What's the deal with hormone replacement therapy?

14:29Emily Oster:We'll find out. And that's it for the health news of the week. After the break, what's the deal with hormone replacement therapy? A win is a win. A win is a win. I don't care what y 'all say. Yep, that's me, Clifford Taylor IV. You might have seen the skits, the reactions, my journey from basketball to college football, or my career in sports media. Well, somewhere along the way, this platform became bigger than I ever imagined. And now I'm bringing all of that excitement to my brand new podcast, The Clifford Show. This is a place for raw, unfiltered conversations with some of your favorite athletes, creators, and voices that not only deserve to be heard, but celebrated.

15:09Emily Oster:One week, I'll take you behind the scenes of the biggest moments in sports and entertainment. And the next, we'll talk about life, mental health, purpose, and even music. The Clifford Show isn't just a podcast. It's a space for honest conversations, stories that don't always get told, and for people who are chasing something bigger. So if you've ever supported me or you're just chasing down a dream, this is right where you need to be. Listen to The Clifford Show on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts. And for more behind the scenes, follow at Clifford and at TikTok Podcast Network on TikTok.

15:41Emily Oster:You can have opinions. You can have like a strong stance. And then there's your body having its own program. I'm Dr. Maya Shunker, a cognitive scientist and host of the podcast,

15:56Perry Wilson:A Slight Change of Plans, a show about who we are and who we become when life makes other plans. We share stories and scientific insights to help us all better navigate these periods of turbulence and transformation.

16:09Emily Oster:There is one finding that is consistent, and that is that our resilience rests on our relationships. I wish that I hadn't resisted for so long the need to change.

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16:59Emily Oster:starting with the mindset shifts too many of us were never, ever taught.

17:04Perry Wilson:Financial education is not always about, like, I'm going to get rich. That's great. It's about creating an atmosphere for you to be able to take care of yourself and leave a strong financial legacy for your family.

17:19Emily Oster:If you've ever felt you didn't get the memo on money, this conversation is for you to hear more. Listen to Money and Wealth with John O 'Brien from the Black Effect Network on the I'd Heart Radio app, Apple Podcasts, or wherever you get your podcasts.

17:38Perry Wilson:Welcome back. So we're going to talk about hormone replacement therapy. And I want to start by saying up front, this is not a full discussion of all of the potential benefits and whether you personally should be on hormone replacement therapy. I think what we find, and Perry, you can correct me if this isn't what you find interesting here, but I think what we have found interesting here is kind of how the discussion of this science has evolved. And so we'll talk a little bit about how we got to where we are now, where we were before, some of the data, and then some of the benefits that are potentially true here.

18:15Perry Wilson:But this is really something where whether one should be on this or not is very dependent on talking to your doctor about where you are.

18:22Emily Oster:Yeah, this is complicated, folks. This isn't red light therapy where it's like, well, it's going to cost you some money, but it's probably not going to kill you. There are benefits. There are risks. We'll touch on some of these. There are subgroups of people that would benefit more. There are subgroups of people that have higher risks. This is like a real deal talk with your doctor, but it's also a completely fascinating area. I do want to give one other disclaimer. There's like sort of an elephant in the room here, which is that I'm a man talking about hormone replacement therapy for women. This could be like the worst case of recorded mansplaining in history.

19:03Emily Oster:Um, so Emily, I think we need like a safe word or something. If I start saying something like boorish or dumb, you know, if I, if I'm like, Oh, menopause, you know, is a really beautiful transition or something like you just say, say rutabaga and, um, I'll, I'll, I'll back off.

19:24Perry Wilson:Safe word, tampon. That's perfect. And, uh, you shut your mouth. That's actually can work. We can use this in all episodes. But yes, I take I I think that is a reasonable point. And I will also say, disclaimer on my side, you know, although I am a woman of perimenopausal age, who is presumably somewhere in perimenopause, the actual experience of a lot of the symptoms that people are using hormone replacement therapy to treat is very different. And so I can say something about what it is like to be a 46-year-old woman, but certainly cannot speak to the experience of all 46-year-old women. So with that lengthy tampon disclaimer and so on, let's go.

20:07Perry Wilson:And I think the place to start here is with the biology of what hormone are we replacing and why. So can you, very briefly, from your doctor's standpoint, tell me what hormone are we replacing and why? Okay.

20:22Emily Oster:So can I say for, again, very briefly, that hormones... Can't find it. Sorry. Sorry. I'll stop. I'm like, I'm just going to like spin my chair around and sit in the corner. Okay. We're talking about steroid hormones, which include estrogen, progesterone, and we'll touch on testosterone at the end as well. And I do want to say something about the biology of what makes steroid hormones, and there are a few others as well, really special in the body. We have these cells in our body, which are like little factories, right? They have a job to do. And most of the way that they sense the outside world or the world outside the cells is through these receptors on their surface.

21:00Emily Oster:And the drugs we take and a lot of the chemicals in our body bind these receptors on the surface of the cells, but they don't get into the cells. They just sort of bind the receptor. They say, hey, we're out here. And it causes the cell to do something else, like produce more insulin. If it's a factory, produce more widgets or something. The steroid hormones receptors are not on the outside of the cell. They're in the nucleus of the cell, which is where the DNA lives. Steroid hormones have the ability to go right through the cellular membrane because they're lipid soluble and into the nucleus where they bind their receptors.

