Latest / Wellness, Actually with Emily Oster & Perry Wilson, MD / What's the deal with hormone replacement therapy?

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What's the deal with hormone replacement therapy? · Wellness, Actually with Emily Oster & Perry Wilson, MD

0:01
Speaker 1: Hi, Perry, Hi, eamily, Are you excited to talk about
0:04
Speaker 1: hormone replacement therapy? I just want to tell the listeners
0:07
Speaker 1: that Perry was extremely reluctant to discuss hormone replacement therapy.
0:12
Speaker 1: Isn't that right that you preferred maybe hair loss, things
0:16
Speaker 1: about hair loss, and no other man topics.
0:19
Speaker 2: It's not for the reason you thought when you pitched
0:22
Speaker 2: hormone replacement therapy. I think I said something like, oh, brother,
0:29
Speaker 2: and you assumed, incorrectly, incorrectly, incorrectly, that I was being
0:35
Speaker 2: a man, and I was like, oh, lady stuff, and
0:37
Speaker 2: that's not true. I said, oh, brother, because it's really
0:42
Speaker 2: really complicated, and I know it's going to take a
0:44
Speaker 2: ton of research to get it right.
0:46
Speaker 1: I'm very excited, But also I wanted to mention, do
0:48
Speaker 1: you know about manopause?
0:51
Speaker 2: I have heard the term of manopause, and I think
0:54
Speaker 2: it's I think it's really good that we're finally recognizing
1:01
Speaker 2: men changes in men's life that are clearly just as
1:05
Speaker 2: severe and disruptive as anything that could possibly happen to
1:09
Speaker 2: a woman. And I say that as a man and
1:11
Speaker 2: as a father of a man.
1:13
Speaker 3: I think you may be in manopause you'll have to actually.
1:15
Speaker 2: Tell me what manopause is, and then I'll.
1:17
Speaker 1: Tell it's when you gradually decay between the ages of
1:20
Speaker 1: forty and fifty.
1:21
Speaker 3: Are you gradually decaying?
1:23
Speaker 2: I mean more or less?
1:24
Speaker 1: I believe it begins with the rotator, cuff at rotator,
1:28
Speaker 1: and then it's all downhill from there. I'm Emily Aster,
1:33
Speaker 1: I'm an economist and a data expert.
1:35
Speaker 2: And I'm Perry Wilson, I'm a medical doctor.
1:38
Speaker 1: It's Thursday, April twenty third, twenty twenty six, and this
1:41
Speaker 1: is wellness actually.
1:43
Speaker 2: Because you're getting a staggering amount of health and wellness
1:46
Speaker 2: information nowadays from every source imaginable, and some of it
1:50
Speaker 2: is awesome.
1:51
Speaker 1: And some of it is well actually both. Fortunately, we're
1:57
Speaker 1: both people who know how to read studies, how to
1:59
Speaker 1: parse data, and can tell you what's worth thinking about
2:02
Speaker 1: and what you can safely ignore.
2:04
Speaker 2: But before we dig in, a note that this podcast
2:07
Speaker 2: is for educational purposes and should not be construed as
2:09
Speaker 2: medical advice. We don't know your unique situation, so talk
2:13
Speaker 2: to your doctor for personal health decisions.
2:15
Speaker 1: This week we're asking what's the deal with hormone replacement therapy?
2:19
Speaker 3: And this is a two Parter.
2:21
Speaker 1: Next week we'll talk about testosterone, Perry and I will
2:24
Speaker 1: give the official smasher pass, and then we'll get to
2:26
Speaker 1: your question of the week. But first, let's do the
2:29
Speaker 1: health news roundup after the break, and now for the
2:44
Speaker 1: health news of the week, Perry, there is a new
2:48
Speaker 1: kind of diabetes, as if we didn't have enough with
2:51
Speaker 1: the first two kinds.
2:52
Speaker 3: It is called type five diabetes.
2:56
Speaker 1: This has been recognized for many years, but it is
2:59
Speaker 1: now official diagnosis. So tell me what is type five diabetes?
3:06
Speaker 1: And what happened to three and four?
3:09
Speaker 2: Yeah? This is this is fascinating. The International Diabetes Federation
3:13
Speaker 2: has officially recognized type five diabetes. After some period of time,
3:18
Speaker 2: I think people listening will know about type one diabetes,
3:21
Speaker 2: which is a childhood onset form usually an autoimmune disorder.
3:25
Speaker 2: Type two diabetes, which is the syndrome of insulin resistance
3:30
Speaker 2: that's associated with overweight and obesity. That's so prevalent in
3:33
Speaker 2: the United States. Type three diabetes does exist. There's like
3:37
Speaker 2: various subsets, but one is caused by damage to the pancreas,
3:43
Speaker 2: like like trauma to the pancreas or severe pancreatitis. For example.
3:49
Speaker 2: Type four is a very rare form of diabetes recognized
3:53
Speaker 2: as insulin resistance in lean older adults, so it's sort
3:57
Speaker 2: of an aging related form of diabetes. And then we
4:00
Speaker 2: have type five, which is really interesting and very different.
4:02
Speaker 2: It's caused by severe malnutrition and actually protein malnutrition. We
4:07
Speaker 2: just did the protein episode. So this is quite common,
4:11
Speaker 2: but not in the developed world. So there are probably
4:15
Speaker 2: ten to twenty million people in sub Saharan Africa who
4:19
Speaker 2: are suffering from type five diabetes. Scientists are still trying
4:23
Speaker 2: to understand the exact causes and treatments of this because
4:28
Speaker 2: it does seem like it is not purely due to
4:32
Speaker 2: issues with insulin sensitivity, and it is driven by protein malnutrition,
4:37
Speaker 2: so these are people who are getting enough carbohydrate, enough fat,
4:39
Speaker 2: but not those essential proteins. It can affect the pancreas.
4:43
Speaker 3: That is extremely interesting. Okay, but this is rare.
4:46
Speaker 1: This is much rareer than either type one, certainly than
4:49
Speaker 1: type two, but even then type one.
4:52
Speaker 2: It is certainly rare in the United States. But you know,
4:55
Speaker 2: twenty five million people around the world probably suffer from this,
4:58
Speaker 2: and so it's good that we're drying some attention to it,
5:00
Speaker 2: hopefully get some research in that area, speaking of research
5:05
Speaker 2: that might start to happen now, NPR and multiple news
5:08
Speaker 2: outlets have reported that some psychedelics, including psilocybin and iyebo gain,
5:16
Speaker 2: may be reclassified by the Trump administration and make them
5:21
Speaker 2: eligible to get an expedited FDA review for mental health conditions.
5:27
Speaker 2: Emill you and I have talked about I think it's
5:28
Speaker 2: on our show, our upcoming show list actually talking about psychedelics.
5:33
Speaker 2: So what do you think about this news that it's
5:35
Speaker 2: going to be easier to study them.
5:37
Speaker 1: I mean, broadly, I would say I'm supportive of this.
5:41
Speaker 1: You know, there was a period of time in the
5:42
Speaker 1: nineteen sixties when psychedelics were something people thought, we're going
5:46
Speaker 1: to be so great, and then they started using them
5:48
Speaker 1: more recreationally and it became, you know, something that we
5:51
Speaker 1: weren't thinking about as medical treatments.
5:54
Speaker 3: But actually seems like in the.
5:57
Speaker 1: Last you know, decade or so, there's been a lot
6:01
Speaker 1: more evidence that used appropriately, psychedelics can actually be quite
6:08
Speaker 1: effective at treating some pretty refractory conditions like pete severe PTSD.
6:13
Speaker 3: There was actually a really interesting episode of.
6:16
Speaker 1: The Daily which I realized is not research, with the
6:19
Speaker 1: reporter sort of talking about his experience doing a sort
6:23
Speaker 1: of particular psychedelic in Mexico as a treatment for kind
6:27
Speaker 1: of long standing trauma issues.
6:30
Speaker 3: So I mean this feels to me like I always
6:32
Speaker 3: like more research.
6:33
Speaker 1: It does feel like an area that's probably under research
6:35
Speaker 1: for reasons that are you know, understandable, but maybe we
6:39
Speaker 1: should try to get past. I will say, of course,
6:42
Speaker 1: for many people, they're going to read some of these articles.
6:45
Speaker 1: Trump made an announcement about this, and Joe Rogan said he
6:48
Speaker 1: texted Trump about I Begain, which is one of these psychedelics,
6:51
Speaker 1: and the President responded, sounds great.
