← The Peter Attia Drive
The Peter Attia Drive
#348 ‒ Women’s sexual health, menopause, and hormone replacement therapy (HRT) | Rachel Rubin, M.D.
02:13:28
Rachel Rubin is a board-certified urologist and one of the nation's foremost experts in sexual health. In this episode, she shares her deep expertise on the often-overlooked topic of women’s sexual health, exploring why this area remains so...
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- [00:11]
Peter Attia
Hey everyone. Welcome to the Drive Podcast. I'm your host Peter Attia. This podcast, my website and my weekly newsletter all focus on the goal of translating the science of longevity into something accessible for everyone. Our goal is to provide the best content in health and wellness and we've established a great team of analysts to make this happen. It is extremely important important to me to provide all of this content without relying on paid ads to do this. Our work is made entirely possible by our members and in return we offer exclusive member only content and benefits above and beyond what is available for free. If you want to take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of a subscription. If you want to learn more about the benefits of our premium membership, head over to peterattiamd.com subscribe My guest this week is Dr. Rachel Rubin. Rachel is a board certified urologist and one of the nation's leading experts in sexual health. She is among a select group of physicians with fellowship training in sexual health for both men and women, bringing a rare and deeply informed perspective to her clinical work. In our conversation today, we focus on women's sexual health. We discuss why sexual medicine, particularly for women, remains so neglected in traditional healthcare the critical difference in how men and women experience hormone decline with age the physiology of the menstrual cycle, including the role of estrogen, progesterone, FSH and LH and why perimenopause is characterized by extreme hormone fluctuations the risks of menopause beyond just symptoms like hot flashes, including the risk of osteoporosis, cardiovascular disease, dementia and recurrent UTIs the long standing controversy around HRT and how a single study, the Women's Health Initiative study, led to decades of fear based medicine and an entire generation of women, by my calculation, more than 20 million deprived of the benefits of HRT how to use estrogen, progesterone and testosterone therapy for women, including dosing delivery method such as oral transdermal, vaginal and why personalized care is essential the overlooked role of testosterone in women's health both before and after menopause the benefits of local vaginal hormonal therapy, a safe, inexpensive and underutilized treatment that prevents urinary tract infections, improves sexual function and dramatically enhances quality of life in postmenopausal women this is a podcast in which I learned a lot, even though I like to think I know quite a bit about this already. But Rachel's expertise here is second to none and I was feverishly Taking notes throughout, and obviously can't wait to implement many of the things I learned into my own clinical practice. So without further delay, please enjoy my conversation with Dr. Rachel Rubin. Rachel, thank you so much for making the trip out to Austin. I have been looking forward to this episode for a while, and I am willing to go on record predicting that this will be a very popular episode given the nature of our discussion.
- [03:22]
Dr. Rachel Rubin
I am so thrilled to be here. I have been nervous for quite a long time, but I'm super happy to be here.
- [03:27]
Peter Attia
I almost don't know where to begin, but it might not be a bad idea to just give people a little bit of a sense of your background. You are a urologist by training. And maybe help us understand how your training in urology led you to what you're doing today. Because most urologists wouldn't be doing exactly what you're doing. When we think of urology, we think about prostates, we think about kidneys, we think about bladders.
- [03:53]
Dr. Rachel Rubin
Yes, but what you forget, Peter, is that urologists are ultimately the quality of life doctors. We deal with urination problems and we deal with sexual medicine. Right. No one cares about erections and orgasm and libido quite the way that a urologist cares about. And when we're board certified, actually, it's not a gender thing. We're not penis doctors only. We're board certified to take care of everybody's genital and urinary tracts. Unfortunately, society has led us to know a lot more about the men's sexual health and men's genitals than female genitals. And so my background, I trained in urology really, because I was interested in women's health, but I also was interested in sexual health, sexual medicine. And I didn't like delivering babies, I didn't like ob gyn. It just didn't fit well with my personality. And what I love about urology is that we can see everybody and we can really dive deep on quality of life issues. And the magic of urology is also that you really get to know your patients. It's not like when you did surgery, you take out someone's appendix and you never see them again. Maybe you do one post op visit. Urologists have deep relationships. We're both surgeons, but we actually care about the medical side of these quality of life issues. And so as I was going through medical school, I really realized that talking about sexual health, quality of life issues, that was fun for me. I was good at that. And in medicine, you gravitate towards what is easy and not what is hard. And so it's just been a joy. And really, I have been working to further the field of urology to make us better at taking care of women. And so really, I do a lot of educating and teaching to my colleagues about how we really need to care about the whole. Like everybody.
- [05:31]
Peter Attia
Yeah. And I really mostly want to talk about it from a female standpoint today, truthfully, because I think this is where there's just a dearth of great information out there, where I think there's an abundance of garbage information out there. So while I appreciate that your breadth of knowledge will cover both sexes, you'll probably notice kind of a bias in what I want to talk about vis a vis women specifically. So let's start with perhaps the biggest and most obvious difference between men and women. And that is from an endocrine perspective, women go through this period called menopause, which is a rather sudden and abrupt loss of their sex hormones. And that's to be contrasted with the way men's sex hormones decline over time, a little more slowly. So, again, the listeners of this podcast are highly erudite and they won't need the lengthy dissertation, but just give us a quick overview of what the heck is happening in menopause, why is it happening, and then we can get into maybe what some of the symptoms are before women might really notice them.
- [06:33]
Dr. Rachel Rubin
I certainly did my research, and I am not a car person, but I know you are a Formula one guy, and I got a very interesting email last week that said, Dr. Rubin, my wife is seeing your practice. Her libido is now like an F1 Formula One race car. And I'm like a 1988 Honda Civic. What can you do for me? My analogy I really like to look at is sort of the gas tank analogy, this idea that men, as they age, sometimes we see a decrease in their gas tank. They're feeling low, they're feeling down, they've got erectile dysfunction, low libido. Whereas women at age 52, their gas tank is empty. This is a castration event. We don't have many castration events in men's health. And so menopause is sort of a. Your gas tank is officially empty. There's not much in the tank. Perimenopause is this time where it's very erratic. The gas tank is over full, and then it goes to empty really quickly without warning. And so I like that analogy because I think it's helpful when we're talking to women about the reason you don't feel like yourself is because there's just no gas in the tank. So we see the ovaries are no longer producing estrogen, progesterone and testosterone the way that they were during your reproductive years.
