Ep. 198 – Dispelling Myths About Hormone Replacement Therapy

I am delighted to have two respected researchers, Dr. Avrum Bluming and Dr. Carol Tavris, joining me today! They are the co-authors of the book, Estrogen Matters.

Avrum Bluming received his MD from the Columbia College of Physicians and Surgeons. He spent four years as a senior investigator for the National Cancer Institute. For two of those years, he was director of the Lymphoma Treatment Center in Kampala, Uganda. For more than three decades, he has been studying the benefits and risks of hormone replacement therapy administered to women with a history of breast cancer.

Carol Tavris received her Ph.D. in social psychology from the University of Michigan. Her books include Mistakes Were Made (But Not by Me), with Elliot Aronson; Anger: The Misunderstood Emotion, and The Mismeasure of Woman.

Estrogen Matters provides a lot of scientific information that refutes much of the fear-mongering around hormone replacement therapy. It is helpful for women who have gone through cancer therapy and those who have not had to deal with cancer, in terms of the conversations they could consider having with their healthcare professionals.

Dr. Bluming and Dr. Tavris are both incredible individuals, and it was an honor to interact with them! In this episode, we dive into statistical manipulation and the influence of the Women’s Health Initiative. We talk about the study limitations and the role of data mining. We discuss the benefits of hormone replacement therapy and its impact on cancer risk, coronary artery disease, bone and brain health, and more. We also look at synthetic versus bioidentical hormones, routes of administration, and what we need to think about in our own hormonal health journeys.

I hope you enjoy my conversion with Drs. Bluming and Tavris today! Stay tuned for more!

“They now report, after twenty years of follow-up, that women who take estrogen as hormone replacement therapy have a reduced risk of breast cancer that is significant; by 23%, and have reduced risks of death from all causes.”

– Dr. Bluming 

IN THIS EPISODE YOU WILL LEARN:

• Dr. Bluming talks about the Women’s Health Initiative and explains why we went off-course after it came out in 2002. 
• The symptoms of menopause are not trivial. They are physically and mentally harmful to the body. 
• We need to understand the social and political trends against hormone replacement therapy.
• We need to understand that estrogen for women in menopause plummets to one percent of what it was before menopause.
• Dr. Bluming discusses the various issues with the article about hormone replacement therapy.
• If a woman starts taking hormones within ten years of her last menstrual period, she will have a reduced risk of heart disease and strokes and also improved longevity. 
• The women who fear taking hormone replacement therapy are afraid of breast cancer. 
• Estrogen reduces the risk of heart disease by up to fifty percent.
• Drs. Tavris and Bluming talk about bone health. 
• The impact of hormone replacement on brain health.
• How the investigators of the Women’s Health Initiative manipulated their findings on dementia.
• How data mining gets used to sub-stratify data that has already been studied.
• The truth about bio-identical hormones.
• There is a lot of misinformation around the route of administration for estrogen.

Bios
Avrum Bluming, MD

Avrum Bluming received his MD from the Columbia College of Physicians and Surgeons. He spent four years as a senior investigator for the National Cancer Institute, and for two of those years, he was director of the Lymphoma Treatment Center in Kampala, Uganda. He organized the first study of lumpectomy for the treatment of breast cancer in Southern California in 1978, and for more than three decades he has been studying the benefits and risks of hormone replacement therapy administered to women with a history of breast cancer. Dr. Bluming has served as a clinical professor of medicine at USC and has been an invited speaker at the Royal College of Physicians in London and the Pasteur Institute in Paris. He was elected to mastership in the American College of Physicians, an honor accorded to only five hundred of the over one hundred thousand board-certified internists in this country. 

Carol Tavris, PhD

Carol Tavris received her Ph.D. in social psychology from the University of Michigan. Her books include Mistakes Were Made (But Not by Me), with Elliot Aronson; Anger: The Misunderstood Emotion, and The Mismeasure of Woman. She has written articles, op-eds, and book reviews on topics in psychological science for a wide array of publications — including the Los Angeles Times, the New York Times Book Review, the Wall Street Journal, and the TLS — and a column for Skeptic magazine. She is a fellow of the Association for Psychological Science and has received numerous awards for her efforts to promote gender equality, science, and skepticism.

Connect with Dr. Avrum Blooming and Dr. Carol Tavris

• On Facebook
• On Twitter

Connect with Cynthia Thurlow

• Follow on Twitter, Instagram & LinkedIn
• Check out Cynthia’s website
• Check out Cynthia’s website

Books mentioned:

Estrogen Matters

Mistakes Were Made (but not by me)

Anger: The Misunderstood Emotion

The Mismeasure of Woman

TRANSCRIPT:

[intro]

Cynthia: Welcome to Everyday Wellness Podcast. I’m your host, Nurse Practitioner Cynthia Thurlow. This podcast is designed to educate, empower, and inspire you to achieve your health and wellness goals. My goal and intent is to provide you with the best content and conversations from leaders in the health and wellness industry each week and impact over a million lives.

Gosh, today was really an amazing opportunity to connect with two researchers, who I respect enormously, Dr. Avrum Bluming and Dr. Carol Tavris, who wrote the book Estrogen Matters. We dove deep into statistical manipulation, the influence of the Women’s Health Initiative, talking about the limitations of the study, the role of data mining. We spoke a great length about the benefits of hormone replacement therapy, the impact on cancer risks, coronary artery disease, bone health, brain health, and more. We also dove into synthetic versus bioidentical hormones, routes of administrations, and things to really consider and think about in terms of our own hormonal health journey. It really was a tremendous honor to interact with Drs. Bluming and Tavris. They are incredible humans and I cannot tell you how grateful I am that they wrote this book, which really provides quite a bit of scientific information that contradicts a lot of the fearmongering that has gone on about hormonal replacement therapy, not only for women who have not dealt with cancers themselves, but also the considerations for women that have gone through cancer therapy, and the conversations that they can welcome having with their healthcare professionals. Enjoy this conversation. 