6:54
Speaker 3: Do you want FDA approval.
6:56
Speaker 1: Let's do it, which of course is not like it's
6:59
Speaker 1: going to cause some people to be like come on,
7:00
Speaker 1: but I actually think we should be researching these.
7:03
Speaker 3: Maybe we don't text FDA approval.
7:06
Speaker 2: Yeah. The categorization of dangerous substances you've heard, like category one,
7:11
Speaker 2: category two, does have implications for research. It does make
7:15
Speaker 2: it much harder to run a placebo controlled trial, like
7:19
Speaker 2: in a university like mine, if you're testing something that's
7:21
Speaker 2: category one or category two. So moving these into category
7:24
Speaker 2: three does just kind of open that door. But you're right,
7:26
Speaker 2: it should follow the pathway like let's find out if
7:28
Speaker 2: these things work. If they work, that's great, and we
7:31
Speaker 2: should learn how to give them safely.
7:32
Speaker 3: We'll see, all right.
7:34
Speaker 1: Speaking of political questions, there is a new nominee for
7:37
Speaker 1: CDC director. This has proven to be an extremely difficult
7:40
Speaker 1: job to fill. People keep getting in and then getting fired.
7:44
Speaker 1: This new person the quote I saw on CNN was
7:49
Speaker 1: we just need someone who is not crazy.
7:52
Speaker 3: So what do you think about the nominee?
7:55
Speaker 2: So this is Erica Schwartz, who is very much a
8:01
Speaker 2: straight down the middle nominee for for the director of
8:06
Speaker 2: the CDC. She is a physician. She's a lawyer who
8:11
Speaker 2: has a master's degree in public health. This CDC position,
8:14
Speaker 2: as you mentioned, has been it's like a defense against
8:18
Speaker 2: the dark arts in the Harry Potter universe. Like it's
8:22
Speaker 2: just a tough one to keep every year different every
8:26
Speaker 2: year someone or more more often than that. This is
8:30
Speaker 2: I think very much a reaction to some real pressure
8:36
Speaker 2: the administration has been getting sort of pushback against the
8:39
Speaker 2: so called Maha agenda. President Trump I don't think is
8:43
Speaker 2: as on board with the full RFK Junior philosophy than
8:49
Speaker 2: that group of people or the people who support those policies.
8:52
Speaker 2: Would like, and there's been you know, particular pushback against
8:55
Speaker 2: the anti vaccine rhetoric in the face of the rising
8:59
Speaker 2: number of measles cases and whatnot. So here we have
9:01
Speaker 2: a CDC director who's like could have been appointed by Biden,
9:05
Speaker 2: could have been appointed by Bush, like you know, an appropriate,
9:09
Speaker 2: down the middle CDC director. What is really going to
9:12
Speaker 2: be interesting if she gets confirmed is like, how does
9:15
Speaker 2: she work with RFK Junior because clearly they have some
9:19
Speaker 2: different policy beliefs.
9:21
Speaker 1: Absolutely, I mean, this feels like someone who can definitely
9:24
Speaker 1: get confirmed on like some of the people they've nominated.
9:27
Speaker 1: But the question of, you know, can can she work
9:29
Speaker 1: inside this administration?
9:30
Speaker 3: I guess we will find out.
9:34
Speaker 2: We'll find out. And that's it for the health news
9:36
Speaker 2: of the week. After the break, what's the deal with
9:39
Speaker 2: hormone replacement therapy?
9:46
Speaker 3: Welcome back.
9:47
Speaker 1: So we're going to talk about hormone replacement therapy, and
9:51
Speaker 1: I want to start by saying up front, you know,
9:53
Speaker 1: this is not a full discussion of all of the
9:57
Speaker 1: potential benefits and whether you personally should be on R
10:00
Speaker 1: replacement therapy. I think what we find in Perry, you
10:03
Speaker 1: can correct me if this isn't what you find interesting here.
10:06
Speaker 3: But I think what we've found interesting here.
10:07
Speaker 1: Is kind of how the discussion of this science has evolved.
10:11
Speaker 1: And so we'll talk a little bit about how we
10:13
Speaker 1: got to where we are now, where we were before,
10:17
Speaker 1: some of the data, and then some of the benefits
10:20
Speaker 1: that are potentially true here. But this is really something
10:24
Speaker 1: where whether one should be on this or not is
10:27
Speaker 1: very dependent on talking to your doctor about where you are.
10:30
Speaker 2: Yeah, this is complicated, folks. You know. This isn't red
10:34
Speaker 2: light therapy where it's like, well, it's going to cost
10:36
Speaker 2: you some money, but it's probably not going to kill you.
10:38
Speaker 2: There are benefits, there are risks. We'll touch on some
10:41
Speaker 2: of these. There are subgroups of people that would benefit more.
10:44
Speaker 2: There are subgroups of people that have higher risks. This
10:46
Speaker 2: is like a real deal talk with your doctor, but
10:49
Speaker 2: it's also a completely fascinating area. I do want to
10:53
Speaker 2: give one other disclaimer. There's like sort of an elephant
10:56
Speaker 2: in the room here, which is that I'm a and
11:01
Speaker 2: no true talking about hormone replacement therapy for women. This
11:06
Speaker 2: could be like the worst case of recorded man'splaining in history.
11:12
Speaker 2: So Emily, I think we need like a safe word
11:14
Speaker 2: or something. If I start saying something like boorish or dumb,
11:19
Speaker 2: you know, if I if I'm like, oh, menopause, you know,
11:23
Speaker 2: is that that ba really beautiful transition or something like
11:27
Speaker 2: you just say say rude, bega and I'll back off.
11:32
Speaker 1: Safe word tampon, that's safe and you shut your mouth.
11:36
Speaker 2: That this actually can work.
11:38
Speaker 1: We can use this in all episodes. But yes, I
11:40
Speaker 1: take I think that is a reasonable point. And I
11:44
Speaker 1: will also say disclaimer on my side. You know, although
11:48
Speaker 1: I am a woman of perimenopausal age who is presumably
11:51
Speaker 1: somewhere in perimenopause, the actual experience of a lot of
11:55
Speaker 1: the symptoms that people are using hormone replacement therapy to
11:58
Speaker 1: treat is very different.
12:00
Speaker 3: And so I can say something.
12:03
Speaker 1: About what it is like to be a forty six
12:05
Speaker 1: year old woman, but certainly cannot speak to the experience
12:07
Speaker 1: of all forty six year old women. So with that
12:10
Speaker 1: lengthy tampon disclaimer and so on, let's go. And I
12:15
Speaker 1: think the place to start here is with the biology
12:20
Speaker 1: of what hormone are we replacing and why so? Can you,
12:25
Speaker 1: very briefly, from your doctor's standpoint, tell me what hormone
12:28
Speaker 1: are replacing.
12:28
Speaker 3: And why.
12:30
Speaker 2: So? Can I say, for again, very briefly, that hormones stop.
12:38
Speaker 2: I'm like, I'm just gonna like spin my chair around
12:40
Speaker 2: and sit in the corner. Okay, we're talking about steroid hormones,
12:45
Speaker 2: which include estrogen progesterone, and we'll touch on testosterone at
12:49
Speaker 2: the end as well. And I do want to say
12:51
Speaker 2: something about the biology of what makes steroid hormones, and
12:53
Speaker 2: there are a few others as well, really special in
12:56
Speaker 2: the body. We have these cells in our body which
12:58
Speaker 2: are like little factory. They have a job to do,
13:01
Speaker 2: and most of the way that they sense the outside
13:04
Speaker 2: world or the world outside the cells, is through these
13:06
Speaker 2: receptors on their surface, and the drugs we take and
13:09
Speaker 2: a lot of the chemicals in our body buying these
13:11
Speaker 2: receptors on the surface of the cells, but they don't
13:13
Speaker 2: get into the cells. They just sort of bind their receptor.
13:15
Speaker 2: They say hey, we're out here, and it causes the
13:17
Speaker 2: cell to do something else, like produce more insulin, you know,
13:20
Speaker 2: if it's a factory, produce more widgets or something. The
13:22
Speaker 2: steroid hormones receptors are not on the outside of the cell.
