What No One Told You About The Connection of Progesterone, Estrogen, and Hashimoto’s with Dr. Felice Gersh (Part 1)

Starts at 2:05 (so minus approx. 2 minutes from the times below)

00:01

You just heard about all of the issues Heather is experiencing. And joining me on the show today is the amazing Dr. Felice Gersh. This is Dr. Gersh’s second time on the show because you all have requested her over and over again. Dr. Felice was actually here for episode 185 where we talked about the role of estrogen in immune balance and boy was it an informative episode. And if you missed that one, you have to go listen.

00:26

And if you’ve already listened, it’s one that you may want to listen to again, because the information that Dr. Gersh shares  is more than what you have likely ever heard from any of your providers on the connection of estrogen, Hashimoto’s, and autoimmunity in general.  And if you don’t know Dr. Gersh, she is a multi-award winning physician with dual board certification  in OBGYN and integrative medicine. Dr. Felice is a prolific writer and lecturer who speaks globally on women’s health.

00:54

and regularly publishes in peer-reviewed medical journals. She is the bestselling author  of the PCOS SOS series and her latest book, Menopause,  50 Things You Need to Know. Dr. Gersh, I am so honored and so excited to have you welcome back to Thyroid Mystery Solved. Well, I’m so happy to be back and to expand everybody’s knowledge about hormones.  Amazing.  I and so many of my listeners love the conversation we had last time.

01:23

It was so eye-opening to see estrogen’s role in immune regulation. It was really just fascinating. So I want to continue that conversation today and get into more details as well as talk about the role of progesterone in this because most people, you know, know the basics, maybe,  but it goes so much deeper than that. Now, before we get into progesterone, can you just give us a quick  recap about estrogen’s role in immune regulation? Well, it’s huge. Well, the first thing is just to know that

01:52

I call estrogen, well, which is a family of hormones. We have to make sure that we know that there is no hormone called estrogen. It’s a family of hormones. And the one made by the ovaries is called estradiol, and it has a big letter E and the number two. And there are only four estrogens in the family of estrogens, they’re steroid hormones, that are found in humans. And only three are found in adults and one is found

02:21

in the fetus, that’s E4-estratol, which is  made in the fetal liver. So there’s a lot of confusion about estrogen. So that’s like an important first step. And then to know that there are receptors that’s how the hormones work in large measure. There’s even other ways it’s more complicated. Nothing is as simple as we’ve  ever thought. But there are different types of receptors  and different types of estrogens have

02:50

different strengths and binding to those receptors, and the receptors have different actions when they’re like turned on or turned off.  And so understanding that there are receptors for estradiol  everywhere in every organ system,  including on the thyroid gland, including throughout the immune system, that every immune cell has estrogen receptors,  and that estradiol

03:19

I call the master of metabolic homeostasis. So metabolism is the creation, utilization, storage, distribution of  energy, the spark of life. You can’t be alive if you don’t make energy and everyone knows how important thyroid is and it’s all interconnected  with estrogens and estradiol.  And because there are so many  roles that estrogen plays throughout the entire body,

03:46

by modulating everything in every organ system, kind of like the master at the top overseeing the other hormones underneath it. And there’s all complex interrelationships. Like I said, nothing is simple.  And in terms of the immune system, which is so critically important for  survival, because estradiol is the modulator of the immune system, it’s so critical that we have the right amount at the right time. Modulation means

04:14

It turns on and turns off inflammation when you need it. And what happens when you don’t have enough estradiol as occurs in certain conditions like polycystic ovary syndrome, like perimenopause, menopause, which can be 50 % of a woman’s life nowadays, could be spent in menopause. When you don’t have enough estradiol, either you don’t make it, it doesn’t work properly, it could be a combination of things.

