Magic pill for weight loss and PCOS? [Podcast with Dr. Felice Gersh]

I think a lot of us, at some point in our PCOS journeys, have been looking for a magic pill. In my journey, I thought that would be metformin and the birth control pill, but instead I ended up feeling worse on those pharmaceuticals. And it wasn’t until I realized that the lifestyle choices I made by thinking, eating, and moving like a PCOS diva was really the magic pill for me.

But lately I’ve been hearing a lot about a new “magic pill” that women with PCOS are talking about, and that is semaglutide marketed under the names Ozempic and Wegovy. They are not only being used by those with type 2 diabetes and women with PCOS, but it’s apparently the hot new weight loss drug in Hollywood.

I believe that knowledge is power when coming to man manage your PCOS, and it’s so important for us to understand what we’re putting in our bodies. So, if you’re considering a new drug to manage your PCOS, it’s really important that you have informed consent.

So, I reached out to one of my favorite PCOS docs to talk to us today about the pros and cons of semaglutide. So, welcome to Dr. Felice Gersh, and thank you for coming on the PCOS Podcast today.

Oh, it is my pleasure. And we all want that magic, just fix-it pill, but every single treatment, every pharmaceutical has side effects. So, I’m totally in the same camp with you about informed consent so you know the pros and cons and you don’t just fall into the hype. So, I’m so happy to have this opportunity to chat about this new “wonder drug”.

Well, I really appreciate your time. You’re a busy lady. You’re a multi award-winning physician with a dual board certification in OB/Gyn and Integrative Medicine. Dr. Felice Gersh is the founder and director of Integrative Medical Group of Irvine, and she is also a bestselling author of two of my favorite books on my bookshelf, PCOS SOS, and PCOS SOS: Fertility Fast Track.

And she’s also a regular contributor to PCOS Diva. We’ve done several podcasts together and articles, which I will make sure that I post in the show notes so you can check out our other interviews. So, welcome Dr. Gersh. And let’s jump right in. What is semaglutide?

So, it’s a GLP-1 agonist is what it’s called. So, what are all those letters even meaning? So, “GLP-1” stands for glucagon-like peptide-1, and “agonist” is the word for a mimic, that it can actually activate the functions that the real thing, the real one would do, but it’s not the real one. It’s a chemical mimic. So, that’s important to note too.

And it’s a mimic for a little, I call it, “hormone/peptide”. So, when it we’re talking about chains of amino acids, and there’s an informal divide between how many amino acids make a peptide, how many make a hormone, but think of it as a signaling agent. And these are made by specialized lining cells in the gut. Of the interesting things that we found out, when I was back in medical school, I had no idea that the gut was a hormone producer. We didn’t know that.

Now, we know there are these special enterocytes, lining cells, that actually can make hormones. And one of them is this specific, we’ll call it peptide/hormone GLP-1. GLP-1 also can be made in the brain, like almost everything in the body. It’s not made in just one site. So, what we need to understand is that the human female body was evolved when things are right to have a very close match between energy consumption, also known as “eating”, and energy utilization.

Now, if you exceed your intake of food, then you will have excessive intake and land up in the camp of obesity. If you have insufficient energy intake, that you don’t eat enough food, then you’ll end up in an underweight situation. Both of those can affect fertility, as I’m sure people who have now absorption issues or they have anorexia and they just don’t eat, they will have often no periods at all.

Women who are obese, whether it’s from PCOS or anything else that is causing it, whether medically or socially created obesity, they will often have infertility as well. Both groups, if they do become pregnant through artificial means, we call it “advanced assisted reproductive technology”, which tricks the body into getting pregnant when it’s really not healthy, let’s be honest about it, then those are the women that will often have serious complications during their pregnancies, and their children are not going to come from an optimal environment in utero, and may have lifetime metabolic problems.

Metabolism is creation, utilization, storage, distribution of energy within the body, the spark of life. So, all of the systems in the female body are basically evolved for reproductive success. Now, we are the only species, we humans, that try to control our reproductive destiny, and I’m all for people having babies when and if they want them at the right time and so on, but recognizing we’re the only animal species on the planet that actually tries to control such things.