13:26
Speaker 2: They're in the nucleus of the cell, which is where
13:28
Speaker 2: the DNA lives. Steroid hormones have the ability to go
13:32
Speaker 2: right through the cellular membrane because they're lipid soluble and
13:35
Speaker 2: into the nucleus where they bind their receptors, and their
13:37
Speaker 2: effect is to change what DNA gets transcribed inside that cell. So,
13:44
Speaker 2: to continue the factory analogy, it's like, you know, most
13:48
Speaker 2: drugs and substances kind of like send a telegram to
13:52
Speaker 2: the factory and are like make more widgets, and steroid
13:54
Speaker 2: hormones go into the factory and can redesign the entire thing,
13:58
Speaker 2: which is why you can take a hormone like testosterone
14:01
Speaker 2: and all of a sudden, a cell that didn't grow
14:03
Speaker 2: hair now grows hair. That also explains why the effects
14:08
Speaker 2: of stereoid hormones are so broad, like they can do
14:13
Speaker 2: so many things, and we don't even fully understand why
14:16
Speaker 2: they do all the things they do, so they really
14:18
Speaker 2: are a special group of things. And that's my very
14:21
Speaker 2: basic biology of what we're talking about here. When we
14:25
Speaker 2: speak about hormone replacement therapy in terms of women in general,
14:30
Speaker 2: we're I mean, it is what it sounds like. We're
14:32
Speaker 2: talking about giving doses of the hormones that go down
14:36
Speaker 2: in perimenopause and postmenopause, which is estrogen and progesterone HRT
14:41
Speaker 2: is supposed to replace those levels, not to make them higher,
14:47
Speaker 2: but to get them back to sort of where they
14:49
Speaker 2: were at baseline. In contrast, for women who are premenopausal,
14:53
Speaker 2: who might have used oral contraceptive pills or something, where
14:57
Speaker 2: the doses of those hormones are much much higher because
14:59
Speaker 2: they're designed to actually suppress the endogenous hormone levels. That
15:04
Speaker 2: wasn't very brief.
15:05
Speaker 3: It was not brief, but it was I thought it
15:07
Speaker 3: was interesting.
15:08
Speaker 1: I think that's great, and I think the kind of
15:10
Speaker 1: big picture here you want to imagine is that during
15:13
Speaker 1: perimenopause and menopause, your estrogen, in particular, although both estrogen
15:19
Speaker 1: progesterone change, estrogen goes down a lot. Estrogen is part
15:25
Speaker 1: of what supports a lot of ways that we feel good,
15:28
Speaker 1: and so hormone replacement therapy is potentially a way to
15:33
Speaker 1: improve some of the symptomatic experiences perimenopause. We'll talk about this,
15:37
Speaker 1: but things like hot flashes or sleep disruptions, which are
15:41
Speaker 1: kind of characteristic of many people during perimenopause, estrogen is
15:46
Speaker 1: a potential treatment. Vaginal dryness is another example of where
15:49
Speaker 1: just as your estrogen fallows, this goes, this symptom gets
15:53
Speaker 1: more significant, and so we're kind.
15:55
Speaker 3: Of all of these reasons.
15:56
Speaker 1: There is a biology behind the idea that replacing some
15:59
Speaker 1: of that SAM would improve some of your symptoms, absolutely
16:04
Speaker 1: make you have more more of the hormone profile of
16:07
Speaker 1: a thirty five year old than of a fifty one
16:10
Speaker 1: year old.
16:11
Speaker 2: Exactly, And that made so much biological sense that for
16:15
Speaker 2: years and years and years this was a very common practice.
16:18
Speaker 2: It was like we had access to these hormones. They
16:22
Speaker 2: were first discovered in the nineteen twenties, I think, and
16:26
Speaker 2: it is true that estrogen to this day is still
16:29
Speaker 2: a lot of the estrogen that people received comes from
16:32
Speaker 2: horse urine. Premarin is pregnant mary urine. There are seven
16:36
Speaker 2: hundred and fifty thousand horses around the world that are
16:39
Speaker 2: giving their urine to make some of these estrogens. Isn't
16:42
Speaker 2: that fascinating? So nice of that all of a sudden,
16:47
Speaker 2: this study happened that essentially overnight tanked the use of
16:53
Speaker 2: hormone replacement therapy in the United States. That's the Women's
16:56
Speaker 2: Health Initiative study. And Emily, can you tell us the
16:59
Speaker 2: story of the Women's Health initiative, because I think it's
17:01
Speaker 2: hard to understand any of this without talking about that.
17:04
Speaker 1: Yeah, So I actually before before I tell you the
17:07
Speaker 1: story of this, I want to spend like I remember
17:10
Speaker 1: how you nerded out on physics. I'm going to nerd
17:12
Speaker 1: out on statistical external validity, just very briefly, and then
17:15
Speaker 1: I will talk about this. So when we talk about
17:18
Speaker 1: scientific studies, we often talk about randomized control trials as
17:21
Speaker 1: kind of the gold standard for generating causal effects. And
17:25
Speaker 1: that's because when you have a randomized trial, you take
17:28
Speaker 1: some people, you divide them up randomly, so you know
17:31
Speaker 1: they're kind of the same at the beginning. You do
17:33
Speaker 1: something to want and not the other, and then you
17:35
Speaker 1: can be confident that for those people, if you see
17:38
Speaker 1: different outcomes, the different outcomes are a result of the treatment.
17:42
Speaker 1: That's like the idea, but that is going to tell
17:46
Speaker 1: you a causal effect for the people that you study.
17:52
Speaker 1: And if that effect is the same across all people
17:56
Speaker 1: in the entire population, then you have learned about the
17:59
Speaker 1: whole population. But if you have a population where the
18:03
Speaker 1: effect might be different than like the rest of the world,
18:06
Speaker 1: then you haven't actually learned about everybody.
18:09
Speaker 3: So like to be simple.
18:11
Speaker 1: Let's imagine that you have a study of a drug
18:14
Speaker 1: and you only include men, and then you want to
18:17
Speaker 1: be like, Okay, this was effective for men, now I'm
18:19
Speaker 1: going to give it to everyone. Well, it's very possible
18:22
Speaker 1: the effect for women could be different.
18:24
Speaker 2: I mean, we did this for fifty years. By the way,
18:26
Speaker 2: this was all of medicine.
18:27
Speaker 3: This is the case.
18:28
Speaker 1: It's worked, and it turns out, actually that doesn't port
18:31
Speaker 1: very well. There are a lot of things where women
18:33
Speaker 1: react differently than men. So this is an idea called
18:36
Speaker 1: external validity. And we worry when we want randomize trials
18:39
Speaker 1: about this external validity. And this is a topic that
18:43
Speaker 1: I work on, so I feel very passionate about it.
18:46
Speaker 1: But I say that at the top, and then I'm
18:48
Speaker 1: going to tell you about the Women's Health Initiative because
18:50
Speaker 1: I think in some ways that's some of the issues
18:52
Speaker 1: that came up with that trial. So the Women's Health
18:56
Speaker 1: Initiative is a study launched by the NIH in the
18:59
Speaker 1: early nineteen nineties. It included about thirty thousand, twenty seven
19:04
Speaker 1: thousand postmenopausal women. These women had an average age of
19:08
Speaker 1: sixty three, and they they randomized them to sort of
19:13
Speaker 1: two different treatments of sort of hormone replacement therapy and
19:19
Speaker 1: also a placebo. And when the follow up was published
19:25
Speaker 1: in two thousand and two, they actually the people doing
19:28
Speaker 1: this study halted the study in two thousand and two,
19:31
Speaker 1: or halted one arm of the study because of a
19:35
Speaker 1: concern that there was an increase in both breast cancer
19:38
Speaker 1: and cardiovascular events which exceeded what they saw as the
19:42
Speaker 1: benefits of this. And it was a relatively small increase numerically,
19:47
Speaker 1: but percentage wise it was quite sizable. So the relative
19:51
Speaker 1: increase about twenty five percent in invasive breast cancer and
19:54
Speaker 1: about thirty percent in cardiovascular events, was actually also an
19:57
Speaker 1: increase in strokes. And with that change, we pretty much
20:03
Speaker 1: saw a absolute tanking of any hormone replacement therapy prescriptions.
20:10
Speaker 1: So this was sort of the end at least for
20:13
Speaker 1: some period of kind of widespread hormone replacement. And I
20:17
Speaker 1: would say that's the nadier and then sort of over
20:20
Speaker 1: time this has returned. But fundamentally the thing to understand
20:25
Speaker 1: is a randomized trial of this which showed some elevated risks.
