Episode 86 - The Women’s Health Initiative

fact vs fiction with bioidential hormone replacement therapy (BHRT)

Speaker 1: 00:03 This is Dr Chad Edwards and you’re listening to podcast number 86 of against the grain.

Speaker 2: 00:18 Welcome back to against the grain podcast. This is Diana Edwards. Uh, 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. Postmenopause

Speaker 1: 00:58 well said. Yes, we are talking about hormones, bioidentical hormone replacement. I mean, we do a lot of that in the clinic. Uh, I am a big fan of biodentical hormones and I will tell you that the vast majority of our female patients, uh, that are post-menopausal, are also huge fans about indigo hormones. But one of the most common questions that I get, what do you think it is? Any idea in postmenopausal women with estrogen? We’re going to give him hormones.

Speaker 2: 01:28 Oh, um, is this going to increase my risk of cancer?

Speaker 1: 01:33 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, I wanted to start with this, uh, 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 a 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 reduced risk of cardiovascular disease. And I remember them just kind of like a, I don’t know, rolling their eyes wasn’t the word, but it was, it was just kinda like, oh, you know, our world just got turned upside down 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.

Speaker 1: 02:32 And there’s an increased risk of this and there’s an increased risk of cardiovascular disease. And so, um, I, you know, at, at the time I didn’t, of course I didn’t know anything about biodentical 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, um, you for four years, in fact, I remember, um, I don’t think my mom would mind me saying this. I remember my mom was on Prem prempro that was know combination hormone replacement therapy, had premarin and a progestin called medroxyprogesterone acetate. And uh, she, uh, she took this stuff to kind of combat the symptoms of menopause.

Speaker 2: 03:21 Your mom was very nice. Mine just went through it.

Speaker 1: 03:26 Are you saying your mom is not nice?

Speaker 2: 03:27 I’m saying I’m an advocate of post menopausal hormone replacement.

Speaker 1: 03:33 We better hope she doesn’t hear this. So, um, so yes, I’m a 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? 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, uh, this study of the women’s health initiative because one, 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 and you know, at least not at, on, at face value. There may have been some under the, under the, under the table shuffling of funds, you know, there’s lobbyists and all of those kinds of things.

Speaker 1: 04:25 But, um, 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 the, some of the crap about some hormones that are out there and why some things are good, some things aren’t. And, and, um, you know, how it relates to bow it and a hormones. So let’s get into this thing. So women’s health initiative was, this large study was started in 1991 and prior to this study there was a lot of observational data, uh, 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 to, uh, to evaluate this. And so the primary outcome of the study was evaluating cardiovascular disease prevention in postmenopausal women using hormone replacement therapy. There were actually a couple of, there were three different arms of the study.

Speaker 1: 05:20 There was a randomized controlled trial looking at, uh, 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, uh, to develop healthful behaviors. So three different arms of the study. I don’t, we’re not for the purpose of this, I’m the to, I almost did it. 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 a postmenopausal women ages 55, zero to 79, uh, that either took premarin and premarin. Diana, what is premarin stand for? Oh, well, I was mortified when I found out it’s horse mayor urine. That’s right. Stands for pregnant mare’s urine primmer rent. So basically it’s worse piss. That’s what you’re taking.

Speaker 1: 06:20 It’s Horse Horse Piss. So, and the reason for that, I think I’ve talked about in another podcast, but basically, uh, you know, they discovered this stuff, I don’t remember off the top of my head. Thirties, forties, fifties, somewhere in there. And they, uh, I think it was thirties or forties and they, they, uh, it was too expensive to make commercially viable. So they finally discovered that they could make this stuff or 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, uh, they made it and you know, the drug company made a lot of money from it. So a premarin and the, there was a perimeter and 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 sort of if you to, if you have a uterus, you need to add a progesterone or a progestin because estrogen is pro growth.

