Perimenopause

Daniel, Kelly, and Katrine discuss what happens during menopause, why evolutionary biologists think menopause occurs, and our current knowledge of the risks of hormone therapy. See omnystudio.com/listener https://omnystudio.com/listener for privacy information.

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

• 0:00Daniel Whiteson?

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• 0:04Speaker 01

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• 2:58Speaker 05

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• 3:05Kelly Weinersmith?

  Hello, friends! We're talking about perimenopause today, so we'll be digging into the details of the human body. Also, I'm not enjoying perimenopause, so there might be some profanity. Our amazing audio engineer, Matt Kesselman, will bleep it out, but just a heads up in case young kids are around. And finally, a medical disclaimer: I am not a doctor. I mean, yes, I'm Dr. Kelly Weiner-Smith, but as my parents often remind me, I'm not really a doctor. Not the kind of doctor most people think of. Not a medical doctor. Anyway, I hope you enjoy the information we'll talk about today, but if you have any questions about whether or not you're experiencing perimenopause, or if you're interested in

• 3:50Kelly Weinersmith?

  the hormone therapies we talk about today, please contact your OB-GYN. Okay, let's get started.

• 4:05Kelly Weinersmith?

  I come to you today sweating profusely in an air-conditioned room. I've had to turn off the fan that usually blows directly into my face because it messes up my audio, and I'm miserable. I'm low on energy and frankly, kinda grumpy all the time. I haven't been sleeping well, and my period is a guest that arrived a week early and has overstayed her welcome by 10 days and counting. And yes, for those of you with medical knowledge, I've gone in for the cancer screening and it all came back negative, thank goodness. And so, like many generations of women who came before, I ask the timeless question: What the fudge? Why is this happening to me?

• 4:48Kelly Weinersmith?

  What possible evolutionary advantage could this miserable experience confer upon our great species? And what are my options? Because I remember my mother going off hormone therapy when the news came out in 2002 that hormone therapy causes cancer. So I guess I'm just stuck? This is my new normal? So today, we're talking about perimenopause. What it is, what other species have to go through it, and why, from an evolutionary perspective, we think it happens. And we're going to look into updates on the risks associated with hormone therapy because it turns out that the press announcements made in 2002 about the risks of hormone therapy were kind of overblown.

• 5:32Kelly Weinersmith?

  It sounded way worse than it might actually be. And the stigma around hormone therapy remains. Welcome to Daniel and Kelly's, or mostly just Kelly's, perimenopausal universe.

• 5:58Daniel Whiteson?

  Hi, I'm Daniel. I'm a particle physicist and I like to zap things with lasers, but I'm not the only one in my family who has that interest.

• 6:05Kelly Weinersmith?

  Okay, that'll get weird by the end of the show. Hello, I'm Kelly. I study parasites and space and I'm going through perimenopause.

• 6:16Kelly Weinersmith?

  This is my coming out party.

• 6:19Daniel Whiteson?

  So my question for you today, Kelly, is, did you ever have conversations about menopause and perimenopause with older generation of women in your family?

• 6:29Kelly Weinersmith?

  Yeah, that's a great question. I don't remember having a conversation with my mom, for example, certainly not my grandmother's. I do remember that in 2002, there was this big study that we are going to talk about towards the end of the show. The results came out and my mom had been on hormone therapy at the time. And because of cancer risk, she got off it. But then she ended up going back on it again because she felt so miserable without it. She felt willing to take the risk. And so, you know, I think there's a huge quality of life improvement for a certain subset of the population for having these therapies. But no, I did feel, I don't want to throw my mom under the bus. She's amazing. I have a notoriously bad memory. Maybe she told me all of this and

• 7:11Kelly Weinersmith?

  I absolutely forgot it. But I was kind of blindsided by the symptoms when they started showing up.

• 7:17Daniel Whiteson?

  And it's amazing, if that's the case for most women, that basically every woman goes through this unprepared, as if they're like the first person to ever experience this, right? Without the benefit of all this human knowledge and experience.

• 7:29Kelly Weinersmith?

  It's, I mean, I, you know, maybe if you get lucky and your mom is an OB or your dad is an OB-GYN, maybe you're less blindsided by it. But, but most of the women in my social circle, you know, will, will sit around and will be like, you know, I'm forgetting a lot of things lately, or my period's been super weird lately. And, you know, a lot of the time, we'll, we'll be like, could it be perimenopause? I don't know. And none of us feel like we know enough to be able to understand all this weird stuff that's happening to us. But, you know, fortunately, sometimes this podcast gives me an excuse to research a topic for many hours.

• 8:02Daniel Whiteson?

  Exactly. And this is something people should know more about because it might or it will happen to them. And so we decided to dig into it because we got an email with a question from a listener. So why don't we play that audio from our listener?

• 8:17Kelly Weinersmith?

  Hello, this is Kelsey, Kelsey from Vermont, Vermont. This is Kelsey from Vermont. I'm writing because I have begun my menopausal transition. I feel like the only thing I've been told about menopause up to this point is that one day I'll get hot flashes for no reason, and that the main treatment for improving quality of life during the menopause transition causes cancer. How do I know so little when 50% of the population will almost certainly experience this? Please tell me more. Thanks. Also, biology is better than physics.

• 8:56Daniel Whiteson?

  Hmm, I think I recognize that voice. Where have I heard that voice before?

• 9:00Kelly Weinersmith?

  I don't know. It sounds like someone who's very smart, maybe also attractive and athletic. You know, it's hard to tell from just a voice, but I'm just guessing.

• 9:09Daniel Whiteson?

  They have a great voice for radio, though. They should do a podcast or something.

• 9:12Kelly Weinersmith?

  Yeah, yeah, they might also have a face for radio, but, but, but anyway, I'm sure they're wonderful. But, but you know, because of this question, this gave me the excuse to spend more than 10 hours reading books about perimenopause, menopause, hormone therapy. And so thank you very much to Kelsey from Vermont for this question, so that I could call my quote unquote work time, time spent towards understanding what's happening to me a little bit better.

• 9:42Daniel Whiteson?

  And to give us a little bit more biochemical perspective on what's happening, and to advocate for shooting stuff with lasers, we also invited Katrina on the podcast to join us for this conversation.

• 9:52Kelly Weinersmith?

  And also, frankly, we invited her because every time we have a show that she's on, afterwards, a million people are like, oh, that was the greatest show ever. We love Katrina. And we also love Katrina. So we're so excited to have her back.

• 10:04Daniel Whiteson?

  We do. We're big fans of her at the Weitzin Research Institute.

• 10:07Kelly Weinersmith?

  Yeah, yeah, we are.

• 10:08Daniel Whiteson?

  So it's my pleasure to welcome back to the podcast our distinguished guest and the endowed Weitzin Fellow for Outstanding Patience at Home, Katrina Weitzin.

• 10:17Speaker 03

  Wow, thank you for the realistic welcome.

• 10:22Daniel Whiteson?

  I'm just trying to pad your CV. I mean, I figure at this point, like your whites and titles are going to fill up the whole first page.

• 10:28Speaker 03

  I can't wait to put this stuff on my CV. I mean, I don't have a cookie recipe, but you know, I'm aspiring to it.

• 10:34Kelly Weinersmith?

  I found myself wanting to ask what you've been patient about recently, but maybe that's too much family drama, uh, shared publicly.

• 10:43Daniel Whiteson?

  Let's just let people imagine. That'll be so much more interesting than the reality of it.

• 10:47Kelly Weinersmith?