- [07:43]
Peter Attia
I love that analogy. I've never heard it before, but it absolutely replicates what of course, we see clinically, which is in perimenopause. Why do we sometimes, when we're measuring a woman's labs, say every three months, see periods where estradiol is through the roof, FSH and LH are low, and three months later it's completely flipped. And of course, with it go symptoms. So can you explain why there's this? If we have hormones running like this during pre menopause, they're like this during menopause. But this transition is nothing linear.
- [08:20]
Dr. Rachel Rubin
It looks kind of like the stock market, actually. It goes up, it goes down, and it's not even just checking it every three months. If you check it every 10 days, you're going to see a fluctuation. I'm obsessed with looking at the menstrual cycle. I'm obsessed with talking about numbers here because it is so fascinating and we are not taught to think this way. And so I have a lot of curiosity about it. So, for example, when you're in your, let's call it, healthy reproductive years, and by the way, nobody is the book, you talk a lot about continuous glucose monitors. I would love continuous sex hormone monitors. And unfortunately, I know there'd be a lot of unintended consequences and bad things that would come of it, but I'd be very interested because the book says our low. So if you have your period that you're Bleeding, that's day one, your low is not zero. In fact, it's probably somewhere 40. 50 is probably what the low should be of estradiol, and that's picograms per milliliter, as opposed to testosterone, which we do nanograms per deciliter, as you know. So PI, let's say 50 is your low. Then you go at ovulate and that's in your mid cycle. And usually it's about 1 50, let's say ish, maybe it's 200, 300, whatever it is, pregnancy, your level is 3,000 or higher, right? It's very high. And so if you are in your normal reproductive cycle, you go from 50 to 150. So let's use the gas tank analogy. You're at a quarter tank at 50 and you go to 3/4 tank at 150, then down to a quarter tank, you can drive wherever you want to go during that time. What happens in perimenopause? And it is this chaos and erratic fluctuation where your body is just wanting more hormone than it has your brain. Your FSH is telling your eggs to do more than they can. Sometimes they overshoot. So now you are overflowing gas. I had a lady come in her day one her estrogen was 200 and her day 10 her estrogen was 900. So this is this wild fluctuation in perimenopause.
- [10:13]
Peter Attia
And what I'd like to do now is make sure that. Anybody listening who wants a more nuanced overview of this, we're going to link to a video that I made a couple of years ago where I walk through the ovulatory cycle and I draw the graph of estrogen, progesterone, FSH and LH according to the nomenclature you're using by days. But let's also have you do an explanation now of the role of FSH and LH on the brain because you've already referred to that and what the feedback cycle looks like with estrogen. I just want to make sure people are following the physiology you're describing.
- [10:48]
Dr. Rachel Rubin
And that video is so fantastic. We actually were talking about it before doing this podcast about that video. And I said, you know, if you asked most OB GYNs to draw the menstrual cycle, many of them wouldn't be able to do so. It's incredibly complicated and it's so confusing and we think our doctors know everything and unfortunately they don't. And so what happens is estrogen, you have your period, your lining of your uterus is shedding, your estrogen is kind of at its all time low.
- [11:13]
Peter Attia
And again, just to make the obvious statement, it's because most of the time when a woman ovulates, she does not get pregnant, right?
- [11:20]
Dr. Rachel Rubin
In this non pregnancy state, you didn't make a baby, you're shedding the lining, your estrogen's about 50, let's say to make it easy. Now it's starting to go up, up, up, up, up. And you're developing this follicle. So this egg is developing and then the LH is sort of your brain's marker of, okay, it's time to ovulate. So that's when you pee on a stick and you're trying to check if you're ovulating, it's checking your LH levels. And so you're going to see this increase in lh. That happens again. Everyone's A little bit different, but it happens kind of mid cycle, day 10 to 14, somewhere around that. Again, urologist, not gynecologist. And so you get this LH surge. The egg pops out, and it is the shell of the egg that creates the progesterone surge. So you actually don't make any progesterone, really, in that first half of your cycle. And then after ovulation, we call the second half the luteal phase, which just means that's when progesterone is around. And so you get this surge of progesterone when there is no fertilization, that shell of the egg evaporates and then you lose your progesterone and it is that withdrawal of that causes the uterine lining to shed. Now, again, this is very confusing for people because hormones, through that time, your progesterone goes from very, very low to after you ovulate, very, very high. And it's that cycle every month. Now estrogen again goes from 50 to 150, back down to 50. That's what the book says. I don't know about you, but my patients are not all on the book.
- [12:43]
Peter Attia
Yeah, a lot of my patients don't read the book about what their physiology is supposed to do. It's very disappointing.
- [12:49]
Dr. Rachel Rubin
I agree completely. And so we're super interested in this. We care about how people are feeling. I may say this a lot during our conversation is there's the book answer, there's the Instagram answer, and then my answer somewhere in the middle is how we sort of talk about it and understand it. Again, I think the numbers are helpful for people to see. When you're pregnant, your estrogen's 3,000. When you're regularly ovulating, it's 50 to 150 perimenopause. It could be zero, it could be 1,000 and down to zero in two seconds flat.
- [13:19]
Peter Attia
So let's talk about why. So why is it that in perimenopause, the fluctuations in estradiol level are so dramatic?
- [13:27]
Dr. Rachel Rubin
I think it has to do with the fact that you have a limited number of eggs. You're sort of getting to that end of your bucket of eggs that you're born with. That's, again, controversial on the Internet. So your body is really trying to do what it has always done, and it's just having trouble. It's having trouble recruiting the egg. Ovulating, you don't ovulate every time. Sometimes you ovulate twice, push out two eggs in this perimenopause cycle. So we can sometimes see really high elevations, which can come with symptoms. And that's the challenge of perimenopause is sometimes you have symptoms because you're too low, sometimes you have symptoms because you're too high. And sometimes it's that fluctuation. Like again, we'll go to the car model, you're driving 100 miles an hour on the highway and you go to empty gas tank immediately, that is not good for a car. That is inflammation, that is irritation, that is a lot of perimenopause symptoms.
