#42–Avrum Bluming, M.D. and Carol Tavris, Ph.D.: A compelling case for hormone replacement therapy

1. 0:00 – 0:04

   Intro

   1. PAPeter Attia0:00

      [upbeat music]

2. 0:04 – 9:00

   Why the Drive Has No Ads and Peter's Case for Hearing About HRT

   1. PAPeter Attia0:04

      Hey, everyone. Welcome to The Peter Attia Drive. I'm your host, Peter Attia. The Drive is a result of my hunger for optimizing performance, health, longevity, critical thinking, along with a few other obsessions along the way. I've spent the last several years working with some of the most successful top-performing individuals in the world, and this podcast is my attempt to synthesize what I've learned along the way to help you live a higher quality, more fulfilling life. If you enjoy this podcast, you can find more information on today's episode and other topics at peterattiamd.com. [upbeat music] Hey, everybody. Welcome to this week's episode of The Drive. I'd like to take a couple of minutes to talk about why we don't run ads on this podcast and why instead we've chosen to rely entirely on listener support. If you're listening to this, you probably already know, but the two things I care most about professionally are how to live longer and how to live better. I have a complete fascination and obsession with this topic. I practice it professionally, and I've seen firsthand how access to information is basically all people need to make better decisions and improve the quality of their lives. Curating and sharing this knowledge is not easy, and even before starting the podcast, that became clear to me. The sheer volume of material published in this space is overwhelming. I'm fortunate to have a great team that helps me continue learning and sharing this information with you. To take one example, our show notes are in a league of their own. In fact, we now have a full-time person that is dedicated to producing those, and the feedback has mirrored this. So all of this raises a natural question. How will we continue to fund the work necessary to support this? As you probably know, the tried and true way to do this is to sell ads. But after a lot of contemplation, that model just doesn't feel right to me for a few reasons. Now, the first and most important of these is trust. I'm not sure how you can trust me if I'm telling you about something when you know I'm being paid by the company that makes it to tell you about it. Another reason selling ads doesn't feel right to me is because I, I, I just know myself. I have a really hard time advocating for something that I'm not absolutely nuts for. So if I don't feel that way about something, I don't know how I can talk about it enthusiastically. So instead of selling ads, I've chosen to do what a handful of others have proved can work over time, and that is to create a subscriber support model for my audience. This keeps my relationship with you both simple and honest. If you value what I'm doing, you can become a member and support us at whatever level works for you. In exchange, you'll get the benefits above and beyond what's available for free. It's that simple. It's my goal to ensure that no matter what level you choose to support us at, you will get back more than you give. So for example, members will receive full access to the exclusive show notes, including other things that we plan to build upon, such as the downloadable transcripts for each episode. These are useful beyond just the podcast, especially given the technical nature of many of our shows. Members also get exclusive access to listen to and participate in the regular Ask Me Anything episodes. That means asking questions directly into the AMA portal and also getting to hear these podcasts when they come out. Lastly, and this is something I'm really excited about, I want my supporters to get the best deals possible on the products that I love. And as I said, we're not taking ad dollars from anyone. But instead, what I'd like to do is work with companies who make the products that I already love and would already talk about for free and have them pass savings on to you. Again, the podcast will remain free to all, but my hope is that many of you will find enough value in, one, the podcast itself, and two, the additional content exclusive for members to support us at a level that makes sense for you. I want to thank you for taking a moment to listen to this. If you learn from and find value in the content I produce, please consider supporting us directly by signing up for a monthly subscription. This week I had the pleasure of interviewing two people, Dr. Avrum Bluming and Dr. Carol Tavris. And if Carol's name sounds familiar to you, it's because it should. I've spoken about her often, as she is the author of one of my absolute favorite books, Mistakes Were Made (But Not by Me) . And if you haven't read it, I recommend you hit pause now, go and buy it, come back. Carol's a social psychologist and an overall great skeptic. Her collaborator in this project, which we'll get to, is Dr. Avrum Bluming, who's a hematologist, medical oncologist, and an emeritus clinical professor at USC. He's also formerly a senior investigator at the National Cancer Institute. The book we discuss today is their most recent project, a book called Estrogen Matters, which as its name suggests, is a book about hormones. In particular, it's a book about hormone replacement therapy in women. Now, I realize at this moment about half the people listening to this, i.e. those of you who are guys, are thinking, "Do I really need to listen to this episode?" And the short answer is, I think you do. At the very least, if you know a woman or care about a woman, you should be listening to this episode. Why? Because in many ways, this topic has created as much confusion and generated as much bad information as any topic in medicine. And yes, I am including nutrition science, which is the absolute bottom of our understanding of science. And the sort of parallels between the story of HRT and the nutritional guidelines in the '70s and '80s is almost uncanny, and that comes across during this interview when Carol and Avrum tell a story that I, I had either forgotten or didn't know. The book is written in, I think, a very clear way, and I do recommend that anyone who is interested in this topic, you know, not just take our word for it in this episode, but instead get the book and go through the references. I spent a lot of time utilizing my team to help prepare for this interview because as familiar as I am with this topic, and I think I'm more familiar with this topic than most physicians, I still felt the volume of information was just so great that I wanted to make sure I had gone back and read all of the studies in preparation for this. And in many ways, I'm glad I did because it allowed us to really get into some of the details here and hopefully do so in a way that isn't confusing for you, but rather at least opens the door to your thinking about this. This is a very polarizing topic. It is almost a religion, so you will see that there are people on both sides of this that are pure zealots. And unfortunately, that just makes it that much more difficult to sort of interpret the literature on this. But in the end, you will have to be the judge of this. It is certainly my view, and I don't hide that view anymore, that most women do benefit from being on postmenopausal hormone replacement therapy. But not all women do, and I think one of the challenges for physicians and patients alike is trying to stratify which patients will receive much more benefit than the risk that's posed to them, and of course, perhaps as importantly, identifying the patients for whom the risk is outweighed, or is disproportionate, rather, to the benefits. The interview largely covers the subject material covered in their book, which is to say the history of hormone replacement therapy, the impetus for the Women's Health Initiative, a very serious critique of not just the initial publication, but the subsequent publications, and then a little bit of a deep dive into each of the clinical conditions for which hormone replacement therapy should at least be considered. And of course, I think the most important of these is in not just cardiovascular disease, which gets a lot of attention, but neurodegenerative disease, and I think Avrum makes a very compelling case for that. So without further delay, here's my interview with Dr. Avrum Bluming and Dr. Carol Tavris. [upbeat music] Before we get to this week's episode, I want to remind everyone that one of the benefits of being a subscriber is a discount program that we've created. Now, the purpose of this was to take the money that companies have offered to pay for advertising and say, "Look, instead of doing that, I'd rather just talk about the companies that have products that I love and use without being paid to do so," and say, "Take that money that you would have given us in advertising and pass that on to discounts as listeners." So the first one's coming out this Wednesday, and if you're not a subscriber yet, that's okay. You've got plenty of time to sign up. Head on over to peterattiamd.com/subscribe where you can have access to this discount and future discounts. And now let's get to this week's episode with Carol and Avrum. [upbeat music]

3. 9:00 – 14:12

   Why a Social Psychologist and an Oncologist Wrote About Estrogen

   1. PAPeter Attia9:00

      You guys, thank you so much for making the trip down from LA today.

   2. CTDr. Carol Tavris9:03

      We're happy to do it.

   3. PAPeter Attia9:04

      This is one of the topics that I have been meaning to explore so deeply over the past two or three years through what was originally going to be a multi-part blog post and a number of other things, and there always was a reason not to do it. And then you and I spoke about a year ago, Carol, and I said, "Carol, I'd love to interview you about Mistakes Were Made," and your response was, "I can't talk about that book anymore. I'm so tired of it. All I want to do is think and, you know, think about this new thing that I'm really excited about, which is Estrogen Matters." And I must admit, I was embarrassed at that point to acknowledge I didn't realize you had been working on it even though I had read the paper that you guys had written in 2009, which we were talking about a few minutes ago. So it was sort of an aha moment for me, and I was delighted because I thought, "Well, you're gonna do a much better job than I would have done, you know, because you're gonna put so much more work into it." So I guess for the listener that's not familiar with you, Carol, let's start with you, Carol. You're a psychologist.

   4. CTDr. Carol Tavris10:03

      Social psychologist, yes.

   5. PAPeter Attia10:04

      Social psychologist. What's a social psychologist writing about estrogen for?

   6. CTDr. Carol Tavris10:08

      My lifelong interest has been in bringing good scientific research in psychology and medicine to public attention. And as you well know, this is an effort that is not always greeted with huzzahs and cheers and, "Thank you ever so much for showing us that our beliefs are wrong and are time to be replaced." But it's my lifelong quest, and that's what I do. And that's, of course, what Mistakes Were Made (But Not By Me) was about, why it is that people resist new information that is better to know, that is beneficial, that improves our knowledge, and that's been my life work. And as a social psychologist, I have always been interested in the barriers to critical thinking and the reasons that people do not accept information when it is in their best interest to do so. So knowing Avrum Bluming for as many years as I have, we have discussed over the years how our shared interest, his in medicine and mine in psychology, uh, reflect the same concerns. What happens when research calls into question some established belief that is widespread in our society?

   7. PAPeter Attia11:20

      You know, I know I've told you this before, but I'll, I'll, I'll repeat it, that Mistakes Were Made (But Not By Me) is-- would certainly be on the list of the three books I have recommended and/or gifted the most. And in fact, I remember reading it and just somehow finding out how to get ahold of you and just calling you and emailing you and inviting you over for dinner. It was-- [laughs]

   8. CTDr. Carol Tavris11:39

      [laughs]

   9. PAPeter Attia11:40

      You must have thought that was the weirdest thing ever.

   10. CTDr. Carol Tavris11:42

       Not at all. I was very flattered and pleased, by the way. And by the way, this work on estrogen that Avrum has so excited me about could be a chapter in that book

   11. PAPeter Attia11:54

       It actually is, as, as are other things that we have discussed, for example, dietary recommendations and things like that, that I know you have contemplated going back on and thinking about that. So Avrum, what, what about you? And tell, tell us a little bit about your, your background, your training as a, as a clinician and, and why in particular this issue has become something that's resonated with you.

   12. ABDr. Avrum Bluming12:12

       I'm a medical oncologist. I've spent over fifty years as a medical oncologist, and my reason for going into the field was to help people live as long and as well as possible, enlisting them helping to decide how best they should be treated. And breast cancer constitutes about sixty percent of my practice. And I've watched the progress in breast cancer very happily noting how many people we now cure, and in fact, our early breast cancer now is about ninety percent curable. And I found that while I was making a lot of people better in terms of the cancer, I was making them worse in terms of the symptoms associated with the treatments they got. And when you treat something for that long, you want to understand what it is so that you can treat it most effectively. And first, let me say at the beginning, I'm a medical oncologist, and I don't yet know what cancer is. And I'm in very good company because I don't know anybody who knows what cancer is, even though many will tell you they do, and they're wrong. And so it was important that I challenge every assumption on which my practice was based, and I've done that continuously. And the major assumption dealing with breast cancer is that estrogen causes breast cancer, and it doesn't. And almost everything we've done in the treatment of breast cancer is based on that assumption, so that women have been denied estrogen for at least the last thirty years, but especially since twenty oh two, and the result is that many women have been hurt by being denied that medicine.

4. 14:12 – 20:25

   History of Treating Women: From Castration to Feminine Forever

   1. PAPeter Attia14:12

      So let's take a step back in history now because in your two thousand and nine paper, it's actually the second table. I was actually reviewing it again this morning. It's a beautiful time course of hormone replacement therapy in women. So I'll let you guys decide how you want to tell the story together, but let's go back to at least the nineteen forties or the nineteen fifties. How did this idea of, "Hey, women go through a pretty abrupt withdrawal of hormones. Let's take a moment to think about how we can make that better," how did that idea come about?