  You know what does require patience, though? Perimenopause.

• 10:52Kelly Weinersmith?

  Do we want to start with, uh, our journeys or should we start with definitions?

• 10:57Speaker 03

  I mean, I feel like it's a societal journey, I guess, more than just a personal one. I think that there, that for a long time, you know, in the way that we would always make sure that girls before they hit 10 or 12 had heard about menstruation. So they didn't think they were going to die when, when that happened. I feel like we haven't done that for women in their 30s who are about to hit perimenopause. So I guess to me, it's not just about any one of us. It's like about a need to educate the whole society about what a big transition this is that, that women go through, you know?

• 11:29Kelly Weinersmith?

  Amen, sister. I've gone to the doctor so many times for like different cancers that I think I have. And they're like, no, no, that's also perimenopause. That does sound weird, though. And I'm like, why didn't anyone tell me about this?

• 11:41Speaker 03

  Well, I'm just glad you had a doctor who knew that because I think that a very common experience is that the doctors don't put that together and they've got about an hour of education to lean on. So it's not like it's their fault either. But I mean, that it's so many disparate systems that are affected that it can actually be really hard to put it together.

• 11:58Daniel Whiteson?

  So this is something that every woman goes through, but doctors are unfamiliar with and aren't educated about? How does that even happen?

• 12:05Kelly Weinersmith?

  To prepare for this chat, I read a bunch of books that were written by women doctors, some of which ended up becoming OBGYNs. And they lamented that there's really not a lot of training about menopause. When you're a doctor, you have to take regular tests to make sure you're up to date on the latest knowledge. And there's not even a lot of menopause related information included there either. And so most of the folks who talk about menopause lament that there's so few specialists who Really understand this thing that happens to so many of us. Yeah.

• 12:34Daniel Whiteson?

  All right. Well, you both just won the White's Medal for Lifetime Achievement in Public Education for Science. So let's dig in. Tell us, what is menopause and what is perimenopause?

• 12:45Kelly Weinersmith?

  So menopause, I think, is the term that most of us have heard, and this is literally a day in your life. It is the day that is exactly one year after your last period. And so on that day, you hit menopause and after that you are post-menopausal. But that journey to your last period can be a real roller coaster ride. And that is called perimenopause. And Katrina, as a person who does more body stuff than I do, feel free to interject if I get any of this wrong. But here's how I understand it. Perimenopause can last for months to years. And what happens essentially is that we are running out of eggs. And so when we're born, we have something like a million eggs.

• 13:28Kelly Weinersmith?

  By the time we're teenagers, we have something like 300,000 eggs. And then every month we lose like a thousand eggs and that varies from person to person. And there's not really good understanding for why we lose so many eggs. I think the going hypothesis is that our body sort of takes out something like a thousand eggs every month, picks the best one and goes with that one. And then the rest of them that weren't up to snuff sort of get reabsorbed and go away.

• 13:54Daniel Whiteson?

  Reabsorbed? So you're just like eating your own potential progeny?

• 14:00Kelly Weinersmith?

  Yeah.

• 14:01Daniel Whiteson?

  Wow.

• 14:02Kelly Weinersmith?

  I think so. Katrina, is that a fair way to categorize it? That's the edge of my knowledge. So it sounds right. Okay. All right. Yeah. And so, so at some point, sometime in your 40s, you start running low on eggs, on your lifetime supply of eggs. And when that happens, your body starts making less estrogen and progesterone. And so those hormones are slowly going down over time. But it's not just like a straight decline. Sometimes they're up, sometimes they're down. It's like a chaotic roller coaster ride that over time trends downwards.

• 14:34Daniel Whiteson?

  Are these two things that are happening at the same time because they have some other cause? Or is one causing the other, like the drop in progesterone and estrogen and the decrease in the number of eggs?

• 14:45Kelly Weinersmith?

  I don't think that's very well understood. And I mean, just to step back a little more, I mean, there is, each person is super individual, different society.

• 14:55Speaker 03

  Societies have different average ages of the start of menopause and different health conditions change when that happens for people.

• 15:02Daniel Whiteson?

  Different societies?

• 15:03Speaker 03

  You know, it's sometimes called ovarian exhaustion. When your ovaries just hit this point where there's not really enough eggs left to keep all the normal hormonal functions going. And so people who have a lot of stress in their lives or have autoimmune conditions or live in a society where there's a lot of stress and the average age of menopause is earlier will have their ovaries become exhausted, which is not a very technical term, but that's the one you read earlier in their lives. And when your ovaries become exhausted, the hormones go on the fritz. And so then instead of having the cycle that we get used to in the menstruating stage of your life, instead the hormones are like going off at crazy times and sometimes having

• 15:45Speaker 03

  very, very low levels, which has huge impact on so many systems in our body. I mean, that's the part that's so crazy. Like you have estrogen receptors in pretty much every cell in your body. So when your estrogen levels go on the fritz, that's where all these different symptoms come in. But most doctors are not familiar with what all those symptoms are. And so that's why there's so much chaos for people.

• 16:09Kelly Weinersmith?

  I have a list.

• 16:10Daniel Whiteson?

  Super naive biology question. You said you have estrogen receptors everywhere in your body. Do you mean you as in one, like all people? Like, do men have estrogen receptors or is it just women have estrogen receptors?

• 16:22Kelly Weinersmith?

  Men have estrogen receptors too, and we have testosterone receptors.

• 16:25Daniel Whiteson?

  Oh.

• 16:26Speaker 03

  Yeah.

• 16:26Daniel Whiteson?

  Amazing.

• 16:27Kelly Weinersmith?

  Yeah, I think we imagine this as a dichotomy where men have testosterone and women have estrogen, but we actually all have both, but just in different concentrations. But I've got my list of symptoms. Okay, so symptoms include hot flushes, night sweats, vaginal dryness, dry skin, irregular periods, insomnia, urinary urgency, breast tenderness, worse, PMS symptoms, anxiety, depression, irritability, joint pain, mouth dryness, excess salivation, fat redistribution, weight gain, hair in places like your upper lips or nipples, changes in sex drive, hair loss or thinning, memory lapses, racing heart and headaches.

• 17:04Daniel Whiteson?

  Wow.

• 17:05Kelly Weinersmith?

  This is what makes it so hard to diagnose is that some, you know, women will have some subset of these symptoms and there's not like, you can't just draw a blood draw and say, oh, your estrogen level is below this amount. So you must be in perimenopause because as we mentioned, the estrogen levels are like up and down and, and so there's no blood test for this. So you just have to sort of generally take into account a bunch of symptoms and then say, you are probably in perimenopause on the journey to menopause, but it's hard to say for sure. Yeah. And things like racing heart get people to the ER thinking that there's like a real emergency. So I know that some of these superstar women who've been writing books about menopause, like Dr. Mary Claire Haver, she now gives workshops for ER doctors

• 17:50Kelly Weinersmith?

  so that they are better prepared when women come in with a racing heart because otherwise they're just told that it's in their head or that they are anxious or something like that, which is so frustrating. I think the number of divorces and like big life changes that have happened to people who didn't understand that this was what was going on is really tragic. And if you look in history and the way women are described, I think a lot of it comes from these symptoms and us not understanding them, you know? And if you look at like when women need their brain to make their career work, like what terrible timing. You're like in your 40s and 50s, you've like got your education and then your brain stops cooperating, you know? And it's just, and nobody understands

• 18:32Kelly Weinersmith?

  it. It's not like something people recognize. And so you're just treated like you're crazy, which is so unfair.

