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Women’s Health Initiative | best of the best
This is Dr. Chad Edwards and you were listening to podcast number 86 of against the grain.
Welcome back to against the grain podcast. This is Diana Edwards. Today we’re going to actually be looking at Tulsa the bio identical hormone replacement therapy that we have available but we’re specifically today going to be looking at the Women’s Health Initiative. Somewhere along the way people began to get a negative vibe and put out negative information about the use of estrogen in post-menopausal women. And so today we’re going to look at this women’s health initiative. We’re going to look at the results and we’re going to find out if estrogen is or is not a good idea. Women’s Health Initiative
Post-menopause Well said yes. We are talking about hormones bioidentical hormone replacement. I mean we do a lot of that in the clinic. I am a big fan of bioidentical hormones and I will tell you that the vast majority of our female patients that are post-menopausal are also huge fans about hormones. But one of the most common questions that I get. What do you think it is. Any idea in post-menopausal women. Yeah. With estrogen we’re going to give them hormones. Oh.
Is this going to increase my risk of cancer.
You hit the nail on the head. It’s one of the most common questions and we’re going to actually do a specific podcast about estrogen and breast cancer. But we wanted to start with this this view of the Women’s Health Initiative as a large study. And I remember sitting in medical school I was on my core rotations and so this would have been like 2000. Women’s Health Initiative
To three. Somewhere in there and we were sitting in this in this room a bunch of medical students on rotations talking to our attending and we said well don’t hormones reduce risk of cardiovascular disease. And I remember them just kind of like. I don’t know rolling their eyes wasn’t the word but it was it was just kind of like oh you know our world just got turned upside down. It is ultimately kind of what it looked like because they were saying well we used to think that but you know this study just came out and it’s showing that there’s actually an increased risk of breast cancer and there’s an increased risk of this and there’s an increased risk of cardiovascular disease and so I. You know at the time I didn’t of course I didn’t know anything about about hormones and you know that was like voodoo and only weirdo people do that. And you know we do traditional medical dogma because that’s what all the studies show is the best thing to do. And I wanted to be a good doctor so that’s what I was going to do. So you know for four years in fact I remember I don’t think my mom would mind me saying this. I remember my mom was on Prempro. That was you know combination hormone replacement therapy had Premarin and a progestin called Madrox the progesterone acetate. And. She she took this stuff to kind of combat the symptoms of menopause.
Your mom’s very nice. Mine just went through it. Women’s Health Initiative
Are you saying your mom’s not nice. Women’s Health Initiative
I’m saying I’m an advocate. Post menopausal hormone replacement.
We better hope she doesn’t hear this.
And so. So yes a make hormone replacement can make a big difference. But again there’s some questions about well is this going to increase my risk of breast cancer or what about colon cancer or what about bone fractures or cardiovascular disease or what are the risks what are the benefits. So you know we’ll be talking more specifically about each one of those components. But I wanted to take some time and talk specifically about this study of the Women’s Health Initiative because what it was a large study to it was funded by the NIH the National Institutes of Health so it wasn’t the drug company that funded this study. You know at least not at. All at face value. There may have been some under the you know. Under just under the table shuffling of funds you know there’s lobbyists and all of those kinds of things. But you know it was it was done by the NIH and I think there’s some really good information here that can help people understand some of them some of the crap about some hormones that are out there and why some things are good some things aren’t. And and you know how it relates to about hormones. So. Let’s get into this thing. So Women’s Health Initiative was this large study it started in 1991 and prior to this study there was a lot of observational data about. And that means we just kind of. Observed that. Hormone replacement we thought it lowered risk of cardiovascular disease.
So they said let’s do this study too to evaluate this and so the primary outcome of the study was evaluating cardiovascular disease prevention in post-menopausal women using hormone replacement therapy. There were actually a couple. There were three different arms of the study. There was a randomized controlled trial looking at the use of hormone replacement therapy at dietary modification trial and some calcium vitamin D supplementation. There was an observational study looking at. Predictors of disease and then there was a study of community approaches to develop healthful behaviors. So three different arms of the study were not for the purpose of this. I almost said I don’t care about those we care about them but that’s not for the purpose of this podcast. So we’re going to focus on the randomized controlled trial of.