Well, I think it really begs to start the conversation. I’m a traditional allopathic trained Nurse Practitioner and certainly, I don’t think I’ve ever shared with my listeners the part of my graduate thesis was talking about endometrial cancer. Because there was one faculty member at Hopkins that I wanted desperately to work with and that was her area of expertise. As you can well imagine, when Women’s Health Initiative results were initially shared, that changed the trajectory of so many people’s lives and certainly, the lives of millions and millions of women. Let’s really start there, because I think you both do such a beautiful job in this book really articulating how we got off course. Because up until the Women’s Health Initiative, it was commonplace and correct me if I’m wrong that women would take hormone replacement therapy, and it was not fearmongered, I feel at this point for every 10 women I say, you really need to read this book, you really need to bring this into your physician or your Nurse Practitioner, whomever cares for you in middle age and beyond. There are just as many people who are terrified of hormone replacement therapy. 

I think on so many levels, I know myself, I feel so much better on hormone replacement therapy that I cannot imagine someone used the terminology of ‘bare backing my way through middle age’ without some degree of support. I think a great deal about brain health. I know we’ll talk more about this. But where did we get so off course and what was the mindset prior to the Women’s Health Initiative study results coming out? Because like I mentioned earlier, it sounds it was much more commonplace and it was certainly more entertained for women to be placed on some degree of hormonal support at this stage in life and beyond.

Avrum: Well, it’s just to place it in some perspective, there was a period I think in the late 1980s, when Premarin, which was the most widely form of estrogen prescribed was the most common prescription in the United States. The numbers vary depending on which census you read, but about 40% of postmenopausal women were taking estrogen for some period of time. With the Women’s Health Initiative as you pointed out, we are inherently risk averse as a species. So that if there was something we’re afraid of and there is also a potential gain from undertaking the activity we’re afraid of. As a species, we will tend to avoid the risk rather than get the game. The risk has been publicized in every major publication in this country and throughout the world. The Women’s Health Initiative, which was published in July of 2002 was a $1 billion study. That’s the most expensive study in medicine ever undertaken anywhere in the world that I’m aware of. The people who were the investigators are among the most prestigious investigators in our country. These are very respected people from very respected institutions and that helped set it off.

Carol: I would add to this a strand of resistance to hormone replacement from the women’s movement. When I was coming up, I’ve been a feminist since I was born. I had no alternative. My mother said, “I have a baby feminist here.” [laughs] But what many women were saying was, “You know what, menopause is just a natural phase of life as menarche is, and you don’t want to medicalize it, you don’t want to treat it, why should you prescribe anything more than just a natural thing and so If you have any symptoms, hot flashes, blah, blah, just suck it up, honey. It’s going to be fine, it’s going to last 20 minutes and you’ll be fine.” When I was a young woman in my 30s, I had the same idea. it was pathologizing menopause. This seems not a good idea. Many of us, I, myself included have been very critical of Big Pharma’s, shall we say, manipulation of research to promote a new drug. You know that’s how Big Pharma is. There are many feminists around the world in medicine and outside, who have really been steering women away from the idea that you need to take any kind of medication in menopause. 

I was at a conference, where a woman from Australia said, “Oh, please, hot flashes. No big deal. Just get a fan.” Oh, God. Okay. Well, as Avrum knows, I was very fortunate. I had no menopausal symptoms. I didn’t suffer from anything. It was really easy for me to scoff at this. “Okay, fine. Get a fan.” But writing with Avrum, of course, in our research, what I learned was that the vast majority of women have symptoms, that the average length of time that women have these symptoms is seven and a half years. This is not trivial. It’s not an overnight thing and that the symptoms themselves are harmful physically and mentally to the body. Years without sleeping well, years of heart palpitations, hot flashes are not trivial. I think this is an important awareness for women, who have been told, “Yeah, menopause, no big deal, just get over it.” I like Barbara Sherwin’s remark in our book, when she was asked, “Well, you know, but isn’t taking hormones and menopause unnatural.” She said, “What is unnatural is living 30 years after menopause. That’s the thing.” My work is on the benefits of estrogen for thinking and cognition and I’m not giving it up. So, I think it’s important to understand what the social and political trends against hormone replacement have been.

Cynthia: I think that’s such a good point, because on a lot of levels, I still clinically will have discussions with women, where there’s a sense of guilt. They feel guilty to even consider hormone replacement therapy, but yet they recognize the degree of brain fog, and their decrease in mental acuity, and their trouble sleeping is a huge issue. We look beyond just the body composition, a lot of women get frustrated with hormonal weight gain that occurs in middle age, and they’re just so troubled when they acknowledge that we spend a significant 40% of our lifetime in menopause, and we want those years to still be vital and capable. For me, because I work in the metabolic flexibility space, a lot of the worsening of those transitional symptoms that are exacerbated even to menopause are really related to the metabolic and flexibility. 

A lot of women that are having tremendous challenges making that transition are women that have insulin resistant or diabetic. As we start to see this population of ours in most Westernized societies becoming less physically healthy, it’s exacerbating a lot of those menopausal symptoms. I don’t think anyone that’s listening should feel like they have to suffer to make that transition. I think there’re so many nice options. I’m so grateful that you plugged in some of the methodology behind the social contributions to considerations of what we can do during this transitional time.

Carol: I just have to say, I’ve wonderful observation in relation to men. If you said to men, “Okay, guys, you’re 50. You don’t need to have sex anymore. So, what if it’s painful and so, what if it’s not very much fun? Too bad? You had enough years of sex. You don’t need to have any more. Just go away and have gin and tonic.” He said, “How many men would stand for that? Give me the bill now.” I want seven of them. But women now have been told that just live with this. 

Avrum: It’s not just a random observation. In fact, prostate cancer is responsible for about as many deaths each year in men as breast cancer is in women. The link between testosterone and prostate cancer is reasonably strong. The question is how many men have been told to stop testosterone or in fact to be castrated if they have serious prostate cancer and what happens to these men, who are castrated versus those who weren’t? The answer is that study has never been done. By the way, it never will be done. Because men simply wouldn’t allow any group to manipulate their bodies, the way women have allowed medicine to manipulate their bodies.

