Estrogen, Progesterone, and Testosterone: The Science of Hormones, Sexual Function, and Menopause

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 https://www.ucsfhealth.org/providers/tami-rowen (UCSF Health) Dr. Tami Rowen https://www.isswsh.org/component/content/article/299-tami-rowen-md-ms?catid=99&Itemid=469 (ISSWSH) Dr. Tami Rowen https://www.instagram.com/drtamirowen/ (Instagram) https://thepauselife.com/blogs/the-unpaused-podcast/estrogen-progesterone-and-testosterone-the-science-of-hormones-sexual-function-and-menopause

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Speaker 00

  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.

• 0:23Dr. Mary Claire Haver?

  Yeah.

• 0:24Speaker 00

  You know, it's a therapy.

• 0:35Dr. 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.

• 0:53Dr. Mary Claire Haver?

  One of the most persistent problems in women's healthcare 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 altogether. 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.

• 1:35Dr. Mary Claire Haver?

  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 progestins, 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,

• 2:18Dr. Mary Claire Haver?

  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. 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

• 3:03Dr. Mary Claire Haver?

  it really takes for women to thrive in the second half of life.

• 3:14Dr. Mary Claire Haver?

  Buy smart, drive for less, and trade for more. That's Toyota affordability, and it all starts with a great deal from your local Toyota dealer. Make a smart buy on an all-wheel-drive Camry, Corolla Cross, or get a Corolla Sedan, packed with the latest features, advanced tech, and head-turning style. Take a test drive in two of Toyota's most popular SUVs, the spacious, family-friendly Grand Highlander and adventure-ready RAV4. And with so many hybrid and plug-in hybrid models available across the lineup, plus efficient all-electrics like the BZ, BZ Woodland, and all-wheel-drive CHR, you can drive your way and skip the pump.

• 3:55Dr. Mary Claire Haver?

  And long after you leave the lot, your Toyota keeps delivering with legendary resale value built on a reputation for quality and reliability. So when it's time for your next Toyota, you could trade in for more. From a great deal today to a great value tomorrow, a Toyota is right for you. Shop toyota.com for deals and details, or stop by your local Toyota dealer today. Toyota, let's go places.

• 4:26Dr. Mary Claire Haver?

  Dr. Rowan, welcome to UnPaused.

• 4:28Speaker 00

  Thank you so much for having me.

• 4:29Dr. Mary Claire Haver?

  Yeah, glad to have you here. Let's dig into hormones. You teach a course, if I have this correctly, called Hormone Therapy, Estrogens and Progestogens. And then you teach another one called Let's Talk Progestins. When I tell you on social media, I get so many questions about hormones. What kinds? 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?

• 5:03Speaker 00

  I am down for this. This is my favorite thing to talk about.

• 5:06Dr. Mary Claire Haver?

  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.

• 5:17Speaker 00

  Okay.

• 5:17Dr. Mary Claire Haver?

  So that's where women are first exposed to hormones.

• 5:20Speaker 00

  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 estradiol. And the thing to understand about estrogen is it is 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.

• 6:04Speaker 00

  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 estradiol. I know you know this, you talk about it. Well, birth control doesn't have any of those three.

• 6:25Dr. Mary Claire Haver?

  Right. And that's where the confusion starts. So what does it typically have?

• 6:29Speaker 00

  It has ethanol estradiol.

• 6:31Dr. Mary Claire Haver?

  Why?

• 6:32Speaker 00

  Because ethanol estradiol 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 estradiol.

• 6:52Speaker 00

  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. Ethanol estradiol 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. Ethanol estradiol feeds back, tells it not to do that. It's not the primary way birth control works. It's the progestin we'll talk about, but it feeds back and then it also stabilizes the lining very well.

• 7:25Dr. Mary Claire Haver?

  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 estradiol, which is not what happens at all. It binds to the receptor 300 times stronger than plain estradiol, which is why it works so well for contraception.

• 7:55Speaker 00

  Yes, so exactly, it's that lock and 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. The, 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 estradiol. And so that was when we started seeing all the blood clotting. And we start saying, well, all estrogen causes blood clots. No, ethanol estradiol is going to do that.

• 8:39Speaker 00

  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 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 estradiol, 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 estradiol does. It's not actually as good in the bones for promoting bone health as natural estradiol. So there is some evidence in younger women. That if they're taking ethinyl 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 twenties.

• 9:23Dr. Mary Claire Haver?

  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 and certain conditions, and I do menopause care because there is a pushback and a certain faction, you know, especially on social media, that all contraception is bad. So that stepping away at all from your natural cycle is, is, is not your best life.

• 9:49Speaker 00

  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.

• 10:13Dr. Mary Claire Haver?

  Right. Yeah, yeah, we're talking a hundred X in your first six weeks postpartum or first two weeks postpartum. Pregnancy is the number one way. We have stasis and hyperacregulability. So, yeah.

• 10:25Speaker 00

  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 a hundred 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 ethinyl estradiol, because it gets confused, especially when we talk about menopause.

• 10:47Dr. Mary Claire Haver?

