Speaker 1: Hello friends.
Speaker 2: We're talking about perimenopause today, so we'll be digging into
Speaker 2: the details of the human body. Also, I'm not enjoying perimenopause,
Speaker 2: so there might be some profanity. Our amazing audio engineer
Speaker 2: Matt Kesselman will bleep it out, but just a heads
Speaker 2: up in case young kids are around. And finally, a
Speaker 2: medical disclaimer. I am not a doctor. I mean, yes,
Speaker 2: I'm doctor Kelly Wienersmith, but as my parents often remind me,
Speaker 2: I'm not really a doctor, not the kind of doctor
Speaker 2: most people think of, not a medical doctor.
Speaker 3: Anyway.
Speaker 2: I hope you enjoy the information we'll talk about today,
Speaker 2: but if you have any questions about whether or not
Speaker 2: your experiencing perimenopause, or if you're interested in the hormone
Speaker 2: therapies we talk about today, please contact your obgyn. Okay,
Speaker 2: let's get started. Come to you today. Sweating profusely in
Speaker 2: an air conditioned room. I've had to turn off the
Speaker 2: fan that usually blows directly into my face because it
Speaker 2: messes up my audio, and I'm miserable. I'm low on
Speaker 2: energy and frankly kind of grumpy all the time. I
Speaker 2: haven't been sleeping well, and my period is a guest
Speaker 2: that arrived a week early and has overstayed her welcome
Speaker 2: by ten days in counting. And yes, for those of
Speaker 2: you with medical knowledge, I've gone in for the cancer
Speaker 2: screening and it all came back negative, thank goodness.
Speaker 1: And so, like many generations of women who came.
Speaker 2: Before, I ask the timeless question, what the fudge?
Speaker 1: Why is this happening to me?
Speaker 2: What possible evolutionary advantage could this miserable experience confer upon
Speaker 2: our great species?
Speaker 1: And what are my options?
Speaker 2: Because I remember my mother going off hormone therapy when
Speaker 2: the news came out in two thousand and two that
Speaker 2: hormone therapy causes cancer. So I guess I'm just stuck.
Speaker 2: This is my new normal. So today we're talking about paramenopause,
Speaker 2: what it is, what other species have to go through it,
Speaker 2: and why from an evolutionary perspective, we think it happens.
Speaker 2: And we're going to look into updates on the risks
Speaker 2: associated with hormone therapy, because it turns out that the
Speaker 2: press announcements made in two thousand and two about the
Speaker 2: risks of hormone therapy were kind of overblown. It sounded
Speaker 2: way worse than it might actually be and the stigma
Speaker 2: around hormone therapy remains Welcome to Daniel and Kelly's, or
Speaker 2: mostly just Kelly's perimenopausal universe.
Speaker 4: Hi, I'm Daniel. I'm a particle physicist and i like
Speaker 4: to zap things with lasers. But I'm not the only
Speaker 4: one in my family who has that interest.
Speaker 2: Okay, that'll get weird by the end of the show.
Speaker 3: Hello, I'm Kelly.
Speaker 2: I study parasites and space and I'm going through paramenopause.
Speaker 1: This is my coming out party.
Speaker 4: So my question for you today, Kelly is did you
Speaker 4: ever have conversations about menopause and paramenopause with older generation
Speaker 4: of women in your family.
Speaker 1: Yeah, that's a great question.
Speaker 2: I don't remember having a conversation with my mom, for example,
Speaker 2: certainly not my grandmother's. I do remember that in two
Speaker 2: thousand and two there was this big study that we
Speaker 2: are going to talk about towards the end of the show.
Speaker 2: The results came out and my mom had been on
Speaker 2: hormone therapy at the time, and because of cancer risk,
Speaker 2: she got off it, but then she ended up going
Speaker 2: back on it again because she.
Speaker 1: Felt so miserable without it.
Speaker 2: She felt willing to take the risk and so, you know,
Speaker 2: I think there's a huge quality of life improvement for
Speaker 2: a certain subset of the population for having these therapies.
Speaker 2: But no, I did feel I don't want to throw
Speaker 2: my mom under the bus. She's amazing. I have a
Speaker 2: notoriously bad memory. Maybe she told me all of this
Speaker 2: and I absolutely forgot it, But I was kind of
Speaker 2: blindsided by the symptoms when they started showing up.
Speaker 4: And it's amazing if that's the case for most women,
Speaker 4: that basically every woman goes through this unprepared, as if
Speaker 4: they're like the first person to ever experience this right
Speaker 4: without the benefit of all this human knowledge and experience.
Speaker 2: It's I mean, I you know, maybe if you get
Speaker 2: lucky and your mom is an OBI or your dad
Speaker 2: is an OBGYN, maybe you're less blindsided by it. But
Speaker 2: most of the women in my social circle, you know,
Speaker 2: we'll sit around and we'll be like, you know, I'm
Speaker 2: forgetting a lot of things lately, or my period has
Speaker 2: been super weird lately, and you know, a lot of
Speaker 2: the time will be like, could it be paramenopause? I
Speaker 2: don't know, And none of us feel like we know
Speaker 2: enough to be able to understand all this weird stuff
Speaker 2: that's happening to us. But you know, fortunately, sometimes this
Speaker 2: podcast gives me an excuse to research a topic for
Speaker 2: many hours exactly.
Speaker 4: And this is something people should know more about it
Speaker 4: because it might or will happen to them. And so
Speaker 4: we decided to dig into it because we got an
Speaker 4: email with a question from a listener. So when we
Speaker 4: play that audio from our.
Speaker 5: Listener, Hello, this is kel c Kelsey from Vermont, Vermont.
Speaker 5: This is Kelsey from Vermont. I'm writing because I've begun
Speaker 5: my menopausal transition. I feel like the only thing I've
Speaker 5: been told about menopause up to this point is that
Speaker 5: one day I'll get hot flashes for no reason, and
Speaker 5: that the main treatment for improving quality of life during
Speaker 5: the menopause transition causes cancer. How do I know so
Speaker 5: little when fifty percent of the population will almost certainly
Speaker 5: experience this. Please tell me more. Thanks. Also, biology is
Speaker 5: better than physics.
Speaker 4: Hm. I think I recognized that voice. Where have I
Speaker 4: heard that voice before?
Speaker 2: It sounds like someone who's very smart, maybe also attractive
Speaker 2: and athletic. You know, it's hard to tell from just
Speaker 2: a voice, but I'm just guessing.
Speaker 4: They have a great voice for radio, though, they should
Speaker 4: do a podcast or something.
Speaker 3: Yeah.
Speaker 2: Yeah, they might also have a face for radio. But anyway,
Speaker 2: I'm sure they're wonderful. But you know, because of this question,
Speaker 2: this gave me the excuse to spend more than ten
Speaker 2: hours reading books about paramenopause menopause hormone therapy. And so
Speaker 2: thank you very much to Kelsey from Vermont for this
Speaker 2: question so that I could call my quote unquote work
Speaker 2: time time spent towards understanding what's happening to me a
Speaker 2: little bit better.
Speaker 4: And to give us a little bit more biochemical perspective
Speaker 4: on what's happening and to advocate for shooting stuff with lasers.
Speaker 4: We also invited Katrina on the podcast to join us
Speaker 4: for this conversation, and.
Speaker 2: Also, frankly, we invited her because every time we have
Speaker 2: a show that she's on, afterwards a million people are like, oh, that.
Speaker 3: Was the greatest show ever.
Speaker 2: We love Katrina and we also love Katrina, so we're
Speaker 2: so excited to have her mad we do.
Speaker 4: We're big fans of at the Whites and Research Institute.
Speaker 1: Yeah, yeah, we are.
Speaker 4: So it's my pleasure to welcome back to the podcast
Speaker 4: our distinguished guest and the endowed whites and fellow for
Speaker 4: outstanding Patients at Home.
Speaker 6: Wow, thank you for the realistic welcome.
Speaker 4: I'm just trying to pad your CV. I mean, I
Speaker 4: figure at this point like your whites and titles are
Speaker 4: going to fill up the whole first page.
Speaker 3: I can't wait to put this stuff on my CV.
Speaker 6: I mean, I don't have a cookie recipe, but you
Speaker 6: know I'm aspiring to it.
Speaker 2: I found myself wanting to ask what you've been patient
Speaker 2: about recently? But maybe that's too much family drama I'd
Speaker 2: shared publicly.
Speaker 4: Let's just let people imagine that'd be so much more
Speaker 4: interesting than the reality of it.
Speaker 2: You know, what does require patients though, paramenopause. Do we
Speaker 2: want to start with our journeys or should we start
Speaker 2: with definitions?
