GLP-1s & PCOS: What The Research Actually Shows

Hello and welcome to the Ark Woman podcast. This is an exploration of woman kind. Here we discuss what it is to be a woman in the modern world while utilizing ancient and modern modalities in tandem to create a bounty of health for the body, mind and spirit. G'day everyone and welcome back to the pod. Hopefully you're having a nice day. Hopefully you're having a nice week. I'm trying to record this so I can get to the airport in time to pick up my best friend. She's coming here to visit me for a few days. I'm so excited about it, but I just felt that it was my due diligence to do my weekly podcast. And before we get into it, I'd like to pay my respects to the elders past, present and future in the tree of the Tasmania, where I am recording this podcast today. Always has, always will be baby. Let's talk about GLP ones. It is a huge being online. I'm not going to go too hardcore into their application. I'm just going to be covering it at the outset if you haven't heard about them. Wow, amazing for you. You must be living under a rock. I know I'm super late to this party, but I just, I like to wait for the dust to settle for the hype to kind of settle down. And then I look at the research and see what is actually being stated in the research, what we're actually looking at in the research, what the research actually suggests, versus what the hype is saying. And I can't really say that much about GLP ones and their broad application to lots of different women's health, but I can speak to PCOS because I've looked into a lot of the research here. And I will say at the outset, there is a huge mismatch between what people are saying online and how we can apply PCOS and what it actually does and what the research has shown. And I've found some clinicians. I've found like health professionals online who are taking pilot randomized control studies with like 28 women and saying, it has this application for IVF, girl, we cannot say that yet. Anyway, I'm going to get into it. Let's talk about GLP ones and what they are. So you actually understand what they are and how they work in the body and how we're kind of hijacking a system. So GLP ones stand for glucagon like peptide one, GLP one. That refers to the naturally occurring increase in hormone made by our body. So yes, our body makes GLP ones, not just synthetic GLP ones, we actually make them in the body. They are produced primarily by the endocrine L cells in the distal small helium. So in our small intestine and in our colon in response to food intake, specifically carbohydrates of fats and specifically a bolus of carbohydrates of fats. So you sit down and have a fat pasta covered in olive oil. Your small intestine is going to release GLP ones in response to that. We also see GLP ones being released in the brain stem. So we have a brain kind of extends down into the upper part of our neck and we're also seeing GLP ones being released from the alpha cells in our pancreas as well. And this acts as a local neurotransmitter and modulator for insulin as well because the pancreas is where insulin is being made and released. So basically what happens naturally we eat a bowl of pasta covered in olive oil. Lots of fat, lots of carbohydrates, awesome macronutrients, we need them. That travels through our small intestine. When it reaches our small intestine, our small intestine goes wow, that's a lot of fat and carbohydrates. What I do in this situation is I release GLP once and that basically will enhance glucose dependent insulin secretion from the pancreatic beta cells. So our pancreas has beta cells, those beta cells release insulin. Insulin's job is to go over to the cell, attach to the receptor side and that basically says there's hints of glucose around my guy. You need to open up your glucose channel so you can use this as energy to power your mitochondrial function and all of the endomatic reactions inside of the cell or we can store it as fat. And we're storing that as fat in our muscle tissue, in our liver and in our adipose tissue, which is our fat tissue. So GLP ones are basically the messenger between we see carbohydrates and fats and we're releasing insulin. It is a peptide that connects these two physiological things that happen every day in our body. It will also at the same time, GLPs I'm talking about will also suppress glucose gone release from the pancreatic alpha cells and that reduces hepatic glucose production. So our body will take other constituents in the body, it will take stored glucose and it will make glucose and put it into the blood system. GLP ones basically say we don't need to do that because we've got heaps of glucose in the blood system already because we've just had a bowl of pasta. You get? And also on top of this GLP ones will promote satiation and reduce your appetite in the brainstem. So that's where some of your appetite centers are in your hypothalamus and your brainstem and GLP ones tend to tell those parts of our brain, hey, we don't need to eat anymore, we're pretty full. The interesting thing about endogenous, so naturally occurring, we produce our own GLP ones, they are rapidly degradated within minutes by an enzyme called