21:29Emily Oster:And their effect is to change what DNA gets transcribed inside that cell. So to continue the factory analogy, it's like, you know, most drugs and substances kind of like send a telegram to the factory and are like make more widgets and steroid hormones go into the factory and can redesign the entire thing which is why you can take a hormone like testosterone and all of a sudden a cell that didn't grow hair now grows hair that also explains why the effects of steroid hormones are so broad like they can do so many things and we don't even fully understand why they do all the things they do. So they really are a special group of things.

22:12Emily Oster:And that's my very basic biology of what we're talking about here. When we speak about hormone replacement therapy in terms of women, in general, we're, I mean, it is what it sounds like. We're talking about giving doses of the hormones that go down in perimenopause and postmenopause, which is estrogen and progesterone. HRT is supposed to replace those levels, not to make them higher, but to get them back to sort of where they were at baseline. In contrast, for women who are premenopausal who might have used oral contraceptive pills or something where the doses of those hormones are much, much higher because they're designed to actually suppress the endogenous hormone levels.

22:55Emily Oster:That wasn't very brief.

22:57Perry Wilson:It was not brief, but I thought it was interesting. I think that's great. And I think the kind of big picture here you want to imagine is that during perimenopause and menopause, your estrogen in particular, although both estrogen and progesterone change, estrogen goes down a lot. Estrogen is part of what supports a lot of ways that we feel good. And so hormone replacement therapy is potentially a way to improve some of the symptomatic experiences. Perimenopause, we'll talk about this, but things like hot flashes or sleep disruptions, which are kind of characteristic of many people during perimenopause.

23:37Perry Wilson:Estrogen is a potential treatment. Vaginal dryness is another example of where just as your estrogen falls, this symptom gets more significant. And so for kind of all of these reasons, there is a biology behind the idea that replacing some of that estrogen would improve some of your symptoms. Absolutely. Make you have more of the hormone profile of a 35-year-old than of a 51-year-old.

24:03Emily Oster:Exactly. And that made so much biological sense that for years and years and years, this was a very common practice. It was like we had access to these hormones. they were first discovered in the 1920s, I think. And it is true that estrogen to this day is still a lot of the estrogen that people receive. It comes from horse urine. Premarin is pregnant mare urine. There are 750 ,000 horses around the world that are giving their urine to make some of these estrogens. Isn't that fascinating? So nice of them. But all of a sudden, this study happened that essentially overnight tanked the use of hormone replacement therapy in the United States.

24:47Emily Oster:That's the Women's Health Initiative study. And Emily, can you tell us the story of the Women's Health Initiative? Because I think it's hard to understand any of this without talking about that.

24:56Perry Wilson:Yeah. So I actually, before I tell you the story of this, I want to spend, like, remember how you nerded out on physics? I'm going to nerd out on statistical external validity just very briefly, and then I will talk about this. So when we talk about scientific studies, we often talk about randomized controlled trials as kind of the gold standard for generating causal effects. And that's because when you have a randomized trial, you take some people, you divide them up randomly so you know they're kind of the same at the beginning. You do something to one and not the other, and then you can be confident that for those people, if you see different outcomes, the different outcomes are a result of the treatment.

25:34Perry Wilson:That's like the idea. But that is going to tell you a causal effect for the people that you study. And if that effect is the same across all people in the entire population, then you have learned about the whole population. But if you have a population where the effect might be different than like the rest of the world, then you haven't actually learned about everybody. So like to be simple. Let's imagine that you have a study of a drug and you only include men. And then you want to be like, okay, this was effective for men. Now I'm going to give it to everyone. Well, it's very possible the effect for women could be different.

26:16Emily Oster:I mean, we did this for 50 years, by the way. This was all of medicine.

26:19Perry Wilson:This is the main way science worked. And it turns out, actually, that doesn't port very well. There are a lot of things where women react differently than men. So this is an idea called external validity. And we worry when we want randomized trials about this external validity. And this is a topic that I work on, so I feel very passionate about it. But I say that at the top, and then I'm going to tell you about the Women's Health Initiative, because I think in some ways that's some of the issues that came up with that trial. So the Women's Health Initiative is a study launched by the NIH in the early 1990s.

26:53Perry Wilson:It included about 30 ,000, 27 ,000 postmenopausal women. These women had an average age of 63. and they randomized them to sort of two different treatments of sort of hormone replacement therapy and also a placebo. And when the follow-up was published in 2002, they actually, the people doing this study halted the study in 2002 or halted one arm of the study because of a concern that there was an increase in both breast cancer and cardiovascular events, which exceeded what they saw as the benefits of this. And it was a relatively small increase numerically, but percentage-wise, it was quite sizable.

27:42Perry Wilson:So the relative increase, about 25 % in invasive breast cancer and about 30 % in cardiovascular events. It was actually also an increase in strokes. And with that change, we pretty much saw a absolute tanking of any hormone replacement therapy prescriptions. So this was sort of the end, at least for some period of kind of widespread hormone replacement. And I would say that's the nadir. And then sort of over time, this has returned. But fundamentally, the thing to understand is there's a randomized trial of this, which showed some elevated risks.

