00:00:00:05 - 00:00:18:02 

Noah Reed 

Welcome back to the Dutch podcast, where integrative medicine providers can expand their understanding of functional endocrinology and testing. And everyone, no matter who you are, can learn more about their bodies. Most Complex Communication System. I'm Noah Reid, vice president of sales and marketing for the Dutch Test. 

 

00:00:18:07 - 00:00:30:14 

Noah Reed 

And coming up on this week's episode, we bring you endocrine essentials with Dr. Bethany Hays. Dr. Hays will give you a high-level view of progesterone. What is it? What does progesterone therapy do and who does it help? 

 

00:00:31:08 - 00:00:50:12 

Noah Reed 

Bethany Hays, M.D., has retired from a long career in medicine, where she was a board certified OB-GYN and practice obstetrics for 29 years. She delivered her first baby in 1972 as a medical student at Baylor College of Medicine in Houston and delivered her last baby in 2001. 

 

00:00:50:21 - 00:01:12:02 

Noah Reed 

She then created a holistic health center in Falmouth, Maine, for 14 years. Dr. Bethany Hays was also the medical director of True North, a nonprofit organization whose mission is to change health care in America. She has been teaching for the Institute for Functional Medicine since 2000 and previously served on their board of directors. 

 

00:01:12:08 - 00:01:26:03 

Noah Reed 

Dr. Hays has been affiliated with Baylor College of Medicine, University of Vermont Medical School, University of New England and Dartmouth Medical School, and is currently affiliated with Tufts Medical School. Now let's get started with the show. 

 

00:01:27:03 - 00:01:50:13 

Mark Newman 

Thanks, Noah, and thanks to Dr. Hays for joining us today to have a little conversation about progesterone. You've always been one of my faves when it comes to providers whose brains I got to pick, because very, very early on you listened and then you critiqued very well and you gave us some really good questions that helped kind 

 

00:01:50:13 - 00:02:02:09 

Mark Newman 

of for what we're doing to sort of take shape and to help us in a healthy way to critique what we were doing and how we were presenting it and bringing up some of those questions that we needed to be asking. 

 

00:02:02:09 - 00:02:18:06 

Mark Newman 

Now, a lot of those centered around estrogen, and we had some great conversations with Dr. Tara Scott about estrogen and its role and what does it mean when it's out of whack. And of course, that gets you right into the dance that estrogen does with progesterone. 

 

00:02:18:13 - 00:02:30:08 

Mark Newman 

So, if you could, I'd like you to just give us your rendition of what progesterone is and what its role is primarily in female physiology. 

 

00:02:31:20 - 00:02:52:10 

Bethany Hays 

Well, first, let me say that I also enjoyed our conversations early on and ever since then, because of your extraordinary understanding of the literature and the laboratory and cleared up a lot of questions that I had that didn't make sense from what I was reading. 

 

00:02:52:23 - 00:03:16:20 

Bethany Hays 

So let me talk a little about progesterone. So, progesterone is often referred to as the anti-estrogen, but it really is probably better thought of as estrogen’s partner. And in most places where you find estrogen receptors, you will also find progesterone receptors and they have some similarities. 

 

00:03:16:20 - 00:03:28:11 

Bethany Hays 

Estrogen has an alpha receptor and beta receptor on the stronger and one is not as strong or one does one thing. And one of those the opposite thing, depending on the tissue it's in and progesterone does the same thing. 

 

00:03:28:11 - 00:03:53:22 

Bethany Hays 

It's got an alpha or a beta sensor, or receptor A and a B, and they do different things depending on what tissue they’re near. So, progesterone is was originally found in the corpus luteum of the ovary, which is the the area of the ovary that produces progesterone after ovulation. 

00:03:54:18 - 00:04:16:03 

Bethany Hays 

And it supports the lining of the uterus to become receptive to the embryo as the embryo comes into the uterus and implants. If progesterone hasn't been there to create a nice, soft, fluffy bed for the embryo landing, it just doesn't land. 

 

00:04:16:03 - 00:04:33:15 

Bethany Hays 

And you don't get pregnant. As soon as the pregnancy is established, then the production of progesterone is turned over slowly over the next several weeks to the placenta. So, during pregnancy, the placenta maintains a lot of her estrogen. 

 

00:04:34:02 - 00:04:54:07 

Bethany Hays 

And what it's doing is to help the uterus grow from a tiny little pear-shaped organ in the pelvis, to this great, big, muscle that holds, nourishes and then gives birth. And in order to make that change, you need a lot of progesterone. 

 

00:04:54:07 - 00:05:17:08 

Bethany Hays 

So, the placenta makes progesterone. And that was where we first discovered progesterone. And so they called this pro gestational hormone. It was the hormone that kept pregnancy going. When the progesterone falls off in the estrogen serious, more irritable, and later begins to purge. 

 

00:05:17:08 - 00:05:40:09 

Bethany Hays 

So, progesterone has an annoying habit from a laboratory point of view of going up and down and up and down and up and down, which makes it very hard to measure. And that's been one of the problems that we've had understanding progesterone is when you measure it, you measure it in the morning, measure it at night, measure it 

 

00:05:40:09 - 00:06:04:17 

Bethany Hays 

in premenopausal women, measured in post-menopausal women. Do you measure the first part of a cycle? Mid-cycle? End of the cycle? And it is a changing hormone, which makes it really interesting. And what what has always sort of been the case is progesterone, which are low progesterone. 