DPP4, which limits the duration of their action. So remember, this is a peptide, so it's made of amino acids that haven't fully formed into a protein just yet. That will basically signal carbohydrates in system, fats in system as well and we need to release insulin. It's only around for a short period of time, right? And it's also around in different parts of our brain to signal that we are full and we don't need to eat that many more carbohydrates. Yeah, pretty interesting. Exogenous GLP ones, these are GLP one receptor agnus, so GLP one arrays, they are medications designed to mimic and enhance the action of natural GLP one, but they resist that rapid breakdown by DPP4, which means it can stay around for a lot longer, it allows longer biological activity. GLP ones have been used forever for type 2 diabetes, weight management, obesity and overweight treatments, and they also have cardiovascular risk reduction indications as well, which makes total sense because if you are obese or overweight, you have too much adipose tissue that's going to put pressure on your cardiovascular system. If you lose the weight, it puts less pressure on the cardiovascular system, so those two things very often go hand in hand. Most GLP ones are administered by a subcutaneous injection using a pre-filled pen, so you can't really, unless you are talking to your doctor about doing different dosages, control the dosage, you can control it by if you're using it once a day, twice a day, once weekly, etc. There is oral formulation, so semioglu tide, those are tablets and they're taking on empty stomach and it's really, really strict how we take these, you have to make sure you're doing it on an empty stomach to ensure absorption and then you're eating a specific food within a period of time after that, and that depends on your dosage, that depends on your doctor, etc. But mostly we're seeing GLP ones are administered by an injection, and so they include dual-gluteide, exanatide, lura-gluteide and semiogluide. So semiogluide is ozampic, that's the most popular one that we've heard about and mongiara as well. So again, once we when we inject a GLP one, whatever one I just said, it will go into the blood system, blood system, go throughout the entire body, and that will bind to receptors in the pancreas, brain and gastrointestinal track and your cardiovascular system as well. There are GLP one receptors everywhere throughout the body, I don't have that much time to talk about it today, it's not really the primary purpose of this podcast, but I just want you to understand that we have GLP one receptors all over the body, but usually they're not very activated because we don't have GLP ones circulating for that long, but this exogenous medication stays around for longer, which means it can attach to receptor sites for longer, stay attached to those receptor sites, and they exhibit their response for longer periods of time. Then we would see endogenous naturally occurring GLP ones from our brain stem and our small intestine. So when we use exogenous GLP ones, they suppress glucose constugration, they reduce hepatic glucose output, they slow gastric emptying, so you feel fuller for longer, and that also means that you aren't as hungry, because GLP ones are also acting on those appetite centers in your brain. We were just talking about in your hypothalamus in your brain stem, it attaches to those receptor sites and says, we don't need to eat, we are full. And so therefore, people don't eat that much and they lose weight. We see that GLP ones improve blood pressure, lipid profiles, hepatic sterosis markers, and secondary metabolic markers, and we can put that all down to the fact that we're losing weight, yeah? So we see those outcomes, even if you're not on a GLP one, we see those outcomes, if you lose weight, GLP ones just help that process along by significantly. So there are a plethora of different benefits associated with GLP ones because of this reason, right? So we're seeing lower cardiovascular risk and we're seeing better cardiovascular outcomes. We're seeing a lower systolic blood pressure, we're seeing better cardiovascular endothelial function, we're seeing improved lipid profiles, we're seeing decreased triglycerides, we're seeing a reduction in the liver fat storage, which is great because that decreases liver disease, and that also decreases GLP ones also enhance insulin sensitivity. So basically our cells have receptors for insulin and they actually start listening to insulin. So a lot of the time when we're talking about insulin, we're talking about the sensitivity that our cells have to insulin. So insulin comes over, attaches to a receptor site that opens up a glucose channel. But in individuals who have had high insulin for a long time, who have had high glucose for a long time, this is very often women with PCOS, what can happen is our cells go, we're not listening to you anymore. There's always insulin around. A bit of a, you know, it's a bit of a situation where these cells are like, okay, insulin, I hear you, I know that you're telling me that there's glucose in the blood system and that I need to open my glucose channel, but I'm actually good. I don't need