20:28
Speaker 2: I want to double click on the relative risk versus
20:31
Speaker 2: the absolute risk, because that's another important concept. That people
20:34
Speaker 2: need to sort of be aware of when they think
20:36
Speaker 2: about these studies. So let's take invasive breast cancer. When
20:39
Speaker 2: that arm of the Women's Health Initiative was stopped, there
20:43
Speaker 2: was a twenty six percent relative increase in invasive breast cancer,
20:47
Speaker 2: and so people interpret that as like, my risk of
20:49
Speaker 2: breast cancer would go up by twenty six percent. But
20:52
Speaker 2: if you look at the absolute numbers, there were thirty
20:55
Speaker 2: cases of breast cancer per ten thousand women per year
21:00
Speaker 2: in the placebo group, so thirty per ten thousand per
21:03
Speaker 2: year in placebo, thirty eight per ten thousand per year
21:08
Speaker 2: in the hormone replacement therapy group. So we're talking eight
21:12
Speaker 2: extra cases per ten thousand women, right, And that doesn't
21:18
Speaker 2: sound as bad as a twenty five percent increase. Here
21:21
Speaker 2: twenty five percent, and they're like, oh my gosh, that
21:23
Speaker 2: means I'm going to have a twenty five percent chance
21:25
Speaker 2: of getting cancer or worse or something like that. Really,
21:27
Speaker 2: the absolute risk is very small, not zero, but very small.
21:31
Speaker 2: And sometimes the way we help explain that to people
21:35
Speaker 2: is with a concept called number needed to harm, which
21:38
Speaker 2: is like, how many people would you need to treat
21:41
Speaker 2: for there to be one extra case of cancer, And
21:43
Speaker 2: in this case, if you do a little math, it
21:45
Speaker 2: would be one thousand, two hundred and fifty women. If
21:48
Speaker 2: you treat one thousand, two hundred and fifty women with
21:50
Speaker 2: hormone replacement therapy, you would get one extra case of
21:53
Speaker 2: invasive breast cancer per year, not nothing. But again, Emily,
21:58
Speaker 2: and you're about to talk to us about this, that's
22:00
Speaker 2: assuming that the women in the study are the same
22:05
Speaker 2: as the women that you're prescribing the hormone replacement therapy too.
22:09
Speaker 2: And is that the case?
22:10
Speaker 1: So first of all, let me just say I hate
22:11
Speaker 1: those number needed to treat things. I understand doctors like
22:14
Speaker 1: those as a way to describe risk size, and they
22:17
Speaker 1: I don't think they make any sense to It don't
22:18
Speaker 1: work for you.
22:19
Speaker 2: People, a right, it doesn't work for me. Listeners tell
22:21
Speaker 2: us if you like number needed to treat.
22:24
Speaker 1: Yeah, I don't like it, but I guess I'm not
22:27
Speaker 1: the only listener, but I'm the first listener and I
22:29
Speaker 1: don't like it. I will say that I think that
22:32
Speaker 1: there is this sort of difference between percent and percentage points,
22:36
Speaker 1: which is very important. People here twenty five percent increase
22:39
Speaker 1: and they immediately think, you know, that raises my risk
22:42
Speaker 1: from zero to twenty five percent as opposed to it
22:45
Speaker 1: is a twenty five percent increase from an already low
22:48
Speaker 1: number relative to a very low number. So I think
22:50
Speaker 1: that's that's like we can talk more at some point
22:53
Speaker 1: about how to talk about small numbers to people. Okay,
22:57
Speaker 1: So getting back to the to the women Tell initiative,
23:00
Speaker 1: you know, in this when this sort of first stuff
23:02
Speaker 1: came out in two thousand and two, I think the
23:03
Speaker 1: prescription rates for HRT drop by like eighty percent. I mean,
23:08
Speaker 1: it was a real tanking. And because it sort of
23:10
Speaker 1: fell to people like so it sounded like the you know,
23:13
Speaker 1: hormonal placement therapy gives you breast cancer. That was kind
23:15
Speaker 1: of like the headline was like, you take this, You're
23:17
Speaker 1: gonna get breast cancer. But then sort of almost immediately
23:23
Speaker 1: things got like quite more complicated. So there was a
23:26
Speaker 1: second arm of the trial that treated in a slightly
23:30
Speaker 1: different way, and that arm was halted in two thousand
23:33
Speaker 1: and four because of a concern about an increased risk
23:37
Speaker 1: of stroke. But actually in that group, the risk of
23:40
Speaker 1: invasive breast cancer had gone down.
23:42
Speaker 3: So now already.
23:43
Speaker 1: There's like a little bit more of a complicated story,
23:46
Speaker 1: which may relate to the overall small numbers could relate to,
23:51
Speaker 1: you know, some actual differences in impacts, but it was
23:53
Speaker 1: sort of made the story immediately more complicated. And then
23:58
Speaker 1: you know, over the past, probably over the ten years
24:02
Speaker 1: or fifteen years following this initial publication, one of the
24:06
Speaker 1: things that became pretty clear was that the age group
24:10
Speaker 1: in the study seemed to matter a lot. So the
24:15
Speaker 1: primary group, the average age of people enrolled in the
24:17
Speaker 1: study was like sixty three, but when they cut the study,
24:22
Speaker 1: they what it's called stratified, divided the study into people
24:27
Speaker 1: who were sort of closer to menopause, so people who
24:30
Speaker 1: were fifty to fifty nine, so the kind of younger
24:33
Speaker 1: group within ten years of menopause.
24:36
Speaker 3: They actually looked like.
24:38
Speaker 1: The treatment decreased their risk of cardiovascular disease and all
24:42
Speaker 1: cause mortality.
24:43
Speaker 3: So actually in that group they seem to have.
24:45
Speaker 1: An overall mortality benefit and a reduction in cardiovascular disease
24:50
Speaker 1: which sort of was offset by these older individuals. So
24:55
Speaker 1: in some sense, what's really important about that is you
24:57
Speaker 1: kind of, again getting back to this external validity point,
25:01
Speaker 1: we put in a bunch of people, we drew some
25:04
Speaker 1: conclusions based on a much older cohort, and then we
25:07
Speaker 1: applied that conclusion to everybody, even though A it looked
25:10
Speaker 1: like the younger cohort, if anything, had some benefits, and
25:14
Speaker 1: B actually treatment with HRT is somewhat more common in
25:17
Speaker 1: these younger cohorts, you know, and that is where this
25:19
Speaker 1: symptomatic stuff shows up most significantly. And so you're sort
25:23
Speaker 1: of learning from a group that's like not even the
25:25
Speaker 1: group you're really interested in treating. And I think that
25:29
Speaker 1: realization over time has kind of we've started to return
25:33
Speaker 1: to the use of HRT, but it has taken a
25:36
Speaker 1: very taken a very long time.
25:38
Speaker 2: Yeah, the Women's Health Initiative study was not designed to
25:41
Speaker 2: test whether HRT reduces the symptoms of menopause, because, as
25:44
Speaker 2: you point out, seventy percent of the women in the
25:46
Speaker 2: study were more than ten years past menopause, like they
25:49
Speaker 2: weren't symptomatic anymore. It was designed to test whether hormone
25:53
Speaker 2: replacement therapy is cardioprotected it protects the heart, because you know,
25:57
Speaker 2: there's long been an observation that women tend not to
26:01
Speaker 2: have heart attacks and stuff until after metopause, and it
26:04
Speaker 2: was thought the asternom to be protective. That obviously didn't
26:07
Speaker 2: pan out in that older group of women. It may
26:09
Speaker 2: among younger women. There's like, the study wasn't designed to
26:12
Speaker 2: test the thing that we're using it for now.
26:15
Speaker 1: Yeah, I think, I mean in some ways many people
26:18
Speaker 1: would say, well, well, like what why not? And you know,
26:21
Speaker 1: one answer is like you know, the patriarchy or something.
26:26
Speaker 1: But you know it really it is a really important
26:28
Speaker 1: point because for many people, the reason to treat this
26:32
Speaker 1: is because of symptomatic you know, because of improvements and
26:35
Speaker 1: in symptoms.
26:36
Speaker 3: This study just wasn't about that.
