unPAUSED with Dr. Mary Claire Haver - Estrogen, Progesterone, and Testosterone: The Science of Hormones, Sexual Function, and Menopause

Episode Date: May 5, 2026

In this episode of unPAUSED, Dr. Mary Claire Haver sits down with Dr. Tami Rowen, an obstetrician, gynecologist, and leading gynecologic surgeon at the University of California San Francisco, and an internationally recognized expert in sexual health and sexual medicine. Together they get precise about some of the most misunderstood terrain in women's health: estrogen, progesterone, progestins, and testosterone for women, what they actually do in the body, how the confusion around them began, and what becomes possible for women when care is evidence-based and not fear-based. Dr. Rowen opens with something most women have never been told: that contraceptive estrogen and menopausal estrogen are fundamentally different molecules with different goals, different mechanisms, and different effects on the body. She walks through why ethinyl estradiol, the synthetic estrogen in most birth control pills, binds to the estrogen receptor 300 times more strongly than natural estradiol, why that matters for everything from blood clotting to testosterone levels to bone density, and why modern contraception is still valuable and worth defending even as we get more precise about how it works. Guest links: Dr. Tami Rowen (UCSF Health) Dr. Tami Rowen (ISSWSH)Dr. Tami Rowen (Instagram) To learn more about listener data and our privacy practices visit: https://www.audacyinc.com/privacy-policy Learn more about your ad choices. Visit https://podcastchoices.com/adchoices

Testosterone levels don't fall off a cliff in menopause. We need to be really honest about that. They actually start to decline in your 30s. They have a slow decline in your 40s. And the year before and the year after menopause, your body isn't like, oh, I suddenly don't have testosterone anymore. It's been low for a while. And so I don't think it's wrong ever to give testosterone. But I don't think we say, well, because now we're in menopause, we're not making testosterone.

That's not actually physiologic. Yeah. You know, it's a therapy. The views and opinions expressed on unpaused are those of the text. and guests alone and are provided for informational and entertainment purposes only. No part of this podcast or any related materials are intended to be a substitute for professional medical advice, diagnosis, or treatment. One of the most persistent problems in women's health care is that we've taken some of the

most complex, intimate parts of women's lives, her hormones, sexuality, pleasure, pain, and identity, and either oversimplified them or avoided them all. together. Today's guest is someone who has spent her career doing the exact opposite. Dr. Tammy Rowan is an obstetrician gynecologist and leading gynecologic surgeon at the University of California, San Francisco, and an internationally recognized expert in sexual health. Her work sits at the intersection of hormones, anatomy, desire, pain, and autonomy. She doesn't just talk about sexual function. She studies it, teaches it, operates on it and defends it in a medical system that has too often dismissed it.

Dr. Rowan understands where so much of the confusion around women's hormones comes from, conflating contraception with menopause hormone therapy, the fear around progestants, the lack of nuance in how we talk about testosterone, and the way sexual pain and loss of desire are still framed as psychological rather than physiological. Today, we're going to slow this down and get precise. We're going to talk about estrogen, progesterone, progestins, and testosterone. What they actually do, where medicine went wrong, and how the confusion continues to harm women. We'll dig into sexual function in midlife, desire, orgasm, pelvic pain, GSM,

and what is truly possible for women when care is evidence-based and not fear-based. based. This is a conversation for women who want clarity, not platitudes, for clinicians who want to do better, and for anyone who's ever been told that sexual health is optional or secondary. I'm Dr. Mary Claire Haver, a board certified obstetrician and gynecologist and certified menopause practitioner. I'm also an adjunct professor of obstetrics and gynecology at the University of Texas Medical Branch. Welcome to Unpaused, the podcast where we cut through the silence and talk about what it really takes for women to thrive in the second half of life. Dr. Rowan, welcome to Unpaused.

Thank you so much for having me. Yeah, glad to have you here. Let's dig into hormones. Okay. You teach a course, if I have us correctly called hormone therapy, estrogens, and progestogens. And you teach another one called Let's Talk progestins. When I tell you on social media, I get so many questions about hormones, what kind? So formulation and delivery, when, how, where, whatever.

And so I promised our audience we would take it slow and I was going to bring on an expert and do a really deep dive. Are you down for this? I'm down for this. This is my favorite thing to talk about. Let's give our listeners a clear hormone 101, explaining the difference.

So the biggest questions for listeners is contraceptive estrogens and progestin. Let's start there. Okay. Because that's where women are first exposed to hormones. Absolutely. So, you know, we're talking about right now the hormones that the ovary produces. So there's hormones made in all different parts of our bodies. You know, we think about thyroid. We think about the pituitary. But in the ovaries, we make estrogen, progesterone, and testosterone. Estrogen is the hormone that will basically grow the lining of the uterus, get it ready for pregnancy. You talk about estrogen all the time. I'm not going to jump too far into it. But when we talk about estrogen in the context of contraceptives, we're talking about ethanol estradial. And the thing to understand understand about estrogen is it as a class of molecules. And so those are just compounds that in the body target a receptor. And so I think about it as a lock and a key, right? The key is the hormone. The

receptor is the lock. And there's going to be different keys that fit into it differently. So in the body, there are three natural progesterones made by girls to adults. And in terms of the estrogens, those are estradiol, estrone, and estriol. I know you know this, you talk about it. Well, birth control doesn't have any of those three. Right. And that's where the confusion starts. So what does it typically have? It has ethanol estradial. Why? Because ethanol estradial is a more potent form that works better for the goals of birth control. And this is the key is that the purpose of birth control is to suppress ovulation, prevent an egg from being released so you can't get pregnant. Now, you can do that with natural estrogen, natural estradial. The issue is that the number one side effect of birth control pills is bleeding. And it is bothersome and people stop taking them because of it. Ethnalestradial actually is very good at stabilizing the lining of the uterus and helping to prevent bleeding while also feeding back on the pituitary. That's the part of the brain that tells the ovary to get an egg ready. Ethnal esteradial feeds back to. Is it not to do that? It's not the primary way birth control works. It's like progestin we'll talk about. But it feeds back and then it also stabilizes the lining very well. And this surprised me because I graduated from my training program, blew the top off my boards. I was always taught and this was probably word of mouth. There's really no big difference between estradiol and ethanol estradiol. Because I've looked at thousands of packets of contraceptive pills that there is ethanol estradiol. And I just assumed the ethanol fell off and you were left with estradial.

estradiol, which is not what happens at all. It binds to the receptor 300 times stronger than plain estrogen, which is why it works so well for contraception. Yes. So exactly, it's that lock in the key. So imagine that you now have this lock that has a key that will not get off. So it is incredibly attracted to the receptor. It stays on it. But it doesn't even just do that. When it's staying on it, you can imagine that there's lots of different bodily functions that respond when there's estrogen in the system. So the main one we think about is the liver. So when the liver sees estrogen, it starts pumping out different types of proteins. And it also pumps out clotting factors.

And so the early birth control pills had about three to four times as much ethanol estradial. And so that was when we started seeing all the blood clotting. And we start saying, well, all estrogen causes blood clots. No, ethanol estradial is going to do that. And then we start talking about things like testosterone in our body. Because if your body sees estrogen, it's going to make a protein to buy. bind some of it up, that protein is sex hormone binding globulin. Well, it's going to make more of it in response to ethanol estradial just because of how potent that molecule is. And when SHBG goes up,

guess what? Testosterone gets bound up and your testosterone goes down. So there's, and there's so many different things that ethanol estradial does. It's not actually as good in the bones for promoting bone health as natural estradial. So there is some evidence in younger women that if they're taking ethanol estradiol birth control compared to those that are just having normal cycles, their bone mineral density looks different by the time they get into their 20s. So I want to be clear, we are not saying that modern contraception is a bad thing. Modern birth control is a bad thing. I am so grateful it is here. I still use it. I still recommend it for certain patients in certain conditions, and I do menopause care, because there is a pushback in a certain faction, you know, especially on

social media, that all contraception is bad. So that's stepping it away. way at all from your natural cycle is is not your best life. I really appreciate you saying that because it's actually something that I've addressed, I would say, on social media. And I think about as someone who's also board certified, subspecialty certified in complex family planning, I am someone who very much supports the use of birth control for many different things. It is incredibly valuable, including for preventing pregnancy. And, you know, if we're worried about blood clots and birth control, where there is nothing that's going to give you a blood clot more than a pregnancy, right? Right. Yeah. We're talking 100 acts in your first six weeks postpartum,

or first two weeks postpartum. Pregnancy is the number one way. We have stasis and hypercugulability. So, yeah, yeah, all the side effects people talk about. They're like, it's going to affect my mood. It's going to affect my clotting. It's going to affect this. And like, all of those things are 100 times worse if you get pregnant. And these medications work to prevent that. And they have many other benefits. So I am not an anti-birth control person at all. But what I do think is important is distinguishing the two between natural estradiol and ethanol astrodial because it gets confused, especially when we talk about menopause. Do you see a world where we would have an oral contraceptive or even transdermal agent that was effective with minimal side effects containing plain estradiol?