anymore glucose. I've had enough stored, we've got like all of our enzymatic reactions happening. We don't need anymore glucose here. So I'm actually, I'm not going to respond to your message. I'm kind of going to ignore it. It's like when your mum calls you and you don't want to answer, yeah, that's what it's kind of like in a way to modernize it and to help you understand insulin sensitivity. But when people take exhaustion as GLP ones, we're seeing that the cells become more sensitive to insulin. insulin. They go, "Okay, yeah, cool. We can take in more glucose no worries." And that stabilizes the blood system that has lots of positive outcomes on cardiovascular, metabolic, and also like our weight management as well, which all positively impacts PCOS. We'll get there eventually. We're also seeing because there is a slower transit time, we're seeing altered viral acid signaling, we're seeing an improved metabolic environment. So lower blood glucose lower insulin. So lower inflammation generally. We're seeing that that indirectly positively influences the microbiome, which is awesome because a lot of women with PCOS generally have a non-diverse, pretty sterilized and inflamed gut. But if we take a GLP1, what we generally see, because have how it impacts our gastric emptying and our blood glucose and blood insulin levels, we're generally seeing the gut microbiome becomes more diverse and can heal a little bit. So we're seeing less intestinal hyperfirmability and less inflammation, which generally is really, really great. Alongside this, GLP1s are so interesting. They impact our hypothalamus and our pituitic gland and how it responds to dopamine and the dopinergic impacts on our brain and circuits in our brain. And a lot of things that I've heard about food and food addiction and binging, which a lot of women with PCOS struggle with, is that they don't feel like they need to do that anymore because GLP1s can impact the dopinergic circuits in our brain. And so we're not addicted to things anymore. So I've heard stories of women who are sharpaholics who just don't necessarily feel like they need to do that anymore. People who are addicted to smoking addicted to alcohol, both incredibly addictive substances, don't really feel the need to drink or smoke anymore. And we also see that with food. So that's another way we're seeing weight reduction is because people aren't drinking that much, people aren't smoking that much, which in both associated with weight increase, and they're also not binge eating and not craving sugary salty, high fat, high carbohydrate, low protein processed foods anymore because it impacts how dopamine is released and circulating in your brain, which is think is really fascinating as well. It's not all good though. There is a massive lawsuit happening at the moment with ozempic. So ozempic is the brand name for semaglutide. So this is a related GLP1 drug and the target manufacturer is Nogo Nordstick and the focus is on serious adverse events that have happened two thousands of people. So litigation started in 2023 in February of 2024. The US traditional panel in Peltz-Norvenia put forward a case. So the case number is MDL number 3094 if you wanted to look it up. Case numbers are expanding really quickly. It originally started with 1,500 and now we're up to beyond 4,000 cases, 4,000 plaintiffs involved in this lawsuit. So it is absolutely huge. It's absolutely massive. In December 2025, there was a multi-district litigation that established focusing on vision loss claims. Originally, this lawsuit only included gastrointestinal problems and adverse reactions, but now we're also seeing that people who have used GLP1s have lost their vision and went blind and have now had vision problems as well. So the primary injuries that we saw originally in the original lawsuit in 2023 was stomach paralysis, leus, bowel obstruction, assistant vomiting, via digestive dysfunction, and now we're seeing vision loss, pancreatitis, gallbladder disease, dehydrated related kidney injury, and thrombotic events. Biggie Ix, that's not very fun. So what the plaintiffs are basically arguing in this lawsuit is they're saying that nausea and GI upset were disclosed and they were told to them in there. The doctor's appointments in the packet insert of ozemic, but the long-term gastric paralysis and severe intestinal injury were not clearly communicated, which is a bit concerning because maybe ozemic didn't know about that. Maybe they released this drug without actually doing proper testing. Biggie Ix. So basically this lawsuit is for $2 billion and the plaintiffs are seeking compensation for medical costs, lost income, long-term disability, pain, and suffering. You really cannot put a price tag on health. $2 billion is gargantuan. I feel like ozemic probably has that money. They're probably trying to deal with this quite quietly, but it's not going that way. And I just want to point that out that like there is serious risk associated with the overuse of certain peptides. Peptides are a massive conversation happening in the health sphere at the moment. GLP ones are like the oldest one that we know about. GLP ones we've known about GLP ones we've been using GLP