• 18:39Daniel Whiteson?

  I'm curious about why it's so hard to diagnose this. I understand that estrogen has cycles and so you can't just take one time point and be like, you're up or you're down. But in principle, if you could take somebody's estrogen levels four times a day and monitor it over their lifetime, would you see this kind of trend and be able to point to it?

• 18:58Kelly Weinersmith?

  Do you think women usually get that level of care, Daniel?

• 19:02Daniel Whiteson?

  No, I'm just wondering, in principle, like, is this something that is impossible to diagnose or just impractical?

• 19:09Kelly Weinersmith?

  My guess is that it would be mostly impractical. So like, sometimes during your period, when you're going through perimenopause, your estrogen levels will be higher than usual. And so if you monitored for a month, you might say, oh, this person has loads of estrogen. It doesn't look like they're going into perimenopause. But if you looked at it three months later, you might see their estrogen levels tank and you'd be like, whoa, that's definitely something weird going on. And so I think that the problem is you'd have to collect a lot of data over a long period of time to get these trends. And I think probably no one has the time for that. What do you think, Katrina? Does that? Yeah, I think just the tests are expensive, so they're not given with a lot of repeat

• 19:51Kelly Weinersmith?

  time points. I think it's possible that if you, with the right person, the repeat time points might reveal something. But there'll be people who have their normal monthly cycle for several times in a row. But that doesn't mean that the backdrop isn't that they're headed towards this kind of chaos. And so they might have a few months of chaos and then go to the doctor. But then by the time they get there, they have a few months of regularity. I mean, I know women sometimes will just like have their period last for three months and be the heaviest period of their life. Like, that kind of stuff happens to people a lot. And I don't think it would be easy to pick that up in the estrogen levels, although, to be honest, I don't know. Those are not tests that are done frequently enough. But I think all the symptoms together, if you are keeping track, you can start

• 20:32Kelly Weinersmith?

  to piece it together. I mean, to be honest, your list was extremely comprehensive, but I can think of other symptoms that weren't even on the list, like vertigo and tinnitus. Those are really common symptoms. You have estrogen receptors in your ears. So that's a really debilitating symptom that affects a lot of people.

• 20:50Daniel Whiteson?

  Do we understand why you have estrogen receptors in your ears? Like, why should your ears be connected to some monthly hormonal cycle?

• 20:57Kelly Weinersmith?

  I think in general, we don't have great answers for that. But I mean, evolution makes use of what it has, and estrogen is a hormone that it has. And I think it's been co-opted for a lot of different functions, some of which maybe don't make loads of sense when menopause kicks in. Yeah, good question. I don't think the monthly cycle of estrogen is its value to those systems.

• 21:19Speaker 05

  My guess, I think of estrogen as like a lubricant and anti-inflammatory signal. So it's like a health hormone that it's like a robustness hormone that comes in and helps grease the wheels or something like that. That's not a very scientific way to put it, but that if you talk to my OB-GYN colleagues, those are the kind of words that they use when they talk about estrogen.

• 21:42Kelly Weinersmith?

  Let's talk about two things that estrogen does that are particularly important during menopause, and one of them is estrogen's impact on calcium retention. And then let's talk about hot flashes, just because everybody likes to complain about hot flashes who have had to go through them. So estrogen is protective for bones, and so it sends your bones this message that it should be holding on to calcium. And part of why we think it does that is because estrogen tends to be high when you're pregnant. And while you do want to make sure that you're the fetus developing inside of you is getting plenty of calcium and building great bones, you also want to make sure that all of the calcium isn't leached from your bones, because you need it too. And so estrogen tells you to hold on to that stuff. And so

• 22:25Kelly Weinersmith?

  as you get older and your estrogen levels start to tank, your bones are no longer getting the message that they need to keep building themselves up and hold on to their calcium. And this is why, post-menopause, a lot of women have increased risk of fractures. And this can be an increased risk of death eventually. So women, you know, for example, if you break your hip bone, the chance that you die in the year after you break your hip bone is, you know, quite a bit higher than if you had not broken your hip bone in that year.

• 22:51Daniel Whiteson?

  Yeah.

• 22:51Kelly Weinersmith?

  So this is one reason why folks like to go on hormone therapy, because it protects their bones a bit.

• 22:56Speaker 05

  Totally agree. I mean, it's amazing how important the bone health is and just how quickly, if you have a bone break, you lose muscle. It's really hard to recover from that as you get older. It's not just bone, it's muscle too, actually, that we lose without those hormones.

• 23:12Kelly Weinersmith?

  Man, I didn't know the muscle part.

• 23:14Daniel Whiteson?

  All this is making me dying to ask why your body would ever decrease the amount of estrogen, but I know we're going to get to that later. So let's talk about hot flashes first.

• 23:21Kelly Weinersmith?

  Yeah. So another thing that estrogen impacts, and I don't think the reason for this is nearly as clear as the reason for its relationship with bones, but Estrogen levels are one of the cues that your hypothalamus uses to regulate temperature. And so when your estrogen levels start, you know, going wild, your hypothalamus gets the message that like, oh, it's hot in here. And when it thinks it's hot in here, it starts dilating the blood vessels like in your face so that, you know, the blood is passing near your skin so it cools off. You also start sweating and your heart starts racing, but it's not actually hot. And, and I've like, you know, spoken with women who have hot flashes that are worse than mine. And like, once I was chatting with a woman I had just met and she's like, oh, I got excited.

• 24:06Kelly Weinersmith?

  And so now I'm sweating and she was dripping all over the place, like this poor woman. And it was not, we were in an air conditioned room. And apparently these fluctuations in hormone levels are more likely to kick a hot flash off at night, which is why women often wake up in the middle of the night with their sheets just covered in sweat. And this contributes to the lower sleep that women usually get when they're getting hot flashes and might also to some extent, explain the memory loss issues. Cause if you're not sleeping enough, you're not consolidating memories. And the mood issues, because not sleeping just ruins everything, as we all know. Yes. Can I ask you, Katrina, have you had hot flashes? Yeah. So, I mean, it's a little, it is personal because I didn't go through this in my 40s.

• 24:48Kelly Weinersmith?

  I went through this in my 30s and I didn't expect it at all. So it was like, it took me years to figure out what was going on, which is embarrassing in a way. I'm a biologist. You'd think I could figure this out, but I was in my 30s. It was during the pandemic for part of it, actually. So I had no idea that the hot flashes were hot flashes. I didn't have them in like as intense a way that I think other people do, but it was happening like once an hour. I was like zooming from home. I thought that I was reading everything. I thought I had B vitamin deficiency, or I thought I had, I can't remember. I had a long list of things that it could have been, but I was in my 30s. My mom and my sisters went through menopause. I have sisters who are much older. Than me. They went through menopause in their mid 50s, like 55. So I thought I was like 15

• 25:32Kelly Weinersmith?

  or 20 years away from this happening. It wasn't even on my list. So actually, while it was happening, I had no idea that that's what it was. And the doctors I went to did not help me figure that out. I went to OB JYNs, I went to endocrinologists, I went to an ENT because I was having vertigo and tinnitus. I went to like all these different kinds of doctors and it was like a strange time because it was during the pandemic for part of it. So I couldn't just like go in person. But that's part of why I feel like it's so important that people know about this in their 30s because it can, it happens to people at a range of ages. The average age of the start of menopause in the United States is 51 and the average age of the start of perimenopause symptoms is 10 years earlier. So early 40s is when most women will start to