  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?

• 10:59Speaker 00

  So there actually is one. And so I-

• 11:01Dr. Mary Claire Haver?

  In Europe, correct?

• 11:02Speaker 00

  In Europe. And I wrote an article actually about it because there was an article that was published comparing, it's a 17 beta estradiol, and it has 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, 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,

• 11:48Speaker 00

  you know, 17 beta estradiol? 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.

• 11:58Dr. Mary Claire Haver?

  What if we had a combination of estradiol and vasodoxapine in a dose high enough to suppress ovulation? Would you buy it?

• 12:06Speaker 00

  I would if it would suppress ovulation.

• 12:09Dr. Mary Claire Haver?

  If it suppresses ovulation.

• 12:10Speaker 00

  I'm not convinced it would, but if it did, that would be great.

• 12:13Dr. Mary Claire Haver?

  Yeah, because we're going in the weeds, but vasodoxapine is a CERM and it protects the endometrial lining. It binds, blocks, and downregulates 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 interactable bleeding with their traditional MHT, we are very quick to reach for.

• 12:33Speaker 00

  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.

• 12:39Dr. Mary Claire Haver?

  Same.

• 12:39Speaker 00

  So the issue-

• 12:41Dr. Mary Claire Haver?

  But we by digress, sorry.

• 12:41Speaker 00

  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.

• 12:57Dr. Mary Claire Haver?

  I did not know that.

• 12:58Speaker 00

  That is a fact. It is the progestin.

• 13:01Dr. Mary Claire Haver?

  I have been practicing OB-GYN for 30 years. I did not know this.

• 13:03Speaker 00

  I honestly am so honored that I came to your podcast and actually taught you something you don't know.

• 13:09Dr. Mary Claire Haver?

  Okay, well, it makes sense because we have progesterone-only contraception, but not estrogen-only contraception.

• 13:13Speaker 00

  And you have to think about what is, what is it doing? Your brain, you're trying to get the brain to tell the ovary not to release it.

• 13:20Dr. Mary Claire Haver?

  Right, right.

• 13:20Speaker 00

  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?

• 13:27Dr. Mary Claire Haver?

  Progesterone.

• 13:28Speaker 00

  So that's the receptor on the pituitary that if you sensitize that receptor, you're going to suppress ovulation.

• 13:37Dr. Mary Claire Haver?

  Okay, menopause hormone therapy. How is that different?

• 13:40Speaker 00

  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 bio identical. 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.

• 14:25Dr. Mary Claire Haver?

  No, it's like random estrilin and things I can't pronounce.

• 14:30Speaker 00

  But as I said, you have an estrogen receptor, or there's actually two, an 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 estradiol.

• 14:51Dr. Mary Claire Haver?

  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, this wave are using pretty much estradiol based and then progesterone. 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 BiEst and TriEst. Explain what those are. What's FDA approved, what's not, and what your thoughts are on those?

• 15:34Speaker 00

  I appreciate that question. So BiEST is kind of short for bioestrogen. And what it is, is it is a combination of estradiol and estriol. So estriol is another form of estrogen that is bio-identical. 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. Estriol is gonna 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.

• 16:19Speaker 00

  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 showing that estradiol is not dangerous

• 16:32Dr. Mary Claire Haver?

  Yeah.

• 16:32Speaker 00

  for the breast. So I don't think, you know, estriol is necessarily better in that way. Both of these are gonna be a wash. And then triest is gonna be the same as, you know, the estradiol, estriol. And then you're gonna throw in the estrone, which is the other form of natural estrogen that's made in menopause.

• 16:49Dr. Mary Claire Haver?

  Is estrone pro-inflammatory? I've read that, but I didn't see good data behind it.

• 16:54Speaker 00

  There's not good data for it. And 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.

• 17:09Dr. Mary Claire Haver?

  Now, where is it made? Let's walk our, I think our audience deserves a little bit of an anatomy lesson.

• 17:14Speaker 00

  Yeah.

• 17:14Dr. Mary Claire Haver?

  So I know it becomes, most understand it becomes the dominant estrogen in post-menopause. Because where are these estrogens made? Review that one more time. And, and, and in what kind of levels at what ages? Let's go through after puberty.

• 17:28Speaker 00

  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 adipocell. So those are fat.

• 17:40Dr. Mary Claire Haver?

  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 estradiol are mainly made in the ovary in something called the granulosa cell. If you want to get into my science textbooks.

• 17:53Speaker 00

  What about body identical versus synthetic?

• 17:56Dr. Mary Claire Haver?

  Lots, lots of drama on the internet about that.

• 17:58Speaker 00

  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 estradiol 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 at 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 were doing.

• 18:43Speaker 00

  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.

• 18:56Dr. Mary Claire Haver?

  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, premenstrual dysphoric disorder, et cetera, to stabilize hormones. So some women do better that way. And then we have our menopause, perimenopausal, postmenopausal treatment. And there is some overlap between the two.

• 19:28Speaker 00

  Yes.

• 19:29Dr. Mary Claire Haver?