So there actually is one. And so I... In Europe, correct? In Europe. And I wrote an article actually about it because there was an article that was published comparing. It's a 17 beta astrodial, as a specific type of progestin. We'll talk about what that means in terms of the other component of it that they think was going to be better for sexual side effects. So they compared the sexual side effects of this pill to the worst offender when it came to sexual side effects of the traditional birth control pill. And I wrote an editorial about it because that's apples to oranges to compare these two. But the reason that we don't have it here, one is that the regulatory environment around birth control is a little bit different. There are different types of birth controls in Europe.

But the big side effect of that medication is abnormal bleeding. And so, yes, we can do it. People ask me that all the time. They're like, why doesn't it have, you know, 17 beta estrogial? I'm like, this isn't a conspiracy. We're not trying to keep people from natural estrogen. We're trying to help them take their birth control. And if they bleed, they won't.

What if we had a combination of estradiol and basidoxamine in a dose high enough to suppress ovulation? Would you buy it? I would if it would suppress ovulation. If it suppresses ovulation. I'm not convinced it would, but if it did, that would be great. Yeah, because we're going in the weeds, but basidoxifine is a serum, and it protects the endometrial lining.

It binds blocks and down regulates the estrogen receptor in the breast and uterus, so people don't bleed on it. So for my menopause hormone therapy patients who are having intractable bleeding with their traditional MHT, we are very quick to reach for. Yeah, I love that medication. And I love it. I'm using it actually all the time in patients who are at high risk of breast cancer. Same.

So the issue... I digress. Sorry. Yeah. The issue is the way that birth control works is mainly through the progesterone and progestins. It's the progestin, specifically, that feedback on the brain to tell the ovary not to ovulate. So the estrogen component is not the most important part of birth control. I did not know this.

That is a fact. It is the progestin. I have been practicing OBGYN for 30 years. I did not know this. I honestly am so honored that I came to your podcast and actually taught you something you don't know. Okay, well it makes sense because we have progesterone-only contraception, but not estrogen-only contraception. And you have to think about what is it doing? Your brain, you're trying to get the brain to tell the ovary not to release it.

Right, right. And the only way it's going to do that is if it thinks it already did. What is the one hormone that is made in response to ovulation? Progesterone. So that's the receptor on the pituitary that if you sensitize that receptor, you're going to suppress ovulation. Damn. Okay, menopausal hormone therapy. How is that different?

Menopausal hormone therapy has a different goal, right? The goal of it is not to suppress ovulation. It is ideal to suppress bleeding, but we do that in many different ways. And you're not going to see the kind of bleeding side effect profile with the dosages necessarily. So menopausal hormone therapy is comprised of two different types of estrogens now. That's what we typically use. So one is either going to be estradiol. These are the FDA approved ones. So that is bioidentical. It looks identical to what the ovary makes. And then the other one is conjugated equine estrogen. And that was developed earlier. You've talked about it on the show before. It has over 50 different estrogens in it. It's actually proprietary. When I looked into the history of this, I actually gave a talk a few years ago on it.

I was like, no one knows what's in this. And so random astrillion and things I can't pronounce. But as I said, you have an estrogen receptor where there's actually two, in alpha and a beta. There's two other minor ones. right? So it doesn't matter what the estrogen is as long as it targets that receptor. So conjugated equine estrogen targets the receptor and it's actually a little bit stronger at the receptor. And that's why we use it at a little bit of a lower dose, but it is more potent than natural

estrogenial. Okay. Staying on the estrogen topic for menopause, I get a lot of questions in the last three to four years when so many of us got educated, scrambled, figured stuff out. Most of us in this wave are using pretty much estradiol based and then progesterate. Okay. But years before, there was a small group of practitioners who were trained, I'm not sure where or how, who were using a lot of compounding because that's what was available. We didn't have a lot of education around the FDA approved options. And they were using something called bi-est and tri-est.

Explain what those are. What's FDA approved? What's not? And what your thoughts are on those? I appreciate that question. So bi-estrogen is kind of short for bi-estrogen. And what it is is, is it is a combination of estradial and estriol. So estriol is another form of estrogen that is bioidentical. It is oftentimes touted as, quote, safer in certain ways. But again, the way to think about this is there is an estrogen receptor. And so there are estrogen receptors all over the body. Estreol. is going to work only on that receptor. And the only difference is what is its affinity? And it actually has about a 30% strength compared to estradiol for that receptor. So the idea that it is somehow safer doesn't actually make a lot of physiologic sense. It's just weaker. And so some thought can be put into, well, is it different? Will it affect the alpha or the beta receptor? This is really detailed. And so people will say, well, it's better at the level of the breast. But we have good data is showing that estradial is not dangerous for the breast.

So I don't think estriol is necessarily better in that way. Both of these are going to be a wash. And then triest is going to be the same as the estradial, and then you're going to throw in the estrone, which is the other form of natural estrogen that's made in menopause. Is estrone pro-inflammatory? I've read that. But I didn't see good data behind it. There's not good data for it.

We know that there is some inflammatory properties of just estrogen, in general, to say it's pro-inflammatory is tricky because, again, it's only acting on a receptor, right? And there are some tissues where the estrogen receptor is pro-inflammatory. Now, where is it made? Let's walk. I think our audience deserves a little bit of an anatomy lesson. Yeah. So I know it becomes, most to understand it becomes the dominant estrogen and postmenopause because where are these estrogens made? Review that one more time and in what kind of levels at what ages. Let's go through after puberty. Yeah. So I said that the ovary is where these hormones, are made, but they're made actually in lots of other tissue. I mean, there is estrogen that is made in

the gut, there's in the brain. And then there's also estrogen that is made in adipose cell. So those are fat cells. And so that's where you're going to see the postmenopausal estrogens made. And that's where estrone is mainly going to be made. Estriol and estradile are mainly made in the ovary in something called the granulosis cell, if you want to get into my science textbooks. What about body identical versus synthetic? Lots, lots of drama on the internet about that. Lots of drama on it. So again, we're talking about some sort of molecule that is affecting a receptor. I think that when we talk about body identical hormones when it comes to estrogens, that there is evidence, I would argue, that estradial in some ways is, it's less potent.

So you're going to see lower rates of increasing in clotting factors with it. We have data on conjugated equine estrogen. That's the other one that's FDA approved for things like dementia. If you give it in an older age, that conjugated equine estrogen is probably not beneficial at an older age for dementia prevention. And so I think that it really is what people tolerate and we are now really favoring the transdermal approaches, which I just tell people, we're just mimicking what your ovaries we're doing. I get this every day. You probably get it too where they're like, is this risky? And I'm like, I'm not giving you anything new. Your body

has been exposed to this hormone, you know, for decades. And we're just replacing what your ovaries are no longer doing. Let's review for our listeners. We talked about contraceptive options. So premenopausal, generally used in premenopause, to prevent pregnancy. We have, that's what is FDA approved for, what it was developed for. We use it off-label for lots of things. Acne, cramps, heavy periods, pre-menstrual dysphoric disorder, etc. To stabilize hormones.

So some women do better that way. And then we have our perimenopausal, post-menopausal treatment. And there is some overlap between the two. Yes. But then in general, postmenopausal hormone therapy is going to be estrodial. For the estrogens. Yeah, because we're basically replacing what the ovaries are no longer making. So there's not really a reason to necessarily give somebody something that's synthetic,

certainly ethanol estrodial, unless our goal is to help prevent abnormal bleeding or they need a contraceptive method. Then estrogens are easy. Now we're going to get into. So the umbrella is progestogen. Yes. And then under that umbrella, we have the progestins, which are created or synthesized. And then we have progesterone, which actually has to be synthesized as well, but it is the

natural occurring form. So they are often portrayed as the villain. We're seeing, and I do want to get into progesterone intolerance. There's so much. So much more than I ever knew. I know. But they are essential to keep you from getting into mutual cancer when you're using estrogens. And they're essential for contraception, which I'm still going to have to marinate on.

that for a little while. Talk to me about what the data shows, about what are progestions? Give me your hormones 101. Yeah. So I, this is my favorite topic because progesterone, everyone's asking, people are, all right, everyone pause, get out your pencils, hit record. Here you go. This is the world's expert, I promise. All right. So progesterone is just the most underappreciated hormone. And we talk about estrogen and testosterone all the time. So you just see me perk out of my cold dead hands. I know. Well, so progesterone is very interesting. So progesterone is one single hormone that is made. There are not multiple types of progesterones made by the human body. There is one. It is progesterone and there is one progesterone receptor. It's actually in the pathway to the production of testosterone and estrogen.

So what I think is so interesting about progesterone and people don't talk about is that this is a molecule that can actually be turned into multiple different really important hormones in our body. And it becomes really relevant when we talk about how the progestins, the synthetic progesterone, how they work. Because natural progesterone has a very strong affinity only for the progesterone receptor. And there's one progesterone receptor. There's one progesterone molecule. And there are progesterone receptors all over the body. Just like estrogen? Yes. Wow. So like where? So there's progesterone receptors in the brain. I know that.