Cynthia: I think that’s a really important distinction that if we look at gender specific variables as they pertain to these discussions that women in many ways, and I know that in the book, and certainly, in other interviews that I’ve listened to the both of you have done, when you look at the way that women were viewed going through menopause, it was histrionics, it was taking out different types of organs to try to see if it had a net impact or improvement, and how they felt. On many levels, I’ve had patients– My whole background was in ER medicine and cardiology, so about as far away from this discussion topic as we could have today. The discussions that I’ve had with male and female patients, when they talk about these kinds of issues, both men who’ve gone through significant prostate history and no longer can have an erection, and they’re dealing with those sexual side effects. Then women disclosing privately some of the challenges that they’re experiencing. They just say, “This isn’t the way that I anticipated my middle-aged years would go. This was really quite a shock.” 

But I think there’s so much conventional methodology, even when I talk to my female family members who are very well educated and certainly have been very successful. Whatever they were told, when Women’s Health Initiative came out, they didn’t even question it. They just stopped everything. They stopped all their hormone replacement therapy. Now, 20 plus years later, we’re starting to see some of the side effects. We’ve had very open discussions with many of my female family members, who have been in menopause for 20 plus years. The side effects, especially the brain changes and I know, we’ll touch on some of these things, with the lack of estradiol, and progesterone, and testosterone signaling has really been concerning for them. I would love for you to speak to the fear that so many of, I’m sure your patients and the clients that you interact with, are these the same types of concerns that people have been echoing over the past 20 years? “This is not the way that I thought my life was going to be? What can I do about it?” Finding clinicians that are willing to prescribe hormone replacement therapy, despite what the Women’s Health Initiative shared so many years ago.

Carol: I want to just interject one very quick point on the subject of testosterone and estrogen, which is I had always assumed that estrogen for women in menopause declined slowly, modestly in the way that testosterone does. It just slows. It’s just a modest decline. What I learned and working on this book with Avrum is that it doesn’t decline, it plummets to 1% of what women’s estrogen levels were before menopause. What? That’s not a slow decline that you can live with. That’s emptying the gas tank. It’s very different in that respect. It becomes more understandable that we really are experiencing a major loss of an important hormone that affects every single tissue in our bodies. So, that’s an important, I think, understanding for women to have. 

Avrum: Is there a question on the table?

Carol: [laughs] The question, what’s the question? Let’s see. [laughs] Oh, what can women do? Well, you raise this issue that 20 years ago, I mean, I remember the immediate panic after the Women’s Health Initiative came out. Doctors were saying their offices were flooded with calls from alarmed and panicked women. One of the most disgraceful things about that with the August New York Times, and its flaring headlines and the press conference was that the article itself in JAMA did not come out for what was it over weeks, or a month, or so– 

Avrum: It was a week and a half. 

Carol: Okay. Doctors get these panic calls and don’t even– Those who want to read the actual data, which I have to say it’s not so many of them. They live by headlines like the rest of us, didn’t even have an article to go to to check the data. I called my gynecologist and he said, “I don’t believe this for one millisecond and I’m waiting for the article to come out.” But he was rare. He was scientifically minded and he wanted to actually see the evidence.

Avrum: Medical studies usually come out in the medical journal first, and the medical journal will then contact the press, and they will put it in the media. That’s not the way this worked. As Carol said, this article came out first in the media, so that physicians didn’t see it at the time it was announced worldwide. In addition, only three of the investigators in the Women’s Health Initiative wrote that article. There were over 40 investigators. When the 40 Investigators were told about the article, most of them said, “Wait a minute, we don’t agree with that.” They were then told, “Well, the article isn’t yet in print, but it has been submitted to the Journal of the American Medical Association.” We happen to be in Chicago and if you just run down the street to the publishing office, see what you can do to change it. They ran down the street and they were told, “I’m sorry, it’s already been printed and it’s going out within a week.” That inside view didn’t really come out until Robert Langer, one of the Women’s Health Initiatives published that insider’s view over 12 years after the Women’s Health Initiative came out. 

The Women’s Health Initiative said, “What we wanted to do is in an unbiased way, evaluate whether hormone replacement therapy was good or bad, since it’s being used so widely.” The unbiased nature of that was challenged when an article written by the lead investigator of the Women’s Health Initiative published an article several years before saying, “It’s time to put an end to the estrogen bandwagon.”

Carol: That guy gets to lead the Women’s Health Initiative. I mean, really.

Avrum: And he succeeded.

Cynthia: He’s obviously so biased. I think it’s important for anyone that’s listening that maybe is not familiar with this Women’s Health Initiative. The health of the participants and this is something that really stood out for me, because I went down this rabbit hole after I listened to your podcast with Peter Attia recognizing that this wasn’t even a healthy population of women that were selected for the study. I think this is important for people to understand, it wasn’t a selection of women that were in early menopause, and ended up being women that were in their 60s with multiple comorbidities, and whether they were obese or overweight, and prior smoking, and high blood pressure or hypertension. So, the data from the very beginning was already skewed.

Avrum: In fairness to the investigators, what they said is our major area of interest is not breast cancer, it’s really heart disease and we want to see whether what we hear about estrogen in that it significantly prevents the risk of serious heart disease. We want to see if that’s valid. Rather than take women, who were between the ages of 45 and 51 around the time when menopause usually starts, they started with a population that had a median age of 63, so that if there would be cardiac events, they would happen sooner. That means the study could be shorter and therefore less expensive. That’s a reasonable reason to do the study. The problem is you point out is that that population, which wasn’t a normal female population. Half the women were overweight, a significant portion was smokers, a significant portion were obese and if you start hormones over 10 years after your last menstrual period, you already have blood vessels that have been narrowed by age that happens to all of us. 

Estrogen can cause platelets, which are small corks that circulate in the blood and help prevent bleeding. Estrogen can cause these platelets to clump. If a platelet clump enters an already narrowed vessel, it can block the blood flow through that vessel and it can compromise blood, especially to the heart or to the brain. At least for the first year, after the Women’s Health Initiative report, what they found during the first year of the study is there was an increased risk small but real of heart attacks and strokes that have subsequently walked back what they said. They now say that there is a 10-year window of opportunity, so, a woman who starts hormones within 10 years of her last menstrual period actually has reduced risk of heart disease, reduced risk of strokes, and improved longevity. That 10-year window has allowed the investigators of the Women’s Health Initiative to walk back every single adverse effect they spoke about. Even estrogen, they now report after 20 years of follow up that women who take estrogen as hormone replacement therapy have a reduced risk of breast cancer that is significant by 23% and have a reduced risk of death from all causes. 