- [14:18]
Peter Attia
So maybe to extend the analogy, part of the reason why a woman during this period of time can experience these enormous surges of estradiol is if you think that there's, say, a kink in the gas line and you really, really want to squeeze the lever to get as much gasoline as you can in the car, sometimes you overshoot and just you get a whole bunch extra in there because there's volatility in the follicle release.
- [14:41]
Dr. Rachel Rubin
I knew you would like this analogy.
- [14:42]
Peter Attia
Yeah, no, I love it. The one other thing I want to talk about, because it's going to come up later when we get to hrt, is do you buy the argument, which is the argument I have found most appealing as to why women have varying degrees of sensitivity to the dramatic reduction in progesterone that they experience in the last quarter of the cycle once the lining sheds. So we talked about how, of course, during the luteal phase, we're building up, progesterone levels are rising, we're building up the endometrial lining in preparation for pregnancy. Most of the times that's not going to happen. Lining sheds, progesterone crashes. This is what's referred to as pms. And some women are somewhat unfazed by that. And other women, that's a big deal. And so the question is, is this about central receptors of progesterone and varying degrees of sensitivity?
- [15:33]
Dr. Rachel Rubin
I think it's a really important question. And we see this clinically all the time. If you give somebody, say, micronized progesterone or e synthetic progestin, say, in birth control, you will see a wide variety of reactions to these different medications. And so I would say it has to probably do with the GABA receptor in the metabolites of progesterone and how the receptors in the brain use these molecules. And so I think we just don't know enough. You know, I tell my patients all the time, I wish, oh, my gosh, we have so much work to do in women's health. We have so much research we need done. This is why I come on this platform. Not because I want to be on this platform, but I need smart people to be listening to this, to ask the research questions and to do this research. Because clinically, we see this all the time. I will put up that menstrual cycle with my patients and say, when do you start to have symptoms? Are you having symptoms when your estrogen is falling? Are you having symptoms when your progesterone is falling? And can we hack this system to help you feel better? And how are you going to respond to it? Because when we give someone micronized progesterone, I would say a third of the patients love it and guzzle it like it's candy. And they're the happiest people in the world. Helps their sleep, reduces anxiety.
- [16:40]
Peter Attia
Oh, my God. Changes their life.
- [16:41]
Dr. Rachel Rubin
Oh, it's absolutely life changing. A third of the patients are like, I don't really notice. It doesn't bother me. I was fine, like.
- [16:47]
Peter Attia
But if you tell me I need to take it, if you tell me.
- [16:49]
Dr. Rachel Rubin
I need to take it to protect my uterus, no problem. And then you've got a third of patients who are very sensitive. And even within that third, it is extreme. I mean, we see progesterone allergies where people have horrible reactions. Two, it makes me too sleepy. It makes me feel bloated. I don't like this. And so I don't, as a clinician and an interested researcher, like, I don't know exactly enough to be able to spot who those people are ahead of time.
- [17:13]
Peter Attia
Okay, so we've established now what's happening. We've established that during the period of perimenopause, the one consistent thing that's happening is inconsistency. At some point, we get to the place where the consistency returns. But now it's a new norm. And that new norm is you don't make estrogen, you don't make progesterone. The signal from your pituitary FSH and LH begin monotonically rising, rising, rising. And so if you were to do the blood work of a woman in her 60s who had never been placed on HRT, you would see a very high FSH, a very high LH, usually above the lab's cutoff for measurement, and then estradiol and progesterone non existent. Let's talk about all the reasons why that woman that I just described in her 60s, who is now 10 years out of any hormones, what are the risks to her physical health, mental health, emotional health, the whole picture of her health, cognitive health, everything. What is she worse off for at that period of time?
- [18:17]
Dr. Rachel Rubin
So I think this is a really important question in the sense of what is the risk of taking hormone therapy in that patient? And what is the risk of not taking hormone therapy? Yeah, that's why I want to start with this. And so I think it's super interesting because we love talking about the risks of medication, but we don't spend a lot of time talking about the risks of not taking medication. So if we think about that woman as she gets older, she certainly will have the microbiome and genital and urinary changes of not having hormones. So as a urologist, this is actually one of the couple things that will kill her. As you lose hormones in the genitals, which are very hormone sensitive, the bladder is very hormone sensitive, you change the microbiome, you decrease the acidity of the tissue, the bad bacteria grow, your risk of urinary tract infections increase drastically. So she may get recurrent urinary tract infections or pelvic pain. She may develop osteoporosis, which we know. More people die of hip fractures, about the same die of hip fractures as die of breast cancer. So the risk of not taking hormone therapy when you get a hip fracture, as all of your listeners know, going back to the life that you lived is very challenging, or you die. There's also the risk of dementia and Alzheimer's much higher in women. And we can argue the data, and I don't think we actually have good data about whether hormones, when to start them, and if they're actually protective and how they're protective. But we also know that heart disease is the number one killer of women. And we know that things get worse as you get older. So I think there are significant risks to that person. And from the mental health perspective, I think there's no question that we see worsening. Now, I will say perimenopause, from what I understand of the data, is actually worse on mental health and can actually level out a little bit once there's less erratic hormones. But again, an empty gas tank is still an empty gas tank. And so we see a lot of challenges in this time period.
- [20:02]
Peter Attia
We talked about, obviously, the risk of dementia, we talked about the risk of osteoporosis, cardiovascular disease, colon cancer. All of these are risks that are pretty clearly going up in the absence of hormones. So do you want to talk about the history of hrt? I mean, it was a largely normal practice in the 1960s, they certainly had some fits and starts. They initially were just replacing estrogen. Figured out pretty quickly, that is, within a few years, that if you only gave a woman estrogen, you were going to run the risk of endometrial cancer going up, because the. The endometrial lining just continued to get bigger and bigger and bigger, and you eventually developed hyperplasia, which presumably became metaplasia, and ultimately cancer. We figured out pretty quickly how to combat that. If you just oppose the estrogen with progesterone, keep the endometrial lining in check. And this largely became the standard of care through the 1980s and into the 1990s. And this was largely validated by epidemiologic observations which showed that women who took hormones did significantly better. Now, people who listen to this podcast are well aware of how critical I am of epidemiology. And it's certainly very easy to make the case that in the 1980s, women who were taking hormones had a healthy user bias. These are women that probably had better access to healthcare. They were probably more health conscious, and as a result, they were probably doing many more things to improve the quality of their health. So the NIH did something that I think made a lot of sense. It was the right thing to do, which was they said, look, we can't rely on this epidemiology. We need to do a randomized control trial. And they did it through something called the Women's Health Initiative, which had two components. A nutritional component that was asking a question about low fat diets, and then a component that was looking at the hrt. So would you like to pick up the story as to how the study was designed, maybe talk about some of the potential pitfalls of it and ultimately how the results of that have been misunderstood and misinterpreted for so long?