   2. ABDr. Avrum Bluming14:44

      I think to give us perspective, let's compare men and women. The number of women with breast cancer in the United States is approximately comparable on an annual basis to the number of men with prostate cancer. Uh, the number of women who die of breast cancer each year is also approximately comparable to the number of men who die of prostate cancer. We like simple answers, all of us. And to think that testosterone is responsible for prostate cancer and estrogen is responsible for breast cancer is a very simple way to go about dealing with this. And what we found is metastatic cancer of the prostate was initially treated with castration. If testosterone causes prostate cancer, taking off the testicles eliminates the testosterone, and in fact, it helps. Doesn't cure, but it helps in some cases. Similarly, we castrated women. Estrogen is made in the ovaries. If we remove the ovaries, we can cause breast cancer to regress once it has spread, and it does help. Not in many cases, but in a significant number, it helps. As far as cancer of the prostate is concerned, that's where we stopped. If castration didn't help, we did what we could to palliate. With breast cancer, what we did if castration didn't help, we went on and removed the adrenal glands of women. Now, the adrenal glands make a small percentage of circulating estrogen, and by the way, they also make a small percentage of circulating testosterone. We never removed the adrenal glands of men. We removed the adrenal glands of women, and as you know, there are hormones made by the adrenal gland that are necessary for survival. So once you remove the adrenal gland, you have to replace the hormones that were necessary for survival, and we did that. If the adrenal gland removal didn't work, we then would take out the anterior pituitary gland at the base of the brain because that gland produces a hormone that stimulates either the ovary or the testicle to make the responsible hormone. And so we used to do hypophysectomies, and while I was in practice, we did that. And as you know, the anterior pituitary makes many hormones that are necessary for survival. So we had to replace many of those hormones, and we didn't really help too many women with that. Let me reiterate, we did nothing like that for men. And we hurt a lot of women by doing that. We did it with good intentions, but we hurt them. What we then found is when women had breast cancer, because we were concerned that it might come back, we prophylactically removed their ovaries, saying, "Well, if estrogen causes breast cancer, this will help prevent it from coming back." And we tested that with seven different studies. None of those studies show that it worked. Did we ever treat men by prophylactically castrating them? Never, and we never will 'cause men still control medicine by and large. So we were doing a lot with good intentions and hurting women. We then were looking at what estrogen is capable of doing, and this goes back to your question. Back in the 1940s, there was a book written called Feminine Forever that essentially said, "Well, women should take estrogen forever, and it'll be a, an eternal fountain of youth." That's not true. That book was oversold. The doctor who wrote that book was paid for by the drug company who made estrogen, and we didn't know that until his son told that to the press after he died. But estrogen did do some very good things, and what we found estrogen is capable of doing is, first, estrogen can relieve the symptoms of menopause. The way menopausal symptoms are viewed as well, it's hot flashes and night sweats, and it'll usually last a year or two, and tough it out, lady, and you'll get through it. And point of fact, there are many symptoms associated with menopause that aren't just hot flashes and night sweats. It includes palpitations. It includes cognitive decline. It includes joint pains.

   3. PAPeter Attia19:34

      Sleep disturbances.

   4. ABDr. Avrum Bluming19:35

      Right.

   5. PAPeter Attia19:35

      Yeah, lots of things.

   6. ABDr. Avrum Bluming19:36

      And it usually lasts about seven and a half years, not two years, and in some women it goes on for decades, and women are taught to suck it up and deal with that. Estrogen is also capable of reducing significant heart disease by up to 50%. There was an article in "The New England Journal of Medicine" in 1991 by Goldman and Tosteson that said, "Time for action, not debate," saying if women took estrogen, they would live longer, they would be healthier. That was 1991, and we now know that estrogen has been shown repeatedly to help diminish the risk for significant heart conditions.

5. 20:25 – 33:19

   What Hormones Do: The Estrogen Cliff and Heart Disease vs. Breast Cancer Risk

   1. PAPeter Attia20:25

      So let, let's pause for a moment because I want to make sure that people listening to this, and, um, I hope it's not just, uh, women, but it should be men as well, unless you're a man who finds himself not knowing any women, then maybe you won't listen to this. But let's explain what these hormones do a little bit. So there are not many papers that I have printed out in my office because we just don't print papers up that much anymore. You know, we don't physically have a paper copy, but there are a handful that I have printed up, and one of them, of course, is the WHI, both the 2002 and then some of the republications, because I do like to show people the actual data which I think speak for themselves. But another thing that I have printed up is the hormone cycle for a woman during her reproductive years, and I started doing this about three years ago, and I was surprised how many women didn't know what estrogen was doing in their body, how it would rise during the follicular phase, peak during ovulation, decline during luteal phase, and come up for a second bump before declining at their period, and similarly how progesterone would, would follow a small thing. Now, we're gonna link to images of that in the show notes, but the point I want to make is, you know, women go through this for, what, 35 years of their lives, maybe longer, maybe 40 years of their lives, and I guess I was just surprised that I remember having a, a patient who was complaining of horrible PMS. And so I said, "Well, it has to do with the reduction of progesterone, and in some women the fall of progesterone during the end of the luteal phase is so rapid that for reasons we don't understand, that's gonna produce a change in something, and you can ameliorate that by doing X, Y, and Z." And the woman looked at me and she was like, "This is incredible. Like, you've made me feel like I'm not crazy because you've shown me this graph that explains what's happening with my progesterone levels." So I do want to make sure that someone listening to this spends a moment to understand what we're actually talking about. You have these hormones that we're gonna hear... You know, we're gonna talk about luteinizing hormone, follicle stimulating hormone. You've alluded to these already coming out of the pituitary, telling the ovaries to make these other hormones. And, and really, is it safe to say at the risk of oversimplifying, the reason it seems that women only experience this during a finite period of their life is that's kind of when evolution wanted women to be able to reproduce. Without this cycle of rising estrogen, progesterone falling levels, women wouldn't be able to reproduce. Is the risk of oversimplifying, is that a fair statement of why they have-- we have this finite window?

   2. ABDr. Avrum Bluming22:56

      Finite window of-

   3. PAPeter Attia22:58

      During which time women have these hormones versus men-

   4. ABDr. Avrum Bluming23:01

      Oh, finite

   5. PAPeter Attia23:01

      ... who have kind of, you know, men have a much more gradual decline in their reproductive hormones.

   6. ABDr. Avrum Bluming23:08

      This is a crucial thing to say, Peter. This is really important. This was something I didn't realize until we began working on this book. I assumed that in menopause estrogen declines. I think that's the way women see it. It just declines the way testosterone declines in a slow, moderate way. No, estrogen plummets to 1% of what it was before menopause. I think most women have no idea that it's that great a drop in estrogen levels, and no wonder that many of the symptoms that women have, which by the way include depression, and they attribute it to a, "Well, it's a midlife crisis I'm having." No, it could be an estrogen depletion crisis as well. And so I think it's really important for women to understand that this is not just a s- a little fall off. It's really a, a major drop. I want to add one th- thing here to this because as the social psychologist of this duo, what interests me is the way women have been

   7. CTDr. Carol Tavris24:07

      Given false information for so many years about so many aspects of their reproductive cycle and experience that it's no wonder that many women have a great skepticism about what medicine has to offer them in reproductive issues. Just what Avrum was saying about th- there was so little hesitation in cutting women up and removing this part and removing that part. Let's try this other thing, things that would never have been tried with men, that men would just never have agreed to. And so women have had an understandable skepticism about the medical establishment's advice. And starting with Feminine Forever, Robert Wilson's ridiculous song of praise to estrogen, women began to think, "Well, you know what? The hell with all of you on this. Estrogen is-- I don't need it. It doesn't make me feminine forever, and who dares to think that I need to be feminine forever in that traditional way, and menopause is just a natural phase of life, and I can deal with it as I dealt with the onset of menstruation." So what I want our conversation to bring here is an understanding of w- why women have been kind of whipped back and forth on whether estrogen is good for them or bad for them.

   8. PAPeter Attia25:19

      And tying onto that, we left out another grotesque example of this, which Sid Mukherjee has written about so eloquently in The Emperor of All Maladies, which is the radical mastectomy, which ties into all of this. You know, Avrum, the points you brought up a moment ago, I wasn't even aware of the pituitary resections. I was aware of the oophorectomies, of course. I had no idea they were resecting adrenal glands, which strikes me as ridiculous, but to actually resect the pituitary gland, I mean, that's macabre. It's, it, it-- Yeah, yeah, exactly. Transsphenoid resections. I mean, it's just hard to believe. And yet lost in that story, which should be added just to complete the sentence is, and up until Bernard Fisher came along, it was viewed as completely nonsensical that you would do anything other than disfigure a woman with breast cancer by removing every piece of tissue above her ribcage. It's an interesting point you raise, right? Which I never really had contemplated, truthfully, which is could that have taken place if the roles were reversed gender-wise? I'd never really thought of it.

   9. CTDr. Carol Tavris26:22

      Think also about hysterectomies, the routine use of hysterectomy on the assumption that a woman, once she's had her children, doesn't need to have her uterus. "And by the way, since we're removing your uterus, let's remove your ovaries as well, because what the hell, they're just there. Let's take them out," as if they have no function. That casual attitude of, "Let's just get in there and get rid of them."

   10. PAPeter Attia26:41

       And the term hysterectomy, you want to maybe provide a bit of context for the listener on what that means?

   11. CTDr. Carol Tavris26:45

       Well, hysteria was thought to be caused by the wandering womb, which detaches itself and wanders through the female body, causing mayhem and despair. Yeah, yeah, part of our more ludicrous notions about the female body.

   12. ABDr. Avrum Bluming27:02

       The point is women weren't treated fairly, and they're still not being treated fairly. And just to amplify one point I made, uh, I mentioned that, uh, estrogen can significantly decrease the risk of heart disease. What many women tell me at that point is, "Well, old women die of heart disease. Young women die of breast cancer. I'd rather not take estrogen if estrogen causes breast cancer." And it's-- the answer to that is twofold. First, estrogen does not cause breast cancer, and we'll get into that in detail. But more than that, in every decade of a woman's life, the incidence of death from heart disease is greater than the incidence of death from breast cancer.

   13. PAPeter Attia27:47

       I, I want to reiterate this point. It's, it's like you were reading my mind. In preparing for this discussion, I, I did something I normally don't do. I normally don't put as much time into prep, but this is such a data-driven d- discussion and, and, and the data are just so voluminous that I, I really had to spend a lot of time preparing, and, and my team helped me greatly. But I have a chart that we will include in the show notes which makes your point very eloquently. If you begin at the age of twenty-five, you take a cohort of twenty-five-year-old women, and you forward-looking project their ten-year mortality from breast cancer and from cardiovascular disease by decade, I'm going to read off the difference in favor of cardiovascular disease. So if the number is greater than one, you'll die, more likely to die of a heart attack than breast cancer. If it's less than one, more breast cancer. Starting at the age of twenty-five, going up in five-year increments with a ten-year forward look. Three point five X, three point five times more likely to die of heart disease. Two point four X, two point one X, two point three X, two point five X, two point eight X, two point four X, two point one X. We're now at thirty-five years old. Two point three, two point five, two point two, three point three by fifty-five, four point one by sixty, five point six by sixty-five, eight point one by seventy, and twelve point four by seventy-five. When you do the math on aggregate across lifetime, it's seven X difference in favor of cardiovascular disease over breast cancer. Where are the red ribbons?

   14. ABDr. Avrum Bluming29:19

       Heart disease kills more women than the next sixteen causes of death, including all forms of cancer, AIDS, and accidents.

   15. PAPeter Attia29:30

       The other thing people listening to this know how near and dear heart disease is to my heart because it is the number one killer for both men and women. There's another area where I think women get a bit of a short straw here, which is women present with heart disease quite differently. Do you want to say something about that?

   16. ABDr. Avrum Bluming29:43

       Sure. The typical presentation of a man is crushing chest pain, pain that goes down the left arm, starting at the left shoulder. Women can often present with an upset stomach. Uh, and because we generally don't think of women as suffering from heart disease, the diagnosis is initially missed quite often, although doctors are getting more and more sensitive to that now.

   17. PAPeter Attia30:10

       All right, so I took us off a bit of a detour. Carol, your point's a great one. I want to come back to make for the first time in my career, because I don't treat many women going through menopause, but any woman who's a patient of mine who's going through it, I'm going to be a part of it. But this past year, I got to see firsthand how quickly a woman can enter menopause, because if you happen to do labs on women frequently enough, you can see the drop. So I had a patient who in August of 2017, I like to check labs on what would be day five so I can really standardize where the FSH and estradiol should be. She had what looked like completely normal levels. Her FSH was something in the neighborhood of 10. Her estradiol was maybe 90. She was starting to have symptoms though. So I said to her, "Look, you are very likely in a perimenopausal state. I expect you will enter menopause in the next three or four years." She was probably 47. Rechecked her blood in November, her FSH was 68. Her estradiol was unmeasurable. I rechecked the labs because I couldn't believe it. Same result. Reached out to one of my mentors, a gynecologist named Riley Lloyd in Chicago, and I said, "Riley, what has happened here?" And he goes, "You just happened to see her fall off the cliff. This happens all the time. It's just we usually aren't looking at laboratory tests that frequently." So it's an interesting point, and I'm glad you emphasized it.

   18. CTDr. Carol Tavris31:34

       And also, you cannot say exactly at what age. One of the women we describe in the book who wrote a blog about this, Katie Taylor, who said she was 42, she was extremely depressed, she was having all sorts of symptoms. She was treated for her depression with antidepressants. That didn't do anything. Her doctor said, "Maybe you should quit your job. That will help your stress levels." Oh, sure. And fortunately, her father is a leading breast cancer specialist in England, and he said, "You know what? You could be in perimenopause." And she was. And she was. So many of the symptoms that women begin to develop in their 40s, they don't associate with menopause. Muscle pain sends them to rheumatologists, and depression sends them to therapists, and fighting with their spouses sends them to family therapy, and they don't think that their changes of menopause might be involved. I want to say, by the way, that I am one of the minority of women who sailed through menopause with no symptoms, and my mother as well. And so I underestimated how many women really suffer. It's not a verb I like to use much, but many women suffer with the symptoms of menopause, which I never did. And I think that many of the women who are kind of casual about menopause, "Oh, you don't need to take anything. This too will pass." This too will pass? Easy for you to say if you're not sleeping for seven years.