04:43

then your immune system is going to become dysregulated and the default system is to become pro-inflammatory. And it’s so complex, mean, we don’t want to recap everything, but the estradiol is critical for maintaining a proper gut microbiome, which is essential for gut integrity. We don’t want to have leaky gut. When you do, you have these endotoxins from inside the gut coming between the cells and that creates

05:11

inflammation because the immune system that resides around the gut says, oh my gosh, know, there’s like toxic stuff coming in. And it responds by making inflammatory cytokines. And then this creates more insulin resistance. This also dysregulates the autonomic nervous system becoming more stressed, what we call sympathetic.  And then that in turn dysregulates the immune system. So there are many different complex inter-related pathways, but

05:41

In the end,  all these systems that control the immune system staying calm, relaxed, or becoming activated  in the inflammatory state, which should only be activated by injured tissue, damaged tissue, or pathogens like bacteria, viruses, fungi coming into the body, the immune system will not work properly in an absence of adequate estradiol because  it goes into this

06:10

pro-inflammatory state instead of the calm state. So the bottom line is every woman needs the right amount of estradiol in the right  relationships with other hormones, in the right rhythms, in order to have an optimally functioning immune system, which is essential for optimal health. Yeah.  Thank you for that. That was,  I know it’s so much to talk about, but I love how you wrap that all up and

06:39

You know, it’s just fascinating how there are still people, you know, even though we know all of this, that are like, oh, it’s okay. I don’t really need it. You know, it’s, it’s so, so important. mean, estrogen is everything. So thank you for that.  So let’s  dive into progesterone a little bit more. Obviously hormones are never there in isolation. They work together with other hormones and it is such a symphony, but tell us a little bit more about progesterone,  its role  in immune regulation as well. And.

07:08

along with estrogen and then we can dive into a lot of the different things within that. Well, I love having this brought up because even among the majority, I mean, it’s shocking really, the majority of OB-GYNs and I’m an OB-GYN as my foundational educational background, they don’t understand anything about progesterone. They think progesterone is in the female body for the purpose of preventing uterine cancer.

07:35

That’s all like if a woman goes into menopause and she doesn’t have a uterus, in other words, she had a hysterectomy for whatever the reason, then  if she goes on hormones, she only needs estrogen. We’ll say, know, estradiol because that’s what’s usually used nowadays. Not always though, still there are products that are not estradiol that are being sold. But the bottom line is they just say, if you don’t have uterus, you don’t need to have progesterone. Like, of course they think

08:05

There’s only the purpose of progesterone for reducing  uterine cancer risk and occurrence,  and of course to make menstrual cycles and support pregnancies, which of course is not the case when you’re in menopause. You’re not talking about pregnancy. They say, don’t need progesterone. Now, where did this idea come from? It’s like crazy. Well, if you go back in history, history of medicine is very interesting.

08:35

Birth control pills were first invented,  even before that, Madroxyprogesterone acetate, they  created these other  molecules that are called progestins. That’s a made-up word for a fake, I don’t know, it’s like, what do you call it? It’s like a fake  mimic of progesterone. Really, what they are are endocrine disruptors for progesterone. And what’s an endocrine disruptor? It can do

09:02

any one of many things that can interfere with the production, the distribution, the receptor function, the degradation, the elimination of a hormone. So when you think about these progestins, they are also, you could consider them progesterone receptor  agonist slash  antagonist. In other words, they combine two receptors for progesterone.

09:29

which is such a complicated, we’ll just touch on that, like the receptors for progesterone. It’s really complex.  And it can bind to receptors, different types of receptors, and it can either turn them on or turn them off. So it has, it’s not the same as real progesterone. They’re not progesterone, they’re something else. Now, the majority  of the so-called progestins are derived from testosterone. So they’re, but they’re not

09:58

progesterone and then you have madroxyprogesterone acetate, is sort of a different category. It’s not from testosterone. And then you have drosperinone, which is derived from spironolactone. But the bottom line is we’re not going to spend a whole bunch of time talking about progestins, but they’re not progesterone.  And  one of the things that happens with like the majority of these progestins, which includes  MPA, madroxyprogesterone acetate, which is