- [22:09]
Dr. Rachel Rubin
The fact that this story hasn't been made into a Hollywood biopic mega drama, I don't know. This is a big deal. A billion dollars of our resources went into doing this study. And there are many things that we learned that were helpful and useful. And this huge set of data that we're still using today to extrapolate information from. And there was a lot of good that came from it, but there was a lot of misinformation and just really bad marketing or really effective marketing, you could argue. Because what is so wild, Peter, is that when this study came out, they did a press conference. Before the study was published, they did a press conference. Have you ever seen the NIH do a press conference that Matt Lauer talked about or that was made it on Good Morning America. Like they did a press conference. I remember, I was in medical school at the time. Like, I remember this happening. And they said, okay, we had to stop the study early. It is increasing the risk of breast cancer and increasing the risk of blood clots and cardiovascular disease and we have to stop the study. There's different statistics out there, but people will say about 40%, maybe of women were on hormone therapy at the time. Overnight, it crashed to nothing. You're talking billions of dollars of an industry went to nothing. And the people who are prescribing the hormone therapy were like, this doesn't make any sense. I do this. I've been doing this for 20 years, 30 years. I don't have a clinic full of people who are dying of blood clots or heart attacks or who get breast cancer. Like, this is not my clinic. Whose clinic is this? Then they published the paper and as we talked about before we did this podcast, is that they misinterpreted the data so drastically and scared everybody with so much fear that you actually have an entire generation that has forgotten how to prescribe hormone therapy. And this is the nightmare that we're living in today because now we realize that the data was misinterpreted. So that whi was one medication, one dose, that's it. And it was a sort of birth control pill style kind of hormone therapy. So a synthetic estrogen and progestin. It was not the, what we call more. And we can talk about the marketing term bioidentical, but the FDA approved products that we use today like estradiol and progesterone. They're different medications that we use today. And so you're talking one medication, one dose. And we are still practicing fear based medicine 30 years later. Whatever it is saying, like we don't practice any other medicine like this. We're like, well, there was one study about surgery 30 years ago and that's the way we practice medicine. We evolve, we learn new things. So what did it show? Let's talk about the good. When you took estrogen and progestin or estrogen alone, you had a decreased risk of colon cancer. You had decreased risk of fractures. Like significant decrease of fractures, decrease of diabetes. Okay, that seems like a good. Those seem like all good things. This is in the hormones. We don't even really prescribe anymore. We saw a decrease in overall mortality, a decrease in cancer specific mortality. And then when you looked at the cardiovascular data over time and again, I'm a urologist. I'm not a heart expert, but you saw there was actually no difference. It actually wasn't so scary. Now, as you get older, we know birth control pills can cause blood clots, so we do worry about giving a birth control pill to grandma because you can increase blood clots. That's true. I agree with that. When it comes to breast cancer, the most fascinating data that didn't make the press conference, women who are on the estrogen alone, so they didn't have a uterus, they didn't need the progestin therapy, had a decreased risk of getting and dying from breast cancer. And it didn't make the news. Even in that study that put the box labeling on all the products, it's not true. So then when you looked at the estrogen and the progestin groups, there was a fear that there was an increased risk of incidence, but not mortality from breast cancer cancer. And even when you look at that data, there is questioning of the fact that the placebo group actually was more protected by breast cancer because many of them had been on hormones in the past. And when you use a correct placebo group, the lines actually go together. And so you're more of a statistics nerd than I am, but the reality is there was no difference. And so we scared an entire generation of people away from hormones because of a bad misinterpretation of statistics.
- [26:14]
Peter Attia
So, Rachel, I don't know how good you are at sensing a person's blood pressure from across the room, but if you were able to sort of project your vision into my carotid artery.
- [26:26]
Dr. Rachel Rubin
I see it bulging.
- [26:27]
Peter Attia
Yeah. You'd notice that my blood pressure is up. I'm probably at 180 over 120 right now. First off, I think that was a remarkable succinct summation of the whi. I'm only going to repeat a few things. Not because I didn't think you did a great job. You did. But because sometimes hearing it twice highlights the egregiousness of this study.
- [26:51]
Dr. Rachel Rubin
Shout it from every rooftop you can find.
- [26:54]
Peter Attia
Truthfully, I have friends, female friends, and I have patients who to this day are paranoid about hormones. And I just want to offer yet another opportunity for them to sort of understand what's going on. So this was a study that had two parallel arms. One where women without a uterus were just randomized to either this synthetic or equine based estrogen versus a placebo, and then one where if you had a uterus, you got mpa, a synthetic progesterone, and the estrogen. As you pointed out, the elephant in the room here, the one finding that got all of the attention was that in the women with uterus group, if you got the synthetic progestin and estrogen, you had an increase in your incidence of breast cancer. It turned out it didn't actually lead to any change in mortality from breast cancer, but there was an increase in the incidence. The number is really scary if it's given in relative terms. It was a 24% increase in the incidence. Incidence for the listener, meaning getting breast cancer. You had a 24% higher chance of getting breast cancer if you took the two hormones. On the surface, that sounds devastating, but again, as people who listen to this podcast know, we always need to think in terms of absolute risk. And relative risk doesn't mean that much if you don't understand absolute risk. So if I said to you, rachel, I have a treatment for you that is going to fix 100 problems, but it increases your risk by 100% of getting hit by an asteroid, would you take the medicine or not? Well, you'd have to know what your base level risk of getting hit by an asteroid is. And given that it's almost zero, doubling it doesn't mean anything. So the absolute risk increase for these women was 0.1%. So to put that in less technical terms, it meant, even if you believe the results of that study, and you've offered a great explanation for why the actual results should be questioned, but even if you take them at face value, for every 1,000 women who were put on HRT, an additional one got breast cancer, though she didn't die from it at any increase rate. To the women who didn't get the hormone, this to me, and I'd like you to push back on this, although I'm worried you won't be able to because you share my bias, this is the greatest injustice imposed by the modern medical system in our lifetime.