 

00:06:05:08 - 00:06:21:21 

Bethany Hays 

You know, it doesn't matter. You can do as much as you want. And people haven't really understood the intricacies of progesterone. So, I've done a few deep dives into progesterone and I keep having to dive back in because they keep finding more and more about it. 

 

00:06:21:21 - 00:06:37:07 

Bethany Hays 

When I first studied progesterone, all you could find was artificial progestit. That's what people were using, and the only reason we used them was to make the uterus stop bleeding and. And so that was all anybody knew about. 

 

00:06:37:16 - 00:06:43:07 

Bethany Hays 

And if you read studies about progesterone, you were reading studies about artificial progestins. 

 

00:06:43:12 - 00:06:44:09 

Mark Newman 

That's one of the most. 

 

00:06:44:16 - 00:06:45:12 

Bethany Hays 

Crazy making. 

 

00:06:45:15 - 00:06:59:22 

Mark Newman 

One of the most frustrating things in the literature, very specifically, is that is that you can go find a paper that will conclude something about progesterone and you get to page three and then you realize, oh, you guys are using the wrong language. 

 

00:06:59:22 - 00:07:17:19 

Mark Newman 

You're talking about a synthetic progestin that in some ways mimics progesterone and in some other ways, they certainly aren't pro-gestation. Right. They're problematic. And it makes it hard to figure out what's actually true of this hormone. So, I appreciate that description. 

 

00:07:18:08 - 00:07:36:17 

Mark Newman 

It's a great introduction to what we're talking about. So. So we're looking at a hormone that's going to stay relatively flat until ovulation. And then there's this surge. And the surge indicates that ovulation happens. When when do we actually want to test women for their progesterone generally in a normal cycle, let's say a 28-day cycle. 

 

00:07:38:03 - 00:07:54:18 

Bethany Hays 

Well, ideally you want to test hormones when they are the highest because that's when they're the easiest to test, and when the results are the most reliable. So, the progesterone in a normal menstrual cycle is the highest at mid-luteal phase, right? 

00:07:54:18 - 00:08:17:05 

Bethany Hays 

So, about a day 21 is in a 28-day cycle is the ideal time to test progesterone. Now, that's not when estrogen is the highest because estrogen peaks at our relationship, right? However, estrogen is produced by the ovary in concert with progesterone. 

 

00:08:17:05 - 00:08:37:12 

Bethany Hays 

So, estrogen levels do go up and they also peak again in the luteal phase. So, the ideal time to measure both is mid-luteal phase, day-21, because then you don't have to do multiple tests and so it's cheaper and it makes sense to be that way. 

 

00:08:37:20 - 00:08:43:00 

Bethany Hays 

And, you know, you've tabulated the levels of estrogen and progesterone go up in the luteal phase. 

 

00:08:43:12 - 00:08:57:07 

Mark Newman 

Right? I've used the word plateau. What I appreciate about what a woman does in days for us, we've looked at the statistics and between about 19 and 22 is a nice little plateau in a normal cycle to see whether there's enough progesterone or not. 

 

00:08:57:11 - 00:09:22:05 

Mark Newman 

So, if my progesterone is really, really low, it implies that the woman didn't ovulate. And if the progesterone is higher than that, but yet still not quite enough, you may say she's ovulated, but she's got insufficient progesterone. So, do you see a distinction in terms of symptoms in a woman, whether she's not ovulating or she's ovulating, but 

 

00:09:22:05 - 00:09:28:09 

Mark Newman 

just not quite making enough progesterone? How would you differentiate between those women in terms of what you expect them to maybe complain about? 

 

00:09:29:21 - 00:09:42:23 

Bethany Hays 

OK well, first of all, let me say that you've got to be sure that you've got the right date for ovulation. So, what you really want to do is test a week after ovulation. And I don't know and I realize that's difficult. 

 

00:09:43:00 - 00:10:02:06 

Bethany Hays 

And some women ovulate early in their cycle and some women ovulate late in their cycle, but at the peak of estrogen and progesterone occurs about 14 days later. So, if you haven't got the right ovulation date, you're not going to get the right lab test information. 

 

00:10:02:06 - 00:10:05:10 

Bethany Hays 

And you may think you have a low progesterone when you just didn't pick the peak. Right. 

 

00:10:05:18 - 00:10:06:03 

Mark Newman 

Right. 

 

00:10:06:11 - 00:10:24:09 

Bethany Hays 

Finally. Right. So how many women will behave when they don't have enough progesterone? Well, the first thing that happens is they have a spotting leading into and out of their period. The progesterone doesn't prepare the lining for menses. And so they tend to dribble. A lot. 

 

00:10:24:13 - 00:10:42:18 

Bethany Hays 

So, they tend to have spotting before and then they dribble out, spot on out. So, you don't have a nice brisk onset of bleeding the last three or four days and then it goes away. Right. And that makes it hard sometimes for women to tell you when the first day of their last period was. 