During so-called mating season in the wild, you never see an antelope say to another, “Let’s pass this year. Not having a baby.” Just doesn’t happen. Only among humans. So, once you recognize, which I did early in my career as an obstetrician, that the prime directive of life is the creation of new life, and so every system in the body is evolved for that.

And it’s such a huge part of being healthy and fertile to have proper energy situations, like you have proper energy storage in your body, you have the right amount of fat, and you have the production of energy, you have mitochondria that can work, and you have release of stored energy in the body in the form that’s glycogen that’s stored in the liver, in the muscles and so on, and fat stores to release them when you need it, for example, if you’re not eating, that’s what we call “fasting” so that you can use your stored energy within the body.

These are really complex systems, and glucagon-like peptide-1 is part of this whole system. And women with PCOS have dysregulated energy systems. They do not have properly controlled appetite, they do not burn fat well. They’re very good at making fat as a general rule. It’s a different skill set to make fat and to burn fat.

So, we have this disconnect where they have a poor control of energy utilization, energy creation, energy intake, when they should eat, when they should not eat. And GLP-1 is part of this system in terms of regulating energy. So, it helps to regulate your appetite, and it helps to create energy by utilizing stored glycogen through the other little peptide, glucagon.

So, we have a system where when everything is right, we have just the right intake and the right output of energy. So, some of the things that GLP-1 does is it helps stimulate the release of insulin at the right time so that you get proper control of your glucose levels in your blood and works through the pancreatic cells, the beta cells, and it also slows stomach emptying so that you feel fuller so that it also helps to control appetite, because we know that when you stretch the stomach, it can affect your sensations in the brain.

There’s so many multidirectional systems in the body. Everything is multidirectional, not just bidirectional. And it also helps to reduce inappropriate release of glucagon to create too much sugar in the body by breaking down the glycogen stores. Then, by doing that, it will help to reduce your appetite and food intake so that all the systems in the body, the yin yang… I don’t know how the Chinese [inaudible 00:09:54] smart.

We have many redundant systems too, more than one thing. We have ghrelin, that’s a little hormone, a different hormone that’s made in the gut from lining cells that promotes appetite. Then, we have hormones that come from the adipose tissue, the fat tissue, like leptin, that are designed to reduce appetite. So, we have so many systems in the body to help regulate energy utilization, intake, storage, and so on.

And GLP-1 is a key player, and women with PCOS, FYI, I bet you’re not going to be surprised at what I’m going to say, they don’t make enough of it. So, there’re the hormones that promote appetite and then there’re the hormones that decrease appetite, and then there are all these little peptides that are running around in your brain, in the nutrient sensors that are located in hypothalamus, that help to also control appetite. It’s just an amazing system.

All of these are offline in people who generally are obese and women with PCOS. So, all of that is to lead into, they created, “they” meaning, the people out there in the pharmaceutical world, a drug that is a mimic for GLP-1 which regulates all these things, appetite, glucose production and stomach emptying and all these things.

So, when you say a mimic, I think of Provera, which is a drug that mimics progesterone that a lot of women are on, but it isn’t the actual natural form of progesterone. Would that be like a… Does that-

That’s a decent analogy, okay? Right. So, you could say the same for a birth control pill. The common estrogen is estradiol. That’s what 99% of birth control pills have as their estrogen. They have ethanol estradiol. So, that’s a mimic for the estradiol that’s made by the ovary, but it’s not the same. That’s such a key point, it’s a mimic. It’s like you might say, it’s a similar, it’s a knockoff. Okay, let’s call a spade a spade. It isn’t the real thing, it isn’t. And that’s why there are side effects that don’t exist with the real thing, and that’s important to know too.

And is it because your body somewhat recognizes the chemical but it isn’t an exact match, so partly you don’t really know what to do with it? Would you say that’s a simple explanation or…

You know what, I think, to say that, it’s like you are putting a peg in a hole and it almost fits right, but it doesn’t quite. So, you squish it a bit, you press on it and you twist it in. So, you get it in, but it’s not perfect, it’s just not perfect. So, I have a little list here of some of the side effects.

So, the real thing, it doesn’t come with a list of side effects. Your natural hormones, they are what they are, but when you create mimics, like birth control pills are not real human hormones. So, most women have been on them, who have PCOS, so they know that there are a whole host of side effects from birth control pills.