Speaker 6: I mean, I feel like it's a societal journey, I
Speaker 6: guess more than just a personal one.
Speaker 3: I think that for a long time, you know, and
Speaker 3: the way that we would always.
Speaker 6: Make sure that girls before they hit ten or twelve
Speaker 6: had heard about menstruation so they didn't think they were
Speaker 6: going to die when when that happened. I feel like
Speaker 6: we haven't done that for women in their thirties who
Speaker 6: are about to hit paramunopause.
Speaker 3: So I guess to me, it's not just about any
Speaker 3: one of us.
Speaker 6: It's like about a need to educate the whole society
Speaker 6: about what a big transition this is that women go through.
Speaker 1: You know Amen's sister.
Speaker 2: I've gone to the doctor so many times for like
Speaker 2: different cancers that I think I have and they're like, no, no,
Speaker 2: that's also paramenopause. That does sound weird though, And I'm like,
Speaker 2: why didn't anyone tell me about this?
Speaker 6: Well, I'm just glad you had a doctor who knew that,
Speaker 6: because I think that a very common experience is that
Speaker 6: the doctors don't put that together.
Speaker 3: And they've got about an hour of education to lean on.
Speaker 6: So it's not like it's their falls either, But I
Speaker 6: mean that it's so many disparate systems that are affected
Speaker 6: that it.
Speaker 3: Can actually be really hard to put it together.
Speaker 4: So this is something that every woman goes through, but
Speaker 4: doctors are unfamiliar with and aren't educated about how does
Speaker 4: that even happen?
Speaker 2: Prepare for this chat, I read a bunch of books
Speaker 2: that were written by women doctors, some of which ended
Speaker 2: up becoming obgyns, and they lamented that there's really not
Speaker 2: a lot of training about menopause. When you're a doctor,
Speaker 2: you have to take regular tests to make sure you're
Speaker 2: up to date on the latest knowledge. And there's not
Speaker 2: even a lot of menopause related information included there either,
Speaker 2: And so most of the folks who talk about menopause
Speaker 2: lament that there's so few specialists who really understand this
Speaker 2: thing that happens to so many of us.
Speaker 4: Yes, all right, well you both just won the Whites
Speaker 4: and Metal for Lifetime Achievement in Public Education for science.
Speaker 4: So let's dig in. Tell us what is menopause and
Speaker 4: what is perimenopause.
Speaker 2: So menopause, I think, is the term that most of
Speaker 2: us have heard, and this is literally a day in
Speaker 2: your life. It is the day that is exactly one
Speaker 2: year after your last period, and so on that day
Speaker 2: you hit menopause, and after that you are postmenopausal. But
Speaker 2: that journey to your last period can be a real
Speaker 2: roller ride, and that is called perimenopause. And Katrina, as
Speaker 2: a person who does more body stuff than I do,
Speaker 2: feel free to interject if I get any of this wrong.
Speaker 1: But here's how I understand it.
Speaker 2: Perimenopause can last for months to years, and what happens
Speaker 2: essentially is that we are running out of eggs. And
Speaker 2: so when we're born, we have something like a million eggs.
Speaker 2: By the time we're teenagers, we have something like three
Speaker 2: hundred thousand eggs. And then every month we lose like
Speaker 2: a thousand eggs, and that varies from person to person,
Speaker 2: and there's not really good understanding for why we lose
Speaker 2: so many eggs. I think the going hypothesis is that
Speaker 2: our body sort of takes out something like a thousand
Speaker 2: eggs every month, picks the best one and goes with
Speaker 2: that one, and then the rest of them that weren't
Speaker 2: up to snuff sort of get reabsorbed and go away reabsorbed.
Speaker 4: So you're just like eating your own potential progeny.
Speaker 2: Yeah wow, I think so, Katrina. Is that a fair
Speaker 2: way to categorize it.
Speaker 3: That's the edge of my knowledge. So that sounds right, okay,
Speaker 3: all right?
Speaker 5: Yeah.
Speaker 2: And so so at some point sometime in your forties,
Speaker 2: you start running low on eggs on your lifetime supply
Speaker 2: of eggs, and when that happens, your body starts making
Speaker 2: less estrogen and progesterone, and so those hormones are slowly
Speaker 2: going down over time, but it's not just like a
Speaker 2: straight decline. Sometimes they're up, sometimes they're down. It's like
Speaker 2: a chaotic roller coaster ride that over time trends downwards.
Speaker 4: Are these two things that are happening at the same
Speaker 4: time because they have some other cause or it is
Speaker 4: one causing the other, like the drop in progesterone and
Speaker 4: estrogen and the decrease in the number of eggs.
Speaker 3: I don't think that's very well understood.
Speaker 6: And I mean, just to step back a little more,
Speaker 6: I mean, there is each person is super individual. Different
Speaker 6: societies have different average ages of the start of menopause,
Speaker 6: and different health conditions change when that happens for.
Speaker 4: People different societies.
Speaker 3: You know, it's.
Speaker 6: Sometimes called ovarian eggs haustion, when your ovaries just hit
Speaker 6: this point where there's not really enough eggs left to
Speaker 6: keep all the normal hormonal functions going. And so people
Speaker 6: who have a lot of stress in their lives, or
Speaker 6: have autoimmune conditions, or live in a society where there's
Speaker 6: a lot of stress and the average age of menopauses
Speaker 6: earlier will have their ovaries become exhausted, which is not
Speaker 6: a very technical term, but that's the one you read
Speaker 6: earlier in their lives, and when your ovaries become exhausted,
Speaker 6: the hormones go on the fritz, and so then instead
Speaker 6: of having the cycle that we get used to in
Speaker 6: the menstruating stage of your life, instead the hormones are
Speaker 6: like going off at crazy times and sometimes having very
Speaker 6: very low levels, which has huge impact on so many
Speaker 6: systems in our body.
Speaker 3: I mean, that's the part that's so crazy. Like, you have.
Speaker 6: Estrogen receptors in pretty much every cell in your body,
Speaker 6: so when your estrogen levels go on the fritz, that's
Speaker 6: where all these different symptoms come in. But most doctors
Speaker 6: are not familiar with what all those symptoms are, and so.
Speaker 3: That's why there's so much chaos for people.
Speaker 4: I have a list super naive biology question. You said
Speaker 4: you have estrogen receptors everywhere in your body. Do you
Speaker 4: mean you as in one like all people? Like, do
Speaker 4: men have estrogen receptors or is it just women have
Speaker 4: estrogen receptors.
Speaker 2: Men have estrogen receptors too, and we have testosterone receptors.
Speaker 4: Oh yeah, amazing.
Speaker 1: Yeah.
Speaker 2: I think we imagine this as a dichotomy where men
Speaker 2: have testosterone and women have estrogen, but we actually all
Speaker 2: have both, but just in different concentrations. But I've got
Speaker 2: my list of symptoms, Okay. So symptoms include hot flushes,
Speaker 2: night sweats, vaginal dryness, dry skin, irregular periods, insomnia, urinary urgency,
Speaker 2: breast tenderness, worse, PMS symptoms, anxiety, depression, irritability, joint pain,
Speaker 2: mouth dryness, excess salivation, fat redistribution, weight gain, hair in
Speaker 2: places like your upper lips or nipples, changes in sex drive,
Speaker 2: hair loss or thinning, memory lapses, racing heart, and headaches.
Speaker 4: Wow.
Speaker 2: And this is what makes it so hard to diagnose
Speaker 2: is that some you know, women will have some subset
Speaker 2: of these symptoms, and there's not like you can't just
Speaker 2: draw a blood draw and say, oh, your estrogen level
Speaker 2: is below this amount, so you must be in paramedic
Speaker 2: pause because as we mentioned, the estrogen levels are like
Speaker 2: up and down, and so there's no blood test for this.
Speaker 2: So you just have to sort of generally take into
Speaker 2: account a bunch of symptoms and then say you are
Speaker 2: probably in peramenopause on the journey to menopause, but it's
Speaker 2: hard to say for sure.
Speaker 6: Yeah, and things like racing heart get people to the
Speaker 6: er thinking that there's like a real emergency. So I
Speaker 6: know that some of these superstar women who've been writing
Speaker 6: books about menopause, like doctor Mary Claire Haver. She now
Speaker 6: gives workshops for er doctors so that they are better
Speaker 6: prepared when women come in with a racing heart, because
Speaker 6: otherwise they're just told that it's in their head, or
Speaker 6: that they are anxious or something like that, which is
Speaker 6: so frustrating. I think the number of divorces and like
Speaker 6: big life changes that have happened to people who didn't
Speaker 6: understand that this was what was going on is really tragic.