We think about it in terms of, yeah, cataminal seizures. We hear about this where if you give people progesterone, it actually raises the seizure threshold, which means it makes them less likely to have a seizure. But there are progesterone receptors in the lung. So we know that people who take progesterone actually may have, it facilitates gas exchange. Now, this is the opposite of estrogen. Estrogen in the lungs can sometimes inhibit it. Right.

Asm gets worse. Yes, asthma gets worse. but progesterone actually can is is beneficial in the lungs. There are progesterone receptors in the gut. And so it helps with gut, you know, I wouldn't say it helps with gut motility. It affects gut motility. Why do we get so constipated in pregnancy, a high progesterone state, right? It slows the gut down.

I had a patient who came to me and she was had really significant constipation and her GI doc sent her to me. And, you know, we see all these zebras where they're like, could it have anything to do with her hormone therapy? And I was like, let me think this through. Yes, you're taking natural progesterone. I bet that this is slowing your gut down and it's causing intractable constipation. There are progesterone receptors in the liver. There's progesterone receptors in the pancreas. There's progesterone receptors all over. So in the breast, obviously, sorry, I skipped that part because it was so obvious. What about muscle and bone? Not, that's not a place that we see a lot of progesterone receptors. But in the breast, absolutely.

So progesterone is what basically really helps with breast development and in pregnancy. It's the progesterone that stimulates the mammary glands to get ready to release milk, but it actually prevents lactation until the pregnancy is over, and it's the drop in progesterone that induces lactation. Now, progestins, and how are they different than progesterone? So progestinns are synthetic progesterone. Essentially, it is a molecule that has been created. Developed to prevent a pregnancy with lots of side effects. Exactly. So that was how they were originally developed. They were part of the combined hormonal contraceptives, and they were at pretty high doses, just like the other, the estrogen component, very high doses. A lot of the early studies and side effects are

from those high doses. But progestins, each of them has a little bit of a different formulation. And remember, they're designed to target the progesterone receptor. They target it better than natural progesterone, at least the progesterone that we take exogenously, which means we take a pill, right? So if we, if we took natural progesterone, it would dissolve immediately in our body. So the way that we take natural progesterone as we micronize it, we turn it into this small molecule that will last longer so that we can get progesterone stimulation in our body. Progestins work better, to be honest, on the progesterone receptor in the uterus, specifically. So they're better at preventing abnormal bleeding. They work better in the brain.

It's incredibly hard to take enough natural progesterone to suppress ovulation. Yeah. So that's why the progestin are much better at telling the pituitary. hey, I've got progesterone, I released an egg, don't release one, right? So the issue with the progestin's, though, is remember how I told you that progesterone can be metabolized into the mineral corticoids and glucocorticoids? Well, progesterone naturally will not target anything but a progesterone receptor, but the progestins will. And so this is we have like 25 on the market, different progestin. Different progestin. And they work differently. One's better for acne. One's better for

sex. Yeah. Because it's not just the mineral cortoid receptor. Where are they buying? They're binding the androgen receptor as well, and they're affecting the androgen receptor. And the antigen receptor is what testosterone binds to. That's why you get different side effects because they target the receptors differently. This is why this is the best topic. So Drospirinone looks very different from most of the common ones. Remember, it is the one that is approved to prevent acne. Well, that's because it blocks the androgen receptor very, very well.

And so that's a really specific type. And so if that's your goal, it's great. Well, as a sexual medicine expert, it has the worst sexual side effects because it blocks the androgen receptors. Anything good for your skin is bad for your sex life. The other ones we talk about a lot are norathendrone and norathendrone acetate. So those, the brand name is Agestin for Norethendron acetate. Norothendron is actually the mini pill.

When we talk about the, you know, very low dose progestin-only birth control, well, norethindrone metabolizes into ethanol estradial. This is a little known fact. How? The molecules are actually very, very low, very. Very similar. Remember how I talked about how progesterone can be turned into estrogen, right? And so if, you know, if progesterone can be metabolized into estradial, well, then norathendron

can be metabolized into ethanol estradial. How did I not know this? This is not common knowledge. But the key, so let's talk about it. Have you heard of ad back therapy? So if you gave Lupron and you give ad back therapy, what are the ad back therapies that you give? It's been a minute. Astrodial.

Estradial and or a gestal. So, okay, why, right? The question is why, so the goal of ad back therapy is to mitigate the side effects of something like Lupron that puts you into menopause, hot flashes, bone loss. So for our listeners, we give Lupron in several situations, like for someone preparing for IVF. We want to kind of block everything to start fresh. But we used it for endometriosis. Exactly. When we could get it approved. Now it's almost impossible. But if you get it approved, then they go into menopause and we're trying to limit their bone loss and their hot flashes. and all the side effects.

Well, why would giving a progestin minimize? No one taught me to ask that question, and I wasn't smart enough to ask it on my own. It's a very reasonable thing. None of us were taught that, but it makes sense, right? Why would this progestin somehow magically be the only one? Because it converts into ethanol estradiol. And so it mitigates hot flashes.

It can prevent bone loss. It also stabilizes the lining of the uterus, partly through its progestin action, but partly through its ethanol estradiol action as well. Provera is another one we use. So that's Medroxy progesterone acetate. We're all very familiar. Yes.

This one is the most potent at the level of the uterus. So it's probably the best, at least in the commercially available doses. North Endrone acetate's actually a little more potent, but we use higher doses of provera. So it works very well to control bleeding. That's why it was used for so long.

Depo modroxy progesterone acetate, that's Deppo Provera. Yeah. Is like a huge dose that we use for birth control. So Provera works very well at suppressing ovulation, blocking the effect of estrogen in the uterus, but it is unique in that it stimulates the glucocorticoid receptor. And that's why people get so bloated on it. So when you see people that have different reactions to different progestins, that's why. And medroxyprogester and acetate in some studies

looks like it could stimulate breast cells in a way that makes you concerned that it could increase the risk of breast cancer. Now, I've talked about what the WHA really showed in terms of breast cancer, but provera was what they used. used in that study, it's always been considered the villain when it comes to things like breast cancer risk. But all the progestins are going to affect breast cancer cells a little different. And natural progesterone seems to be the least likely to stimulate breast cancer cells. And the data we have, we only have five years worth of any natural progesterone. There's never been an increased risk when natural progesterone.

What if the problem isn't your skin? It's the makeup. Because at a certain point, the products that used to work, Just don't anymore. Foundation starts to look flat. Blush sits differently, and by 3 p.m., everything feels dry, heavy, or overdone. The reality is, a lot of traditional makeup was never designed with changing skin in mind. That's where OG comes in, a certified organic beauty brand that delivers luxury-level performance.

Instead of loading products with fillers and heavy pigments, OG's Crystal Contour Collection, is made with nearly 90% skin care ingredients, green coffee oil, hajoba, elderberry extract, ingredients that nourish the skin while you're wearing the makeup. And the best part, OG is NSF certified organic, one of the most rigorous standards in the beauty industry. So every product is made without synthetic fragrance, artificial fillers, or unnecessary additives.

The routine itself could not be easier. be easier. Copper adds warmth and definition. Rose quartz gives that fresh pop of color, and opal creates the prettiest glow. Everything blends effortlessly and melts right into the skin, so your makeup looks natural, radiant, and like it's working with your skin instead of against it. If you're ready to raise your beauty standards, OG's got you covered. Go to OG.com forward slash unpaused and use the code unpaused for 20% off. That's OGEE.com slash unpaused and enter the code unpaused to get 20% off. History That Doesn't Suck is a legit, hard-hitting American history podcast told through entertaining stories. As we approach America's 250th anniversary,

now might be the time to go back and learn how we got here. With more than 200 episodes, you can binge your way, decade by decade, defining event to defining event from the founding into the 20th century. Join me, Professor Greg Jackson, for History That Doesn't Suck, an Odyssey podcast, available on Apple Podcasts, Spotify, or wherever you get your podcasts.

So when I was utilizing oral hormone and contraception to birth control pills, or the patch or the ring, you know, for my patients, I, to be honest, knew some of the side effect profiles, but I kind of had an idea of where to start, but got, knowing, you know, no one ever sat us down,

and walked us through the end of chronology of it all and how it worked. And that would have just made prescribing and explaining to patients. I would basically say there's a lot of stuff we can try. Yeah. And we don't know what's going to happen to you. And you could have all these things. Or you could get on it and it's the greatest thing since sliced bread and you're doing great. But it may take a lot of trial and error. I will say no one ever had this conversation or lecture with me. And I went to the top family planning program in the United States. The way I was taught, and this is not to throw shade on my, you know, wonderful, wonderful professors, but it was pick a pill, any pill, they all work the same. When I got into practice, I was like, they don't all

work the same. And I started looking into this, and I started realizing that they target different receptors. Some of them metabolize into each other. So leave an agestrel is one that we see all the time. It's used in IUD. It's used in birth control pills. Well, many of the other types of progestions just metabolize into leave an agestral. So if you're like, oh, I'm going to try a different one, well, it's just going to turn into leave an gestural in the body. And so knowing, you know, Why would somebody do well with the next planon, knowing that the type of progestin in the next planon, that's the subdermal implant, is identical to the progestin that's used in the vaginal ring contraceptive, right? So if someone didn't do well on this method, I'm not going to give them the vaginal ring necessarily. And so getting really familiar with the progestin just opened up this whole world.