28:20Emily Oster:I want to double click on the relative risk versus the absolute risk because that's another important concept that people need to sort of be aware of when they think about these studies. So let's take invasive breast cancer. When that arm of the Women's Health Initiative was stopped, there was a 26 % relative increase in invasive breast cancer. And so people interpret that as like my risk of breast cancer would go up by 26%. But if you look at the absolute numbers, there were 30 cases of breast cancer per 10 ,000 women per year in the placebo group. So 30 per 10 ,000 per year in placebo, 38 per 10 ,000 per year in the hormone replacement therapy group.

29:03Emily Oster:So we're talking eight extra cases per 10 ,000 women, right? And that doesn't sound as bad as a 25 % increase. People hear 25 % and they're like, oh my gosh, that means I'm going to have a 25 % chance of getting cancer or worse or something like that. Really, the absolute risk is very small, not zero, but very small. And sometimes the way we help explain that to people is with a concept called number needed to harm, which is like how many people would you need to treat for there to be one extra case of cancer? And in this case, if you do a little math, it would be 1 ,250 women. If you treat 1 ,250 women with hormone replacement therapy, you would get one extra case of invasive breast cancer per year, not nothing.

29:49Emily Oster:But again, Emily, and you're about to talk to us about this, that's assuming that the women in the study are the same as the women that you're prescribing the hormone replacement therapy to. And is that the case?

30:02Perry Wilson:So first of all, let me just say, I hate those number-needive treat things. I understand And doctors like those as a way to describe risk size. And I don't think they make any sense to actual people. It doesn't work for you? Oh, all right.

30:11Emily Oster:It doesn't work for me. Listeners, tell us if you like number needed to treat.

30:16Perry Wilson:Yeah, I don't like it. But I guess I'm not the only listener. But I'm the first listener and I don't like it. Okay. I will say that I think that there is this sort of difference between percent and percentage points, which is very important. people hear 25 % increase and they immediately think, you know, that raises my risk from zero to 25 % as opposed to it is a 25 % increase from an already low number relative to a very low number. So I think that's like we can talk more at some point about how to talk about small numbers to people. Okay. So getting back to the Women's Health Initiative, you know, when this sort of stuff came out in 2002.

30:55Perry Wilson:I think the prescription rates for HRT dropped by like 80%. I mean, it was a real tanking and it, cause it sort of fell to people like, so it sounded like the, you know, hormonal placement therapy gives you breast cancer. That was kind of like the headline was like, you take this, you're going to get breast cancer. But then sort of almost immediately things got like quite more complicated. So there was a second arm of the trial that treated in a slightly different way. And that arm was halted in 2004 because of a concern about an increased risk of stroke. But actually in that group, the risk of invasive breast cancer had gone down.

31:34Perry Wilson:So now already there's like a little bit more of a complicated story, which may relate to the overall small numbers, could relate to, you know, some actual differences in impacts, but it was sort of made the story immediately more complicated. And then, you know, over the past, probably over the 10 years or 15 years following this initial publication, one of the things that became pretty clear was that the age group in this study seemed to matter a lot. So the primary group, the average age of people enrolled in the study was like 63. But when they cut the study, they, what's called stratified, divided the study into people who were sort of closer to menopause, so people who were 50 to 59, so the kind of younger group within 10 years of menopause, they actually looked like the treatment decreased their risk of cardiovascular disease and all cause mortality.

32:35Perry Wilson:So actually in that group, they seem to have an overall mortality benefit and a reduction in cardiovascular disease, which sort of was offset by these older individuals. So in some sense, what's really important about that is you kind of, again, getting back to this external validity point, we put in a bunch of people, we drew some conclusions based on a much older cohort, and then we apply that conclusion to everybody, even though A, it looked like the younger cohort, if anything, had some benefits, and B, actually treatment with HRT is somewhat more common in these younger cohorts, you know, that is where this symptomatic stuff shows up most significantly.

33:14Perry Wilson:And so you're sort of learning from a group that's like not even the group you're really interested in treating. And I think that realization over time has kind of, we've started to return to the use of HRT, but it's taken a very long time.

33:30Emily Oster:Yeah. The Women's Health Initiative study was not designed to test whether HRT reduces the symptoms of menopause, because as you point out 70 of the women in the study were more than 10 years past menopause like they weren't symptomatic anymore it was designed to test whether hormone replacement therapy is cardio protected protects the heart because you know there's long been an observation that women tend not to have heart attacks and stuff until after menopause and it was thought the estrogen would be protective that obviously didn't pan out in that older group of women it may among younger women.

34:02Emily Oster:But it was like, this study wasn't designed to test the thing that we're using it for now. Yeah.

34:08Perry Wilson:And I think, I mean, in some ways, many people would say, well, like, why not? And, you know, one answer is like, you know, the patriarchy or something. But, you know, it really, it is a really important point because for many people, the reason to treat this is because of symptomatic, you know, because of improvements in symptoms. This study just wasn't about that. It's not that it evaluated symptom profile and showed that it didn't work or anything. It's just like that wasn't one of the outcomes. And it wouldn't have made sense with this age cohort because, again, the sort of symptomatic pieces of menopause are earlier.