Speaker 6: And if you look in history and the way women
Speaker 6: are described, I think a lot of it comes from
Speaker 6: these symptoms and us not understanding them, you know. And
Speaker 6: if you look at like when women need their brain
Speaker 6: to make their career work, like what terrible timing. You're
Speaker 6: like in your forties and fifties, You've like got your education,
Speaker 6: and then your brain stops cooperating, you know, and it's
Speaker 6: just nobody understands it. It's not like something people recognize,
Speaker 6: and so you're just treated like you're crazy, which is
Speaker 6: so unfair.
Speaker 4: I'm curious about why it's so hard to diagnose this.
Speaker 4: I understand that estrogen has cycles, and so you can't
Speaker 4: just take one time point and be like you're up
Speaker 4: or you're down. But in principle, if you could take
Speaker 4: somebody's esigen levels or times a day and monitor it
Speaker 4: over their lifetime, would you see this kind of trend
Speaker 4: and be able to point to it.
Speaker 1: Do you think women usually get that level of care, Daniel, No, I'm.
Speaker 4: Just wondering in principle, like, is this something that is
Speaker 4: impossible to diagnose or just impractical?
Speaker 2: My guess is that it would be mostly impractical. So
Speaker 2: like sometimes during your period, when you're going through perimenopause,
Speaker 2: your estrogen levels will be higher than usual, and so
Speaker 2: if you monitored for a month, you might say, oh,
Speaker 2: this person has loads of estrogen. It doesn't look like
Speaker 2: they're going into perimenopause. But if you looked at it
Speaker 2: three months later, you might see their estrogen levels tank
Speaker 2: and you'd be like, WHOA, that's definitely something weird going on.
Speaker 2: And so I think that the problem is you'd have
Speaker 2: to collect a lot of data over a long period
Speaker 2: of time to get these trends, and I think probably
Speaker 2: no one has the time for that.
Speaker 1: What do you think Katrina does that?
Speaker 5: Yeah?
Speaker 6: I think just the tests are expensive, so they're not
Speaker 6: given with a lot of repeat time points. I think
Speaker 6: it's possible that if you with the right person, the
Speaker 6: repeat time points might reveal something.
Speaker 3: But there'll be people who have their.
Speaker 6: Normal monthly cycle for several times in a row. But
Speaker 6: that doesn't mean that the backdrop isn't that they're headed
Speaker 6: towards this kind of chaos, and so they might have
Speaker 6: a few months of chaos and then go to the doctor,
Speaker 6: but then by the time they get there, they have
Speaker 6: a few months of regularity. I mean, I know women
Speaker 6: sometimes will just like have their period last for three
Speaker 6: months and be the heaviest period of their life. Like
Speaker 6: that kind of stuff happens to people a lot, and
Speaker 6: I don't think it would be easy to pick that
Speaker 6: up in the estrogen levels. Although to be honest, I
Speaker 6: don't know. Those are not tests that aren't done frequently enough.
Speaker 6: But I think all the symptoms together, if you are
Speaker 6: keeping track, you can start to piece it together. I mean,
Speaker 6: to be honest, your list was extremely comprehensive, but I
Speaker 6: can think of other symptoms that weren't even on the list,
Speaker 6: like vertigo and tinitis. Those are really common symptoms. You
Speaker 6: have estrogen receptors in your ears, so that's a really
Speaker 6: debilitating symptom that affects a lot of people.
Speaker 4: Do we understand why you have estrogen receptors in your ears? Like,
Speaker 4: why should your ears be connected to some monthly hormonal cycle.
Speaker 2: I think in general we don't have great answers for that,
Speaker 2: But I mean, evolution makes use of what it has,
Speaker 2: and estrogen is a hormone that it has, and I
Speaker 2: think it's been co opted for a lot of different functions,
Speaker 2: some of which maybe don't make loads of sense when
Speaker 2: menopause kicks in.
Speaker 3: Yeah, good question.
Speaker 6: I don't think the monthly cycle of estrogen is Its
Speaker 6: value to those systems, is my guess. I think of
Speaker 6: estrogen as like a lubricant and an anti inflammatory signal,
Speaker 6: So it's like a health hormone that is like a
Speaker 6: robustness hormone that comes in and helps grease the wheels or.
Speaker 3: Something like that.
Speaker 6: That's not a very scientific way to put it, but
Speaker 6: that if you talk to my obgy and colleagues, those
Speaker 6: are the kind of words that they use when they
Speaker 6: talk about estrogen.
Speaker 2: Let's talk about two things that estrogen does that are
Speaker 2: particularly important during menopause, and one of them is estrogen's
Speaker 2: impact on calcium retention. And then let's talk about hot flashes,
Speaker 2: just because everybody likes to complain about hot flashes who've
Speaker 2: had to go through them. So estrogen is protective for bones,
Speaker 2: and so it sends your bones this message that it
Speaker 2: should be holding on to calcium. And part of why
Speaker 2: we think it does that is because estrogen tends to
Speaker 2: be high when you're pregnant. And while you do want
Speaker 2: to make sure that your the fetus developing inside of
Speaker 2: you is getting plenty of calcium and building great bones,
Speaker 2: you also want to make sure that all of the
Speaker 2: calcium isn't leached from your bones because you need it too,
Speaker 2: and so estrogen tells you to hold on to that stuff.
Speaker 2: And so as you get older and your estrogen levels
Speaker 2: start to tank, your bones are no longer getting the
Speaker 2: message that they need to keep building themselves up and
Speaker 2: hold onto their calcium. And this is why post menopause,
Speaker 2: a lot of women have increased risk of fractures, and
Speaker 2: this can be an increased risk of death eventually. So women,
Speaker 2: you know, for example, if you break your hip bone,
Speaker 2: the chance that you die in the year after you
Speaker 2: break your hip bone is you know, quite a bit
Speaker 2: higher than if you had not broken your hip bone
Speaker 2: in that year. So this is one reason why folks
Speaker 2: like to go on hormone therapy, because it protects their bones.
Speaker 3: A bit totally agree.
Speaker 6: I mean, it's amazing how important the bone health is
Speaker 6: and just how quickly if you have a bone break
Speaker 6: you lose muscle.
Speaker 3: It's really hard to recover from that as you get older.
Speaker 6: It's not just bone, it's muscle too, actually that we
Speaker 6: lose without those hormones.
Speaker 1: Man, I didn't know the muscle part.
Speaker 4: Oh, this is making me dying to ask why your
Speaker 4: body would ever decrease the amount of estrogen. But I
Speaker 4: know we're going to get to that later. So let's
Speaker 4: talk about hot flashes first.
Speaker 2: Yeah, so another thing that estrogen impacts, and I don't
Speaker 2: think the reason for this is nearly as clear as
Speaker 2: the reason for its relationship with bones. But estrogen levels
Speaker 2: are one of the cues that your hypothalamus uses to
Speaker 2: regulate temperature. And so when your estrogen levels start, you know,
Speaker 2: going wild, your hypothalamus gets the message that like, oh,
Speaker 2: it's hot in here, and when it thinks it's hot
Speaker 2: in here, it starts dilating the blood vessels, like in
Speaker 2: your face so that you know the blood is passing
Speaker 2: near your skin so it cools off. You also start
Speaker 2: sweating and your heart starts racing, but it's not actually hot.
Speaker 2: And I've, like, you know, spoken with women who have
Speaker 2: hot flashes that are worse than mine. And like once
Speaker 2: I was chatting with the woman I had just met
Speaker 2: and she's like, oh, I got excited and so now
Speaker 2: I'm sweating and she was dripping all over the place,
Speaker 2: like this poor woman, And it was not we were
Speaker 2: in an air conditioned room. And apparently these fluctuations and
Speaker 2: hormone levels are more likely to kick a hot flash
Speaker 2: off at night, which is why women often wake up
Speaker 2: in the middle of the night with their sheets just
Speaker 2: covered in sweat. And this contributes to the lower sleep
Speaker 2: that women usually get when they're getting hot flashes, and
Speaker 2: might also, to some extent, explain the memory loss issues,
Speaker 2: because if you're not sleeping enough, you're not consolidating memories.
Speaker 6: And the mood issues because not sleeping just ruins everything,
Speaker 6: as we all know.
Speaker 1: Yes, can I ask you, Katrina, have you had hot flashes? Yeah?
Speaker 6: So, I mean it's a little it is personal because
Speaker 6: I didn't go through this in my forties.
Speaker 3: I went through this in my thirties.
Speaker 6: And I didn't expect it at all, So it was
Speaker 6: like it took me years to figure out what was
Speaker 6: going on, which is embarrassing in a way.
Speaker 3: I'm a biologist.