ones for tattoo diabetes and obesity and overweight individuals forever, but because they are popular I believe that they have been overused, they've been dozed too high, and we actually haven't seen individuals eating enough. So the problems associated with weight loss at that rate are all of these other issues that these plaintiffs have experienced as well. So I don't want anyone like taking a GLP ones after they see an Instagram post because someone said that it helped them with their PMDD. And I'm not going to discredit the use of GLP ones for things like that, but I'm just saying that there is serious risk associated with this. When you look in the packet inserts they will say it's rare that you'll get pancreatitis and it's rare that you'll get blood, that you'll get blindness and things like this. But you have to understand there is a dose dependent risk associated with the use of GLP ones and you need to be so bloody careful with who is consulting you on the use of GLP ones, how much of a dose they're giving you. Like you just need to go really really slow with this peptide because our body is not actually built to have so much of this in the system. If we really understand that we only release it under a very certain condition for a short period of time, then we have an enzyme to break it apart really quickly. There's a reason why there is an enzyme to break it apart really, really quickly. I think overuse of this medication is going to have negative health outcomes and there is risk associated with it. So that's why I'm going to sound this podcast. This is not a consulting. I'm not consulting you on the use of GLP ones. I'm not encouraging the use of GLP ones. I'm also not saying don't use them. I'm just saying here is the information that we know about. Please take this to your health practitioner and your health provider. So you can make an informed choice. That's what this whole thing, that's what all of my work to do with our Corbin is. So you can I can give you the research and say hey this is what we know. So you know so you can make informed decisions about your body. I'm not telling you what to do. I'm not telling you not what to do. I'm just saying hey this is what we know and this is what we don't know. Okay, okay. So let's look at the research on GLP ones specific to PCOS. So I've sit you through quite a lot of the research. There are PCOS focused randomized control trials. There are prospective cohorts. There are matter analysis, reporting reproductive and endocrine outcomes, apart from weight loss, which includes menstrual cyclicity. So how regular your periods are ovulation, whether people are ovulating or whether they're not. Androgen profile. So DHAS, pre-testosterone, sex hormone binding, globulin, ovarian morphology, inflammation markers, CIP, being one of them. Insulin sensitivity and fertility outcomes, including IVF and also people spontaneously conceiving as well. We're also going to be looking at the mechanistic literature on ovarian and centroid reproductive axes. So your hypothalamic pituitary gonadotropin. So that's a HPG axis or HPO axis in women. That's relevant to PCOS. So all the research I'm going to be looking at now is on PCOS. So if you have endometriosis, if you're a manipul, or none of these researches really go into apply to you. I have to just say this at the outset. 80 to 90% of the research that we have on GLP ones and the application to PCOS is in overweight, no beast individuals. If you have PCOS and your at weight, maybe you have a little bit of extra weight, but you're not classified as OB sort overweight, we don't know about you. We really don't. We don't have that much research. And the reason why is because when we reduce weight, we improve insulin markers. When we improve insulin markers, we improve ovarian and androgen and insulin and inflammatory markers. That's kind of how it works. So if you are at weight, if you are under weight, if you are fit and healthy, and you're considering GLP one, because you've heard they're good for PCOS, we simply do not have the research on you. Almost all of the research is on women with PCOS who are overweight or obese. And alongside this as well, literally every study I looked at, the max it ran for was 26 weeks. So very few track what happens beyond that. They're a really small open label, low participant studies that might look beyond that, but you know, those studies are really inconclusive as well. So when people are making broad overarching statements about PCOS and their application for things beyond weight management, I just read you find that. I didn't see that. I don't know where that is. If you find those research papers, please put them in comment section and make me aware of them because I haven't seen them. Okay, okay. Let's get into the research. Shall we? A GLP once in PCOS research. I looked at a large prospective randomized open label trial of Metformin Plus semi-glutide. So that's Metformin Plus ozempic basically versus Metformin alone. And so the treatment was for 16 weeks. They had 40 women for reproductive follow-up. They reported higher rates of menstrual cycle recovery, which basically means they had periods more regularly. So the group