445: The Controversial Hormone Cycling Method That's Dividing Doctors (And Why It Matters) with Dr. Salome Masghati

Estrogen is your builder. It's the party girl, right? It loves being loud and building and socializing, making connections and building all these tissues everywhere in your body. And then progesterone is more the introvert. And it comes in and it's like, I call it the janitor. And it comes and it cleans up. And when both of them are in a rhythm, you get the best of both worlds.

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Hormone replacement is such a confusing topic, and no matter who you interview, no matter who you ask, no matter what you read, you get a different opinion. Should we do it? Should we not? Is there really such thing as bioidentical or is it all synthetic? And what are the right doses? And how do we take it? And is there a difference between optimal levels and just getting by to avoid symptoms? And where do we even start? How do we dig in? And how do we learn how to trust ourself and our own knowledge around that? Today I've got a very special guest. I've got Dr. Salameh Mascati on, and I specifically wanted to interview her. She came from my dear friends at Wise and well, and I had asked them specifically, who can talk to me a lot more about cycling, even post menopause, so we can create a period who can talk to me about optimal levels and some of the things like the Wiley protocol that I had heard about and I didn't know what that was, and also rhythmic psychological dosing. Now, everything we're going to be sharing today is just information for you. This is not meant to substitute what you're getting from your own, doctor, But I do think it is very important for us as midlife women to really learn and understand this ourself so we are better equipped with better questions and we can start really advocating for ourselves. So thank you so much for being here, doctor.

Oh, God, I'm so happy to be here. Thank you for having me.

Now, you are a trained gynecologist, you're an MD and You really started shifting recently into hormones and even more recently into this idea of the rhythmic psychological dosing. Can you tell me a little about that?

I'm sorry, Physiologic.

Physiologic. Physiologic, yeah. The rhythmic physiologic dosing, yes. Can you talk to us a little bit about, like, where you made that pivot because you're a traditional trained gyn.

Yes, I was traditionally trained, but also a surgeon. I did two years fellowship with robotic surgery. I had a lot of patients with, you know, endometriosis and fibroids. And it just made sense to want to learn about hormones, right? But when I learned about them, I was more scared of them. It was more about, oh, you, you gotta. You gotta, you know, stay away from estrogen because of the endo or the fibroids. And then when I had menopausal patients, I would put them on a small dose of patch, and that was it, and I'll send them home. So then after that, I got into. And it was during COVID as I was finishing up my fellowship, I got into functional medicine. So I learned more about hormones through that. I loved it. I learned to understand, you know, adrenals and thyroid and all of that, in addition to the estrogen and progesterone. Then about a year and a half ago, I got introduced to higher dosing of hormones through physiologic restoration. And the difference is, is that you can give someone hormones back in a static way where every day it's the same dose, or you can do it where you give it rhythmic, according to their cycles. And so you. You can say, okay, a woman is in menopause now and she no longer cycles, but you kind of mimic how her cycles were before menopause. And the idea behind it is that you are going to vary your dosing throughout the month. And the idea is that you. This is better for the receptors, this is better for the organ system everywhere, because now you're getting the hormone levels to a higher degree than they used to be when you just. Sorry, not they used to be, but when you get them with the static hormones. So that's kind of what it is. And I explained to patients, we are learning so much about hormones more and more every day, right? We have new studies coming in, but a lot of the studies that scared women away were based on types of hormones that really not a lot of people use anymore. Not many people use the synthetic or oral estrogen so much, or the synthetic progestins not as Many, they might still use them, but not as much. And then so from that also, like using more bioidentical, more like hormones that are closer to what your own body makes them, you can then decide also to do it where every day you give the same dose or you do it more rhythmic. And there's some data that rhythmic might be preferential. For example, with progesterone, we know that if you cycle progesterone, there's some data that it's better for the bone, for osteoporosis outcomes. They compared it to women who got it daily and then women who got it cyclically, better outcome. There is some studies that potentially it's better for plaque buildup in the brain as well to actually do it cyclically instead of daily for the progesterone. And there's some data that. And this is again, that was just in vitro, like it was in a.

In a cell study. But then there's also another study where they looked at vasodilation of vessels and that if you gave progesterone, you got more vasoconstriction if your estrogen wasn't above a certain level. So then we're finding all these things that maybe for cardiovascular health, maybe for BR health, maybe for bone health, C. Glucose might be better. Now, a lot of women don't want to have periods, so we say, listen, the period is not really the goal, but it's a side effect of getting the better benefits for every other organ system.

Okay?

It has to be a conversation to be had with the women once they understand it. I think the book that wise and well wrote, the Great Menopause Myth, explains it so well. Once you understand it has to do with the stimulation of growth hormones and stem cells everywhere in the body, then the shedding that also comes with that makes a lot of sense because think of it that way. Estrogen is your builder. It's the party girl, right? It loves being loud and building and socializing, making connections and building all these tissues everywhere in your body. And then progesterone is more the introvert. And it comes in and it's like, I call it the janitor. And it comes and cleans up. And when both of them are in a rhythm, you get the best of both worlds. And when you. When you. When you cycle estrogen and you don't give it every day the same dose, but you actually give it a peak, you stimulate.

Growth. So arrest of the growth. So we call it cell arrest. And I'm trying to not use too many complicated Words, but basically, you want to stop the cells. It stops the cells from growing too much. So it has its own safety mechanism. And so estrogen getting higher and lower doses actually has different effects on the genes. And then progesterone, also not just being the same level, but peaking, stimulates P53, which is a tumor suppressor gene. So based on those.

Mechanisms that we know work in premenopausal women, they applied that to menopausal women. It was based on the Wiley protocol, but they changed it up and made it a little bit better, where there is more estrogen on board on day 12 and a little bit less progesterone, the luteal phase. Now, I explain all of that to my patients, and I have patients who say, this is too much for me to do. I don't want to cycle, just optimize my estrogen. I'll still work on it.

Okay, I've got. I got a lot of questions here, so I'm going to back. I'm going to back up a few steps.

Yes.

Because there are some people listening that I'm going to start really, really basic here. There's some people that are not on any hormone replacement at all. They're either in perimenopause or they're in menop, and they're not on any. And they are, step one, deciding, is this right for me? Can you just share some basics you want women to know about hormone replacement in general? We'll start there, and then I'm going to get into the difference about the optimizing and cycling and all of that.