- [29:39]
Dr. Rachel Rubin
You are not going to get pushback from me on that. This is a disaster. I just got back yesterday from teaching at the largest internal medicine conference, acp, the American College of Physicians. And you're talking more than 20,000 internal medicine physicians. And what a wonderful thing. I was asked to give a course on female sexual dysfunction, and it was wonderful. I talked a lot about menopause. There was no other menopause content at this course. There was no courses how to prescribe. Given everything you've done, my colleagues and myself have done to bring it into just popularity. Patients are coming in asking questions, and there wasn't even a course to learn. I can't say that's true for GLP1s or any of these lipid lowering agents or all of the things that you've been pushing. The problem is you now have a brain drain, I think because the doctors who prescribed hormone therapy either retired or died and there was no one they taught ahead of them. Now, I was very lucky. I had very good mentorship and incredible experience. But we are now trying to make up for lost time to train people how to write prescriptions. So it's not enough to say, hey, the WHI was misinterpreted and we've done a bad thing for women. People don't know how to do this. It's a huge problem. And the reality is this is half the population, this is not niche medicine. The fact that menopause medicine is the tiniest little room of subset of gynecology, which it should not be under gynecology, this is whole body medicine. And yet nobody seems to care.
- [31:13]
Peter Attia
Yeah, it's really interesting to hear you say that because you're highlighting something that's as dramatic and potentially more dramatic than the thing I've tended to focus on. I've focused more. So maybe I just take for granted that I got lucky and I had amazing mentors and they taught me how to do this stuff. But it's also the nature of my personality to just be endlessly curious and show up in somebody's clinic for two weeks and do this. I've tended to focus on the lost generation of women. So I had my analysts do this analysis two years ago, and I don't remember the exact numbers, but the analysis was calculate for me or estimate for me the number of women who were deprived of HRT because of the whi and calculate the excess mortality that was achieved through that injustice, through hip fractures, cardiovascular disease. We just went through the entire list. Calculate the number of lives that were lost, the amount of disability that was incurred, because to your point, even if you don't die from a hip fracture, 50% of survivors never regain the same level of function. And I didn't even know how to quantify all of the sexual side effects that women unnecessarily endured. All of the vasomotor side effects that they unnecessarily didn't even try to quantify that because I don't know how to. But that's the thing that I focus on. And again, it's personal to someone my age because my mother and my mother in law are in that category. They're the ones that got absolutely screwed by this system. You're highlighting something equally catastrophic with potentially a greater impact, which is we failed to train a generation of doctors to do anything about it. And if that's not reversed, the problem doesn't get much better.
- [33:00]
Dr. Rachel Rubin
Yeah, I mean, the data is very clear on this. Less than 6% of internal medicine, OBGYN or family practice doctors get even an hour of menopause education in their training. Do you remember learning about menopause in your medical school? 01 minute. I didn't learn one minute of it.
- [33:17]
Peter Attia
I did learn that hormones were bad.
- [33:19]
Dr. Rachel Rubin
Oh, yeah, you learned. Right, Right. So because you are taught hormones are dangerous, or the bodybuilders take the hormones, the snake oil salesmen take the hormones, we don't talk about this in real medicine. Everyone says, it's not my industry, it's not my thing. I went to this internal medicine conference yesterday, and all the internal medicine doctors were saying, but this isn't my field. I don't feel comfortable. Right. An endocrinologist was standing there saying, I don't feel comfortable doing this. I said, you're a hormone doctor. That is what you do. It is so embarrassing. I've been asked to speak at multiple academic centers to teach on hormone therapy. And every time I'm like, is this real life? I am a urologist teaching hormone doctors about how to prescribe hormone therapy. And it is real life. And this is why I'm so loud about it, because we have to change this. We have to change this on a big level, because I need the ICU doctors and the pulmonologists and the heart doctors and all the doctors to know that menopause affects their organs. Colon cancer. Why aren't GI doctors talking to women that estrogen prevents colon cancer? Why are we checking dexas at 65? Why are rheumatologists not prescribing hormone therapy? I found out recently that psychiatrist. Because I do a lot of teaching about how to prescribe hormone therapy. A few of us are very passionate about it. And I was like, sit with me. I will teach you how to write the prescriptions. I've had psychiatrists tell me their malpractice insurance will not cover them if they prescribe hormone therapy. And I said, wait a minute. You prescribe postpartum depression drugs, which are progestin based. You do reproductive psychiatry, which means birth control is a part of what you do, and you're being told you're not allowed to prescribe hormone therapy when hormone therapy is one of the greatest antidepressants in the history of medicine. It is insanity. We're living in a nightmare.
- [35:07]
Peter Attia
Let's talk a little bit about how we go about doing things. So there are two hormones we've talked a lot about, but there's a third that we haven't yet talked about that is very linked to these two hormones. Doesn't get enough attention in women. And of course that's testosterone. So before we get into how one should think about replacing hormones, can you talk about the relationship of testosterone to women's sexual health and what's happening to testosterone levels during this transition from peri to menopause? Because of course, I want to bring this into the HRT discussion.
- [35:40]
Dr. Rachel Rubin
Super interesting. And I'm very passionate about this topic. And so I think it comes from this idea that I do testosterone for men all the time. I'm very confident. I love prescribing testosterone for men's sexual health. And actually, very interestingly enough, when we prescribe testosterone for men, remember, their gas tank doesn't get empty, it gets lower. It's off label. We are doing off label testosterone therapy in men. Unless they have Klinefelters or some significant medical problem. We're doing off label testosterone for men. And it's very understood. It's talked about. The FDA just three weeks ago removed the labeling on testosterone therapy, saying it no longer is a cardiovascular disease risk. So that's great news. So the thing about women in testosterone is it's actually not a menopause thing. Testosterone is an age related decline. So in your 30s, you're starting to drop your testosterone and testosterone. I don't know who decided that men get testosterone and women have estrogen like we both have both of the hormones.
- [36:37]
Peter Attia
You've probably heard me make this point before because you alluded to it a few minutes ago. We measure testosterone in nanograms per deciliter. We measure estradiol in picograms per milliliter. If you normalize those to the same level, women are shocked to learn that they have 10 times the amount of testosterone in their body that they do estradiol at peak estradiol way more.