10:28

what was used in the Women’s Health Initiative study that ended 23 years ago that ended up creating this cascade of negativity towards hormones, which is still a legacy that is hard to eradicate.  We’re still working on getting rid of all the negative thoughts that came from that study, which were  unfounded when applied to bioidentical hormones. They applied to what was studied, which was conjugated equine estrogens, which is the

10:58

estrogens and other stuff that was derived from pregnant horse  urine,  including all kinds of stuff that never would be found in a human. And then even orally, which has a whole different effect on the liver with  the progestin, madroxyprogesterone acetate. And it turns out progesterone, we’ll talk about some of its amazing attributes.  One of its attributes is like estradiol,  it increases the production of nitric oxide, which is a

11:27

critical gas for vascular health and function,  and madroxyprogesterone acetate and the other, most all the progestins, they actually  decrease the production  of  nitric oxide, which is terrible for vascular health. So of course you’re going to have worse outcomes if you use a product that has a totally different and negative effect. But what happened was,

11:53

because they couldn’t give bioidentical progesterone. First it had to be invented, how to make it, and then it had to be created in a way that it could be delivered. And they didn’t have a way of getting into the body bioidentical progesterone.  And it was very short acting when they gave it, if they gave it at all. And so when you try to create something like birth control pills, you need to have a really high dose of these progestins.

12:22

because the way they work is they block ovulation. And so you couldn’t mimic that with natural progesterone. So what became the norm was not to give bioidentical progesterone, but these fake mimics called progestin, which have  negative effects in a variety of ways. So if possible, the doctors would avoid using them when a woman had a hysterectomy, but then when bioidentical progesterone,

12:51

was able to be created and then utilized, they never really got that message, you know, that there’s a difference. And in fact, you can see high-end medical journals publishing articles where they mix up the words and they use the word progesterone, which is what is made in the ovaries and in the brain, which is the bioidentical hormone that humans make, and they mix it up in the article.

13:20

with progestin, they’ll use the word progesterone when they should be using the word progestin. So  doctors are confused, patients are confused. They don’t know the difference. And because there are negative things that happen with these fake progesterones and progestins, the whole mantra of don’t use progesterone if you can avoid it became the norm and it’s crazy. the whole, what does progesterone do? What is real?

13:47

bioidentical progesterone functions in the body just never got relayed, never got into the educational system. And in fact, after the Women’s Health Initiative, apparently all education stopped on menopause and hormones to doctors of every type. So including endocrinologists, they don’t know anything. They were taught nothing. The only thing they know is what they learned on their own. They weren’t taught it in any educational setting, whether it was residency fellowship or medical school.

14:17

Like it’s a big blank. So progesterone, as bad as it is with estrogens, it’s even worse with progesterone. So if we look at progesterone, I consider it the sidekick of estrogen, sort of like Batman and Robin in the feminine role who have to turn them in. But of course these hormones are in men, but just differently in terms of amounts. Now progesterone and estrogens, the estradiol in particular, they are also known as

14:47

neurosteroids. So they’re actually so important, they’re actually made in the brain and  because they’re so important for neurological function.  so in terms of like some of the things that  real progesterone does, which is not even  recognized by the vast majority of doctors, including OB-GYNs, is that there are receptors throughout the body for progesterone  as well. There’s no hormone.

15:15

There’s no neurotransmitter. There’s no enzyme that does  one thing in one place. But the most doctors  and then of course other people, because they don’t know either and they’re listening to what they’re told, they think that progesterone only works in the uterus.  No, there are receptors all over, including involving the immune system as well. And in the brain and on neurons, for example, progesterone is  neuroprotective  and it

15:44

is very critical for the production and stability of the myelin sheath. That’s like the insulation of nerves. That’s what is lost in women who have, for example,  multiple sclerosis. And we know that leads to a whole host of neurological consequences. Well, progesterone helps maintain it. Progesterone maintains neurological health.  And when you lose progesterone, like with aging,

16:11

then what happens is there’s a more risk of developing what are called senior seizures, actual seizures in the brain and having this like type of a seizure that’s from not having enough progesterone. If we look at bone, there are receptors involving bone on the skin. And if we look at the immune system, so there’s this beautiful intersection, interconnection between estradiol and progesterone. And this is a foundational thing that everyone should know.