   19. PAPeter Attia32:59

       Well, that's really interesting, Carol. I wasn't going to ask you that on the mic, but I was planning to actually ask you that after, which was what is your personal experience with this and how much of a role has that played in your motivation? And I'm interpreting your answer to mean your motivation for this is more in the spirit of truth-seeking than it is a personal vendetta.

6. 33:19 – 38:14

   Motivations and Personal Stories

   1. CTDr. Carol Tavris33:19

      Absolutely, and I'm glad you brought that up because it's the first thing people want to know is do you have a vested interest in this? Do you want to defend your own decision to be taking hormones? Are you getting money from the drug companies? So let's make this very clear here now. Neither of us has a vested interest in this. Neither of us has taken any money from drug companies. I have been a vociferous critic of big pharma and a lot of its manipulations of research and its inflated claims. And no, I don't have a personal interest in defending HRT. In fact, as a feminist psychologist for many years, I was really critical of the kind of take it for granted assumption that once a woman hits menopause, then you got to fill her tank with hormones to get her back to being a real woman. I was very critical of that, which was easy for me to do when I was 35.

   2. PAPeter Attia34:08

      And Avrum, I want to just maybe give you a chance to say the same sort of thing. You've obviously provided a CV that provides an interesting explanation for why you would care about this given the volume of patients you would have taken care of, but is there something more personal? Was there a particular patient that sort of broke your heart, meaning the experience that she went through broke your heart and is something that you think about a lot as you're on this crusade?

   3. ABDr. Avrum Bluming34:31

      Some particular thing, no, but in fairness, let me tell you that when my wife reached 45, she had breast cancer, and she was treated by me with chemotherapy, and she went into menopause. And unlike Carol, she was very symptomatic, and she didn't complain for two years. She had the night sweats, the difficulty sleeping, the joint pains, the palpitations, but women are supposed to suck that up and take it, and she did. And then she started to find that reading, which is her passion, was now being challenged because when she'd read a book, she couldn't remember what she had read two or three pages before. She did numbers in her head. She's one of the smartest people I know, and she was unable to remember telephone numbers, and that's when she spoke to me. And she is one of the first people I put on a study, which we'll get to later, which is a study of hormone replacement therapy in women with a history of successfully treated breast cancer. And it took about two weeks, and she was back, and she would never go off them.

   4. PAPeter Attia35:45

      So I guess while we're on that topic, I'm going to tell my story of why I started to care about this so deeply. A woman came to me about five years ago who had survived an ER/PR positive breast cancer. So for the listener, that means she had a breast cancer that showed sensitivity to estrogen, progesterone. It was not HER2-neu, I believe. So it was ER/PR positive, HER2-neu negative. She was very young. She was probably in her early 40s at the time of this diagnosis. She underwent a hysterectomy, oophorectomy. At the time, she also underwent her mastectomies. She basically became lost. So she described it to me -- This was before I knew her. She described it to me as being unable to get off the couch. She described the fog of being something that her doctors at the time attributed to chemotherapy, and they said to her, "Once the chemo is done, you will feel better." Three years after the chemo, she felt worse, and it finally occurred to her and to her husband that maybe this had something to do with the fact that at, at the age of 42, overnight, she lost every sex hormone in her body. She couldn't find any doctor on the planet who would prescribe hormone replacement therapy to her, because as a breast cancer survivor who's ER/PR positive, how could you do such a thing? Though she did eventually find someone who was willing to give her a trial. She felt immediately better. I mean, immediately better, sort of as you describe it. Within weeks, she felt like she got her life back, could do everything again. And by the time I met her, she was on a very clever regimen, which was mostly estriol, so topical estriol, not estradiol, and we can get into the details of that later, along with... She didn't need the progesterone, obviously, because she, she had a hysterectomy, and a physiologic replacement of testosterone to reduce sort of about, to about half a nanogram per deciliter level. And her case interested me so much because I started thinking, "Wait a minute. Isn't she increasing her risk of breast cancer?" And I won't get into, you know, the details of where that took me, which rabbit hole, but it obviously in some way led to a converging discussion that we're having today. So I want to go back to now we're in the 1950s. You've got the snake oil salesman out there. He's telling every woman she must be on estrogen. When did the tide change, or when did the nuance start to emerge about different levels of replacement?

7. 38:14 – 46:01

   Rise and Fall of HRT Use and the Setup of the Women's Health Initiative

   1. ABDr. Avrum Bluming38:14

      In the 1970s, uh, let's just go back, uh, Premarin, which is an acronym for pregnant mare urine, which was an inexpensive way to manufacture a lot of estrogen, and was and still is the dominant form of estrogen sold in the United States. And that is the company. The company that makes Premarin is the one that was supporting Robert Wilson. Premarin was being used on women who were going into menopause. And in the early 1970s, we found that there was a significant rise in the incidence of uterine cancer. And as you mentioned, estrogen alone does increase the risk of uterine cancer as much by, uh, as fivefold. And so estrogen prescriptions fell off dramatically in the early 1970s. By the late 1970s, we had learned that giving progesterone together with estrogen, either on a cyclic or a continuous regimen, nullified that increased risk of uterine cancer. And so at the end of the 1970s, hormone replacement therapy started to increase again. It continued that way until about 2002, and in 2002, it is estimated that about 16 million women in the United States were taking hormone replacement therapy, either estrogen alone if they didn't have a uterus, or the combination if they did have a uterus, and that constituted about 22% of the appropriate age population in the United States. That was 2002. By 2004, it was down from 22% to 10%. By 2010, it was down to 5%, and that was due primarily to the publication of a single large study called the Women's Health Initiative, which you alluded to earlier.

   2. PAPeter Attia40:19

      Now, prior to that, there was a large cohort-based study called the Nurses' Health Study, and many people looked at that and said, when you look at the Nurses' Health Study, which is an epidemiologic study, so there was no randomization, the benefits of hormone replacement therapy for women who had a uterus or estrogen replacement therapy for women who did not seemed quite compelling. And didn't some people actually ask the question, is it even ethical to conduct a Women's Health Initiative, which would, by definition, subject some women to a placebo arm?

   3. ABDr. Avrum Bluming40:52

      Two things to that. First, the Nurses' Health Study was a study that was done out of Harvard where 120,000 nurses were followed for up to 30 years. And yes, it wasn't randomized, but the thought was that nurses were sophisticated enough to be able to report symptoms and to keep careful count of the medicines they were taking, and it's a classic study. It still is. And what they found, as you point out, is women who took it for five years or 10 years or 15 years had no increased risk of breast cancer. And so when the Women's Health Initiative was first undertaken, the ostensible rationale was not to see whether it increased breast cancer. What they wanted to see is, did it really have a beneficial effect on the heart and the brain and the bones? That's the reason it was set up. And there were some studies that said it did, and there were two studies that questioned whether it did. And so the theoretical rationale, and I say theoretical because there were motives that weren't immediately apparent when it was first set up, but the theoretical rationale was to see if it was as good as we thought it was.

   4. PAPeter Attia42:13

      Now, one of the things that I didn't learn until probably three years ago, because My first interest in the Women's Health Initiative was in the nutritional study, which was by budget the smaller of the two. I think you probably know these numbers. I'm probably guessing somewhat, but the WHI was about a two and a half billion dollar study. Is that correct?

   5. CTDr. Carol Tavris42:37

      Was one billion.

   6. PAPeter Attia42:37

      Just one billion for both arms.

   7. CTDr. Carol Tavris42:39

      Right.

   8. PAPeter Attia42:40

      Just, yeah, just-

   9. CTDr. Carol Tavris42:40

      Compared to the wall, it's not a lot, but it's still a billion dollars.

   10. PAPeter Attia42:43

       Okay. I, I thought for some reason the one billion was just one arm and the, and the other one, but never nevertheless, it was really two completely separate studies, right? There was the nutritional study, which we're not gonna get into, and then there was the study that you're talking about. This was initiated in what year? About '92?

   11. CTDr. Carol Tavris43:00

       '96.

   12. PAPeter Attia43:01

       '96. Okay. And the fact that I'm alluding to or the fact that I was alluding to a second ago that I'll get to now, that when I saw it three years ago, I thought, "That has to be a mistake," was the, the quality of the health of the women enrolled in that study. Do you wanna say a, a little bit about, for example, the prevalence of obesity, smoking, hypertension-

   13. CTDr. Carol Tavris43:25

       Oh, sure

   14. PAPeter Attia43:25

       ... and other conditions?

   15. CTDr. Carol Tavris43:26

       Their average age was 63, 10 years after the average age of a woman entering menopause. 70% of them were seriously overweight or obese. Uh, more than half were smokers. Uh, they had high rates of hypertension, and this was not an ideal healthy sample by any means.

   16. PAPeter Attia43:46

       In, in fairness, if they were looking to see the benefit on heart disease, what they said was, "Well, we're going to take an older population because the incidence of heart events would be greater in that population. We would see a difference sooner between the women who were on hormones and those who weren't." And so for economic reasons, it made sense to choose an older population, but this was never a normal population, and as soon as the study came out in 2002, it was immediately extrapolated to all women everywhere.

   17. CTDr. Carol Tavris44:25

       And there's one other detail about this study that I think you, you will shed more light on, and you do so in your book, which when I first read it, I thought, "That can't be right." But women who were especially symptomatic were excluded because of a concern that if you took in women who had s- serious vasomotor symptoms and they were randomized to the placebo, your dropout rate would be too high. Is that correct?

   18. PAPeter Attia44:49

       That's correct, and that would be all right if you acknowledge that up front. But three years after the study was first published, there was a study saying that it has absolutely no benefit on quality of life, and the first question when you read that is what planet were these people living on? And the reason they found that is because women who were significantly symptomatic were excluded for just the reason you stated, that if they had been randomized to placebo, the fear was they would stop the placebo and drop out of the study. And so what the report said is, "Well, among these women, the majority of whom were not symptomatic, we found no improvement in the symptoms that weren't there." But The New York Times headlined it saying, "Hormones have no benefit even on quality of life." By the way, the 13% of the women who were symptomatic had a significant improvement, but they were lost among the entire population.

8. 46:01 – 57:21

   How the 2002 WHI Results Were Announced and Interpreted

   1. CTDr. Carol Tavris46:01

      Yeah, you, you would've been very statistically underpowered to catch them because, yeah, they represent such a small subset of the cohort. Let me, let me just give you one bit of, of history here. When the Women's Health Initiative, it did one of these stop the presses thing, you know? "We've found this increased risk of hormones on, uh, breast cancer, so we have to stop our study immediately and have press conference and announce this, this, uh, this terrifying finding," okay? And I remember clearly Avrum calling me up and saying, "Carol, they're announcing this alleged increase in the risk of breast cancer." Number one, the journal article in JAMA has not even been published yet. You could not go directly to the journal itself and look up the findings for yourself. This is a big no-no in scientific communication and publication. But also, the increased risk, this alleged increased risk of breast cancer, was not statistically significant. It wasn't statistically significant. In my business, you don't get to go into publication and say, "Gee, you know, we didn't get any significant results here. We found something that looks problematic or interesting, and maybe we need to do more research," but not significant. And that's what really first gave us pause. Why are they heralding this strange finding? For what purpose, and why are we wanting to scare an audience in advance of actually offering the real data? And that's what got our skeptical neurons flaring.

   2. PAPeter Attia47:42

      I want to come back 'cause we're gonna go really deep on the difference between absolute risk, relative risk, the difference between the CEEs versus the CEE plus MPA group. I want to go deep on that. But I want to pause here for a moment to ask you an honest question, which is you hear this and it stinks of conspiracy theory, except that I'm the most anti-conspiracy theory guy out there. I typically attribute to incompetence rather than malice. You know, I mean, like it's Oswald killed Kennedy. There's no two ways about it. We don't want to believe that. We want to create a bigger narrative because Kennedy was so significant and Oswald was so insignificant, but the reality of it is conspiracy theories almost never hold up. W- was there a conspira-- I mean, I, I'm using the word loosely and I'm trying to... It's, I, I'm asking it in a loaded way, but when you look back at it through the lens of what we know today, it seems improbable that this cluster could have taken place.