So I love taking these histories and then figuring out, and I've had a really good success, helping people find a progestin that works for them. I was a residency program director until 2018. So we're going on 10 years. This was not part of the curriculum. Is it part of the curriculum now? I've been away from academic. It's not. I will say that when I was taking my complex family planning board,

so what's nice is when that became a subspecialty certification, for those of us that didn't do a fellowship, we could actually just take the exam and then get certified in it. This was something that came up and we were teaching each other about it. And I was so excited because I already knew about it. And it started getting more discussed. But I am not sure even in our residency if we're getting this. But I talk about it when I give grand rounds and when I give my progestin lectures

because I get really excited about this. It's important. I think it's so important. What advice would you give a woman who is struggling to find the right combination to work for her? Yeah, so this is really tricky. If we're using it for birth control purposes, it has to have a progestin. But if we're using it for menopausal hormone therapy, if you have a uterus, we have to do something to protect your uterus. So we can do trial and error of different ones.

What I oftentimes find, I will say, is that because Drosperinone has a very different molecular structure than the other progestins, it usually is kind of my go-to when everything else has failed. And it's been shown in PMDD, for example, premenstrual dysphoric disorder. It's the only FDA-approved medication for that because all the other birth controls don't work. It became my go-to. Yeah, because they act like progesterone in the brain. So instead of being like, I'm only going to have progesterone, you know, two-weeks.

a month, now you've got it four weeks a month when you're taking a traditional birth control. And that's why Drosperinone works better. If you could correct three myths about progestins, what are three things you would, like, correct about? I would say the progestogens in general, one is that they're dangerous. I mean, I think that, you know, everything we do is a balance of risks and benefits. The fact that people think they all work the same, they don't, they work differently, and the idea that they're identical or interchangeable with progesterone, they're not, they're different.

You said the magic word, testosterone. I know you've co-authored major reviews on testosterone and women, including the methodological challenges in studying it. For our listeners, what is the evidence support for testosterone today? So in women, the best evidence that we have shows that the only true indication that shows that if you give testosterone compared to a placebo, you're going to see an improvement in sexual desire and, you're going to see an improvement in sexual desire. potentially satisfying sexual events in mainly postmenopausal women and then I would argue also in perimenopausal women. That's where the best data lives. And we can talk about what the evidence is for a lot of the other reasons that people like to use testosterone. Let's go because the internet's exploding right now. It is very, very, very interesting. All right. Let's go organ system by organ system. Brain. Okay. Start with cognition. Yeah. There are multiple studies looking at testosterone and cognition. And the tricky thing about cognition is how you measure it. So there's a Lots of different ways.

What Lisa Muskoni taught me was forever the cognition studies were, does she have dementia or not? Not was she a high functioning attorney and now cannot remember her words, but she does not have dementia. You know, like it was like, does she have dementia or not? That was the scale. Not has she lost something so critical for her day-to-day activity, but she still doesn't have dementia. Well, it's the same thing as people saying, you know, dementia or brain fog, right? And so it's like if people say, well, if I take this, it's for a brain fog, that means it prevents dementia. No, those are two different things.

Yeah. And if your hormone is keeping you from having brain fog, that's actually very evidence-based. So Lisa says, brain fog is, I can't find my keys. Yes. Dementia is, I don't know what my keys are for. That is a very good way of putting it. So when we study cognition, there's the shopping list memory test. There's the how did you perform on this verbal recall test?

There's lots of different tests. And what you're going to find is with, in the test, Testosterone studies where people were given testosterone and then asked to perform various tasks, you're going to see a big variety in whether or not they got a benefit. So one study will say, okay, they had, you know, verbal memory recall was better, but the shopping list recall wasn't. If you gave them numbers, they remembered it, but then the shopping wasn't. And they get these really granular outcomes. If you look at all the cognition studies together and you look at was this, quote, statistically significant. That means does it look like the, if there's a benefit, could it have not been due to chance?

almost all the studies show that any benefit could have also been due to chance when it comes to cognition. That's my takeaway from what the evidence shows, but I always talk about the difference between group data and individual data, right? If a woman tells me I started taking testosterone and I felt like I could remember my shopping list better and I could remember where I put my keys and that brain fog went away, I'm not going to tell her that that's not true. Why not? Because there are people trying to control this narrative on testosterone who are telling women that's not true. I think you can say the studies of 100 women, and this is where I know that the, you know, other people listening here who go based on all the studies are going to be like, how can you say

this? Well, this is group data. If you take 100 women, you give 50 of them a placebo and 50 of them the medication, there's going to be 20 women in that medication group that did get better. And maybe in the placebo group there's a similar amount. That doesn't mean those 20 women didn't get better, you know? And so if you look at an individual, they may see an improvement, but across an entire group of people, you didn't see the signal that met significance. How do you counsel your patients then? That's what I tell them. I usually say, you know, there's group data versus individual data. I don't believe that the group data on testosterone shows that it improves cognition because it doesn't.

That's really where the data is. But if someone is taking testosterone and they say, I feel good on this and my cognition is better, I'm not going to tell them that, A, that's not true or B, we're going to take it away because I might have given it to them for libido. And maybe their libido didn't get better, something else did. Okay. Let's go to mood. Stay in the brain. Mood. Yeah. So if you look at, there's actually several studies looking at mood. And I just put together a talk because I'm giving a, you know, a long course at the International Society for the Study of Women's Sexual Health. Of which you are the president elect. Thank you. President, Dr. Tammy Rowe. I'm so honored, actually, to have been elected into this role. I give all of the Sunday

closing lectures, which is, you know, it's a lot to keep people there. But I, this is where I've given my progestin lectures and, you know, my PMDDD lectures. But the testosterone lecture has been really the funnest one to put together because I know how much is out there in social media. So the mood data is actually really interesting. Almost all of the studies looking at mood and testosterone actually favor testosterone, but all of the, quote, confidence intervals cross one, which means that they are not statistically significant. But it's different than like cognition where you see it kind of all over the place. The mood ones actually consistently trend towards a benefit. But again, if you are looking at, could this be due to chance? Absolutely. And could it be due to the placebo effect? Absolutely.

Things like mood are incredibly affected by the placebo effect. Right. And if we talk about the story of libido and testosterone, I've got a great story about how the placebo effect is the entire reason that we don't have an FDA approved product for women. It's because of that placebo effect. Do you want to hear that story? Yes. Okay. So in the early 2000s, there was, was a lot of data coming out looking at testosterone for low libido. There was a patch, a 300 microgram patch that was studied. It was brought to the FDA around 2007 for approval. And the FDA said we can see that it seems to improve libido, so sexual desire, as well as satisfying sexual events, but we are not comfortable with the safety data. We do not have enough safety

data to prove that it doesn't cause breast cancer, for example. Now, remember, this was in the aftermath of the WHI. Viagra had six months of safety data just to whisper that there. We've covered that ad nauseum on this podcast, but say it again. I'll say it again. People died in the Viagra trials, but we did not. We did not. People have died from Viagra. They did, and they still got fast track approval in six months. There was such an unmet need of erections. I will say, being married to a urologist who also focuses in sexual medicine, we have wonderfully robust debates when I talk about this because he will definitely argue on behalf of men and their sexual function. And I have a lot of empathy for what it means for men after going to

all these sexual medicine meetings. And I have even more for women because we can't get a product approved because we have to prove that it doesn't cause breast cancer. The amount of money that would be needed to do that when in the patch studies there was no increased risk of breast cancer. We have lots of data showing actually that it doesn't seem to increase the risk of breast cancer. either way. What's so interesting is there was a company that then said, okay, we will do this. We will pay for the study that is required to show that there is not a signal for breast cancer that it is safe. And it was a gel. It was a 1% gel. It was biosanti was the company. The medication was called Libby Gel. And the Phase 1 and Phase 2 trials were absolutely amazing. Well, on the phase three trials, these were the randomized controlled trials. They showed that those that took the testosterone gel had four more satisfying sexual events. And then the phase one, per month than before they took the gel. That is like Viagra level effect, right? That is more than any of the patch studies showed it's better than any of the other studies. The problem was so did the placebo group. Both groups had this huge increase in sexual desire and satisfying sexual events so that

it was not statistically significant. The company went bankrupt and this is why we do not have a product now. So that is the power of the placebo effect. Okay. Giving a woman permission. To use a product. Yeah. Turn the key for some of those women. Yeah. Okay. So we don't have an FDA-approved product. How do we get it? So the way that we get it now is we can use FDA-approved products that are approved for men. I borrow the men's version. Exactly. The benefit of the FDA-approved product is you know what you're getting, right? These are well-regulated. You know exactly what's in them. The problem with the FDA-approved products is that it's a pretty simple calculation to talk about the difference between how much testosterone a man has versus what, a woman has. Now, the goal when we're treating with testosterone is to restore the level to what it was