Yes, absolutely. So the hormones have a lot more effects for us than just regulating periods and fertility. Because nature was interested in us keeping us healthy to be fertile. All the organ systems are affected by hormones because nature wanted us to be healthy, to get pregnant, and then when we're pregnant, to stay healthy. Yes. So because of that, our brain, our bones, our hearts, our skin, our GI tract, our gut microbiome, our vaginal health, the way our mood is, everything is affected by hormones. And so understanding that, and the more we understand that we have hormone receptors throughout our whole body, the more we understand that as we are losing these hormones, and maybe some of those changes are taking place that are associated with what we call aging. Right. Our organ systems then age because they no longer have those hormone levels. So then you could think about it this way. You could say, hey, I don't need them because nature wanted me to lose them. Sure. I mean, that is absolutely your decision, but I see it Every day how much it affects women. It's not really an empowering process. It's actually very affecting them in ways that are not even aware, they were not even aware of five years ago ago. Until we had such amazing voices in the menopause space come up and talk and you know, you know your mood going down, that could be your estrogen or your progesterone, or the fact that you have rage or the fact that you have depression or anxiety, or suddenly you are diagnosed with rheumatoid arthritis. These are not normal changes happening. This is related to your hormones and maybe we could prevent that. So if before that you were only thinking of hormones, as of hot flashes, you would have missed all those effects of hormones. But now that you know, now that women are getting really a lot of amazing knowledge through social media and all these amazing people out there talking about hormones, they understand, hey, this is affecting me in so many multiple ways. I have no idea about that. Could even be something as simple as like ear itching or developing something like pots where suddenly when they get up, they get dizzy. That is absolutely estrogen related because it affects your kidneys function and how much aldosterone you produce and how much water you retain or you getting up at night twice to pee, that's not normal. Or you do no longer desire having sex with your husband or you're more snippy at your children. I mean, you could say these are natural changes. But if you could do things about it where you and you optimize everything, your diet, your exercise, and you still can't get a grip of it. I mean, because hormones are so powerful, you need that as part of your whole toolbox with everything else that you.

Do fully, fully agree. So if somebody sees that and they are not on them yet, and then they go to their doctor and before we even talk about cycling and they just say, oh, you can just take birth control pills, synthetic hormones, can you explain what goes wrong if we choose that versus doing like bioidentical replacement?

So birth control pills have benefits for contraception. Beyond that, there's a lot of things that we're not told about. For example, because the estrogen in the birth control pill is a synthetic form, it's not bioidentical. The progesterone in it is synthetic as well. So they don't completely dock on the receptors the same way they don't have the same function as your own body's hormone. By doing that, they also give feedback to the brain to make less of your own hormones. Like it, the FSH and LH will go down, which are the signaling from brain to the ovaries. And your own ovaries will make less of estrogen and progesterone. I know that because I check hormone levels on my patients birth control, and often I will see their own hormone production goes down. So that's one issue, because already you are in perimenopause, for example, in your 40s, and you're losing your bone density. Now I'm lowering your own body's production as well. Then in addition to that, they go through the liver because they're oral, and they increase two things. They can increase the clotting factors for the liver, and they can increase CRP and inflammatory factor. They also increase SHPG production. And SHPG is a protein that binds our own estrogens and testosterone in our blood. And so if we have more SHPG now, we have even less free levels of estrogen and. And free levels of testosterone. But by doing so, oral birth control changes all these mechanisms in the body. So people like Dr. Gersh, Felicia likes to call oral birth control endocrine disruptor, because it's not the same as your own body's hormones and it doesn't dock on the receptors.

The same makes total sense. So then if we look at, we start actually doing HRT hormone replacement, what is the difference between bioidentical and synthetic? And how do people know if what they're taking is bioidentical versus synthetic? So, like, I'll hear somebody saying they're taking a combination of a pill that's. That's estrogen and testosterone, and their doctor told them it was bioidentical. Is that true? Is there. Where does the line draw there?

Absolutely. You can have oral formulations of bioidentical hormones.

Okay.

It's just the formulation. The chemical formulation is closer to the, to the how the molecule looks when your own body makes it. And so some people will say, well, that's actually less organic or less natural than Premarin, because Premarin was from horse urine and oral bioidentical estradiol is from yams. That depends how you want to define.

Right.

Formulation of the yams derived estradiol is closer to your own formulation versus the Premarin is a combination of this horse urine's, you know, excreted estrogen with all its metabolites. Right, right. Other metabolites of estrogen that have been already metabolized for the liver. So, yes, maybe it's naturally derived because the horse is an animal, but it is not. It's not bioidentical.

So that makes sense.

Very complicated for women. Just think of bioidentical. Of the formulation is very similar to what your own body makes.

So when someone ask about, like plant based bioidentical, what they're really talking about is what you just said. The yams, it's made from. It's made from yams.

It's made from yams. They're all made from yams. And so some of them soy, but yams is actually better quality. And then you can make that into oral, you can make that into a cream, you can make that into a gel, you can make that into a patch. Patch.

Even for what they use for the pellets, That's a bioidentical estradiol. That just doesn't mean. So now you have bioidentical, but then you have also the method. So if I were to choose among all these methods, I would rather go with a method that avoids the oral. Okay, right. Because very similar to the oral birth control, even though to a lesser degree, it still will increase your clotting factors a little bit.

Makes sense.

It might increase your CRP inflammation marker a little bit, and it will increase your shpg. So if you take oral estradiol, you will raise your shpg, which then will bind up more of your testosterone, which will be less available. And a lot of women in midlife, they're also making less testosterone. Yes. And so if I have the choice, I'll not go with oral, and I would go with something called transdermal. What does that mean? It means through the skin. Now, that can be a gel, cream, patch, or injections. You ask me my favorites because I like getting the estradiol levels above what the average estradiol level with a patch would be. I love creams and injectables. Got it.

Okay. Okay.

So palettes are a different category, but they would be bioidentical. I just don't love them because they're a little bit more of a roller coaster.

Makes sense.