34:43Perry Wilson:And so it really is an example of a place where I think a lot of people's lives were made substantially worse by this research, which in principle was very well-meaning and from which perhaps we did learn something. but it caused a lot of people to not have symptom relief who could have. So we then find ourselves in the current moment where I think, like, overall, we are starting to see HRT. It's like it's having a moment. It's like having a comeback.

35:16Emily Oster:Absolutely.

35:17Perry Wilson:People are into it.

35:18Emily Oster:Yeah, I think the word has gotten out and it's making people very curious. But part of this is word of mouth because unlike a lot of drugs we take and give ourselves, like hormone replacement therapy really works for symptoms of menopause. And so if you are a woman or know a woman who has those symptoms and then they start taking HRT, they'll tell you how much better it is and that's real. And so this percolates really quickly.

35:44Perry Wilson:But can I like sort of set back one sec, which is, you know, looking at the Women's Health Initiative results, sort of what would you think we should have taken away from that? From the initial results? Yeah. In 2002, what would you have had them do, sort of do or say differently?

36:01Emily Oster:To be honest, because the purpose of the study was to determine whether hormone replacement therapy reduced the risk of cardiovascular disease, and it didn't in the overall population, I think I would have said, okay, you should not give hormone replacement therapy to reduce the risk of cardiovascular disease.

36:18Perry Wilson:In postmenopausal women.

36:19Emily Oster:In postmenopausal women. And I would probably still say that today, to be honest, although you could maybe convince me. But the problem is when we extrapolate from one outcome to all outcomes. And we'll get to some of those other outcomes. But I did want to give, I think, women who are reading about this, it can be very confusing what is out there, right? I said estrogen and progesterone in terms of the biology, but there are so many different types and preparations. I think it's worth just giving people a framework to sort of think through how to take these hormones. And so the framework that I have found useful is to remember that really the hormone that you want to get for hormone replacement therapy is estrogen.

37:08Perry Wilson:Yes, that's the best one. Estrogen is a great hormone.

37:11Emily Oster:It's a great hormone. We love estrogen. Estrogen is responsible for what makes women women, the secondary sexual characteristics and a lot of other things. Progesterone is there to stop you from getting uterine cancer. I mean, that's really what it is. So estrogen flogs the lining of the uterus to grow and develop. That's one of its jobs during the menstrual cycle. If you don't allow the lining of the uterus to settle down and mature, which is what progesterone does, and it keeps getting hit by estrogen, the risk of uterine cancer really does increase. And so you want the estrogen, you need the progesterone if you have a uterus.

37:54Emily Oster:And that other arm of the Women's Health Initiative study that you alluded to was an estrogen-only arm, and you could only to get in that arm if your uterus had already been removed for some reason. And I mentioned that because a lot of the outcomes for estrogen only hormone replacement therapy are actually a little bit better than estrogen and plus progesterone therapy. It's just like not everyone is eligible for that. So particularly breast cancer, for example, the risk in the overall women's health initiative was elevated. But among those women who were on estrogen only because they didn't have a uterus, the risk was slightly reduced.

38:28Emily Oster:So really interesting there and something to keep in mind. So ask about the uterus. The other thing is whether you're taking these as pills or not as pills. The pill forms have to get digested and pass through the liver before they get to your blood. And depending on the type of estrogen, the liver can break down like straight up estrogen, like 17 beta estradiol, which is the estrogen that women make in their own bodies. You can take that in pill form. And if you do, your liver will break down 95 % of it before it gets to the rest of your blood. So you're actually taking pretty high doses to get like relatively normal blood levels in contrast to a patch, which goes right through the skin.

39:07Emily Oster:You know, there's transvaginal or like vaginal preparations as well, which can get right into the bloodstream and the doses are much lower. That's worth mentioning because some of the risk of clot seems to be driven by these oral preparations. And I don't think people are entirely sure why there's a higher risk there. But if you've got the liver breaking down 95 % of stuff, you know, that's going to be variable woman to woman because everyone's liver is a little bit different. And I bet dosing is just trickier to get right in those situations. So I just wanted to, that's the framework.

39:38Perry Wilson:I think partly that somewhat complicated framework illustrates why this is a challenging thing to talk about in a podcast. And, you know, because everybody's Not for us, but for other people, you know, because everybody's needs here are going to be somewhat different. So there's an oral preparation. There is a patch, which I know is what a lot of people like.

40:04Emily Oster:And there's a shortage of right now.

40:06Perry Wilson:And there's a shortage. There are, you know, vaginal creams, which really are kind of intended to treat or are effective mostly at treating the specific issue of vaginal dryness. So people experience that symptom. A vaginal estrogen-based cream can be very effective, can also be usable even for people potentially who would not be wanting to take estrogen-only therapies in other ways because of other risks. So it's sort of like all about what are the particular symptoms that I am experiencing? What are the other risk factors that I'm holding onto? and then what's the right way to address those symptoms.

40:47Perry Wilson:And getting back to the idea that a lot of what we're trying to do with this hormone replacement therapy in contrast to what the Women's Health Initiative was evaluating, a lot of what we're trying to do is dial down symptoms of perimenopause and menopause, which are very disruptive to people's lives. So let's talk about the symptoms.