Speaker 1: 07:28 And I always describe it as a, it’s like taking or it’s fertilizer for the lining of the endometrium so it makes the endometrium thicker. And uh, 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 tissue keeps growing. Exactly. Okay. So you, um, well at least that’s one of the mechanisms are one of the thoughts. So we counterbalance that with progesterone. So here you have a, you divided everybody out by. You got a uterus or not. You know, as I guess I think about the, uh, the Dr Seuss and you know, the, the, uh, the stars upon stars, you know, they have stars and those are cool people in these are, you know, so anyway, so the, uh, they had a group that was, that didn’t have a uterus and that was the 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, a sugar pill, and then you have the study group which was permanent and they took a premarin alone.

Speaker 1: 08:41 The other group of, of uh, the other part of the study was that the, uh, 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 okay, you don’t have a uterus, you’re either going to get estrogen or placebo. Nobody knows who it’s double blinded. So the people giving it out, don’t know the people taking it, don’t know, and we’re just going to follow it over time. Uh, and they, they, uh, they did this study, uh, for several years. I don’t remember the average follower, the, uh, the follow up, I think, uh, I think it was basically seven years, seven or eight years that they followed these women on average. Um, so the first thing that I want to say about this group that took premarin is that premarin is not bioidentical estrogen, so the human body has estrogen, Estradiol 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, uh, estrogens.

Speaker 1: 09:52 But then there’s also some other hormones including androgens and progestins that are also in there, but they’re in really small amounts, uh, and basically there is extremely small amounts of estrogen that is a, that is pretty darn close, if not identical to estrogen in the human body. So the main dominant hormone in this is where the chemical anyway is sodium estrone sulfate at 49 point three percent. The second one, sodium [inaudible] sulfate, exelon equine, that’s horse horse estrogen. Great. If you’re a horse, a horse, not so good. If you’re a woman, a human woman, uh, so, and that was at 22 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 it the.

Speaker 1: 10:54 So the, the liver gets first crack at it and it makes ’em some metta, a 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, but, uh, there’s three different pathways. There’s the two hydroxy, four hydroxy 16 hydroxy pathway, and then there’s two phases to detoxification where you have a hydroxylation and then you have either glucuronidation, 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 and 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 for that either.

Speaker 1: 11:45 Not for that. You’re not going to sign up for, for Premarin. Okay, I’ll, I’ll make sure I know prescription please. Yep, exactly. Yeah. So I think it’s important to understand that at the foundation, but, uh, these, you know, these women that took Premarin, uh, so they were on these estrogen compounds, which there are estrogen activities effects in the body, and these, the test group took premarin zero point six, two five milligrams every day, kind of a standard dose. There are other doses, but that’s kind of a fairly standard one. Um, and 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 of 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.

Speaker 1: 12:42 So they went ahead and stop 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 and another year. So they said, let’s just go ahead and take what we got and we’ll call it good. So the findings of the Premarin only group, and we’re going to look at both groups, premarin and the prem program. We’re going to look at, um, uh, it looks like six factors that we’re going to look at. The first one’s cardiovascular disease. So in the premarin only group, there was no increase nor decrease in the risk of heart attacks. Didn’t change and it had no effect. 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 a beneficial for cardiovascular disease?

Speaker 1: 13:26 And they said no, it actually raises risk of cardiovascular disease. That was not because of the cardiovascular did a, 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, or the second thing, 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 uh, uh, uh, 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 10,000 women. So it’s not like a, what’s that a point zero, eight percent increase, something like that. It’s not severe. But again, there were more strokes and the authors, you know, went on to say in the, in the, uh, their publication, they said any increased risk of stroke is unacceptable.

Speaker 1: 14:27 And I agree with that. Um, 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, the benefits may be worth it. So, you know, we’ll just kind of watch through that. Um, so, um, that’s the main reason that they stopped the study, but there was a slightly increased risk of stroke. The third thing we’re going to look at is fracture. 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 primary group. So estrogen replacement does reduce risk of fractures, um, in, at least as reflected in the women’s health initiative study. Now we get into the big one where we talked about does it increase risk of cancer?