26:37
Speaker 1: It's not that it was it evaluated symptom profile and
26:41
Speaker 1: show that it didn't work or anything. It just like
26:42
Speaker 1: that wasn't one of the outcomes, and it wouldn't have
26:44
Speaker 1: made sense with this age go work because again the
26:47
Speaker 1: sort of symptomatic pieces of menopause are earlier, and so
26:52
Speaker 1: it really is an example of a place where I
26:55
Speaker 1: think a lot of people's lives were made substantially worse
26:59
Speaker 1: by this research, which in principle was very well meaning
27:03
Speaker 1: and from which perhaps we did learn something, but it
27:06
Speaker 1: caused a lot of people to not have symptom relief
27:09
Speaker 1: who could have. So we then find ourselves in the
27:15
Speaker 1: current moment where I think like overall we are starting
27:18
Speaker 1: to see HRT. It's like it's having a moment, it's
27:23
Speaker 1: like having a comeback.
27:24
Speaker 3: Absolutely, people are into it.
27:26
Speaker 2: Yeah, I think that the word has gotten out and
27:29
Speaker 2: it's making people very curious. But part of this is
27:32
Speaker 2: word of mouth, because unlike a lot of drugs we
27:35
Speaker 2: take and give ourselves, like, hormone replacement therapy really works
27:39
Speaker 2: for symptoms of menopause. And so if you are a
27:43
Speaker 2: woman or no, a woman who has those symptoms and
27:46
Speaker 2: then they start taking HRT, they'll tell you how much
27:48
Speaker 2: better it is, and that's that's real. And so this
27:51
Speaker 2: percolates really quickly.
27:53
Speaker 1: But can I like sort of set back one STEC,
27:55
Speaker 1: which is, you know, looking at the Women's Health Initiative results,
27:59
Speaker 1: sort of what would you think we should have taken
28:00
Speaker 1: away from.
28:01
Speaker 2: That from the initial results?
28:03
Speaker 1: Yeah, in two thousand and two, what would you have
28:06
Speaker 1: had them do sort of do or say differently?
28:09
Speaker 2: To be honest, because the purpose of the study was
28:13
Speaker 2: to determine whether hormone replacement therapy reduce the risk of
28:16
Speaker 2: cardiovascular disease, and it didn't in the overall population, I
28:21
Speaker 2: think I would have said, Okay, you should not give
28:23
Speaker 2: hormone replacement therapy to reduce the risk of cardiovascular disease
28:26
Speaker 2: in post menopausal women, in post menopause women. And I
28:29
Speaker 2: would probably still say that today to be honest, although
28:33
Speaker 2: you know, you could maybe convince me. But the problem
28:37
Speaker 2: is when we extrapolate from one outcome to all outcomes. Yeah,
28:41
Speaker 2: and we'll get to some of those other outcomes. But
28:43
Speaker 2: I did want to give I think, you know, women
28:46
Speaker 2: who are reading about this, it can be very confusing
28:49
Speaker 2: what is out there? Right, I said estrogen and progesterone
28:52
Speaker 2: in terms of the biology, but there are so many
28:56
Speaker 2: different types and preparations. I think think it's worth just
29:01
Speaker 2: giving people a framework to sort of think through how
29:04
Speaker 2: to take these hormones. And so the framework that I
29:08
Speaker 2: have found useful is to remember that really the hormone
29:13
Speaker 2: that you want to get for homone replacement therapy is estrogen.
29:17
Speaker 3: Yes, that's the best one. The Estrogen's a great hormone.
29:19
Speaker 2: So it's a great hormone. We love, we love estrogen it.
29:23
Speaker 2: Estrogen is responsible for what makes women women, the secondary
29:27
Speaker 2: sexual characteristics and a lot of other things. Progesterone is
29:31
Speaker 2: there to stop you from getting uterine cancer. I mean
29:33
Speaker 2: that's really what it is. So estrogen flogs the lining
29:39
Speaker 2: of the uterus to grow and develop, that's one of
29:42
Speaker 2: its jobs during the menstrual cycle. If you don't allow
29:46
Speaker 2: the lining of the uterus to settle down and mature,
29:49
Speaker 2: which is what progesterone does, and it keeps getting hit
29:51
Speaker 2: by estrogen, the risk of uterine cancer really does increase.
29:54
Speaker 2: And so you want the estrogen, you need the progesterone
30:00
Speaker 2: if you have a uterus. And that other arm of
30:03
Speaker 2: the Women's Health Initiative study that you alluded to was
30:05
Speaker 2: an estrogen only arm, and you could only get in
30:07
Speaker 2: that arm if your uterus had already been removed for
30:10
Speaker 2: some reason. And I mentioned that because a lot of
30:14
Speaker 2: the outcomes for estrogen only hormone replacement therapy are actually
30:18
Speaker 2: a little bit better than estrogen and plus progesterone therapy,
30:22
Speaker 2: it's just like not everyone is eligible for that. So
30:24
Speaker 2: particularly breast cancer, for example, the risk in the overall
30:29
Speaker 2: Women's Health Initiative was elevated, but among those women who
30:32
Speaker 2: were on estrogen only because they didn't have a uterus,
30:35
Speaker 2: the risk was slightly reduced. So really interesting there and
30:38
Speaker 2: something to keep in mind. So ask about the uterus.
30:40
Speaker 2: The other thing is whether you're taking these as pills
30:43
Speaker 2: or not as pills. The pill forms have to get
30:47
Speaker 2: digested and pass through the liver before they get to
30:50
Speaker 2: your blood, and depending on the type of estrogen, the
30:54
Speaker 2: liver can break down like straight up estrogen, like seventeen
30:57
Speaker 2: beta estra dial which is the norm the that women
31:00
Speaker 2: make in their own bodies. You can take that in
31:02
Speaker 2: pill form, and if you do, your liver will break
31:04
Speaker 2: down ninety five percent of it before it gets to
31:06
Speaker 2: the rest of your blood. So you're actually taking pretty
31:08
Speaker 2: high doses to get like relatively normal blood levels. In
31:12
Speaker 2: contrast to a patch which goes right through the skin.
31:16
Speaker 2: You know, there's transvaginal or like vaginal preparations as well,
31:19
Speaker 2: which can get right into the bloodstream and the doses
31:21
Speaker 2: are much lower. That's worth mentioning because some of the
31:25
Speaker 2: risk of clot seems to be driven by these oral preparations,
31:29
Speaker 2: and I don't think people are entirely sure why there's
31:32
Speaker 2: a higher risk there. But if you've got the liver
31:34
Speaker 2: breaking down ninety five percent of stuff, you know that's
31:37
Speaker 2: going to be variable woman to woman because everyone's liver
31:39
Speaker 2: is a little bit different. And I bet dosing is
31:41
Speaker 2: just trickier to get right in those situations, so I
31:44
Speaker 2: just wanted to that's the framework.
31:46
Speaker 1: I think partly, that somewhat complicated framework illustrates sort of
31:51
Speaker 1: why this is a challenging thing to talk about in
31:55
Speaker 1: a podcast. And you know, because everybody's not for us,
32:01
Speaker 1: but for other people, you know, because everybody's needs here
32:04
Speaker 1: are going to be somewhat different. So there's an oral preparation.
32:08
Speaker 1: There's a patch, which I know is what a lot.
32:11
Speaker 2: Of people like, and there's a shortage of right now, and.
32:14
Speaker 3: There's a shortage.
32:16
Speaker 1: There are you know, vaginal creams which really are are
32:19
Speaker 1: kind of intended to treat or are effective mostly at
32:23
Speaker 1: treating the specific issue of vaginal dryness, so people you know,
32:28
Speaker 1: experience that symptom. A vaginal estrogen based cream can be
32:32
Speaker 1: very effective. Can also be usable even for people potentially
32:36
Speaker 1: who would not be wanting to take estrogen only therapies
32:41
Speaker 1: in other ways because of other risks. So it's sort
32:43
Speaker 1: of like all about you know, what are the particular
32:46
Speaker 1: symptoms that I am experiencing, what are the other risk
32:49
Speaker 1: factors that I'm holding on too, and then what's the
32:51
Speaker 1: right way to address those symptoms and getting back to
32:56
Speaker 1: the idea that a lot of what we're trying to
32:58
Speaker 1: do with this hormone replacement therapy, in contrast to what
33:01
Speaker 1: the Women's Health Initiative was evaluating, a lot of what
33:03
Speaker 1: we're trying to do is, you know, dial down symptoms
33:06
Speaker 1: of perimenopause and menopause, which are very disruptive to people's lives.