 

00:10:43:20 - 00:10:58:15 

Bethany Hays 

You have to ask the women, when was the first heavy day of bleeding? Not, when was the first day you bled? Right. And so I learned to say, like, you're on day one of your cycle is the first of week. So that's the first thing is the spotting. 

 

00:10:59:10 - 00:11:22:23 

Bethany Hays 

The second thing is women get premenstrual symptoms. So, you know, think of all the symptoms that you associate with premenstrual syndrome, you know, headaches, irritability and breast tenderness. So practically anything you can think of that women complain about is going to sort of end up in that in that area of their menstrual cycle. 

 

00:11:22:23 - 00:11:50:19 

Bethany Hays 

And and a lot of them have to do with either too much estrogen or too little progesterone. So, these two hormones have to play together. And if they're not playing together, you're going to throw things out of whack because so many organ systems and tissue types require a change to get ready for a pregnancy or change to create a 

 

00:11:50:19 - 00:12:04:11 

Bethany Hays 

pregnancy and maintain it. And then a change starts over those fast-growing parts of the system don’t just take off and get into trouble with things like cancers. 

00:12:04:19 - 00:12:20:06 

Mark Newman 

Right. If you're talking about breast tenderness, the breast tenderness would be the proliferation from the estrogen without progesterone there and adequate levels to balance that and to bring that back into what's what's normal? Is that a fair description of what's going on there? 

 

00:12:20:17 - 00:12:43:23 

Bethany Hays 

It can be. Breast tenderness. Progesterone causes more growth, but it also causes maturation of breast tissue. So, it turns it into the kind of tissue you're going to need to nurse a baby and and then the progesterone drops off and those cells go into apoptosis. 

 

00:12:44:09 - 00:13:03:21 

Bethany Hays 

And if you don't get that drop-off in progesterone you don’t get the apoptosis. And so your breasts get more and more and more uncomfortable with each cycle. So, when the estrogen goes up, a breast that is not cycling properly is going to be more uncomfortable. 

 

00:13:04:17 - 00:13:30:23 

Bethany Hays 

And it's interesting because, you know, progesterone in the uterus makes cells stop growing and progesterone in the breast makes cells grow. And it's actually in the uterus progesterone is making cells grow, it’s the stromal cells that it's stimulating to become decidualized, whereas in the breast it is the glandular tissue as well as stromal tissue that is stimulated to 

 

00:13:31:13 - 00:13:58:16 

Bethany Hays 

prepare the breast for breastfeeding. So, estrogen is kind of a one-trick pony. It makes things grow. And progesterone is a modulator. And it can do both depending on what may end up being dependent on depending on not only the level of progesterone in the tissue, which is hard to measure, but also the metabolites of progesterone 

 

00:13:59:08 - 00:14:04:05 

Bethany Hays 

that may be different for different people. Just like estrogen metabolites are different for different people. 

 

00:14:04:18 - 00:14:17:15 

Mark Newman 

Oh, interesting. Maybe we'll maybe we'll come back to that. That might be interesting to pick out a little bit as far as progesterone metabolites. So, we're talking about women who don't make enough progesterone, which is the usual topic about progesterone. 

 

00:14:17:21 - 00:14:30:22 

Mark Newman 

Let me just ask you briefly, though, if I dose you with progesterone, obviously, I can get you into a place where you have too much and you might feel particular symptoms. Is it is it really something we even have to think about? 

 

00:14:30:22 - 00:14:38:15 

Mark Newman 

About a premenopausal woman, ovulating, making progesterone, and making too much progesterone. Does that happen? And if so, what does that look like? 

 

00:14:39:13 - 00:14:58:08 

Bethany Hays 

Well, you can overdose people with progesterone. There are two things that I've seen happen. One was a woman who had a lot of premenstrual symptoms and estrogen dominance symptoms, and she was put on progesterone and she felt better. And then after a while, she didn't feel so good. 

 

00:14:58:08 - 00:15:12:12 

Bethany Hays 

So, she took some more progesterone around and feel better and she started not feeling so good and so she took more progesterone. And then she began to. So, she came to see me and she was on. Yes, I think she was on 

 

00:15:13:15 - 00:15:16:02 

Bethany Hays 

4,000 milligrams of progesterone a day. 

 

00:15:16:12 - 00:15:17:11 

Mark Newman 

Oh, wow. 

 

00:15:18:00 - 00:15:31:12 

Bethany Hays 

And I said, whoa, wait a minute. You can't. You can't do that. She said, well I can’t get off the progesterone. So, I said, well, let me tell you what you're doing with your progesterone. The reason you don't feel good is your estrogen level is high and your testosterone level is high but 

 

00:15:31:19 - 00:15:52:21 

Bethany Hays 

the reason is you're driving progesterone down those pathways. And if you get off the progesterone, your estrogen testosterone will drop and you'll feel better. So, you can go as slow as you want to, but you've got to wean yourself down to, I don't know, maybe 400 milligrams a day and we’ll recheck. 

00:15:53:02 - 00:15:59:18 

Bethany Hays 

So, we rechecked her hormones at 400 milligrams a day and her estrogen and testosterone were boom, back into the normal range. 

 

00:16:00:10 - 00:16:02:20 

Mark Newman 

She taken it orally or as a cream or what. 