16:40

I figured it out early in my career when I was delivering thousands of babies, is that whether we do or don’t wanna have babies, that’s okay. I want women to decide when they want them and when they don’t. But the prime directive of life and the way the female body evolved was for the creation of new life, okay? And remember, only humans are the species that tries to determine their own reproductive destiny. I mean, if you had a bunch of dogs together, they don’t say, hmm.

17:10

I don’t think we should make puppies this year. They do not even think about that, okay? So, know, procreation is  what all species do. This is what plants do. This is what animals do. Bacteria, they make new bacteria. So humans were designed to make new humans and the female body evolved for reproductive success. And to that end, we have this beautiful menstrual cycle and understanding

17:39

What happens in the menstrual cycle with the hormones helps to understand some of the role of these hormones that go beyond just the obvious menstrual cycle and then through the rest of the body. So if we think about the menstrual cycle, you start with the first day of the cycle, that’s called day one, and that’s the first day of the period of bleeding. That’s called day one. If we have a 28-day cycle, that’s like the normal. Of course, there’s some variation.

18:07

During the first two weeks, we have just estradiol being produced, a smidgey, smidgey amount of progesterone, but it’s like a drop in the bucket. But so the vast majority, it’s estradiol and it starts really low. It’s very low estradiol during the menstrual cycle. And we’ll talk about why that is. And there’s virtually like no progesterone. And then the estradiol starts to rise. And then  after…

18:33

about 12 days you get this giant spike of estradiol that triggers a giant spike of luteinizing hormone, that’s a pituitary hormone, and that triggers  ovulation, okay?  Once ovulation occurs, a new structure is developed in the ovary called the corpus luteum, which continues to make estradiol and that was made previously in the granulosa cells, and now you make progesterone and it starts low.

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it rises, it plateaus, and if you’re not pregnant, it comes down, okay? And then the estradiol also comes down and that triggers the new menstrual cycle. Now,  remember, prime directive of life, creation of new life. So, to that end, during the menstrual cycle, when there’s no progesterone and there’s very low estradiol, it’s the most pro-inflammatory time of the cycle  because

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you’re creating pro-inflammatory prostaglandins. These are like little fatty acid signaling agents that are produced in the uterine cavity that create some contractions. Now it shouldn’t be over the top. That’s real horrible menstrual cramps. It should just be enough like a mini, mini, mini version of labor. It’s actually like a mini version. And in labor, you make prostaglandins too. In fact, we use them to ripen the cervix and

20:02

to help initiate labor in women when we want to induce them. So you get this prostaglandin production in the uterus, and normally you should have a little bit of cramping for the purpose of expelling the dead and dying cells of the uterine lining so that we can start over again because pregnancy didn’t occur. So you want to expel the uterine lining, and you want to do it in an efficient, easy way, and that involves having cramps.

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and that is a pro-inflammatory process. In fact, if you have a woman who goes into labor to have a baby, what precedes it? A big drop in progesterone, and it triggers the same thing. The body mirrors itself in different ways at different times. Pathways are replicated in  different times and different sites. So in this case, it’s a pro-inflammatory state. So remember,  low progesterone,  low estradiol is more

21:00

inflammatory at that time. Now, when you have your spike of estradiol, that’s the most anti-inflammatory time  of the menstrual cycle for the  estradiol. Now, why would you want to have low inflammation when you have high estradiol? Because you want to reduce the inflammatory response so that you don’t have your own immune cells kill the sperm coming in, right? Because that’s how you make a baby, you know, you…

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fertilize the egg with the sperm. So the sperm are now hopefully coming in, that’s the whole point, right? And then if the sperm  are aliens, they have different protein antigens on them. So the immune system, if it has its way, and this unfortunately does happen in some patients who have infertility, it will kill the sperm, right? Because it’s like alien, alien, know, like could be bacteria or an virus and the immune system will kill it.