The only argument we still have with the Women’s Health Initiative is whether the combination of estrogen and progesterone use this hormone replacement therapy increases the risk of breast cancer. Remember, I said that breast cancer was not their primary area of interest. It was a secondary area of interest, but breast cancer made the headlines, breast cancer is the red flag, breast cancer is the reason that the frequency of hormone prescriptions fell so precipitously, and the women who are terrified of taking hormone replacement therapy are terrified of breast cancer.

Cynthia: What’s interesting for listeners who may not be aware of this, we as women are actually more likely to die of cardiovascular disease than we are of breast cancer. But yet, there’s not enough focus on that. I think that’s certainly something that’s really important for us to understand. One thing that you mentioned– [crosstalk] 

Carol: Breast cancer survivors themselves are more likely to die of heart disease than of breast cancer recurrence. Staggering, right? 

Cynthia: Yeah, it’s unbelievable. 

Avrum: Remember, Cynthia, when people say, “Well, more women die of heart disease than die of breast cancer. The usual response is well, but old women die of heart disease and young women die of breast cancer, and that’s not true. In point of fact, for every decade after the age of 40, more women die of heart disease than die of breast cancer and that difference increases every decade. Estrogen, we now accept reduces the risk of heart disease by up to 50%.

Cynthia: That’s really significant. My whole background as a Nurse Practitioner has been in working predominantly for 16 years in cardiovascular disease and I can’t tell you how many patients of mine would tell me, “I felt great while taking hormone replacement therapy. But since I’ve had a heart attack, I’m no longer allowed to be on hormonal therapies.” They would talk to me and I know in your book, you are very transparent about your wife, and your daughter, and the choices that they made after being diagnosed with cancer. I think I’ve been sharing your work so much. I think that it’s really important for us to be having these discussions. One thing that I thought was really interesting is specific to talking about cardiovascular disease in particular is that the leading cause of death in the United States, 290,000 people is more than seven times the number projected to die from breast cancer. Our focus is really on the wrong thing that HRT actually gives you a 50% reduction in the risk of coronary event in women with unopposed oral estrogen, and then estrogen and progesterone together is better in reducing the risk of myocardial infarction or heart attacks, really important for people to understand that and you’ve already touched on the changes that go along intravascularly. Inside those vessel walls that estrogen actually helps dilate the blood vessels that there are all these small vessel changes that occur later in life. I know when I was working clinically in cardiology, the thought process was women present differently with cardiovascular disease, they present later, so by the time they usually get diagnosed, it’s much more progressive. But we also talk a lot about the small vessel disease. I wonder how much of that is really related to this decrease in elasticity in the blood vessels themselves with the loss of estradiol.

Avrum: Yes, estrogen does increase the ability of blood vessels to dilate. It keeps them younger, they’re more elastic. They don’t compromise an end organ when you’re exercising, because blood supply can be increased. But as we said earlier, blood vessels that are already sclerotic, blood vessels that are already narrowed are at risk of being further compromised by platelet clumps that estrogen can cause. So that especially in women who have had heart attacks before, taking hormones must be a balanced risk benefit. It’s not something we would say everybody should do.

Carol: Well, and I would say, you’ve had so many messages from women saying, “Wait a minute, I’m 65 now and I just read your book. Can I start taking estrogen right now, please?” Of course, the answer is they’ve been past that 10-year window, most of them with the issue that Avrum just mentioned in the first year of beginning hormones.

Avrum: Which doesn’t mean, no, they can’t. 

Carol: Exactly.

Avrum: But it means they should initiate a discussion with their physicians, look at where they stand individually, and then discuss benefit versus risk, so that it is a joint decision of an informed physician with an informed patient, and not some kind of dictatorial statement from the doctor saying, “I don’t even want to talk about it.”

Carol: Exactly. And of course, for a woman has menopause, the question of whether she has high risk factors for Alzheimer’s, or for bone fractures, for osteoporosis, or for any of the other things that we know estrogen is really beneficial in preventing. That’s also part of that calculation.

Cynthia: Absolutely. I think bio individuality rules and what we’re all speaking from as a place of advocacy, having the discussion making sure you’re having those conversations with your healthcare professionals. I would love to touch on bone health, because as someone who is a thin, framed Caucasian woman with a strong family history of osteoporosis, I was shocked to realize the insignificance of the term ‘osteopenia.’ 

Carol: [laughs] 

Cynthia: Because this was one of the things that my GYN came after me about and said, “You’re already–” At this time, I was still in my 40s. “You’re in your 40s, you are already osteopenic.” I would love to touch on this because bone health is obviously and you’re laughing already. You know where I’m going. 

Carol: [laughs] 

Cynthia: The insignificance of osteopenia that even the World Health Organization doesn’t acknowledge this. This new age social construction I’m using your words invented and sustained by marketers, drug companies, and other vested interests. 

Carol: You bet you. I’ve been ranting about osteopenia for so long. I can barely remember when I started. [giggles] Osteopenia is what is particularly annoying phenomenon for me. But it’s part of the many– Well, you know what I mentioned earlier about medicalization, there is a big incentive for the pharmaceutical industry to create disorders that can then be treated with, we just happen to have a drug for this. If we don’t have a drug for it, then never mind it’s not a condition. But we see this in many domains in which there is a medical concern, let’s say, problems with hearts, or bones, or whatever else. By expanding the boundaries of how we define what the disorder is, we can expand the number of people that we can treat or that we could offer our services to. Osteoporosis is a diagnosable condition, of course, but wait, what about people who are pre-osteoporotic? What are we going to do with them? Well, they don’t have it yet. But osteopenia was just a manufactured term for women, who didn’t have osteoporosis, but might. Well, if you’re measuring bones with somebody who’s 50 or 55 and you say, “You know what, your bones aren’t as strong as they were when you were 20.” Well, yeah, [laughs] not much is the same as it was when I was 20. Why is this a condition that needs treatment? 