that had Metformin and ozempic, they had regular cycles, 72.5% of the time versus the Metformin group alone, which is 42.3%. So that's pretty cool. And the higher pregnancy rates as well. So the ozempic and Metformin group, they felt pregnant at a rate of 35% versus the Metformin group felt pregnant at a 15% rate. So that's really cool. Alongside this as well in this study, it's not entirely clear whether all of these women were trying to fall pregnant. So I think that's interesting. But even if we took that into mind, 35% versus This 15% is pretty cool, as well as larger improvement improvements in sex hormone binding globulans. So we want higher sex hormone binding globulans in women with PCOS because it binds up all of those excess testosterone so that free testosterone. We're seeing lower free androgen index, total testosterone lowered, so did CRP. So the between group differences and HOMA II change were not significant, despite within group improvements. So these absolute differences did appear pretty notable. So that's that first study. And this is a trend that we generally see in research involving GLP1s and PCOS is very often it's in combination with a different medication that improves insulin sensitivity. And what we're generally seeing is that GLP1's plus metformin or some other insulin medication is going to work better than metformin on its own. Which I think a lot of people just hearing that at the outset are going to go dull because we have two different medications working on different aspects of insulin sensitivity. Of course it's going to do better. So first study in is GLP1 a miracle cure for PCOS? This study doesn't suggest that. As we're talking about pregnancy, let's talk a little bit about IVF because a lot of women with PCOS will go down the IVF and IUI road. So the evidence for IVF outcomes is really sparse with a small pilot study. So it was a randomized control study that used a GLP1 and metformin versus metformin on its own in obese infertile PCOS patients. And that reported markedly higher pregnancy rate per embryo transfer. So the group that used metformin and a GLP1, their embryo transfer rate was really high. It was 85.7%. That's really cool. That's super significant. And that is really cool in comparison to the metformin group. So the metformin group, their pregnancy rate per embryo transfer was only 28.6%. And that's after a drug washout period as well. I have to really say that. We can't really use GLP1's in close contact with pregnancy. So we're using GLP1's in metformin. And then we're stopping the GLP1. And then we're waiting a few months for that drug to wash out. That's called a drug washout period. And then those women are falling pregnant with IVF. And we're seeing even though there was a drug washout period and the GLP1 wasn't present at pregnancy, we're seeing the IVF pregnancy transfer rate was really high at 85.7% in comparison to 28.6%. So that's really interesting. The problematic thing about this study is that I've seen this study doing the rounds quite a lot. I'm not going to name names, but some pretty reputable Instagram accounts and clinicians and things like that. Sighting this study and saying, this is amazing. Go and get GLP1 prescription and get more formin at the same time and then do IVF. OK, this is a small pilot study. When we see a study like this, with such amazing outcomes, I'm so hopeful about that. I think that's amazing. But in this case, it doesn't mean let's treat women with this information. No, it means, wow, this is really interesting. We need to do more studies. We need to replicate this study with more participants and we need to do it over a longer period of time. And then we can make conclusions. We cannot make conclusions from this study is that it is a small pilot study, which is, it means it is the first of its kind. We cannot make conclusions from this study. So from a guideline perspective, the International Evidence-Based Guideline for the Assessment and Management of Policis to Govary Enzyndrome advises that GLP1 receptor agonists, like ozempic, may be considered for weight management in women with PCOS. But it emphasizes that we cannot use GLP1s for the treatment of infertility because we cannot use anti-obesity agents close to pregnancy. So that basically means the International Evidence-Based Guideline has spoken on PCOS and its use of GLP1s for contraception and said, we cannot market this. We cannot use this as a contraceptive improver. We cannot do that. It's basically saying it is unsafe, cannot treat women who are in fertile with PCOS with GLP1s. Okay, and that was in 2023 and they still stand by that statement. So it's really concerning when I'm seeing people online saying, you know, GLP1s' improved fertility outcomes go and get your GLP1s. Okay, the position statement from this organization is vehemally against that and they've stood by that statement for three years now. They haven't updated it. So there's that. Okay, so those are outcomes for pregnancy. Let's look at GLP1s and menstrual regularities. So how regular your cycle is, this is a common thing with PCOS. Your cycle might be every 42 days, it might be every 28 days, it's not regular and that is