33:11
Speaker 2: So let's talk about the symptoms.
33:12
Speaker 3: Let's talk about the symptoms.
33:14
Speaker 2: Does hormone replacement therapy Yes, work for hot flashes, It really.
33:19
Speaker 3: Really really does. So hot flashes, you.
33:21
Speaker 1: Know, vasomotor symptoms are very very common experience of perimenopause.
33:27
Speaker 1: This is like the like joke on television shows where
33:30
Speaker 1: someone's sticking their head and the refrigerator that's that's a
33:33
Speaker 1: hot flash.
33:34
Speaker 3: People get a lot.
33:35
Speaker 1: Of these at night, and it's very disruptive at night
33:40
Speaker 1: because you know, you sweat, you wake up, your bed
33:43
Speaker 1: is completely soaked, and then you know you can't.
33:47
Speaker 3: Just go back to sleep because you're like literally.
33:49
Speaker 1: Drenched, and it is very unpleasant having had this happen.
33:54
Speaker 1: It's very unpleasant, and hormone replacement therapy reduces the risk
33:58
Speaker 1: of hot flashes and these studies by some like seventy
34:00
Speaker 1: to eighty percent, So can be really really effective at
34:04
Speaker 1: what is probably the most disruptive experience in perimenopause that
34:10
Speaker 1: people have.
34:11
Speaker 2: And perimenopause can go on for quite some.
34:14
Speaker 1: Time, it goes I mean yes, it can go on
34:17
Speaker 1: for many years, so people maybe it's worth saying. So
34:21
Speaker 1: menopause actually defined as twelve months. You sort of are
34:25
Speaker 1: in menopause when you are twelve months past your last period.
34:30
Speaker 1: So it's a thing that sort of defined retroactively. So
34:33
Speaker 1: there's like a moment at which your last period was
34:35
Speaker 1: twelve months ago and now you are in menopause. Perimenopause
34:39
Speaker 1: is the sort of period leading up to that when
34:41
Speaker 1: periods get less frequent or more frequent, like they kind
34:45
Speaker 1: of mess around. Your cycle isn't so regular, and that
34:48
Speaker 1: is where many of these symptoms start showing up.
34:51
Speaker 2: And I want to be clear that perimenopause has nothing
34:55
Speaker 2: to do with Perry Wilson. There's no relation.
34:57
Speaker 3: It's no, it's not even spelled the same.
35:00
Speaker 2: You know, I was not named after after you.
35:03
Speaker 1: I don't know if menopausad Perry.
35:10
Speaker 2: I think though hot Flashes clearly works. You talked about
35:15
Speaker 2: the general urinary symptoms, where the topical preparations are probably
35:19
Speaker 2: superior to oral preparations. Another reason to kind of discuss
35:23
Speaker 2: with your doctor about how exactly you are going to
35:26
Speaker 2: go about this. But it's the vaguer symptoms I think
35:30
Speaker 2: that are where a lot of women who I talk
35:32
Speaker 2: to are really have their questions like, yes, that's great,
35:35
Speaker 2: I don't want to have hot flashes, but also what
35:37
Speaker 2: about my brain? What about sleep? What about you know, memory?
35:41
Speaker 2: And you'll hear people online saying that, like they start
35:45
Speaker 2: a hormone replacement therapy and the scales fell from their eyes,
35:50
Speaker 2: and you know, it was like they were granted a
35:52
Speaker 2: whole new lease on life, which, to be honest, and
35:55
Speaker 2: maybe this is another safeword thing I'm always skeptical of naturally,
35:59
Speaker 2: just because I never think there's like any one thing
36:02
Speaker 2: that can be that transformative except the power of love.
36:06
Speaker 2: Oh my god.
36:08
Speaker 1: So I let me say sort of two things about that.
36:11
Speaker 1: So one is, you know, if you think about the
36:14
Speaker 1: the sort of experience of the menstrual cycle, there is
36:17
Speaker 1: a period of the of the menstruds is like before
36:19
Speaker 1: the men's recycle, when your estrogen is higher in the
36:21
Speaker 1: kind of pre ovulatory phase and then the estrogen falls,
36:25
Speaker 1: and a lot of people do experience fairly substantial mood
36:29
Speaker 1: shifts with those cycles. So the idea that estrogen could affect.
36:33
Speaker 2: That's why whenever a woman's in a bad mood, my
36:35
Speaker 2: first question is like, where are you?
36:38
Speaker 1: That's my question where that's where you want to start
36:40
Speaker 1: totally totally is this, yeah, and that's where I that's
36:43
Speaker 1: always That actually is a great marriage tip that many.
36:46
Speaker 3: People could we should.
36:49
Speaker 2: We could help so many people.
36:50
Speaker 3: We could help so many people.
36:51
Speaker 1: So I think it's not crazy to imagine that estrogen
36:55
Speaker 1: could affect your mood. I think a lot of that experience,
37:00
Speaker 1: the brain fog, the fatigue, whatever, is in fact sleep.
37:04
Speaker 1: So if you think about there's a sort of evidence
37:07
Speaker 1: that that hormone replacement therapy improves people's sleep, that maybe
37:11
Speaker 1: because of a reduction of basil motor symptoms, there may
37:13
Speaker 1: be other you know, they're like, no, you're not waking
37:17
Speaker 1: up in the middle of the night to change the bed.
37:18
Speaker 1: But it may also have sort of other other things
37:22
Speaker 1: that impact sleep. If you have slept better, you feel better.
37:25
Speaker 1: And so if the whole whole thing here was just
37:28
Speaker 1: improving sleep, I actually could explain a fair amount of
37:31
Speaker 1: just a general set of like, boy, do I feel
37:33
Speaker 1: a lot better? Yeah, the same way the first time
37:35
Speaker 1: your baby sleeps to the night you're like, oh my god,
37:37
Speaker 1: I'm going to conquer the world because I haven't, you know,
37:40
Speaker 1: because I've I've slept.
37:42
Speaker 2: Right, absolutely, And this is randomized trial level data. There's
37:45
Speaker 2: been a number of trials, but one called the Keeps trial.
37:48
Speaker 2: This was in sort of just recently. Menopausal woman showed
37:52
Speaker 2: a pretty significant improvement in global sleep quality scores in
37:56
Speaker 2: the group that got hormone replacement therapy compared to place ebo.
37:59
Speaker 2: As you mentioned, Emily, when they stratified that population by
38:03
Speaker 2: women who were having severe vasomotor symptoms, severe hot flashes, like,
38:07
Speaker 2: that's where a lot of the benefit accrued. So it
38:10
Speaker 2: might just be that you'll see people online talking about
38:14
Speaker 2: progesterone actually in particular binding the GABBA receptor in the brain.
38:19
Speaker 2: That's the same receptor that alcohol and benzodiazepines bind to,
38:23
Speaker 2: one of my personal favorite receptors. But not much data
38:28
Speaker 2: beside the mechanistic like petri dish stuff that would suggest
38:32
Speaker 2: that progesterone is a calming factor. But I think if
38:36
Speaker 2: you're certainly if you're waking up with hot flashes like
38:39
Speaker 2: this can be really good.
38:41
Speaker 1: The other thing we should say is that there's some
38:43
Speaker 1: evidence of an improvement in fractures, so people are risking
38:46
Speaker 1: oft osteoporosis. That's another that's another place where we see
38:50
Speaker 1: some hormonal placement therapy benefits.
38:54
Speaker 2: Yeah, no, I mean it's it's so important. I looked
38:57
Speaker 2: also a little bit more into brain stuff. The problem
39:01
Speaker 2: with brain fog is it's a bit of a Potter
39:03
Speaker 2: Stewart thing, you know, Potter Stewart, the Supreme Court justice.
39:06
Speaker 1: So like pornography, you know, and if you you know
39:08
Speaker 1: when you see it, you know when you see it
39:10
Speaker 1: right now, when you see it? Is that in my
39:11
Speaker 1: class literally all the time, I'm constantly telling them it's
39:13
Speaker 1: like what the Supreme Court's out of pornography, And people were.
39:16
Speaker 2: Just like as they like load up Browns, like report
39:20
Speaker 2: your professor page.
39:22
Speaker 1: I don't let them have devices in classes, just to
39:24
Speaker 1: avoid that kind of behavior.
