Do Men And Women Respond Differently to GLP-1s A Critical Analysis
Something I've been piecing together over the last 18 months. Women seem to respond differently to GLP-1 peptides than men do. They often need higher doses, titrate up faster, and deal with more side effects. So I started digging into why.
What I've Noticed
Between coaching thousands of people in Fully Optimized Health and watching my own household, the pattern is consistent.
Women typically end up at higher doses than men. They build tolerance faster. They report more nausea and GI distress. And the appetite suppression seems less reliable.
My girlfriend Taylor and I both run tirzepatide. Same lifestyle, same training, same diet. She doesn't get the same appetite suppression I do at her dose. Her sister, who recently started tirzepatide, told me the same thing. Some weeks the GLP-1 feels like it's working, other weeks it doesn't.
For men, the response is usually pretty linear. For women, it's a different animal.
A Quick Refresher on GLP-1
GLP-1 stands for glucagon-like peptide 1. It's an incretin hormone made in your intestines in response to food.
It does four main things. Stimulates insulin secretion, inhibits glucagon, slows gastric emptying, and promotes satiety in the brain.
GLP-1 peptides like semaglutide and tirzepatide are synthetic mimetics that do the same thing, just stronger and longer-lasting.
Body Composition Plays a Role
Women typically carry more body fat than men, pound for pound. That's normal female physiology, not a flaw.
But higher body fat shifts the hormonal environment. Higher leptin levels. More potential insulin resistance. Different receptor sensitivity and density in the brain.
If a lean man and a higher body fat woman take the same dose, the woman's tissue distribution and receptor response is going to look different. Generally, the leaner you are, the lower the dose you need to feel the effect.
The Hormonal Roller Coaster
This is the big one. Men's hormones are basically a flat line through the month. Women's hormones look like a roller coaster.
Estrogen can enhance GLP-1 sensitivity, but it fluctuates. Progesterone modulates GLP-1 activity, and it fluctuates too. So the same dose can hit very differently depending on where she is in her cycle.
Taylor and I have tracked this. Regardless of her tirzepatide dose, certain phases of her cycle she's just hungrier. The cravings are dampened compared to no peptide at all, but they're still there.
Post-menopausal women often need even higher doses because hormone levels drop and GLP-1 sensitivity changes again.
Slower Gastric Emptying
Women generally have slower gastric emptying than men. Period.
This cuts two ways. The GLP-1 may absorb differently, which could mean a higher dose is needed for full appetite suppression. But that same slower emptying may also be why women get more nausea and GI side effects at the same dose a man tolerates fine.
Muscle Mass and Insulin Sensitivity
Muscle is a sump pump for glucose. More muscle, more insulin sensitivity.
Men typically carry more muscle, so they tend to be more insulin sensitive at baseline. Less muscle means more insulin resistance, and insulin resistance blunts the effectiveness of appetite-suppressing hormones, including GLP-1.
This is why I'm always pushing resistance training alongside any GLP-1 protocol. You're literally building the tissue that makes the peptide work better.
Thyroid Function Is Huge
Most women in their 40s and 50s have compromised thyroid function. Especially after two or more kids.
Thyroid regulates metabolism and body temperature. If your thyroid is shot, it doesn't matter how much GLP-1 you have on board. The downstream metabolic machinery isn't running.
When a woman tells me she got zero results from semaglutide or tirzepatide, the first two questions are always about resistance training and thyroid labs. Nine times out of ten, one of those is the issue.
Liver and Kidney Differences
Sex differences in liver enzyme activity can mean women metabolize GLP-1 peptides faster. Faster clearance means shorter duration of effect, which can mean a higher dose to maintain results.
Kidney filtration rates differ too, which affects peptide clearance.
Other Factors Stacking Up
A few more things layering in.
Leptin levels are typically higher in women, which interacts with GLP-1 pathways. Gut microbiome composition differs between sexes and affects native GLP-1 secretion. Cortisol tends to run higher in women in our modern stress environment, and cortisol interacts with GLP-1 signaling.
Then there's medication. A lot of women are on antidepressants or anti-anxiety meds, and almost no one talks about how those interact with GLP-1s. I'd bet there's something there.
So What Do You Actually Do
Hormone optimization first. Always.
Before chasing a higher GLP-1 dose, get your labs done. Testosterone, estrogen, progesterone, full thyroid panel. If those are out of whack, you're trying to fix the problem with the wrong tool.
Eat enough protein. Most women I coach are way under on protein and have no idea. That alone affects satiety, body composition, and how the peptide works.