Again, my wonderful gynecologist, who of course, had gotten the machine to measure bone density and so forth, because it was such a great machine and he could not give it for all his patients, and he said, “You have osteopenia,” and then he burst out laughing, which we both did. But many do not, of course. By the way, it’s also the same with other things such as cholesterol measurements to determine whether you need to have a need to have a statin. The drop in the levels of cholesterol that supposedly warrant statins contributed to making statins, the biggest selling drug of the century I would say. Whereas we know, so the routine prescription of statins for women, who have not had a heart attack, who do not have heart disease, but if their cholesterol is high enough, well, we better give you a statin honey. Well, there’s no evidence that it reduces their risk of heart attack or mortality from heart disease.

Avrum: The evidence is really evidence on male studies. Traditionally, medical studies have been done on men. The results were then extrapolated to women, who were like men, but not really. Bernadine Healy, who was the first and thus far the only head of the National Institutes of Health in the United States also a cardiologist said, “It’s time we had a study for women about women.” The Women’s Health Initiative really developed at the instigation of Bernadine Healy, who wrote a book in 1995 saying, “From what I know based on largely cardiology studies, but from everything, as soon as I reach menopause, I will start hormones without a blink.” If Bernadine Healy knew what the Women’s Health Initiative had evolved into and what it had caused, she would turn over in her grave, she sadly died. There are two statements I’d like to make. One, Carol always insists that we say this, which is Carol and I are not on the payroll of any pharmaceutical house of any industry at all. The only interaction I ever had with a pharmaceutical firm was I was called as an expert witness to testify in a case where a woman was suing a pharmaceutical house for having taken hormones and develop breast cancer. I was paid on an hourly basis and that’s the only relationship we have and we stick by that. 

In addition, when we talk about osteoporosis and hip fracture, it’s worth saying first that approximately as many women will die during the first year after a hip fracture as die annually of breast cancer. It’s not because of an underlying condition that may have been responsible for the hip fracture, it’s because of the complications of the hip fracture. Hormones, estrogen especially, but also progesterone will reduce the risk of osteoporotic hip fracture by up to 50%. Having said that, Carol spoke about this wonderful machine that her gynecologist has. In fact, the best way to check for bone fragility or loss of the tensile strength of bone, which means how much you can bend bone before it breaks. The best thing to do is to take a long bone in the body, and put it in a vise, and exert pressure, and see just how much pressure is required before you break the bone. Clearly, that’s not a feasible test to do. Instead, bone mineral density is being used to test for osteoporosis and it’s not a great test. It’s the best we have, but it’s not a great test. Osteopenia, we’ve already discussed, that’s nothing. But clearly, women get bone fractures even if they don’t have reduced bone mineral density and people with good bone mineral density, which really means the calcium shell on the bone, not the intrinsic tensile strength of the bone. People with good mineral density can also get fracture and estrogen reduces that risk across the board.

Carol: Avrum, I want to underscore what you said maybe make this point more clearly, because many women have been told, “Just take calcium. Just take enough calcium, dear, with maybe some vitamin D and that will keep your bones strong.” That’s exactly the wrong thing. Would you like to comment on that [crosstalk] please?

Avrum: Sure. Calcium and Vitamin D were advertised heavily around the same time the bone mineral density study was able to diagnose osteopenia. I remember Lauren Hutton, a model was on the air pushing that extensively. What you do with calcium and vitamin D as I mentioned is you can strengthen the shell of the bone which if anything makes the bone less flexible. But it does nothing to the tensile strength of the bone. If you were just interested in bone mineral density, if you take a lot of fluoride and I am not recommending this, but if you take a lot of fluoride, your bones will be incredibly dense. You will walk home with a 10-10 for your bone mineral density and your risk of hip fracture will be increased. Calcium and vitamin D can help improve bone strength in a pre-menopausal woman or a woman on hormones, especially one who exercises, so she was also strengthening her bones. But in a postmenopausal woman not on hormones, these two agents do nothing.

Cynthia: I’m so glad that you brought that up, because this is a question that gets asked so frequently across social media, so much so that my team actually, we now have a canned response about that specifically. Very important that everyone understands, calcium and vitamin D does not prevent or treat bone loss and that’s an important distinction. However, we know estrogen, and progesterone, and hormone replacement therapy can be certainly an important addition to that. I would love to touch on the impact of hormone replacement therapy on brain health. I think, as I get older, I start taking greater concern/interest in all things cognitive function and brain health. I think that there’s so much concern about how women’s brains change going from peak cycling years, perimenopause, into menopause, 12 months without a menstrual cycle, and how they seem to be at greater risk for type 3 diabetes or Alzheimer’s. I don’t know if it’s all attributable to the loss of estradiol signaling in the brain or it’s also a combination of insulin resistance and we know that estradiol can be very insulin sensitizing. What are your thoughts on this as it pertains specifically to menopausal brains?

Avrum: Well, we spoke about fear being a very strong motivator. If there is one thing that women fear even more than breast cancer, which by the way is 90% curable when diagnosed early and appropriately is cognitive decline. Alzheimer’s disease being the most famous form of that. Estrogen will reduce the risk of cognitive decline depending on which study you read by between 25% and 65%. People say, “Well, there’s never been a prospective randomized study of that.” That’s true. But you can’t study cognitive decline over 20 years to afford the study and make it an unchallengeable study. But the data are reasonably consistent in that. You mentioned briefly– My wife had breast cancer. When we treated her with chemotherapy, she went into a precipitous menopause, and she was able to tolerate the hot flashes and the night sweats, and even the palpitations although they were annoying. What she couldn’t tolerate is she is very bright and reads a great deal. She found that she was unable to remember two pages back in a book that she was reading and that was intolerable. When we placed her on hormone replacement– Well, when she elected to take hormone replacement therapy, she’s back, and she’s bright as ever, and remembers everything.