39:25
Speaker 2: Mart So, I think brain fog is you know, we're
39:29
Speaker 2: all like, oh, yeah, I know what that is. And
39:31
Speaker 2: then but no one's study there's no randomized trials of
39:34
Speaker 2: like brain fog because that's what do you mean, Like,
39:37
Speaker 2: how do you quantify that? And so what you do
39:39
Speaker 2: get is you get randomized trials of neurocognitive testing, which
39:45
Speaker 2: is across a variety of domains, you know, executive function,
39:48
Speaker 2: verbal memory, physical memory, like all these different tests that
39:51
Speaker 2: you can put people through, and the data is really
39:55
Speaker 2: not super compelling that there are dramatic brain improvement effects,
39:58
Speaker 2: with the only exception being verbal memory. There did seem
40:02
Speaker 2: to be an uptick in verbal memory. And again just
40:06
Speaker 2: you know, get out your your your your shock buzzer
40:09
Speaker 2: or whatever we're using for me here. But I did
40:13
Speaker 2: feel like there, I was like, oh, that's kind of
40:15
Speaker 2: like a mom brane thing, like you can't find the
40:17
Speaker 2: word for X y Z right.
40:18
Speaker 3: That's called fatigue.
40:21
Speaker 1: I mean, I just I feel like so hard to
40:23
Speaker 1: separate all this stuff from being tired.
40:24
Speaker 3: But all right, so let's let's just leave.
40:28
Speaker 1: The hormone replacement therapy at You know, this is especially
40:32
Speaker 1: if you are someone who is experiencing symptoms of perimenopause.
40:36
Speaker 1: This is something you for sure would like to discuss
40:40
Speaker 1: with your doctor, absolutely right.
40:43
Speaker 3: What about testosterone?
40:46
Speaker 1: So that feels like we're diving in a little more
40:50
Speaker 1: more talk about testosterone for men separately, but testosterone for
40:54
Speaker 1: women feels like is it? I always think of this
40:57
Speaker 1: as like, this is how I could cheat in my
41:00
Speaker 1: sports performance.
41:01
Speaker 2: Oh, but you will not be allowed to because testosterone
41:04
Speaker 2: hormone replacement therapy is banned by almost every international sports
41:09
Speaker 2: authority and by the wellness actually metric of is it
41:13
Speaker 2: banned doesn't work?
41:15
Speaker 3: It does work?
41:16
Speaker 1: Yes, So why are people using this in menopause? And
41:21
Speaker 1: are there reasons they should do it?
41:23
Speaker 2: Yeah? So women do have testosterone just like men have
41:27
Speaker 2: some estrogen. It's just men have about ten times the
41:30
Speaker 2: testosterone and women have about ten times the estrogen and
41:33
Speaker 2: Viva la de France. Women's testosterone levels peak around age
41:40
Speaker 2: twenty and sort of decline slowly thereafter. They do not
41:44
Speaker 2: suffer the same menopausal cliff as estrogen and progesterone, so
41:48
Speaker 2: they do sort of more the male thing, which we'll
41:50
Speaker 2: talk about next week, which is kind of like a slow,
41:52
Speaker 2: steady decline over time. The interest in testosterone is really
41:58
Speaker 2: more recent than for women at least is much more
42:01
Speaker 2: recent than the broader HRT, in part because this is
42:05
Speaker 2: a hormone that people associate with, you know, muscle growth,
42:09
Speaker 2: and maintenance vigor to some extent, and to be honest,
42:14
Speaker 2: a lot of the research has been driven by sexual dysfunction.
42:19
Speaker 2: So testosterone in women's sort of first foray into organized
42:23
Speaker 2: research was to treat what's called hyperactive sexual desire disorder.
42:29
Speaker 2: You know, there's no there's no viagra for women yet,
42:32
Speaker 2: and so testosterone was sort of used for this purpose.
42:37
Speaker 2: Does it work?
42:39
Speaker 3: Yeah, pretty it does. It does work for.
42:44
Speaker 2: Sexual stuff. It works. The largest meta analysis comes from
42:49
Speaker 2: the Lancet combining data for multiple studies about eighty five
42:53
Speaker 2: hundred women total randomized trial data. And there's a bunch
42:58
Speaker 2: of different ways to to measure sexual satisfaction, but the
43:03
Speaker 2: women for getting disastroone replacement therapy had approximately one additional
43:07
Speaker 2: satisfying sexual event per month. So a satisfying sexual event
43:12
Speaker 2: could be with a partner, it could be alone. It
43:15
Speaker 2: doesn't necessarily mean there is an orgasm. It just has
43:18
Speaker 2: to be satisfying. Beyond that, though, yeah, I don't have
43:22
Speaker 2: much for a testosterone I don't think.
43:24
Speaker 3: It feels so like.
43:26
Speaker 1: We know that tesosterone is a part of why people
43:29
Speaker 1: no offense. Men like sex more than women on average,
43:33
Speaker 1: or at least on average, desire that's true. That's true
43:35
Speaker 1: in the data men men would like. The optimal amount
43:38
Speaker 1: of sex that men want is more. I want to
43:40
Speaker 1: be offended that you're not. You don't be offended, and
43:44
Speaker 1: so I don't think it's that surprising that if you
43:46
Speaker 1: gave people you're more of this this hormone, they might
43:49
Speaker 1: be more excited about sex. But the sort of other benefit,
43:53
Speaker 1: which is like a real benefit, I mean again, if
43:55
Speaker 1: you like, if you have a mismatch sexual desire with
43:58
Speaker 1: your partner, or you miss how much used to like sex,
44:01
Speaker 1: this is this sort of interesting thing too to think about.
44:06
Speaker 1: The other benefits don't really seem to be there. And
44:09
Speaker 1: of course there are some symptomatic side effects of testosterone,
44:13
Speaker 1: the same kinds of things you see if you use
44:15
Speaker 1: it to improve your sports performance, like hair growth and
44:19
Speaker 1: acne and other and other things. So certainly not something
44:23
Speaker 1: you should be purchasing, you know, along with your peptide
44:26
Speaker 1: stack from foreign countries.
44:28
Speaker 3: On the internet or whatever.
44:30
Speaker 2: Yeah, and testosterone is probably not as beneficial for heart health.
44:39
Speaker 2: If estrogen is beneficial for heart health, testosterone is not.
44:41
Speaker 2: It is sort of the yang to the yin of estrogen.
44:45
Speaker 2: I'm not sure which one is the sort of more
44:47
Speaker 2: like violent one, but testosterone supplementation can increase cholesterol levels
44:51
Speaker 2: potentially promote athrosclerosis. So it's like, I don't think we're
44:54
Speaker 2: all there yet, but you're going to see more and
44:58
Speaker 2: more of it, and especially as we just have to
45:01
Speaker 2: mention there's an entire industry that is out there that
45:05
Speaker 2: is selling hormone replacement therapy to women and men, you know,
45:10
Speaker 2: using telemedicine, the sort of direct to consumer prescription model.
45:15
Speaker 2: And I'm not weighing in on, you know, the like
45:19
Speaker 2: ethics or legality of that. I'm just saying it is there.
45:22
Speaker 2: So people have access to these treatments in a way
45:26
Speaker 2: that they've never really had before. And so you're going
45:29
Speaker 2: to see more and more and more of this, and
45:32
Speaker 2: it makes it all that much more important to like
45:34
Speaker 2: be really cognizant and talk with someone really knowledgeable before
45:38
Speaker 2: you start, so you know what you want to get
45:40
Speaker 2: and that you can make sure wherever you're getting it
45:42
Speaker 2: from is legitimate.
45:45
Speaker 1: So Perry, of course, people can buy these hormones online.
45:48
Speaker 1: But the other thing I see a tremendous amount of
45:49
Speaker 1: is these tests, Like you know, get this blood test.
45:51
Speaker 1: It's going to tell you where you are and your
45:53
Speaker 1: different thing and which kinds of things you need. Is
45:56
Speaker 1: that I, of course I've had all of these tests
45:59
Speaker 1: because crazy person. But is there a sort of actionable
46:03
Speaker 1: piece of that? Is that just selling people nonsense? Should
46:07
Speaker 1: I care about my T three free number is not
46:10
Speaker 1: as good as I whoop says it should be saving?
46:15
Speaker 2: Honestly, No, when it comes to estrogen progesterone levels, yes,
46:19
Speaker 2: you can certainly buy tests online to measure your levels,
46:22
Speaker 2: but no, they don't really change the treatment paradigm, which
46:25
Speaker 2: is how we decide whether a test is valuable or not. So,
46:28
Speaker 2: particularly in perimenopause, the levels can be all over the place.