Resistance train. Build the muscle that makes you insulin sensitive. Do your cardio.
Stay on the lowest effective dose. I see women on 10mg or 22.5mg of semaglutide all the time, and almost always it's because everything else around the peptide is off. Fix the foundation and you usually don't need the megadose.
My take
Women aren't broken, they're just hormonally more complex than men, and GLP-1 peptides interact with that complexity. The answer isn't to keep cranking the dose. The answer is to build the symphony around it. Optimize thyroid, sex hormones, muscle mass, protein intake, and training. When those pieces are in place, a low dose of a GLP-1 can do incredible work. Without them, you're going to chase the dose forever and get diminishing returns with worsening side effects.
Full transcript click any paragraph to jump video
Hey everybody, this is Hunter Williams. I hope you were doing amazing wherever you are out in the world. Today's video is going to be the GLP one hormone battle of the sexes. Now, uh, there's going be a little bit of a deviation from the typical teaching, but, ah, This is something that just in my own experience, I've started a piece together over really probably the last 18 months. And the reason is, I have a question about why women seem to respond differently on GLP-1 peptides than do men.
And I was actually making this video yesterday and it was funny because I talking to my girlfriend's sister and she's recently been using Truzapotide. And she actually was explaining this to me that it's like sometimes a GLP-1 feels one way and sometimes it doesn't whereas for men, typically they have a very similar response. So I also started to notice just from the group coaching, you know, fully optimized health and from individuals that I've coached that women typically always seem to be higher dosing, or seem to be at a higher dose with GLP-1s, they seem have to titrate the dose faster, and they seemed to have more side
effects than do men. Now, I'm not saying men don't have go to a high dose, but it seems like more often than not, it's women that experience more negative side-effects and also seem you have increase the dosage to get the same effect than men do. So I started to think and started piece together some information and understand that actually men and women have different GLp-one hormone sensitivity. And as such, as men and women have vastly different hormonal sensitivities as it relates to testosterone, estrogen, and a ton of other hormones,
GLP-1 hormone also have differences. So when women are using a GLp-2 peptide or GL1 agonist peptides, they're going to respond differently to it than men. Now we're still going get more or less the same result, but they may have to increase the dose more. They may to account for more side effects and be more vigilant when it comes to some of the side-effects that may occur. So what I want to do today is explain why women respond differently to GLP-1 peptides than do men. And that's what we're going to walk through. I'm going give you some reasons as to why that may be the case. At the end of the day, it's just going come down to being smarter about dosing.
You're always going have to measure and monitor yourself. No one can do that for you, even if you're getting these prescribed from a doctor, and definitely if your doing it your own route. So that's what we're going to talk about today. Before I share my screen and go into the slides, I just want to thank everyone so much. The channel has been growing a lot lately. All the comments have been amazing and everything, so thank you guys. Without you there is no me. And then I'll just remind everyone to sign up for the Peptide Cheat Sheet down below. If you like topics like these, these are what a full bore in the fully optimized health group.
So you can join that. It's $99 a month. You can cancel any time, but we have, you know, like over 470 people, almost 500 people in there at the time of this video. I appreciate you guys much love. And without further ado, I'm going to share the screen and we're going find out today why women may respond differently to GOP1 peptides than men. Alright, this is going to be the GOP one hormone battle of the sexes. So let's get into why men and women may respond differently.
GOP1 means glucagon, like peptide one. It's basically an incretin hormone primarily produced in the intestines in response to food intake. So plays a crucial role in regulating glucose metabolism by the following way. so it stimulates insulin secretion. Basically that means it enhances insulin release from the pancreas in respond to high blood sugar levels to bring those blood sugars levels down. It also inhibits glucagon secretion. So it reduces the release of glucogon, which is a hormone that increases blood glucose levels. It's also slows gastric emptying, so it delays the empting of the stomach contents into the intestines which helps regulate postprandial blood-glucose
levels and almost also promotes satiety which just the feeling of fullness. That acts on the brain to induce feelings of fulness, reducing appetite and food intake which why they help people lose weight. Now that's the hormone. What do the peptides do? So pretty much the same thing. A GLP-1 peptide is a synthetic analog or mimetic of the natural GLP-1 hormone designed to enhance its beneficial effects. So they're using the treatment of conditions like type 2 diabetes and obesity and overall physique enhancement for all you biohackers out there. But basically they work by, again, enhancing insulin sensitivity. So basically this improves the body's response to insulin, which leads to better blood glucose control.