Speaker 1: 15:16 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 estrogen group, and in fact there were six less cases of breast cancer per 10,000 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 the investigators even stated, and this is in quotes, what is clear now is that overall postmenopausal 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 people. So estrogen alone in this study did not increase the risk of breast cancer.

Speaker 1: 16:12 I thought that was fascinating because there’s. There is some data, some, some, some, some. And we’ll talk about in another podcast that shows a slight increased risk of breast cancer with estrogen replacement not in the women’s health initiative. So I thought that was really, really interesting. So the fifth thing that we’re going to look at our blood clots or we call venous thromboembolic events and there was an increased risk of blood clots in the perimeter and group and again, that’s oral estrogen will go over more of this and another, uh, in another podcast, basically the ester trial, e s, t e r a trial showed that when you use topical or transdermal estrogen or other forms of estrogen besides a 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.

Speaker 1: 17:03 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 a primary group and the placebo group leads, no statistically significant difference. So the take homes 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, a, a increased risk of blood clots, but there was really reduced risk for everything else. So I was, uh, I was fascinated by that. In fact, there was lower risk of breast cancer in this study. So then we get into the pro group and this is where things really start getting interesting. Uh, and again, just like we talked about with the premarin group, um, and maybe we, I’ll tell you what, let’s go ahead and take a little break and then we’ll come back and we’ll talk about the prem pro group. Sounds Fair. Sounds great. You guys hang tight. We’ll be right back.

Speaker 1: 18:16 Okay. We are back and we’re talking about the women’s health initiative study. The first portion of the podcast, we were talking about a horse piss as estrogen or they hear that and exactly. So we’re drinking horse urine at, for our estrogen replacement. That’s awesome. Uh, so now we’re going to talk in about the, uh, the prim pro, which is premarin. Now I’m dealing with, that’s correct. That’s correct. So we had to give some provera that goes along with it, and again with the Premarin, I had to give the disclaimer that premarin is not bioidentical estrogen in this case, provera also called medroxyprogesterone. 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.

Speaker 1: 19:14 It bio identical. 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 16,608 postmenopausal women ages 50 to 79 who were enrolled in this 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. Premarin portion was zero point six, two five milligrams just like in the primary and only study. And there were two point five milligrams of provera or medroxyprogesterone acetate. The plan was to continue to study for eight point five years. They didn’t make it. And we’ll talk about why. So the, um, and we looked at six factors on what we’re looking at for the primary and we’re gonna look at those same six factors here for cardiovascular, for, for prempro.

Speaker 1: 20:14 The first one is in cardiovascular disease. And in the, uh, well let me, let me make one other statement here at. So I’m going to be talking about what’s called a hazards ratio or a risk ratio. And the hazard ratio is basically a statistical analysis term, uh, where it’s, where you’re looking at the relative risk of a given event. So it, 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, uh, a number. So a one score of one would be the two groups have the same risk. If the study group has a lower risk than the number will be less than one. If they have a higher risk. It will be greater than one, for example, the first section that we’re looking at cardiovascular disease, and they noticed that there was an increased risk of cardiovascular disease events with a hazard ratio of one point two nine. That means there is a 29 percent increased risk of heart attacks kind of events, cardiovascular disease, 29 percent. That’s the hazard ratio of one point two nine.

Speaker 2: 21:21 And this is because of the addition of the, um, the pro.

Speaker 1: 21:24 It’s basically, yes, because we didn’t see that in the only group. Now, can we say it’s because of the project, you’re the provera where the [inaudible] progesterone acetate or is it that it’s a combined issue? They’re still taking this orally, correct? That’s correct. So I would argue that yes, it’s the, the freaking battery acid that, I mean, I hate this stuff. It’s awful. Um, but, and, and how you really feel, but the data is here. Um, so, you know, unfortunately, uh, 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, but we misinterpret this stuff across the board. So cardiovascular disease, increased risk of events, one hazard ratio of one point two, 9:29 percent increased risk of cardiovascular disease. So Diana, what about strokes?