  But then in general, postmenopausal hormone therapy is going to be estradiol.

• 19:34Speaker 00

  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 estradiol, unless our goal is to help prevent abnormal bleeding or they need a contraceptive method.

• 19:51Dr. Mary Claire Haver?

  Then estrogens are easy. Now we're going to get into, so the umbrella is progestin.

• 19:56Speaker 00

  Yes.

• 19:57Dr. Mary Claire Haver?

  And then under, 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

• 20:16Speaker 00

  So much.

• 20:16Dr. Mary Claire Haver?

  So much, more than I ever knew.

• 20:18Speaker 00

  I know.

• 20:19Dr. Mary Claire Haver?

  But they are essential to keep you from getting into menstrual cancer when you're using estrogens. And they're essential for contraception, which I'm still gonna have to marinate on that for a little while. Talk to me about what the data shows, about what are progestins? Give me your hormones 101.

• 20:35Speaker 00

  Yeah, so I, this is my favorite topic. Because progesterone

• 20:38Dr. Mary Claire Haver?

  Everyone's asking, people are, alright, everyone pause, get out your pencils, hit record, here you go. This is the world's expert, I promise. Alright.

• 20:47Speaker 00

  So progesterone is just the most underappreciated hormone. We talk about estrogen and testosterone all the time, so you just

• 20:54Dr. Mary Claire Haver?

  You will take it out of my cold, dead hands.

• 20:57Speaker 00

  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.

• 21:41Speaker 00

  And there's one progesterone receptor, there's one progesterone molecule. And there are progesterone receptors all over the body.

• 21:47Dr. Mary Claire Haver?

  Just like estrogen?

• 21:48Speaker 00

  Yes.

• 21:49Dr. Mary Claire Haver?

  Wow. So, like where?

• 21:51Speaker 00

  So it is, there's progesterone receptors in the brain, so we

• 21:54Dr. Mary Claire Haver?

  I know that.

• 21:55Speaker 00

  We think about it in terms of, yeah, catarneal 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.

• 22:17Dr. Mary Claire Haver?

  Right, asthma gets worse.

• 22:18Speaker 00

  Yes, asthma gets worse. But progesterone actually can, is beneficial in the lungs. There are progesterone receptors in the gut, and so it helps with, 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. Breast.

• 23:02Speaker 00

  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 progestins 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.

• 23:46Speaker 00

  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 is we micronize it, we turn it into this small molecule that will last longer so that we can get progesterone stimulation in our body.

• 24:27Speaker 00

  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 progestins 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 progestins, 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

• 25:07Speaker 00

  We have like 25 on the market, different progestins. And they work different. One's better for acne, one's better for sex, one's Yeah, because it's not just the mineral Where are they binding? They're binding the androgen receptor as well, and they're affecting the androgen receptor. And the androgen 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 for acne, 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.

• 25:51Speaker 00

  Anything that's good for your skin is bad for your sex life. The other ones we talk about a lot are norahindron and norahindron acetate. So those, the brand name is Agestin for norahindron acetate. Norahindron is actually the mini pill when we talk about the, you know, very low dose progestin only birth control. Well, norahindron metabolizes into ethanol estradiol. This is a little known fact. How? The molecules are actually 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 estradiol, well, then norahindron can be metabolized into ethanol estradiol.

• 26:28Speaker 00

  How did I not know this? This is not common knowledge, but the key, so let's talk about it. Have you heard of add back therapy? So if you gave Lupron and you give add back therapy, what are, what are the add back therapies that you give? It's been a minute. Estradiol. Estradiol and or Agestin. So, okay, okay, yeah. Right? The question is why? So the goal of add back therapy is to mitigate the side effects of something like Lupron that puts you into menopause, hot flashes, bone loss.

• 26:58Dr. Mary Claire Haver?

  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.

• 27:07Speaker 00

  Exactly.

• 27:08Dr. Mary Claire Haver?

  Um, when we could get it approved.

• 27:09Speaker 00

  Yeah.

• 27:10Dr. Mary Claire Haver?

  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.

• 27:17Speaker 00

  Yeah. Well, why would giving a progestin minimize?

• 27:20Dr. Mary Claire Haver?

  No one taught me to ask that question. And I wasn't smart enough to ask it on my own.

• 27:24Speaker 00

  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 midroxiprogesterone acetate. You're, we're all very familiar.

• 27:51Dr. Mary Claire Haver?

  Yes.

• 27:51Speaker 00

  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. Northindron acetate is 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 midroxiprogesterone acetate, that's Depo Provera.

• 28:10Dr. Mary Claire Haver?

  Yeah.

• 28:10Speaker 00

  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.

• 28:29Dr. Mary Claire Haver?

  Mm hmm.

• 28:29Speaker 00

  And midroxiprogesterone 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 WHI really showed in terms of breast cancer, but, but Provera was what they 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 with natural progesterone.

• 29:14Dr. Mary Claire Haver?

  So when I was utilizing oral hormonal contraception, so 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 God, knowing, you know, no one ever sat us down and walked us through the endocrinology 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.