 

00:16:03:09 - 00:16:07:07 

Bethany Hays 

She was using and cream. And she did it all the time. 

 

00:16:07:08 - 00:16:08:03 

Mark Newman 

Okay. Wow. 

 

00:16:08:04 - 00:16:23:01 

Bethany Hays 

It was like getting a brain hit every time she put progesterone on her skin. Wow. And so she would come into my office, get out her progesterone, put it on her skin. She, she couldn’t go more than, you know, two hours without some progesterone. 

 

00:16:23:04 - 00:16:23:22 

Mark Newman 

Oh, interesting. 

 

00:16:24:08 - 00:16:37:15 

Bethany Hays 

So, I've seen that. You know, another thing you see is people say, I got that progesterone, but, boy, I’m like low. I can't drive to work when I take that stuff. So, you need to tell people the first time they take it. 

 

00:16:37:18 - 00:17:05:04 

Bethany Hays 

Take it at night. Pay attention to are you to out of it to drive or, you know, to take care of the kids or whatever you have to do. And so I have seen people who got too much bioidentical progesterone, which, of course, is metabolized in the brain active metabolite allopregnanolone, which makes people feel good 

 

00:17:05:07 - 00:17:24:00 

Bethany Hays 

some of the time. I mean a lot of people with irritable brains from too much estrogen, estrogen kind of makes you irritable. Progesterone smooths that out, and they love that. In fact, women on birth control pills are missing that, and give them a little progesterone and they're happy to stay on their pills. 

 

00:17:24:18 - 00:17:44:00 

Bethany Hays 

But, if you give too much progesterone and maybe if you have somebody that has a big, upregulated metabolism of allopregnanolone and you can make people feel pretty spacey. It's the alpha-gamma receptor agonist. A function of progesterone and of course, GABA receptors as well. 

 

00:17:44:12 - 00:17:51:08 

Bethany Hays 

That's why we take in anxiolytics and sleep medicine and all of those things. So you can get that right. 

 

00:17:51:08 - 00:18:07:21 

Mark Newman 

Right. Which is why we pay a lot of attention when people take, in particular, oral progesterone to not just what those levels are, but which where they pushing it towards the alpha metabolite of progesterone, which is in that family of allopregnanolone or down the less active beta pathway. 

 

00:18:08:17 - 00:18:22:22 

Mark Newman 

Let me pick at the supplementation a little bit. You know, we've talked before about the fact that the literature doesn't seem to support well enough the use of a progesterone cream to support someone who's on estrogen replacement therapy. 

 

00:18:23:02 - 00:18:37:18 

Mark Newman 

Typically it's oral and it's progestin and it's vaginal progesterone where we see the evidence in the literature that it does enough to balance the endometrium. But let me let me rewind the clock on you to the premenopausal woman who's 35, had two kids, just doesn't feel very well. 

 

00:18:37:18 - 00:18:54:17 

Mark Newman 

And so the picture in your mind is estrogen dominance. She's ovulating, but not making enough progesterone. What are you doing with that woman? First thing I want to ask you is, are there things you pursue outside of progesterone supplementation to help support the woman's natural production of progesterone? 

 

00:18:54:17 - 00:18:59:07 

Mark Newman 

Again, if she's ovulating, but just making insufficient progesterone to balance that estrogen. 

 

00:19:00:11 - 00:19:10:13 

Bethany Hays 

Well, the first thing to think about is if we want to balance, estrogen is she making too much estrogen? Right. So, I'm going to be giving her supplements to help her get her estrogen out of the way. 

 

00:19:10:21 - 00:19:24:19 

Mark Newman 

So, when we when we find a woman who's got some dysfunction as it relates to progesterone, we want to be looking at the picture comprehensively. We like that. But when you start giving again a premenopausal woman who's got insufficient progesterone. 

 

00:19:25:20 - 00:19:36:05 

Mark Newman 

Are you reaching for progesterone as a cream or oral progesterone or what? What do you tend to reach for in your toolbox with a premenopausal woman who's just a little short on progesterone? 

 

00:19:37:09 - 00:19:56:03 

Bethany Hays 

Well, I want to start with transdermal progesterone, and you can give it as a cream or you can give it a drops in propylene glycol, which I got really good at doing. And the time where I would switch to oral progesterone, it's when I want that first pass through the liver. 

00:19:56:14 - 00:20:10:19 

Bethany Hays 

So, I want to get it for our craving to help with sleep. Gotcha. You're taking a pill at bedtime, and most women are happy to do that. Some women really hate the creams, and a lot of women hate vaginal cream because it 

 

00:20:12:02 - 00:20:28:06 

Bethany Hays 

it's a nasty discharge. But so often they don't mind the cream and, you know, the buy it over-the-counter and it works pretty well. And so if they don't have to use too much of it, they do really well. 

 

00:20:28:07 - 00:20:40:20 

Bethany Hays 

And so I asked them to put it over blood vessels because I really would like it to go into the circulation and not epo in fat. And so I don't tell them to put it on their abdomen and I don’t tell them to put it on their wrists. 

 

00:20:40:20 - 00:20:51:19 

Bethany Hays 

I tell them to put it on their elbows, their wrists, maybe even their neck. I don't think you have to worry as much about contaminating your husband and your children. 