Speaker 6: You'd think I could figure this out, but I was
Speaker 6: in my thirties. It was during the pandemic for part
Speaker 6: of it, actually, so I had no idea that the
Speaker 6: hot flashes were hot flash. I didn't have them in
Speaker 6: like as intense a way that I think other people do.
Speaker 6: But it was happening like once an hour. I was
Speaker 6: like zooming from home. I thought that I was reading everything.
Speaker 6: I thought I had B vitamin deficiency or I thought
Speaker 6: I had I can't remember. I had a long list
Speaker 6: of things that it could have been, but I was
Speaker 6: in my thirties. My mom and my sisters went through menopause.
Speaker 6: I have sisters who are much older than me. They
Speaker 6: went through menopause in their mid fifties, like fifty five,
Speaker 6: so I thought I was like fifteen or twenty years
Speaker 6: away from this happening.
Speaker 3: It wasn't even on my list.
Speaker 6: So actually, while it was happening, I had no idea
Speaker 6: that that's what it was, and the doctors I went
Speaker 6: to did not help me figure that out. I went
Speaker 6: to Objyn's, I went to endocrinologists, I went to an
Speaker 6: e antigues.
Speaker 3: I was having vertigo in tanitis.
Speaker 6: I went to like all these different kinds of doctors,
Speaker 6: and it was like, oh, strange time because it was
Speaker 6: during the pandemic for part of it, so I couldn't
Speaker 6: just like go in person. But that's part of why
Speaker 6: I feel like it's so important that people know about
Speaker 6: this in their thirties because it can have It happens
Speaker 6: to people at a rain of ages. The average age
Speaker 6: of the start of menopause in the United States is
Speaker 6: fifty one, and the average age of the start of
Speaker 6: perimenopause symptoms is ten years earlier. So early forties is
Speaker 6: when most women will start to have those symptoms. And
Speaker 6: I had no idea. I thought of it as this
Speaker 6: thing that was still fifteen years away, but yeah, I did.
Speaker 6: I mean it was really really uncomfortable. It interrupted my sleep.
Speaker 6: It was kind of lucky for me that part of
Speaker 6: it was during the pandemic because it was easier to
Speaker 6: deal with on zoom than if I had been in person. Yeah, So,
Speaker 6: I mean, there's a lot to say, but I just
Speaker 6: found it shocking that I had so little knowledge that
Speaker 6: that was going to happen. And then I got really
Speaker 6: interested in it, because you guys know, I'm a microbiome scientist,
Speaker 6: and so I started reading about how in Japan people
Speaker 6: don't have hot flashes as much, and maybe it's because
Speaker 6: they eat more soy products that have estrogen like molecules
Speaker 6: in them, and maybe it's because their vascular health is better.
Speaker 6: So when you were talking about the blood vessels constricting
Speaker 6: in your face, I mean, it turns out that in
Speaker 6: societies where people have better vascular health, on average, the
Speaker 6: age of menopauses later and the symptoms associated with it
Speaker 6: are much smaller. So there are entire swats of the
Speaker 6: world where hot flashes are not really a thing.
Speaker 3: So I was like, man, sign me up.
Speaker 2: Like wow, I think it's a little too late for me.
Speaker 2: I couldn't just move to Japan. The damage is done.
Speaker 2: But man, yeah, I wish I had been born in Japan.
Speaker 6: Well, I think they do have some symptoms there too,
Speaker 6: it's just less and it's very individual.
Speaker 3: That's true here too.
Speaker 2: I have a friend who also went into menopause in
Speaker 2: her late thirties, and it happened to her really fast,
Speaker 2: and her doctors. She went to a bunch of different specialists,
Speaker 2: none of them could figure out what was happening. And
Speaker 2: she literally thought she was dying because she's like, I
Speaker 2: just keep feeling worse and worse and worse, and nobody
Speaker 2: can tell me why. And then finally she found the
Speaker 2: right doctor who's like, you just went into menopause really early,
Speaker 2: That's what it was. And I think she was on
Speaker 2: birth control, so she wasn't having periods anyway, so she
Speaker 2: wasn't like realizing that her period wasn't coming and anyway, Yes,
Speaker 2: we all should know a lot more about this.
Speaker 6: Yeah, Actually, that's that was a big part of why
Speaker 6: I couldn't figure it out either because I had an IUD,
Speaker 6: so I didn't Once I had the IUD, my period
Speaker 6: became irregular, So that was like otherwise a really critical.
Speaker 3: Piece of information that was just missing.
Speaker 6: So that's actually kind of an important thing to tell
Speaker 6: someone in their thirties when they get an IUD, that
Speaker 6: you know this is.
Speaker 3: It's just it would have helped me to have that
Speaker 3: be on my radar. I wasn't.
Speaker 6: I just you don't think of yourself as older than
Speaker 6: you are. You always think of your like you're kind
Speaker 6: of stuck in the last couple of years in your head.
Speaker 6: I always feel like I'm not, like always looking five
Speaker 6: years ahead, and it would have helped me to have
Speaker 6: a doctor do that for me.
Speaker 3: But I mean, in my case, I figured it out.
Speaker 4: By reading another benefit of rounding your age upsy.
Speaker 3: Oh my god, Daniel welcomed me to the round up
Speaker 3: to fifty club on my forty fifth birthday, which was
Speaker 3: not the favorite thing anybody said to me in my life.
Speaker 2: Let me just tell you, I see why you were
Speaker 2: given an award for patients Katrina.
Speaker 4: Yes, exactly, well earned, well earned. I was wondering if
Speaker 4: we could dig in a little bit more into the biochemistry.
Speaker 4: We've been talking about esgen and how it affects all
Speaker 4: of these systems, and we use this phrase esgen receptors,
Speaker 4: and like, what's going on here? I'm the last person
Speaker 4: to ask for the chemistry details, but like, you got
Speaker 4: one molecule bumping into another molecule, can you tell us
Speaker 4: a little bit about what's happening there?
Speaker 2: Oh, come on, Daniel, a chemistry question. You've got to
Speaker 2: be kidding me, all right, I'll do my best, Okay.
Speaker 2: So there's something like four different kinds of estrogen receptors,
Speaker 2: and depending on what kind of receptor is bound, the
Speaker 2: cell will get a different kind of message for what
Speaker 2: it's supposed to do. So if a certain kind of
Speaker 2: receptor gets bound, certain genes inside the cell will be
Speaker 2: told to turn on and start making certain kinds of products.
Speaker 2: So essentially, when the hormone binds to receptor, the cell
Speaker 2: gets a message that it's time to do something in particular.
Speaker 2: And I think that's about as detailed as we need
Speaker 2: to get.
Speaker 6: You asked another question earlier about why you would ever
Speaker 6: stop this central system in your body, like why you
Speaker 6: know that doesn't happen to men. Testosterone keeps on kicking
Speaker 6: for men's whole lives. And I know there's like lots of,
Speaker 6: especially recently social media ideas about like what you can
Speaker 6: do to increase your testosterone, like get yourself in the
Speaker 6: sun every day and stuff like that, So it's not
Speaker 6: like it's a total constant. There are some things you
Speaker 6: can do to impact your testosterone levels, which sometimes go
Speaker 6: hand in hand with other things we associate with health.
Speaker 6: But estrogen for all women is going to just stop
Speaker 6: at some point, which is a really different.
Speaker 3: Way to live.
Speaker 6: I mean, it's crazy, right if that happened to men,
Speaker 6: think of all the research we would have done to
Speaker 6: try to help men have the end of their life
Speaker 6: make more sense. Or maybe it's a big part of
Speaker 6: why we treated women differently because they lose this central.
Speaker 3: Feature of health earlier in their lives, which you know
Speaker 3: has big impact.
Speaker 1: And let's get into some of those reasons.
Speaker 2: Let's take a quick break, and when we come back,
Speaker 2: we'll talk about why we think menopause even happens at all.
Speaker 1: Okay, we're back.
Speaker 2: Before the break, we were talking about how men don't
Speaker 2: have anything like menopause, but for women, something like a
Speaker 2: third of our lives on average will be spent in
Speaker 2: this postmenopausal period. And so why, from an evolutionary perspective,
Speaker 2: are we spending so much time not being able to
Speaker 2: have babies when you would suspect that evolution would like
Speaker 2: us to be able to keep having babies. So do
Speaker 2: you two want to share what hypotheses you've heard already
Speaker 2: because I feel like some of them are out in
Speaker 2: the ether and I collected some extra during my reading.
Speaker 6: Oh cool, Well, I mean I always like the grandmother
Speaker 6: hypothesis and how it actually helps to have the grandmother
Speaker 6: there to help with her daughters or her children's children,
Speaker 6: which makes a lot of sense to me.
Speaker 3: I mean, who doesn't want a grandmother in their corner?
Speaker 3: You know?