- [37:02]
Dr. Rachel Rubin
And I love sharing that when you put everything in the same units. We are testosterone driven beings. Both of us, right, Are testosterone driven beings. We don't teach this to OB GYNs. No, OBGYN knows some do, but very few know about the role of testosterone in women's health. And so we love to gaslight women and say, well, if you have your period, your hormones are normal. Drives me insane. Women are told this all day, every day is, well, you can't possibly have a hormone problem because you're getting your period regularly. And the reality is is that's not true. Why that curve? That curve we were just talking about? Testosterone is nowhere on that curve. And so we know there's a peak of testosterone around ovulation. That is nature's way of saying, let's make a baby. We know that. We know that your libido goes up around ovulation because your testosterone goes up. And so there is this age related decline in testosterone. And here's another big problem. We give women birth control pills all the time. How does birth control work, by the way? Birth control is high dose hormone therapy. We love hormone therapy and birth control. But as soon as you become menopause, everybody's afraid of hormone therapy. It makes no sense. So birth control is high dose. I would argue the hormone therapy we're talking about, the WHI that is more synthetic, that has side effects that have issues like that. So birth control turns off your ovaries and it adds back ethynetradiol and a synthetic progestin. It doesn't add back testosterone. So we are botching testosterone for women along the life cycle, to be honest. But if you take someone who's never been on birth control, their testosterone starts to drop in their 30s. So what are they complaining about? It's not just a libido thing. We know there are testosterone receptors all throughout the genitals and the urinary tract. So we see women have an increased risk of UTIs. We see an increased risk of pain with intercourse or pelvic pain conditions. We see there are some studies that indicate potentially depression and anxiety can increase because we do think there's a testosterone effects on the brain. But we have global consensus. And I don't know if you've read the news lately, Peter, but we don't agree on too much as a globe. But there is global consensus that testosterone in women works for low libido. And so specifically the data is on postmenopausal women. That's where the global consensus is. But there is data in perimenopause and much smaller studies before that. The consensus is it works, but everyone has emotions about testosterone. I didn't think testosterone was a feeling, but apparently it is a feeling for people because people hate talking about it. And again, nobody taught you how to prescribe it. And there's no FDA approved product for women except in Australia. It's approved by their governing body and so you have a lost art of knowing how to give people back testosterone when they are symptomatic.
- [39:45]
Peter Attia
I think this is an area where women sometimes are also a bit concerned about what happens if I take testosterone, because testosterone understandably conjures up images of all sorts of things, from large muscles, big mustaches, lots of other things. So how do you talk to women about this? We enjoy having these discussions and also acknowledging side effects. The most common side effect we see in women is acne. I don't think I've ever gotten to the point where I've seen any of the really dramatic side effects. But I do tell women, I say, look, there's a decent chance if you were shaving your legs every five days, you're gonna be shaving them every three days. That's a chance. If you were kind of susceptible to acne growing up, you might get a little bit more of it and we'll have to back off. How do you talk about the risks of testosterone therapy?
- [40:35]
Dr. Rachel Rubin
I love talking about this and I'm actually grateful for celebrities because just in the news in the past few weeks, Halle Berry says she's on testosterone. Kate Winslet says she's on testostero therapy. They look pretty amazing to me and they don't look androgenized at all. And so I actually want to do this study. It's something my research team's working on is I think I have more patients who never start testosterone therapy because of the fear of side effects than actually stop testosterone therapy because of the side effects. That's my observation in doing a lot of this. Now, when we talk about side effects, I tell them, think about a horny teenager. They have these great libidos, but they have some oily skin, acne. But that's when you get really high with your doses. We really don't see it clinically. Yes, I use FDA approved testosterone for men. Just it doses 1/10 the dose. In a way, they rub it on their leg because if they do get hair on their leg. People are used to having hair on their leg and so they shave it, they wax it, they laser it, whatever it is that they do with leg hair. I don't have that many patients stop for acne, oily skin. I think there's that fear when you get really high in the dose. So I'm not a pellet promoter or user because you get super physiologic levels and I can't take it out if you get a pellet put in. And so if you have deepening Voice or clitoromegaly, hair issues. These are the challenges with some of these super physiologic levels. But when we're using reasonably dosed topicals, we really see magic happen. And I can't tell you when we get estrogen and progesterone right for our patients, it is by adding that third piece that testosterone, because your ovary does, probably does more than three things. But at this point, estrogen, progesterone and testosterone. When we add that testosterone piece, it's wild. All the patients come back and they say, me, wow, I feel like me again. It's wild. That's the piece. Wow. I didn't realize how badly I felt. Wow. That was the missing piece. I hear it over and over and over again. I can't not want that for all women. I can't not want to give them that as an option on the menu.
- [42:31]
Peter Attia
So let's just finish the swing on testosterone. Do you prefer then to rely on the topical version of which would be like an androgel type product and just dose it at a much smaller dose?
- [42:44]
Dr. Rachel Rubin
Yeah, that's typically how we do it and how our guidelines look at it. So iswish the International Society for the Study of Women's Sexual Health. Fabulous organization. You can find any doctor to help you with menopause and sexual health by going to their website. They came out with a really lovely how to practice guideline that they took from the global consensus and they do recommend using that FDA approved testosterone for men and using it at appropriately doses for females. So I like Testim, which is sort of the 1% generic testosterone gel. I'll show it to you. I brought it for you to show you. It's a 5 milliliter tube of gel. Our male patients would use the whole tube of gel, rub it on their chest every day. I have very few men who do that by the way. Injections, orals, those are much better. And so I tell my patients use a blob or 0.5ml so they can put it in a syringe if they want to and dose out that 0.5 MLS. They take a blob, they rub it on their calf every day and so just don't use the whole tube. Should last you about a week or 10 days. It's an ish. It's not an exact precision science, but the patients can figure this out. It's not that challenging. I will say this and I think I have colleagues who disagree with me on this and I would love to know your Experience, I think testosterone, I think for men too, but that's my bias. It takes a while to kick in. I will tell patients you need to do this regularly. And I think it's going to be three, four, even five months before you're gonna really wake up and say, wow, this is working. Oh my gosh. Someone just walked across the street and I did a cartoon style head turn with my eyes popped out of my head. Oh my gosh. I initiated sex. Wow. That orgasm was easier to have. These are the things that patients notice. I also get patients telling me their stress incontinence is slightly improved. Why? Because the urethra has testosterone receptors in it. We know that for all genders. These are the kinds of things my patients will report. I don't know. What do you think? I think it takes a while. Hmm.