• 29:43Speaker 00

  Yeah.

• 29:44Dr. Mary Claire Haver?

  And we don't know what's going to happen to you. And you could have all these things, and 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.

• 29:54Speaker 00

  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-in 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 progestins just metabolize into leave-in agestrel. So if you're like, oh, I'm going to try a different one. Well, it's just going to turn into leave-in agestrel in the body. And so knowing, you know, why would somebody do well with the Nexplanon, knowing that the type of progestin in the Nexplanon, that's the subdermal implant,

• 30:39Speaker 00

  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 progestins 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.

• 31:01Dr. Mary Claire Haver?

  I was the residents program director until 2018. So it's, you know, 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.

• 31:10Speaker 00

  It's not. I will say that when I was taking my complex family planning boards. So, you know, 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, 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.

• 31:41Dr. Mary Claire Haver?

  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?

• 31:49Speaker 00

  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 Drospeiranone 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.

• 32:21Dr. Mary Claire Haver?

  It became my go-to.

• 32:22Speaker 00

  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 Drospeiranone works better.

• 32:34Dr. Mary Claire Haver?

  If you could correct three myths about progestins, what are three things you would like correct about?

• 32:41Speaker 00

  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.

• 32:56Dr. Mary Claire Haver?

  You said the magic word, testosterone. I know you've co-authored major reviews on testosterone in women, including methodological challenges in studying it. For our listeners, what is the evidence support for testosterone? Today.

• 33:13Speaker 00

  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 potentially satisfying sexual events in mainly postmenopausal women. And then in, 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.

• 33:40Dr. Mary Claire Haver?

  Let's go because the internet's exploding right now.

• 33:43Speaker 00

  It is very, very, very.

• 33:45Dr. Mary Claire Haver?

  All right, let's go organ system by organ system, brain.

• 33:47Speaker 00

  Okay.

• 33:48Dr. Mary Claire Haver?

  Start with cognition.

• 33:49Speaker 00

  Yeah, there are multiple studies looking at testosterone and cognition. And the tricky thing about cognition is how you measure it. So there's lots of different ways.

• 33:57Dr. Mary Claire Haver?

  What Lisa Moscone taught me was forever, the cognition studies were, does she have dementia or not?

• 34:05Speaker 00

  Exactly.

• 34:06Dr. Mary Claire Haver?

  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?

• 34:21Speaker 00

  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. And if your hormone is keeping you from having brain fog, that's actually very evidence based.

• 34:35Dr. Mary Claire Haver?

  So Lisa says, brain fog is, I can't find my keys.

• 34:38Speaker 00

  Yes.

• 34:39Dr. Mary Claire Haver?

  Dementia is, I don't know what my keys are for.

• 34:42Speaker 00

  I, that is a very good way of putting it. So, 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 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, 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?

• 35:25Speaker 00

  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 I, that brain fog went away. I'm not going to tell her that that's not true.

• 35:49Dr. Mary Claire Haver?

  Why not? Because there are people trying to control this narrative on testosterone who are telling women that's not true.

• 35:55Speaker 00

  I think you can say that the studies of a hundred 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 a hundred 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.

• 36:29Dr. Mary Claire Haver?

  How do you counsel your patients then?

• 36:30Speaker 00

  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. You know, and maybe their libido didn't get better, but something else did.

• 36:55Dr. Mary Claire Haver?

  Okay, let's go to mood. Stay in the brain, mood.

• 36:57Speaker 00

  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.

• 37:06Dr. Mary Claire Haver?

  You are the president-elect, President Dr. Tammy Rowan.

• 37:10Speaker 00

  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 PMDD lectures. But the testosterone lecture has been really the funnest one to put together because I know how much is out there on 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.

• 37:42Dr. Mary Claire Haver?

  Okay.

• 37:43Speaker 00

  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.

• 38:03Dr. Mary Claire Haver?

  Right.

• 38:04Speaker 00

  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?

• 38:19Dr. Mary Claire Haver?

  Yes.

• 38:20Speaker 00

  Okay. So in the early 2000s, there 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 WHO. Viagra had six months of safety data, just to whisper that there.

• 38:58Dr. Mary Claire Haver?

  We've covered that ad nauseam on this podcast, but say it again.

• 39:01Speaker 00

  I'll say it again. People died in the Viagra trials, but we did not, we did not, people have died from Viagra.

• 39:08Dr. Mary Claire Haver?

  They did, and they still got fast track approval in six months? There was such an unmet need of erections?

• 39:14Speaker 00

  I will say, as 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.

• 39:55Speaker 00

  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 Biosante was the company. The medication was called Libby Gel. And the phase one and phase two trials were absolutely amazing. Well, in the phase three trials, these were the randomized controlled trials.

• 40:12Dr. Mary Claire Haver?

  Mm hmm.

• 40:12Speaker 00

  They showed that those that took the testosterone gel had four more satisfying sexual events 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.

• 40:43Dr. Mary Claire Haver?

  Okay.

• 40:44Speaker 00

  So that is the power of the placebo effect.