   3. CTDr. Carol Tavris48:35

      I think they were behaving just like scientists who went into this research with a strong belief that HRT is harmful to women, and in particular increases the risk of breast cancer. Jacques Rousseau, who was the cardiologist who led the Women's Health Initiative, had published an article in, I don't remember which medical-

   4. ABDr. Avrum Bluming48:56

      1996

   5. CTDr. Carol Tavris48:57

      ... 1996, basically saying it's time to bring the HRT bandwagon to a halt. The HRT bandwagon. He says too many women are, are on HRT, this is not a good thing, and it's time to, it's time to stop the rolling bandwagon. So he himself clearly had some kind of bias going into the direction of this study. I don't think it's a... It's not a conspiracy. You as a reader of Mistakes Were Made, But Not By Me know-

   6. PAPeter Attia49:23

      [laughs]

   7. CTDr. Carol Tavris49:24

      ... that when you go into a research project with a belief that you really are sure of, you see in the data what you expect to see in the data. I mean, I remember years ago, the first book I ever wrote, which was on anger. In those days, people thought that ulcers were caused by suppressed anger. And I would go and look at these journal articles. These were not malevolent people or fraudulent researchers, but they so deeply believed that suppressed anger causes ulcers, that they would say, "Well, we didn't actually get a significant result here, but it's looking like that's what it would be if it were significant." I mean, really.

   8. ABDr. Avrum Bluming50:01

      Let me add two things to that if I can. First, uh, the article says, this is the 2002 article of the Women's Health Initiative, says that this increased risk of breast cancer almost reached nominal statistical significance. I don't know of any other article anywhere that states that. Statistically significant doesn't mean it's true, but it means the finding has a less than one in 20 chance of being a coincidence, so it's worthy of investigation. But almost reached nominal statistical significance, that sounds like you're straining to reach a conclusion that you didn't reach.

   9. PAPeter Attia50:43

      But there had to be other accomplices here, so on some level, the journals had to at least make a case here. By the way, uh, out of curiosity, why did this end up in JAMA, not New England Journal of Medicine, the initial publication? Any-

   10. ABDr. Avrum Bluming50:57

       They've published in both JAMA and the New England Journal of Medicine.

   11. PAPeter Attia51:00

       Yeah, but the first one. Why? I wonder why the-

   12. ABDr. Avrum Bluming51:01

       The first one was JAMA.

   13. PAPeter Attia51:03

       Hmm.

   14. ABDr. Avrum Bluming51:03

       JAMA may have accepted it first, and JAMA came out with the press release. I don't know of any other situation where JAMA or the New England Journal came out with a press release before the published article was available to doctors to read.

   15. CTDr. Carol Tavris51:21

       Well, and you saw, of course, in our chapter on this, Robert Langer writing last year, why he waited so long, we don't know, but he was one of the investigators who revealed the background story about this. There were 40 principal investigators distributed across the country. They were summoned to a meeting to discuss the paper that was going to appear in JAMA. They were told for the first time what this article was gonna consist of. It had been written by three members of the writing committee for the Women's Health Initiative. They said, "You, [laughs] you can't do this." And they were told, "Well, okay, let's see. It's 9:00 AM. You have until noon to read this report and offer your criticisms." And at noon, when they offered whatever they could put together in three hours, they were told, "Too late. The article's been published in JAMA and it's at the warehouse ready to be sent out." So for conspiracy, who? Most of the investigators themselves never saw that first JAMA article.

   16. ABDr. Avrum Bluming52:19

       I invited one of those three investigators to come speak at my local hospital several months after the study was published, and he was asked by one of the doctors in the audience about the significance of the findings and how come this was published around the world, it was responsible for a 50 to 70% drop in hormone prescriptions, and yet it looks as though the data aren't statistically significant. "What am I missing?" the doctor asked, and he was told by one of the three, "You know, this is the most expensive study ever done. By the time we're finished, it will cost about a billion dollars. And so if we think we have found something and the results don't quite add up," and this is a direct quote, "the statistical police have to leave the room." And the medical audience was aghast.

   17. PAPeter Attia53:15

       Who were the three writing authors of the study?

   18. ABDr. Avrum Bluming53:18

       Rowan Chlebowski was the doctor who's a professor at UCLA who was talking. Uh, Jacques Rousseau, uh, was the principal investigator, and I'm not sure-

   19. CTDr. Carol Tavris53:30

       Garnet Anderson, no?

   20. ABDr. Avrum Bluming53:31

       Garnet Anderson was the statistician. I'd have to check and see if she was one of the three.

   21. CTDr. Carol Tavris53:36

       She was one on the press release anyway.

   22. ABDr. Avrum Bluming53:38

       Yes.

   23. CTDr. Carol Tavris53:38

       She was the one who said, when, sort of when asked about these findings, she said, "Well, when it's an issue as important to women as breast cancer, we intentionally set the bar low. If there's any dangerous information that we found any danger, we set the bar low." No, no, that's not how you do a study.

   24. PAPeter Attia53:55

       What's sort of disturbing when in reliving this story, 'cause I read your book like six months ago, so I feel like I'm reliving this, this bears an uncanny resemblance to another story that took place in the mid-'80s when the, uh, dietary guidelines were being set. And there was basically an NIH consensus that took place, and I was giving a, a talk, it was at Grand Rounds at UCSD in 2011, I believe, or maybe 2012, and I gave the talk about how there was this consensus and everybody went in a room, and 36 hours later they came out with this consensus But the problem was the consensus didn't match the data. It wasn't orthogonal to the data, but it was very far from what the data were. And I believe it was Mark Hegsted, who's no longer alive, who at the press conference said when asked something about, "Don't you feel like maybe we need to know the answer a little bit more?" And he basically made a similar argument, which was, "With the stakes being as high as they are, we don't have time to wait for definitive answers." So I give the, I give my talk. After the talk, a woman comes up to me and she says, "I was an endocrinologist at NIH, and I was one of the..." And I can't remember how many people were in the room, call it, you know, 40 people or whatever. "I was one of the people invited to that." I think it was Basil Rifkind. I can't remember who was the person that was running the section, but she said... And I'm not making this up, though I obviously am paraphrasing. She said, "When we sat down in the room, they closed the door and they said, 'Here it is. We've already written the consensus statement. Nobody leaves this room until we all agree to this statement.'" And she said they were basically held hostage in that room until they agreed to the consensus statement, which 36 hours later they basically did and they all left the room. I, I even remember her making a case about how they brought in really crappy Chinese food to sort of feed them a little bit, give them enough food. But, I mean, that story, I've never forgotten that story, and it was very upsetting, and it really is an extreme example of mistakes were made, but not by me. I do believe that, you know, Basil Rifkind and Mark Hegsted and all these guys had good intentions, but they were now so far gone from any sense of understanding what data meant that it was irrelevant. I mean, they had gone purely into the role of evangelists, and the story you just told sounds so unfortunately similar that, that like I, it's like I'm in a bad movie. It doesn't even, it's not, doesn't sound possible.

   25. CTDr. Carol Tavris56:25

       The other thing, of course, is the negativity bias which cognitive psychologists have studied finds that people are more drawn to negative news than to positive news, and certainly negative news is what sells, what gets attention. I think if the Women's Health Initiative had stopped the presses to say, "We c- we are happy to report that HRT is beneficial for women and prolongs their lives and makes them feel better," this would not have been as newsworthy or as shocking. Uh, you know, and Jacques Rousseau told a reporter from The New York Times that they wanted to do it this way to break into the noisy news cycle and get attention for the study. Mm, would be nice if you had good data behind your press release, but so there were, there were a number of motives. If, if so much money had been spent on this, don't we have to have something really worthwhile to say to warrant that expenditure?

9. 57:21 – 1:09:07

   Absolute vs. Relative Risk and the WHI Breast Cancer Numbers

   1. PAPeter Attia57:21

      So let's talk a little bit about the statistics. So one of the tables I have, uh, printed up in my office is from, I think it's the 2014 or 2015 JAMA paper that went back and looked at all the data, because a lot of times women will say to me, "Doesn't HRT increase the risk of breast cancer by 25%?" That's, that's the common question I get asked: Doesn't HRT increase the risk of breast cancer by 25%? So where'd they get that number, right? They're getting that number from the news. So l- let's talk about where that number came from.

   2. ABDr. Avrum Bluming57:52

      Well, the first number is 26%.

   3. PAPeter Attia57:54

      Mm.

   4. ABDr. Avrum Bluming57:55

      J- just to be a stickler.

   5. PAPeter Attia57:56

      Yes, exactly.

   6. ABDr. Avrum Bluming57:57

      Okay.

   7. PAPeter Attia57:57

      But we, we round. We round to the nearest five here.

   8. ABDr. Avrum Bluming57:59

      I understand. Well, because they came out two years later with 24%.

   9. PAPeter Attia58:02

      That's correct.

   10. ABDr. Avrum Bluming58:02

       The initial 26% was among women who took hormone replacement therapy, meaning the combination of estrogen and progesterone. If you look at estrogen alone-

   11. PAPeter Attia58:15

       Let me, let me interject for a moment 'cause I should have done this earlier. Let's explain what the study looked like in terms of randomization. You had two cohorts of women, correct? You had women who had already undergone a hysterectomy, and they were randomized to-

   12. ABDr. Avrum Bluming58:28

       Estrogen or placebo.

   13. PAPeter Attia58:30

       Correct. So CEE, so conjugated equine estrogen or a placebo, and women whose uterus was still in place were randomized to CEE plus MPA versus p- uh, placebo, correct?

   14. ABDr. Avrum Bluming58:42

       Correct.

   15. PAPeter Attia58:42

       Was the randomization one to one to one through all of that?

   16. ABDr. Avrum Bluming58:44

       Yes. Yes.

   17. PAPeter Attia58:45

       Okay.

   18. ABDr. Avrum Bluming58:46

       The women who were randomized to estrogen had no increased risk of breast cancer.

   19. PAPeter Attia58:51

       In fact, if you want to be a stickler and play the same game, my recollection is those women had a hazard ratio of 0.79, and the confidence interval ended up at 1.01. To translate that into English, the women who were on estrogen only had a 21% risk reduction, but the 95% confidence interval crossed unity, which meant it was not statistically significant. The P value was 0.07, if my memory serves me correctly, which meant there was a 7% chance that that effect was random, meaning it didn't hit the 5% threshold.

   20. ABDr. Avrum Bluming59:27

       Right. But the-

   21. PAPeter Attia59:27

       Did I remember that mostly?

   22. ABDr. Avrum Bluming59:29

       Pretty, pretty close. The, the fact is there was no real increase among the women who got estrogen alone that we would hang our hat on. There was one paper that came out that actually showed a 30% significant decrease, but that didn't hold up in, in subsequent papers. So let's say there's no increased risk with estrogen alone. With estrogen and progesterone, there was a reported 26% increase, and it's important that we understand what that is. First, that was not statistically significant, so that by scientific standards, we think that could have been caused by chance alone.

   23. PAPeter Attia1:00:10

       What was the P value?

   24. ABDr. Avrum Bluming1:00:12

       I don't remember the P value.

   25. PAPeter Attia1:00:13

       But it was, you're saying it was-

   26. ABDr. Avrum Bluming1:00:14

       It was not statistically-

   27. PAPeter Attia1:00:15

       ... definitely below-

   28. ABDr. Avrum Bluming1:00:16

       It was not-

   29. PAPeter Attia1:00:16

       It was above 0.5.

   30. ABDr. Avrum Bluming1:00:17

       Yes, it wasn't statistically significant. But in order for there to be a 26% increase, you have to know what the actual risk in numbers were was for women who got the, the estrogen plus progesterone-
10. 1:09:07 – 1:22:55

    Progesterone, Premarin, Bioidenticals and WHI Follow-ups

    1. PAPeter Attia1:09:07

       So another interesting aspect of looking at the Women's Health Initiative, which it's very hard to look at the data and not ask the question, what is the role of MPA? Because when you look at the women who had a uterus, these are women who got estrogen and progesterone, synthetic progesterone, progestin, versus placebo, there was a trend towards a higher breast cancer. But when you look at the opposite, the women who had no uterus and therefore only needed estrogen, the trend was in the exact opposite direction to the exact same magnitude. I mean, it almost looks like you couldn't make it up. They are m- they are mirror images of each other, so you have to ask the question, what are the differences? And there are two. One of them had a uterus, one did not, and one took synthetic progestin, and one did not. So the question is, does not having a uterus or, and/or does taking synthetic progesterone make a difference?