• 26:17Kelly Weinersmith?

  have those symptoms. And I had no idea. I thought of it as this thing that was still 15 years away. But yeah, I did. I mean, it was really, really uncomfortable. It interrupted my sleep. It was kind of lucky for me that part of it was during the pandemic because it was easier to deal with on Zoom than if I had been in person. Yeah. So I mean, there's a lot to say, but I just found it shocking that I had so little knowledge that that was going to happen. And then I got really interested in it because you guys know I'm a microbiome scientist. And so I started reading about how in Japan, people don't have hot flashes as much. And maybe it's because they eat more, more soy products that have estrogen like molecules in them. And maybe it's because their vascular health is better. So what you,

• 26:59Kelly Weinersmith?

  when you were talking about the blood vessels constricting in your face, I mean, it turns out that in societies where people have better vascular health on average, the age of menopause is later and the symptoms associated with it are much smaller. So there are entire swaths of the world where hot flashes are not really a thing. So I was like, man, sign me up. Like, what's they even there? I think it's a little too late for me. I couldn't just move to Japan. The damage is done. But, but man, yeah, I wish I had been born in Japan. Well, I think they do have Some symptoms there too, it's just less. And it's very individual, that's true here too. I have a friend who also went into menopause in her late 30s and it happened to her really fast. And her doctors, she went to a bunch of different specialists.

• 27:43Kelly Weinersmith?

  None of them could figure out what was happening. And she literally thought she was dying because she's like, I just keep feeling worse and worse and worse. And nobody can tell me why. And then finally she found the right doctor who's like, you just went into menopause really early. That's what it was. And I think she was on birth control, so she wasn't having periods anyway. So she wasn't like realizing that her period wasn't coming. And anyway, yes, we all should know a lot more about this. Yeah, actually, that was a big part of why I couldn't figure it out either because I had an IUD. So I didn't, I, once I had the IUD, my period became irregular. So that was like otherwise a really critical piece of information that was just missing. So that's actually kind of an important thing to tell someone in their 30s when they get an IUD. That, you know, this is, it's just, it would have helped me to have that be on my radar.

• 28:27Kelly Weinersmith?

  I wasn't, I just, you don't think of yourself as older than you are. You always think of your, like, you're kind of stuck in the last couple of years in your head. I always feel like I'm not like always looking five years ahead. And it would have helped me to have a doctor do that for me. But in, I mean, in my case, I figured it out by reading.

• 28:44Daniel Whiteson?

  Another benefit of rounding your age up, see.

• 28:47Kelly Weinersmith?

  Oh, my gosh. Daniel welcomed me to the Roundup to 50 Club on my 45th birthday, which was not the favorite thing. Anybody said to me in my life, let me just tell you. I see why you were given an award for patience, Katrina.

• 28:59Daniel Whiteson?

  Yes, exactly.

• 29:02Daniel Whiteson?

  Well earned, well earned. I was wondering if we could dig in a little bit more into the biochemistry. We've been talking about estrogen and how it affects all these systems. And we use this phrase estrogen receptors. And like, what's going on here? I'm the last person to ask for the chemistry details, but like you got one molecule bumping into another molecule. Can you tell us a little bit about what's happening there?

• 29:22Kelly Weinersmith?

  Come on, Daniel, a chemistry question? You gotta be kidding me. All right, I'll do my best. Okay, so there's something like four different kinds of estrogen receptors. And depending on what kind of receptor is bound, the cell will get a different kind of message for what it's supposed to do. So if a certain kind of receptor gets bound, certain genes inside the cell will be told to turn on and start making certain kinds of products. So essentially, when the hormone binds to receptor, the cell gets a message that it's time to do something in particular. And I think that's about as detailed as we need to get.

• 29:59Speaker 03

  You asked another question earlier about why you would ever stop this central system in your body, like why, you know, that doesn't happen to men. Testosterone keeps on kicking for men's whole lives. And I know there's like lots of, especially recently, social media ideas about like what you can do to increase your testosterone, like get yourself in the sun every day and stuff like that. So it's not like it's a total constant. There are some things you can do to impact your testosterone levels, which sometimes go hand in hand with other things we associate with health. But estrogen, for all women, is going to just stop at some point, which is a really different way to live. I mean, it's crazy, right? If that happened to men, think of all the research we would have done to try

• 30:43Speaker 03

  to help men have the end of their life make more sense. Or maybe it's a big part of why we treated women differently because they lose this central feature of health early in their lives, which, you know, has big impact.

• 30:58Kelly Weinersmith?

  And let's get into some of those reasons. Let's take a quick break. And when we come back, we'll talk about why we think menopause even happens at all.

• 31:14Speaker 01

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• 33:16Speaker 02

  Hey, it's Nile Rodgers, host of Before the Moment, a Lincoln original series. I'm driving across the country, meeting some of today's most fascinating artists. We're exploring the stories before the moment that changed everything. This week, I'm joined by Miguel. My small experience with the discrepancy in the business of music made me angry in the best way, and I wanted to, I wanted to finish. So I started really leaning into my theory.

• 33:45Daniel Whiteson?

  Trying to get down to like, what matters now? Somewhere Miguelito felt like he didn't have a place to say how he felt. And music was the place that I went to to say how I felt. Experience before the moment. A Lincoln original series on the iHeart Radio app, YouTube, or wherever you get your podcasts.

• 34:16Kelly Weinersmith?

  Okay, we're back. Before the break, we were talking about how men don't have anything like menopause. But for women, something like a third of our lives on average will be spent in this post-menopausal period. And so why, from an evolutionary perspective, are we spending so much time not being able to have babies when you would suspect that evolution would like us to be able to keep having babies? So do you two want to share what hypotheses you've heard already? Because I feel like some of them are out in the ether and I collected some extra during my reading.

• 34:48Speaker 03

  Oh, cool. Well, I mean, I always like the grandmother hypothesis and how it actually helps to have the grandmother there to help with her daughter's or her children's children, which makes a lot of sense to me. I mean, who doesn't want a grandmother in their corner, you know?

• 35:01Kelly Weinersmith?

  Heck, yeah.

• 35:02Daniel Whiteson?

  Depends on the grandmother, I mean.

• 35:03Kelly Weinersmith?

  Yeah, that's right. I'd like to have my step-grandma in my corner, but I don't know about my biological grandma. Throw in shade. Yeah, so the idea behind the grandmother hypothesis, I think it's a super interesting idea. But when I was reading about it, it kind of breaks down when you look at other animals who go through menopause. So the mammal that goes through menopause that has been the most well-studied are orcas. And so they've looked at orcas and they've seen like, okay, do the grandmothers spend more time with their kids and grandkids, trying to like, help raise them? Do they find more food for them? Do they teach them how to hunt? And the answer is no. Orca grandmas.

• 35:45Daniel Whiteson?

  Are they just playing mahjong? What are they doing?

• 35:47Kelly Weinersmith?

  They do. So they are more likely to be like, helping everybody navigate long distances and stuff. And so it looks like there's some. Evidence that having grandmas around is great because they have all of this like historical knowledge that they can use to help the entire pod. But are they specifically helping grandkids? No, they're not. So it's good to have them around, but not for the reasons we thought. And we've recently got some evidence that chimpanzees might also be going through something like menopause. But the grandmother hypothesis breaks down with chimpanzees too, because chimpanzees don't tend to stay in the same community as their daughters and granddaughters. They're not even around to be helping them out.

• 36:29Kelly Weinersmith?