Speaker 2: 22:22 Definitely increased risk of stroke. There was a hazard ratio of one point four one. So I’m going to see that as an increase of 41 percent.

Speaker 1: 22:30 You got it. So there were 41 percent more strokes in the treatment group than in the placebo group. Uh, what about fractures?

Speaker 2: 22:38 Uh, you have a decreased risk of hip fracture, so now you have a decreased risk which the premarin did as well. Correct.

Speaker 1: 22:47 The primary did show a decrease risk as well. So yes.

Speaker 2: 22:52 All right, so we’re still helping with the fracture issues. Um, now your breast cancer, increased risk of breast cancer, your ratio there is one point two six. So you have an increase of 26 percent risk of breast cancer taking your prempro.

Speaker 1: 23:09 Exactly. And the thing is that was not seen in the premarin alone group. It wasn’t the estrogen, it was the Madonna, oxy, progesterone Acetate, the provera, 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 we’ll come back to that in just a minute. Uh, blood clots or venous thromboembolic events, uh, there was an increased risk of pulmonary embolism, which is a clot in your lung. Usually they come from, uh, the, you know, the lower extremities are up in the pelvis. Uh, and so it is a venous thromboembolic event or a blood clot a. and there was a hazard ratio of two point one 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 permian group alone that, I mean, you might, again, you might as well be drinking battery acid.

Speaker 1: 24:13 And finally, with colon cancer, there was a decrease risk of colon cancer with a hazard ratio of points three, because that battery acid is burning everything that 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. I’m. And if you think back of the root word of facetious, and we’re talking about colon, so they go together. I think so. Um, so again, like I said earlier, this, uh, this part of the study was stopped early due to an increased risk of breast cancer. They meant the steady to go eight point five years, but they stopped three point three years early because of these risks. And again, it wasn’t increased rate in the one increased 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.

Speaker 1: 25:04 They were also using prempro and there was no reduced risk of cardiovascular disease, uh, in, in that they, they also didn’t show a real increase, if I remember correctly, uh, in cardiovascular disease. And so, you know, one of my passions is talking about this, uh, 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 stat. And then all of those were secondary prevention trials. But that’s another topic for another day. So in the hearst to study, they noted that prempro lowered ldl cholesterol, that’s the bad cholesterol lowered at 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 cholesterol doesn’t cause heart attacks.

Speaker 2: 26:07 So when I guess what, what I want to know now is now that we’ve talked about the women’s health initiative, what does it tell me about our bioidentical hormone replacement therapy or Bhrt?

Speaker 1: 26:19 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 a biogenical hormone replacement therapy, it doesn’t tell us anything about, about hormone replacement therapy because they’re not biogenical exactly. And so I use the analogy of, you know, I remember several years ago and some people may, this, some people may not, um, several years ago, the, um, uh, the national highway traffic safety administration launched an investigation, in fact that year was in 2000 looking at Ford Motor Company and firestone tires. And they found that the combination of the, uh, 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, in, in accidents that they attributed to the Ford explorer and the firestone tires.

Speaker 1: 27:17 So the combination of these two things resulted in an, in a vehicle that was unstable in, in its handling and at risk because of the tire separation. Uh, and so, um, it was the, uh, 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 I’ll 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 A. 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.

Speaker 1: 28:26 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, uh, you know, understanding premarin and Provera as in, in the women’s health initiative and um, you know, understanding that they’re non bioidentical hormones, it’s just not the same thing as using bioidentical hormone replacement therapy like we do in our clinic. There’s just a big, big difference and it’s as big of a difference as suv tires. 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 and 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.