So, here’s some of the known. A lot of them are not life-and-death kinds, but they will cause people to stop, which I want to reference in a study that was published in the Journal of the American Medical Association, JAMA, that was just recently this September 2022. That was one of the main studies on semaglutide, which is probably the leader of the pack of the GLP-1 agonists.

So, nausea and vomiting is not rare. It’s actually fairly common with this drug. Diarrhea is another common side effect. Stomach pain, fatigue, hypoglycemia, which is low blood sugar. Then, the more serious ones, I mean, those are misery, but they’re not going to kill you, but the more serious ones can be pancreatitis and gallbladder disease and kidney damage. And these are not the whole list.

So, in the study, I can go over the actual data that they published, and of course, big surprise, it wasn’t on women with PCOS. So, we don’t really have specific data for women with PCOS. But I can tell you right out the gate that when they looked at people with confirmed type 2 diabetes, the results were much inferior, much less successful with actual type 2 diabetes. So, that’s sad. We don’t know.

And I’ll tell you right up front too, and I’ll tell you why in another minute, why I think that this drug as a general statement, there’s so much variation among women with PCOS, it’s such a spectrum condition, but for many of the women, unless we do something, add, I’m going to say, the secret sauce, which I’m going to tell you about, I don’t think you’re going to get the same results as some of these other people are getting in the studies.

So, the thing is that there are many people who were in the study. In fact, I looked at the data and about 40%, and now, here’s the rub, they all needed to lose weight, they all wanted to lose weight, they all agreed to be in the study, and about 40% dropped out. Now, they do not say, every single person, why they dropped out, but often that is because they didn’t like the regimen, they weren’t feeling good. That’s a big one, they weren’t feeling good.

If you feel nausea and you’re having diarrhea and you’re having stomach pains, you may say, “I can’t do this, I can’t keep doing this.” Then, I’m going to also tell you, you’d like to hear how you can naturally get your own GLP-1 rev up the machine to make that more yourself since that is a natural product and how this all links with PCOS.

So, the bottom line is that this is a mimic, it’s a knockoff. It has a fairly substantial array of side effects. Most people who would take it would not die from it. It’s not like it has a high fatality rate or anything like that. But it doesn’t take… What if you said 7% of people or 5% had a fairly serious side effect? Well, it’s more likely than not, more medically probable than not that you wouldn’t be that one, but you might be.

So, every time you go into taking a drug or having a procedure, you can’t assume you won’t be the one who actually has the serious side effect because somebody gets it. So, you have to go in with your eyes open. That’s the whole informed consent decision, which I don’t think happens in much of anything, really, except surgical procedures. But it really should be part of everything when you have a choice. Under every circumstance, you always have a choice unless you’re unconscious.

So, the thing is that this has shown, this drug, semaglutide, and it’s known also, another word for it is “incretin”, the incretins are drugs that modify the output of the glucagon, that little other hormone that comes also from the GI tract that helps regulate in the opposite direction so it puts out sugar. In any case… Oh, go ahead.

Oh, I was just going to say that this drug isn’t like metformin in the fact that it’s cheap, it’s been around for a long time-

Oh, my goodness.

… and you take it orally. It’s in a different category.

Right. So, this family of drugs has been around for many years. So, this family of drugs, I remember learning about Byetta. So, there were drugs in this family. We called them in “incretins” when they first came out. Now, they’d always say GLP-1 agonist, but we used to call them in “incretin”. And it was a daily shot.

And there was actually some published data, quite a few years ago, on another family member of these drugs, like Victoza. And there’s a couple little studies on it for women with PCOS for weight loss, predominantly to precede what? IVF, right, to try to just get some weight off of women before going into IVF, with not fabulous success. That’s why you may never have heard of it. Also, you had to use double the dose for women with PCOS to get any weight loss benefit.

And of course, it wasn’t covered by insurance. It cost a fortune, and it was a daily shot. Now, they have created a weekly shot. So, instead of having to get poked every day, you get poked once a week. Nevertheless, it is not going to be covered for weight loss.

Unless you can show as usual every other drug and your diabetic, you’re a full-blown diabetic, every other drug in the category of diabetes drugs has been tried and failed in some form or fashion, you’re not going to get insurance to cover it, and then your doctor would have to do a prior authorization with all these explanations for why they should cover the cost of this, which is depending on the dose.