I did. I did a lot of palettes in the past, and I checked people's. There was one or two people that were agreeing to let me check their levels throughout the whole thing. And oh, my God, it was like a lot of up and down. And so that's not very physiologic for receptors. Think of it. When your ovaries are still working, they're pulsing all day long. Right. They're not just secreting something once every four months. So the receptors love the More physiologic docking. And the rhythm makes total sense. So that's my opinion. But a lot of people love them, and I don't judge anybody for that.

Now, what about that makes sense for estrogen and for testosterone, but what about progesterone? Because that seems to only be prescribed in oral form. And is that having an issue or is there any issue with taking progesterone orally?

Fantastic question. Wonderful. We just had a conference last week and there was like this roundtable and Dr. Gersh was saying, you know what? I'm going to change my mind. I'm changing my mind about oral. Because it gets metabolized through the liver, over 80% of it gets actually into the metabolite. That's called allopregnanolone. And that can have more sedative effects. It can have amazing effects on brain protection, neuroprotection, calming effects. It's almost like nature Xanax. Right. But it can also help with PMS or pmdd, like premenstrual syndrome. But for some people, first of all, depending on what their genes allow them to metabolize things more or less, they can be more sensitive to the oral progesterone. And Dr. Gersh is believing that too much of allopregnemolone is not good, so she was looking into other forms. But then other people on the panel were, like, not agreeing with it. Here's what my takeaway is. In the physiologic restoration or in the rhythmic physiologic restoration, what we do. We actually also are open to using creams. Right. That's the original Wiley protocol. And the cream, even though it's not standard approach and a lot of people feel like it's not enough for uterine protection, there is actually a study that showed that it can be, because they did biopsies and they found that transdermal progesterone was having effect on the lining. And we know that women that are on this type of protocols and they shed their lining regularly, they actually have a period. In order to have a period, the progesterone must be working on their lining. Does that make sense? Yeah. So it's just not measured well in the blood. Anything that's transdermal from progesterone has more lymphatic absorption, it's more absorbed through the lymphatics, and it doesn't show up on the blood circulation. But there is a lot of methods to a lot of doctors out there, they love transdermal progesterone. Dr. Rosensweet is one of those people, and he doesn't do the physiologic restoration, but he uses transdermal. There are a lot of people who love transdermal, but you need to monitor them in a different way.

For example, okay, I'm going to ask about cycling, but before I do that. So I'm going to come back to that. For those listening that are like, what does she mean about cycling and rhythmic physiological dosing? I'm going to come back to that. But I want to go over, like, some. The thought process behind optimal and average. So I think when mo. Most. I'm speaking for most, not everybody. When most people in my communities go to their doctor, their regular doctor, and they say, test my hormones, what they're hearing is, you are average. You are in average range for your age, and that's fine. And there's a difference between average range and optimal. And then there's places in between. So I want to talk a little bit about that. And I want to go over, because people sometimes will say, what doses are you on? And I want people to instead be looking at levels, not doses. Like, what's your blood level? What's your level first? And then you look at doses. So I want to just kind of. And I'm all. And we can use mine as an example if we need to, but I want to talk through kind of like three for women in their 50s. Let's start with that kind of as an idea. So think you're either close to menopause or you're post menopause. When you say, like, average levels, like, for most people versus optimal, like, what specific specifics are we talking about? Like, can we. Let's talk about estradiol, for example. Like, what is. If you don't do any hormone replacement and you are Postmenopausal in your 50s, like, what is a normal estradiol and what is then an optimal one?

Yeah. So depending on how much body fat someone has, they will have some conversion of androgens into estrogens. Okay. So even though they're not on hrt, they might still have estradiol levels in the serum around 30s or 40s. But really, most menopausal women are going to be below 35.

Wow. Okay.

Okay. Optimal. That's a topic where we can, you know, where some of the people that like lower doses than physiologic, they're going to differ. But what the studies show is that minimum for bone protection, most of them say 60. Other studies say 80 picograms. Of estradiol.

Okay.

Brain. There's some data that 100 might be even better for the brain.

Okay.

A study with Dr. Bredesen's group, where they're going to check it with levels that are going to be around 100 because they want to optimize it even better. They found that estradiol is really important for brain health. Right.

Makes sense. And then heart. What about for heart?

So nobody knows. Right. This is why, doctor. What. The studies that Dr. Gersh mentioned at a 4M was so cool. Right. Because she showed that when the estradiol levels were around 80. But you brought daily progesterone. Yes. Women had. On flow metry, they had vasospasms. So maybe it's dependent also on everything else. For example, progesterone, when it comes in, it downregulates estrogen. So if you give daily progesterone, maybe your baseline estrogen should be higher. Right. These are just basic based on studies.

Can I. Yeah, no, that's great. That's what I want, because I want people to have some kind of range.

So.

And I'll use guys, my, me as an example. When I tested my estrogen, my estradiol was 20, and I was having major, major hot flashes. Like, major hot flashes constantly. So I am on the patch, and my patch was not getting me high enough. So I wear two patches. Yeah, two patches, y', all. To get me to, like, literally like 85. So just. Just. So that's not even. So if I'm hearing you correct, that's kind of like great for bone. It's getting close to brain, but it's not even the protective dose that we're talking about for optimal. Is that accurate, and we need more studies on that.

It's hard because I'm going to use my anecdotal data, but I believe that we will have more and more studies on that.

That makes sense.

I would wish that.

Yeah. And I just want my women to. Because I want people to hear. Because they have no comparison or they're not getting. They're getting told, like, 20 is normal for post menopause. And that's why I wanted to ask you for sure.

Let me tell you something. I have a lot of patients that I get around 100, and they're still not happy because actually their FSH is still going to be high. And FSH is the feedback mechanism to estradiol. And FSH is what the brain releases as a response to how much estradiol docks into the pituitary. Okay.

So let's talk about that one. What number should that one be?

So. So above. So it goes above 20.

Okay.

When you are in menopause or later perimenopause, as a sign off, your ovaries no longer make enough estradiol. So you would want to optimize it below 20, because there's some studies showing that FSH above 20 has its own effects on brain or bone. Wow.

Okay.

So if you don't check FSH and your estradiol looks great, but your FSH is still high, you need more estradiol.

So more estradiol helps lower your fsh.

And then beyond that, I want you to know I have a lot of patients whose mood, depression, migraines, mast cell activation, immune issues, joint pain is not even touched below an estradiol of 200.