• 40:46Dr. Mary Claire Haver?

  Okay. Giving a woman permission to use a product.

• 40:49Speaker 00

  Yeah.

• 40:50Dr. Mary Claire Haver?

  Turn the key for some of those women.

• 40:52Speaker 00

  Yeah.

• 40:52Dr. Mary Claire Haver?

  Okay. So we don't have an FDA approved product. How do we get it?

• 40:56Speaker 00

  So the way that we get it now is we can use FDA approved products that are approved for men.

• 41:01Dr. Mary Claire Haver?

  I borrow the men's version.

• 41:02Speaker 00

  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 twenties.

• 41:26Dr. Mary Claire Haver?

  So physiologic ranges. We, we, 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 US.

• 41:33Speaker 00

  Got it. So in the US, 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 for, 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

• 42:17Speaker 00

  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 twenties, 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 peri or postmenopausal woman, nanograms per deciliter. That's physiologic.

• 43:02Speaker 00

  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 1/10th to 1/20th, right? That's our target. So you want to be using 1/10th. We always say 1/10th, but the truth is it's really 1/10th to 1/20th. And so I typically will tell people to get a PPD syringe, like a, you know, a small 1

• 43:41Speaker 00

  cc, 1 milliliter syringe, draw up between 0.3 and 0.5 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 growth at 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.

• 44:26Speaker 00

  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 superphysiologic levels mean, because this is something that I think we're seeing all the time.

• 44:36Dr. Mary Claire Haver?

  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 didn't start using testosterone until about three and a half years ago. And thank God, my Ishwish 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, you know?

• 45:07Speaker 00

  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.

• 45:21Dr. Mary Claire Haver?

  Okay.

• 45:22Speaker 00

  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.

• 45:37Dr. Mary Claire Haver?

  I did not know that.

• 45:38Speaker 00

  You want the tubes, you do not want the packets. And so I put all over my prescription, tubes, not packets. And the pharmacist 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.

• 45:53Dr. Mary Claire Haver?

  Okay, that is, I did not know this.

• 45:54Speaker 00

  It's very, yeah, it's a very misunderstood aspect.

• 45:56Dr. Mary Claire Haver?

  I use the pump, 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.

• 46:04Speaker 00

  I don't think compounding is the devil, the way a lot of people do.

• 46:08Dr. Mary Claire Haver?

  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.

• 46:14Speaker 00

  Exactly. So I think, you know, compounding pharmacies are not bad people. I do think that there was-

• 46:19Dr. Mary Claire Haver?

  No, I use them all the time.

• 46:20Speaker 00

  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 a testosterone cream in that sense. So we want a one, I usually will get a 1% cream. And my goal is two to five milligrams a day. So I'll oftentimes start at two 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 five, right? So we just do the kind of simple math. So that's our goal when we're doing the compound.

• 47:01Dr. Mary Claire Haver?

  When I started prescribing testosterone, I did compounded. 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.

• 47:12Speaker 00

  Exactly. It was just very reasonable.

• 47:13Dr. Mary Claire Haver?

  Before I became comfortable doing the FDA approved options.

• 47:16Speaker 00

  Yeah, it's, 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, 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 and 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.

• 47:56Speaker 00

  And we have to then give them spironolactone 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.

• 48:17Dr. Mary Claire Haver?

  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 dosed. But what does that mean?

• 48:38Speaker 00

  So super physiologic means that your level is above that target that we talked about earlier. Right. So what is the 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 is 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 physiologic.

• 49:09Dr. Mary Claire Haver?

  Right. I mean, I've heard as high of 100.

• 49:10Speaker 00

  Yeah, again, this is not.

• 49:11Dr. Mary Claire Haver?

  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.

• 49:26Speaker 00

  Absolutely. 100%.

• 49:28Dr. Mary Claire Haver?

  Like, I 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.

• 49:39Speaker 00

  100%. So, you know, people are familiar with the condition of PCOS.

• 49:42Dr. Mary Claire Haver?

  Yeah, I had 90.

• 49:43Speaker 00

  But exactly.

• 49:44Dr. Mary Claire Haver?

  90 was my testosterone level with PCOS.

• 49:46Speaker 00

  You don't see people with levels above 100 with PCOS.

• 49:48Dr. Mary Claire Haver?

  And I had horrible acne and hair growth everywhere. I didn't want it.

• 49:52Speaker 00

  I'm sorry.

• 49:52Dr. Mary Claire Haver?

  It's okay. We managed it.

• 49:54Speaker 00

  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.

• 50:03Dr. Mary Claire Haver?

  I'm Cajun.

• 50:04Speaker 00

  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 the 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, you know, 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.

• 50:49Speaker 00

  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 super physiologic 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.

• 51:24Dr. Mary Claire Haver?

  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?

• 51:32Speaker 00

  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.

• 51:45Dr. Mary Claire Haver?

  Which is basically the safety data.

• 51:47Speaker 00

  That's the safety data.

• 51:49Dr. Mary Claire Haver?

  That is the safety data is on the transgender population.