Speaker 4: Heck, yeah, depends on the grandmother.
Speaker 1: I mean, yeah, that's right.
Speaker 2: I'd like to have my step grandma in my corner,
Speaker 2: but I don't know about my biological grandma throw in shade.
Speaker 1: Yeah.
Speaker 2: So, so the idea behind the grandmother hypothesis, I think
Speaker 2: it's a super interesting idea, But when I was reading
Speaker 2: about it, it kind of breaks down when you look
Speaker 2: at other animals who go through menopause. So the mammal
Speaker 2: that goes through menopause that has been the most well
Speaker 2: studied are orcas.
Speaker 3: Huh.
Speaker 2: And so they've looked at orcas and they've seen, like, Okay,
Speaker 2: do the grandmothers spend more time with their kids and
Speaker 2: grandkids trying to like help raise them.
Speaker 1: Do they find more food for them? Do they teach
Speaker 1: them how to hunt? And the answer is no, orca grandmas.
Speaker 4: Are they just playing it?
Speaker 1: What they do?
Speaker 2: So they are more likely to be like helping everybody
Speaker 2: navigate long distances and stuff, and so it looks like
Speaker 2: there's some evidence that having grand around is great because
Speaker 2: they have all of this historical knowledge that they can
Speaker 2: use to help the entire pod. But are they specifically
Speaker 2: helping grandkids. No, they're not, So it's good to have
Speaker 2: them around, but not for the reasons we thought. And
Speaker 2: we've recently got some evidence that chimpanzees might also be
Speaker 2: going through something like menopause. But the grandmother hypothesis breaks
Speaker 2: down with chimpanzees too, because chimpanzees don't tend to stay
Speaker 2: in the same community as their daughters and granddaughters. They're
Speaker 2: not even around to be helping them out. And so
Speaker 2: maybe the grandmother hypothesis works for humans, but it doesn't
Speaker 2: look like it is a good way of understanding in
Speaker 2: general why menopause happens. And we think maybe it happens
Speaker 2: with like an elephant, maybe a giraffe. I think there's
Speaker 2: a beetle species that has something like menopause.
Speaker 6: Oh, well, the beetle is interesting because to me, it's
Speaker 6: like a mammalian thing. Although then I started thinking about chickens,
Speaker 6: and chickens must stop laying eggs at some point, so
Speaker 6: they must lose their hormones too.
Speaker 4: Yeah, is it widespread or is it pretty rare?
Speaker 1: I think we really don't know.
Speaker 2: That's crazy, I know, right, So I mean the number
Speaker 2: of animals that we've watched throughout their entire lifetime, and
Speaker 2: you know, like if you've got them in a zoo,
Speaker 2: you might not necessarily be trying to breed them, so
Speaker 2: you might not be keeping notes on like chimpanzee B
Speaker 2: has her period right now, Like I don't do chimpanzees
Speaker 2: get periods.
Speaker 6: I think they do, and like and mice, for example,
Speaker 6: mice and rats, we are obviously extremely well studied in labs,
Speaker 6: and we definitely see them going through menopause, although most
Speaker 6: studies don't go so long because it's expensive to keep
Speaker 6: the animals going, so a lot of animal studies and
Speaker 6: when the animals.
Speaker 3: Haven't entered menopause.
Speaker 6: But I've been working on Alzheimer's disease in mice for
Speaker 6: the last five years and I've actually learned a lot
Speaker 6: about mouse menopause and mice definitely go through menopause, Okay.
Speaker 3: Because our studies go long enough to see it.
Speaker 2: I think there's a lot more menopause happening in the
Speaker 2: mammalian world. Than I had realized, So we're not so alone.
Speaker 4: Well that's interesting because if it's widespread, it seems like
Speaker 4: it must be something fundamental we all have in common,
Speaker 4: or maybe there's an advantage to it for some reason.
Speaker 6: I mean, it must be that after you, you know,
Speaker 6: once you hit a certain point in your life, your
Speaker 6: health does start to change, and so just taking on
Speaker 6: the stress of pregnancy is not something you can do.
Speaker 3: That's like something you have to be very fit to
Speaker 3: pull off. So maybe it has to do with that.
Speaker 2: And we talked to Venki Rama Krishnan and our Aging
Speaker 2: episode a bit about this, and so anyone who's interested
Speaker 2: in a little bit more information about why do we
Speaker 2: age and why do things change as we get older
Speaker 2: should pop back over to that episode and listen to it,
Speaker 2: because Venk did a great job of explaining it, and
Speaker 2: I'm not going to do as well if I try
Speaker 2: to repeat it.
Speaker 4: All Right, So we have this grandmother hypothesis that maybe
Speaker 4: it's good to have some female members of the community
Speaker 4: not having children so they can be grandmas, But that
Speaker 4: doesn't seem to actually pan out.
Speaker 2: What are the other hypotheses, So another one that it
Speaker 2: came across was that maybe eggs just have like an
Speaker 2: expiration date, like fifty years is as long as you
Speaker 2: can expect eggs to be able to hold out. But
Speaker 2: there are elephants and whales that give birth into their sixties,
Speaker 2: and those are also mammals, So there are other mammals
Speaker 2: that are still giving birth way after human women have
Speaker 2: stopped giving birth, which suggests that there's not just like
Speaker 2: mammalian eggs just can't last sixty years.
Speaker 4: Ooh, now you've biologic question again. Do we understand why
Speaker 4: eggs are only made at the very beginning of life,
Speaker 4: like very early in the development of the female, whereas
Speaker 4: like sperm are constantly being regenerated.
Speaker 5: I don't think we do.
Speaker 1: We'll get back to you, Daniel.
Speaker 2: And then there was this other idea that I came
Speaker 2: across that maybe Homo species, so not just us, but
Speaker 2: like you know, our ancestors and us often didn't live
Speaker 2: to be sixty or older, and so we're just sort
Speaker 2: of optimized for a shorter life span, and so we
Speaker 2: just kind of run out of eggs because we were
Speaker 2: never really expected to live this long anyway. And I
Speaker 2: know there's a lot of folks who don't like this argument.
Speaker 2: I think some of them argue that, you know, we
Speaker 2: don't really know if women were living regularly past.
Speaker 1: Their sixties for these other species.
Speaker 2: We just don't have enough good evidence, and I think
Speaker 2: some people don't like it for I guess cultural reasons or.
Speaker 4: Like business, also based on a misunderstanding of the statistics.
Speaker 4: I mean, it's often said that like people only lived
Speaker 4: to average age of thirty five a long time ago,
Speaker 4: But I thought the reality was that lots of babies
Speaker 4: died and then lots of people lived what we would
Speaker 4: call normal lives in the average of that was thirty five,
Speaker 4: not that nobody lived past thirty five, which is very different.
Speaker 2: Yeah, so that is a great point, but I still
Speaker 2: think that doesn't change the fact that we aren't exactly
Speaker 2: sure how old like our homo ancestors lived. But yes,
Speaker 2: I think you're right, humans in general have lived for
Speaker 2: a pretty long time. When you look at like the
Speaker 2: average lifespan past five years old or something like, if
Speaker 2: you survive the first five years, you can expect to
Speaker 2: have a much longer life.
Speaker 4: But also that wouldn't really be an explanation if most
Speaker 4: people died when they were sixty. That doesn't suggest your
Speaker 4: body should like shut down an important central function around sixty, Like, okay,
Speaker 4: let's all get ready to die. You know, as Katina
Speaker 4: was saying earlier, estrogen plays an important role in lots
Speaker 4: and lots of systems. Why would your body ever want
Speaker 4: to shut it down? Is there some danger to estrogen?
Speaker 4: Is there some downside to it? What is the benefit
Speaker 4: of menopause to the individual?
Speaker 2: I don't know that there is much of a benefit
Speaker 2: to menopause to the individual, but you're right, Like, if
Speaker 2: we all could only expect to live to be sixty,
Speaker 2: why are men still making sperm after sixty?
Speaker 1: Like, doesn't seem worth it.
Speaker 6: Well, it's just a smaller cost for guys to make
Speaker 6: sperm though, So it might just be that the trade
Speaker 6: off of trying to keep pregnancy going as a woman
Speaker 6: is getting older becomes too costly.
Speaker 1: Yeah, that's a good point.
Speaker 3: Both for the baby and the mom. It's not easy
Speaker 3: to pull that off.
Speaker 6: Yeah, but it's hard to imagine a selection that would
Speaker 6: lead to that, Like, I mean, we all know that
Speaker 6: evolution works through selection, through natural selection, and so it's
Speaker 6: hard to imagine how that would actually have been selected for.
Speaker 4: And it seems like there'd be selection pressure against it
Speaker 4: because women who lose this estrogen suffer all these things,
Speaker 4: which makes it harder for them to function normally.