Carol: I’m fascinated by medical detective stories. As a social psychologist, one of the things that’s always fascinated me that even scientists, even doctors, when they are so blinded by a belief, so convinced that something is so that they become blind to their own data. They don’t see their own numbers in their own study. One of the great questions we get so often is, why did the investigators of the Women’s Health Initiative strangle their data to come out with scary findings that are not there? We don’t have an answer to this but as we delved into what the Women’s Health Initiative papers and findings were, it was truly an astonishing story. So, take dementia. Take dementia and hormones. One of the big scare story is, “Taking HRT increases a woman’s risk of dementia. Oh, really? Oh, my God. Let’s scare us even further. It’s not just breast cancer, it’s dementia, and it’s heart attack, and stroke, and thousand to pick.” Fine. We look at what they did with dementia. What they did was, they’re doing now a sub study of their major sample. We now eliminate all the women with healthy cognitive functioning. We just leave them out, and now we take a sub-sub sample of women who already have mild cognitive impairment, and we follow them over time. Guess what? We discover that women with mild cognitive impairment get worse. We don’t even look to see whether women who do not have mild cognitive impairment are how they are affected by taking hormones. 

They manipulated their data this way in on almost every scare story that they came out with. Then interestingly, as I say it for me as a social psychologist, where are the headlines, where’s the press conference, where is the press conference now 20 years later saying, “Hey, everybody, guess what? We’re really sorry. We scared y’all. But actually, we were wrong, we apologize.” They come out with paper after paper showing this, but there has been no national attention to this walking back of their original findings the way there was to begin with. We have our publisher led us right up an afterword to our book, which had come out a few years ago and editions of the book going forward will have this new afterword. But basically, what it says is, “the Women’s Health Initiative has walked back almost just every single one of its early scare findings.” We’re still waiting for the press conference.

Avrum: The best example of the manipulation of data is a year after the Women’s Health Initiative was first published in July of 2002, there was a 2003 paper saying that hormones have no effect on women’s quality of life. 

Carol: [laughs] Oh, yeah. That was good.

Avrum: The question is, what planet were you studying? Because clearly on this planet, that’s not valid and that was the abstract in the headline. In fact, Gina Kolata in the New York Times wrote a piece saying, “Not only do hormones do all these bad things, it doesn’t even improve quality of life.” Well, when you look at the study, and you have to read the article, the article said, “This is a prospective, double-blind randomized study,” which means neither the patients nor the physician knew whether the patient was getting the hormone or a placebo pill. We the investigators knew that symptomatic women, women with menopausal symptoms, who were randomized to placebo would drop out of the study and we didn’t want to lose so many women entering the study. We selectively chose only those women who didn’t have symptoms. By the way, the women who didn’t have symptoms had no improvement in the symptoms they didn’t have even if they got hormones. 

Carol: [laughs] Yeah, make this up. 

Avrum: When you look even further, they said, “Well, actually 13% of the women did have symptoms.” Yes, those 13% did have significant improvement, but that was swallowed up by the other 87% that didn’t have symptoms. So, the overall conclusion is it has no effect on quality of life. 

Cynthia: It’s just unbelievable. There was a term in your book that I wanted to interject, because it seems timely data mining. The concept of data mining, it’s when researchers fail to find a statistically significant association. They hypothesize would exist between a possible risk factor and a disease, go back into their data, and rummage around looking for factors that might show a statistical link.

Carol: There must be a pony in here somewhere, right? That’s what that’s about.

Avrum: There is a very good example of that. In Lancet, there was a study published showing that men, who were admitted to the hospital with a heart attack, who took aspirin had a better overall prognosis. They did better, they survived better than men who weren’t on aspirin at the time they had their heart attack. They sent that article into the Lancet, which is a very prestigious British publication. The Lancet editors said, “Well, we like that study and we’d like to publish it. But we’d like you to stratify the population. We want to know the age of the men, and the race of the men, and maybe what they ate.” The author said, “Well, we didn’t study that. Those might be appropriate future studies, but we didn’t study that. Beforehand, we didn’t state that that was what we were going to be studying. So, why don’t you just publish our overall result. Then these additional studies could be done later.” Lancet said, “If you don’t stratify your population that way retrospectively, we’re not going to publish the paper.” “Good enough,” the author said. We’ll stratify and they did. 

They stratified by everything including astrological sign. They found that men born under two astrological signs that might have been Leo and Taurus, but I don’t remember, actually did better than men who were born under all the other astrological signs, whether or not they got aspirin. The editors of Lancet said, “Well, we will accept the paper now, but you have to lose the astrology.” The author said, “Not a chance. You wanted us to sub-stratify. You publish the paper.” They did. So, the paper is published with the astrological signs, but it points out the absurdity of sub-stratifying already studied data.

Carol: Let me add an explanation of why you don’t get to do this. It seems counterintuitive that you shouldn’t be able to go back and rummage in your data and see what might be lurking there. The reason is that when you’re doing a study, especially in epidemiology, where you have many, many hundreds or even thousands of people in your study, the thing you’re looking to study is what you’re looking to study. But if you then go back in and look for other relationships, you will find some that are significant just by chance like the astrology finding, just by chance. But because it’s not been part of your original study protocol, you don’t know if that’s a chance effect or a real one. If by the way you see it, you don’t publish it, you then go and do a study, [unintelligible [00:44:27] astrology really make a difference with heart disease. It seems counterintuitive, but it’s really important to understand. We saw in our book over and over again, over and over and over again when researchers failed to find a connection between HRT and some disease or concern, notably breast cancer. They didn’t say, “What good news? Hurray, there’s no relation between HRT and breast cancer. Let’s go publish that.” No, they said, “There’s got to be something bad in here somewhere. Let’s just keep going until we find it.” Sometimes, their findings were just as preposterous as the astrology. Among 10 women, six were more likely to get breast cancer. The numbers were preposterous, but those got the publications and the attention.