at our peak, and that would be in our mid-20s. So physiologic ranges. There's a lot of misunderstanding about this. So I want you to throw out numbers in the way they're traditionally measured in the U.S. Got it. So in the U.S., we measure testosterone in nanograms per deciliter. And so the normal range you'll oftentimes see quoted between 15 and 70, but that's, the 70 is kind of on the extreme, I have to say. The best study that was done, it was published in the Journal of Sexual Medicine. The numbers looked more like between, you know, 15 and 45, but the truth is those were using old, outdated ways of measuring testosterone. And this is why the level question gets so confusing. There are two different ways to measure hormones. And the one in almost all of the

studies that we look at, even for menopausal hormone therapy, used an older way of measuring that oftentimes overestimated, because remember, we talk about how estrogen, testosterone, progesterone, they're all related to each other. Well, their metabolites would all show a signal. And so they would get overestimated, right? And so the newer ways that we measure it are not included in most of the studies. So I just put that out there for the levels. But the natural physiologic level, if you look at my lab, it tells me at UCSF, if the level is above 50 to 55, it's in the high range. That's outside normal. And if I test someone in their 20s, say I'm working them up for irregular periods, for example, I'll usually see levels around 30s to 40s for normal

these patients don't have PCOS. So that's what I usually think of as like the physiologic level. So that's kind of my goal. I usually say my goal is 40 to 50 in a pariah postmenopausal woman nanograms per deciliter. That's physiologic. Okay. All right. So formulations, so the formulations, if you're going to give the male product, right, men will usually use these products, either a tube or a gel, they'll use one pump or one tube a day. Now, you have to remember that the average male level, right, I just told you my goal is 40 to 50 nanograms per deciliter, well, men have like 400 to 800 nanograms per deciliter of testosterone. So we're looking at one-tenth to one-twentieth, right? That's our target. So you want to be using one-tenth. We always say

one-tenth, but the truth is it's really one-tenth to one-twentieth. And so I typically will tell people to get a PPD syringe like a small one-cc, one-millimeter syringe, draw up between 0.3 and 05 of a tube of gel, and then rub that into their inner thigh someplace where you don't want children to touch, right? These are women who oftentimes have small children or where they don't mind hair growing because you can actually get hair grow without the site of where you place it. If you're going to do the pump, so for the men, there are pumps, they use one to two pumps a day. women can use those pumps, but then you're going to want to be doing like one to two pumps a week. And so what you're going to end up getting with that is these peaks in levels and then a valley, right? If you use it on Monday, you're going to feel probably absolutely amazing because you have a very superphysiologic level.

And then it's going to crash before you get the next one. And so it can be hard to dose. And we should talk about what super physiologic levels mean because this is something that I think we're seeing all the time when they come from other clinics through compounding and especially through pellets. So women have been prescribed testosterone for decades with no FDA approved option. And because we were never trained, I never touched testosterone ever in residency. And I did start using testosterone until about three and a half years ago. And thank God my is-swish friends taught me how to use it and sent me the guidelines. Depends on the clinician if she likes the packets or she likes the pump.

So I do want to just put a statement about the packets specifically. So packets are oftentimes, if you order testosterone as a 1% gel, testim, they'll give you packets. You do not want to use packets for women. Okay. And I've seen this actually like, you know, in some documentaries about testosterone use where we, you know, show the packet. Packets have alcohol in them. It will dissolve. So if the minute you open it, you take one dose out, it's done for.

So you want to be very specific. You want the tubes. I did not know this. You want the tubes. You do not want the packets. And so I put all over my prescription, tubes not packets. And the pharmacists will say the only thing we have are packets and I'll show them the generic tubes that are available where they can order them from and be like, no, you can find these. Okay.

That is, I did not know this. It's very, yeah, it's a very misunderstood aspect. I use the pump. Yeah. So it's, I mean, I prescribe the pump and I use it myself. Talk to me about, well, we can't say much about compounding other than it's out there. I don't think compounding is the devil the way. A lot of people do.

And I don't want to demonize a pellet. It is simply a method of getting something inside someone's body. But let's talk about what's actually happening in real life. Exactly. So I think, you know, compounding pharmacies are not bad people. I do think that there was- No, I use them all the time. All the time, right?

They are a drug delivery system, you know? And so people who can't get hormones a different way, it's a wonderful way to do it. And testosterone doesn't have a lot of options for it. So going compounding, the problem with the compounding pharmacy, so these are pharmacies that will take the raw material and formulate it into a product. And so we're usually going to be using testosterone cream in that sense. So I usually will get a 1% cream. And my goal is 2 to 5 milligrams a day.

So I'll oftentimes start at 2 milligrams and work my way up. So remember when we talk about those tubes, right? If the FDA approved product, it's a 50 milligram tube. One tenth of that is 5, right? So we just do the kind of simple math. So that's our goal when we're doing the compound. When I started prescribing testosterone, I did compounded. Yeah.

I went to the guy down the street. had a long conversation with the pharmacist. We did the math together, and we started with five. Exactly. It was just very reasonable. Before I became comfortable doing the FDA-approved options. Yeah, it's very reasonable to start with five. Now, the other way that people do it is some people do subcutaneous injections.

I'm familiar with people doing injections of testosterone because I take care of transgender people who do inject themselves. And cis men inject themselves with testosterone at very high doses, though. And then pellets, physiologically, I'm not here to demonize them. I get why people like them. Someone doesn't want to use the medication every day. You say, okay, we're going to put an insert under your skin. The problem with the pellets is you have no idea how they're going to be absorbed. And so you will see people with incredibly high levels of testosterone coming in, losing their hair, covered in acne.

And we have to then give them spironylactone and other medications to counteract the effect of the testosterone they were taking. So that's the problem with pellets. Some people will argue, well, you can get pellets in these really, low doses. And I still say, again, you can't take it out once it's in. You don't know how you're going to respond. So I don't recommend pellets. I understand why people use them. I just don't recommend them. Most of the practitioners in our area are using a certain company. And in my clinic, when I'm seeing a patient, I'm always checking a testosterone level, especially if they've been prescribed. I want to see how they're absorbing and where they are before we restart the medication. And I've

never seen a patient who wasn't super physiologically dose. But what does that mean? So super physiologic means that your level is above that target that we talked about earlier, right? So what is that kind of in a naturally physiologic state, right? You don't have a other condition like PCOS, right, or an ovarian tumor, adrenal tumor. What is a normal circulating state? So we already talked about, really, I think of the goal as 40 to 50 nanograms per deciliter. I've seen people, you know, quote up to 70 is reasonable to say if you look at the literature. I've heard people on other podcasts or big names, say up to 80, which is not based on physiology. At that point, you're now super a physiologic. Right. I mean, I've heard as high of 100. Yeah, again,

this is not. But over 100, like, let me explain to our listeners, if we have a woman come to clinic and we're working her up for acne and hair and whatever, we check a testosterone level. If it's above 100, and she's not on any medication, we are obliged to check her for a tumor. Absolutely. 100%. Like, I would just want people to understand the gravity of, like, when in a normal, healthy woman who's not on meds, if we see a testosterone over 100, it is malpractice if we don't work her up for a tumor. A hundred percent. So, you know, people are familiar with the condition of PCOS. Yeah, I had 90. But 90 was my testosterone level with PCOS. You don't see people with levels above 100 of PCOS. And I had horrible acne and hair growth everywhere I didn't want it. I'm sorry.

That's okay. We managed it. What's so interesting about that, though, is, you know, I do see women who have testosterone levels above 100 and they don't have acne and they don't have all the hair growth all over their face. I'm Cajun. No. Well, but it goes to show that, you know, these people with super physiologic levels, I'm seeing them all the time. Now, oftentimes it's not me that's giving them that dose.

I mean, it never really is, but sometimes I'll give somebody that normal dose and I'll check a level and they're super absorber. And so they have really high levels. And the truth is, some of them feel fabulous. And they really are getting all these benefits without all of the side effects. And then it turns into a conversation. And I just want to be real about this. At that point, I'm not here to say it's bad. I've oftentimes hear people say it's dangerous. I take care of transgender men who have testosterone levels in the 500s and 600s. They have uteruses and ovaries. And the data actually shows they have lower rates of breast cancer. There's some question about cardiovascular risk, question about diabetes. I'm not here to say it's not without risk. But what I want to be really honest about is at that point, this is not menopausal medicine. This is not physiologic replacement. This is a performance-enhancing drug.

And if you are taking it at those levels, that's what it is. And I'm not here to pass judgment. I just think we should all be honest. If we're at superphysiologic levels, that that's what testosterone is. And that's oftentimes people who have some of the strongest side effects in terms of benefit. Right. Do you remember the New York Times article that recently came out? It's because they're on a performance-enhancing level of testosterone.