 

00:20:52:07 - 00:20:53:09 

Mark Newman 

With progesterone. 

 

00:20:54:03 - 00:21:20:00 

Bethany Hays 

With progesterone as you do with estrogen. We do have to worry about that with estrogen. But progesterone has so many pathways of metabolism that it almost disappears before you can use it. So, it's been one of the problems with progesterone, and that's the reason we can buy progesterone cream over the counter is for a long time, physicians thought it didn't do anything because 

 

00:21:20:02 - 00:21:34:00 

Bethany Hays 

you couldn't measure progress in the blood. And so people thought, well, it must be safe because, you know, you don't get a blood level, so it can't be a problem. But I think that's not true. I think you can overdose on transdermal progesterone. 

 

00:21:34:19 - 00:21:53:20 

Mark Newman 

Right. Yeah. And we've talked about before how tricky the lab picture is with the creams that I think there's a pragmatism to them helping women to feel better in the premenopausal phase. But but getting a number that says you should up or lower the dose, the really the evidence doesn't really support that. 

 

00:21:54:06 - 00:22:08:19 

Mark Newman 

One of the reasons that I wanted to kind of pick your brain on this topic is since progesterone sort of emerged, we say, you know, in the maybe the early nineties and became more popular in its use and rightfully so in some respects. 

 

00:22:09:06 - 00:22:23:18 

Mark Newman 

Can you take us back a little bit to what kind of led to that emergence and what we learned from that that was positive? And maybe if there are some areas where that pro progesterone message kind of went off the tracks? 

 

00:22:24:15 - 00:22:45:00 

Bethany Hays 

Yeah. Well, we knew we wanted something that acted like progesterone in the uterus to stop the over-proliferation that we got from estrogen. And so we came up with artificial progestins that were well absorbed orally, you could take them in a pill, and they had a huge effect on the endometrium. 

 

00:22:45:12 - 00:23:00:12 

Bethany Hays 

They clamped that sucker down and got rid of the bleeding, but they didn't do the same thing in other tissues in the body. So, women didn't feel as well on them and they didn't have the same cardiovascular effects and bone effects. 

00:23:00:12 - 00:23:28:11 

Bethany Hays 

And so the people who were really paying attention said we ought to get something that works more like bioidentical progesterone. And so they began working on who do we get bioidentical progesterone molecules into a pill that will actually have an effect? And they discovered if you micronize progesterone, you can put it in a pill and people would absorb it in high 

 

00:23:28:12 - 00:24:00:00 

Bethany Hays 

enough amounts to actually get a level in the uterus that could balance estrogen. The micronized progesterone came out. And, you know, I picked up on things that happened before I really knew about natural progesterone, but it was around. And there were some people who were really playing with studying and looking at bioidentical estrogen and bioidentical progesterone. 

00:24:00:15 - 00:24:24:15 

Bethany Hays 

All the conventional world got to bioidentical estrogen estradiol much faster than they got to bioidentical progesterone. They’re still catching up on the bioidentical progesterone, but they began noticing that birth control pills and post-menopausal hormonal therapies were, they just weren’t studying anything but estradiol anymore. 

 

00:24:25:01 - 00:24:43:22 

Bethany Hays 

And you could buy other stuff because they've been studied and so forth. But but they began really pushing towards estradiol. But the progesterone, they couldn't still couldn't figure out how to know if on board even with micronized progesterone. 

 

00:24:43:22 - 00:25:10:14 

Bethany Hays 

So they're just now beginning to put together replacement therapy, you know, FDA approved hormone replacement therapy that has estradiol and identical progesterone. And I'm waiting for the birth control pill that has those two things in it. I think that's going to be a much, much better, much more acceptable drug for women. 

 

00:25:12:17 - 00:25:33:21 

Bethany Hays 

So, you know, back in 90s, that's when I sort of came into the complementary alternatives scene. Right. And John Lee had written his book, which said progesterone was magic, and you could use it for everything. Right. 

 

00:25:34:09 - 00:25:54:19 

Bethany Hays 

And I kind of immediately go, wait a minute, that’s never the case. You know, like, what's what's right about that? Why is he getting good results in a lot of people? And what's wrong about that? And so that was probably the first point at which I began to use progesterone and see what it could do and what it 

 

00:25:54:19 - 00:26:12:01 

Bethany Hays 

couldn't do. And so I would use some artificial progestins if I wanted a powerful effect in the uterus. Right. You know, we call it a medical D&C and if you really want to empty out the uterus and start over with the lining of the uterus 

 

00:26:12:02 - 00:26:29:16 

Bethany Hays 

you use an artificial progestin, but you just do it for one cycle, maybe two. But if you want continuous therapy for women who who need to balance estrogen and progesterone and aren't making enough progesterone and you can't deal with the stress for various reasons 

 

00:26:29:16 - 00:26:53:17 

Bethany Hays 

then using progesterone bioidentical progesterone in addition to their normal ovulation, I think is is pretty easy to learn to do and pretty safe. It’s you know, the nice thing about progesterone is you get the same kind of horrible side effects that you do if you overdose on estrogen. 

 

00:26:53:21 - 00:26:54:05 

Mark Newman 

Right. 