    2. ABDr. Avrum Bluming1:10:06

       First, on the synthetic progesterone, it's, uh, MPA, medroxyprogesterone acetate, which was used in the Women's Health Initiative because that was the most widely prescribed progesterone available in the United States. First, let me go back to saying that the increased risk seen with the combination was not statistically significant, did not hold up, and was due largely to a problem with the control group. If you accept that, anything we say at this point is-

    3. PAPeter Attia1:10:39

       Speculation

    4. ABDr. Avrum Bluming1:10:39

       ... and, and irrelevant, really, but I'll take your question. So what has resulted from that is people are saying, "Well, the problem really isn't estrogen. We'll give estrogen a pass. The problem is progesterone and, in fact, this particular synthetic progesterone." Well, I'm not sure there's a problem because the numbers don't really bear that out. But if there is a problem, there are now forms of progesterone which are not synthetic, uh, that are now being advised and used and thus far have not been associated even with any finding of an increased risk of breast cancer. But in addition, progesterone also has been used to treat breast cancer, and progesterone works as well as tamoxifen does to treat breast cancer. In a randomized trial comparing tamoxifen to progesterone in the early '70s when tamoxifen was first produced and marketed, progesterone did a little better than tamoxifen. But because in the doses used, it was associated with increased fluid retention and women became nauseated, it lost out to tamoxifen. But it was used to treat breast cancer. There was a study that came out of India by a, an investigator trained in England who found that if he gave an injection of progesterone around the time of surgery to remove primary breast cancer, he significantly improved the prognosis, decreased the risk of recurrence. So making a lot of noise around progesterone doesn't really fit the available data that we have.

    5. PAPeter Attia1:12:42

       So two things. One, I actually had a discussion with JoAnn Manson about this a few years ago, which was Why did you use that crappy estrogen and progestin? Why didn't you use what we would use today, which is bioidentical estrogen, bioidentical progesterone? And, uh, I've always had a lot of respect for JoAnne, by the way. I don't know if you guys were able to... Did you interview her for the book? I don't... Yeah, I didn't think so. And she, she gave me an answer that I thought was very logical, and you've alluded to it already. She said, "You're probably right, Peter. I mean, I, I think the bioidentical hormones are likely better. But we had to do it with what was available in the... We had to test what was being used by the average physician at the time." And certainly people at the time were making some noise that shouldn't we at least use bioidentical human hormones, which intuitively makes more sense. But she said a study testing that wouldn't have made sense in the '90s because that wasn't what the average woman was being tested. So that said, most women today are using bioidentical progesterone, aren't they, when they're, when they're, uh, receiving, um, hormone replacement therapy?

    6. ABDr. Avrum Bluming1:13:47

       No.

    7. PAPeter Attia1:13:47

       They're still using synthetic progesterone?

    8. ABDr. Avrum Bluming1:13:49

       Well, first Premarin.

    9. PAPeter Attia1:13:50

       Yes.

    10. ABDr. Avrum Bluming1:13:51

        Let's talk about the estrogen. The word bioidentical is a buzzword. As you know, bioidentical really refers to estradiol, which is the leading circulating estrogen in a woman's body. And there are pharmaceutically prescribed estrogens that are made by significant manufacturers that we have no problem with, and I want to get back to that in a minute. But bioidentical is also used for what is prepared by pharmacists based on prescriptions written by local practitioners where quality control is lacking, there is no clear dose equivalency, and every responsible investigator I know wants to make the point that buying something because it's got the word bioidentical, which sounds comforting, is a mistake. Second, Premarin, which is pregnant mare urine, and I say that rubbing your face in it because it sounds so terrible, is the longest studied form of estrogen, and we now have 60 years of data with Premarin. And most of the studies that show the benefit for estrogen are studies that were done on Premarin for the same reason that JoAnne Manson gave you. It's the one that was used most often. In addition, Premarin contains at least 10 different forms of estrogen, including some that are the most beneficial forms of estrogen for brain health, which is not present in estradiol or estriol. So that my preference based on data only is Premarin because we have the most data supporting it. Now, as far as progesterone is concerned, yes, micronized bioidentical progesterone appears to be the safest form of progesterone administration.

    11. PAPeter Attia1:15:51

        What do you think explains... This is a bit of a pivot, but what do you think explains the mechanism of action? So, so I'll take a step back and preface this with the following. You alluded to this earlier. Most people intuitively think testosterone must be driving prostate cancer. But the problem is men tend to get prostate cancer when their testosterone levels are at their lowest, not their highest, and men with high testosterone when they're young don't seem to get prostate cancer. So it's just a bit confusing. And in fact, there's more recent data to suggest that the lower the testosterone, the more likely the probability of a high grade prostate cancer. So everything seems to be moving in the wrong direction as testosterone goes down.

    12. ABDr. Avrum Bluming1:16:29

        May I just interrupt that it's the same with estrogen.

    13. PAPeter Attia1:16:31

        Yes.

    14. ABDr. Avrum Bluming1:16:31

        As women get older and have lower estrogen levels, the rates of breast cancer increase.

    15. PAPeter Attia1:16:36

        So therein lies my point. What do you think explains the mechanism by which estrogen withdrawal and/or removal, and the same for progesterone, is increasing this risk? And why, Avrum, can you point out these examples of administration of these things that seem to potentially improve the condition? What do you think is happening at the molecular level, acknowledging what you said at the outset, which is we don't have a goddamn clue what cancer is?

    16. ABDr. Avrum Bluming1:17:04

        We have clues, but I said I don't understand what cancer is.

    17. PAPeter Attia1:17:07

        [laughs]

    18. ABDr. Avrum Bluming1:17:08

        And the reason I said that right at the beginning is to try to forestall just this kind of question. The best answer I can give is we think we understand the environment that is friendly to a cancer, which is the environment in which the cancer develops, and we try to change that environment to make it less conducive to the continued growth of the cancer. That means in a low estrogen environment, you might use estrogen because that is now unfriendly to the cancer. In a high estrogen environment, you might remove estrogen. Same with testosterone. But exactly how that works, I would use a lot of fancy words, and they would try to cover my ignorance.

    19. PAPeter Attia1:17:54

        Mm-hmm. Appreciate the honesty. Most of us tend to use those fancy words and hide our ignorance behind them. So in 2002, the JAMA study comes out, and there were a bunch of follow-ups. So there was a 2003, a 2004 follow-up. What did each of these follow-ups attempt to do?

    20. ABDr. Avrum Bluming1:18:12

        The 2002 follow-up said that the combination of estrogen and progesterone increases the risk of breast cancer. Not true. We've discussed that. Increases the risk of heart attacks, increases the risk of cognitive decline, decreases the risk of colon cancer, and helps protect the bones. That's really what it said. And then there were all these arguments about the statistical significance of the breast cancer finding. And so in 2003, they came out with a second article showing borderline statistical significance for the increased risk of breast cancer.

    21. PAPeter Attia1:18:53

        And this is the point you alluded to earlier, and this is actually the paper that I am looking at more often because this is the one that went from point, 1.26 as the hazard ratio to 1.24, and this is the one where the P value actually went to 0.5 from, I believe, 0.07, 0.05 to 0.07

    22. ABDr. Avrum Bluming1:19:12

        And the confidence level showed that it was-

    23. PAPeter Attia1:19:15

        That's right

    24. ABDr. Avrum Bluming1:19:15

        ... borderline statistically significant. But in 2006, a follow-up article said that that reported increased risk in that population had disappeared with continued follow-up, and that article never made the headlines, and most people aren't even aware of it.

    25. PAPeter Attia1:19:35

        And in fact, people like JoAnn, and I think this is why I respect JoAnn a lot, she is one of those investigators from the WHI who I believe is trying to course correct it. I remember driving to work one day and hearing her on NPR, and this was probably, like, maybe five years ago, and she was being interviewed. And I don't know if I'll be able to fi- you know, if we can find the link to this, that would be great. I, I doubt we will, but she basically made the point. She said, "Look, I think, I think the recommendations went too far." And, you know, I, I could at least respect that she was now walking it back. Now, she may come to a different conclusion than the one you've come to, but she was at least willing to say, "Look, I think there really are a subset of women, especially those entering menopause who have symptoms, who deserve to be treated, and we made a mistake." That, that was really my interpretation of what she said.

    26. CTDr. Carol Tavris1:20:23

        S- they were willing, willing to say that it was okay for women to take hormones. This is the mantra that women hear all the time, "The smallest dose for the least amount of time. The smallest dose for the least amount of time." And as Avrum keeps pointing out, there is absolutely no empirical evidence to support that advice. It's a bit like saying, "Smoke the fewest cigarettes for the shortest amount of time, and you'll be f- you know, you'll get the benefit of smoking, but without the lung cancer." It's not so, but I think it does represent a compromise in terms of the Women Health- Women's Health Initiative's realization that HRT really was beneficial for quality of life issues for women in menopause. What they were not prepared to do was to consider HRT's benefits over the long haul for women in later years in reducing the risk of osteoporosis, dementia, and heart disease. That, they are not willing even yet to suggest that HRT has any prolonged benefits over time.

    27. ABDr. Avrum Bluming1:21:21

        You don't have to go back to NPR. I, I believe it was 2017 when JoAnn Manson published a paper saying just what you said. First, yes, we went too far. Second, we found that women who are on hormones had a lower risk of breast cancer, lower death from breast cancer, and in fact, lower death from all causes compared to women who weren't taking hormones. But she didn't endorse the use of hormones. She fell back on, uh, the lowest dose for the shortest period of time, which would be okay if hormones weren't so beneficial. A study that came out, uh, by Nandita Cole from Boston, which we quote in the book, showed that if every woman in the United States took hormone replacement therapy, uh, now admittedly, this is before the Women's Health Initiative was published, it would increase the median survival of women by 3.3 years in this country.

    28. CTDr. Carol Tavris1:22:26

        There's no other intervention I can think of that has such a great consequence for longevity. And Phil Sorensen at Yale calculating how many women might have died prematurely from heart disease because they went off HRT was thousands and thousands of women per year.

    29. ABDr. Avrum Bluming1:22:42

        The number he came up with was 50,000 women between 2002 and sometime in the early teens might have died as a result of being taken off hormone therapy.

11. 1:22:55 – 1:26:54

    Alzheimer's Disease and the Brain

    1. PAPeter Attia1:22:55

       One of the diseases, and I'd like to do this a bit more systematically now because you guys have done in the book such a great job. Your book is organized, basically, once you go through the case you've made, you then basically have a chapter for each outcome. So let's start with one of them. Let's start with the brain. Near and dear to my heart as well. Um, as you think about longevity, you have to think about delaying the onset of dementia. And again, what most people don't realize, in fact, I think it's one of those six things where I remember the first time I learned it, I thought, "How did I not know this already?" The great divide in chronic disease is Alzheimer's disease. It's the one that disproportionately targets women. So women are two times more likely to die of Alzheimer's disease than men. And let's put that in context for a moment. Can you imagine if, I don't know, women were two times more likely to die of heart disease or of pick a given cancer, pancreatic cancer, you know, something that's not sort of gender specific. You'd be, like, scratching your head thinking, "How is this possible?" And so what's the explanation for that? I'm not going to offer one, but I will offer a hypothesis. The most obvious difference between men and women is not the rate of longevity in women, which would be the knee-jerk response to why that's occurring. Women living a year and a half, two years longer must explain it, but those data don't bear out. So another hypothesis might be women have an abrupt loss of hormones. Men have a gradual loss of hormones. So say a little bit more about what your beliefs are now with respect to the data and what they tell us about the risk of Alzheimer's disease.

    2. ABDr. Avrum Bluming1:24:31

       For every woman diagnosed over 60 with breast cancer, two women are diagnosed with Alzheimer's. The cure rate for early diagnosed breast cancer is now approximately 90%. The cure rate for Alzheimer's disease is zero. We have treatments for breast cancer that we haven't gone into, but it's not really the subject of this podcast, and there is no treatment for Alzheimer's. If there is one disease that women fear more than breast cancer, it's Alzheimer's. And Exercise and diet and, uh, mental gymnastics and even a product of jellyfish has nothing to do with preventing Alzheimer's disease. The one potential preventive medication is estrogen, and that can reduce the incidence of Alzheimer's disease by between 20 and 50%, depending upon the study you look at.

    3. CTDr. Carol Tavris1:25:31

       In that chapter where we review those studies, uh, animal studies, lab studies, real life field studies, uh, randomized controlled studies, the findings converge from all of those directions of research to show the benefits of estrogen on the brain. Barbara Sherwin at McGill, who has studied this question for many years, she's someone from my side of the professional fence, Avrum, a psychologist, and she was asked about taking estrogen for many years and so forth, and she said, "You know, I get so cross when people say taking HRT is not natural." She said, "What's not natural is for a woman to live to be 85 or 90 years old, and if estrogen is something that can help women to live with healthy mental functioning in those later years, then I am all for it."

    4. PAPeter Attia1:26:20

       Yeah, that's a great point you raise, which, uh, it goes so much beyond all of this, but that, that really envelopes this discussion. What, what does natural mean?

    5. CTDr. Carol Tavris1:26:28

       Exactly.

    6. PAPeter Attia1:26:28

       If natural means what evolution intended, we're all irrelevant by the time we're my age. I mean, let alone your age, right? I mean, so if we've decided to live in a society where we value living beyond our reproductive years, then why aren't we entertaining things that are, quote unquote, "unnatural"?

    7. CTDr. Carol Tavris1:26:46

       Mm-hmm. Exactly.