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So we don’t want to have that happen. So we have this big amount of estradiol and then, it won’t kill the sperm. Well, what else could happen? You could make an embryo. Well, that’s alien too, right?  The antigens, the tissues, the proteins are different because it’s not a replica of you. It has combined the DNA and such that’s coming from the sperm. So it’s a hybrid, right? So it also is alien tissue.  And so then,

22:29

What happens is you have all this progesterone. Progesterone is very, very anti-inflammatory and it stays high.  If you get pregnant, you have really high progesterone throughout the whole pregnancy until you go into labor, then it comes down.  So what happens is you don’t want your immune cells.  Whoa, you do not want your immune cells to kill your

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embryo and it’s really complex. So there are all these different effects on the immune system on natural killer. Natural killer cells are critical for implantation of the embryo and  everything is related to a whole new system that’s involved. It’s not new, it’s just new that we didn’t know too much about it and that’s the endocannabinoid system. And of course endocannabinoid system

23:26

Well, maybe it’s not of course, but it’s sort of interesting.  It was discovered, but nobody knew exactly what it was, but we knew that there was something that bound to cannabis. Cannabis is a plant,  it can bind to our own receptors, but we didn’t know what those were. We didn’t know anything about it. And when they discovered them, they named  our system  after cannabis. They called it the endo for within.

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cannabinoid system like cannabis. So, but of course we have our own endocannabinoids that are made that bind to our own receptors. Cannabis is a plant. I’m not at, believe me. That’s why we never, never want marijuana anywhere near a pregnant woman or someone who’s trying to get pregnant. Cause it interferes with this whole system that’s so intricate and so important. So what happens is the

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there are endocannabinoid receptors on all the immune cells. the  production of endocannabinoids is regulated by estradiol and progesterone in terms of when it goes up and estradiol causes them to rise and you have the spike of the endocannabinoid production when you have the spike of estradiol and then progesterone  down regulates the production of endocannabinoids. It’s a whole complicated system.

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but the progesterone upregulates the receptors for endocannabinoids on the  immune cells too, because they’re also very anti-inflammatory. But we won’t go into all the complexity of this because  most doctors don’t know anything. But the point is that it’s a complex system and it’s involved with progesterone. So the takeaway is progesterone  is very  anti-inflammatory. Now, why would nature do this?

25:19

Well, because we don’t want to have our immune system attack and kill the embryo and then the fetus. Okay, and we know sometimes that sort of thing does happen. And that’s when they give all kinds of drugs to try to block that. Right, right. It starts with aspirin. So the bottom line is just take away. It’s complex and it’s all about reproduction. The immune cells are very regulated by both estradiol and by progesterone.

25:49

And just for people who may know about this, there’s a condition that is not rare. It’s actually like at least 10 % of reproductive age women called endometriosis. And by the way, it’s not uncommon in women who have Hashimoto’s because there’s a lot of interconnection with these different conditions that women have. There are often many times  multiple things in the same human female that are happening. It’s not rare at all.  And the  endometriosis,

26:19

is a condition of progesterone receptor resistance. The receptors for progesterone are not working properly  and therefore they don’t control the inflammatory response properly when you have the retrograde menstruation. Because every time a woman has a period, some of the cells and blood from the  uterine lining go out backwards through the fallopian tubes into the

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peritoneal cavity into the abdomen and create  like an explosion of inflammation.  And that is controlled by proper preparation of the immune cells that occurs involving the endocannabinoid system and progesterone. But when the progesterone receptors on those immune cells are not working properly, then they don’t get properly primed to be calmer and they go  exploding with inflammation.