41:04Emily Oster:Let's talk about the symptoms. Does hormone replacement therapy work for hot flashes?

41:10Perry Wilson:It really, really, really does. So hot flashes, vasomotor symptoms are very, very common experience of perimenopause. This is like the joke on television shows where someone's sticking their head in the refrigerator. That's a hot flash. People get a lot of these at night. and it's very disruptive at night because you sweat, you wake up, your bed is completely soaked and then you can't just go back to sleep because you're literally drenched and it's very unpleasant. Having had this happen, it's very unpleasant. And hormone replacement therapy reduces the risk of high flashes in these studies by something like 70 to 80%.

41:53Perry Wilson:So it can be really, really effective at what is probably the most disruptive experience in perimenopause that people have.

42:03Emily Oster:And perimenopause can go on for quite some time.

42:07Perry Wilson:It goes, I mean, yes, it can go on for many years. I mean, so people, maybe it's worth saying, so menopause actually defined as 12 months, you sort of are in menopause when you are 12 months past your last period. So it's a thing that's sort of defined retroactively. So there's like a moment at which your last period was 12 months ago, and now you are in menopause. Perimenopause is the sort of period leading up to that when periods get less frequent or more frequent. Like they kind of mess around. Your cycle isn't so regular. And that is where many of these symptoms start showing up.

42:44Emily Oster:And I want to be clear that perimenopause has nothing to do with periwilson. There's no relation.

42:49Perry Wilson:There's no relation. It's not even spelled the same. No, no.

42:53Emily Oster:I was not named after.

42:54Perry Wilson:Even after you. I don't know. That's a tampon safe word, Perry.

43:01Emily Oster:I think though, hot flashes clearly works. You talked about the genital urinary symptoms where the topical preparations are probably superior to oral preparations. Another reason to kind of discuss with your doctor about how exactly you're going to go about this, but it's the vaguer symptoms, I think, that are where a lot of women who I talk to really have their questions. Like, yes, that's great. I don't want to have hot flashes. But also, what about my brain? What about sleep? What about, you know, memory? And you'll hear people online saying that, like, they started hormone replacement therapy, and the scales fell from their eyes.

43:42Emily Oster:And, you know, it was like they were granted a whole new lease on life, which, to be honest, and maybe this is another safe word thing, I'm always skeptical of naturally just because I never think there's like any one thing that can be that transformative except the power of love. Oh my God.

43:59Perry Wilson:So let me say sort of two things about that. So one is, you know, if you think about the sort of experience of the menstrual cycle, there is a period of the menstrual, it's like before the menstrual cycle when your estrogen is higher in the kind of pre-ovulatory phase and then the estrogen falls. And a lot of people do experience fairly substantial mood shifts with those cycles. So the idea that estrogen could affect - That's why whenever a woman's in a bad mood,

44:27Emily Oster:my first question is like, where are you in your cycle? That's my question.

44:31Perry Wilson:That's where you want to start. Totally. Totally. Yeah. I mean, that's where I, that's always, that actually is a great marriage tip that many people could use.

44:40Emily Oster:We could help so many people.

44:42Perry Wilson:We could help so many people. So I think it's not crazy to imagine, that estrogen could affect your mood. I think a lot of that experience, the brain fog, the fatigue, whatever, is in fact sleep. So if you think about there's a sort of evidence that hormone replacement therapy improves people's sleep, that may be because of a reduction of vasomotor symptoms. There may be other, you know, like you're not waking up in the middle of the night to change the bed, but it may also have sort of other things that impact sleep. If you have slept better, you feel better. And so if the whole thing here was just improving sleep, that actually could explain a fair amount of just a general set of like, boy, do I feel a lot better?

45:26Perry Wilson:Yeah. The same way the first time your baby sleeps through the night, you're like, oh my God, I'm going to conquer the world because I haven't, you know, because I've slept.

45:33Emily Oster:Right. Absolutely. And this is randomized trial level data. There's been a number of trials, but one called the KEEPS trial, this was in sort of just recently menopausal woman showed a pretty significant improvement in global sleep quality scores in the group that got hormone replacement therapy compared to placebo. As you mentioned, Emily, when they stratified that population by women who were having severe vasomotor symptoms, severe hot flashes, like that's where a lot of the benefit accrued. So it might just be that. You'll see people online talking about progesterone, actually, in particular, binding the GABA receptor in the brain.

46:11Emily Oster:That's the same receptor that alcohol and benzodiazepines bind to, one of my personal favorite receptors, but not much data beside the mechanistic like Petri dish stuff that would suggest that progesterone is a calming factor. But I think if you're certainly, if you're waking up with hot flashes, like this can be really good.

46:33Perry Wilson:The other thing we should say is that there's some evidence of an improvement in fractures. So for people who are at risk of osteoporosis, That's another place where we see some hormonal placement therapy benefits.

46:46Emily Oster:Yeah. No, I mean it's so important. I looked also a little bit more into brain stuff. The problem with brain fog is it's a bit of a Potter Stewart thing. You know Potter Stewart, the Supreme Court justice.