 

00:26:55:20 - 00:27:15:19 

Bethany Hays 

So, I so I often use that and I began to learn that timing was important. You don't want to use the progesterone before the ovulation happens because you can inhibit ovulation. And so if you start progesterone, you know, if you only go off for one week. 

 

00:27:16:14 - 00:27:27:21 

Bethany Hays 

I've seen some protocols where you take it for three weeks, then you're off for a week. Well, then what happens is you go back on it before you’ve ovulated. And you may not ovulate then. Or you may not 

 

00:27:27:21 - 00:27:46:12 

Bethany Hays 

ovulate well. And I'm telling you, the corpus luteum can make a lot more progesterone than I can give in a pill. So. So I'm careful about trying to time my progesterone with ovulation and stop it when the first heavy day of bleeding starts. 

 

00:27:47:06 - 00:28:08:14 

Bethany Hays 

And that's I’ve had pretty good success treating pretty women that way both pre and and I have a different sort of plan post-menopause as you know I have a tendency to say Mother Nature has been doing this for several billion years and I've only been doing it for about 44 years, maybe she knows more about this than I 

 

00:28:08:14 - 00:28:22:03 

Bethany Hays

And I should like try to do it the way she does. And so I've always tried to mimic Mother Nature when I use hormones and that’s part of why I use progesterone and part of why I use is way right.

 

00:28:22:03 - 00:28:35:14 

Mark Newman 

So meaning when a premenopausal woman you're expecting about a two week surge of progesterone and you mimic that in the supplementation and in dosing progesterone the last two weeks of the cycle and then not the first two weeks of the cycle, is that right? 

 

00:28:36:00 - 00:28:36:12 

Bethany Hays 

Exactly. 

00:28:36:22 - 00:28:57:09 

Mark Newman 

And then in a post in a postmenopausal woman, you know, we know the studies don't support its use entirely to protect the endometrium if it's given as a cream. So, in the postmenopausal scenario, we're not going to get deep into HRT, but your go-to in terms of route of administration, general dosing and how many weeks on 

 

00:28:57:09 - 00:29:04:12 

Mark Newman 

and off, what what does that look like for you in a sort of stereotypical estrogen-replacement therapy case for a postmenopausal woman? 

 

00:29:05:07 - 00:29:16:03 

Bethany Hays 

Okay. So first of all, you have to ask, are you early postmenopausal or late postmenopausal? Because early postmenopausal women still have quite a bit of estrogen around. 

 

00:29:16:05 - 00:29:16:13 

Mark Newman 

Right. 

 

00:29:17:01 - 00:29:36:03 

Bethany Hays 

And you got quite a bit of estrogen around. Then you're going to need progesterone in your supplementation, and you may need to cycle it depending on how much estrogen there is. If you have continuous progesterone, you're going to get breast tenderness like you wouldn't believe. 

 

00:29:36:09 - 00:29:37:05 

Mark Newman 

So, you want to cycle. 

 

00:29:37:23 - 00:29:53:11 

Bethany Hays 

So, I try to judge, well, how long have they how long has it been since your last period? And I will give progesterone alone until I get progesterone alone and I don't get any bleeding at that point, I begin to add low-dose estrogen back in. 

 

00:29:54:08 - 00:30:13:06 

Bethany Hays 

Now, when you ask what does Mother Nature do here? When she gets to the part where there's not enough estrogen to create bleeding? The progesterone comes from the adrenals, right? It is produced more or less continuously in low doses. 

 

00:30:13:12 - 00:30:31:16 

Bethany Hays 

Unless you're stressed out and you're stealing all your progesterone away to make cortisol. So those are the women that are going to have trouble with the early menopause and sometimes late menopause. And some of them may need progesterone in order to keep that balance going. 

 

00:30:31:22 - 00:30:48:20 

Bethany Hays 

But what you want to do is address the problem and not the symptoms. The problem is the stress and the cortisol issue. And he can get that under control. And you don't really need to give much progesterone, maybe none, depending on whether you're giving a lot of estrogen. 

 

00:30:48:20 - 00:30:59:20 

Bethany Hays 

So, if you're someone who is trying to return women to premenopausal levels of hormones, you're going to have to give progesterone and you're going to have to cycle and they're going to have periods. 

 

00:31:00:03 - 00:31:06:04 

Mark Newman 

And in those cases, are you typically using oral progesterone in those cases? 

 

00:31:08:09 - 00:31:16:12 

Bethany Hays 

Yes. If had to get enough progesterone on board, I would give oral. I wouldn't give oral if I wasn't giving estrogen. I might try using a progesterone cream. 

 

00:31:16:15 - 00:31:17:20 

Mark Newman 

Right. That makes sense. Yeah. 

 

00:31:17:21 - 00:31:37:05 

Bethany Hays 

The what I believe about the progesterone cream in endometrium is it will inhibit proliferation of the endometrium, but it's not enough to bring on a period. So, they won't have a period, but they also don't get a endometrial hyperplasia. 

 

00:31:39:02 - 00:31:56:01 

Mark Newman 

The nerdy laboratory side of the oral progesterone is interesting in that if you go back to the 80s, you see these luteal meaning sufficient levels of progesterone with oral, which gave confidence. And then we know from the studies that it worked right. 