  And so maybe the grandmother hypothesis works for humans, but it doesn't look like it is a good way of understanding in general why menopause happens. And we think maybe it happens with like an elephant, maybe a giraffe. I think there's a beetle species that has something like menopause.

• 36:44Speaker 03

  Oh, well, the beetle is interesting because to me it's like a mammalian thing. Although then I started thinking about chickens and chickens must stop laying eggs at some point, so they must lose their hormones too.

• 36:55Kelly Weinersmith?

  Yeah.

• 36:56Daniel Whiteson?

  Is it widespread or is it pretty rare?

• 36:59Kelly Weinersmith?

  I think we really don't know.

• 37:00Daniel Whiteson?

  That's crazy.

• 37:01Kelly Weinersmith?

  I know, right? So I mean, the number of animals that we've watched throughout their entire lifetime. And, you know, like if you've got them in a zoo, you might not necessarily be trying to breed them. So you might not be keeping notes on like chimpanzee bee has her period right now. Like, I don't do chimpanzees get periods?

• 37:18Speaker 03

  I think they do. And like, and mice, for example, mice and rats, we are obviously extremely well studied in labs. And we definitely see them going through menopause, although most studies don't go so long because it's expensive to keep the animals going. So a lot of animal studies end when the animals haven't entered menopause. But I've been working on Alzheimer's disease in mice for the last five years and I've actually learned a lot about mouse menopause and mice definitely go through menopause.

• 37:49Kelly Weinersmith?

  Okay.

• 37:49Speaker 03

  Because our studies go long enough to see it.

• 37:51Kelly Weinersmith?

  I think there's a lot more menopause happening in the mammalian world than I had realized, so we're not so alone.

• 37:59Daniel Whiteson?

  Well, that's interesting because if it's widespread, it seems like it must be something fundamental we all have in common, or maybe there's an advantage to it for some reason?

• 38:08Speaker 03

  I mean, it must be that after you've, you know, once you hit a certain point in your life. Your health does start to change. And so just taking on the stress of pregnancy is not something you can do. That's like something you have to be very fit to pull off. So maybe it has to do with that.

• 38:25Kelly Weinersmith?

  And we talked to Venky Ramakrishnan in our aging episode a bit about this. And so anyone who's interested in a little bit more information about why do we age and why do things change as we get older should pop back over to that episode and listen to it because Venky did a great job of explaining it. And I'm not going to do as well if I try to repeat it.

• 38:43Daniel Whiteson?

  All right. So we have this grandmother hypothesis that maybe it's good to have some female members of the community not having children so they can be grandmas. But that doesn't seem to actually pan out. What are the other hypotheses?

• 38:55Kelly Weinersmith?

  So another one that I came across was that maybe eggs just have like an expiration date, like 50 years is as long as you can expect eggs to be able to hold out. But there are elephants and whales that give birth into their 60s. And those are also mammals. So there are other mammals that are still giving birth way after human women have stopped giving birth, which suggests that there's not just like mammalian eggs just can't last 60 years.

• 39:19Daniel Whiteson?

  Ooh, naive biology question again. Do we understand why eggs are only made at the very beginning of life, like very early in the development of the female, whereas like sperm are constantly being regenerated?

• 39:30Kelly Weinersmith?

  I don't think we do.

• 39:33Kelly Weinersmith?

  We'll get back to you, Daniel. And then there was this other idea that I came across that maybe homo species, so not just us, but like, you know, our ancestors and us often didn't live to be 60 or older. And so we're just sort of optimized for a shorter lifespan. And so we just kind of run out of eggs because we were never really expected to live this long anyway. And I know there's a lot of folks who don't like this argument. I think some of them argue that, you know, we don't really know if women were living regularly past their 60s for these other species. We just don't have enough good evidence. And I think some people don't like it for, I guess, cultural reasons or like

• 40:10Daniel Whiteson?

  Isn't this also based on a misunderstanding of the statistics? I mean, it's often said that like, people only lived to the average age of 35 a long time ago. But I thought the reality was that lots of babies died. And then lots of people lived what we would call normal lives and the average of that was 35. Not that nobody lived past 35, which is very different.

• 40:31Kelly Weinersmith?

  Yeah, so that is a great point, but I still think that doesn't change the fact that we we aren't exactly sure how old like our homo ancestors lived. But yes, I think you're right. Humans in general have lived for a pretty long time. When you look at like the average lifespan past five years old or something like if you survive the first five years, you can expect to have a much longer life.

• 40:54Daniel Whiteson?

  But also, that wouldn't really be an explanation. Like if most people died when they were 60, that doesn't suggest your body should like shut down an important central function around 60. Like, OK, let's all get ready to die. You know, as Katrina was saying earlier, estrogen plays an important role in lots and lots of systems. Why would your body ever want to shut it down? Is there some danger to estrogen? Is there some downside to it? Is there? What is the benefit of menopause to the individual?

• 41:20Kelly Weinersmith?

  I don't know that there is much of a benefit to menopause to the individual, but you're right. Like if we all could only expect to live to be 60, why are men still making sperm after 60? Like, doesn't seem worth it.

• 41:31Speaker 03

  Well, it's just a smaller cost for guys to make sperm, though. So it might just be that the trade off of trying to keep pregnancy going as a woman is getting older becomes too costly.

• 41:44Kelly Weinersmith?

  Yeah, that's a good point.

• 41:45Speaker 03

  Both for the baby and the mom. It's not easy to pull that off.

• 41:49Kelly Weinersmith?

  Yeah.

• 41:49Speaker 03

  But it's hard to imagine a selection that would lead to that. Like, I mean, we all know that evolution works through selection, through natural selection. And so it's hard to imagine how that would actually have been selected for.

• 42:03Daniel Whiteson?

  And it seems like there'd be selection pressure against it because women who lose this estrogen suffer all of these things, which makes it harder for them to function normally.

• 42:10Speaker 03

  But those things all occur after the point of selection.

• 42:13Daniel Whiteson?

  Oh, I see. Yeah.

• 42:14Speaker 03

  But then why would they happen at all? I mean, that is a really

• 42:17Daniel Whiteson?

  Interesting question.

• 42:19Kelly Weinersmith?

  Yeah, I think it's a really interesting question. And to, I guess, bottom line this point, we really don't know. I think the grandmother hypothesis is the most popular idea right now, but it doesn't hold with other species. And that's kind of where we are at the moment. And so Daniel asked, is there any benefit to this happening? And I don't know if there's a benefit, but I do know that there's a lot of health risks when you enter menopause. So we've talked about osteoporosis. Estrogen also is important for things like how cholesterol is managed in your body. And so whereas women have better cardiovascular health on average than men before they hit menopause, after menopause, that benefit goes away. And now our cardiovascular risk becomes even with men. And so this is one reason why people are interested in looking at

• 43:04Kelly Weinersmith?

  menopause hormone therapy, which is also known as hormone therapy or hormone replacement therapy. It goes by lots of different names.

• 43:10Daniel Whiteson?

  Well, I'm really curious about why we can't just replace that estrogen, right? Like, we know that women's bodies stop making it. Why don't women just take that estrogen to replace it? Can we basically just out engineer menopause? So let's dig into that after a break.