46:58Perry Wilson:Like pornography, you know, and you know when you see it. You know when you see it, right? You know when you see it. I use that in my class literally all the time. I'm constantly telling them. It's like what the Supreme Court said about pornography. People were just like, okay. Okay.

47:09Emily Oster:As they like load up Brown's, like report your professor page. I don't let them have devices in class just to avoid that kind of behavior. So I think brain fog is, you know, we're all like, oh, yeah, I know what that is. And then, but no one studied, there's no randomized trials of like brain fog because that's, what do you mean? Like how do you quantify that? And so what you do get is you get randomized trials of neurocognitive testing, which is across a variety of domains, you know, executive function, verbal memory, physical memory, like all these different tests that you can put people through.

47:44Emily Oster:And the data is really not super compelling that there are dramatic brain improvement effects with the only exception being verbal memory. There did seem to be an uptick in verbal memory. And again, just, you know, get out your shock buzzer or whatever you were using for me here. But I did feel like there – I was like, oh, that's kind of like a mom brain thing. Like you can't find the word for X, Y, Z, right?

48:10Perry Wilson:Yes, that's called fatigue. I mean, I just I feel like so hard to separate all this stuff from being tired. But all right. So let's let's just leave the hormone replacement therapy at, you know, this is especially if you are someone who is experiencing symptoms of perimenopause. This is something you for sure would like to discuss with your doctor.

48:34Emily Oster:Absolutely.

48:35Perry Wilson:Right. What about testosterone? So that feels like we're diving in a little more. We're going to talk about testosterone for men separately, but testosterone for women feels like, is it, um, I always think of this as like, this is how I could cheat in my sports performance.

48:53Emily Oster:Oh, but you will not be allowed to because, uh, testosterone hormone replacement therapy is banned by almost every international sports authority. And by the wellness actually metric of, is it banned? Does it work? then yes. It does work. Yes.

49:09Perry Wilson:So why are people using this in menopause and are there reasons they should do it? Yeah.

49:16Emily Oster:So women do have testosterone, just like men have some estrogen. It's just men have about 10 times the testosterone and women have about 10 times the estrogen and viva la difference. Women's testosterone levels peak around age 20 and sort of decline slowly thereafter, they do not suffer the same menopausal cliff as estrogen and progesterone. So they do sort of more the male thing, which we'll talk about next week, which is kind of like a slow, steady decline over time. The interest in testosterone is really more recent than, for women at least, is much more recent than the broader HRT, in part because this is a hormone that people associate with muscle growth and maintenance, vigor to some extent, And to be honest, a lot of the research has been driven by sexual dysfunction.

50:10Emily Oster:So testosterone in women's sort of first foray into organized research was to treat what's called hypoactive sexual desire disorder. You know, there's no there's no Viagra for for women yet. And so testosterone was sort of used for this purpose. Does it work? Yeah, pretty.

50:32Perry Wilson:It does. It does work.

50:35Emily Oster:For sexual stuff, it works. The largest meta-analysis comes from the Lancet, combining data for multiple studies, about 8 ,500 women total, randomized trial data. And there's a bunch of different ways to measure sexual satisfaction, but the women who are getting testosterone replacement therapy had approximately one additional satisfying sexual event per month. So a satisfying sexual event could be with a partner. It could be alone. It doesn't necessarily mean there is an orgasm. It just has to be satisfying. Beyond that, though, yeah, I don't have much for testosterone.

51:15Perry Wilson:I don't think it feels so like we know that testosterone is a part of why people, no offense, men like sex more than women on average or at least on average desire. That's true. That's true in the data. Men would like the optimal amount of sex that men want is more. I know, but I want to be offended by that. You're not. Don't be offended. And so I don't think it's that surprising that if you gave people more of this hormone, they might be more excited about sex. But the sort of other benefit, which is like a real benefit. I mean, again, if you like, if you have a mismatched sexual desire with your partner or you miss how much you used to like sex, this is a sort of interesting thing to think about.

51:58Perry Wilson:The other benefits don't really seem to be there. And of course, there are some symptomatic side effects of testosterone, the same kinds of things you see if you use it to improve your sports performance, like hair growth and acne and other things. So certainly not something you should be purchasing, you know, along with your peptide stack from foreign countries on the Internet or whatever.

52:22Emily Oster:Yeah. And testosterone is probably not as beneficial for heart health. If estrogen is beneficial for heart health, testosterone is not. It is sort of the yang to the yin of estrogen. I'm not sure which one is the sort of more like violent one, but testosterone supplementation can increase cholesterol levels, potentially promote atherosclerosis. So it's like, I don't think we're all there yet, but you're going to see more and more of it. And especially as we just have to mention, there's an entire industry that is out there that is selling hormone replacement therapy to women and men, you know, using telemedicine, this sort of direct to consumer prescription model.

53:07Emily Oster:And I'm not weighing in on, you know, the like ethics or legality of that. I'm just saying it is there. So people have access to these treatments in a way that they've never really had before. And so you're going to see more and more and more of this. And it makes it all that much more important to like be really cognizant and talk with someone really knowledgeable before you start. So you know what you want to get and that you can make sure wherever you're getting it from is legitimate.