- [44:35]
Peter Attia
That's an interesting question. I mean, I definitely agree that that's true for some people. That said, I've also seen people who within weeks report feeling better. Now, the challenge here, of course, is the only way you could understand this is through blinding. We just don't know how significant the placebo effect is. And therefore it's hard for me to discount or know.
- [44:56]
Dr. Rachel Rubin
We have studies on testosterone which show.
- [44:58]
Peter Attia
Oh, sorry. I mean, within my observation.
- [45:00]
Dr. Rachel Rubin
I hear you. Yes.
- [45:02]
Peter Attia
I want to ask you another question about Natesto. So Natesto for the listener is a nasal formulation. It's an FDA approved formulation. In theory, it seems like a great idea. In practice, it has not really panned out just based on its messiness. It's a gel, a nasal gel. We've had women use it vaginally, nasally, like, what's your experience been with it?
- [45:25]
Dr. Rachel Rubin
It's getting harder and harder to find these days. And so I think similarly we've been interested in it and people have played with it before this idea. Can you one squirt into your. Nobody likes to squirt things in their nose. It turns out it's a challenge. Now, any of these topical testosterone formulations, a lot of them have alcohol in them. So I don't recommend putting them on your genitals directly. But I do think it needs to be studied. It's challenging finding the formulation of testosterone that is low enough, like from the male side, because we have lots of formulations for men that is low enough to kind of give an appropriate dose.
- [45:57]
Peter Attia
Why isn't a female formulation being made?
- [46:00]
Dr. Rachel Rubin
Buckle up, buttercup. So here we go. We had a billion dollars that was put into it. A billion dollars and a five year study that was Done at the fda. And it showed it was safe, it showed that it was effective. It showed that it was. The TLDR on testosterone is. It's not that serious. We want it to be serious again, not a feeling. We want it to be like all about aggression. It's not a feeling. It truly isn't. So they did five years of study. A billion dollars went into it, and the FDA came back and they said, ooh, women have breast tissue. So we're going to need five more years of data and another billion dollar study. And every company was like, I'm out. The benchmark was different for women. Men, six months.
- [46:38]
Peter Attia
And this was a real goalpost move.
- [46:40]
Dr. Rachel Rubin
Yeah, they just keep moving the goalpost everywhere. They move the damn goalpost. Okay, I talked about the labeling on testosterone being removed, that it doesn't worsen cardiovascular disease. Why? Because they did the Traverse study that your listeners know about that proved it. The box labeling on estrogen products which says that estrogen causes stroke, blood clots, heart attacks, probable dementia. We just got done saying that. That study didn't show that. So why is that box labeling still there? We're killing women by trying to protect them.
- [47:10]
Peter Attia
Why do you think this is happening? If you try to steel man the case for the other side, where are they in their thinking on this?
- [47:21]
Dr. Rachel Rubin
I think medicine has a humility problem and a deeply ability to say, hey, we didn't know what we didn't know back then. We're learning and we're adjusting. They don't like to say, I don't know. They don't like to evolve in their thinking. And for some reason, women's health comes with so much bias. The amount of money that goes into women's health research is worse than it was 10 years ago.
- [47:46]
Peter Attia
But is this a paternalistic? I mean, I hate to put sociology on top of this. As you know, I spoken with one of the PIs from the WHI and I think she is by far the most honest broker of that group. And I don't have good things to say about that group. I really don't. But I also can't even wrap my head around their thinking. Like, I can't steel man their case.
- [48:10]
Dr. Rachel Rubin
I wake up in the morning, I'm like, how is this real life? Okay, I'll give you an example. We met with a chief before the administration changed. We met with the. I think it was the chief medical officer of the fda. We met with someone high up at the fda. It was a room full of perimenopausal women. I was like, yeah, we got this. It's a room full of perimenopausal women. And we presented our case about vaginal hormones, which is basically microdosing hormones, and they prevent UTIs by more than half. When you use vaginal hormones, you treat the genitourinary syndrome of menopause. And we said to them, we said, you labeling this should not have the same labeling of all estrogen products. You should remove the labeling. And they said, well, we're really going to need industry to come at us to remove the labeling. I said, you didn't need industry to put the box on. Why do you need industry to remove the box? We no longer have industry in this field in any significant way because the WHI destroyed that industry. So we have a huge problem where you actually don't have any money to women's health. I think Pfizer completely fired their women's health division, saying, yeah, we're going to look at allergy. Now you have entire departments. We did a study once on pelvic pain. We were looking at botulinum toxin and pelvic pain. And I was on the call where they said, ooh, we have a new CEO now and women's health is no longer a priority. Like, I heard those words. So we do have a paternalistic problem. It's true. And unfortunately, it's not getting any better.
- [49:31]
Peter Attia
I usually do not subscribe to theories like that. I usually find myself thinking there are alternative explanations and we're just pointing to the most sensational ones. But it gets hard to dismiss an argument as follows, which is, if the tables were turned and the WHI was really the mhi, the Men's Health Initiative, and it produced equally idiotic results, would we be in the same place we are today? Or would men have said, oh, hell no?
- [50:05]
Dr. Rachel Rubin
The traverse trial. Right. Yeah. There were two bad studies that were done, horrible studies that made no sense, that showed testosterone had some dangers. The FDA threw that box labeling on said, oh, my gosh, within minutes, they created the traverse trial. It got done in five years, and within minutes, when it was finished and it got published in the New England Journal of Medicine, the box was removed.
- [50:25]
Peter Attia
And by the way, the Traverse trial's not even a great trial. I've been so critical of the traverse trial.
- [50:30]
Dr. Rachel Rubin
Amen. Right.
- [50:31]
Peter Attia
I think you could have come to the same conclusion of the Traverse trial if you knew how to read all of the data before it. I actually don't think the traverse trial added much, but anyway, totally look at data.