Basically it kind of takes what our pancreas is producing in insulin and has a better response so we're able to bring blood, glucose down better, Which obviously keeps us from putting on fat. It also reduces glucagon secretion. By lowering blood-glucose levels, it helps decrease glucogon production. And then it also delays gastric emptying. So it slows the rate at which food leaves the stomach, helping to moderate post-meal blood glucose spikes. Also in doing so, it's going to help promote a feeling of fullness because you're digesting a little bit slower.
And it then also suppresses appetite. It increases satiety signals to the brain, which helps reduce food intake and promotes weight loss. Basically, in a nutshell, I know most of you know that that's what's kind of going on. What have I noticed as someone that has used these extensively on myself and obviously the thousands of people I teach in my videos and courses and coaching and stuff. So I've noticed that women typically have more of the deleterious side effects from these peptides. I have noticed the women often need higher doses for the same effects, not always, but often higher.
And women tend to build up tolerance to doses faster. Um, so I notice this again in thousands, all women I coach, my girlfriend and I are both using Trisapatite at the same time, she does not get the appetite suppression as me from the dose. And so the question I was just like, why, what's going on here? So as I do, I'll do some digging. So let's look at how these GLP-1 peptides are metabolized. GLPs suppress appetite by acting on GLp1 receptors in the brain, particularly in hypothalamus, which is what regulates our hunger and feeling of fullness
or satiety. So they slow gastric emptying and obviously promote feelings of fullness. So what does our body fat have to do this? So the first thing I was thinking like, okay, women typically will always have higher bodyfat than men. Now I know obviously some men have a higher fat than women, but pound for pound women are always going to have high bodyfats because of the nature of their anatomy and physiology. Individuals with higher bodies fat levels often have different hormonal environment, including higher levels of leptin and insulin resistance. the hormonal milieu can affect how the brain responds to appetite signals.
Also, different body fat levels impact receptor sensitivity. So this is where I was like, oh, okay, there's probably something to this, you know, because typically men and women are going to have different levels of body fats. Higher body, fat, levels might affect GLP-1 receptor, sensitivity or density in the, brain, which potentially requires different dosing to achieve the same levels. Appetite suppression sounds like. Oh, so If a woman, even so, like if I'm 10% body fat and a women is 18% fat, she's going to be healthy, I am going healthy.
But her higher bodyfat levels are going affect the distribution, the sensitivity and the receptor density of the GLP-1 hormone. in response to these peptides. So it also, we can look at insulin resistance. People with higher body fat often experience insulin resistant, which can influence how their body responds to a society signal. Insulin resistance can blunt the effectiveness of the appetite suppressing hormones, including GLP-1. Basically, if someone that is 40% bodyfat versus me at 10% fat take the same amount of a GLp-I, the fact that they are more insulin-resistant is going
to blunt effectiveness. The leaner you are, more effective and lower dose you will have to do. which is starting to come together. So why are women different? So first, women are going to potentially have a different baseline GLP-1 level in sensitivity. Studies suggest that women might have higher baseline GLP- 1 levels and a more pronounced insulinotropic response. This could potentially mean that woman are more sensitive to GLp- one and might not necessarily need higher doses compared to men. He's like, okay, if that's the case, then they wouldn't need high doses, right?
Well, let's look at body composition. Differences in body composition, such as higher body fat percentage in women and higher muscle mass in men, can affect the pharmacokinetics and pharmacodynamics of GLP-1 agonists. So women's higher, typical higher-body fat might influence the distribution and metabolism of the drug, which potentially requires more frequent dosing adjustments. And then we have the whole hormonal fluctuations. Obviously, Even after menopause, typically women are going to have a little bit more of a hormonal fluctuation.
Obviously, pre-menopausal, they're vastly hormonally different to men. Whereas men's hormones, throughout the month, are more a straight line. Women's more on a roller coaster based on their reproductive hormones. Uh, menstrual cycles, pregnancy menopause, they can all impact GLP one activity and the overall metabolic response. So these fluctuations might necessitate periodic dose adjustments after, um, uh, a consistently high dose. And then if we look at clinical trials, Hey, They've shown variations of weight loss, glycemic control and side effect profiles between men and women.