53:37Perry Wilson:So Perry, of course, people can buy these hormones online. But the other thing I see a tremendous amount of is these tests, like, you know, get this blood test, it's going to tell you where you are in your different thing and which kinds of things you need. Is that, I, of course, I've had all of these tests because I'm a crazy person, but is there a sort of actionable piece of that? Is that just selling people nonsense? Should I care about my T3 free number is not as good as, whoops, as it should be?

54:07Emily Oster:Honestly, no. When it comes to estrogen and progesterone levels, yes, you can certainly buy tests online to measure your levels, but no, they don't really change the treatment paradigm. which is how we decide whether a test is valuable or not. So particularly in perimenopause, the levels can be all over the place. Estrogen can go up and then crash and kind of go up again. That's part of the difficulties of perimenopause. And so the indications for treatment with hormone replacement therapy is, are you at an age where it's reasonable that you're in perimenopause or menopause? And do you have symptoms of perimenopause or menopause?

54:42Emily Oster:And that's it. So, you know, Getting you to spend a subscription fee to continually measure these hormones over and over or even once, I think, is a bit of a cash grab.

54:53Perry Wilson:Okay. Fair enough. Thank you. Smash or pass, Perry? Hormone replacement therapy.

55:01Emily Oster:Smash. I'm going to go with a lot of the society guidelines, which say perimenopause, first 10 years of menopause, potentially five to seven years of therapy. is a clear smash. Probably need some more data on how long you can extend this into menopause. Emily, smash your breath.

55:22Perry Wilson:I'm going to go with a smash based on my friends who say that it's great. And when I feel like I need it, I'm going to be trying it.

55:31Emily Oster:Let us know.

55:32Perry Wilson:All right. That's it for hormone replacement therapy. Your mailbag question of the week after the break.

55:39Emily Oster:a win is a win a win is a win I don't care what y 'all say yep that's me Clifford Taylor IV you might have seen the skits the reactions my journey from basketball to college football or my career in sports media well somewhere along the way this platform became bigger than I ever imagined and now I'm bringing all of that excitement to my brand new podcast The Clifford Show this is a place for raw unfiltered conversations with some of your favorite athletes, creators and voices that not

56:14Emily Oster:We'll be right back.

56:37Emily Oster:behind the scenes, follow at Clifford and at TikTok Podcast Network on TikTok. You can have opinions, you can have like a strong stance, and then there's your body having its own program.

56:52Perry Wilson:I'm Dr. Maya Shunker, a cognitive scientist and host of the podcast, A Slight Change of Plans, a show about who we are and who we become when life makes other plans. We share stories and scientific insights to help us all better navigate these periods of turbulence and transformation.

57:10Emily Oster:There is one finding that is consistent, and that is that our resilience rests on our relationships. I wish that I hadn't resisted for so long the need to change.

57:22Perry Wilson:We have to be willing to live with a kind of uncertainty that none of us likes. Listen to A Slight Change of Plans on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts.

57:58Emily Oster:how to build real wealth starting with the mindset shifts too many of us were never ever taught.

58:04Perry Wilson:Financial education is not always about like I'm gonna get rich that's great it's about creating an atmosphere for you to be able to take care of yourself and leave a strong financial legacy for your family.

58:19Emily Oster:If you've ever felt you didn't get the memo on money this conversation is for you to hear more. Listen to Money and Wealth with John O 'Brien from the Black Effect Network on the I'd Heart Radio app, Apple Podcasts, or wherever you get your podcasts. Hi, Emily and Perry. This is Mary from Toronto, and I have a question about Lyme disease. I've heard that dogs can get vaccinated for it, but I can't. Does Lucy the Beagle know something I don't.

58:53Perry Wilson:Thanks so much. Okay, Perry. I love this question because it is asked in my household all the time. Like if there, if, and when there is a Lyme disease vaccine for humans, my husband will literally be the first person to get it. Like if there's a line, he is standing. He's like, he's like the people who wanted to buy the first iPhone. That's my husband is going to be like that for a Lyme disease vaccine. No, he hasn't had it, but he's like a, he's like a tick lunatic. He's like afraid every night when it gets to tixies and every night when we get into bed he's like okay can you check me for tix every single night oh i find that kind of romantic actually it's a

59:29Emily Oster:little it's like a it's like a grooming primate thing do you eat the tix if you find them

59:35Perry Wilson:uh there's one summer i found like five tix on my kid anyway um we never got we never got lyme disease okay so uh so there is a lyme disease for dogs but not for humans and there used to be a Lyme disease vaccine for humans.

59:49Emily Oster:Yeah, yeah, yeah. It existed. Late 90s, it came out. And basically, the only reason we don't have it anymore is it was a commercial failure. There are a few reasons for that. One is the vaccine schedule wasn't great. I think it was zero. So you got one and then you had a booster a month later and then another one 12 months later. So it's like a series of three vaccines, which is a little bit annoying because Lyme disease is not transmitted human to human. The it sort of shifts the public health landscape of the vaccine. So the Lyme vaccine was never going to be part of like the childhood vaccination schedule, which is really designed to protect all of society.

1:00:32Emily Oster:Right. Like Lyme disease really only the vaccine is really only going to protect the person. The other thing about Lyme disease is it's a bacteria, not a virus. We have antibiotics that can treat it. So it's not, you know, the sort of risk isn't there. But I mean, we had it was FDA approved. You could have gotten it and then just stopped making it because they weren't making enough money.