Wow.

That's.

Yeah, that's what Maria and Kristen said for them.

That's what they like to individualize people.

Yes. That means.

I had a patient called this morning. Her estradiol was really great, looking like 250. She was weeping. She was weeping. And we previously had her a little bit higher, and I just lowered it because of some other things, but she can't tolerate lower than that. She needs those hype. Yeah. Really directly affects her. Like, she feels so much better on higher doses.

Okay.

If I really want to individualize, I need to take that into.

Makes sense. Okay.

That's what precision medicine is. But you're going to hear from people. No. You're not optimizing other things. No, we're talking about someone who went through amazing, like, lifestyle changes. She's doing totally. And. And she's noticing that change. And you have to allow those individual changes for people. You have to allow these levels to be optimized. A lot of women are going to be scared that more estrogen means more risk factors for other things. Well, here's the only thing you have to consider. If your estradiol goes above 100, you are going to get more of that proliferative effect on the stem cells, on the growth factors that you want. You get more of the goodies for the brain and the bone, but you are also going to build the lining. It's going to be harder to not want to shed it.

That's right.

You go up on the progesterone to 200, 300 daily. You're gonna get the lining thicker. So that's where the cycling comes definitely into.

Okay.

If you want to have higher estradiol doses, you have to get some sort of cycle. Yep.

And I'M not going to forget to ask about cycling. We're going to come back to that. But I want to make sure I'm getting levels first, then we're going to talk about. There's a lot of benefits to cycling that I want to ask you about, especially based on our genetics and things like that. So, but, but hang on to that thought for a minute. I want to ask about just kind of going down the list. So estradiol, if I'm hearing you correctly, you want to be above 60 to 85 at least. And then depending on you and your personality and your goals, there's studies saying 100 and even 200 or higher. And part of going with the higher estradiol is you want to make sure your FSH is going lower because there's protective mechanisms there. So then, so then let's add in, let's, let's jump to progesterone. I'm gonna come back to DHEA and testosterone. So then progesterone. And we're still not gonna talk about cycling yet, but just progesterone in general. What's an ideal? Like what's the average level postmenopausal and what is optimals there?

Yeah, so pre menopausal, in the luteal phase, we want your progesterone to be above 15 now. Okay, but postmenopausal, it's not as clear. Nobody has really looked, look as much at it. There is some studies, but usually people say anywhere between, you know, 3 to 15. Sometimes patient serum levels will come at 20, 25. You want to monitor that because if it's too high, the metabolism is slow and they're retaining a lot of it. And if it's too low, maybe they're not absorbing it that well. Okay, but with the cream you can't measure the serum levels. Right. So then with the cream you need to monitor it through cycling. Okay.

Okay. So minus three. So I'm on the lower side. So it's, it's still, it's in the normal range, it's just on the lower side. Got it. Okay.

And we're talking for all of this serum. Some people believe you should check saliva. When I did my deep dive into it, I couldn't find enough data to justify saliva other than for cortisol testing. And then some people believe that you should do a 24 hour urine test.

Urine test?

Yeah. Or a Dutch test. I want to explain the difference. A Dutch test is a spot urine test of the one time draw in the urine for the metabolites it doesn't tell you how much we did in 24 hours. Then there is a 24 hour urine collection. That's different. It's a little bit more complicated because you have to collect your urine for the many hours. That's what, for example, Dr. Rosensweet's method is. But that I couldn't find a ton of data that, that was related to all the studies we have in terms of serum testing for estradiol, for example, all the levels, I told you for bone or brain, they checked that serum. They didn't check 24 hour urine.

Makes sense.

The levels that we use, it's more targeted towards the studies. But people could do the 24 hour urine. I'm not someone who does that, but that makes sense. I will tell you, all the levels I'm giving you is for, for serum testing. Yep.

Okay. That makes total sense. So now let's go to. And I've got a bunch more to ask, but I want. Let's talk about testosterone for a minute here.

Yes.

So what I want to know is also average, optimal, and then the difference between total and free testosterone. And, and, and this is important, y', all, because, like, I'll just give you guys my example. My testosterone was 55, very low. And I felt it. I did injections, went up to 215 and I heard that's too high. That's too high. But my free was only two. My free was only two. So let's talk about that. You can use me as an example or you could just talk in General.

Check your SHPG.

H. We took. Checked my SHBG. Yes. Which was 85.

85. Okay. So some people believe that when you order testosterone and you order it as an assay with total and free testosterone, the free testosterone is not accurate for women because their levels are so low that the essay cannot even like really catch it really well. So what people believe, if they want to be very precise, is they could use a formulation like the vermillion formulation, and you can put it in a website and you put like your achpg, your total testosterone and your albumin, and you get your albumin from a basic metabolic panel.

Okay.

Or comprehensive metabolic panel. And so like, you know, a cmp. So you could order a CMP for the patient, see what their albumin, which is another protein the liver makes is. Then look what the SHPG is, which is another protein the liver makes. And that SHPG carries testosterone. It can bind to testosterone. Albumin can also bind hormones to a lesser degree. And then you could calculate the free and buy.

I have my albumin, so let's talk about mine's 4.6. Yeah, but it doesn't matter.

Your SHPG is kind of within the range. You want it kind of between 40 to 80. If someone gets, gets above 120, 150, I'll tell them you're not gonna feel the effect of your testosterone as much because you have such high ach.

Got it. But that's not actually high, the 85.

No. So I think what is missing with you. Can I see what your estradiol then is? I don't think your testosterone is so much of a problem, Esther.

You guys, if you have your labs, you can pull this out and do it along with us. So estradiol 75.5.

Okay. And what was the FSH, huh?

FSH, 21.

Okay.

Testosterone total 215.

Okay.

Free testosterone, 2.04.

Okay, well, okay, so free testosterone, if you calculated that with the formula that I told you just online, you put testosterone calculator, you want it to be above 1.5, but you don't want it to be higher than 5. That's usually where PCOS patients are. And you're like, well, you don't want it to be, you know, become insulin resistance and have, have issues with metabolic markers. But yours looks okay. What the problem in my opinion with you is. And I'm not.

No, it's okay. I'm asking because people are asking me this. So I want to ask you.