27:16

and then that inflammation activates the production locally in the pelvis of estrogens that create more hat. It’s like all uncontrolled, you it’s taking good regulatory. And it turns them on its head.  bottom line is that progesterone is critically important for regulating the immune system, nitric oxide, neurological health. It’s not just,

27:43

It is  very much involved in fertility and menstrual cycle functioning, of course, but it goes beyond that because the immune system is not just in the uterus where you involve it in terms of creating implantation. It’s like so complex. Yeah. And motility of the fallopian tubes and all these things are all interconnected.  But these  systems are replicated all over the body. So if you want to have

28:12

a good healthy set of bones, a good brain function,  and the gut,  you want all these things functioning properly. You want an immune system that isn’t in a hyperinflammatory state. Then you need to have adequate progesterone. It’s not optional.  And progesterone has like, there’s both membrane receptors.  It’s like estrogen, even more complicated.

28:38

There are multiple  membrane receptors, that means on the cell membrane, and then there are nuclear receptors, so the progesterone has to get into the cell, into the nucleus to activate the production of proteins.  are even receptors that are turning off the receptor.  It’s like,  oh my goodness, progesterone is a very complicated hormone,  and  all of this is very interconnected.

29:08

When women go through menopause, this is like a critical hormone to have on board. But it’s also important to recognize that progesterone has both a synergy and also an antagonism. Because what happens is when you have a menstrual cycle and you have more production of  estradiol,  estradiol upregulates its  own receptors up to a point.

29:36

If you have really high estradiol, it actually then downregulates the alpha receptor. So there’s this beautiful feedback system.  Estradiol  upregulates, it means it makes more functional progesterone receptors,  thyroid receptors. Yes, that is a big… Oh my gosh, testosterone receptors, so that when you have that spike of estradiol, that upregulates the testosterone receptors so the testosterone works better.

30:06

increasing sex drive, sexual response, interest in sex for the purpose of making a baby.  Because you can  only fertilize the egg for 24 hours. It only lives for 24 hours. So you want to make sure the woman says,  I think I want to have sex today. And that’s when she’s fertile, right? So the sperm can live for several days waiting for that egg. But the bottom line is that we need to make sure that we have

30:35

the right hormones and the right rhythm because when you make progesterone, progesterone  down-regulates estrogen receptors because you don’t want to keep growing the uterine lining. has to, it grows, that’s why they call it proliferative in the first half of the menstrual cycle. Then when you make progesterone, it stops the growth by  down-regulating the receptors of estrogen that create growth factors and then

31:04

the progesterone causes it to be what we call secretory. It’s like blossoms and blooms. And so progesterone has to be given in a cyclic way. Yeah. Unless you’re always affecting the estrogen receptors in a  negative way. Right. So I want to dive into that. But before we dive into that, I just want to say, first of all, thank you for this summary, because that’s, I think, the most comprehensive way I’ve ever heard anyone talk about it. Why isn’t everyone talking about this? But that’s a whole other question.

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But I think what’s so interesting and for everyone listening who has Hashimoto’s and autoimmunity, it’s,  even if someone is not trying to get pregnant, right? Because so many people, you know, might be, but there’s so many other people that might be in perimenopause or menopause that are listening. So, but I think what’s so important is the way that you explain it is that it still goes back to, yeah, even if you’re not trying to have a baby, the way you understand progesterone is that the body works from that method even later in life, which is why…

32:00

We, I mean, this is also why, and I love what you said about how progesterone drop is so inflammatory because so many people with Hashimoto’s have flares every month. And guess what? Well, it’s going to be around their cycle because inflammation goes up and the same about postpartum, right? We always think, we’re just going to say that postpartum is

32:20

there’s flares of all the auto-. Autoimmune, exactly. And it’s not just a drop in estrogen, it’s progesterone too, like you explained. Exactly, exactly. And the purpose of explaining the menstrual cycle  isn’t because everyone wants to get pregnant at all. It’s just understanding, like you said, the foundation of what these hormones do, and then whether you want to get pregnant or not, understanding that the relationships and the action and the way it works on the receptors doesn’t change and that these are