• 51:51Speaker 00

  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.

• 52:12Dr. Mary Claire Haver?

  And the cis patients are frustrated because it is FDA approved for the transgender patients, but not for them.

• 52:16Speaker 00

  That is a very fair point. And it should be, you know, it's not, well, I wouldn't say it's FDA approved for the transgender patients. It's covered by insurance.

• 52:24Dr. Mary Claire Haver?

  By insurance.

• 52:25Speaker 00

  And so that is a very, very.

• 52:26Dr. Mary Claire Haver?

  But that is a very good point. Caveat. They are frustrated because they can't get their medication covered.

• 52:31Speaker 00

  And they should be.

• 52:32Dr. Mary Claire Haver?

  By insurance. And it absolutely should be.

• 52:34Speaker 00

  Yeah.

• 52:43Dr. Mary Claire Haver?

  We had talked about the metabolites of estrogen and progestins. Can you cover the breakdown of testosterone in central and peripheral acting?

• 52:52Speaker 00

  So testosterone is actually metabolized in some tissue into estradiol. And so in the ovaries, you see it metabolized into estradiol. 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 dihydrotestosterone. And so DHT is important because, exactly, you're pointing to your face because of acne. So the thing to understand, you know, I keep talking about receptors because I'm a nerd. There is no testosterone receptor. There is no DHT receptor. There is an androgen receptor. And so that is a lock that is then signaled by two keys.

• 53:32Dr. Mary Claire Haver?

  So it's by.

• 53:33Speaker 00

  DHT 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 androgen 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 minoxidil, 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 DHT levels.

• 54:15Dr. Mary Claire Haver?

  How does spironolactone work?

• 54:16Speaker 00

  Great question. So spironolactone 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 spironolactone. And you will also see menstrual cycle effects from spironolactone 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 spironolactone.

• 54:47Dr. Mary Claire Haver?

  Okay. What about local activity of testosterone in the general urinary system?

• 54:51Speaker 00

  So we've learned over the years that the dogma that the genital 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 lactobacilli, right? Anybody who knows anything about the vagina knows lactobacilli.

• 55:24Dr. Mary Claire Haver?

  It's the good bacteria.

• 55:25Speaker 00

  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.

• 55:49Dr. Mary Claire Haver?

  Oh, my God. So for recurrent BV, how are you treating this?

• 55:52Speaker 00

  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 prosterone. And even for premenopausal women, I'll do that. If I'm, if the FDA approved regimens aren't working, I think about what's going on in this microbiome.

• 56:12Dr. Mary Claire Haver?

  Before we pivot, talk to me about the Dutch test, since you are the endocrine goddess.

• 56:19Speaker 00

  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.

• 56:40Dr. Mary Claire Haver?

  Right. And you talked about the metabolites and how they can convert to one another.

• 56:44Speaker 00

  100%.

• 56:44Dr. Mary Claire Haver?

  So what you're excreting doesn't represent what's in your blood.

• 56:48Speaker 00

  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, it's a little different. It's lower, actually. But if you, we could have two patients with the exact same estradiol levels with totally different side effects because of how, what's happening at the level of the receptor. Same is going to be for 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. Asexual 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.

• 57:32Dr. Mary Claire Haver?

  Do you ever check levels?

• 57:34Speaker 00

  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 normal-ish 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, right?

• 57:52Dr. Mary Claire Haver?

  Okay.

• 57:52Speaker 00

  And then if I'm treating them continuously with testosterone, then I'll recheck it 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 estradiol in a pre-menopausal woman. But remember, in pre-menopausal women, our estradiol levels are in the multiple of hundreds, you know, around the time of ovulation.

• 58:25Dr. Mary Claire Haver?

  Talk to me about absorption. We use a lot of transdermal estrogen. I don't use much, I never use transdermal progestins anymore.

• 58:34Speaker 00

  You shouldn't.

• 58:35Dr. Mary Claire Haver?

  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.

• 58:56Speaker 00

  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 oophorectomy. She elected for an oophorectomy because, you know, she really wanted to not have her ovaries and have control. There's a risk, obviously, of giving someone estradiol 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 and head to toe in patches. 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.

• 59:40Speaker 00

  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.

• 1:00:00Dr. Mary Claire Haver?

  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 and brain. And no.

• 1:00:07Speaker 00

  Thank you for the clarification. If you give a dose high enough, not any of the FDA approved products or how we do anything.

• 1:00:14Dr. Mary Claire Haver?

  Like this is very special.

• 1:00:16Speaker 00

  Or fem ring, just to be specific. Exactly. There is one systemic vaginal estradiol 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.

• 1:00:50Dr. Mary Claire Haver?

  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 transdermal patients, do a three month check.

• 1:01:02Speaker 00

  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.

• 1:01:23Dr. Mary Claire Haver?

  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?

• 1:01:33Speaker 00

  Okay, so progesterone intolerance is the fact that progesterone affects a lot of different receptors. 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, that when someone's gonna maybe be predisposed, if there's somebody that was sensitive to their own endogenous, their own natural menstrual cycle.