Post-menopausal women ages 50 five zero to 79 that either took Premarin and Premarin what was Premarin stands for. Well I was mortified when I found out it’s. Horse. Mayre. Urine. That’s right. Stands for pregnant mares urine Premarin. So basically.
It’s horse piss. That’s a that’s what you’re taking. It’s horse horse piss. So reason for that I think I’ve talked about another podcast but basically you know they discovered this stuff. I don’t remember off top of my head 30s 40s 50s somewhere in there. And they think it was 30s or 40s. And they they. It was too expensive to make commercially viable so they finally discovered that they could make this stuff. You know they can use the urine of horses and extract the estrogens from it. And that was beneficial and was estrogen. So we started giving people this and they they made it and you know the drug company made a lot of money from it. So Premarin and though there was a Premarin only group and there was a Prempro group. The reason that there’s a difference here is because Premarin if you take estrogen only. And. Do not have a uterus. You’re fine. A. You know sort of. If you to if you have a uterus you need to add a progesterone or a progestin because estrogen is pro-growth and I always describe it as it’s like taking or it’s it’s fertilizer for the lining of the enemy Druim so it makes the enemy TROM thicker. And so it’s a pro growth. Type. Hormone. So if you have a uterus and you’re on estrogen without or what we call unopposed estrogen without progesterone then your risk of uterine cancer goes up quite a bit. So the tissue keeps growing. Exactly. So you.
Well at least that’s that’s one of the mechanisms or one of the thoughts. So we counterbalance that with progesterone. So here you have. Divided everybody out by you got a uterus or not. You know I guess I think about the Doctor Susan you know the the the stars upon Mars. And you know those that have stars and those are cool people and these are you know so go anyway. So the they had a group that was that didn’t have a uterus and that was the Premarin only group. And so they had the study group and the control group. So you have the they were the control group was given a placebo like a sugar pill and then you had the study group which was Premarin and they took. Premarin alone. The other group. Of the other part of the study was that the women that had a uterus and they took Prempro because they needed this progestin. So we’re going to start off with the Premarin group. And so these women were randomized. So that means. OK you don’t have a uterus. You’re either going to get estrogen or placebo. Nobody knows who is double blinded. So the people giving it out don’t know the people taking it don’t know and we’re going to follow it over time. And they they they did this study. For several years and I remember the average follower the the the follow up I think I think it was basically seven years seven or eight years that they followed these women on average. So the first thing that I want to say about this group that took Premarin is that Premarin is not bio identical estrogen.
So the human body has estrogen. Esther Dile as trial and this will be in the show notes. But Premarin contains. Let’s see one two three four five six seven eight nine 10 11. 11. Estrogens. But then there’s also. Some other hormones including androgens and progestins that are also in there but they’re in really small amounts and basically there is extremely small amounts of estrogen. That is. That is pretty darn close if not identical to estrogen in the human body. So the main dominant hormone in this is the chemical anyway is sodium estrogen sulfate at forty nine point three percent. The second one. Sodium equil and sulfate equil an equine That’s horse horse estrogen. Great if you’re a horse. I am not a horse. Not so good if you’re a woman human woman. Yeah. So and that was at twenty two point four percent. So these things are not bio identical. It’s not going to behave the exact same way in the body. It’s going to have different properties that’s going to have different issues. The second thing I want to say is that these were oral estrogens and estrogen is it goes to the liver and you have what’s called a first pass effect. And so the liver gets first crack at it and it makes some mega. Metabolite products and so some different types of estrogen breakdown products. I talk about that in another podcast you can go back and look through that. Women’s Health Initiative
But there’s three different pathways there’s the two hydroxy for hydroxy 16 hydroxy pathway and then there’s two phases to detoxification where you have Hydrox elation and then you have either Glueck or on a nation sulfation methylation. Those kinds of things. And so a lot of factors will influence that. But when you take oral estrogen your liver gets first crack at it and it’s a greater likelihood that if you have a problem with like methylation detoxification that it’s going to cause more problems. So I’m I am not in favor of oral estrogen number one and number two.
I’m not in favor of horse piss in humans so I’m not I’m not for that either not for that. You’re not going to sign up for Premarin. No thank you. OK. I’ll. Make sure I’m. No prescription please. Yeah exactly. So I think it’s important to understand that at the foundation. But.