 

00:31:56:01 - 00:32:12:14 

Mark Newman 

And then as the analytical types go back in and dig into it, you find that those luteal levels are actually wrong, that a lot of that's you're using an amino assay and when you give progesterone orally, your gut makes lots of stuff that look an awful lot like progesterone and those cross-react with the amino acids. 

 

00:32:12:18 - 00:32:33:05 

Mark Newman 

So, those numbers are wrong and they're actually oftentimes not luteal. But then you succeed. They're sort of by accident because you still are getting endometrial protection. Endometrial protection because a lot of the impact that's progesterone-like is coming from that little bit of progesterone that escapes the gut and also all of those progesterone metabolites that have some 

 

00:32:33:09 - 00:32:49:11 

Mark Newman 

progesterone impact. So, it's an interesting case study in just how complex these things get. But we do know from the studies that oral progesterone works, the serum values aren't particularly helpful because they're inflated by all those metabolites cross reacting with the assay. 

00:32:50:06 - 00:33:02:02 

Mark Newman 

So, for us, you know, we're not really able to say what's going on in the endometrium. We know those doses work and then what we're looking at is, well, if you're taking it orally, it's going to help with with sleep. 

 

00:33:02:02 - 00:33:17:10 

Mark Newman 

Well, progesterone doesn't help with sleep. It really acts as a pro hormone in that case. Right. Which is feeding that allopregnanolone, which hits the gamma-receptor and helps with sleep. Have you found that helpful in women who are on oral progesterone at looking at the way their body? 

 

00:33:17:10 - 00:33:30:18 

Mark Newman 

And I guess specifically you'd say their gut is shuttling the progesterone either towards that alpha-progesterone metabolite pathway or to the less active beta-progesterone metabolite pathway. Have you found that helpful in, in those women? 

 

00:33:31:12 - 00:33:57:00 

Bethany Hays 

You know, I, I my approach to progesterone was a lot less scientific and a lot more related to the results I got in terms of symptoms. So, I can't say that I know whether it was the the which pathway women were metabolizing down and was that why they had better or worse brain response from it? 

 

00:33:57:06 - 00:34:23:16 

Bethany Hays 

But the what I understand about progesterone metabolites is they are not they are not DNA driving receptors. They are they are driving things out in the in the cell membrane, just like some of the estrogen effects are cell membrane effects, the progesterone metabolites affect the cell membrane. 

 

00:34:24:15 - 00:34:50:17 

Bethany Hays 

Well, that gives you like another whole level of complexity. And so that kind of makes me wonder, you know. Is it the metabolites in the gut that we're dealing with? And you're saying that those metabolized were all over the place and building up what we saw were progesterone levels when really we were using metabolites like crazy. 

 

00:34:51:00 - 00:34:57:08 

Bethany Hays 

So maybe we need to go back and do these studies again and look at the metabolites. 

 

00:34:57:16 - 00:35:14:00 

Mark Newman 

Yeah the progesterone story is interesting in a sort of complex way in that, you know, in the urine, in the absence of supplementation, you know, we've published our data that says, hey, those each of those metabolites just taken as individual markers, predict serum progesterone really well. 

 

00:35:14:00 - 00:35:26:16 

Mark Newman 

So, in that sense, they're helpful as a surrogate, you measure them both and you've got a pretty good idea of how much progesterone the patient's making. And then you start asking questions about, well, does it matter which one that you're making? 

 

00:35:26:16 - 00:35:45:03 

Mark Newman 

Either the alpha or the beta, which one you're preferring? And we tend to look at that story more with supplementation. We talked before about John Weebe's work, which, you know, hasn't really been fleshed out entirely. But what he showed is that those alpha metabolites, when you look at those given to breast cancer cells, that they're proliferative. 

 

00:35:45:08 - 00:36:06:07 

Mark Newman 

So, there's this interesting story about the woman who shoves her progesterone down that alpha pathway and maybe some caution to use about not overdoing the use of progesterone to create the alpha metabolites to help with sleep. Because in overdoing that, there might be a breast cancer story that's that's interesting and noteworthy, but that work hasn't really been 

 

00:36:06:07 - 00:36:24:16 

Mark Newman 

followed up on to the level that we can we can look at that with confidence, but we still talk about that with our providers because there is, you know, potentially an association there. As you know, we've showed of alpha metabolites being proliferative and that maybe that's something to be to be cautious of. 

 

00:36:25:15 - 00:36:46:13 

Bethany Hays 

I think you're I think you're right about that. You know, I've been, you know, always cautious about progesterone because of its it's proliferative capability. And a lot of people say, no, no, the bioidentical progesterone doesn't pose breast cancer because we know that from the E3N study. 

 

00:36:47:06 - 00:37:09:16 

Bethany Hays 

But if you actually read the study and not just the abstract, what it shows is on average, it doesn't increase breast cancer. But if you look at it over time, the older you are, the farther you are from menopause. In other words, the lower your estrogen levels, the more progesterone becomes proliferative and can increase breast cancer risk. 

00:37:09:17 - 00:37:31:01 

Bethany Hays 

So. So, I've been curious about the proliferative aspects of prednisone. We get into the cell cycle in some interesting ways. And if you give a load of progesterone, you get a cell cycle turnover and then you get the maturation aspect of progesterone. 