So, the problem is, for adequate weight loss, you have to use a much higher dose, and of course, with a higher dose comes more side effects, the side effect profile goes up. And there’s really a fairly substantial difference in weight loss between the entry level dose that’s used for diabetics and the weight loss dose that’s used for maximum weight loss. There we’re talking almost two and a half times additional dosing regimen, and it’s just not going to be covered.

So, it can range from one, $2,000 a month. And we were talking about this before we got on together for the podcast, and I wanted to reiterate what you were talking about with me is, there is no exit strategy. I always say that with every drug. I like to think of pharmaceuticals. I’m an MD, I do prescribe pharmaceuticals when necessary. But I like to think of them as a bridge to health. Hopefully not a permanent part of that new ecology of the body, but sometimes with blood pressure, sometimes if you’re late stage disease, you’re not going to get people off of certain drugs.

But here’s a drug that can be given to very young women, but they have now data on teens. They just came out with a new study on teenagers, adolescents. Where is the exit strategy? There is no exit strategy. The drug company doesn’t even want to talk about an exit strategy because they want you to stay on the drug forever. And of course, do we have long-term data? Zero long-term data. Like anything, they don’t need to get long-term data to get it approved.

But what little data we have is when people stop it, they regain the weight, they regain the weight. Then, some people may have some other side effects when they get off, and we have no good data on that, no published good data on, well what happens when you get off of it. Just like birth control pills, they were never put on the market to be used for 30 years straight, but yet I have so many patients, that’s what they did. Then, when they stop it, there are problems.

So, I’m not going to think there wouldn’t be problems if you’re modifying receptors by putting in a foreign knockoff that is not the same, similar but not the same. It can modify how the receptors work so that when you get rid of it and then you put the real item in, it doesn’t work properly. Like SSRIs, the antidepressant drugs, even people who weren’t depressed, when you try to get off the drugs, they have problems.

The same thing with PPIs, the acid blockers. You could take healthy people, put them on the drug and then when you take the drug away, they’re all sick from a drug problem because their bodies haven’t adapted to not having that drug. So, it’s a crazy thing. So, I don’t know of any published data on withdrawal from these GLP-1 agonists, but you’re mucking around with your hormones and receptors.

I totally would expect that there will be some problems, and probably it should be a weaned off thing, not just abruptly stop, because the body has more difficulty with that. And they have warnings now that should… Some of these are very long-lasting, well relatively, not years, but maybe a few months, that there’ll be some effects. Now, they’re saying, this seems like the antithesis of what you’d want if you wanted to get pregnant, you should stop them about three months before you want to get pregnant.

It’s the exact opposite of what they were doing with the Victoza when they were giving it to them right up to trying to start IVF, and they didn’t really know… And that’s a shorter acting one. It’s a shorter acting one. That’s why you have to give the shot every day. But the longer acting ones, like the weekly, apparently there’re some effects that last in the body for, could be three months.

Now, they’re saying, “Stop it if you want to try to get pregnant,” and then what, you’re going to gain all the weight back just before you want to try to get pregnant? So, there are some real concerns, I would say, in terms of the actual data that was published in JAMA. I have it here. And the data was pretty encouraging for the short term. So, what they found was, in these somewhat overweight people, none of them had PCOS. And like I said, there was about a 40% dropout rate, which really shocked me.

So, if you look at six months, remember this is six months, not five years or anything, about close to 90%, just over 87%, had a 5% or more weight loss. Now, if you figure someone, just make this up, if they’re 200 lbs, so what are we talking about, 10 lbs? It’s, “I think I could do that in other ways.” So, that’s almost 90%.

Now, in terms of losing 10%, so if you had a 200-pound person, that would be 20 lbs lost. That was just under 55%. So, it’s almost 50-50 that about half the people lost 10% or more, but the other half didn’t. So, if you weigh 200 lbs, after six months you didn’t even lose 20 lbs. Well, you decide in your own mind if that sound fabulous or not.

Then, 23.5% achieved a 15% weight loss or more. So, that would be 30 lbs for a 200-pound person, but now we’re less than a quarter. Then, just under 8% lost 20%. So, that would be a big 40 lbs. That would be great, but that was, out of 102 people who lasted the six months, there was a total of eight people.