• 1:02:11Dr. Mary Claire Haver?

  So that should be a red flag.

• 1:02:12Speaker 00

  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 worse symptoms in menopause because progesterone levels fluctuate. They don't get high, they're actually lower as you are in the 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 anyone off, but it happens. And so, 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.

• 1:02:54Dr. Mary Claire Haver?

  And I've seen the paradoxical effect for sleep. And so what do you do for those patients?

• 1:02:58Speaker 00

  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. And it's not algorithmic. So you can't just say if this do that. It's like everybody's individual. You got to take a history, right? And think about what's going to work for them. So I do prefer to start with micronized progesterone 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 devil. They work very well. And so typically, the one I will give, I like northindron acetate, agestin. I like that better than Provera. We've talked about, you know, we just don't use Provera

• 1:03:39Speaker 00

  outside of, you know, get your bleeding to stop, you know, emergently. But it's not, 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 WHI, 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 in 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 Northindron acetate and then I'll also do a lot of Drospirinone these days.

• 1:04:11Dr. Mary Claire Haver?

  Okay.

• 1:04:12Speaker 00

  And so people tolerate it. Northindron acetate looks a little bit more like progesterone.

• 1:04:17Dr. Mary Claire Haver?

  What about CombiPatch?

• 1:04:18Speaker 00

  CombiPatch is a combination of Northindron and estradiol. It's a great method. I actually give a lot of patches.

• 1:04:26Dr. Mary Claire Haver?

  That's how I started.

• 1:04:27Speaker 00

  The combination. And you know, people again are like, oh, everything has to be bio identical. But I'm like, you need to just be able to take it, right? Like if people just want one thing, the CombiPatch is great. It's hard to get covered by insurance and it has, but it's Northindron. Climera Pro is another combination patch that has leave-in agestrel. We haven't talked about that as much, but that's another really good progestin. Both of them are designed to protect the uterus.

• 1:04:49Dr. Mary Claire Haver?

  Okay.

• 1:04:49Speaker 00

  If people can't tolerate those forms, SLYND is a great method.

• 1:04:53Dr. Mary Claire Haver?

  What is SLYND?

• 1:04:54Speaker 00

  Drospirinone only medication. You can also do a leave-in agestrel 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 DOAVY. 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 DOAVY. Then you add in a SERM. 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.

• 1:05:39Speaker 00

  I know you've had Avram Bluming on here who debunked the myths around it.

• 1:05:42Dr. Mary Claire Haver?

  Yeah.

• 1:05:43Speaker 00

  But there are people who are still concerned, but there are people with, you know, high risk biopsies, people with...

• 1:05:47Dr. Mary Claire Haver?

  We use it because women who are survivors, pre-vivors, high risk, have nowhere to go. They end up in our clinic.

• 1:05:54Speaker 00

  Me too.

• 1:05:55Dr. Mary Claire Haver?

  And so I use DOAVY probably 100 times more than anyone else in Texas.

• 1:05:59Speaker 00

  I believe it.

• 1:06:00Dr. Mary Claire Haver?

  Who doesn't practice my kind of medicine.

• 1:06:02Speaker 00

  The other group that I love using DOAVY for, two, two groups. One is the endometriosis patients.

• 1:06:06Dr. Mary Claire Haver?

  Oh, okay.

• 1:06:07Speaker 00

  Because the estrogen is going to stimulate any, you know, endometriosis. So you've got now this SERM that'll block. Now remember, 30% of endometriosis isn't sensitive to progesterone. And so that... Those are endometrial cells.

• 1:06:18Dr. Mary Claire Haver?

  I did not know this.

• 1:06:19Speaker 00

  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 in endometriosis looks very different than natural endometrial tissue, very different receptor morphology. So I like DUVE for those patients. And then the other patients I like DUVE 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.

• 1:06:44Dr. Mary Claire Haver?

  And that's premenstrual dysphoric disorder.

• 1:06:46Speaker 00

  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 DUVE, and I have saved so many women by giving them Lupron plus DUVE for refractory premenstrual dysphoric disorder.

• 1:07:12Dr. Mary Claire Haver?

  Unbelievable.

• 1:07:15Dr. Mary Claire Haver?

  Welcome back to another Midi Paus. 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 Midi 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

• 1:08:00Dr. Mary Claire Haver?

  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.

• 1:08:43Dr. Mary Claire Haver?

  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 in 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. HRT can help address the hormonal root cause of this fat shift.

• 1:09:26Dr. Mary Claire Haver?

  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 Midi approach centers on a holistic combination of solutions. From medications like weight loss medications to lifestyle changes. And a care plan that works for your body and your needs. By doing so, Midi Health is setting a new standard for healthcare. As the nation's fastest growing women's telehealth company, Midi provides accessible, insurance-covered services. Building on its leadership in perimenopause and menopause, Midi fills the critical health gaps women face at every age and life stage.

• 1:10:08Dr. Mary Claire Haver?

  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 joinmidi.com. Join M-I-D-I dot com and connect with one of their clinicians today.