Speaker 6: But those things all occur after the point of selection. Oh,
Speaker 6: I see, yeah, but then why would they happen at all?
Speaker 3: I mean that is a really interesting question.
Speaker 2: Yeah, I think it's a really interesting question. And to
Speaker 2: I guess, bottom line this point, we really don't know.
Speaker 2: I think the grandmother hypothesis is the most popular idea
Speaker 2: right now, but it doesn't hold with other species. And
Speaker 2: that's kind of where we are at the moment. And
Speaker 2: so Daniel asked, is there any benefit to this happening?
Speaker 2: And I don't know if there's a benefit, but I
Speaker 2: do know that there's a lot of health risks when
Speaker 2: you enter menopause. So we've talked about osteoporosis. Estrogen also
Speaker 2: is important for things like how cholesterol is managed in
Speaker 2: your body. And so whereas women have better cardiovascular health
Speaker 2: on average than men before they hit menopause, after menopase pause,
Speaker 2: that benefit goes away, and now our cardiovascular risk becomes
Speaker 2: even with men. And so this is one reason why
Speaker 2: people are interested in looking at menopause hormone therapy, which
Speaker 2: is also known as hormone therapy or hormone replacement therapy,
Speaker 2: it goes by lots of different names.
Speaker 4: Well, I'm really curious about why we can't just replace
Speaker 4: that estrogen, right, Like, we know that women's bodies stop
Speaker 4: making it, Why don't women just take that estrogen to
Speaker 4: replace it? Can we basically just out engineer menopause? So
Speaker 4: let's dig into that after a break.
Speaker 2: And we're back, And I would like to reiterate a
Speaker 2: point I made at the very beginning of the show,
Speaker 2: which is that we are not providing medical advice, and
Speaker 2: if you are interested in hormone therapy, you should talk
Speaker 2: to your obgyn. And there's lots of great books out
Speaker 2: there now that you can read about this to prepare
Speaker 2: for chatting with your obgyn.
Speaker 4: Especially me. I'm definitely not providing medical advice. I know
Speaker 4: the least about this of anybody.
Speaker 1: That's right.
Speaker 4: Kelly says, that's right. Don't listen to.
Speaker 2: Daniel about almost anything but this in particular.
Speaker 4: Fair, fair, no.
Speaker 2: Nor unless it's about aliens, in which case definitely there's
Speaker 2: no one better to talk to than Daniel.
Speaker 4: But there are people out there doing research on this.
Speaker 4: This is not completely unstudied. Right, So what does the
Speaker 4: research say about taking hormones to reduce the impact of menopause.
Speaker 2: Well, the research says lots of different things because most
Speaker 2: of the research can't be done as a randomized, double
Speaker 2: blind trial. So this is the golden standard of how
Speaker 2: science is done. So you essentially take a group that
Speaker 2: you're interested in studying, and half of them get the
Speaker 2: actual treatment, half of them get the placebo, which is like,
Speaker 2: you know, a shot, but it doesn't actually do the thing.
Speaker 2: It's like a shot with just saline or something. And
Speaker 2: then you compare the outcomes for those two groups, but
Speaker 2: nobody knows what group they're in. That's the golden standard
Speaker 2: for doing this stuff. But for a lot of reasons,
Speaker 2: it's often not ethical to, you know, withhold a medication
Speaker 2: from someone who thinks they need it. But there was
Speaker 2: this one big study where we did do a randomized
Speaker 2: double blind control and this is called the Women's Health Initiative.
Speaker 2: And what they did here was they had planned on
Speaker 2: tracking women for up to fifteen years and they enrolled
Speaker 2: tens of thousands of women and they ended up in
Speaker 2: one of two different kinds of treatments. So women who
Speaker 2: still had their uterus got estrogen plus progestin, and so
Speaker 2: progestin is another hormone that's usually associated with women. Progestine
Speaker 2: is a synthetic lab made version of progesterone, And so
Speaker 2: half of women who had their uterus got estrogen plus
Speaker 2: progestine and half of them got a placebo, but nobody
Speaker 2: knew what they were getting, including their doctors, and then
Speaker 2: the women who didn't have a uterus got only estrogen.
Speaker 2: And the reason that this happened is because if you
Speaker 2: have a uterus and you take just estrogen, you have
Speaker 2: an increased risk of endometrial cancer. So the endometrius is
Speaker 2: the lining of the uterus. So if you are someone
Speaker 2: who has had your uterus removed, you don't have to
Speaker 2: worry about the risk of that cancer. But if you
Speaker 2: are women who still has her uterus and you add progestin,
Speaker 2: that seems to completely eliminate the risk of getting this cancer.
Speaker 2: And I think that's because estrogen is telling the lining
Speaker 2: of your uterus to like divide, divide, divide, divide, divide
Speaker 2: at certain times of the month, and progesterone's job is
Speaker 2: to tell your body stop dividing, stop dividing, Stop dividing
Speaker 2: and divide, divide, divide is the sort of thing that
Speaker 2: cancer does, and so progestine is sending the stop dividing message.
Speaker 2: And so that is why you are less likely to
Speaker 2: get cancer if your hormone replacement therapy treatment also includes progestine.
Speaker 4: Oh I see.
Speaker 2: So they had these two different groups. The study was
Speaker 2: being done, and the best way that science can be done,
Speaker 2: they were supposed to be followed for you know, eight
Speaker 2: and a half to fifteen years, depending on what group
Speaker 2: they were in. But in July of two thousand and two,
Speaker 2: they shut down the study for the group that was
Speaker 2: getting estrogen and progestine, and they reported that they shut
Speaker 2: it down because they had noted an increased risk of
Speaker 2: breast cancer and cardiovascular issues for this group of women.
Speaker 2: They also noted a reduction in colon cancer and a
Speaker 2: reduction in osteoporosis related fractures. But they got worried about
Speaker 2: the breast cancer and the cardiovascular risks and they shut
Speaker 2: it down. But what they probably should have done is
Speaker 2: made the scientific paper with these results available to everybody
Speaker 2: immediately when they announced it was getting shut down. But
Speaker 2: instead what happened was there was a press conference and
Speaker 2: they announced were shutting it down because there's a twenty
Speaker 2: five percent increase in breast cancer risk, and that seems
Speaker 2: to be the only thing that the press heard, and
Speaker 2: so in a bunch of different press outlets they were announcing,
Speaker 2: you know, estrogen increases breast cancer risk by twenty five percent,
Speaker 2: and the percent of women who were getting hormone therapy
Speaker 2: dropped overnight. Something like fifteen million women had prescriptions from
Speaker 2: menopausal hormone therapy in the nineteen nineties, and by two
Speaker 2: thousand and nine, seventy percent fewer insurance claims for hormone
Speaker 2: therapy were being made. So anyway, hormone therapy use dropped
Speaker 2: a lot in the United States, in the United States
Speaker 2: and worldwide. Actually I think in Canada dropped too when
Speaker 2: people heard the results of these things, But you're right,
Speaker 2: my numbers were from the United States. Then they announced
Speaker 2: that the group that was just getting estrogen also was
Speaker 2: going to be stopped early because of a slight increase
Speaker 2: in stroke. They didn't see an increase in breast cancer
Speaker 2: or heart disease, and they noted a lower fracture rate
Speaker 2: and lower colon cancer rates, but because of this cardiovascular issue,
Speaker 2: they shut it down. So there's a lot of problems
Speaker 2: with this study, and one problem was with the way
Speaker 2: the results were interpreted and released, So doctors who weren't
Speaker 2: part of the study didn't get access to the scientific
Speaker 2: manuscript for a week after, so they weren't able to
Speaker 2: answer any questions about why this study got shut down.
Speaker 4: But in principle, it's not wrong to shut down a
Speaker 4: study if you do see increased risks for the people
Speaker 4: in the study, right, that's.
Speaker 2: Okay, that's right, But let's talk about that risk. So
Speaker 2: for the placebo group, so the group who was not
Speaker 2: getting hormones, the risk of breast cancer was four out
Speaker 2: of one thousand women. For the women who had estrogen
Speaker 2: and progestin, five out of one thousand women were getting
Speaker 2: breast cancer.
Speaker 4: Is that where the twenty five percent comes from? You
Speaker 4: go from four to five.
Speaker 2: Yes, that's where the twenty five percent comes from. And
Speaker 2: so that's what we call relative risk. But your absolute risk,
Speaker 2: your absolute risk of getting breast cancer, has only gone
Speaker 2: up by zero point zero eight percent. This one study
Speaker 2: found this small increased risk, but the way it was
Speaker 2: reported made people feel like the risk was huge.