For instance, gastrointestinal side effects such as nausea are pro more pronounced than women, which could affect the adherence to therapy and effective dose required. Let's look at why women may need higher doses. So the first one, like I mentioned, is hormonal cycles. Women's monthly hormono changes due to the menstrual cycle can lead to fluctuations in the metabolism of the GLP-1 peptide, which potentially requires higher dosage to maintain consistent efficacy. And it's funny, so Taylor and I have kind of tracked this Regardless of the dose of trisapatite, if she is in a certain phase of her menstrual cycle,
she's going to be hungrier. And yes, her cravings can be less than they typically would be without the presence of Trisapatite. But there's still a hormonal cascade in the body that's gonna cause her to crave more things than she typically will. As opposed to me, my hormones are relatively steady as a man because I don't have a menstruation cycle. That could be something that influences her sensitivity to this versus mine. We also have the idea of estrogen. So while estrogen can enhance GOP1 sensitivity, it can also create variability in response because remember, again, estrogen is kind of ebbing and flowing
throughout the menstrual cycle. And because of this, It can necessitate higher doses at different times to achieve the same consistent therapeutic effects. We also have progesterone levels. So pro gesterones can modulate GLP-1 activity and its fluctuating levels may mean women need higher doses to maintain stable outcomes. Obviously, again, pro-gesteron is different at different times in their menstrual cycle. Like I said, body composition is a higher body fat percentage in women on average. Again, I know that's not always the case. Some women are way leaner than men.
But they can affect the drug distribution, which requires higher doses to ensure sufficient GLP-1 peptide reaches the target tissues, i.e. the brain. So then we also have gastric emptying. Women generally have slower gastroc empting rates than men, period. And so this can alter GLp-2 peptides absorption, potentially necessitating higher for appetite suppression and glucose control. And then also too, to go back to the side effects side of things, because they typically have slower gastric emptying than men, maybe the same dose for them is going to cause them to have much more distress from that side things than a man would.
So moving along, we have insulin sensitivity. Differences in insulin sensitivities between men and women may lead to a need for higher doses of women. And I really wanna bring this up because typically men are gonna have more muscle mass and muscle acts like a sump pump, meaning that more muscles means more insulin sensitivity. So the more muscular we have in our body, the insulin sensitive we're gonna be. Typically, not always, but if that holds true, then a woman with less muscle is going to have problems with insulin sensitivities,
which could affect their outcome as it relates to metabolizing a GOP-1 peptide. Then we have leptin levels. So women typically have higher lepton levels, which can interact with GLP-1 pathways and associate to higher doses for appetite suppression. Then, we also have fat tissue distribution. Differences in adipose or fat-tissue distribution can affect drug metabolism, Which could potentially lead to women needing higher dose. We also have the lens of liver function. So sex differences in liver enzyme activity can result in faster metabolism of GLP-1s in women requiring higher doses.
Because women may have different enzymatic activity going on in their liver, they may actually metabolize the GLp-2 peptide faster, which could lead to more variability in the response and the side effects and a whole host of other things. Then we also have kidney function. So variations in kidney functions and filtration rates between women can impact peptide clearance, and this could potentially mean that women need higher doses. We also have genetic variations. So there are genetic polymorphisms that affect GLP-1 receptor expression and function.
We don't exactly know what those are at this point, at least not that I could find, but that could affect it as well. Uh, we also had the reproductive hormone, like I talked about. Testosterone in men and estrogen in women have different effects on GLp-one pathways. which could potentially mean that women need higher doses. We also have the whole idea of menopause, and post-menopausal women experience changes in hormone levels that can decrease GLP-1 sensitivity, which can necessitate higher dosage. It seems to be, too, that woman after menoppause typically may need more of a dose of GLp-2 than a man.
Obviously pregnancy, now that's not something I really want to get into of taking a GOP when I'm pregnant. I don't think it's necessarily a bad thing. Before getting pregnant, women could definitely use that to help heal the body, but that could also potentially have a whole cascade of different things that can result in different metabolization of the peptide. Then we have thyroid function. This is a huge one because most women, especially in their 40s and 50s, have very little to no thyroid functions. So difference in thyroid hormone levels can impact overall metabolism in GLP-1 action, which potentially necessitates higher doses in women.
And most women, unfortunately, their thyroids are shot, especially having two or more kids. So that's a huge reason as to why they would respond differently in terms of appetite suppression at fat loss than men would. A lot of times too, if I hear a woman that says like, I took drusaptide or semaglutide and I got absolutely no results. One I'm saying like are you exercising and resistance training? Then also too I would immediately look at their thyroid because thyroid is what regulates our metabolism and temperature in the body. And if we don't have that, it doesn't really matter how much GLP-1 hormone we have in our body or a peptide.
Also, muscle mass or lower muscle loss in women affect drug distribution, like I said a second ago. So that potentially requires higher doses. We also have fatty acid metabolism. Men and women metabolize fatty acids differently, which could influence GLP-1 peptide activity, of course could mean more of a higher dose in woman. Gut microbiome. Obviously men and woman have slightly different composition of their gut microbiota,which affects GLPs secretion, and this could potentially mean that women need more And then dietary habits too.