Okay. If you have a woman who feels absolutely fantastic is not having side effects, what do you do? Do you leave her on it? To be honest, yes. And I know that that's against the guidelines. And I'm putting this out there for the world. But the truth is I talk about, you know, where we have the data, where we don't have the data. I know the transgender literature very well. So, but remember, they also have levels, you know. Which is basically the safety data. That's the safety data. That is the safety data is on the transgender population. It's true. And I want to include them in this conversation because we talk about testosterone for women, for sexual function, for, you know,

in this idea of gender affirmation to feel more like themselves to, you know, have all these benefits. And yet we're trying to take it away from our transgender people right now. And it feels like there's this, you know, like contradiction. And the data that we have is from the transgender people. And the cis patients are frustrated because it is FDA approved for the transgender patients. It's covered by insurance. And so that is a very, very, very, but that is a very good point. And it's a very fair point. And it's not, well, I wouldn't say it's FDA approved for the transgender patients. It's covered by insurance. And so that is a very, I apologize. I apologize. But that is a very good point. caveat. They are frustrated because they can't get their medication covered. And they should be by insurance. And it absolutely should be. Yeah. We had talked about the metabolites of estrogen and progestins. Can you cover the breakdown of testosterone and central and peripheral acting? So testosterone is actually metabolized in some tissue into estradial. And so in the ovaries, you see it metabolized into estradial. In the bone and in the peripheral tissue, there's androgen receptors, but there's also estrogen receptors, so you're seeing it broken down there and where you're getting some of the benefits.

But it's also converted into another hormone called dihydro testosterone. And so dh-hty is important because exactly, you're pointing to your face because of acne. So the thing to understand it, you know, I keep talking about receptors because I'm a nerd. There is no testosterone receptor. There is no dh-t receptor. There is an androgen receptor. And so that is a lock that is then signaled by two keys. So it's fine.

and testosterone. So only testosterone and DHT bind to the androgen receptor. And so DHT binds with twice the affinity and five times as sticky, right? It doesn't want to come off. And the DHT is where you're going to see the endogen receptors affect the skin and the hair. And that's why it's the villain when it comes to male pattern baldness or excess testosterone hair loss that we see in women as well as acne. So when we're trying to treat acne and hair loss, that's, you know, the monocidil, these various things that are actually blocking the conversion to DHT. So we're not going to affect testosterone levels. We're going to affect dhhty levels. How does spurnalactone work? Great question. So spurnalactone works by blocking production of testosterone and blocking the androgen receptor. So it will affect your testosterone.

And so it's different. And so that's why you will sometimes see sexual side effects from spironylactone, and you will also see menstrual cycle effects from spironylactone in some people, because you are now affecting the metabolism of estrogen in the body because you can't make estrogen without making testosterone. So some people actually stop their menses when they take spironalactone. Okay. What about local activity of testosterone in the general urinary system? So we've learned over the years that the dogma, that the genitone urinary system, the vulva and the vagina are only sensitive to estrogen is actually untrue. So remember I talked about the receptors. There's estrogen receptors and androgen receptors all over the vulva. And it actually is going to play a

big role similarly to the way that the estrogens do in terms of blood flow. I actually get really nerded out on this, that it helps to produce glycogen. So that is a sugar. That sugar is fed upon by lactobacillac, right? Anybody who knows anything about the vagina knows lactobacillin. It's the good bacteria. It's the good bacteria. What does lactobacilli make? Lactic acid? What does lactic acid do decreases the pH of the vagina and keeps it healthy? When you lose your androgens and your estrogens, you see a cascading pathway that will lead

to an increase in the pH lack of that lactobacilli and then a recolonization with unhelpful bacteria. Oh, my God. So for recurrent BV, how are you treating this? So I want to restore the natural microbiome. So I will give people, I mean, especially in menopausal women, like the bottom line is we need to restore their estrogens. And then I'll give them androgens as well in the form of prasterone. And even for premenopausal women, I'll do that. If the FDA-approved regimens aren't working, I think about what's going on in this microbiome.

Before we pivot, talk to me about the Dutch test, since you are the endocrine goddess. No. Okay. Why? So it's this idea of they're testing usually salivary hormones. and salivary hormones have never been shown to be correlated to blood-level hormones. And again, I'm going to go back to the receptor.

The hormone in your saliva looks different than the hormone that's in your blood. And the hormone that's in your blood is the one that is directly acting on the receptors. Right. And you talked about the metabolites and how they can convert to one another. 100%.

So what you're excreeding doesn't represent what's in your blood. Nor what's going on in your cells. This is why we could have two different patients. One has a, you know, estradiol level of 80. And so with, you know, estradiol, we're talking about picograms per liter. So it's a little different. It's lower, actually. But if you, we could have two patients with the exact same estradial levels with totally different side effects because of how what's happening at the level of the receptor. Same is going to be the true for testosterone. That's why when people say test my testosterone level, you know, prove to me that I have low sexual desire. I'll say I have two patients with the exact same testosterone level. A sexual desire is. much more complicated than just testosterone, but that's why you see people feel good at different levels of hormones. Now, I'm not somebody who treats to levels. I treat to symptoms for this reason. Do you ever check levels? I do, actually. So with testosterone, I always want to get a baseline. I want to know where we're starting. I don't, you know, some people say if the testosterone level

is in the kind of higher normalish range, they may not get a benefit. I disagree with that. Again, how sensitive are the receptors? If I give them a little bit more, they might feel a little bit better, And then if I'm treating them continuously with testosterone, then I'll recheck at six weeks to see what the level is at, certainly depending on their symptoms. estrogen, it'll be the same. If I give somebody menopausal hormone therapy for estradiol and they're not getting a benefit, I'll absolutely check and I'll see how much room do we have. And I have patients who really feel better at really high levels and we have to have a conversation that this is higher than a, you know, average circulating estrogenial in a premenopausal woman. But remember, in premenopausal women, our estradial levels are in the multiple of hundreds, you know, around the time of ovulation.

Talk to me about absorption. We use a lot of transatlital. We use a lot of transatlose. instrumental estrogen. I don't use much. I never use transomal progestins anymore. You shouldn't. I always do oral micronized and we'll talk about progesterone insensitivity, which is a whole topic. But, you know, I was thrilled to see the data come out of the clinic in the UK from Louise Newsom's clinic and her data. Talking about, hey, not everybody absorbs the same. Turns out a significant percentage of us are poor absorbers. Me. I had a patient. Oh, my gosh, I loved this patient. She had terrible endometriosis. She was in her 30s, and we did a hysterectomy and an ophrectomy. She elected for an ophrectomy because, you know, she really wanted to not have her ovaries and have control. There's a risk, obviously, of giving someone

estrogen after an endometriosis surgery, but she wanted it. So I gave it to her, and she felt absolutely nothing. And she said she took the entire box and put every single patch on her. And I just, I picture this woman covered an head to tone matches. And I'll never forget this because I tested her levels and they were postmenopausal. And that was when I had this epiphany. This woman would not absorb transdermally. And so I gave her oral estrogen and she did. We always talk about oh, we have to do it one way or the other. No, you do it the way that works for the woman. And some people don't absorb through their skin. And so give it to them orally. It's fine. You can also give it to them vaginally. the vagina is the most sensitive tissue for absorbing hormone.

You know, it goes directly into the bloodstream through the vagina. Now, I don't want to confuse patients to think, oh, my vaginal estrogen, my doctor prescribed me for GSM is going to treat my bones in brain and no. Thank you for the clarification. If you give a dose high enough, not any of the FDA approved products or how we do anything. Like this is very special. Or femurring, just to be specific.

Exactly. There is one systemic vaginal estradial ring that you can use 100%. Thank you for the clarification. When we are using vaginal estrogen, the goal is to treat the vagina, it will not go into the bloodstream. But if you want to get a blood level that's high in the system, you actually can put high doses in the vagina of all of the hormones, estrogen, testosterone, and progesterone. Anybody who's been through fertility treatments is aware of this because they're putting a bunch of progesterone pills into their vagina. Why are they not taking it orally or why are they not injecting it? Because it works better to take it vaginally.

Okay. They have better absorption rates. We do a lot of transdermal. It's just easier to check everybody rather than wait to see who's absorbing, not absorbing. So like for all our transomal patients, do a three-month check. I think that's great. I mean, you could do it just, you know, again, I think it's a very reasonable approach. Sometimes if somebody, you know, is worried, you can check earlier just because the minute you give them a patch within a few days, you know, we hear their symptoms get better. What I do sometimes worry about is this idea if you get a level and they're like, oh, but that's not what my friend's level was or that's not the level I read about. It becomes, a little bit tricky. And this has got the nuance. Some clinics are doing, everybody gets the same thing, and it's a one-size-fits-all, and there's so much nuance to this. Now, what is progesterone intolerance? Okay. So progesterone intolerance is the fact that progesterone affects a lot of different receptors. And we already talked about that there's progesterone receptors in the brain, but some people are incredibly sensitive to progesterone. And we know that because think about

premenstrual dysphoric disorder. That is progesterone intolerance. So that is when you get, you know, anxiety, depression, all kinds of symptoms that start at ovulation, peak mid-cycle, and then go away when the period starts. Well, that is based on your progesterone levels. So we can already see that when someone's going to maybe be predisposed, if there's somebody that was sensitive to their own endogenous, their own natural menstrual cycle. So that should be a red flag. It's a red flag. Someone who had postpartum depression, that's somebody who was very sensitive to progesterone fluctuations. These are people who are going to be more likely, oftentimes also to have worse perimenopausal

symptoms and more symptoms in menopause because progesterone levels fluctuate. They don't get high. They're actually lower as you are in a perimenopausal transition. But some people, when you give them progesterone, I mean, I had a patient who was suicidal from her progesterone. We've seen this. And she had to be hospitalized. So that's the extreme.