46:33
Speaker 2: Estrogen can go up and then crash and kind of
46:35
Speaker 2: go up again. That's part of the difficulties of perimenopause.
46:38
Speaker 2: And so the indications for treatment with hormone replacement therapy
46:43
Speaker 2: is are you at an age where it's reasonable that
46:46
Speaker 2: you're in perimenopause or menopause, and do you have symptoms
46:48
Speaker 2: of perimenopause or menopause? And that's it, so, you know,
46:53
Speaker 2: getting you to spend a subscription fee to continually measure
46:56
Speaker 2: these hormones over and over air event or even once,
46:59
Speaker 2: I think is a bit of a cap.
47:01
Speaker 1: Okay, fair enough, Thank you, smash your past Perry.
47:06
Speaker 3: Hormone replacement therapy smash.
47:10
Speaker 2: I'm going to go with a lot of the society
47:14
Speaker 2: guidelines which say, you know, Perry, menopause, first ten years
47:18
Speaker 2: of menopause, you know, potentially five to seven years of
47:21
Speaker 2: therapy is a clear smash. Probably need some more data
47:25
Speaker 2: on how long you can extend this into menopause, Emily
47:29
Speaker 2: Smash Paths.
47:30
Speaker 1: I'm going to go with a smash based on my
47:32
Speaker 1: friends who say that it's great, and when I feel
47:36
Speaker 1: like I need it, I'm gonna be trying it. Let
47:39
Speaker 1: us know, all right, that's it for hormone replacement therapy.
47:42
Speaker 1: Your mail bag Question of the Week after the Break.
47:50
Speaker 4: Hi, Emily and Perry. This is Mary from Toronto and
47:54
Speaker 4: I have a question about lime disease. I've heard that
47:58
Speaker 4: dogs can get vaccinated for it, but I can't. Does
48:02
Speaker 4: Lucy the beagle know something I don't?
48:05
Speaker 3: Thanks so much, okay, Perry.
48:08
Speaker 1: I love this question because it is asked in my
48:12
Speaker 1: household all the time, like if there, if, and when
48:14
Speaker 1: there is a lime disease vaccine for humans, my husband
48:16
Speaker 1: will literally be the first person to get it, Like,
48:18
Speaker 1: if there's a line, he is standing. He's like, he's
48:21
Speaker 1: like the people wanted to buy the first iPhone. That's
48:23
Speaker 1: my husband is going to be like that for a
48:25
Speaker 1: lime disease a vaccine. No, he hasn't had it, but
48:28
Speaker 1: he's like a he's like a tick lunatic. He's like
48:31
Speaker 1: afraid every night when he gets to Tix season. Every
48:34
Speaker 1: night when we get into bed, he's like, Okay, can
48:36
Speaker 1: you check me for ticks?
48:36
Speaker 3: Every single night?
48:37
Speaker 4: Oh?
48:38
Speaker 2: I find that kind of romantic. Actually, it's a little
48:41
Speaker 2: it's like a rooming prime thing. Do you eat the
48:44
Speaker 2: ticks if you find them?
48:47
Speaker 1: Uh, there's one summer I found like five ticks on
48:49
Speaker 1: my kid. Anyway, we never got we never got lime disease. Okay,
48:53
Speaker 1: so uh so there is a lime disease for dogs
48:56
Speaker 1: but not for humans. And there used to be a
48:59
Speaker 1: lime disease vaccine for humans.
49:01
Speaker 2: Yeah, yeah, yeah, it existed nineteen late nineties. It came
49:06
Speaker 2: out and basically the only reason we don't have anymore
49:09
Speaker 2: is it was a commercial failure. There are a few
49:13
Speaker 2: reasons for that. One is the vaccine schedule wasn't great.
49:16
Speaker 2: I think it was zero, like so you got one
49:19
Speaker 2: and then you had a booster a month later, and
49:21
Speaker 2: then another one twelve months later. So it's like a
49:24
Speaker 2: series of three vaccines, which is a little bit annoying.
49:28
Speaker 2: Because lime disease is not transmitted human to human, it
49:32
Speaker 2: sort of shifts the public health landscape of the vaccine.
49:37
Speaker 2: So the line vaccine was never going to be part
49:39
Speaker 2: of like the childhood vaccination schedule, which is really designed
49:42
Speaker 2: to protect all of society, right like lime disease really
49:46
Speaker 2: only the vaccine is really only going to protect the person.
49:49
Speaker 2: The other thing about lime disease is it's a bacteria,
49:52
Speaker 2: not a virus. We have antibiotics that can treat it,
49:56
Speaker 2: so it's not you know, the sort of risk isn't there.
50:00
Speaker 2: But I mean, we had its AFT approved, you could
50:02
Speaker 2: have gotten it and then just stop making it because
50:05
Speaker 2: they weren't making enough money.
50:06
Speaker 1: But exciting news is that there is actually a new
50:13
Speaker 1: lime vaccine that is in phase three trials and they've
50:16
Speaker 1: just announced that. Basically, I think the phase three trials
50:19
Speaker 1: went well. This is like a very recent announcement, and
50:22
Speaker 1: so I do expect there to be a line vaccine
50:25
Speaker 1: coming down the line. And although you're right, I think
50:27
Speaker 1: the commercial success was somewhat limit. I actually think people
50:30
Speaker 1: have gotten more concerned about the sort of long.
50:33
Speaker 3: Term impacts of lime disease.
50:34
Speaker 1: And it is true that although if you notice the
50:37
Speaker 1: tick and you get treatment, basically you can avoid getting
50:40
Speaker 1: long term lime disease, many people don't. And so this
50:43
Speaker 1: is you know, it can be a very significant it
50:46
Speaker 1: could be incredibly debilitating if people don't have My brother
50:50
Speaker 1: hadline disease.
50:51
Speaker 2: Once, my daughter HADLME disease.
50:54
Speaker 3: Because you live near lime, Connecticut, that's what.
50:58
Speaker 2: My backyard is mostly ticks.
51:01
Speaker 3: Yeah, that's where they live.
51:04
Speaker 1: And so yeah, I mean it's like, you know, it's
51:06
Speaker 1: a there's a telltale rash. If your child has a tick,
51:09
Speaker 1: watch for the rash. But I am excited about the
51:13
Speaker 1: line vaccine.
51:14
Speaker 2: Yeah, tick checks. You have twenty four hours after the
51:17
Speaker 2: tick has bit to get it off with before it
51:19
Speaker 2: can transmit the bacteria. So tic checks on a daily
51:22
Speaker 2: basis if your kids are outside.
51:24
Speaker 1: Yeah, my brother did not get My brother he got
51:27
Speaker 1: treated and he did not have lun He did not
51:29
Speaker 1: have any significant long term yeah.
51:31
Speaker 2: Line, Yeah, you can save the tick if you want
51:33
Speaker 2: to show your doctor. They'll have fun with it. But
51:36
Speaker 2: a lot of the time if the tick has been on,
51:38
Speaker 2: and certainly if there's that target lesion, you'll get empiric antibiotic.
51:42
Speaker 3: Treatment Taxi cyclin for the win.
51:47
Speaker 2: All Right, that's it for us today. Stick with us
51:49
Speaker 2: next week when we'll ask what's the deal with testosterone
51:53
Speaker 2: for men?
51:54
Speaker 3: Yay, finally we're studying men. Phew.
52:00
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52:06
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52:35
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52:36
Speaker 3: We'll let the influencers have the last word.
52:38
Speaker 5: Ladies, I want you to know these symptoms of perimenopause
52:41
Speaker 5: and menopause. These are thirty four common symptoms acne allergies, anxiety, floating, constipation,
52:48
Speaker 5: body odor, breast soreness, brtal nails, cholesterol changes, depression, difficulty concentrating,
52:55
Speaker 5: dizzy spells, fatigue, gum problems, hair loss, headaches.
52:59
Speaker 6: And migraines from palpitations, hot flashes, irregular periods, irritability or rage,
53:06
Speaker 6: itchy skin, joint and muscle pain, libido changes, loss of breastfulness,
53:12
Speaker 6: memory lapses
53:13
Speaker 5: Mood swings, nausea and night sweats, osteopenia and osteoporosis, pain
53:19
Speaker 5: during sex, panic disorder, sleep issues, baring countenance, vaginal dryness,