Cynthia: Really amazing when you think about it that the more we understand about how research is done. There’s good research, there’s bad research, there are people who have high integrity or doing research, and then others who are not. But ultimately, it can trickle down to our lives. That’s why it’s so important that we’re made aware of what goes on. I would love to touch on and I know this is a probably hot topic. You get this question quite a bit. When we’re talking about synthetic hormones versus bioidenticals, there were a lot of questions. When I indicated on social media that we were connecting that women really wanted to better understand the existing research, is there superiority of one over the other? Because there’s so much misinformation along with compounding. That’s another hot topic. A lot of confusion and analysis paralysis.

Avrum: Well, each one of us could talk about this for the next hour and a half. 

Carol: [laughs] 

Avrum: Let me try to summarize it in just a few sentences. First, the word ‘synthetic’ is pejorative. Any hormone that you buy from any pharmacy, it doesn’t come straight from whatever. It is processed intensively. The Women’s Health Initiative used Premarin as their form of estrogen. Premarin is an acronym for a pregnant mare urine. You can’t say pregnant mare urine, nobody would buy it, so Premarin. Because the Women’s Health Initiative incorrectly showed that hormones do these bad things. It was a marketing niche so people could say, “Well, sure, Premarin is bad.” But I have something here which isn’t Premarin, which is hormones. Whatever words you want to use to market it, I’m going to use, so that bioidentical sounds really good. Bioidentical, does that mean you’re taking it from another human being and it’s just like mine? No, actually, we’re taking it from a yam. Well, I’m not a yam. Well, no, but we can work on the yam, put it through a lot of chemical processes, and we can extract estradiol, which is the form of estrogen that is the most common, the most concentrated form of estrogen in the body of a premenopausal woman, and we will give you estradiol, and to help sell it, we’re going to call it bioidentical and boy, did it work? That it isn’t Premarin, it’s bioidentical whatever, and it sells very well. It is only estradiol, almost only estradiol. Premarin has at least 10 different estrogenic compounds in it and Premarin is the best studied. We’ve studied Premarin now over 60 years. We know more about its benefit and its problems than any other form of hormone. It’s for that reason only that I like Premarin. 

One investigator once said to me, this isn’t the major investigator and has nothing to do with the Women’s Health Initiative. “Well, why would a woman want to taste a pill that tastes like urine?” I had to take a Premarin and bite into it. I didn’t swallow, but it doesn’t taste like anything. 

Carol: [laughs] 

Avrum: No surprise. Bioidenticals did so well that there are now people around the world, who say, “I’m going to customize your hormones. I’m going to take samples of your urine, and your hair, and your saliva. I’m going to see exactly what you need and I’m going to fashion a hormone formula that will be developed just for you.” Well, bioidentical hormones, never mind the name, that are FDA approved and put out by respected pharmaceutical companies are fine. We could talk about the differences between Premarin and those, but Carol and I have no problem with those. Compounded bioidentical hormones are done by individual pharmacies along the lines that this is compounded, especially for Mr. or Mrs. X. Well, first, that specialization is inappropriate. We don’t know enough to be able to make individual preparations for people. It doesn’t really matter. There are ways of assessing adequacy of hormone replacement and that’s not one of them. 

But my biggest problem with that is compounded bioidentical hormones are not FDA approved. The few studies that have been done looking at the quality control within compounded bioidentical hormones have found wide variation, so that, although, there are compounding pharmacies that are meticulous and do a very good job of many, many compounded bioidentical hormones have either little or too much hormones in them, and it’s just not a responsible way of prescribing hormones. The one exception might be in women who are allergic to components of hormones, who really need preparations that are made for them, and made without the allergen that can cause an allergic reaction in them. That’s more than two sentences. But that’s what I have.

Carol: I would add to this that this has been a way, women have known that estrogen benefits them. They feel better when they’re on estrogen. These products and you go into a drugstore and you see a zillion things with estrogeny like names. You know what? The idea is okay, you’re not supposed to have real estrogen, because we know it causes breast cancer. But since we also know that you want to take estrogen, here are these estrogen-like products that actually don’t contain estrogen or that contain estradiol. It’s a way to help women direct them to what they know will benefit them, but without the fear. I would say one of the thing about this targeted to each woman, you’re now, this is your own medication, especially for you, I think it also reflects the uncertainty, loneliness, and anxiety that women in menopause feel in a culture that is so disdainful of menopause. Because menopause for women raises so many psychological concerns. Of course, change of life, and I’m getting older, and this is changing, and that’s changing, and I don’t like any of it, and what can I do. It’s still considered what unseemly, slightly squeamish to be talking about menopause. Here’s the doctor saying, “Just sit down here honey. Let me spend time talking to you about your feelings, and how you’re responding to menopause, and what your body is saying.” That in itself is I think what many women are seeking. Somebody’s taking their symptoms seriously, not dismissing them, not trivializing them, but maybe not giving them the best appropriate medication either.

Cynthia: I think that’s a really good point. It’s something that now that I’m a middle-aged person, I am exquisitely sensitive to the terminology, the words that women use, the language that women use to describe themselves, how they feel. In fact, I oftentimes will take notes when I’m working with patients, because sometimes, it’s painful for me to hear how they feel invisible, invalidated, negated. Oftentimes, they feel talked down to. I just want to touch on two more things. I want to be respectful of your time. I got a lot of questions about route of administration for estrogen in particular. Because for listeners, route of administration is speaking to oral, transdermal, absorbed through the skin, intravaginal estrogen, because there appears to be again, a lot of misinformation. There are a lot of women who want to take estrogen, but they’re not sure what the best route of administration is. I know I probably have a preference, but obviously, this is something I’m not doing with as much frequency as I once did. What are your feelings? What has been your experience in terms of what has worked most effectively and what has protected women the most?

Avrum: Genital urinary syndrome is the syndrome, where a woman has drying vaginal mucosa, so that it can burn when you urinate, frequent urinary tract infections can complicate your life, sex is not only not desirable, it’s often painful even if you force yourself to have it, and if that’s your major symptom and that affects the overwhelming majority of menopausal women. Unlike most of the symptoms of menopause, which might clear over a median follow up or seven and a half years as Carol said, that just gets worse and worse. Intravaginal or transvaginal estrogen is very good treatment for that. To date that is approved without reservation. That doesn’t seem to be a problem. Women with a history of breast cancer can take it. It’s not an issue. I don’t know anybody who puts up an argument against intravaginal or transvaginal estrogen.