So I think a lot of women taking these have no idea how much protein they're consuming and they are not conscious of that whatsoever. And so if you have a woman that's not eating enough protein, there's probably going to be something going on with the thermoregulation in her body that could potentially affect how the GLP-1 peptide is getting metabolized. Then also having the intended effect, which again could require a higher dosage. You know, like if a woman is like, I'm taking this, but I've still hungry, which is not getting enough protein, you know? It's like okay, well, are we getting that protein to help you feel full anyway?
So also the stress response to women's different stress responses. Obviously this is huge because women typically In our world today are in a more sympathetic driven nervous system state. Hence they have higher levels of cortisol and things in their body, um, which can influence hormone regulation and GOP one action. You know, I don't want to get into that, but cortisol interacts with GO P one as well. Um, so you could look at that. And then we also have physical activity. So typically, Men and women are going to differ in their physical activity. And even if they don't, a lot of times the energy expended could be different.
So this could lead to different effectiveness of the GLP-1. There's also age-related change. Metabolic changes with aging differ between the sexes, obviously. This can affect the dose that a woman would need. Then we also have comorbid conditions. So higher prevalence of certain conditions like diabetes, obesity, and cardiovascular disease could necessitate higher dosages. There's also medication use. I think they could go to infinity, but I would be interested to see if there are interactions with a lot of the psychotropic medications that women are
on typically in the presence of these. And no one's really talking about that, like if they're using an antidepressant or an anti-anxiety medication alongside the GLP-1 hormone, and obviously that can influence the effectiveness. Then we have inflammatory markers. Sex differences in levels of inflammatory marker can impact the metabolism and action of GLp-2 peptides, again, which could require a higher dose for a woman. So all of that being said, that is the slides. And that's why women are different when it comes to the metabolization of GLP-1 peptides than men.
So I guess from here, the question is, so what should we do? Well, one, I think women need to be much more conscious of hormone optimization as it relates to using GLp-2 peptide. What are your levels of testosterone, estrogen, progesterone? What is your thyroid looking like when you are starting GLP one? And I would say, obviously this is like what I teach with Jay and everything is that like, if you're getting on these, but you not doing everything else right, then you really wasting your money. And, I've seen people take as high, you know, it's like.
like 10 milligrams of semaglutide or 22 and a half milligrams. And typically those doses, all the ones that I've seen at my anecdotal experience have been women. I think a lot of times women are much more hormonally screwed for lack of a better term in our world today than our men. There's a lie going on with their thyroid function, with the reproductive hormone function. Obviously too, they have a menstrual cycle. So a lot of that is going to lead to a different metabolization of these medications, which could potentially mean that they need a higher dose.
I am always of the school or the thought that you should try to stay on a low dose as possible. So what does that mean? Well, for a woman, it means getting hormonally optimized. It means eating enough protein. That means doing resistance training. I means, doing cardio in order to get the most bang for your buck. And I'll probably do a video cause it probably felt like I was calling out women a lot in this video and I'm not. Um, but I wanted to understand why these seem to act different in men and women, especially like in the case of my personal life with my girlfriend, we pretty much do the same thing.
So we resistance train the saying we do, the cardio is saying, We eat the food and everything. and she can have a vastly different response depending on where she's at in her menstrual cycle. Obviously she is using hormone optimization and everything like that. So, you know, where do we go from here? Well, it's always looking at other hormones in the body and trying to create the symphony. And I think when you have the Symphony of the other Hormones in The Body going the right direction, the GLP-1 could be magic for fat loss and stuff. But if you're not, stuff that you are not going to get results, there's not gonna be as good. Then you gonna play this game of keeping upping the dose, uping the dos, up in a dose.
and seeing less and less benefit in more and more side effects. So that is kind of why. Hopefully that makes sense to you guys. If you have questions, comments, or your own experience, definitely drop in the comments below. What's cool now is the comment section is becoming kind its own little community, which is awesome to see all the people giving their feedback and their experience. Definitely drop those below and if you like this type of video, let me know so I can do more stuff like these of kind examining the difference between sexes. Uh, cause it's something I'm fascinated by because as much as I can teach women, I will never be a woman. Um, so it always, as they say, seek to understand and not be understood.
So I seek understand, uh, rather than be. I appreciate you guys much love. Thank you everyone so much for the port for this port. Uh don't forget to check out the peptide cheat sheet and our private community down below. And I'll talk to you again in the next one. Peace.