Speaker 1: But again, I'm not a doctor.
Speaker 4: So I love how we're on one hand saying you
Speaker 4: should talk to your doctor about this, we are also saying, wow,
Speaker 4: doctors don't seem to know what they're doing or don't
Speaker 4: seem to be well educated on this topic.
Speaker 1: That's a good point.
Speaker 2: So I read a book called The New Menopause by
Speaker 2: you said her name earlier, Katrina.
Speaker 3: Mary Claire Haver. Yeah, and she.
Speaker 2: Noted that there is now training through some medical association
Speaker 2: where people can pass a test and show that they
Speaker 2: have been trained on the cutting edge of our knowledge
Speaker 2: of menopause. And so you can find these lists of
Speaker 2: obgyns who have this training online.
Speaker 3: From the Menopause Society.
Speaker 2: Yeah, yes, great, thank you, And so you should search
Speaker 2: out one of these people, because you're right exactly, most
Speaker 2: doctors don't know, but there are experts.
Speaker 1: Thank you. That's a good question.
Speaker 4: Don't ask your dentist about menopause, Go find somebody who
Speaker 4: knows what they're talking about.
Speaker 6: That there was a really interesting article in the New
Speaker 6: York Times about to years ago about the history of
Speaker 6: hormone replacement therapy that actually cited the data from the
Speaker 6: study that you just talked about.
Speaker 3: So that was the first time I got.
Speaker 6: To see that data, and my jaw dropped just from
Speaker 6: the numbers. You were talking about that those tiny numbers
Speaker 6: influenced so many people. And my own doctor had been
Speaker 6: very convinced by that study and was unwilling to look
Speaker 6: when I showed her the numbers, Like you know, this
Speaker 6: was not something that they were open to changing their
Speaker 6: mind about. Now, they'd spent two decades telling thousands of
Speaker 6: people that hormone replacement therapy was dangerous because of increased
Speaker 6: breast cancer risk, and those ideas are very solidified in
Speaker 6: people's minds. But I actually have a visiting sabbatical researcher
Speaker 6: in my lab right now from Taiwan and obgyn and
Speaker 6: I asked her how this study influenced medical practice in Taiwan,
Speaker 6: and she said that actually they did not take the
Speaker 6: data seriously.
Speaker 3: They saw those.
Speaker 6: Numbers, and they did not change the recommendations about hormone
Speaker 6: replacement therapy in Taiwan, which I thought was fascinating. So
Speaker 6: they had him, honestly a more scientific, rigorous look at
Speaker 6: the data. And I was really glad to see that
Speaker 6: there are societies where people look at the science and
Speaker 6: make decisions that are sometimes more rational.
Speaker 3: I think everyone was doing their best.
Speaker 6: In this situation, but it had a lot of negative
Speaker 6: impact on people's lives. There was another problem with the study,
Speaker 6: I think, which is that the age group didn't reflect
Speaker 6: younger women who were.
Speaker 3: Just entering menopause.
Speaker 6: I think the average age of the women in that
Speaker 6: study was maybe sixty, I don't remember the details, but
Speaker 6: that was another reason that the risks would be very
Speaker 6: different compared to what they would be for a younger woman. So,
Speaker 6: from what I understand, the safest thing to do not
Speaker 6: medical advice, but from what I understand, the safest thing
Speaker 6: to do is to replace the hormones as you're entering menopause,
Speaker 6: so that you have a more seamless supply of the hormones.
Speaker 6: And the hormones are given at levels that are much
Speaker 6: much lower than you would biologically have access to them,
Speaker 6: so it's still a trickle compared to what your ovaries
Speaker 6: would produce, but it's enough to be a little bit
Speaker 6: protective of joints and bones and so on.
Speaker 4: I think this also speaks to something else people struggle
Speaker 4: with understanding, like statistically, which is that like inaction and
Speaker 4: caution is not always safety. Right. Yeah, just because I
Speaker 4: understand these people like don't want to give cancer the
Speaker 4: people in their study, right, But you know, stopping the
Speaker 4: treatment doesn't necessarily mean saving people's lives. It's just like
Speaker 4: we haven't studied the effect of tileol and pregnancy because
Speaker 4: you can't do studies on pregnant women. It's not ethical.
Speaker 4: That doesn't mean that if you're pregnant and you have
Speaker 4: a fever, you shouldn't take tilent all, right, Like sometimes
Speaker 4: inaction is more dangerous than action.
Speaker 6: Yeah, Like taking tail and al when you have a
Speaker 6: fever and you're pregnant is critical. That's way safer for
Speaker 6: your baby. Like, having a fever while you're pregnant could
Speaker 6: be quite dangerous.
Speaker 4: So not medical advice.
Speaker 3: Not medical advice. Yeah, definitely not medical advice.
Speaker 2: Talk to your doctor if you're pregnant you have a fever.
Speaker 2: But to go back to Katrina's point about the age
Speaker 2: of the participants, so, yeah, the average age was sixty three.
Speaker 1: They were almost certainly postmenopausal.
Speaker 2: And now there's pretty good evidence that estrogen is good
Speaker 2: at preventing problems, but it's not a cure once the
Speaker 2: problems have kicked in. And so if you start estrogen
Speaker 2: therapy before you've completely entered menopause or pretty soon after.
Speaker 2: Then this seems it seems to actually help with a
Speaker 2: lot of things, particularly quality of life, but maybe even
Speaker 2: things like osteoporosis, risk, cardiovascular health, stuff like that. But
Speaker 2: if you start the therapy ten years after menopause has begun,
Speaker 2: then you suffer increased risks of a lot of things.
Speaker 2: And so it does seem like there's this critical window
Speaker 2: where you have to do it. And so this study
Speaker 2: sort of set itself up for finding failure by looking
Speaker 2: at women who were beyond the age. And I think
Speaker 2: at this point we didn't know that there was an
Speaker 2: age where it was good to take it and an
Speaker 2: age beyond which should seem to have more n negative impacts.
Speaker 2: But it's important to keep that in mind when you're
Speaker 2: thinking about the results of this study, that this is
Speaker 2: not the typical person who would even be considered for
Speaker 2: these therapies anymore. And these days we use a lot
Speaker 2: of different kinds of estrogens and progesterone, So for example,
Speaker 2: there's some risk that these hormone therapies can increase clotting,
Speaker 2: and clotting can be bad for a lot of reasons.
Speaker 2: If a clock gets stuck in your brain you can
Speaker 2: have a stroke. But if you take the hormone therapy
Speaker 2: on a patch on your arm instead of on a pill,
Speaker 2: it looks like that reduces the clotting risks. So something
Speaker 2: about the hormones needing to go through your liver before
Speaker 2: they can make it into your blood to do their
Speaker 2: work increases the risk of clotting. But if you just
Speaker 2: put it on your arm, it goes right into your bloodstream,
Speaker 2: it bypasses the liver, and your risk of clotting goes
Speaker 2: way down. And so there's a lot of different kinds
Speaker 2: of hormones now, a lot of different ways that we
Speaker 2: administer it. That makes this Women's Health Initiative study, you know,
Speaker 2: maybe not really relevant to what we have today and
Speaker 2: the groups of women that we would be thinking about
Speaker 2: giving this therapy too.
Speaker 4: And is there some plan for a new study to
Speaker 4: sort of complete the task that this earlier study was.
Speaker 1: Aiming for, Not as far as I know.
Speaker 2: So I read there's this book called Estrogen Matters, and
Speaker 2: it's an incredibly critical look at the Women's Health Initiative
Speaker 2: And at the end, one of the points they make
Speaker 2: is that it's sort of unfortunate that we're in this
Speaker 2: position where this is the only big, random, double blind
Speaker 2: control study that has been done on this and for
Speaker 2: a variety of reasons, the study design wasn't great, and
Speaker 2: so we're sort of left without having really great data
Speaker 2: to make these decisions, and so people get observational data
Speaker 2: where they can, and you know, we're coming closer to
Speaker 2: understanding the risks, but there's still a lot of question marks.
Speaker 2: And so when if you have a good doctor, this
Speaker 2: will be a discussion about the risks and the benefits,
Speaker 2: and they won't be able to give you a solid answer.
Speaker 2: You're just going to have to weigh for yourself what
Speaker 2: risks you're willing to take relative to the benefits that
Speaker 2: you want to get.
Speaker 6: Yeah, and I think it's really hard to do these
Speaker 6: kind of studies. It's why we can't agree on whether
Speaker 6: eggs are healthy. I mean, there have been actually quite
Speaker 6: a few big association style studies.
Speaker 4: Eating chicken eggs, I mean chicken eggs.
Speaker 3: Yeah, that's ironic for this conversation.