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doing multiple things throughout the body and understanding this interconnection between the hormones that they turn  on and off and up and down regulate each other’s receptors.  And that there’s  a method to this madness of the menstrual cycle. And it’s not superfluous because what’s happened now and it breaks my heart  is that the standard way of

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prescribing hormones to women in the menopause makes  absolutely no sense. But if you don’t have any foundational understanding of what anything does of all this complexity, then like, duh, it’s like, who cares? But it does matter. So this is what’s the standard  hormone,  like way that people are getting it and it’s getting prescribed is that they get this really tiny dose of estradiol.

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And why would they do that? Why would anybody prescribe a tiny dose? Because they don’t understand that estradiol does all these amazing things in the body and that dose matters. That a low dose is like more pro-inflammatory and a higher dose. We’re not talking about above physiologic levels. We’re talking about the higher of the normal levels, right? And Dr. Gersh,  what blood, you know, speaking of estrogen and prescribed because that is still coming, but we’ll do such low doses. But do you have, and of course every person is different,

34:15

if someone is in menopause already, right? So they’re not having any type of cycle. If they do a blood test,  where would you ideally want to see the estradiol levels? Because so often people say, oh, I’m an estrogen, my estradiol levels are 40. And it’s like,  What do you think? Well, of course we need more research. So I go back, and by the way, this is  not the, we’ll say conventional standard approach.  So I want to make sure people know I’m an outlier.

34:43

The standard approach, the standard acceptance of hormones in menopause is this old mantra that developed from fear and hate really of hormones, which came after the Women’s Health Initiative, which is hormones are kind of intrinsically bad and the less we give the better. I mean, it’s crazy when you know that. So the mantra was the lowest dose. Well, we don’t do the lowest dose for anything that’s good for us.

35:13

optimal dose, whoever heard of giving thyroid hormone to give the absolute lowest dose to keep you alive? No, that doesn’t make, who does the, the lowest amount  of exercise? Why don’t you exercise five minutes a month? Like, who would recommend that? know, one bite of vegetables a year. mean, it’s crazy. We don’t do the lowest dose. We do the optimal dose. You know, there’s too much of a good thing and there’s too little of a good thing. But if you don’t think it’s a good thing,

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then it would be like skull and crossbones, but that’s not what hormones are. They’re like not poison, they’re beautiful, they’re wonderful, they’re life-giving. So we want to give a  dose that is going to give us a level that is somewhere in the physiologic range, like  what would be seen in a normal menstrual cycle. I’m still a work in progress on this as well, because if you look at the hormones, of course, of a menstrual cycle, they’re not static.

36:12

They’re  changing all the time. But if you look at just sort of a general thing, the amount of estradiol produced is higher in the luteal phase, but it’s countered by the progesterone, which downregulates its receptors. So it’s a complex interconnection there. And of course, it’s rising. So if you look at sort of average levels, my trend, and right now I’m giving this most of the time, the same amount of estradiol throughout the whole created cycle.

36:41

But that may change because I’m thinking and looking at some of the research that it may make more sense to increase the dose of estradiol when you give the progesterone for the second two weeks of the cycle. So if you try to  mimic a menstrual cycle somewhat, it’s not exact. We don’t have that ability yet.  The best would be we get a new set of ovaries, but that’s not happening yet. So during  the first half of the menstrual cycle,

37:10

it would be good to try to get a level. It has to be over 50.  Once you get below, this is in the measurement in the US, is picograms per mil for estradiol.  In Europe, they use a different measurement. you can’t, the numbers can be converted, but they use a different measurement. So we use picograms per mil. So you wanna get it over 50. Under 50 isn’t going to be, that’s like getting into menopausal range. So you don’t wanna,

37:38

give hormones that keep you in the menopausal range. So you gotta get over 50. Probably the sweet spot is going to be more in the neighborhood of like 80, but it could be anywhere from say 60 to 120. Okay, now. And this is of just estradiol, right? Not total estrogen. Oh no, don’t measure total estrogens. Just measure estradiol. And so this is going to be for estradiol.