• 43:34Speaker 03

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• 44:19Speaker 03

  Zepbound is a prescription medicine used with a reduced calorie diet and increased physical activity to help adults with moderate to severe obstructive sleep apnea, OSA, and obesity to improve their OSA. Zepbound is approved as a 2.5, 5, 7.5, 10, 12.5, or 15-milligram injection. Zepbound contains trisepotide and should not be used with other trisepotide-containing products or any GLP-1 receptor agonist medicines. It is not known if Zepbound is safe and effective for use in children. Don't share needles or pens, or reuse needles. Don't take if allergic to it, or if you or someone in your family had medullary thyroid cancer, or if you've had multiple endocrine neoplasia syndrome type 2. Tell your doctor if you get a lump or swelling in your neck. Stop Zepbound and call your doctor if you have severe stomach pain or a serious allergic

• 45:04Speaker 03

  reaction. Severe side effects may include inflamed pancreas or gallbladder problems. Tell your doctor if you experience vision changes before scheduled procedures with anesthesia, if you're nursing, pregnant, plant-to-be, or taking birth control pills. Taking Zepbound with a sulphonal urea or insulin may cause low blood sugar. Side effects include nausea, diarrhea, and vomiting, which can cause dehydration and worsen kidney problems.

• 45:27Speaker 05

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• 45:35Speaker 04

  Hey, it's Niall Rogers, host of Before the Moment, a Lincoln original series. I'm driving across the country, meeting some of today's most fascinating artists. We're exploring the stories before the moment that changed everything. This week, I'm joined by breakout singer-songwriter Alex Warren. I'm like a kid when I play music and I make music, and I'm constantly asking questions. You know, whether it's an instrument I haven't played, or it's a melody that seems foreign. You know this, every night you play a show, and it's the same set, but it's not the same show. At a certain point, your brain kind of goes on autopilot. When I'm in the studio, or if I'm making music, that's where that curiosity kind of comes back, you know? I haven't lost it yet, but I'm also on my sophomore album, so, and you, you obviously

• 46:19Speaker 04

  are an expert here. Experience Before the Moment, a Lincoln original series on the iHeartRadio app, YouTube, or wherever you get your podcasts.

• 46:41Kelly Weinersmith?

  And we're back. And I would like to reiterate a point I made at the very beginning of the show, which is that we are not providing medical advice. And if you are interested in hormone therapy, you should talk to your OB-GYN. And there's lots of great books out there now that you can read about this to prepare for chatting with your OB-GYN.

• 46:57Daniel Whiteson?

  Especially me. I'm definitely not providing medical advice. I know the least about this of anybody.

• 47:03Kelly Weinersmith?

  That's right.

• 47:04Daniel Whiteson?

  Kelly says, that's right. Don't listen to Daniel.

• 47:07Kelly Weinersmith?

  About almost anything, but this in particular.

• 47:11Daniel Whiteson?

  Fair, fair.

• 47:12Kelly Weinersmith?

  No, no.

• 47:12Daniel Whiteson?

  All right.

• 47:13Kelly Weinersmith?

  Unless it's about aliens, in which case, definitely, there's no one better to talk to than Daniel.

• 47:17Daniel Whiteson?

  But there are people out there doing research on this. This is not completely unstudied, right? So what does the research say about taking hormones to reduce the impact of menopause?

• 47:27Kelly Weinersmith?

  Well, the research says lots of different things because most of the research can't be done as a randomized, double-blind trial. So this is the golden standard of how science is done. So you essentially take a group that you're interested in studying, and half of them get the actual treatment, half of them get the placebo, which is like, you know, a shot, but it doesn't actually do the thing. It's like a shot with just saline or something. And then you compare the outcomes for those two groups. But nobody knows what group they're in. That's the golden standard for doing this stuff. But for a lot of reasons, it's often not ethical to withhold a medication from someone who thinks they need it. But there was this one big study where we did do a randomized, double-blind control.

• 48:11Kelly Weinersmith?

  And this is called the Women's Health Initiative. And what they did here was they had planned on tracking women for up to 15 years. And they enrolled tens of thousands of women, and they ended up in one of two different kinds of treatments. So women who still had their uterus got estrogen plus progestin. And so progestin is another hormone that's usually associated with women. Progestin is a synthetic, lab-made version of progesterone. And so Half of women who had their uterus got estrogen plus progestin and half of them got a placebo. But nobody knew what they were getting, including their doctors. And then the women who didn't have a uterus got only estrogen.

• 48:54Kelly Weinersmith?

  And the reason that this happened is because if you have a uterus and you take just estrogen, you have an increased risk of endometrial cancer. So the endometrius is the lining of the uterus. So if you are someone who has had your uterus removed, you don't have to worry about the risk of that cancer. But if you are a woman who still has her uterus and you add progestin, that seems to completely eliminate the risk of getting this cancer. And I think that's because estrogen is telling the lining of your uterus to like, divide, divide, divide, divide, divide at certain times of the month. And progesterone's job is to tell your body, stop dividing, stop dividing, stop dividing. And divide, divide, divide is the sort of thing that cancer does.

• 49:38Kelly Weinersmith?

  And so progestin is sending the stop dividing message. And so that is why you are less likely to get cancer if your hormone replacement therapy treatment also includes progestin. Oh, I see. So they had these two different groups. The study was being done in the best way that science can be done. They were supposed to be followed for, you know, eight and a half to 15 years, depending on what group they were in. But in July of 2002, they shut down the study for the group that was getting estrogen and progestin. And they reported that they shut it down because they had noted an increased risk of breast cancer and cardiovascular issues for this group of women.

• 50:21Kelly Weinersmith?

  They also noted a reduction in colon cancer and a reduction in osteoporosis-related fractures. But they got worried about the breast cancer and the cardiovascular risks and they shut it down. But. What they probably should have done is made the scientific paper with these results available to everybody immediately when they announced it was getting shut down. But instead, what happened was there was a press conference and they announced, we're shutting it down because there's a 25% increase in breast cancer risk.

• 50:52Daniel Whiteson?

  Ooh.

• 50:52Kelly Weinersmith?

  And that seems to be the only thing that the press heard. And so in a bunch of different press outlets, they were announcing, you know, estrogen increases, breast cancer risk by 25%. And the percent of women who were getting hormone therapy dropped overnight. Something like 15 million women had prescriptions for menopausal hormone therapy in the 1990s. And by 2009, 70% fewer insurance claims for hormone therapy were being made.

• 51:20Daniel Whiteson?

  Wow.

• 51:21Kelly Weinersmith?

  So anyway, hormone therapy use dropped a lot. In the United States. In the United States. And worldwide, actually, I think in Canada, it dropped too, when people heard the results of these things. But you're right, my numbers were from the United States. Then they announced that the group that was just getting estrogen also was going to be stopped early because of a slight increase in stroke. They didn't see an increase in breast cancer or heart disease, and they noted a lower fracture rate and lower colon cancer rates. But because of this cardiovascular issue, they shut it down. So there's a lot of problems with this study, and one problem was with the way the results were interpreted and released. So doctors who weren't part of the study didn't get access to the scientific manuscript for a week after.

• 52:04Kelly Weinersmith?

  So they weren't able to answer any questions about why this study got shut down.

• 52:08Daniel Whiteson?

  But in principle, it's not wrong to shut down a study if you do see increased risks for the people in the study, right? That's okay.

• 52:15Kelly Weinersmith?

  That's right. But let's talk about that risk. So for the placebo group, so the group who was not getting hormones, the risk of breast cancer was four out of 1,000 women. For the women who had estrogen and progestin, five out of 1,000 women were getting breast cancer.

• 52:35Daniel Whiteson?

  Is that where the 25% comes from? You go from four to five?

• 52:38Kelly Weinersmith?