So, when you talk about percentages, that’s one thing. Let’s talk about absolute numbers. So, it’s eight people. But we don’t know what happened to those eight people over the next six months after the drug was stopped, because guess what, they were getting that drug for free. They were part of the study. “Oh, study’s over. Good luck folks.” Now, “Oh-oh.” They’ll never publish that. They’re not going to publish-

Of course. And what led me to reach out to you about this is I was on some different PCOS boards as well as the PCOS Diva private community, and people were talking about this new magic pill that was getting a lot of good results from women in the PCOS community, but when I started digging, I was seeing that women were saying they couldn’t afford it anymore. So, there you go with the exit strategy. Now, their hunger signals and cues came back a lot stronger.

Yeah, I am not surprised. Just like I see women who’ve been on birth control pills for many years, and they went on them for reasons that had nothing to do with PCOS. It was, they had maybe heavy periods but they were perfectly regular, or they became sexually active when they were only 15, unfortunately. So, they were put on them really early, sometimes for no good reason, or they had a little tiny bit of teen acne, no talk about nutrition. They just got put right away. This happens all the time.

Then, they’re on them for 20 straight years, and then they go off and they have explosive PCOS. I think that’s birth control pill induced. I think we do have problems getting off of these drugs. So, that’s a really important thing. Then, I wanted to tell you what I think makes women with PCOS… Remember also, I told you these were not diabetic people. When they did studies with true type 2 diabetics, their outcome was significantly less favorable. They did not lose as much weight, and that was what it was-

Wow.

… for that number with a 40% dropout rate. And their drug was free, so there you have it. And there are articles published on this and I talk about this. So, GLP-1 is something that’s natural. So, what in the body naturally encourages you to make this appetite energy regulator? Well, some of it is the food we eat. And we know that eating a high fiber diet, and that means things like whole grains that are not processed into powder. It means that you’re having nuts and seeds, you’re having legumes, like beans and lentils. These have wonderful fiber in them, and it’s because everything works with the microbiome in some form or fashion.

So, the microbial population of the gut is going to have a significant impact on properly making this wonderful little peptide/hormone GLP-1. So, you need to feed those little microbes we talk about all the time. Please feed them, please feed them, nurture them, love them, and realize that they are your best buddies, those little critters down in there. So, they love fiber, all different kinds of fiber, polyphenols, all the different plants, all the different colors of the rainbow, and that sort of thing.

They also like to be fed on schedule, like your dog. So, give them breakfast, give them lunch, give them dinner, don’t snack all day long because then they’ll get weird and wired. You don’t want little wired weird microbes. So, you’ve got to take care of them, and so that diet is very helpful. What else is really helpful? It’s the missing ingredient that never gets talked about and most doctors don’t know a darn thing about it, and that’s estradiol.

So, estradiol is essential for the production of GLP-1. And in fact, there are studies published showing that if you give to… Who were they studying? Women with PCOS? Of course not. They’re studying menopausal women. They’re a clear target of low estrogen production from their ovaries, none if you’re in menopause. So, they gave estradiol, the estrogen made by the ovaries.

And just as a quick side note, estrogens are a family of hormones. There’s no N estrogen, just like there’s not a B vitamin. B vitamins come in 12 varieties, and estrogens come in different varieties. And they use endocrine disruptors or xeno estrogens, which are the phony mimics that are found in plastics of all different kinds; soft plastic, hard plastic, flame retardants, heavy metals. All kinds of other chemicals are actually xeno estrogens. So, they are mimics of estrogen in a very bad way. They harm our bodies.

And sometimes people refer to them as estrogen. It’s crazy. They’re endocrine disruptors and hormones that are made to be similars. They sometimes call them “hormones”. They’re meant to be in a human. And the GLP-1 agonist also, technically, you could call it an endocrine disruptor. If you really go by the definition, it’s a mimic. It’s a pseudo of the real thing that combine to receptors and activate them, but it’s not the real thing. Like you said, it’s a knockoff. So, we need to always keep these things in mind.

But when you have estradiol, the ovarian-produced estrogen during the reproductive years, it has this beautiful synergy with the gut, with the gut microbial population. I’m sure you’ve talked about so many times the gut microbiome in women with PCOS. It’s dysbiotic or it’s abnormal. And that is heavily related to the fact they have these hormonal imbalances, which includes for most women with PCOS.