And I don't want to scare anyone off. I don't want to scare. but it happens. But it happens. And so that is, it's so people can get really significant mood changes. Some people just get too sleepy on it. Some people get horrible headaches. I've seen the paradoxical effect for sleep. And so what do you do for those patients? Great question. And again, this is where there's so much nuance and I love this conversation. And this is why menopausal medicine is so, it's so fun. It's so fun. And it's not algorithmic. So you can't just say if this do that. It's like everybody's individual, you've got to take a history, right? And think about what's going to work for

them. So I do prefer to start with micronized progester. if they have a uterus for endometrial protection. And then for some people who don't even need it, some people do get a benefit from it. But if I give them, you know, micronized progesterone and they start having these side effects, I will switch to a progestin. As I said, these are not the double.

They work very well. And so typically the one I will give, I like Northandrone acetate, Agestin. I like that better than Provera. We've talked about, you know, we just don't use Provera outside of, you know, get your bleeding to stop, you know,

emergently. But it is not a medication to take long term. It's not just the concern. about the breast. It's actually vasoconstrictive. If you look at the WHA, I know you've spent a lot of time with this, but if you look at the cardiovascular outcomes, they were worse in the combined group. We always talk about the breast cancer group, worse than the combined group, too, because Provera had is vasoconstrictive. And so cardiovascularly in the older women, they did worse with it. It's just not a good medication. So anyways, I go with North Endurone Acetate, and then I'll also do a lot of drospirinone these days.

Okay. And so people tolerate it. North Endrone Acetate looks a little bit more like, progesterone. What about compi patch? Combi patch is a combination of norithendrone and estradial. It's a great method. I actually give a lot of patches. That's how I started. And, you know, people again are like, oh, everything has to be bioidentical, but I'm like, you need to just be able to take it, right? Like, if people just want one thing, the combi patch is great. It's hard to get covered by insurance, and it has, but it's a northendron. Climera Pro is another combination patch that has leave and adjuster. We haven't talked about that as much, but that's another really good. progestin, both of them are designed to protect the uterus. If people can't tolerate those forms,

Slind is a great method. What is Slind? Jospirinone-only medication. You can also do a leave-in-agestral IUD. So that's going to be an IUD that goes directly into the uterus. It's putting the progestin. It's the best way by far to protect the endometrium. It not only prevents uterine cancer, it cures it in about half of people who have an early stage cancer. It is the best for that purpose. and then if they can't tolerate any of them, then I will do do a V. Or if they don't want to take anything else but one pill, and if they're at high risk of breast cancer, we already know that conjugated equine estrogen prevents breast cancer on its own. That's what's in doofy.

Then you add in a serum, oh my God, you get even more bang for your buck. So patients that are really concerned, again, I've got a lot of opinions about the breast cancer risk. I know you've had Avram Blooming on here who debunked the myths around it. Yeah. But there are people who are still concerned, but there are people with, you know, high risk, biopsies, people with... We use it because women who are survivors, pre-vivors, high-risk have nowhere to go.

They end up in our clinics. Me too. And so I use Do-OVee probably a hundred times more than anyone else in Texas. I believe it. Who doesn't practice my kind of medicine? The other group that I love using Do-O-V-4, two groups.

One is the endometriosis patients. Oh, okay. Because the estrogen is going to stimulate any, you know, endometriosis. So you've got now this serum that'll block. Now remember, 30% of endometriosis isn't sensitive to progesterone. And so those are endometrial cells. I did not know this. Yes. That's why they don't work for so many people. That's why you end up needing surgery in so

many things. Otherwise, it would be okay. No, endometriosis looks, the tissue and endometriosis looks very different than natural endometrial tissue, very different receptor morphology. So I like do-a-V-4. And then the other patients I like do-a-v-for is refractory PMDD. And, you know, they don't respond to birth control pills because you're giving them another progestin, so their body's exposed to it. And that's premenstrual dysphoric disorder. Thank you. Yeah. So that's the progesterone hypersensitivity.

So what I do for those patients is I actually suppress their menstrual cycle entirely. We already talked about Lupron. So that will just shut off their menstrual cycle. But they need hormone. But I don't want to give them any progestin. I refuse to give unopposed estrogen. I just want to say that's my practice. I just refuse.

Then I give them duiv and I have saved so many women by giving them Lupron plus du duvie for refractory premenstrual disorder. And the disorder. Welcome back to another midi pause. I'm Dr. Mary Claire Haver, host of Unpaused. If your clothing has been fitting differently lately and you haven't changed a thing about how you eat or move, you're not imagining it. And it is not your fault. Today we're talking about changes in body composition.

Hormonal weight gain can be one of the most frustrating parts of the midlife journey. But with the right support, from medication to lifestyle tweaks, you can feel like yourself again. That's why Middy Health is dedicated to changing the way menopause is treated, with a personalized approach to each woman's specific needs. Women come to Midi Health to address the symptoms of menopause they see and feel every day. They partner with you to find a treatment, whether that's HRT or a non-hormonal solution, a weight loss medication, or simply a lifestyle change. Hormones play a major role in midlife weight gain.

When estrogen levels begin to drop during perimenopause, our bodies can start to change, even if our diet and exercise routines have not. Instead of accumulating in the hips and thighs, it moves to the abdomen and that visceral fat. The kind wrapped around your organs raises your risk of heart disease, diabetes, and dementia. This isn't vanity. This is a health issue that deserves real solutions. The good news? Visceral fat responds to lifestyle changes, and here's where to start.

Number one. Prioritize protein, fiber, and reduce your sugar intake. Aim for at least 30 grams of protein per meal and 25 grams of fiber per day. Cut added sugar to under 25 grams daily. These three shifts alone can meaningfully reduce belly fat over time. Number two, lift weights. Resistance training is the single most effective tool for changing your body composition and menopause. Number three, protect your sleep and manage stress.

Both poor sleep and chronic stress drive cortisol up. cortisol feeds visceral fat. You cannot out-exercise a stress response. Number four, consider a conversation about hormone therapy. H.R.T. can help address the hormonal root cause of this fat shift. Women who start estrogen therapy early in menopause often see a meaningful improvement in body composition. Ask your clinician. Progress starts with a personal plan. That's why the Mitty approach centers on a holistic combination of solutions, from medications like weight loss medications to lifestyle changes, in a care plan that works for your body and your needs. By doing so, Miti Health is setting a new standard for health care.

As the nation's fastest growing women's telehealth company, Mitty provides accessible insurance-covered services. Building on its leadership in perimenopause and menopause, Mitty fills the critical health gaps women face at every age and life stage. If you want a clinician in your corner who understands what your body and brain need right now, that's exactly what MIDI is built for. Go to join midi.com. Join MIDI.com and connect with one of their clinicians today. I've got a few questions coming from my listeners and on social media.

You ready? Always. Okay. What do you wish women in their 30s and 40s understood about? choosing contraception for pregnancy prevention cycle control mood and sexual function. So I think what I wish they would understand is that birth control is not bad. It does so many good things. I just talked about the fact that, you know, if you are sensitive to your hormonal fluctuations and you want them to go away, you're going to get that only with birth control. I mean, there's

nothing else that does that. The natural hormones don't. No. No. Sorry. If you want to stabilize your hormones, you got to use birth control. And so what I would say is I take a really good history when I'm picking a pill to figure out what people's priorities are. So what are their worries and their priorities if it's around bleeding, if it's around sexual dysfunction, if it's around acne? And so I am, again, not a pick-a-pill, any-pill person, and I will tailor which one I recommend based on their priorities. Hormonal contraception seems to be being blamed for ruining libido. So there is a biological explanation for how this does it in some women, okay? And this is the key. We talked about group data versus individual data. If you look at the group data,

you're going to find that there are many women who actually feel a benefit from birth control. Both, like, I think not just the psychological freedom of it. I mean, birth control was the original sex med drug, all right? This allowed us to be honest about why people have sex. You know, you take birth control so you can actually enjoy sex, right? That's what it's for. We're not trying to destroy libido. But again, combined hormonal contraception will increase sex hormone binding globulent and decrease testosterone levels and everybody that takes it. doesn't mean they're all going to have a sexual side effect. They just will have lower testosterone. Some of them are anti-androgenic, like Drosperinone, right? So that's your Yaz, your Yas, your Yasmin.