You have a low estradiol in my opinion, and FSH is not optimized. And what happens is when your estradiol is not optimized, you're not building enough testosterone receptors. Understand this. When you look, look at a pre menopausal 25 year old woman that we use as an example of a hormonally healthy woman of her fertility, what do you think the total testosterone of those women are that are not pcos? They're not.

I mean, maybe, maybe it's a few hundred. I don't know.

No, that's good to know what it is. It's actually between 55 to 65.

Oh yeah.

Total, total or free?

Total or. But that's at their peak. Wow. That's after ovulation. Right. When they pee. Right. Because nature wants us to peak testosterone around ovulation so that we want to have sex. Right. Well, that's not that high. So with injections and pellets, they get people higher than that. And so I say the problem is because they're not optimizing people's estrogen.

So this is really interesting. Okay, so the reason I want to go a little deeper right here real quick is, is there's very confusing information about testosterone. So we hear different things from, like, some people are on pellets and their testosterone super high. Some are not getting any at all, and it's super low. And then what I keep hearing, and maybe this is completely a myth, is that it doesn't matter your total. What matters is you're free. And what if I'm hearing you correctly? It's not. That's not true. Or is that true?

No, no. I was using this study because that study didn't look at hbg. Okay, Right. For those women. But at the very least, they told us how high the total goes. Right. Just to have that. I think it's good to have comparisons. Right?

Totally.

Now, let's say you are trying to optimize your testosterone, and your Testosterone goes to 100, but your HPG is 150 or 200. You're gonna have less of that free unbound testosterone available. And I encourage people to calculate their free testosterone.

Yes.

Not based on the lab, but just calculated themselves for their achpg, albumin, and total testosterone. If they do that, they will see that they have less of that bio available or that free testosterone available. So maybe they need to be hanging out at 100 or. I don't like to go that much higher than 100.

Yes, that makes sense.

It really is supraphysiologic. I will tell you, the reason that women feel that the testosterone is not working enough is. Is the SHBG to a certain degree. So if their SHPG is really high above 100, 120, they're not going to feel that testosterone. The other reason is they're not optimizing the estradiol.

That makes sense. Okay.

For the testosterone receptors.

Okay, we're about to come back to estradiol, but I do want to ask one more marker that people ask about about dhea. What is that, and what does that have to do with testosterone and everything else?

Yeah. Such a great question. So DHEA is mainly made in our androgens to a little bit to a lesser degree, also in the periphery. But DHEA for women, mainly in the adrenals, it is made. It's also steroid hormone, just like testosterone. It's the precursor to testosterone in the adrenals. So from dhea, we make testosterone in our adrenals. Right. And DHEA is measured best as a DHEA sulfate in the serum. And ideal levels would be anywhere between 150 to 200. If you fall below 100.

It might be an indicator that your adrenals are slowed down, and it could affect maybe your energy levels, also your libido, maybe your overall wellness makes sense. If it's very high, above 250, it could be a sign that it. It's overcompensating for cortisol. Or it is. You have some genetic predisposition to high. I see this a lot in my Southeast Asian patients. Right?

Yes.

So they are very pcos. Like, like. And they have this adrenal type of pcos. So if the DHEA is very high, you want to kind of. It is an indicator of insulin resistance. Do you want to add address insulin resistance and the DHEA will come down. Makes sense. One address insulin resistance. Then there is another form of really high DHEA that would be from adrenal tumors, adenomas of the adrenals. And that's usually when it's about 350, 400, like really high. And you could do like, an ultrasound or an MRI of things to rule that out. I've diagnosed that in my career maybe one time.

Wow.

So it's not common or high DHEA than that. Yes, it's a lot more common that it's from high insulin or inflammation or stress than it is from a tumor.

So that's what makes total sense. Okay, so now, okay, let's go back to estrogen, and then we're talking about cycling. So estrogen. There's two other things that come up around estrogen. One, people say that they are estrogen dominant. And I just want to clarify what that means, because estrogen dominant doesn't necessarily mean you have high levels of estrogen. It just means you have more estrogen than other things. What does estrogen dominant mean?

Yeah, So I think it comes from the idea that in the luteal phase, when a lot of people have higher estrogen and not enough progesterone, they can get some symptoms like breast tenderness and, you know, PMS and all that. In my experience, I think people are overestimating the occurrence of estrogen dominance and underestimating how much women are lacking estrogen. Because now that I'm checking it, I'm seeing that estradiol levels, even for younger patients, are not that adequate. Right. For example, at your peak at day 12, you should be between 300 and 500 picograms. In your day 21, 22, you're probably going to be around 250 to 350. Right. Your progesterone then would be around, like, 15 and more. You kind of want to make sure there is a balance. Like if you have no progesterone, but you have a lot of estrogen, sure. That's not good at all. They're yin yang to each other. You need the janitor to come out and sweep the old cells. You need both of them to work together. But I think that using that in menopausal women, for example, makes absolutely no sense because most menopausal women are not even optimized on their.

Got it. So. So these, like when we hear these little things like you're low estrogen, but you're estrogen dominant. I'm not. That didn't really sound right to me either. So let's talk about.

So there's.

There's two reasons that I'll hear women talking about using things like broccoli sprouts or dim or D glucuronidate. And what I hear on those is either they were told they were estrogen dominant. That's one option. Number two, maybe they did some gut testing and saw they were. They had some different markers and they're not processing estrogen well. Or the third reason is I'll hear that they had a DNA marker that they don't. They don't process estrogen well. So those people then, and me included, at some points will take dim. I'll hear broccoli sprouts. I'll hear. You've heard all this, too. Deep glue gluconidate. Is that what it's called when you do those things? Is it myth or truth? Does that just help get out the unused estrogen or is that actually lowering our levels altogether? And where do you. Where do you stand on those things?

Yeah. Okay. Lots of questions. So I.

And I know cycling is going to answer a lot of this, too, but I wanted to build this up first. Yeah, for sure.

I think that the way your liver metabolizes and your gut metabolizes estrogen is key for you to do well with hormones. So I absolutely agree with that. DIM addresses the phase one detox, but it also overall decreases estradiol levels. So it's a little bit less of a favorite of mine because, again, as I said, in menopausal women, most women are already not optimized. And you don't want to. You could support that with sulforaphane or broccoli sprout extract a lot better.