1:00:55Perry Wilson:But exciting news is that there is actually a new Lyme vaccine that is in phase three trials. And they've just announced that basically I think the phase three trials went well. This is like a very recent announcement. And so I do expect there to be a Lyme vaccine coming down the line. And although you're right, I think the commercial success was somewhat limited. I actually think people have gotten more concerned about the sort of long-term impacts of Lyme disease. And it is true that although if you notice the tick and you get treatment, basically you can avoid getting long-term Lyme disease.

1:01:30Perry Wilson:Many people don't. And so this can be a very significant, it can be incredibly debilitating if people don't have it. My brother had Lyme disease once.

1:01:40Emily Oster:My daughter had Lyme disease.

1:01:42Perry Wilson:Yeah, because you live near Lyme, Connecticut. That's where my brother got it.

1:01:46Emily Oster:My backyard is mostly ticks.

1:01:49Perry Wilson:Yeah, that's where they live. And so, yeah, I mean, it's like, you know, it's a, there's a telltale rash. If your child has a tick, watch for the rash. But I am excited about the Lyme vaccine.

1:02:02Emily Oster:Yeah, tick checks. You have 24 hours after the tick has bit to get it off before it can transmit the bacteria. So tick checks on a daily basis if your kids are outside.

1:02:12Perry Wilson:Yeah, my brother did not get, my brother, he got treated and he did not have any significant long-term Lyme. Yeah, yeah.

1:02:20Emily Oster:You can save the tick if you want to show your doctor. They'll have fun with it. But a lot of the time, if the tick has been on, and certainly if there's that target lesion, you'll get empiric antibiotic treatment.

1:02:31Perry Wilson:Doxycycline for the win.

1:02:35Emily Oster:All right, that's it for us today. Stick with us next week when we'll ask, what's the deal with testosterone for men?

1:02:42Perry Wilson:Yay, finally, we're studying men. Phew. Wellness Actually is produced in association with iHeart Media. Our senior producer is Tamar Avishai. Our executive producer at iHeart is Jennifer Bassett. Our theme music is by Eric Deutsch. And our content is for educational purposes only.

1:03:02Emily Oster:If you like the show, help other people find us. Leave a rating and review on Apple Podcasts or your podcatcher of choice. And help us spread the word about the show. You can follow us on Instagram at wellnessactuallypod. And don't forget, we want to hear from you. Head over to wellnessactually.fm and leave us a question for our mailbag. Or suggest a topic for a future show.

1:03:24Perry Wilson:We'll let the influencers have the last word. Ladies, I want you to know the symptoms of perimenopause and menopause. These are 34 common symptoms. acne, allergies, anxiety, bloating, constipation, body odor, breast soreness, brittle nails, cholesterol changes, depression, difficulty concentrating, dizzy spells, fatigue, gum problems, hair loss, headaches and or migraines, or palpitations, hot flashes, irregular periods, irritability or rage, itchy skin, joint and muscle pain, libido changes, loss of breast fullness, memory lapses, mood swings, nausea, night sweats, osteopenia and osteoporosis, pain during sex, panic disorder, sleep issues, ulterior incontinence, vaginal dryness.

1:04:20Emily Oster:Peace to the planet. Charlamagne Tha God here and listen, we are back. The Black Effect Podcast Festival is back in Atlanta on April 25th at Pullman Yard. and the full lineup is nuts. We got the Grits and Eggs podcast, Deontay Kyle and Big Ice Cup Cat. We got Club 520 with Jeff Teague and the gang. Don't call me white, girl. Mona will be there. Keep it positive, sweetie, with Crystal Renee. We got Reality with the King with Carlos King. And yes, Drink Champ will be in the building. Plus, you know, we're going to have a lot of guests. So you need to join us. And we got the Black Effect Marketplace, the picture podcast, and everything you expect from the Black Effect Podcast Festival.

1:04:58Emily Oster:Tickets are on sale right now. Go get yours at blackeffect.com slash podcast festival. Don't play yourself, okay? Pull up.

1:05:09Emily Oster:A win is a win. A win is a win. I don't care what y 'all say. Yep, that's me, Clifford Taylor IV. You might have seen the skits, my basketball and college football journey, or my career in sports media. Well, now I'm bringing all of that excitement to my brand new podcast, The Clifford Show. This is a place for raw, unfiltered conversations with athletes, creators and voices that not only deserve to be heard, but celebrated. So let's get to it. Listen to The Clifford Show on the iHeartRadio app, Apple Podcasts or wherever you get your podcasts. And for more behind the scenes, follow at Clifford and at TikTok Podcast Network on TikTok.

1:05:45Emily Oster:Then she says, have you seen a photo of my son? And I'm like, who is this person? Welcome to the Boys and Girls Podcast.

1:05:51Perry Wilson:Arranged marriage is basically a reality show And you're auditioning for your soulmate And who's judging? Only your entire family I sacrificed myself to this ancient tradition Hoping to find love the right way And instead, I found chaos, comedy, and a lot of cringe Listen to Boys and Girls on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts This is an iHeart Podcast Guaranteed Human