And PCOS comes in different flavors, and it’s like a spectrum, like we talked about. It’s based on symptoms more than anything. And sometimes we lump in adrenal androgen excess disorders and with ovarian-related testosterone excess. So, they’re not even all one, and it gets all mixed up in people’s minds. But if we think about the ovarian type version of PCOS, those women have a problem in the production of estradiol. They don’t make enough estradiol.

Estradiol is critical for all of the energy facets of the body. That includes energy intake and energy expenditure. So, estradiol helps control your appetite, your energy distribution, where fat goes in your body, and burning fat. The mitochondria rely on estradiol and GLP-1 and other peptides in the brain, the kisspeptins that signal, ultimately, through the hypothalamus, the gonadotropins through the center, and the hypothalamus that puts out the little factors that talk to the pituitary to make LH and FSH.

And coming from the master clock that judges light and dark and nutrients, the super cosmetic nucleus, the master clock of the circadian rhythm, which has estradiol receptors, puts out other little hormone/peptides like vaso intestinal peptide, VIP, and oxytocin. All of these things are heavily regulated by estradiol because the energy utilization systems in the body are heavily related to the reproductive systems.

Which of course makes sense because a woman who is going to be pregnant needs to have energy stores, the right amount of fat, the right metabolism to survive and get through what is really a major stress on the female body, which is pregnancy. And many women are failing that, especially women with PCOS, with high levels of pregnancy-related complications.

So, understanding that estradiol, the ovarian-produced estrogen, is not produced adequately in a very high percentage of women with PCOS. And this hormone from the ovaries, estradiol, is critical for all of the energy regulatory systems in the body, everyone, from the creation, the storage, utilization, distribution of energy, estradiol is the master of all of that.

And that includes under its auspices, under its umbrella, GLP-1. Without adequate estradiol, and this is what’s underlying a lot of the metabolic dysfunctions of women with PCOS, they do not have adequate production of GLP-1, they have dysregulated leptin, they have dysregulated oxytocin, they have dysregulated kisspeptins in the brain. All of these things are dysregulated.

And there’s actually published data, and once again, in menopausal women, that if you combine estradiol with a GLP-1 agonist, like Wegovy, Otezla… I mean Ozempic. I always get those mixed up. They always start with Os. Okay, Ozempic. Otezla is for skin, don’t take that one. So, Ozempic, the semaglutides, it works in synergy with it. And it showed that, without that estradiol dial added in the menopausal women, it didn’t work well. And I think that this is an important thing.

If you go to your doctor, and this is not common knowledge among doctors, I’m just telling you, most of them don’t even know what estrogen is. It’s so embarrassing when I say that-

No, I think we all know that.

Oh, okay. I didn’t want to-

Oh, the frustration to find a good doctor. I know.

You’d think OB-Gyns and endocrinologists would know what estrogen is, what it does, yet they don’t. So, they don’t know that you can’t work this beautiful synergy of these hormones unless you have estradiol. But if you give estradiol, if someone needs it, I always believe in monitoring and testing so I know what it will actually do.

When you give estradiol, it helps the body to actually heal so that you can then get the body to get metabolically healthy, and then you can remove the estradiol. So, I think of it as training wheels on a bicycle that no one wants to wear training wheels forever or bumpers when you go bowling. So, hopefully you get good, and then you take them away and then you can do it on your own. But a lot of times you can’t get metabolically healthy in a state of estradiol deficiency.

I deal with this of course all the time with my menopausal women. You can eat, you can meditate, you can exercise, and all those things are wonderful and essential, but it’s not the same as replacing a hormone that’s literally missing in your body that creates the whole energy system of the body. It’s not like an optional hormone.

It’s like if you took out someone’s thyroid gland because they had a gigantic goiter, you wouldn’t say, “Now, all you have to do is meditate and exercise and take these herbal green medicines and so on.” You’d say, “Well, I’m gonna give you thyroid hormone,” and then do all that other good stuff too. So, that’s how I feel, that there’s no replacement.

Now, there’re adjuncts, but there’s still no replacement for estradiol. Even, I’m a big fan of phytoestrogen foods, but they’re not going to be the same as having functioning ovaries. We see this in menopause. And many of the conditions that are metabolically dysfunctional in women with PCOS are identical to what happens to women after menopause because they both have a commonality of theme of low estradiol through totally different reasons.