Okay.

Other things that help deliver detox, like, yeah, nac. I have a glutathione product I love you can do, you know, just, just make sure you don't drink too much alcohol or sugar. Things that the liver doesn't like. And then you want to also address the gut microbiome. Right. Doing a GI stool testing you will find that if women have dysbiosis and overgrowth of some bad bacteria or overgrowth of fungus that can the placebo picture can drive up the beta glucorin days. Right. The estrobolomic, the gut bacteria that metabolize estradiol and estrogen. And so if those are upregulated, then you know that they basically are going to try to.

Bring more estrogen back into circulation. The thing is people see it sometimes the wrong way too because they see that upregulated and in absence of dysbiosis think they should still take a calcium declutch chloride. But what they actually should be doing is address the dysbiosis because that will a lot of it. Right. So the calcium D glucorate can be amazing for like mold detox and really when acute phases of your trying to help your estrogen metabolism. First of all long term we don't know if that's good. And second of all, that's not what the purpose of these gut bacteria is. They're just reacting to things. They're up regulated because there's dysbiosis or they're upregulated because you're menopausal and you have too little estrogen to begin with. So it wants to bring back more into your circulation. If you're going to downregulate them, maybe you're affecting that too. So I think it depends on the context. Get a gut stool testing. Look, if you have dysbiosis, address the dysbiosis it often regulates.

Makes total sense. But I'm hearing you, Craig, like, but broccoli sprouts are good. So you can eat broccoli sprouts and that's a natural. And then the NAC and the glutathione. Yes, that that's also helps with the detox pathway.

Absolutely. And make sure you're pooping every day because it doesn't matter how much calcium declutter you're taking, you're not getting rid of the toxins.

Wow. Okay, this is super helpful. Okay, now I want to get into the cycling and the bleeding because this is fascinating to me all and I am not doing this yet, but I have a feeling I'm going to, I'm going to want to learn. So I recently learned that and tell me if I'm correct me if I'm giving misinformation here but that when you, when you are menstruating so you are perimenopause or you are not even in perimenopause, your body gets rid of extra estrogen, extra everything, the lining, when you have your period, when you are in menopause and you're now doing hormone replacement, that extra, if you, if you are have extra estrogen based on your DNA. Some of us we're storing that in fat and that's where it can get dangerous if we're over storing estradiol in fat. Now tell me if I'm, if I might be completely wrong here. I'm just based on different interviews I've done and what people have told me. So what I'm putting together is you have to have a way to get rid of it. So adding back into a cycle would help you get rid of it. Is that part of why we would cycle or is that completely not. Am I completely off track there?

Yeah, I've never thought about it. No, I don't believe that's what it is. So what I would say is this. Let's start with the fat tissue. Okay, so in the fat tissue, because I hear this argument a lot. Hey, you store estrogen in the fat so you don't need external estradiol. The problem is in the fat you're going to convert mostly into estrone and estrone is a different docs only primarily on alpha receptors. It doesn't dock on better receptors of estrogen. Okay, you're not getting the same effect. It also also doesn't dock on the G coupled receptors still and also it's going to be lower levels. It's not going to be enough to make up for all these like loss of bone and loss of brain function and cardiovascular health. So even though you convert some estrogen in your fat tissue from androgens to estrone, it's just not a lot. And that estrone some of it converts to estradiol. Correct. But if you were to measure those serum levels of the estradiol, you're always going to find maybe at most they're going to be at 40, right? 40. I've never seen 50 in a menopausal with but it could be right. Like if she's very, a lot of fat tissue and for example if she's going to be on ozempic and a lot of this fat is going to. There's going to be lipolysis. The fat cells release and they shrink. They're going to release some of those hormones with them, right? Actually, fat cells are organically very active metabolically. They can also store heavy metals or other things. So a lot of people, when they lose fat with GLP 1 months, they'll have Herxheimer reactions from like.

Makes sense.

So you have to make sure you bind things and you use binders and you poop enough and you sweat enough, all of that. But having said that, in my experience, and I'm not speaking for everyone in the world, in my experience, when a woman comes to me, even if they have a higher BMI and they have fat tissue, their serum estradiol is never enough to get them to where I want them to be to protect the bone and the brain and the heart. Now, the cycling doesn't get rid of that stored estrogen. The cycling resets the receptors in the lining. And with that, it's a sign of apoptosis and programmed cell death everywhere in the body. Think of it this way. Your breast tissue every month cycles. Your bone tissue every month cycles. You're just not getting a bleeding from it, but they actually grow and then they shed. They grow and they shed the tissue. So the menstrual cycle is a surrogate marker for the cycling in every organ system of the proliferation and then the programmed cell death where you get rid of the old cells. And that is what the line, what the shedding of the lining stands makes sense.

Okay, so if we wanted to. Okay, talk to us about why you would want to cycle hormone replacement therapy, even if you're postmenopause, like, help us understand why you would want to, why people choose to. And then if you wanted to, how is the proper way to do it?

Well, because I explained to women, like, we have data where we did biopsies of the breast, for example, and in the first half of the cycle, when they were in the follicular phase, there was proliferation of the ducts. And then in the second half, when estrogen, progesterone were together, they could see a lot of them, like, you know, apoptosis dying off and shedding. So women understand now that if it's in that rhythm, done in that rhythm, they're getting that renewal of their cells every month in their breast tissue. We know it from bones, like osteoblasts and osteoclasts. They respond differently to when these hormones come in. And if they're in a rhythm and what levels. So once they understand that this is a rhythm that applies to every organ system. They're like, yeah, I don't want just static. I want that optimization of all organ systems. This is not a widely accepted accepted or based on randomized control studies. I don't want people to come at me and say you're spreading misinformation. This is nowhere I'm seeing. We're using the data from premenopausal women now contra arguments could be who knows if what's good for a premenopausal woman is good for a postmenopausal woman. We don't have the studies correct. Totally using it as based on their physiologic effects on the epigenetic, you know, downstream effects that they have. And so and we have a lot of anecdotal data. I think that the people that I'm mentored with and I'm mentored by and that I'm learning from that have been doing this for 15 years. Publish their data because people the world needs to hear that this is safe, it can be done.