Those also have a double hit then. Some of the birth controls don't do that. So the IUDs don't is really what it comes down to, even the hormonal one. Levinidigestrel actually is a little pro-androgenic. So that's why people get acne with the IUD, right? And so that's the main thing. And then there is also a subgroup of people who I just saw somebody yesterday who I cured. I'm sorry. I'm so, so happy when I see people who had sexual pain from long-term birth control use. There's a subset of women who do develop a vulva-dinia. This doesn't happen to everybody. Again, don't stop your birth control for this reason. But if you over time develop sexual pain, it could be due to long-term use of birth control. And so if that's happening, see somebody who knows that and knows how to treat it. How did you

fix her? I gave her back compounded estradiol and testosterone. It's the, FDA approved, I'm not going to just give her estuary screen. She's got androgen and estrogen receptors. So I give her a little bit of a higher concentration than what you can get FDA approved estradial and then a very low dose of testosterone. And then she don't want to get off that birth control. I always switch them to something that is, you know, equally as effective because you really can do that. She was questioning it and then her physical therapist, you know, because she's going to PT and pelvic floor PT. Yeah, pelvic floor PT. It's not doing anything because it's not a muscular issue. Yeah. And a smart PT was like, you really should get off your,

you know, this particular birth control. And she did. And she's like, it was, it's so satisfying as a sexual medicine provider to, like, do an exam. And I'm like, you're a different person. And she's so happy. How would you help a woman navigate perimenopause? I think it depends on what their symptoms are. So the earliest symptoms of perimenopause, we know this, are not the ones that we always think about, like the cycle irregularity or the hot flashes. It's sleep and mood. And so I honestly have found that in the early stages of perimenopause, you know, I always talk about how people have a progesterone sensitivity. That is one place. I see people that do good if I give them solo progesterone therapy. How do you give it? So I give micronized progesterone. I usually will have them take it orally at night.

Now, progesterone works twice as well absorbed if you take it with food. So we always tell people to take it at night, but it's not going to work as well if they're too far from their last meal. So I usually tell people to take it right after their last meal. It's going to work better. They may be tired within two to three hours. So it just depends on what their, you know, bedtime is. I heard take it with a scoop of peanut butter.

That is a reasonable way to do it. It's an oil-based molecule. It'll bind up to that peanut butter and then get absorbed. So that's probably why you would do it with the peanut butter. So anyway, so again, if the goal is sleep, then I have them take it orally. The sleepy side effect of progesterone is actually probably due to its metabolites. So what it's broken down into. So if people get too sleepy on it, but their mood is better, I have them place it vaginally. Because then it's not being broken down.

The same little tablet. You can just take the little tablets, the prometrium micronized progesterone. It's a little tablet. Just put it in the vagina. Amazing. Why does my orgasm change in midlife? Oh, I wish it didn't. A couple different reasons. So orgasms are very complicated. You've had lots of good speakers talk about this. But, you know, in midlife, there is a change. First off, we're aging and we have to be real that not everything is hormones, but some of it is. And so if the tissue is getting more, we call it atrophic. We don't like that word.

But if you're getting thinner tissue because of lack of hormone, you're going to have less blood flow. you will oftentimes, if you are someone who gets clitoral, you know, orgasms, you can see adhesions that form. The vagina also gets thinner. People also get a lot of stimulation from their vagina. So it can be hormonal. It also can be the nerves that are aging. And so that is something that is a little bit hard to, you can't treat that as easily as you can treat the hormonal changes. And then there's a musculoskeletal component. So orgasm has a lot to do with your muscles. And so if somebody depending on if they have laxer muscles or overactive muscles, they may also notice a difference. Why don't I want to have sex anymore? I feel broken. Oh, I, you know, I'm giving you the easy ones.

And these are so hard. So sexual desire lives in the brain. The brain is the biggest sex organ. And there are so many reasons that people don't want to have sex. I wish it were as simple as testosterone. I think we have to be really honest about what happens to testosterone levels. What percentage of people? Like walk me through the success of testosterone. What does that really look like? So if you look at the data, about 50% of people get better, I will say clinically. I don't see that number. I wish I did. I see less. But you're kind of a clinic of last return. You know? That is fair. That is totally fair.

I mean, other people are possibly getting it. And it's not because I'm not giving them the way to do it, you know, appropriately. But I will say that, you know, if you look at the data, it's about 50%, which is the same for the other sexual medicine drugs. If you're keeping them physiologic, I will say when people come in with superphysiologic levels, they may see the difference. Now, again, I'm not promoting superphysiologic levels. Okay.

Most of the data, again, all the studies we have on libido were. at some of, again, if you look at the old assays they were using, some of them really were superphysiologic, but that's in the weeds. So I would say it works probably for about half of people. But again, you know, testosterone levels don't fall off a cliff in menopause. We need to be really honest about that. They actually start to decline in your 30s. They stay, you know, they have a slow decline in your 40s. And the year before and the year after menopause, your body isn't like, oh, I suddenly don't have testosterone anymore. It's been low for a while. And so I don't think it's wrong ever to give testosterone, but I don't think we say, well, because now we're in menopause, we're not making testosterone.

That's not actually physiologic. Yeah. You know, it's a therapy. It's not a replacement. It's a therapy for symptoms. Sexual desire in pharmacologic management. So there's too much that are FDA approved also. You want to just briefly cover them?

Absolutely. So remember, I said, the biggest sex organ is the brain. And the way to understand sexual desire is that it's neurotransmitters. It's the way that the brain cells talk to each other. So testosterone modulates those neurotransmitters. it's dopamine and noropenephrine. There are two medications that also affect those neurotransmitters. One is called phlebancerin.

It's a mixed serotonergic drug. So it works on serotonin, which then modulates dopamine. It is a nightly medication, 100 milligrams at night. It works, again, in about 50% of people. You see similar results in the testosterone studies as in the flabanserine studies in about half of people. But those that it works in, it can work very well. So it helps people sleep.

They're not too drowsy the next. day. They've done next day driving studies where they did even better. It takes about two to three months to see an effect. Because it works on serotonin receptors, oftentimes people say, I just feel better. They actually will say the same thing. They feel about testosterone. Wasn't it originally developed to treat depression or something? It was. Yeah. So because it was a serotonergic drug. So in the 90s, they were using it to treat depression and it didn't meet clinical endpoints. But the people reported an increase in libido. Now, what does that sound like? Biagra. Biagra was originally developed as a blood pressure medication, didn't work for blood pressure medication, but the men wouldn't give it up, right?

So it's very similar, but it is not the female Viagra. People oftentimes say that. Biagra works on blood vessels, right? It vasodilates. It causes an erection. Flaancerin works in the brain. So it's about two to three months. A lot of people just say they feel better on it. And then the other drug is brimelanatide. And so that is an injection. It's a melanocortin receptor agonist. And so again, these are just functional molecules in the brain work the same way. increase your dopamine, increase your norapinephrine, mainly dopamine. It's as needed. So it's different than these other medications like testosterone or phlebancerin that you have to take every day. The biggest side effect from brimalanatide is nausea. And so the more you take it, the less likely

you are to have nausea. The benefit of it is if it doesn't work, it's not going to work. So it's like flabanserin, which I use all the time. Then you have three months to figure out. You have three months to figure it out. With brimalanatide, if you use it three or four times and you don't get a benefit, you'll know. And if you use it and you get a benefit, you'll know. This is the thing about sex med. I say all the time. There's no condition in medicine that everybody has a relationship to. We talk about the fact that everybody with ovaries is going to go through menopause, right? That's 100% of people with ovaries. But 100% of people have a relationship to sex. They may not have ever had a heart attack or diabetes or anything else. And our own relationship

to sex, we project onto other people so much. And I think this is why it's been so hard for people to get care because they'll say, well, nobody wants sex at this age or I didn't want sex. You know, or sex is not spontaneous desire is not good or it is good or receptive desire. Everybody's an individual. And our goal is to support those individuals and not project our stuff onto them. Excellent. Well, thank you so much for joining us on Unpaused. And I think our listeners are going to benefit so much.

Thank you so much for having me. It's been a total pleasure. You can find Dr. Rowan on Instagram and TikTok at Dr. Tammy Rowan. She is also the president-elective. Ishwish, a major resource in sexual health for clinicians, researchers, advocates, and consumers, and can be reached at info at iswish.org. If you're a prospective patient, you can find her at www.w.UCSFhealth.org, where she is available for surgical and procedural consults, as well as complex sexual health menopause and survivorship consults. You could find full episodes of Unpaused on YouTube

at Dr. Mary Claire. I'd love to hear from you about this topic and anything else that's on your mind. You can find me on Instagram at Dr. Mary Claire and get honest and accurate information on health, fitness, and navigating midlife at thepawslife.com. My new book, The New Perimenopause, is available now on Amazon.

If you're loving this podcast, I have an important request. Please take a moment to follow Unpaused on your favorite podcast app. Following and listening is what pushes this information to more women who need it. So if this podcast has helped you feel seen, understood, or supported, hit follow right now so you've never missed an episode.

Thank you for being here with me. Let's keep going, Unpaused. Unpaused is presented by Odyssey in conjunction with Pod People. I'm your host, Dr. Mary Claire Haver. The views and opinions expressed on Unpaused are those of the talent and guests alone and are provided for informational and entertainment purposes only. No part of this podcast or any related materials are intended to be a substitute for professional medical advice, diagnosis, or treatment.