Speaker 1: It's been a while since we've had a cannibalism joke
Speaker 1: on the show. Thanks you for.
Speaker 3: Wow.
Speaker 6: Not where I was going, But yeah, I just mean
Speaker 6: these kind of studies where it's very individual.
Speaker 3: But the way that we can we need data to
Speaker 3: come from.
Speaker 6: Large studies can be really hard just because we're all
Speaker 6: so different. Like my personal favorite study designs for my
Speaker 6: microbiome studies are actually not randomized control where you have
Speaker 6: a placebo group and a treatment arm, because people tend
Speaker 6: to be so different that it doesn't actually work very
Speaker 6: well to assume that your treatment arm and your placebo
Speaker 6: arm are at the same point in the start. So
Speaker 6: I actually prefer longitudinal studies where you use the starting
Speaker 6: point as the control and then you like watch what
Speaker 6: happens through time to each person as they go through
Speaker 6: the intervention.
Speaker 4: So just to clarify, instead of comparing one group with
Speaker 4: another group, you're comparing each person with their past exactly.
Speaker 6: Yeah, and sometimes household controls can be really valuable because
Speaker 6: people live in similar conditions in their households and their
Speaker 6: microbiomes tend to be very consistent within a household. That
Speaker 6: would be harder to do for a hormone replacement therapy
Speaker 6: study because it's not that often that you have women
Speaker 6: of the same age going through menopause in the same household.
Speaker 6: But maybe there would be ways to study that.
Speaker 3: I don't know.
Speaker 6: Yeah, but I think that you know, we now have
Speaker 6: these options, and as Kelly said, you can talk to
Speaker 6: your doctor about the options and think about more than
Speaker 6: just this tiny risk of breast cancer that was revealed
Speaker 6: in a study that might not have had a good design,
Speaker 6: because some of the other benefits, you know, can be
Speaker 6: quite substantial and unrelated to breast cancer.
Speaker 4: Well, speaking of cutting edge research, Katuna, can you tell
Speaker 4: us about your research which involves lasers?
Speaker 6: WHOA, Okay, yeah, I guess that was actually the real
Speaker 6: reason I was invited to this episode, isn't it. It
Speaker 6: sounds like science fiction, but believe it or not, I
Speaker 6: have a collaboration with scientists in the Beckmann Laser Institute
Speaker 6: here at the University of California, Irvine, where the treatment
Speaker 6: to help with the genito urinary syndrome of menopause.
Speaker 3: Is to use a laser, which I haven't actually seen.
Speaker 4: It with my oar tell us where you're putting the
Speaker 4: laser in.
Speaker 6: The laser is being used to treat the vaginal epithelia
Speaker 6: and the purpose of this is to improve the vaginal
Speaker 6: wall thickness and circulation. So a really big symptom of
Speaker 6: menopause is vaginal dryness, urinary tract infections, and just general
Speaker 6: discomfort related to vaginal dryness. And so one measure of
Speaker 6: vaginal health is the thickness of the wall of the
Speaker 6: vaginal lining, and that can become thinner after you stop
Speaker 6: producing estrogen. And so in this study, the treatment is
Speaker 6: to use a laser, which you know is being used
Speaker 6: in a.
Speaker 3: Controlled manner.
Speaker 6: To release a predetermined dose of lasery goodness usepping it.
Speaker 2: But what does the lasery goodness do? Is it like
Speaker 2: the damage that thickens the wall or is it not? Like, yeah,
Speaker 2: what's going on there?
Speaker 6: Damage sounds like destructive in a way that is maybe
Speaker 6: too extreme, but yes, it basically is almost like a
Speaker 6: swelling associated with wound healing, which brings liquid and circulation
Speaker 6: and in healing to that area. And so what you
Speaker 6: find after the laser treatment is an increase in circulation
Speaker 6: and vaginal wall thickness and a decrease in vaginal dryness,
Speaker 6: in improvement and symptoms.
Speaker 3: And it's not just for research.
Speaker 4: Well, you know, lasers are physics. So I'm just going
Speaker 4: to chalk this up to the you know, the famous
Speaker 4: physics biolence.
Speaker 3: Yes, very important connection right there.
Speaker 6: It does sound like science fiction, and it's being done
Speaker 6: as part of a research study here at the University
Speaker 6: of California. In fact, we're still recruiting, so women both
Speaker 6: before and after menopause, paramenopause, postmenopause, premenopause.
Speaker 3: Are all invited to enroll in this study.
Speaker 6: And one of the benefits is that you might have
Speaker 6: the opportunity to learn about the composition of your vaginal microbiome,
Speaker 6: which is my contribution to the study.
Speaker 3: And this is not only done.
Speaker 6: In an experimental way, so in other parts of the world,
Speaker 6: it's a normal treatment that's offered to menopausal women to
Speaker 6: use this laser treatment to improve vaginal dryness and the
Speaker 6: vaginal wall thickness. The other standard treatment is estrogen cream,
Speaker 6: so locally applied estrogen cream will also increase vaginal wall
Speaker 6: thickness and circulation.
Speaker 3: So these are we actually.
Speaker 6: Are comparing those kinds of treatments in our study because
Speaker 6: when you add estrogen locally like that, it has really
Speaker 6: positive impact on vaginal health. But I can tell you
Speaker 6: from the vaginal microbiome perspective that when we got our
Speaker 6: first data set as part of the study back normally
Speaker 6: we have to do really subtle statistics, and it's sometimes
Speaker 6: hard to kind of tell the difference between the groups
Speaker 6: in our studies, but when you look at pre in
Speaker 6: post menopausal vaginal microbiomes, you see really clear differences. And
Speaker 6: in a healthy vaginal microbiome normally see domination by lacto bacillis.
Speaker 6: Certain there's certain few different strains that can be the
Speaker 6: dominant ones. They're acid producing, so the vaginal microbiome thrives
Speaker 6: in a low pH like high acid environment, and that's
Speaker 6: really happening in the premnopausal women in the study, but
Speaker 6: for the postmenopausal women, you can see that the lactobacillis
Speaker 6: become less abundant. And I don't mean to call it unhealthy,
Speaker 6: because actually there's a huge swath of society that live
Speaker 6: perfectly healthy lives and don't have just one lacto bacillis
Speaker 6: dominating their vaginal microbiome. So I always take issue when
Speaker 6: people try to define what health means, because there's a
Speaker 6: lot of ways to be healthy. But to me anyway,
Speaker 6: it was just so striking that you could really see
Speaker 6: a signal in the vaginal microbiome postmenopausal.
Speaker 1: So that the lasers bring back the lacto bacillis.
Speaker 3: That's the question. So actually I don't know the answer
Speaker 3: to that yet.
Speaker 6: We're still recruiting, so actually, I hope that's that's kind
Speaker 6: of what I'm expecting. I'm very curious to see what happens,
Speaker 6: and I think we'll be able to see difference is
Speaker 6: between what hormone replacement therapy does and what the lasers do,
Speaker 6: or maybe they'll look similar. But yeah, that's the goal
Speaker 6: is to figure that out. So I'll probably need like
Speaker 6: two years to answer that question.
Speaker 1: If I'm honest, we'll bring you back on in two years.
Speaker 4: Well, I don't know if this reflects some so like
Speaker 4: genius experimental design, like understanding how photons interact with the biology,
Speaker 4: or if it's just like, well let's just zap it
Speaker 4: with a laser and see what happens. Which is it?
Speaker 6: I think my colleagues would have a more reasoned response
Speaker 6: that was not just random zapping with lasers.
Speaker 2: You're being very patient again, Katrina, she's got to earn
Speaker 2: that medal. She has earned that met Okay, So I
Speaker 2: learned a lot from this conversation from Katrina. I learned
Speaker 2: a ton while researching this. There's a lot of books
Speaker 2: out there that you can read now if you want
Speaker 2: to learn more about paramenopause. And there's still a ton
Speaker 2: that we have left to learn. So I hope that
Speaker 2: we are investing more in women's health so more women
Speaker 2: don't end up, you know, going to the doctor and
Speaker 2: being told we don't know what's wrong with you when
Speaker 2: it's menopause, and that should be one of the first
Speaker 2: things that people expect for women in the thirties, forties,
Speaker 2: and fifties. But one thing that really hit home while
Speaker 2: I was researching this and came across the list of
Speaker 2: all the symptoms is that middle aged women are totally
Speaker 2: badass because we are accomplishing great things while dealing with
Speaker 2: all of this stuff on top of everything else, and
Speaker 2: you know, jobs and sometimes kids and.
Speaker 1: Anyway way to go.
Speaker 2: Fellow uterus has or fellow women out there, I'm proud
Speaker 2: of us.
Speaker 4: I'm a big fan.
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