And do you personally do it? Do you personally do it for you? You do. And did you notice a difference in how you feel and markers as when you did this?

Okay, so I'm in perimenopause later. I've never.

Did static to begin with. I honestly just got into even checking my levels last year because I was like yes, learning all these things about the hormones and I haven't even done my.

You're learning and you were doing with patients but you yourself are walking through it now. Got it.

Yes. But on. On patients I can tell you I have women that switch from this. The lower dose status. Yes, this and they're saying the changes are incredible. Is it for everyone? Absolutely not. Does everyone do amazing on it right away? No, it needs a lot of titration. Makes sense and attention. It's much easier to give someone just a patch and send them their way.

Totally. So for me, for me personally, I feel really good not cycling and I'll just tell you why I was one of those people and some of you listeners can relate where I had very extreme pms when I had menstrual cycle it was a very like I'd feel good part of the month. I'd feel not good. Like my husband would know exactly when I I'm where I was in my cycle based on my mood and all the stuff. So one of the things I've actually liked about like being later perimenopause and menopause is that evenness Like, I like the evenness. However, I didn't like the massive drop in hormones. So for me personally, being on the patches, being on testosterone, which I'm still figuring out the right levels, being on the progesterone, it like kind of keeps me even keel. And when I, when Kristen and Maria convinced me to cycle and so did Anna Kabeca, I tried. And then I couldn't sleep and I was like, this isn't gonna work. So that was, this is my experience, not anybody else's. So I'm like, for me, cycling progesterone made me miserable. I couldn't sleep. I also, for me, learned that I've gotta go a little bit higher on estradiol or I don't sleep well either. Like, so there's this, this balance here. I'm still figuring out testosterone. So what would you tell someone like me or anyone listening? They're on some good levels from their doctors. They're feeling pretty good. Do they venture into to this cycling? Is there benefits that? Or do you advise them to kind of stay where they are?

Yeah. So comment on yours. Right now, your estradiol testosterone ratio is not optimized. You, in fact, are not working in favor of your metabolic health. Your testosterone is overdosed and your estradiol is underdosed. So you are going to be more prone to insulin resistance and lipid markers change. That might not happen to you. Right. Your visual fat might not change, but you're more in a PCOS like picture than you are when you are, you know, because in a physiologic level, even though everybody says we have more testosterone and estrogen. Yes, in absolute number, because it's nanograms versus picograms. But in numbers wise, our estradiol will be anywhere between 500. Our testosterone, as I told you, in 25 year olds maybe comes up right. 70.

Now, in fairness, y', all, in fairness, y', all, this test that I'm talking with her about is three months old. I did a new test this morning, so I, and I changed things. So I'll be, I'll have to have to report back, like, what the difference is. So.

Absolutely. I'm just explaining that because.

No, it's great.

Women that are getting injectables or pellets from testosterone. Now, the other thing is, and that might not affect you in the same way because you work out or you're super healthy and your insulin is like super great. I'm just saying for the.

What about doctors that say, sorry, I don't want to, I Don't mean to interrupt, but I wanted to, want to get ahead because some doctors tell you the opposite. Like so like a doctor told me that another one I interviewed said some. Maybe this again myth, I don't know, some women do better. More testosterone, less estrogen. Is that a complete myth or is.

That as these doctors. Then why are we regarding PCOS as a disease? What it is is that you have too much androgens, the SHBG is low and often estradiol is actually not that high. Maybe some women, but they don't. Why don't we then ask them that? Because why would.

A state that we had regard as a disease in PCOS patients? I again, it's going to be very individualized. You want to look at the as well and how they individually react. But nowhere in a normal physiology of a woman of a 25 year old is total sense going above 100. So why are we doing that for women in menopause? That's my only question. And again, I did that. I inserted palates. I'm not, not, you know, I'm not arguing with anyone in that sense. I'm just saying I don't think it was the most physiologic way of.

Do you think they're doing it because it just feels good? Like I think maybe when people get that testosterone, we feel good.

I think because it's easier. You don't deal with the shedding of the lining, but you downregulate A lot of the symptoms, like the hot flashes get away, the energy goes away. But I had a lot of women that despite really high testosterone didn't feel good. I'm glad it works for you, but it's. I have a lot.

Well, I don't know if it works. These numbers did not work. I re, I changed things and now I have new numbers that I'll have soon. I just did new testing today, so I'm, I didn't, it wasn't working. I did not feel good with these labs, so I changed it. I'm very curious how they landed. I went down on testosterone, I went up on estradiol. So I'm, I'm, I'll be curious and I'll have to report back.

What if I ask you, the estradiol, are you doing it as a patch?

You said I'm wearing two patches.

Okay, so then let me address something else you said. What about someone who has. Has comt gene? I didn't say the comp gene, but I think, but that's the gene.

I'm Talking about.

That's the gene that you're talking about. So. So then I ask people, okay, what's your stress level? Because it competes with adrenaline. So if you're very stressed or you have high cortisol or you take coffee five cups a day, it's going to be competing with the estrodite. You're not going to sleep great. You have to calm down your nervous system. The other thing is often as we age, our circadian rhythm gets disrupted too. We actually make less melatonin after the fourth decade. Still, after melatonin at night can downregulate that estrogen effect that keeps people awake. You have to look at your nervous system. You probably haven't addressed your symptomatic nervous system. And I have people, oh, I'm guilty of that. Oh, initially, when I got them on the higher estradiol levels, they didn't sleep well. After three months, everyone was corrected and they sleep right now. You have to ask yourself, why are you so dependent on a progesterone to sleep? You did not have progesterone the first half of your cycle in your 40s or 30s, and you slept well.

No, I'm totally. It's a drug. I get it. I admit it.

It's two things. Because our growth hormone declines, our sleep disruption is worse. So I often use like peptides and other things to help people sleep. But also because your melatonin cortisol is disrupted and so you, you can't blame the estrogen for that. You never had progesterone. The first half of your follicle makes sense. So you were able to sleep, so you can't be dependent on that allopregnanolone. And I think the studies that doctor brought up at Ephraim, they do have to make us think, is daily progesterone really the best way? Because maybe we are down regulating estrogen too much. Maybe we're not getting the benefits from bone and cardiovascular health the way we thought. Now, again, do I have patients on daily progesterone? Absolutely. I'm just asking questions. Totally now makes sense. And then your estradiol is not optimized. And what people don't know is that you need to optimize it for the receptors of progesterone to build. And you need to optimize estrogen and you have to give it time for the tissue to be able to process it. And you need to deliver detoxification. You need to reset your receptors, you need to make sure your micronutrients are okay. There's so many things to sleep. That is so hard to answer. But overall, if you have comt, you can still be on high estrogen. I actually have two patients with COMT mutations that I'm doing the physiologic restoration. And then you asked me one more thing. You said, so well, I want to.