These you know these women took Premarin. So they were on these estrogen compounds which there are estrogen activity’s effects in the body. And these the test group took Premarin zero point six to five milligrams everyday kind of a standard dose. There are other doses but that’s kind of a fairly standard one. Again this this study was to identify the risks and benefits excuse me of Premarin which is. Estrogen replacement on other health factors. They meant to stop the study. They intended to stop the study in 2005 but in early 2004 they looked at the data that they had and they felt that they had enough information not that there was too much harm or anything like that. They just felt that nothing was really going to change over another year so they went ahead and stopped the study a little bit early. And part of that. Was because there was a mild increased risk of stroke. So they felt that the data wasn’t going to change in another year or so they said let’s just go ahead and take what we got and we’ll call it good. So the findings of the primmer and only group and we’re going to look at both groups Premarin and the Prempro group we’re going to look at what. Looks like six factors that we’re going look at. The first one is cardiovascular disease. So in the Premarin only group there was no increase or decrease in the risk of heart attacks didn’t change didn’t had no effect. Women’s Health Initiative
So going back to that medical school time period where I was sitting there and we were talking with our attending and said isn’t hormone replacement therapy beneficial for cardiovascular disease and they said no it actually raises risk of cardiovascular disease. That was not because of the cardiovascular did that was not because of the Premarin only group because that was not the case in this group. So I thought that was interesting. Part Number two with the second that we’re going to look at a stroke. There was an increased risk of stroke in the estrogen only group the Premarin group. And again it goes back to the when you take oral estrogen there is an increased risk of of. Blood clots and things like that. I don’t know if that’s why there were more strokes but to be clear there was eight cases. There were eight more cases of stroke per 10000 women. So it’s not like was that a point zero 8 percent increase. So it is not severe it’s not severe. But again there were more strokes and the authors you know went on to say. In through the publication they said any increased risk of stroke is unacceptable and I agree with that. It was it was a small increase but why would we do anything that’s going to increase risk. So let’s not do that unless patients understand there’s a slightly increased risk. But you know the benefits may be worth it. So you know we’ll just kind of watch through that. So that’s the main reason that they stopped this day but there was a slightly increased risk of stroke. The third thing we’re going to look at is fracture. Women’s Health Initiative
Now when you take estrogen of course I’ve heard for years in fact that one of the big reasons that my mom took it was because there was a decreased risk of hip fracture in the Premarin group. So estrogen replacement does reduce risk of fractures in at least as reflected in the women’s health initiative study. Now we get into the big one where we talked about does an increased risk of cancer and I have so many women that will say Well is there an increased risk of breast cancer. So for the Premarin only group breast cancer there was no statistically significant difference between the placebo group and the Esterne group. And in fact. There were six less cases of breast cancer per 10000 women on Premarin versus placebo. So it was not statistically significant. It wasn’t a big difference but being on Premarin had a lower risk of breast cancer. And this was a large study but. The study investigators even stated and this is in quotes what is clear now is that overall post-menopausal women without a uterus who choose to take estrogen alone do not have an increased risk of breast cancer at least over the first seven years of treatment because that’s how long they followed. So. Estrogen alone in this study did not increase the risk of breast cancer. I thought that was fascinating because there is there is some data some some some some. And we’ll talk about it in another podcast that shows a slight increase risk of breast cancer with estrogen replacement not in the Women’s Health Initiative. So I thought that was really really interesting. So the thing that we’re going to look at our blood clots or we call venous thrombosis Bolick events.
And there was an increased risk of blood clots in the Premarin group and again that’s oral estrogen will go over more of this and another in another podcast. Basically the Esther trial yes TTR trial showed that when you use topical or transdermal estrogen or other forms of estrogen besides. Oral estrogen that it did not increase the risk of blood clots so it’s not estrogen. It’s the first pass effect on the liver and the effect. Exactly. It’s how it’s being done. So it’s one of the reasons one of the many reasons I’m not in favor of oral estrogen. So the sixth thing that we look at is colon cancer. There was no difference between the prairie group and the placebo group but it’s no statistically significant difference. So the take home for this is when I started looking into this data the Premarin or the estrogen alone not nearly as harmful as we originally thought. There was an increased risk of stroke. There was a. Increased risk of blood clots but there was really reduced risk for everything else. So. I was. I was fascinated by that in fact there was lower risk of breast cancer in this study. So then we get into the Prempro group and this is where things really start getting interesting. And again just like we talked about with the primmer in group maybe. Let’s say what let’s go in and take a little break. And then we’ll come back and we’ll talk about the Primm pro group. Sounds fair.