    8. PAPeter Attia1:26:47

       It, it really is an asinine, uh, argument to me, uh, but, uh, obviously I'm biased. [laughs]

    9. CTDr. Carol Tavris1:26:51

       [laughs] So are we [laughs] in that respect, absolutely.

12. 1:26:54 – 1:38:26

    Heart Disease, Timing of Hormone Initiation, and Bone Health

    1. PAPeter Attia1:26:54

       So let's now talk a little bit about heart disease, because if the increase in breast cancer was the screaming headline in 2002, the second headline had to be heart disease and stroke.

    2. ABDr. Avrum Bluming1:27:08

       As Carol pointed out, with a median age of 63, with 70% of the population overweight, a significant number of whom were obese, with half-

    3. PAPeter Attia1:27:18

       I believe about 30%, 34% were obese, if I recall.

    4. ABDr. Avrum Bluming1:27:21

       Yes, that's right. With half of them, or 40%, smokers, and with a significant number having high blood pressure that was treated, this doesn't represent a cardiovascular healthy population. We know that estrogen is capable of causing platelet clumping. Platelets, as you know, are small corks that circulate in the blood that help prevent bleeding by going to a site of bleeding and plugging it up. Estrogen can cause these platelets to clump, and if you already have blood vessels that are narrowed by preexisting heart disease, a platelet clump can further narrow the blood vessel and cause a cardiac event. And as a result of that, it is recommended that women with preexisting cardiovascular disease not start on hormone therapy, and the ideal time to start is around menopause, sometime within the first 10 years of cessation of your periods. Now having said that, that doesn't mean that older women must never take it. In fact, that increased risk of cardiovascular events is seen generally during the first year that a woman starts hormones.

    5. CTDr. Carol Tavris1:28:37

       Point of clarification, that increased risk, but that's after the window of opportunity, 10 years after-

    6. ABDr. Avrum Bluming1:28:44

       Yes

    7. CTDr. Carol Tavris1:28:44

       ... menopause begins.

    8. ABDr. Avrum Bluming1:28:45

       That's correct. Thank you.

    9. CTDr. Carol Tavris1:28:45

       There is no increased risk if a woman begins HRT at the time of menopause.

    10. ABDr. Avrum Bluming1:28:50

        With no preexisting cardiovascular disease.

    11. PAPeter Attia1:28:52

        Okay, th- this is actually what I wanted to ask you about, so thank you for clarifying this. Let's make sure that the listeners are crystal clear on this. If you take a woman entering the normal perimenopausal to menopausal state, and she has no preexisting cardiovascular disease, and I want to come back to how we'll define that, but let's wait on a moment, the data make it pretty clear there's no increase in her risk of cardiovascular disease ongoing.

    12. CTDr. Carol Tavris1:29:15

        Correct.

    13. PAPeter Attia1:29:15

        Not just for five years.

    14. CTDr. Carol Tavris1:29:17

        Correct.

    15. PAPeter Attia1:29:18

        Okay. Case two, you take a woman who is, let's just make the math easy, she's 60 years old and she went into menopause at 50, so she has a window now that is 10 years. There is zero evidence that she has existing cardiovascular disease. She begins hormone replacement therapy. How clear are the data that she is also not increasing her risk of cardiovascular disease?

    16. ABDr. Avrum Bluming1:29:40

        Well, it depends on the studies you've done to show that she has no narrowed blood vessels.

    17. PAPeter Attia1:29:46

        Let's, let's go gold standard to the best of our ability. Calcium score is zero, CT angiogram shows nothing, lipids are beautiful.

    18. ABDr. Avrum Bluming1:29:53

        Then she's probably okay. But let us say we are not here trying to increase sales of hormones.

    19. PAPeter Attia1:30:01

        No, no, I understand.

    20. ABDr. Avrum Bluming1:30:02

        That what we want to do, and just to make it clear, is empower women so they not be given some curt answer when they ask about it. This is a legitimate course of action to follow, but with and after a discussion with your physician.

    21. PAPeter Attia1:30:18

        Yeah, what I'm mostly trying to do is identify the women who might be at risk and who need to think twice about it, which sounds like it's women who are, who have been completely deprived of hormones, meaning they went through menopause, they have been off hormones, they are now, call it 10 years out, and they have some preexisting clinical or subclinical athero- atherosclerosis. Is their risk only one year after starting therapy and then it returns to baseline?

    22. ABDr. Avrum Bluming1:30:48

        Uh, their risk is highest during that first year, and then it diminishes and diminishes and diminishes. There haven't been the kind of studies that I can tell you it returns to baseline, and I, I can't say that with assurance. But the major risk is during the first year, and if during the first year it doesn't occur, the likelihood is they will be well and won't have one of these events.

    23. PAPeter Attia1:31:15

        This is interesting because there was a similar st- there was a study com-- I shouldn't say similar. There was a parallel study to this idea published, I, I want to say it was in JAMA, but it might have been in the New England Journal of Medicine a few years ago, that looked at men with-- older men who were not particularly healthy put on testosterone replacement therapy. And one year after the study, the men on the testosterone group had a higher incidence of cardiovascular disease. Three years after the study initiated, the risk was equal, and at five years, the men receiving testosterone had a lower risk of heart disease than the men on the placebo. It, it's actually quite interesting that it mirrors what you've just described, and I'd never made that connection until now.

    24. CTDr. Carol Tavris1:31:56

        It is quite interesting, and it's the question we get most often from women who entered menopause and were scared off hormones because of their doctors, and now ten years later or even more than that, they-- th-this is one of the most common questions that, uh, Avrum gets. "Can I go back on it now? I've been off this for, you know, for ten years. Is it safe to go back on? Because I'm suffering because I'm having so many symptoms, because I'm really in discomfort and the quality of my life is terrible. I would like to go back on hormones. Is it safe?" So we understand the importance of this question and how an individual woman really needs to assess what her particular risks are.

    25. PAPeter Attia1:32:33

        And, and Carol, that case study that you, you know, hypothetically put forth, that kind of flies in the face of what most people think. Most people think a sixty-year-old woman who took hormones eight years ago and has not been on them anymore can't possibly have symptoms, right? It must be something else.

    26. CTDr. Carol Tavris1:32:50

        No, they do indeed have symptoms. Avrum said earlier the average length of time a woman has symptoms during menopause is seven years. That's the average. For some women, it's ten or twelve or fifteen. Avrum gets letters from former patients saying, "You know, I'm in my seventies here or my eighties, and I'm having this terrible trouble sleeping, and my doctor won't renew my prescription. Won't renew my prescription. I'm seventy-eight years old. [laughs] You know, I'm doing fine on hormones. Please." And the minute they go off, then th-their symptoms often return.

    27. PAPeter Attia1:33:20

        So let's talk about an area that doesn't seem to have that much controversy, but just for the sake of completeness, let's, let's talk about bone mineral density and osteoporosis for a second.

    28. ABDr. Avrum Bluming1:33:29

        First, let's talk about bone mineral density. Bone mineral density is used as a substitute marker for osteoporosis. It is a bad substitute marker. It's the best one we have, but it's not a good test. And one of the ways to explain that is bone elasticity is what allows bones to bend without breaking and allows us to be active without suffering acute fractures. Bone elasticity is due to the girders within the bone that are made of collagen and that are broad and healthy and bend. The bone mineral density measures the envelope in which those girders are contained. The envelope is the cortex of the bone, and the cortex of the bone is made largely of calcium. To show you what a bad measure bone mineral density is, and I'm sure you know this, Peter, if you give patients fluoride, you will dramatically increase bone mineral density, and the bone will become thick and break easily and have no elasticity, and that's not a good treatment for osteoporosis. The best way to check for osteoporosis is to take a bone in the body and put it in a vise and see how much pressure you can exert before the bone snaps. The problem is that's-

    29. PAPeter Attia1:35:09

        Well, you know, it's funny, I do that test on most of my patients.

    30. ABDr. Avrum Bluming1:35:12

        [laughs] Good.
13. 1:38:26 – 1:48:31

    Colon Cancer, Diabetes, Clots, Gallbladder and Counseling Women

    1. PAPeter Attia1:38:26

       All right, Carol, tell me about colon cancer. What does HRT do to increase or decrease a woman's risk of colon cancer, which is a cancer that, you know, a lot of people don't realize how high that is on the mortality table because its lethality is, of course, nowhere near as bad as sort of pancreatic and lung, but it's, it's more lethal than... Again, it depends on how you define it, but it's going to be more lethal than breast cancer. So this is a big problem.

    2. CTDr. Carol Tavris1:38:53

       This was almost an unintended or unexpected, uh, discovery about the benefits of estrogen in reducing the rates of death from colon cancer. I think it was kind of off the mental chart of is this something we want to even think about as a, as being a benefit of estrogen, but a number of significant studies have shown that it does indeed redu-reduce the risk of colon cancer.

    3. PAPeter Attia1:39:16

       This was one of the few things that didn't... If I, my recollection is this was one of two or three findings in the Women's Health Initiative that was not really changed over time and not particularly controversial. Is that, is that correct?

    4. ABDr. Avrum Bluming1:39:27

       Yes. There are other studies, including the Nurse's Health Study, that showed that. There are many studies that showed a 20, 25% decreased risk of colon cancer among women taking estrogen, but we don't know why.

    5. CTDr. Carol Tavris1:39:42

       I will say here at the beginning with the Women's Health Initiative, the first thing they wanted to say in that, those first years was something they called their Global Health Index. Is that what they called it, Avrum? This was supposed to be a sort of an overall measure of, uh, health and longevity, claiming that, uh, estrogen reduced longevity and increased women's mortality from all causes over the years. I mean, it was quite a, quite an exaggerated claim, and over the years they have been walking back from that one. Well, okay, it doesn't really increase the risk of dying from all other diseases that there might ever be. I mean, they were really looking to scare people for some reason at that point. Then they stopped talking about this global mortality rate, uh, statistics, especially because they began looking at individual risks of death from various diseases and finding that there was no increased risk.

    6. ABDr. Avrum Bluming1:40:36

       Diabetes is another one that estrogen seems to decrease.

    7. PAPeter Attia1:40:40

       In the Women's Health Initiative, diabetes was self-reported. I've never-- Can you explain why the hell that was the case?

    8. ABDr. Avrum Bluming1:40:45

       No.

    9. PAPeter Attia1:40:46

       [laughs] There are so many gaping holes in my understanding of how the Women's Health Initiative came to be.

    10. ABDr. Avrum Bluming1:40:53

        Ours too.

    11. PAPeter Attia1:40:53

        And that's yet another example of rather than actually make diabetes a secondary or tertiary outcome, we'll make it a self-reported outcome. I, I don't even... I've never seen a study where that's been the case. Have you?

    12. ABDr. Avrum Bluming1:41:06

        S-single most expensive study ever done in this country, and that's the third time one of the people around this table has said, "I've never seen that-"

    13. PAPeter Attia1:41:15

        [laughs]

    14. CTDr. Carol Tavris1:41:16

        [laughs]

    15. ABDr. Avrum Bluming1:41:16

        "... in the medical literature before."

    16. PAPeter Attia1:41:18

        So tell me why you believe that HRT might actually reduce the probability of diabetes rather than increase it.

    17. ABDr. Avrum Bluming1:41:26

        Because the numbers suggested it. That's all. I would like to see many more studies before we reach that conclusion, and you'll note we didn't mention diabetes in the book.

    18. PAPeter Attia1:41:37

        No. Yeah, th-this is something I just brought up from actually mining, looking through the data myself because it was so counterintuitive. Let's talk about the real downsides. It's hard to dispute that there was a real increase in pulmonary embolism and venous thromboembolism. You alluded to it already because you talked about platelet activation. Let's put it in context. Can we talk about the magnitude? So we saw the increase was clear and relative. How big was the absolute increase?

    19. ABDr. Avrum Bluming1:42:04

        It's very small, and a, a clot, a thrombophlebitis, a swollen leg because of a clotted vein, is usually not very serious unless, as you mention, a piece of the clot breaks off, goes to the lung. That's a pulmonary embolus, and that can be fatal. The incidence is small. I, I don't have the number in my hand. It's, it's significant enough that if the patient is, has a condition or is taking something that can predispose to that kind of clot, it must be a consideration before somebody starts on hormones.

    20. PAPeter Attia1:42:41

        The other thing that stood out to me was the increase in the incidence of gallbladder disease, though it was never really clear to me what the hell they were talking about. Did they mean cholelithia-- Like, did they mean stones in the gallbladder?

    21. ABDr. Avrum Bluming1:42:55

        They meant stones.

    22. PAPeter Attia1:42:55

        Yeah.

    23. ABDr. Avrum Bluming1:42:56

        And that seems to be a statistically valid finding, and cholecystectomy, removing a gallbladder among women who are on hormones, is a not infrequently reported finding and has to be thought of.