And of course women with PCOS have the capability of making estradiol, menopausal women don’t. And it’s not zero from a menopausal ovary, it’s just reduced. So, women with PCOS can heal and they can do better and we can modulate their gut microbiome, so everything’s multidirectional and help women. And if a woman goes on one of these drugs like the semaglutides, they need to go in with a plan. Don’t just go on it and think my savior has arrived because not true.

Remember, in this study, which had a better outcome than what it would be, but most studies have better outcomes than in the real world use because these are motivated people who signed up for the study. Even then, they had 40% dropout rate. So, study outcomes usually are not matched by real world outcomes. So, really, that’s an important takeaway.

And even with the study you still had not that great, it was still just a little over 50% of people had a weight loss of 10% at six months. Remember, out of 200 lbs, almost half of them couldn’t even get a 20-pound weight loss. And that doesn’t mean that they sustained it, even the ones who did get 20-pound weight loss. And there are other ways that we can help people to do that.

I can tell you that, just by lifestyle changes, by timed eating, by exercise, by meditation or other-mind-body practices, by removing toxic, everything toxic, people, toxic food, toxic, lifestyle choices, toxic, pollutants, we can do so much to lose that amount of weight and sustain it.

Exactly.

And this is not a standalone. So, if anyone uses this drug, and I’m telling you, we don’t have the data because no one’s done the data collection on PCOS, but it’s going to be inferior to this. It has to be because a significant percentage will have estradiol deficiency. And this group had an average age, here it shows, of 49. So, these were not, in large measure, fully menopausal women. So, they weren’t completely estrogen deficient, I would bet.

So, the thing is that it’s going to be harder to get even those results in a group of women, PCOS, because they had the same problem with diabetics, because diabetics already have inflamed pancreases and their beta cells are already dysfunctional, and the glucagon like peptide-1s work a lot on the beta cells in the pancreas. It’s just, you’re not going to get as good a result. So, prepared for that.

But hopefully you’ll prove me wrong, please. Please prove me wrong. Or at least you be that [inaudible 00:43:26] one who has a stellar outcome. But plan what’s your exit strategy with your doctor. So, how you’re going to get off, how you’re going to stay on. If you’re thinking of pregnancy, they’re now telling you get off three months ahead. So, what’s going to happen in that three months that you’re going to go off? What are you going to do lifestyle-wise, because no drug should be a standalone and replace lifestyle.

And do you have low estradiol? Has it ever been looked at? And what is your LH/FSH? By the way, that’s a clue. If you have really high LH and low FSH, you have that huge ratio differential, that’s a big clue that you don’t have enough estradiol. Why is that? Because LH triggers testosterone production in the ovary, which is, by the way-

Ah, okay.

… another different skill set. So, you have LH producing all that testosterone, and then FSH is malfunctioning and not as much. And FSH is critical for the action of aromatase, the enzyme that converts testosterone in the ovary, in the granulosa cells, into estradiol. So, the brain, which is full of sensors, says, “I don’t have enough estradiol, I don’t have enough estradiol.”

So, it tells the pituitary to make more LH because the LH triggers the ovary to make more testosterone. All estradiol everywhere in the body, of course, including the ovaries, is derived from the conversion of testosterone, a 100%. There’s no other path. So, testosterone turns into estradiol. But in women with PCOS, it doesn’t do that well, in most cases. So, the brain says, “More estradiol please,” and it does that by telling the ovary to make more testosterone.

Ah, that’s interesting.

It’s like a glitch in the assembly line. So, you keep putting out more testosterone and LH goes really high, but FSH, there’s a problem with the FSH. And there may be autoimmune-related things. We don’t even fully understand. And by the way, it’s related to the high levels of anti-Müllerian hormones, another talk for another day.

Yeah, exactly.

But the point is that that’s a clue that if you have that, because many doctors, they don’t measure estradiol, which they should, but they do measure LH and FSH. I don’t know what they think why that’s happening, but that’s why it’s happening is because there’s this glitch in the conversion of testosterone into estradiol. So, if you have a really high LH and a lowish FSH, you probably are not capable, your ovaries, of making adequate amounts of estradiol, and you would probably benefit from having an estradiol patch.