  Yes, that's where the 25% comes from. And so that's what we call relative risk. But your absolute risk, your absolute risk of getting breast cancer has only gone up by 0.08%. This one study found this small increased risk, but the way it was reported made people feel like the risk was huge. But again, I'm not a doctor, so.

• 53:00Daniel Whiteson?

  I love how we're on one hand saying, you should talk to your doctor about this. We are also saying, wow, doctors don't seem to know what they're doing or don't seem to be well educated on this topic.

• 53:09Kelly Weinersmith?

  That's a good point. So I read a book called The New Menopause by, you said her name earlier, Katrina.

• 53:15Speaker 03

  Mary Claire Haver.

• 53:17Kelly Weinersmith?

  Yeah. And she noted that there is now training through some medical association where people can pass a test and show that they have been trained on the, you know, cutting edge of our knowledge of menopause. And so you can find these lists of OB-GYNs who have this training online.

• 53:35Speaker 03

  From the Menopause Society, yeah.

• 53:37Kelly Weinersmith?

  Yes, great, thank you. And so you should search out one of these people because you're right.

• 53:41Daniel Whiteson?

  Exactly.

• 53:41Kelly Weinersmith?

  Most doctors don't know, but there are experts. Thank you. That's a good question.

• 53:45Daniel Whiteson?

  Don't ask your dentist about menopause. Go find somebody who knows what they're talking about.

• 53:48Speaker 03

  But there was a really interesting article in the New York Times about two years ago about the history of hormone replacement therapy that actually cited the data from the study that you just talked about. So that was the first time I got to see that data and my jaw dropped just from the numbers you were talking about, that those tiny numbers influenced so many people. And my own doctor had, you know, been very convinced by that study and was unwilling to look when I showed her the numbers. Like, you know, this was not something that they were open to changing their mind about. Now, they'd spent two decades telling thousands of people that hormone replacement therapy was dangerous because of increased breast cancer risk. And those ideas are very solidified in people's minds.

• 54:32Speaker 03

  But I actually have a visiting sabbatical researcher in my lab right now from Taiwan, an OB-GYN. And I asked- Asked her how this study influenced medical practice in Taiwan. And she said that actually, they did not take the data seriously. They saw those numbers and they did not change the recommendations about hormone replacement therapy in Taiwan.

• 54:53Kelly Weinersmith?

  Wow.

• 54:53Speaker 03

  Which I thought was fascinating. So they had him honestly, a more scientific, rigorous look at the data. And I was really glad to see that there are societies where people look at the science and make decisions that are sometimes more rational. I think everyone was doing their best in this situation, but it would, it had a lot of negative impact on people's lives. There was another problem with the study, I think, which is that the age group didn't reflect younger women who were just entering menopause. I think the average age of the women in that study was maybe 60. I don't remember the details, but that was another reason that the risks would be very different compared to what they would be for a younger woman. So from what I understand, the safest thing to do,

• 55:38Speaker 03

  not medical advice, but from what I understand, the safest thing to do is to replace the hormones as you're entering menopause so that you have a more seamless supply of the hormones. And the hormones are given at levels that are much, much lower than you would biologically have access to them. So it's still a trickle compared to what your ovaries would produce. But it's enough to be a little bit protective of joints and bones and so on.

• 56:04Daniel Whiteson?

  I think this also speaks to something else people struggle with understanding like statistically, which is that like inaction and caution is not always safety. Right?

• 56:14Speaker 03

  Yeah.

• 56:15Daniel Whiteson?

  Just because I understand these people like don't want to give cancer to the people in their study. Right? But you know, stopping the treatment doesn't necessarily mean saving people's lives. It's just like, we haven't studied the effect of Tylenol in pregnancy because you can't do studies on pregnant women. It's not ethical. That doesn't mean that if you're pregnant and you have a fever, you shouldn't take Tylenol.

• 56:34Speaker 03

  Right?

• 56:35Daniel Whiteson?

  Like sometimes inaction is more dangerous than action.

• 56:38Speaker 03

  Yeah, like taking Tylenol when you have a fever and you're pregnant is critical. That's

• 56:43Kelly Weinersmith?

  Way safer for your baby, like having a fever while you're pregnant could be quite dangerous. So.

• 56:47Daniel Whiteson?

  Not medical advice.

• 56:48Kelly Weinersmith?

  Not medical advice. Yeah, definitely not medical advice. Talk to your doctor if you're pregnant and you have a fever, but to go back to Katrina's point about the age of the participants. So yeah, the the average age was 63. They were almost certainly postmenopausal. Oh, wow. And now there's pretty good evidence that estrogen is good at preventing problems, but it's not a cure once the problems have kicked in. And so if you start estrogen therapy before you've completely entered menopause or pretty soon after, then this seems it seems to actually help with a lot of things, particularly quality of life, but maybe even things like osteoporosis risk, cardiovascular health, stuff like that. But

• 57:28Kelly Weinersmith?

  if you start the therapy 10 years after menopause has begun, then you suffer increased risks of a lot of things. And so it does seem like there's this critical window where you have to do it. And so this study sort of set itself up for finding failure by looking at women who were beyond the age. And I think at this point, we didn't know that there was an age where it was good to take it and an age beyond which should seem to have more negative impacts. But it's important to keep that in mind when you're thinking about the results of this study, that this is not the typical person who would even be considered for these therapies anymore. And these days, we use a lot of different kinds of estrogens and progesterone. So for example, there's some risk that these hormone therapies can increase clotting and

• 58:12Kelly Weinersmith?

  clotting can be bad for a lot of reasons. If a clot gets stuck in your brain, you can have a stroke. But if you take the hormone therapy on a patch on your arm instead of on a pill, it looks like that reduces the clotting risk. So something about the the hormones needing to go through your liver before they can make it into your blood to do their work increases the risk of clotting. But if you just put it on your arm, it goes right into your bloodstream, it bypasses the liver, and your risk of clotting goes way down. And so there's a lot of different kinds of hormones now, a lot of different ways that we administer it, that makes this Women's Health Initiative study, you know, maybe not really relevant to what we have today and the groups of women that we would be thinking about giving this therapy to.

• 58:53Daniel Whiteson?

  And is there some plan for a new study to sort of complete the task that this earlier study was aiming for?

• 59:00Kelly Weinersmith?

  Not as far as I know. So I read, there's this book called Estrogen Matters, and it's an incredibly critical look at the Women's Health Initiative. And at the end, one of the points they make is that it's sort of unfortunate that we are in this position where this is the only big, random, double-blind control study that has been done on this. And for a variety of reasons, the study design wasn't great. And so we're sort of left without having really great data to make these decisions. And so people get observational data where they can. And, you know, we're coming closer to understanding the risks, but there's still a lot of question marks. And so when, if you have a good doctor, this will be a discussion about the risks and the benefits, and they won't be able to give you a solid answer. You're just going to have to wait for yourself,

• 59:44Kelly Weinersmith?

  what risks you're willing to take relative to the benefits that you want to get.

• 59:48Speaker 03

  Yeah. And I think it's really hard to do these kinds of studies. It's why we can't agree on whether eggs are healthy. I mean, there have been actually quite a few big association-style studies.

• 59:58Daniel Whiteson?

  You mean eating chicken eggs?

• 1:00:00Speaker 03

  I mean, chicken eggs. Yeah, that's ironic for this conversation.

• 1:00:05Kelly Weinersmith?

  It's been a while since we've had a cannibalism joke on the show. Thank you, Katrina.