one of the diagnostic criteria underneath the Rotterdam criteria that we use to diagnose women with PCOS. So the evidence that we have on GLP1s based therapy improves menstrual regularity. This does exist, but the magnitude and the consistency depend on the comparator and how menstrual outcomes were basically noted in these studies. So bleeding ratio, menstrual frequency and cycle recovery. So there are a lot of different ways that we can look at the metrics of the regularity of a cycle and each study is going to be looking at different metrics basically. So in a study where they use semi-glucard and metformin in a randomized control trial, menstrual cycle recovery was 72.5 versus 42.3 after 16 weeks. So women were on metformin or metformin and ozampic at the same time and they looked at how regular their cycles became and the group that were on a GLP1 and they were also on metformin, their cycle recovered and was cyclical and we could not we know what it came and it was more regular. So we could have a full period of time and we could have a full period of time and we could have a full period of time and I post about PCOS pretty much every single day. So if you wanted to learn more about that there is lots of resources that have made on PCOS but you can go and find. In another study I found they used a placebo controlled Lyrogluc tide, a trial. They found that both a variant dysfunction and cycle regularity improved in both groups but the between group difference in cycle regularity was 0.14 so that favored the GLP1 over the placebo. When we look at meta-analysis, so meta-analysis is when we find a lot of different randomized control trials and we pull them into one and we look at the data and we pull apart different data points and we talk about the data that's found in a group of studies. So meta-analysis are at the top of the evidence hierarchy so meta-analysis and systematic reviews are really, really amazing when you're looking at anything. So there is a meta-analysis I found that used ERP1, PCOS. And so the results are really, really mixed. And the results really, really mixed because we're using different combinations of platforms and ERP1 receptor agonists. We have different obesity and obese classes of women with PCOS. The dosage and length is different and what they're testing and what they're basically looking at different metrics in the human body and what they're looking for to change is different as well. So when we looked at that pooled evidence in that systematic review meta-analysis, we're seeing large standardized improvement in cycle regularity. So overarchingly we are seeing the cycles of becoming more regular with the use of metformin and a ERP1 or a ERP1 on their own. So whenever there is a ERP1 around in this meta-analysis they found that cycles were more regular, which is really, really great. In a different meta-analysis though, so this meta-analysis looked at Exanotide, which is a specific type of ERP1 versus metformin. So in this meta-analysis they looked at lots of different randomized control trials that tested the same thing. They found that cycle regularity did not clearly differ between the drugs suggesting that suggesting that any cycle regularity benefit may be less robust when comparing to insulin sensitizing weight affecting agents and comparing it to a placebo. So basically in English what that means is, didn't really matter. Like ERP1s didn't really stand out when we're looking at outcomes of cycle regularity in comparison to other insulin sensitizing drugs that we have on the market, metformin being one of them. So yeah, basically what I'm trying to say there is cycle regularity, pretty mixed, generally looking pretty good, but looking pretty mixed, depending on what research you're looking at. Okay, so let's look at ERP1s and ovulation rates because women with PCOS are commonly anovulatory, so they're not ovulating, and that's because the thicker and granulosa cells are too thick and it can't actually break open in the follicle, can't do its job, and break open, that's why LH goes higher, and that's why we get these cascades of hormonal events. So what we see in a meta-analysis of randomized control trials with the ERP1 called exenotide, that increased ovulation rate in comparison with metformin. So when we looked at metformin on their own and how often women with PCOS were ovulating, versus the ERP1, the ERP1 worked a little bit better. I have to rehash this again. If you are listening to this, if you have PCOS and you're considering a ERP1 4 fertility outcomes, you cannot use it close to the time when you're getting pregnant, you need to have a drug out, wash out period. Hopefully your practitioner is really open with you about that. Just to go back to the 2023 International PCOS guideline, we're seeing that ERP1's are superior to metformin for most reproductive outcomes and ovulation rate is inclusive in that. So generally we're seeing ERP1's improved ovulation, but we cannot take ERP1's close to pregnancy. I'm going to read from the guideline here. It still recommends using anti-obesity agents, so ERP1's, for reproductive outcomes only in research settings, and also in research settings. So if you have