    24. PAPeter Attia1:43:12

        So when you take a step back and think about all of this, I think we're just as a society very conditioned to want binary answers. Something is good, something is bad, something is all good, something is all bad. For the unfortunate reasons you've described, HRT Following the Women's Health Initiative fit into the all bad category. I don't think you're here saying it's all good, but it sounds like it's more good than bad, and obviously that's my belief as well. How should a woman who's listening to this, who is either not in menopause yet, in menopause, past menopause, how would you counsel her to think about this as she approaches her physician who may already have a very strong point of view about this?

    25. ABDr. Avrum Bluming1:44:02

        I recently got back from London, where I gave a talk at The Royal Society on the book in a discussion on the pros and cons of hormones. And when you walk into The Royal Society in London, emblazoned across the front in Latin, it says, "Take no one's word for it."

    26. PAPeter Attia1:44:20

        And there was an interesting guy who was the first president of that. I'm blanking on his name. Isaac... What was it? Somethi-

    27. ABDr. Avrum Bluming1:44:26

        Newton.

    28. PAPeter Attia1:44:27

        Newton, that's it. Yeah. Yeah, yeah. Yeah, so you're in heady company there.

    29. ABDr. Avrum Bluming1:44:30

        Ex- exactly right. And the reason we wrote the book with references on every chapter, trying to give people the data on which our conclusions are based was, as I mentioned, to empower women, so that the book is meant to make you a better consumer of healthcare, so that when you go to your physician, you and your physician together can work out the best program for you to follow. And our conclusion from the book is that the benefits of hormones far outweigh the downsides, and hormones have been unfairly excluded from medical regimens that women should at least be offered for consideration.

    30. CTDr. Carol Tavris1:45:25

        I would add to this, because I come from a history, of course, of feminist criticism of m-medicine and psychology and the bias in the nature of research and so forth, and gender research. And so I am well aware of and h-- for a long time supported many of the feminist criticisms of HRT and of, in general, the medicalizing of normal problems of life. The less is more movement in, uh, medicine is designed to educate the public that sometimes you don't need to medicate every possible problem you could ever have in your life, and that we're taking too many medications and too many drugs and so forth and so forth. And with much of this, I completely agree. But the alternative to over-medicalizing our problems is not to under-medicalize them either. And I think that many women influenced properly by feminist critiques of medicine have become... You know, think that there's something unfeminist about taking HRT. You know, something anti-woman about taking HRT. "I'm not enough of a woman if I need to take hormones," or that kind of argument. And I think it's as much a feminist argument to say what is best for women overall, what is best for a particular woman who is dealing with symptoms that are painful and difficult and complex. You know, I'm, I'm going to be speaking at a meeting of-- where it was interesting, the, the board told me, "Well, we can't possibly invite you to come and talk about your book because everybody on this board is anti-HRT, and they're feminists, and they've been anti-HRT all of their lives," and so forth. And then she called me the next day and said, "Well, the board has decided unanimously to ask you to come talk about this book on account of they're now all in menopause and suddenly saying, 'You know what? My body is talking to me, and I need to listen.'" So I think that the issue of HRT for women is not there's a correct ideological stance to be taken, but rather one that needs to look at what is best for most women and for any given woman making this decision.
14. 1:48:31 – 1:59:22

    RCTs vs. Observational Studies and the Problem of Data Dredging

    1. PAPeter Attia1:48:31

       These are all such important questions. In fact, when you think about what we've just talked about, we have talked about cancer, we have talked about atherosclerosis or all of the cardiovascular and cerebrovascular diseases, and Alzheimer's disease. So you've basi-- And then when you add fractures to that, you have basically, if I'm doing the math right, accounted for about 80 to 85% of deaths that women will experience. And you're talking about something that could move the needle by, let's be conservative and call it 10 to 20%. Potentially more, but let's say conservatively 10%. Will there ever be a correctly done Women's Health Initiative that will include these other questions? We've never asked the question about other forms of estrogen. We've never asked the question about testosterone, which most women don't realize this, but even during her reproductive years She has 20 to 100 times more testosterone in her body than estrogen, even at ovulation, and she's losing that as well as losing her estrogen. But to your point, we don't have a clinical trial that asks that question. Will we?

    2. ABDr. Avrum Bluming1:49:46

       No. And the reason we won't is the idea that every truth can only be determined by a prospective, double-blind, randomized study is simply not holding up. In fact, there are now many articles appearing in the general medical literature talking about well-followed, carefully put together observational studies that can give us information that we simply can't get from double-blind randomized trials. I think when we begin to understand better what cancer is, we will have better answers. The data that we try to string together are data based on studies which follow our ignorance and our attempt to see through this darkness to work out the best treatment for any individual patient.

    3. PAPeter Attia1:50:45

       Do you think there's something else at play, which is notwithstanding the complexity and the cost of repeating a study of that magnitude? Is there-

    4. CTDr. Carol Tavris1:50:55

       Notwithstanding? Notwithstanding the complexity and cost? No, that's what's standing.

    5. PAPeter Attia1:51:00

       [laughs]

    6. CTDr. Carol Tavris1:51:00

       That's what's standing in the way, of course.

    7. PAPeter Attia1:51:02

       Well, I guess that's my point, is it, is the issue that the NIH, which is really the only entity that could ever fund a study of this magnitude, right? There is no industry version of this study. Has, has this been-- I mean, did you interview folks? I'm trying to remember who you interviewed from NIH. Do you get the sense that this is case closed in the same way that unfortunately many still view the dietary studies of the '70s and '80s as a bit of a case closed?

    8. ABDr. Avrum Bluming1:51:30

       Let, let me just add that people ask us why we are a voice in the wilderness, voices in the wilderness. Well, we're not. And if you look at the people who have endorsed our book, they include Vince DeVita, who is the director of the National Cancer Institute, part of the NIH.

    9. PAPeter Attia1:51:49

       Yeah, Vince actually, along with, uh, Steve Rosenberg, my mentor, and I forget the name of the-- there was a radiation oncologist. Sam-

    10. ABDr. Avrum Bluming1:51:56

        Sam Hellman.

    11. PAPeter Attia1:51:56

        Sam Hellman.

    12. ABDr. Avrum Bluming1:51:57

        Right.

    13. PAPeter Attia1:51:57

        They write the bible on oncology.

    14. ABDr. Avrum Bluming1:51:59

        They write a very important book called Cancer. That's correct. Jerry Kassirer, who is the editor-in-chief of The New England Journal of Medicine, endorsed our book. Lesley Turnberg, who is the president of the Royal Society of Medicine in England, endorsed the book. These are very well-informed people, as many female groups endorsed the book as well. Phyllis Greenberger, who's the CEO of the Women's Science Cooperative, endorsed the book. These are people who are aware of the data, are aware of the limitations of the data available to us, and they strongly recommend that this book be read not just by women, but I have men who come up to me who thank me for saving their lives because of their wives getting better, and that was killing them.

    15. PAPeter Attia1:52:54

        Yeah.

    16. CTDr. Carol Tavris1:52:54

        But you see, your question I think, Peter, too, is what kind of research needs to be done to help us answer the questions that we have remaining? What kind of research? So there won't be anything as big as the Women's Health Initiative, as costly as that, as the statistical police have to leave the room because we're never gonna be able to do anything this big and this elaborate again. I think that's true. But what I think-- what I'm seeing that I find really interesting, and Avrum alluded to this already, is that we now can do studies comparing the outcome of randomized controlled trials with observational studies, and it turns out we've all thought, "Oh, the RCT is the gold standard, and if it isn't the RCT, then forget it. I don't want to even look at any observational study. I don't care what other field studies you've-- I don't want to see any other kind of data. If it's not an RCT, I'm done." And I know, you know, some scientists have that view. What really impressed us in gathering the research we did was that when you look at different methods of investigation across many different samples, many different countries, many different times, when you start to get a convergence of evidence where you don't just have one outlier here saying, "Oh look, HRT is beneficial," but no, there's a convergence from so many different directions, then you can feel a little more secure that you're really on solid ground. And I'm finding, too, the-- as Avrum just said, I want to underscore this, not every RCT is bias free and reliable as we've just been seeing, and not every observational study is to be thrown out because it's only an observational study.

    17. PAPeter Attia1:54:28

        Yeah, and there's another point here that so much of our thinking about epidemiology is based on nutritional epidemiology, which John Ioannidis has recently described as, I mean, effectively garbage. I mean, I think he even went so far as to say that, and if you know John, he's quite measured in his words. But I mean, he's basically said there's no role for nutritional epidemiology. And so you might say, "Well, then there's no room for all epidemiology." But there is a difference, I think, and it's subtle, but it's important. Part of the trouble with nutritional epidemiology is it relies on things like food frequency questionnaires, which anybody who's ever actually tried to fill one of these things out realizes they're almost impossible to gather data. Whereas epidemiology may in fact have less of the data crisis when the intervention is simpler, and certainly taking HRT is simpler than remembering what you ate over the past seven days. Point two is-- So this is-- By the way, I have no overarching point. I'm just stating a bunch of thoughts as I try to wrestle with what you're saying. Point two is I think we have seen that it is impossible to eliminate healthy user bias from epidemiology. There are no branches of statistics that can eliminate this, and we must always acknowledge that, and that is why we have to be careful when we look at epidemiologic studies of things where the intervention is more likely to appear in a healthier group or a more health-conscious group or a more affluent group. The third point, which I want to highlight what you've said is we are lulled into a false sense of confidence with randomized controlled trials, and yet virtually all of them have some measure of what's called performance bias, which, you know, PREDIMED, which is generally regarded as the best nutritional study despite the, you know, change in the statistics around the randomization, suffered a very large performance bias, meaning the group that was treated was given much more attention than the group that was the placebo, and therefore they were probably or at least possibly more likely to change behaviors in other ways that could have impacted the outcome. So your point is correct, which is just because something is a randomized controlled trial doesn't mean it is free of bias.

    18. CTDr. Carol Tavris1:56:45

        I want to add something I think really crucial here that's in a way a, a theme throughout our book, which is that the demands on researchers to publish or perish has meant a proliferation of badly analyzed studies. So this is where you're an epidemiologist, you've got a thou- you've got thousands and thousands of people in your sample, and you don't find what you thought you would find. You find no connection between cucumbers and bunions, right? And so instead of saying, "Gee, we find no connection between these two things," they then engage in these statistical practices that are no-nos for any statistician or scientist to do, and yet the results find homes in medical journals. I go back into my data, I rummage around until I find some tiny subset of the sample that seems to support my hypothesis. You don't get to do that. And yet in these studies over and over as we show in our book, not only do they get to do that, but they get published. That's the reason for that, the wonderful table with the list of risks of increased risks of breast cancer that include using an electric blanket for more than six months but less than two years and eating, uh-

    19. PAPeter Attia1:58:01

        I have the-

    20. CTDr. Carol Tavris1:58:01

        ... grapefruit and so forth. Those were preposterous findings that weren't replicated, and yet all of them found homes in medical journals, and that's the concern.

    21. PAPeter Attia1:58:10

        Yeah, I have the table here. I, I was actually reading it, uh... Well, actually, I was reading this in your 2009 paper, and it's great. You know, fish intake, 14% increase in the risk of breast cancer. French fries, 27%.

    22. ABDr. Avrum Bluming1:58:22

        Well, french fries, one extra helping of french fries.

    23. PAPeter Attia1:58:25

        Oh, that's right. That's right. It was just one additional serving of french fries.

    24. ABDr. Avrum Bluming1:58:28

        Per week-

    25. PAPeter Attia1:58:29

        Per week

    26. ABDr. Avrum Bluming1:58:29

        ... in the preschool population.

    27. PAPeter Attia1:58:31

        Yeah. No, no, look, I mean, if you're eating fries at the age of four, I promise you that's a... Uh, grapefruit, 30% increase in breast cancer.

    28. ABDr. Avrum Bluming1:58:38

        But only if you eat half a grapefruit.

    29. CTDr. Carol Tavris1:58:41

        Yeah.

    30. PAPeter Attia1:58:41

        That's right. Three, three-quarters of a grapefruit ameliorated the risk entirely.
15. 1:59:22 – 2:13:51

    Rethinking Cancer, Critics, Race and International Views

    1. ABDr. Avrum Bluming1:59:22

       One, one other point to put in. When we started by saying we don't know what cancer is, let me tell you one of the things we do know. One of the hardest malignancies to treat when I started was called acute promyelocytic leukemia. This is a condition where the bone marrow is full of very immature angry cells called promyelocytes or promyeloblasts, and chemotherapy, even intensive chemotherapy, was associated with a 2 to 5% possible response rate with no complete remission, and everybody died. And about 15 years ago, several investigators found that the problem with promyelocytic leukemia is not that these terrible looking cells are multiplying too quickly. It's that these cells are facing a maturation arrest, that immature cells multiply very quickly. That's how we go from being two cells to being an organism in nine months. And then they start multiplying slowly. As cells mature, they multiply less actively. If there's a maturation arrest, so the cell cannot mature beyond a particular point, the cells grow very quickly, and they kill the patient. If you give something, and in the case of acute promyelocytic leukemia, it's a form of vitamin A called trans-retinoic acid. If you give that to the patient, you remove the maturation arrest. The abnormal leukemic cells proceed through normal maturation. The disease disappears, and the patient is better. And so looking at the tumor cell as the enemy instead of as the smoke behind the fire of the maturation arrest was misguided. And I think we're going to find in many malignancies that our understanding of what cancer is is going to change, and we're going to stop trying to identify the tumor cell as the enemy. But we're not there yet.