• 1:00:11Speaker 03

  Wow, not where I was going. But yeah, I just mean, these kinds of studies where it's very individual, but the way that we can, we need data to come from large studies can be really hard, just because we're all so different. Like, my personal favorite study designs for my microbiome studies are actually not randomized control where you have a placebo group and a treatment arm, because people tend to be so different that it doesn't actually work very well to assume that your treatment arm and your placebo arm are at the same point in the start. So I actually prefer longitudinal studies where you use the starting point as the control, and then you like, watch what happens through time to each person as they go through the intervention.

• 1:00:55Daniel Whiteson?

  So just to clarify, instead of comparing one group with another group, you're comparing each person with their past?

• 1:01:02Speaker 03

  Exactly. Yeah. And sometimes household controls can be really valuable because people live in similar Conditions in their households and their microbiomes tend to be very consistent within a household. That would be harder to do for a hormone replacement therapy study because it's not that often that you have women of the same age going through menopause in the same household. But maybe there would be ways to study that. I don't know. Yeah, but I think that, you know, we now have these options and as Kelly said, you can talk to your doctor about the options and think about more than just this tiny risk of breast cancer that was revealed in a study that might not have had a good design.

• 1:01:43Speaker 03

  Because some of the other benefits, you know, can be quite substantial and unrelated to breast cancer.

• 1:01:51Daniel Whiteson?

  Well, speaking of cutting edge research, Katrina, can you tell us about your research which involves lasers?

• 1:01:56Speaker 03

  Whoa, okay, yeah, I guess that was actually the real reason I was invited to this episode, isn't it? It sounds like science fiction. But believe it or not, I have a collaboration with scientists in the Beckman Laser Institute here at the University of California Irvine, where the treatment to help with the genitourinary syndrome of menopause is to use a laser, which I haven't actually seen it with my

• 1:02:26Daniel Whiteson?

  Tell us where you're putting the laser, Katrina.

• 1:02:29Speaker 03

  The laser is being used to treat the vaginal epithelia. And the purpose of this is to improve the vaginal wall thickness and circulation. So a really big symptom of menopause is vaginal dryness, urinary tract infections, and just general discomfort related to vaginal dryness. And so one measure of vaginal health is the thickness of the wall of the vaginal lining. And that can become thinner after you stop producing estrogen.

• 1:03:09Speaker 03

  And so in this study, the treatment is to use a laser, which, you know, is being used in a controlled manner. To release a predetermined dose of lasery goodness.

• 1:03:29Daniel Whiteson?

  You're zapping it.

• 1:03:30Kelly Weinersmith?

  But what does the lasery goodness do? Is it like the the damage that thickens the wall? Or is it not like? Yeah, what's going on there?

• 1:03:39Speaker 03

  Damage sounds like destructive in a way that is maybe too extreme. But yes, it basically is almost like a swelling associated with wound healing, which brings liquid and circulation and in healing to that area. And so what you find after the laser treatment is an increase in circulation and vaginal wall thickness and a decrease in vaginal dryness and in improvement in symptoms. And it's not just for research.

• 1:04:12Daniel Whiteson?

  Well, you know, lasers are physics. So I'm just going to chalk this up to the, you know, the famous physics biology.

• 1:04:17Speaker 03

  Yes, very important connection right there. It does sound like science fiction and it's being done as part of a research study here at the University of California. In fact, we're still recruiting. So women both before and after menopause, perimenopause, postmenopause, premenopause are all invited to enroll in this study. And one of the benefits is that you might have the opportunity to learn about the composition of your vaginal microbiome, which is my contribution to the study. And this is not only done in an experimental way. So in other parts of the world, it's a normal treatment that's offered to menopausal women to use this laser treatment

• 1:05:00Speaker 03

  to improve vaginal dryness and the vaginal wall thickness. The other standard treatment is estrogen cream. So locally applied estrogen cream will also increase vaginal wall thickness and circulation. So these are, we actually are comparing those kinds of treatments in our study. Because when you add estrogen locally like that, it has really positive impact on vaginal health. But I can tell you from the vaginal microbiome perspective that when we got our first. Data set as part of the study back. Normally, we have to do really subtle statistics and it's sometimes hard to kind of tell the difference between the groups in our studies.

• 1:05:42Speaker 03

  But when you look at pre and post menopausal vaginal microbiomes, you see really clear differences. And in a healthy vaginal microbiome, you normally see domination by lactobacillus. Certain, there's a few different strains that can be the dominant ones. They're acid producing, so the vaginal microbiome thrives in a low pH, like high acid environment. And that's really happening in the pre-menopausal women in the study. But for the post-menopausal women, you can see that the lactobacillus become less abundant. And I don't mean to call it unhealthy because actually there's a huge swath of society that live perfectly healthy lives and don't have just one lactobacillus dominating their vaginal microbiome.

• 1:06:27Speaker 03

  So I always take issue when people try to define what health means because there's a lot of ways to be healthy. But to me, anyway, it was just so striking that you could really see a signal in the vaginal microbiome post-menopausal.

• 1:06:38Kelly Weinersmith?

  So that the lasers bring back the lactobacillus?

• 1:06:41Speaker 03

  That's the question. So actually, I don't know the answer to that yet. We're still recruiting. So actually, I hope I, that's, that's kind of what I'm expecting. I'm very curious to see what happens. And I think we'll be able to see differences between what hormone replacement therapy does and what the lasers do. Or maybe they'll look similar. But yeah, that's the goal is to figure that out. So I'll probably need like two years to answer that question, if I'm honest.

• 1:07:04Kelly Weinersmith?

  We'll bring you back on in two years.

• 1:07:08Daniel Whiteson?

  Well, I don't know if this reflects some sort of like genius experimental design, like understanding how photons interact with the biology. Or if it's just like, well, let's just zap it with a laser and see what happens. Which is it?

• 1:07:21Speaker 03

  I think my colleagues would have a more reason. Response that was not just random zapping with lasers.

• 1:07:31Kelly Weinersmith?

  You're being very patient again, Katrina.

• 1:07:34Daniel Whiteson?

  She's got to earn that medal. Yeah.

• 1:07:36Kelly Weinersmith?

  She has earned that medal.

• 1:07:39Kelly Weinersmith?

  Okay, so I learned a lot from this conversation from Katrina. I learned a ton while researching this. There's a lot of books out there that you can read now if you want to learn more about perimenopause. And there's still a ton that we have left to learn. So I hope that we are investing more in women's health. So more women don't end up, you know, going to the doctor and being told, we don't know what's wrong with you when it's menopause. And that should be one of the first things that people expect for women in their 30s, 40s, and 50s. But one thing that really hit home while I was researching this and came across the list of all the symptoms is that middle aged women are totally badass because we are accomplishing great things while dealing with all of this stuff on top

• 1:08:24Kelly Weinersmith?

  of everything else. And, you know, jobs and sometimes kids. And anyway, way to go fellow uterus havers or fellow women out there. I'm proud of us.

• 1:08:34Daniel Whiteson?

  I'm a big fan.

• 1:08:41Kelly Weinersmith?

  Daniel and Kelly's Extraordinary Universe is produced by iHeartRadio. We would love to hear from you.

• 1:08:47Daniel Whiteson?

  We really would. We want to know what questions you have about this extraordinary universe.

• 1:08:53Kelly Weinersmith?

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• 1:08:59Daniel Whiteson?

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• 1:09:06Kelly Weinersmith?

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• 1:09:16Daniel Whiteson?

  Don't be shy. Write to us.

• 1:09:19Daniel Whiteson?

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