an IVF doctor, if you have an IVF doctor, If you have a health practitioner telling you, oh, you want a pregnant, go on a GLP1, this is awesome. No, we are only using GLP to enhance and promote fertility in research facilities and even in research if you're involved in a study. It's not yet clinical. We can't use it to clinically improve fertility outcomes in room with PCOS yet. I've said that a few times because I just really want to tell you guys that because that is something that I'm seeing a lot online. That people are like, you know, I feel pregnant on a GLP1. And, you know, it might be safe. It might not also be. I just, yeah. If anyone listened to this and they took this information and made a choice to take a GLP1 and then they felt pregnant, there were risks associated with that. That's, we just don't know the risks, basically. Okay, let's look at GLP1s and Androgens. So basically Androgens are your male hormones. I don't want to say male hormones because we produce them as well and testosterone is really important for overall women's health. It does a lot of different things in your body. It supports muscle mass. It improves libido, which is why a lot of women with PCOS have really great, high, amazing sex drives. But it can also decrease the hair on top of your hair head. So we're seeing male pattern baldness in the middle of our head here. We're also seeing acne in the jawline and around the mouth. We're also seeing more hair in this area, hair, your arms, hair, your legs as well. So that's what testosterone can do. Because testosterone just works on the hair follicle and that's what it does, basically. It improves hair growth in areas and it basically can cause baldness in other areas as well. So there are a few studies here. Number one, exanotide versus vet formant. So the first study we're seeing here is exanotide versus vet formant. This is a meta-analysis. So we're seeing exanotide, which is a geography one. That increased sex hormone binding globulin by four nanomoles per liter. That's pretty cool. So we're increasing sex hormone binding globulin, which means for testosterone decreases. And we do see that. DHES decreased by 16.47 nanograms per deciliter. We're not seeing total testosterone differ significantly overall, but we are seeing a lower DHES. So that will basically mean that someone's skin will be clearer, that they might ovulate more frequently, et cetera. We're seeing in another meta-analysis that exanotide modestly reduced total testosterone and it improved sex hormone binding globulin. So that's cool. In another study looking at a GLP1 plus mitt formant versus just mitt formant on its own. So that used semi-glutide. So that's exemptic. Semi-glutide plus mitt formant produced larger improvements than a mitt formant alone. So we saw sex hormone binding globulin increased. We saw testosterone decreased as well. In comparison to the group of women with PCOS who only took mitt formant. When we look at GLP1 receptor agonist as a monotherapy, so we're not using them in tandem with mitt formant. We are seeing that ovarian dysfunction increased. We're seeing that sex hormone binding globulin increased by 7.4 nanomoles a liter. And we're seeing that free testosterone decreased as well quite marginally, but it did decrease. So even if you use a GLP1 on its own without mitt formant, we are seeing improvements specific to antigens. So we're seeing generally in that study sex hormone binding globulin increased and free testosterone decreased, which is awesome. Okay, let's move on and talk about GLP1s and inflammatory markers. Specifically, it's going to be CRP, see reactive protein. So that's a liver inflammatory marker, which generally is pretty elevated in women with PCOS. So we're generally seeing that when women with PCOS use a GLP1, that inflammatory marker specifically CRP decreases quite significantly. So in an open label exanotide study, we're seeing in four months where there were 30 enrolled and only 20 completed. So there's 10 who dropped out in that study, which is a bit sus. So we're seeing HSCRP decreased from 8.5, 0.8 or 1.4. So that's a pretty significant improvement in CRP. When we looked at another study, so Santa Glutide and mitt formant in an randomized control trial, CRP decreased significantly within the combination arm. So the people who took a mitt formant and GLP together, their CRP significantly decreased in comparison to the group that only took mitt formant. Okay, let's look at GLP1s and insulin sensitivity. I don't know why I didn't do this up earlier because that's basically what GLP1s all about. GLP1s are designed and used predominantly for weight management and obesity and type 2 diabetes because of its impact on insulin because that's what it basically does in the body. It is a messenger for insulin in the pancreatic beta cells of our body. So understandably, because of this, we're seeing improvements in insulin resistance and sensitivity among the most consistent effects of GLP1 receptor agonists in PCOS because that's what it's used for. So generally, we are seeing improvements in home IR when we're just using GLP1 on its own versus GLP1s with mitt formant. Again, when we see GLP1s and mitt formant