That’s what I was going to ask is how you to administer-

Yeah. You can just get a patch, like a 0.1 patch. By the way, remember I said that women with PCOS and women as a general group because of their estrogen fluctuations and changes in malfunction, are more prone to eating disorders, right?

Yes.

Eating disorders can be male, but they’re way more prevalent in females, both under- and over-consumption eating disorders. And they actually had published articles showing binge eating disorder, which is so prevalent in women with PCOS, can be successfully treated with an estradiol patch.

Oh, that’s fascinating.

Plus, estradiol regulates all of the energy systems of the body because energy systems are essential for successful reproduction and survival. So, these are all really important things to know so that you can get the proper treatment. And if you get GLP-1 agonists, if you go on Wegovy and you’re spending all that money and you have really low estradiol, you’re not going to get the results. I’m just saying there’s published articles on that. Tell your doctor there are published articles showing that when you give the two combined, to obviously appropriate women, that you will get a better outcome. So, those are important things to understand, and your doctor may not know that.

Yeah. And that’s it, as I introduced this podcast, that’s why knowledge is power, and we have to be our own advocates. And I so appreciate you, Dr. Gersh, because you are just a wealth of knowledge, and I appreciate you sharing that knowledge with the PCOS Diva community. I feel I got a two-for-one today. We not only talked about semaglutide and whether that’s right for you, but we also got a great education on estradiol and what that means. I know.

Well, that’s this tricky thing about the body, it’s all interconnected. So, to understand one thing, I learned that you’ve got to know the next thing in the list, next thing and next thing, or else, you end up really in a confused state. And I want all of your listeners to understand so that they can make the informed decision and help their doctors. It’s a team, think of it as a team, that if you need to help your doctor to understand, you as a patient, that you’re unique and you have special needs, we’ll say. So, don’t just take the drug and think that that’s your magic bullet, okay?

And I want you to tell women how they can learn more about working with you. You were talking about lifestyle changes, you have a plethora of ideas in your book, SOS PCOS, and My Healing PCOS book as well. But how can women find more about your work?

Well, other than my books, I’m here talking to you right now from an exam room. I have a patient to go see. I’m still an old-fashioned doctor. I actually have a practice. I have an office with lots of lovely exam rooms and a waiting room where we try not to have you wait, and I also do telemedicine under the legal restrictions that exist to enable me to see people in different locations. And I love taking the one-on-one approach because every woman is unique.

And I don’t just have an assembly line. I treat every woman as the unique person she is. PCOS is not the same in every woman. Nothing is the same in every person. So, I like to evaluate each person for their uniqueness and then create, together, a strategy, a therapeutic plan. And I have, what I consider, I call it my “expanded therapeutic toolbox”. As an integrative doctor, I can access all the lifestyle approaches.

We have a gym in my office, we have nutrition, we have modified for biofeedback, for stress and other mind-body practices. So, we have vascular ultrasounds and echocardiograms. So, I try to cover most of the bases that women need within one place. So, I have a bigger toolbox to use, to access for therapeutic modalities. So, herbals when appropriate, nutritional supplements, targeted supplements, all evidence-based.

Everything I do, I can back up with peer-reviewed published studies. And I’m very much into, we were talking before, mechanisms, “Why is this working, what’s this doing in the body,” so I can come up with my own synthesized version of what’s going on in people. And I do have pharmaceuticals, I do procedures when necessary. So, I’m a regular practicing doctor.

Yeah, you’re a rare breed, honest, in a very good way. It’s hard to find-

I still feel that you still need to do exams, you still need to touch people and see them in-person, but also combine it with telemedicine because everybody is not within five miles of me. And I love to do speaking engagements, podcasts, health summits. I have a little Instagram live and I have a YouTube channel, so those can also be utilized for-

Yeah. And we will put all of that contact information in our show notes, and I’ll ask you, Dr. Gersh, to send me that JAMA link that you-

Oh, sure.

… and we will put that… If you want to see that study that Dr. Gersh was referring to, that will be in the show notes as well. So, thank you, again, for joining us. I think this might be our 5th podcast together. I know it’s-

Yeah, right. Well, we never lack for things to discuss.

I know, I know. And thank you all for taking the time to listen, and I look forward to being with you again very soon.