Sounds great you guys hang tight. We’ll be right back.
OK we are back and we’re talking about the Women’s Health Initiative study the first portion of the podcast we were talking about horse piss as estrogen they the liberty to get orally. And exactly. So we’re drinking horse urine for our estrogen replacement. That’s awesome. So now we’re going to talk about the Prempro which is Premarin. Women’s Health Initiative
I don’t have a uterus now I’m dealing with. That’s correct.
That’s correct. So we had to give some Provera that goes along with it. Again with the Premarin I had to give the disclaimer that Premarin is not bioidentical estrogen in this case Provera also called Madrox the progesterone acetate is about on par with drinking battery acid as far as being beneficial for you. The stuff is horrible. I would never recommend anyone take this and you’ll see why I say that it has a number of effects and it is not bio identical progesterone bioidentical progesterone has a markedly different effect in the human body and it is not nearly as detrimental as this crap is for your overall health. So.
Let’s get into this part. So there were sixteen thousand six hundred eight post-menopausal women ages 50 to 79 who were enrolled in the study. These women had never had a hysterectomy so they still had their uterus and they were randomized to either receive the placebo which is just like the sugar pill or Prempro which is the Premarin plus Provera. The Premarin portion was zero point sixty five milligrams just like in the primmer and only study and there were 2.5 milligrams of Provera or Madrox progesterone acetate. The plan was to do this study for 8.5 years. They didn’t make it. And we’ll talk about why. So the. Way we looked at six factors on you know what we’re looking at for the Premarin were to look at those same six factors here for cardiovascular for for Prempro. The first one is cardiovascular disease. And in the. Well let me let me make one other statement here. So I’m going to be talking about what’s called the hazards ratio or a risk ratio and the hazard ratio is basically a statistical analysis term where it’s where you’re looking at the relative risk of a given event. So you know if we’re talking about cardiovascular disease and comparing placebo versus the treatment group what is the difference in risk for the placebo versus the treatment group and. A number. So a 1. Score of 1 would be the two groups had the same risk. If the study group has a lower risk then the number will be less than one if they have a higher risk it will be greater than one. Women’s Health Initiative
For example the first section that we’re looking at is cardiovascular disease. And they noticed that there was an increased risk of cardiovascular disease events with a hazard ratio of one point to nine. That means there is a 29 percent increased risk of heart attacks. Kind of it’s a cardiovascular disease. 29 percent. That’s a ratio of 1.2 9.
And this is because of the addition of the pro. Women’s Health Initiative
It’s basically yes because we didn’t see that in the private and only group can we say it’s because of the you know the Provera or the matter exper just run acetate or is it that it’s a combined issue. They know they’re still taking this early. Correct. That’s correct. So I would argue that yes it’s the the freaking battery acid. The. Thing. That I hate this stuff. It’s awful. But you really can’t put to death either. So you know unfortunately they.
You know we will we will misplace interpreting all of this stuff because of this particular portion not all hormones are bad even though I think Premarin alone is not the best way to go. What we misinterpret this stuff across the board. So cardiovascular disease increase risk of events. One has a ratio of 1.2 nine twenty nine percent increased risk of cardiovascular disease. So Diana what about strokes.
Definitely increased risk of stroke. There was a hazard ratio of 1.4 one so I’m going to see that as an increase of 41 percent.
You got it. So there were 41 percent more strokes in the treatment group than in the placebo group. What about fractures.
You have a decreased risk of hip fracture. So now you have a decreased risk which the Premarin did as well correct. The Premarin did show a decrease risk. As well. Yes. All right. So we’re still helping with the fracture issues. Now your breast cancer. Increased risk of breast cancer your ratio there is one point to six. You have an increase of 26 percent risk of breast cancer taking Prempro.
Exactly. And the thing is that was not seen in the Premarin alone group. It wasn’t the estrogen it was the. Madrox the progesterone acetate.