• 1:10:27Dr. Mary Claire Haver?

  I've got a few questions coming from my listeners and on social media. Can I, you ready?

• 1:10:32Speaker 00

  Always.

• 1:10:33Dr. Mary Claire Haver?

  Okay. What do you wish women in their 30s and 40s understood about choosing contraception for pregnancy prevention, cycle control, mood, and sexual function?

• 1:10:41Speaker 00

  So I think what I would, 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, if you are sensitive to your hormonal fluctuations and you want them to go away, you're gonna get that only with birth control. I mean, there's nothing else that does that. No supplements, no. Sorry. If you want to stabilize your hormones, you gotta 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.

• 1:11:26Speaker 00

  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 gonna 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 globulin and decrease testosterone levels in everybody that takes it. Doesn't mean they're all gonna have a sexual side effect. They just will have lower testosterone.

• 1:12:10Speaker 00

  Some of them are anti-androgenic, like throstirinone, right? So that's your Yaz, 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. Levenagestrel 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 the, 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 vulvodynia. 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.

• 1:12:55Speaker 00

  Of 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 estradiol. 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 estradiol. And then a very low dose of testosterone. And then she didn't want to get off that birth control. I always switch them to something that is, you know, equally as effective. Cause you really can do that. She was questioning it and then her physical therapist, you know, cause 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 A miracle.

• 1:13:37Speaker 00

  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.

• 1:14:22Speaker 00

  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, um, why you would do it with the peanut butter. So anyways, 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. Cause then it's not being broken down. Same little tablet.

• 1:14:58Speaker 00

  Same little tablet. You can just take the little tablets, the mic, the Prometria 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. Couple of 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.

• 1:15:43Speaker 00

  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.

• 1:16:02Dr. Mary Claire Haver?

  Why don't I want to have sex anymore? I feel broken.

• 1:16:05Speaker 00

  Oh, I, you know, I'm giving you the easy ones.

• 1:16:10Speaker 00

  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.

• 1:16:22Dr. Mary Claire Haver?

  What percentage of people, like, like walk me through the success of testosterone? What does that really look like?

• 1:16:27Speaker 00

  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.

• 1:16:35Dr. Mary Claire Haver?

  But you're kind of a clinic of last return, you know?

• 1:16:38Speaker 00

  That is fair. That is, that is totally fair. I mean, other people are possibly getting, 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 super physiologic levels, they may see the difference. Now, again, I'm not promoting super physiologic levels.

• 1:16:58Dr. Mary Claire Haver?

  Okay.

• 1:16:58Speaker 00

  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 super physiologic, 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.

• 1:17:37Dr. Mary Claire Haver?

  Yeah.

• 1:17:37Speaker 00

  You know, it's a therapy. It's not a replacement. It's a therapy for symptoms.

• 1:17:41Dr. Mary Claire Haver?

  Sexual desire and pharmacologic management. So there's too much that are FDA approved also. You want to just briefly cover them?

• 1:17:49Speaker 00

  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 norepinephrine. There are two medications that also affect those neurotransmitters. One is called flibanserin. 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 flibanserin studies in about half of people. But those that it works in, it can work very well. So it helps people sleep. It's, they're not too drowsy the next day. They've done next day driving studies where they did even better. It takes about two

• 1:18:34Speaker 00

  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.

• 1:18:42Dr. Mary Claire Haver?

  Wasn't it originally developed to treat depression or something?

• 1:18:44Speaker 00

  It was, yeah. So because it was, it's 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? Viagra. Viagra was originally developed as a blood pressure medication, didn't work as 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. Viagra works on blood vessels, right? It vasodilates, it causes an erection. Flibanserin 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 bremelanotide. 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.

• 1:19:28Speaker 00

  Increase your dopamine, increase your norepinephrine, mainly dopamine. It's as needed. So it's different than these other medications like testosterone or flibanserin that you have to take every day. The biggest side effect from bremelanotide 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 not like flibanserin, which I use all the time.

• 1:19:50Dr. Mary Claire Haver?

  Then you have to three months to figure it out.

• 1:19:51Speaker 00

  To figure it out. With bremelanotide, 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.

• 1:20:28Dr. Mary Claire Haver?

  Right.

• 1:20:28Speaker 00

  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.

• 1:20:40Dr. Mary Claire Haver?

  Excellent. Well, thank you so much for joining us on UnPaused and I think our listeners are going to benefit so much.

• 1:20:46Speaker 00

  Thank you so much for having me. It's been a total pleasure.

• 1:20:50Dr. Mary Claire Haver?

  You can find Dr. Rowan on Instagram and TikTok at Dr. Tammy Rowan. She is also the president-elect of Ishwish, a major resource in sexual health for clinicians, researchers, advocates and consumers, and can be reached at [email protected]. If you're a prospective patient, you can find her at www.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.

• 1:21:35Dr. Mary Claire Haver?

  Dr. Mary Claire and get honest and accurate information on health, fitness, and navigating midlife at thepauselife.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 never miss 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.

• 1:22:19Dr. 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.