Carol: I just want to add one, if I may interrupt— Just one point about this, because I know a number of sex therapists and sex researchers, who tell them that they tell their patients go home and get a vaginal tablet that it’s completely safe, even the Women’s Health Initiative says it’s completely safe. They get it, they go home, and they read the instructions, where there is a black box warning that’s still there from the FDA. “This medication increases your risk of breast cancer, and uterine cancer, and hangnails. Don’t take this.” So, they don’t. They know they say, “Gee, I’d rather not have sex than die.” So, just to say that those alarmist warnings are still with that product.

Avrum: Okay, and that brings us to the pill versus the patch or the gel. Most of the studies have been done on the pill on oral administration. The pill helps brain function better than the gel and the pill may be better protective for heart disease in the future more than the gel. These differences are very small, which is why it’s important that you have a discussion with your doctor and work out what’s best for you. The biggest advantage to the gel over the pill is, there is a lower risk of venous clots of clots in veins called thrombophlebitis. It’s important to separate a clot that develops in a vein, which can cause swelling of your leg usually, and a clot that develops in an artery, which can block circulation to your heart or your brain. We’re talking about clots that develop in the leg, in the vein, not in the artery. The difference is very small. The difference is something like 20 out of 100,000 women taking hormones for a year will develop a clot in a vein compared to women who aren’t taking hormones for a year. 20 people out of 100,000. It’s actually 20 out of 100,000 for women who don’t take anything, 40 under 100,000 who take the pill, and 60 out of 100,000 of women who are pregnant. That’s a risk. But it’s clearly a very small risk. 

If I can just circle around to one of the things, we’ve spoken about breast cancer, we’ve spoken how it’s a red flag, we’ve mentioned that estrogen alone decreases the risk of breast cancer by 23% that the major standing finding of the Women’s Health Initiative is the combination of estrogen and progesterone they say increases the risk of breast cancer. Carol and I challenged that, and it’s challenged in the medical literature, and this will be in the afterword as well. What the Women’s Health Initiative found is progesterone is given to women, who are taking estrogen and still have a uterus. Because estrogen alone does increase the risk of endometrial cancer or uterine cancer. If you take progesterone as part of your hormone replacement therapy, that increased risk is eliminated. Women who are taking the combination are still told, “Well, that can increase your risk of breast cancer.” That’s really strange. We used to think in a simple way that estrogen causes breast cancer. After all, it happens hundred times more common in women than in men, it must be estrogen. 

One of the things that women Health Initiative did tell us is actually, followed now for over 20 years, although, they took it for only two years. There was no increased risk of breast cancers, there was even a decreased risk of breast cancer. Progesterone, women who are congenitally deficient in progesterone have five times the risk of developing breast cancer compared to women, who aren’t deficient in progesterone. Progesterone is as effective as tamoxifen in the treatment of measurable growing breast cancer. Why should the combination of estrogen and progesterone increase the risk of breast cancer? Well, it doesn’t. What the Women’s Health Initiative found is, if you look at the women, who got estrogen and progesterone and compared to the women who got a placebo, there was an increased risk. But it wasn’t that there was an increased risk among the women taking the hormones. There was a decreased risk among the women who were taking placebo. That is a different placebo group than the group that was compared with the group taking estrogen alone. That’s an increased risk, but the increased risk isn’t because of something that the combination is doing. 

The question is why does that particular control group have a reduced risk of breast cancer? The answer is, women in that control group, a significant number had been taking estrogen before entering the study and being randomized to the placebo. We just said that estrogen seems to decrease the risk of breast cancer. If you reanalyze the data and simply eliminate the women who had been taking estrogen before starting placebo, the control group risk rises and the difference disappears. Thus far, the Women’s Health Initiative hasn’t addressed that issue, although, it was reported in several journal articles challenging them. They haven’t responded to it thus far. By the way, even the Women’s Health Initiative that said, “There’s an increased risk of breast cancer if you take the combination,” a statement we are challenging say, but there’s no increased risk of death from breast cancer, if you were taking home–

Cynthia: Well, this has been an incredible conversation. I could probably speak to you both for hours. What are you working on next? Are you doing any new book? I know that now things are starting to open up at the tail end of the pandemic, I hope. They’ll probably be more speaking opportunities for you as well.

Carol: [laughs] 

Avrum: [crosstalk] is really the unknown. As you might be able to tell from this interview, Carol and I really enjoy working together. How could you not enjoy working with Carol now that you see who she is? 

Carol: I feel that way about him. 

Avrum: Yeah. 

Carol: [laughs] 

Avrum: I’m looking forward to a lunch date that we’re going to have in a week, which is really nice. Long-term plans are all in abeyance until we see what happens with the pandemic and the world. My God, we are right on the threshold of a possible war in Europe, which is frightening. As far as writing another book, we actually are halfway through a book that we wrote before this one, but I’m not sure that’s going to develop into a book and we’ll have to see. 

Carol: Have to see. 

Avrum: Carol?

Carol: I continue writing about mistakes in science and medicine, the resistance of people to admit they might have been wrong in a belief. My book with Elliot Aronson Mistakes Were Made (But Not by Me) could have had a whole chapter on the estrogen HRT issue, because it’s about how difficult it is for people to change their minds when the evidence finally shows that it’s time. Well, we’ve seen that in our country, have we not with vaccines and with health issues of all kinds, the polarization of these issues, and what does it take to get people to say, I was wrong, not such an easy thing. That keeps me rather busy. Of course, I often use the HRT example in my own talks and writings. So, that’s what we’re doing. [crosstalk]

Cynthia: No, thank you so much for your contributions. As I stated before and I’ve been very transparent with my listeners that I believe in taking inspired action, and listened to your podcast in November, and immediately reached out, and I got an immediate response. I’m so very grateful that your incredible book, which is part of my must reads for my ladies. I’m so grateful for the work that you both are doing and I look forward to continuing to follow your progress.

Carol: Thank you so much. Thank you.

[outro]

Cynthia: If you love this podcast episode, please leave a rating and review, subscribe, and tell a friend.