It’s it just it never ceases to amaze me that the misinformation that gets propagated but increased risk of breast cancer and this is why they stopped the study early was because of this increased risk of breast cancer. And and we’ll come back to that in just a minute. Blood clots or venous thrombosis Bolick events. Now there was an increased risk of pulmonary embolism which is a blood clot in her lung. Usually they come from the you know the lower extremities or up in the pelvis and so it is a venous thrombosis Baalke event or a blood clot. And there was a hazard ratio of 2.1 three. That’s a 113 percent increased risk. For blood clots. And again we did see an increased risk of clots but not to that extent in the Premarin group alone. I mean you might again. You might as well be drinking battery acid. And finally with colon cancer there was a decreased risk of colon cancer with a hazard ratio of points to 63. Women’s Health Initiative
I guess maybe that battery acid is burning everything probably you die of everything else before you get colon cancer. That’s that’s not true.
I’m just I’m I’m being facetious. And if you think back of the word of facetious and we’re talking about colon so they go together I think so. So again like I said earlier this this part of the study was stopped early due to an increased risk of breast cancer. They meant the study to go eight point five years but they stopped 3.3 years early. Because of these risks. And again it was an increase in the increase in the estrogen alone. I just it’s it’s fascinating to me. There’s another study that was done called The hers study and that also showed an increased risk of blood clots. They were also using Prempro and there was no reduced risk of cardiovascular disease in that. They also didn’t show a real increase if I remember correctly in cardiovascular disease. And so you know one of my passions is talking about this this load of crap about cholesterol causes heart disease. And one of the things that’s interesting to me because we’ve seen study after study after study after study after study where you lower cholesterol and it doesn’t make any difference it doesn’t make a hill of beans bit of difference in cardiovascular disease events unless you are using a Statten and all of those were secondary prevention trials but that’s another topic for another day. So in the first two study they noted that Prempro lowered LDL cholesterol that’s the bad cholesterol lower to 11 percent and it increased the good cholesterol the HDL 10 percent. But it made no difference in cardiovascular events. So that’s just further information that this.
Load of horse manure since we’re talking about Premarin has nothing to do with cholesterol or at least you know cholesterol doesn’t cause heart attacks.
So what I guess Well what I want to know now is not that we’ve talked about this women’s health initiative what does it tell me about our bioidentical hormones replacement therapy or B HRT. Yeah so basically what I would say the take home message when you compare Premarin and Provera in the women’s health initiative and help us understand. About hormone replacement therapy it doesn’t tell us anything. About.
About hormone replacement therapy because they’re not. Exactly. And so I use the analogy of you know I remember several years ago and you may remember this some people may not. Several years ago the National Highway Traffic Safety Administration launched an investigation. It was in 2000 looking at the Ford Motor Company and Firestone tires and they found that the combination of the Ford Explorer with these Firestone tires which had a known tread separation at high speeds started causing all kinds of problems in fact 823 people were killed because of the combination of accidents that they attributed to the Ford Explorer and the Firestone tires. So the combination of these two things resulted in a vehicle that was unstable in its handling and at risk because of the tire separation. And so it was the tires and the vehicle that both contributed to these fatalities. Now if we said well my goodness SUV and tires are bad because they cause all these deaths. No that’s not the case. It was Firestone tires because they had a known issue and it was the Ford Explorer which had a known issue. You combine the two together and now you have a risk. It was not SUV and tires. So you can’t draw a conclusion across the board and say all SUV tires are bad. And that’s what we have done in the medical community and you’ve heard me talk about other physicians as hypocrites. But that’s kind of I mean you know we’ve got to be very careful in the way we interpret this data. Because you cannot take data about Premarin and say all estrogen is bad.
And you can’t take data about Provera and say progesterone is bad. They are not the same thing. You cannot draw that conclusion from from this data. They are different and distinct entities. And so I think you know understanding Premarin and Provera as in in the women’s health initiative and. You know understand that they’re not on bioidentical hormones. It’s just not the same thing as using bioidentical hormone replacement therapy like we do in our Tulsa clinic. There’s just a big big difference and it’s as big of a difference as SUV is entires. So I think looking at this study and knowing what the data says really can help us understand about the safety and the risks with these hormones that. You know I didn’t know I didn’t know these things and so many of my colleagues also don’t know this stuff. We got to understand this stuff and understand what our risks are and where the benefits lie. Women’s Health Initiative