Know how to, how to cycle. Like people that are like, I want to learn to cycle, what do they do? Like, how do you cycle all three?

I don't know if I can actually say that. Okay, but that'd be enough. I mean, I feel like you have to be under the care of someone. Got it.

Okay.

But.

Okay, so without giving me a Zach protocol, in general, is it like you're taking estrogen half the month or progesterone half the month?

Is there anything general in a regular cycling woman? They always have estrogen on board. In fact, their estradiol Never falls below 80 picograms if you look at the lab. And then at best they go high, like higher, like 300 to 500. And then progesterone comes in in the second half. Yes. We make little progesterone in peripheral tissue, but it's so tiny it never translates into serum levels in premenopausal women. So you know that the majority of it comes from the corpus luteum and it's in the second half. So it's around day 14 to 28 in a 28 day cycle.

Got it.

Testosterone in a woman that is still cycling naturally, her levels fluctuate, but also the receptors fluctuate. They actually get upregulated after estrogen after day 12. Estrogen makes testosterone work better, hence why we get so horny when we're still cycling. Right. Estrogen, testosterone, what are optimal levels? I think I mentioned them again. Look at a 25 year old, maybe you don't want to go above like 65 or 70 if you are around 100, but you have a high ACHPG. Don't worry, SHPG is making up for it. Now, I want to say very quickly also, the SHPG being very high can sometimes be a problem because it could mean that you really are not feeling your hormones very well. And you want to look at liver disease, you want to make sure you're not undereating, you want to make sure your thyroid is not overactive, because these are all things that can affect the ACHG being too high. Right. And so sometimes I have to do a liver detox for these people and then I have to make sure the macronutrients and the Nutrition is dialed in, so kind of that. But when you look at a PCOS patient, they're not your ideal picture you want to imitate. They have lower shpg, the androgens are more free, more. More available to the tissue. They often have high DHEA or high androgens, and they have insulin resistance. They have obesity. They are not metabolically healthy. They have dyslipidemia. So that's not an. That's not a picture you want to imitate, you know?

No, that makes total sense. Gosh, I learned so much for you. I do have one kind of like. Well, okay, so when. When you are. So if I'm hearing correctly, when you're cycling these, you want to be under a doctor's guidance. Don't try to do this on your own. But if I'm hearing you correctly, you're kind of on estrogen the whole month, but it's like, kind of going up and then back down. Progesterone is the second half of the month. Testosterone is, like, rising after. So it's kind of there.

But, yeah, you could keep it the same dose, but because of estrogen changing, it will change, also change all of that.

Okay, so it's mostly the estrogen we're paying attention to, to make. To do. To do those changes. Yeah, but you want to be under a doctor's care with that one more part that we didn't touch on. And I know this is a whole different topic, but I just want to get your thoughts, because you said that your thyroid does affect a lot of this, especially your shbg. A lot of doctors aren't testing all the thyroid markers. Like, they're just looking at tsh. Where do you stand on that? Do you feel people need to have their free T3 checked? What's your opinion?

Absolutely. I actually believe that's probably the most important one. There are now people who just don't even check TSH anymore. They just take. And I believe that that's what's. Again, what's the important one. Understand that estradiol, as you raise it, it's going to produce more thyroid binding globally in the liver, and that might bind some of your free thyroid. You might have to adjust your thyroid medication based on that. You definitely always want to measure the free T3, 3, T4, and with the TSH. And then, you know, interestingly, low thyroid function can affect achpg, too. Can it cause it? Yes, Lower. So you want to optimize your thyroid because it's going to affect how all the other hormones are Going to be, you know, received as well, right? No, because no thyroid means low shpg meaning like other hormones don't look like too much androgens available. Like it affects everything right now when.

You are trying to optimize thyroid and there's a lot of confusion around thyroid medications too. Like some people say you just need to take like compounded T3 or combination, like what do what. Can you give any insight to people what they should be asking their doctor there?

Sure. I have patients on all forms. I have people because it's individual. I have people on armor or np Thyroid which is a combination or I have some people on a cytomel lyophyronine like T3 alone.

Yeah.

Some people prefer the compounded version of that or a slow release version. Yes. With the compounding you can make it slow release versus fast acting. So it really depends on the person, on their symptoms. Often it's a lot of trial and failure. I love the com. The combined though, like the armor NP. Okay. Probably the easiest because if the T4 is also not optimized, you're putting, you're putting something into the T4 and into the 3 and so you're up and you're allowing the body to decide how much of the T4 it wants to convert into the T3. But then you have to support the body with the nutrients it needs for that conversion as well.

Gosh, this was so helpful today. You answered so many of my questions. Thank you. These are like I had a million questions clearly from all the interviews I've done. I hope this was helpful to my listeners. Where can they learn more about you? Can people work with you? How do, how do they. They find out more.

Yeah. So people can follow me on Instagram under my name, Dr. Salma Scotty MD and then they can also check my website, Dr. Salamascati.com and then apply for a consultation. And I recommend that, you know, people also check out Wise and Wells book.

Yes, for sure.

A lot of what I said in there, I feel like it helps them to be.

Already I've had them on my show so many times and I. Their book is amazing. So. Yes, absolutely, I agree.

And I think like some sort of, you know, educating yourself already ahead of the time really helps you. But I will, I will be there to clarify questions. I love, I love getting all these kind of questions and being challenged and. Yeah.

And do you work with people if they're not in your location in Florida, can they work?

Yeah, so I have multiple state licenses. They're. They are in my Instagram, but it's like Nevada, California, Virginia, New York, New Jersey, and oh wow. And then if they come to see me in Florida, then I can just help them in person. That would be.

That's amazing. Well, thank you so much for all your help today. Thank you.

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