreases the level slightly in a dose-dependent manner of gonadotropin-releasing hormone which is released at night. And that goes down to the pituitary where it releases LH and FSH. After menopause, women are particularly good melatonin candidates, because the LH and FSH are particularly high because there's not that feedback inhibition. So, those individuals as long as you're not metabolizing it too slowly. I love to use melatonin, the main patient population that I'm very careful not to use consistently is pediatrics.


Cynthia Thurlow: And that makes sense. I have teenagers and one of them was at a new high school and was feeling stressed. And so, he was taking melatonin until I realized he was taking it every night and I just tried to explain to him we don't want to suppress your own endogenous secretion of this hormone. It's different if dad or I take it, but certainly very different if you're taking it and so I'm glad that I'll make sure that he listens to that part of the podcast that it will provide validation other than just hearing it from his mom. What are your thoughts about GABA?


Kyle Gillett: GABA is gamma-aminobutyric acid, so it's the main inhibitory neurotransmitter. There's no such thing that's too good to be true, heavy dopamine agonists or like this, for example, dextroamphetamine, heavy GABA agonists are like this as well, for example, benzos like Xanax, GABA is more mild than that. But if you take it consistently, it just doesn't work as well. A lot of sleep supplements have a small amount of GABA in it, which is potentially okay. But you don't want to only go along the GABAergic access. Glycine is another inhibitory neurotransmitter that's easy to take. So, if you're going to take something that's inhibitory every night, I prefer glycine over GABA, GABA every once in a while, is fine to take.


Cynthia Thurlow: Yeah, it's interesting. When I listened to that podcast with Dr. Huberman and yourself, I was like, "Hmm, I've been taking GABA most nights I probably need too- and I started doing it every other night just to see if I noticed any change in my sleep, which I didn't for which I'm really very, very thankful. Now, one thing that would be helpful to pivot and look at is looking at, as we are getting older as we are-- our body is producing less endogenous sex hormones so testosterone, progesterone, and estrogen. And again, speaking in generalities, when a woman is in perimenopause, I see a lot of women that are putting on oral contraceptives IUDs to help control and manage their symptoms, because many women have very heavy menstrual cycles. What are your thoughts on oral contraceptives at this stage of life? Do you think that there are benefits beyond just controlling symptoms? Because I've also seen some reports of when women are taking oral contraceptives that can actually hasten the ovarian follicle, demise.


Kyle Gillett: Yeah, sometimes, the most complicated topics are more simple. So, I think of oral contraceptives as synthetic HRT. And I think that simplifies things a lot. Whether you're talking about synthetic progestogens, also known as progestins, or synthetic progestogens, or synthetic estrogens, or even synthetic androgens, they almost always have an activity at receptors different in the bio-identical form. So, whether that's the glucocorticoid receptor, whether that's a stronger binding, which is known as agonism in the liver or stronger effects to produce more SHBG or more platelets, by the way, those two things SHBG, which is the protein that binds up estrogens and androgens and also platelets. The higher those increase, when you start an oral contraceptive, you have a slightly higher blood clot and stroke risk as well. And then of course, people who have migraine with aura are not good candidates for COCPs at all. So, I think of them as synthetic HRT. And as most people know, I'm generally a fan of bioidentical HRT. It eliminates so many confounding variables. And most of the time I see people on synthetic HRT or COCPs or whatever you want to call it. There's a cascade of side effects, a prescribing cascade where you're starting one thing because of something else.


Cynthia Thurlow: I think a lot of women, especially younger women are probably surprised when they're put on oral contraceptives, that the sole purpose for many people is for contraception and all of a sudden, they then have no libido because the sex hormone binding globulin is impacting their testosterone levels, and they're no longer as interested in sex, which is a cruel irony. I think that more often than not, I'm seeing women that are put on progestin IUDs to help control symptoms, they then have no idea where they are in terms of how close they are to going into menopause because they're no longer having cycles. Same thing with women that have ablations. How do you help women navigate decision-making about utilizing when to start utilizing hormonal replacement therapy? I think for a lot of women, they would benefit from starting some type of bioidentical therapy prior to, going through menopause.


Kyle Gillett: Yeah, informed consent is certainly an important piece of this. Another good rule of thumb is synthetic HRT is inherently more complicated. Not that regular HRT is not complicated, it is slightly more complicated. So, if there's a provider that does not feel comfortable with bioidentical HRT then perhaps seek out a provider that is and then have them manage your oral contraceptives as well. Pretty good rule of thumb. But anyway, as far as like when to start HRT, you're just getting all the different positives and all the different negatives weighing them out like a balance scale. And then if the benefit outweighs the detriment, you start as early as possible, as whatever estrogen-progestogen and androgen decrease.


Cynthia Thurlow: I think that's a good rule of thumb. It's interesting that-- I think the Women's Health Initiative is one example, left an entire generation of women and clinicians that were oftentimes fearful of prescribing hormone replacement therapy, or any hormones for that matter. And the reason why I say this is I probably get multiple DMS almost every day, and I'm no longer prescribing medication. So, I'm referring people out. But I'm grateful for the work that you and your team are doing to help educate people about options that you don't, per se, need to navigate middle age, if you choose to do hormone replacement therapy, great, there are options if you choose not to do hormone replacement therapy, there are options for you as well. Are you starting to see that there's more clinical acceptance from your patients? Or do you still feel like you've got a pretty varied population of women in terms of middle age and helping make those informed decisions?


Kyle Gillett: I find that my patient population is certainly happy to make decisions and act proactively even like before they're feeling severe symptoms. It depends, though, many women don't like going to the doctor, and they feel that it is unnatural. And I've said many times before, I'm as natural as they come, granola tree hugger, whatever you want to say, whatever terms you want to call, but at the end of the day, Physiology of aging is also a natural process. And it is more than okay to fight it. So that's the way I think of it is if you're going to be completely natural, that is okay. But just know that I also think the natural human instinct is to use tools in order to help make our lives better. And medications and supplements are just two of those tools.


Cynthia Thurlow: I think that's very prudent and wise, I think for a lot of women, there's this tipping point, they'll get one symptom, either it's the erosion of sleep, or they start getting genital urinary symptoms, and sex becomes painful, or maybe they're having brain fog. And that's particularly bothersome, especially for some of my very successful patients that need to be feeling like all their cylinders are firing properly that may then be the impetus to consider hormone replacement therapy. And more often than not, I do find that women feel significantly better, even if it's initially a localized product. And we can briefly touch on the fact that there are different options, there are systemic options, there are localized options, if a woman is coming to you, and let's say, for instance, she's not ready to use a patch or the cream, and maybe she just wants a localized product, do you have preferences for intro vaginal estrogens, or androgens to utilize to help replenish that part of her body, so maybe she can get back to a point where she's having sex comfortably with her partner or significant other.


Kyle Gillett: Yeah, sometimes it's both, sometimes one or the other depending on the situation. I'm not in the camp that only starts with topical estradiol or topical estrogen. Some people still use primer as well. Interestingly enough, the UK just made low-dose intravaginal estrogen over the counter. So, UK docs, often patients will have tried that before.


Cynthia Thurlow: Well, it's nice that they're pretty benign options that people don't feel like require injections or, more sophisticated means of getting the medications. And when you're talking to women about some of the changes that happen with their bodies. And this is going to align itself back with a pillar, I think the concept of sarcopenia, or this muscle loss with aging and the large ramifications of what happens in a male or female for that matter, as they start replacing muscle with adipose tissue. When you're working with your patients, are you guiding women into talking about strength training and the importance of