 

00:37:31:01 - 00:37:45:15 

Bethany Hays 

So, I think you have to be kind of careful about progesterone. And I also think you have to be careful about cyclic progesterone. Each time you cycle, you're putting themselves through a cycle of cell cycle of division. 

 

00:37:45:23 - 00:37:58:23 

Mark Newman 

It's interesting that I think some things medicine's easier. I think if you can simplify concepts, but then you also have to continue to dig. Because I just read a study the other day that was talking about the four hydroxy estrogens. 

 

00:37:59:05 - 00:38:14:20 

Mark Newman 

This was in a rat study, but we only think of that metabolite in its negative context, and we often only think of progesterone in its positive context. And what this paper was showing is that four hydroxy estrogens have some neuroprotective behavior in a certain scenario in a rat model. 

 

00:38:14:20 - 00:38:35:01 

Mark Newman 

And it just got me thinking about, you know, just the proper perspective that everything that has the power to help, generally has the power to hurt in a certain context. And I think with with progesterone, you know, being conscious of what the literature says and but also being careful of not treating it, you know, like something like 

 

00:38:35:01 - 00:38:45:00 

Mark Newman 

vitamin C, that, you know, if a little is good that just, you know, getting more and more of it is necessarily something that we should ever consider without some caution. 

 

00:38:45:22 - 00:39:00:04 

Bethany Hays 

So, I think, you know, I go home to mama, you know, try to do what Mother Nature does and start low workup slow and tell your patient it's not like a pill. You're not going to have total reversal of all your symptoms. 

 

00:39:00:04 - 00:39:12:08 

Bethany Hays 

20 minutes after you take a pill, you're going to have to work your way into the right balance of hormones. And we're going to start here and then we're going to see where we are and we're going to see how the symptoms are. 

 

00:39:12:12 - 00:39:35:07 

Bethany Hays 

And then we may go up a little again. And I let patients do that, that slow increases on their own until they tell me that they might feel at that point we measure hormone levels and find out if we sent somebody over over the hill with too much hormone or we don't really have enough hormone and. 

 

00:39:35:16 - 00:39:51:23 

Bethany Hays 

Much more likely to be happy with not enough hormone and no symptoms. Then I am somebody who is complaining of symptoms, but their hormone levels are way high and it's out of whack because what that usually means is it's not your hormones that are causing those symptoms. 

 

00:39:52:14 - 00:40:09:07 

Bethany Hays 

There's you know, there's almost nothing almost no symptom I saw that was just one hormone, you know, it's the everything works in a symphony. You know, they work in concert. They talk to each other. One raises this one, this one more of this one. 

 

00:40:09:07 - 00:40:25:19 

Bethany Hays 

And you have to understand some of those relationships before you, you know, the first one. You're going to be real surprised at some of the weird things that happen to your patient when you get on a hormone that you thought was going to, you know, make them feel better for this particular symptom. 

 

00:40:25:19 - 00:40:47:05 

Bethany Hays 

And suddenly you're somebody who metabolizes that hormone completely different orit jacked up some other hormone they're taking, or, God forbid, they're on five different medications. Right. You know what their hormones do. So, I, you know, start slow, start slow, work up, and listen to symptoms. 

 

00:40:48:00 - 00:40:56:05 

Bethany Hays 

And then when you feel like you've done things where you want them and that's when you want to come back and do your next hormone level. 

 

00:40:56:19 - 00:41:12:15 

Mark Newman 

And I think the evaluation I mean, that's why for us, we've been so passionate about the comprehensive nature of testing that when, you know, if you isolate the story to progesterone and you have a patient that has an HPA axis that's going crazy or has a concurrent estrogen issue or an estrogen metabolism issue, much as we want 

 

00:41:12:15 - 00:41:31:04 

Mark Newman 

to simplify the story, you know, for us, we want to look broadly at reproductive and adrenal hormones and see what's going on. And that's where the complexity of that means we have to educate. And that's been really great to to hear use or tell that progesterone story, which I think I think highlights that in a way that 

 

00:41:32:00 - 00:41:44:10 

Mark Newman 

allows our providers to understand it at a deeper level as we try to help patients who have these imbalances in their reproductive hormones. So, thank you for joining us today and making that story a little bit clearer for us. 

 

00:41:44:10 - 00:41:45:00 

Mark Newman 

I appreciate it. 

 

00:41:45:20 - 00:41:46:14 

Bethany Hays 

I hope so, thank you.

00:41:47:01 - 00:42:02:00 

Noah Reed 

Doctor Hays, thank you so much for joining us today. We now have a much better understanding of progesterone and its purpose. Thanks to your insights. On next week's episode, we'll continue to dive into our endocrine essential series with the DUTCH expert, Dr. Debbie Rice. 

 

00:42:02:12 - 00:42:17:08 

Noah Reed 

She'll be talking about all things estrogen and estrogen detox. This will be an exciting episode where you'll get to go deeper in your understanding of how your body creates and detoxifies estrogen. I'm Noah Reed. Thanks for joining us today. 

 

00:42:17:15 - 00:42:18:10 

Noah Reed 

Until next time.