    2. PAPeter Attia2:01:33

       There are people that are really talking, and this has been, this has been something, this has been a voice that people have been, um, starting to, to-- starting to gain some volume is, you know, look at the role of stromal cells, for example. So we, we have focused as you're pointing out almost exclusively on the actual cell that has undergone the genetic alteration to render it, uh, cancerous. But the stromal cell that surrounds it, the, the environment in which it lives in cellularly, um, is, is now-- I think people are starting to realize there's something there.

    3. ABDr. Avrum Bluming2:02:03

       Absolutely.

    4. PAPeter Attia2:02:04

       And now how we target that for treatment becomes a second question. But this is a great point. And I want, I want to thank you for writing this book because I don't know how much you guys thought about it before you did it, but you know you're going to make some enemies writing a book like this because you're going up against effectively established medical entities that have a position, and it becomes easy to discredit people who come across as zealots. And I'm not saying you're coming across as zealots, but anybody who writes a book that basically says some very obvious, you know, well-laid-out conclusion is incorrect, you don't get to say that meekly, right? You have to say that with a megaphone to overcome the noise. And when you do that, it looks like, well, you're a zealot.

    5. ABDr. Avrum Bluming2:02:49

       And we welcome the criticism and the discussion. And rather than make enemies, we welcome critics, and that way we will all learn. We don't claim to have the final answer, but we think that this book represents an important step forward in empowering women and helping them live longer and live better.

    6. CTDr. Carol Tavris2:03:11

       And Avrum, you know, when Avrum has debated those who have a publicly different point of view and has said, "Okay, here's my point of view. Here's the data. Here's what I find. Please tell me why you disagree." And they don't. They can't. They haven't. And-

    7. PAPeter Attia2:03:29

       Well, well, what is the best, what is the best counterargument you have heard to your point of view? And even if it's not at a macro level, but to specific issues.

    8. ABDr. Avrum Bluming2:03:39

       It is incredible how silent the other side is. Incredible. I, I've debated people in public. I debated a leading advocate of hormone replacement therapy who, in the course of a debate-

    9. CTDr. Carol Tavris2:03:55

       A leading opponent.

    10. ABDr. Avrum Bluming2:03:56

        Said-

    11. CTDr. Carol Tavris2:03:56

        A leading opponent

    12. ABDr. Avrum Bluming2:03:58

        ... in the course of the debate said, "Look, if all you care about is looking good, feeling good, and living a long time, then take estrogen." [laughing] And I sat down.

    13. PAPeter Attia2:04:07

        [laughs] It's very rare in life that your opponent actually does the mic drop for you.

    14. ABDr. Avrum Bluming2:04:13

        I put that on a slide and used it in future talks. [laughs]

    15. CTDr. Carol Tavris2:04:19

        [laughs]

    16. PAPeter Attia2:04:19

        It's almost hard to believe. One thing we didn't touch on is race. So we've talked about preexisting heart disease, and that may be a fork in the road. That may be a place where we need to reconsider or restratify. When we talk about race, we know that there are different racial predispositions to breast cancer. Has anything come out of all of the reevaluations of the data that would suggest one way or another that Caucasian, African American, Hispanic, Asian women might actually benefit or be harmed differentially from hormones?

    17. ABDr. Avrum Bluming2:04:53

        The first answer to the best of my knowledge is no. But the reason for that is the overwhelming majority of the studied patients are Caucasian. There was a report in two thousand and three that said that the incidence of breast cancer has dropped precipitously. And people in the Women's Health Initiative said, "Well, we published this study in two thousand and two, and the incidence of hormone replacement therapy went down significantly. And while we can't claim credit, we can't think of a better explanation than that." Well, that's preposterous. It's preposterous first because cancer doesn't start and develop within six months. Some people think it takes as long as twenty years. And when they were greeted with that, the answer was, "Well, we agree. We didn't decrease the risk of cancer starting, but what we did is cancers that were subclinical, therefore not diagnosable, that would have been stimulated to grow by the hormones," never mind that the hormones don't stimulate the cancers to grow, "they diminished, and that's the reason for the decline." Well, first, you don't know how many of the women who didn't get breast cancer were or were not taking hormones. But even if your point is right, then the decline should have been among the very early small cancers that just peeked through as a result of the stimulation that you are postulating, and the incidence of cancer diminished, not among that population, but among the more advanced, larger cancers. And by the way, the decline started in nineteen ninety-nine, not in two thousand and two. And yet in the literature, they take credit for that decline.

    18. CTDr. Carol Tavris2:06:50

        But has the decline occurred among all groups, African American-

    19. ABDr. Avrum Bluming2:06:53

        Oh, and I'm sorry. And the point I was making is the decline did not occur among Black women, that it was only seen among Caucasian women. I-

    20. PAPeter Attia2:07:03

        Do we have data on the different uses of HRT among women at that time?

    21. ABDr. Avrum Bluming2:07:08

        Not that I know of. It also didn't occur-- The decline wasn't seen in Norway, which is largely Caucasian.

    22. CTDr. Carol Tavris2:07:17

        Of course, most research has been conducted on white women and not on African American women. Although, I mean, the, the ethnic question and the regional question is a very important one. And I think for that reason, the fact that national menopause societies in every country from India and African nations and South America and Canada and that long list of, of-

    23. ABDr. Avrum Bluming2:07:39

        Thirty-three

    24. CTDr. Carol Tavris2:07:39

        ... menopause-- and thirty-three menopause societies all have endorsed, uh, the use, the, the beneficial use of HRT for women.

    25. ABDr. Avrum Bluming2:07:47

        And have argued against take the smallest dose for the shortest period of time.

    26. PAPeter Attia2:07:52

        Does that make the United States one of the more anti-HRT countries?

    27. CTDr. Carol Tavris2:07:57

        It does. Well, I would say so. See, it's, it's interesting in, um, in England where Premarin is on the national health and is routine, it's kind of considered the old-fashioned, you know, HRT, and bioidenticals are somehow trendier and better, but there isn't the quite the antipathy toward HRT that we see here. Nonetheless, the Women's Health Initiative had international repercussions.

    28. PAPeter Attia2:08:22

        I mean, it certainly has in Canada, where I naively, stupidly tried to have this discussion with my mom's doctor, and I mean, she looked at me like I had 12 heads before basically saying, "Son, we're in Canada here. We don't do that."

    29. CTDr. Carol Tavris2:08:41

        There you are.

    30. PAPeter Attia2:08:42

        I mean, it-- there was no discussion. Th- this was not, "Let me hear why you think your mom would benefit from being on hormones." It was full stop, "We'd have an easier time if you were asking me to attach a third arm to your mom."
16. 2:13:51 – 2:20:36

    HRT After Breast Cancer and Closing Thoughts

    1. ABDr. Avrum Bluming2:13:51

       Well, it's a pleasure. We, we didn't discuss hormone replacement therapy after a diagnosis of breast cancer. We touched on it, but chapter six in the book does discuss that, and that's still an open question. But it's an open question. It's not an obvious conclusion. As I mentioned, getting pregnant after having a diagnosis of breast cancer does not compromise the prognosis. In fact, it might improve the prognosis, that a pregnancy which floods the body with estrogen before age 20 is associated with a 70% decreased risk of eventual breast cancer. We used to tell women if they got pregnant and they had breast cancer, they must abort, and it turns out that's not true, and in fact, aborting can negatively affect prognosis. And we present all the findings in that issue so that it's something worth discussing. There are 15 studies in the literature looking at hormone replacement therapy after breast cancer, and all but one of them show no increased risk of recurrence. And the one that shows an increased risk of recurrence was stopped prematurely, had a follow-up of two and a half years, and is a worthwhile study to look at, but clearly should not be the last word, including the senior author of that study said this should not be the last word in this subject.

    2. PAPeter Attia2:15:23

       Yeah. I'm glad you remembered to bring that up because that was another... You know, look, I've always personally thought a patient with a personal history of breast cancer, not to say... So we'll talk, we'll come back to family history. Personal history of breast cancer, with the exception of that one patient who was adamant. I mean, her words were, "I would rather be on HRT than... I would rather be dead than not be on HRT." But I've always felt that that is, that is a really scary place to be.

    3. CTDr. Carol Tavris2:15:50

       One of the interesting things that we talk about in the, in the heart chapter is precisely because so many women are surviving breast cancer and living for many years after breast cancer, that then their increased risk of heart disease in- increases, and so now there is a new specialty of cardio-oncology, in which the issue is how do we assure the prolonged survival of our breast cancer patients who are now at risk of dying of heart disease? And so-

    4. PAPeter Attia2:16:20

       And Alzheimer's disease.

    5. CTDr. Carol Tavris2:16:21

       Exactly.

    6. ABDr. Avrum Bluming2:16:22

       Yes. And osteoporosis.

    7. PAPeter Attia2:16:24

       Yeah. So you're right. It's, it is not something that we can just say, "Well, that's a narrow subset of women. If you've had breast cancer, we're gonna take you off the table," because we're neglecting, as you said, 19 out of 20 of these women, or certainly 9 out of 10 of them, are not going to die from breast cancer.

    8. ABDr. Avrum Bluming2:16:41

       At least five million in the United States now.

    9. CTDr. Carol Tavris2:16:43

       When Avrum went to talk to the FDA to secure their approval for doing his study of administering HRT to his patients who had had breast cancer, one of the doctors on the committee said to him, "What do you want to do this study for? Aren't all your patients gonna die anyway?" And Avrum said, "No, uh, actually."

    10. PAPeter Attia2:17:06

        Person doesn't know much about breast cancer. [laughs]

    11. CTDr. Carol Tavris2:17:07

        [laughs] No.

    12. ABDr. Avrum Bluming2:17:08

        But he sat on the committee. Yeah.

    13. CTDr. Carol Tavris2:17:11

        So.

    14. ABDr. Avrum Bluming2:17:11

        Actually, it was a she.

    15. PAPeter Attia2:17:13

        Hmm.

    16. ABDr. Avrum Bluming2:17:13

        We eventually did get FDA approval to do the study, which we did for 14 years and reported the results every year.

    17. PAPeter Attia2:17:20

        What, what are the, what are the... What are the reports, what are the results as of today?

    18. ABDr. Avrum Bluming2:17:22

        Well, it, it, our study was a small study, but it fit in with the other 14-

    19. PAPeter Attia2:17:25

        Mm-hmm

    20. ABDr. Avrum Bluming2:17:26

        ... showing no increased risk of local recurrence, contralateral breast cancer, or distant recurrence among the women who took hormones compared to the women who didn't when they were matched stage for stage.

    21. PAPeter Attia2:17:37

        Oh, so, okay. Got it. Well, um, [laughs] I could go on, but I, I mean, I think, I think the point, I think the point's been made loud and clear. Again, I want to thank you for writing the book. I think this was, uh... This is one of those books where there's a lot of work that went into it. I mean, frankly, I think your 2009 paper is itself a great paper, in itself is, was a lot of work. That's a ton of literature to review, and I do hope that, that women, men, anyone listening to this who knows a woman comes away at least thinking if they have a strong point of view on this, which many people do, that they could at least revisit that. And take the time. You know, JFK said something, it's one of my favorite quotes, and I'm gonna paraphrase it, but the gist of it is we, we too often enjoy the comfort of opinion without the discomfort of thought.

    22. CTDr. Carol Tavris2:18:24

        [laughs]

    23. PAPeter Attia2:18:24

        And, uh, he says it much more eloquently, but this is one of the case studies for that, right? There are way too many people that I speak with who immediately believe, unilaterally believe HRT is anathema to life, and yet when you ask them why, they can't give you a single reason other than the WHI said so.

    24. CTDr. Carol Tavris2:18:51

        There you are.

    25. ABDr. Avrum Bluming2:18:52

        A quote that I like is, "The more you know, the less you fear."

    26. PAPeter Attia2:18:57

        Very well.

    27. CTDr. Carol Tavris2:18:58

        Exactly.

    28. PAPeter Attia2:18:58

        And on that, I want to thank you guys for making the trip down here, and I want to wish you all of the best as you continue to get this message out there.

    29. CTDr. Carol Tavris2:19:06

        Thank you, Peter.

    30. ABDr. Avrum Bluming2:19:06

        Thank you, Peter. [outro music]

Episode duration: 2:20:36