38:06

Now, of course, it’s going to vary from  even the time of day.  If you’re getting hormones, you know, the type of delivery system, it should be transdermal through the skin, but whether you’re using a patch, a gel, or a compounded cream, and there’s even a ring that’s used vaginally, that’s not too often though, you know, you’re going to have some fluctuation from day to day. So this is what I call ballpark medicine. And if you look at menstrual cycle hormone levels,

38:33

of fertile women, women who successfully conceive, they don’t have all the same exact numbers, the same exact levels. There’s actually a range and it’s pretty significant range. So we wanna be in the ballpark, that’s what I say. You don’t wanna be like too low, you don’t wanna be crazy high. There is a safeguard with estradiol that if it gets too high, it actually down-regulates its own receptor, the alpha receptor, which is what creates growth factors.

39:01

So, but you know, the goal is just to get in a rational range. Now, this is where I’m rethinking a lot of this. In the luteal phase, which is the part where you have the progesterone, in a normal menstrual cycle, the levels go higher. There is some data, but it’s not enough. I’m trying to get more studies to be actually done, and I’m in the process of working on that. In the study, it showed that if you increase the amount of estradiol

39:31

when you added the progesterone, it had a better effect  on vascular dilation. So I’m thinking that, you know, because we don’t want to have anything that can counteract, you know, all the estrogen’s effects. And  there is some down regulation of the estrogen receptors by progesterone, which is the way it’s supposed to work. And that’s why in nature, the amount rises. So I’m thinking that maybe we should increase

39:59

by maybe 50 % or maybe more, have to check levels to try to get up more into like the 120s or even up to like 200 because in a normal menstrual cycle, often, estradiol levels will go into the 200s. So we can go higher. So these are areas where I’m trying to get research because I know no one in the conventional medical world will ever accept anything without clinical studies.

40:28

But we have science and we have little bitty studies like a couple of months with 35 women, but they won’t buy that. Those are like pilot studies. We have to more studies, but we have science and we have our menstrual cycle. We know what happens and then of course we know what happens when you lose your hormones and that is not good  because these hormones are doing all these things. It’s like thyroid. If you just take out somebody’s thyroid, maybe they had this gigantic  goiter.

40:57

And you know, it’s like, Oh, I can’t like swallow, you know, and there’s nothing you can do to shrink this giant goiter. Okay. So they have to, this happens rarely, fortunately, they have to take out the thyroid gland. Okay. So now you have no thyroid for whatever reason, you have no thyroid gland.  No one would say, well, that’s okay, lady. Why don’t you, why don’t you meditate more or,  or exercise more or, know, I’ll give you Prozac. It’s like.

41:23

No, I mean, if you don’t have a hormone, you give a hormone,  know. you have autoimmune, we want to try to reverse it as best we can, especially in the early stages. But if you really, really have low thyroid or you don’t have a thyroid gland, the solution has to be you give the hormone.  If you don’t have these hormones, you have to give the hormones. And we would want to give it in a way that is consistent with optimal health, not like… Not lowest dose. Not the lowest dose, the optimal dose.

41:53

So that’s where the levels come in. And the  gold standard is blood testing. Now that may change  in terms of  saliva testing, but right now it is not validated. So I discourage doing salivary testing.  Urine metabolites are useful if you’re doing menstrual mapping where you can get multiple levels of these hormones through measuring

42:22

urine metabolites and it gives you a good idea of what’s happening during a menstrual cycle because you wouldn’t want to have blood tests done, you know,  11 or more times.  That would be, you know, to go in and keep getting blood tests done all the time  would be very unpleasant. So you can do these urine metabolites. But as a general rule for just measuring,  I  use the gold standard, which is a blood test.