together, we're seeing that their insulin sensitivity improves and insulin resistant decreases. And we're seeing generally that insulin works better in the body when we're using a combination of GLP1s and mitt formant together as opposed to a monotherapy of GLP1s on their own. So hopefully you understand the research a little bit more. If you wanted the article on this, it's on my Patreon and Substac next week with all of the references and I'll put all of the references in here as well if you wanted to look at the research. But I just at the end, I just want to talk about this research and its gaps, its limitations and its clinical implications. So overarchingly, this is what I've repeated a lot is that the biggest problem with these studies that we have on GLP1s is that they are really short, they're really small, they only include women who are overweight, no beasts and have PCOS. We don't know how GLP1s work in lean PCOS types. We don't know how they work for teenagers if they've even been used for teenagers and any other PCOS type. Most of these studies as well, there's four different types of PCOS. It wasn't really talked about what type of PCOS these women were, what diagnosis they had. So PCOS is going to change in its name at the end of this month or next month, I believe. There are researchers together now kind of formulating a new name. So PCOS is going to change because so many different women can have PCOS and have very, very different symptomology. So you can have PCOS and not have many, cis on the ovaries. You can have no cis on your ovaries and still be diagnosed with PCOS because your antigens are higher because your insulin is higher and because you're overweight. But someone can have PCOS and have cis on the ovaries and not be overweight. So you understand why the research is a little bit messy is because the diagnostic criteria and the name that we have for PCOS doesn't really fit what women are actually experiencing. So that explains why partially, why this research is a little bit bitsy, basically. And the undercurrent of it is, GOP1s work predominantly really well when they're used in combination with metformin. Metformin itself is quite affordable. GOP1s are not. And you have to be very, very careful with them. Another problem that I have with these studies is how they measured the outcomes. So menstrual and ovulation results are not measured the same way in these studies. They also, when we're looking at ovarian structure, when we're looking at ovarian morphology, when we're looking at psycho-regularity, if this study doesn't go beyond 24 to 26 weeks, and we're actually starting to see changes at 30 to 40 weeks, which I think is totally plausible in this group of women with PCOS. We're not actually capturing that result, which I think is really, really sad. Like most of these studies don't even go longer than 16 weeks. So these studies are really short. They only include a certain PCOS type. And we're not actually seeing that they're measuring outcomes in the same way. So again, that's why the research is really, really messy. That's why the research is for the most part pretty inconclusive as well. I don't want to be your doom and gloom. I just want to end this on a happy note. I am stoked about GOP1s and the application for PCOS. I think there can be really great outcome. I am hopeful. I think the research around GOP1s is really great. And I'm genuinely excited about it. It's promising, right? But what I just wanted to make this podcast about is like, this is the research we have. This is how it's being conducted. This is how long it's for, and this is the type of people that they're testing on and they're researching on. And that doesn't fit every single woman with PCOS. And the studies that we do have that are really, really interesting, like the IVF pregnancy outcome, that was really, really great. 85% of women having successful IVF transfers and pregnancies in comparison to what 30% that's really significant. But if that's being cited a lot on Instagram, by clinicians that people trust, the risk is that women will go out and use that to fall pregnant. They won't know about the risks of using GOP1s close to pregnancy. And they also won't know that it might not work because that study only included 28 women. So that's kind of all I needed to do today. I just wanted to say my piece on PCOS and GOP1s, I think they can be effective. They're mostly effective with metformin. So if you're on metformin already, maybe adding a GOP1 might be effective, but it might not be as well. It will be effective if you're overweight, no bees, but it might not be effective if you're lean because you might not have insulin sensitivity problems, basically. Thanks for listening to my Little Mini rant on this and I'll see you on the next one. Thank you so much for taking the time out of your busy day to listen to this episode. If you loved it, please remember to like, subscribe, and send to a loved one. If you want to learn more from our women, please check out the website at rquoman.com.au where you can find a plethora of offerings like charts, masterclasses, courses, and organic clothing. 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