- [50:40]
Dr. Rachel Rubin
Oh, there was an Increased fractures from the. Oh, testosterone causes fractures. That makes no sense. We know that's not true. We know testosterone helps bone mineral density. And so you can make the same arguments of how you look at these studies, how these studies are designed, the flaws of them. You're going to do a study for five years. Why are you giving people gels? Is that the right thing? So why do we care what the people of the Women's health initiative said 20 years ago? Why is that even news? And why can't it die? And because you don't have enough people like you standing up. You don't have the internal medicine doctor standing up and saying this is wrong because they're not teaching it. You don't have the OB GYN saying this is wrong because they're delivering babies and women are dying in childbirth. Women's health, menopause health in particular is important to nobody. When it's nobody's problem, nobody takes ownership of it.
- [51:30]
Peter Attia
I mean, I do believe this is going to change. And I don't know who said this, but it's a great quote that said, funeral by funeral science makes progress. That's not a great explanation for what's about to happen temporarily because it's going to be a while before everybody who held that belief in their soul is no longer around. But it does give me hope that a new generation of women will come along and take ownership over their health. And look, I've seen a change in 10 years. Ten years ago, when I was prescribing hormones to women. You cannot believe the fights I would have with their other doctors. And I don't mean, like, we weren't fist fighting, but they were scolding me, like, how dare you? But it came with an arrogance, a lack of willingness to even look at the data, which I found ironic. If you want to scold me, you better know as much as me and hopefully more. But this arrogance of, I'm going to scold you, but I know nothing and I'm not actually willing to have a discussion with you because I'd be like, great, turn to figure two in the JAMA paper. And let's look at this and look at the appendix and look at the supplemental data. Like, are you seeing the same thing I'm seeing? Can we at least agree on the facts?
- [52:46]
Dr. Rachel Rubin
No, we can't. And it's so fascinating because I would never. I do sexual medicine. So I look at the whole patient, I look at everything. And I would never say to them, hey, you have to stop this beta blocker, right? Now because it's causing your erectile dysfunction. I would never tell a patient that though the beta blocker may be worsening his erectile dysfunction. But I would never say, stop this medicine, it's hurting you. I would talk to their doctor, I would have a conversation. But there's something about hormones that doctors who know nothing feel very confident in saying, you can't be on this, you must stop this. Without even having that curiosity of, huh, I wonder if the person who prescribed it actually knew what they were talking about. And it is everywhere. We see this all the time.
- [53:31]
Peter Attia
Now let's talk about the flip side, because the unfortunate nature of everything we've just described is you create a fringe movement. And unfortunately I've seen a lot of dock on a box hormone practices that are, I believe, putting women at risk and I believe are doing bad things to women in the name of doing good. And I don't believe that these are inherently bad individuals. I think they're ill informed, I think they're just not that bright. And maybe some of them are just actually charlatans and they're seeing an enormous opportunity here. As a general rule, I tell patients, be very, very suspicious of a doctor that is selling you hormones. Be incredibly suspicious of any physician who has their own compounding pharmacy within the practice and is giving you compounded formulations and also making money on it. Talk a little bit about, I don't want to call it the dark side, but just the fringe side of this world.
- [54:34]
Dr. Rachel Rubin
So I would argue that people care about their pain points, people want to feel better, people will go to anyone who tells them there's a whole supplement aisle at CVS that makes all these wildish claims that we're going to help you with everything. And the reality is, is I just got done saying your gynecologist and your internal medicine doctors are going to, in that 10 minute visit tell you that you don't need this, this is not going to help you. And so enter the fringe people, the snake oil salesmen, the people who are doing wildly inappropriate things. That doesn't mean the hormones themselves are bad. It just means we have a marketing problem here. If we're not doing it and helping people. They hear their friend did it, they hear their neighbor did it and they said, I want what she's having. This is why we call ourselves the Menopausy. This is why we teach so loudly, is because we're trying to bring it back into medicine and evidence based medicine and say, you can actually do this quite reasonably. In fact, there are many FDA approved products that work much better, that are more regulated, that are totally safe. Here's what they are. They should be covered by your insurance and giving them that knowledge. Because the problem is, is it's too quiet. No one is giving people answers. No one's even looking at the questions. So then the fringe people take over and are unfortunately doing very inappropriate things. You know what? Men's health too, as a urologist, we see shot clinics and all these wild PRP clinics and testosterone pellet clinics and compounded pellets and all of these things. Because my colleagues, we are not doing enough to take care of men's sexual health. And so these clinics exist to prey on those patients who deeply want to connect and get their answers. Which is why my colleagues and I are even loud about it for everybody.
- [56:14]
Peter Attia
Yeah, the number of online testosterone clinics is mind boggling. And a lot of them are prescribing, I think, second tier drugs.
- [56:23]
Dr. Rachel Rubin
And you know what I say? I say, you know, with these things is the people who need it are not being offered it and the people who don't need it are abusing it. And that is true for hormones, for everybody. I talked about this at the last menopause meeting. Less than 4% of women are on hormone therapy right now. Less than 4%.
- [56:40]
Peter Attia
4% of women who would theoretically be required.
- [56:43]
Dr. Rachel Rubin
Less than 4%. That's worse.
- [56:45]
Peter Attia
That's worse than I would have guessed.
- [56:47]
Dr. Rachel Rubin
That's worse than 10 years ago. It is so bad out there. I did the same calculations you did when I was on my Uber on the way over. I said, how many women are over 40? It was something like 84 million, according to AI. And there are about 3,000 people on the Menopause Society website. That doesn't mean everybody knows what they're doing or that they all do the same thing. But divide 84 million by 3,000. It's a big number. And we can't see patient panels of 27,000 people. The math doesn't math there. So we need people to step up. And so who should be writing estrogen prescriptions? Who?
- [57:21]
Peter Attia
Every doctor who sees a woman of that age.
- [57:23]
Dr. Rachel Rubin
Every doctor who sees a woman of that age. And so who actually does. Nobody.
- [57:27]
Peter Attia
Yeah. Let's talk a little bit about the playbook. I want to tell you how we do it. I'm not saying we do it right because I don't think there's a right way to do it, but I mostly want to hear how you do it because I bet you're way better than we are. Maybe we take a step back and explain. We've already alluded to it twice, but I just want to make sure people are understanding this. If a woman has a uterus, you have to protect that endometrial lining. So even if she's in the camp of women who don't notice being on progesterone, you have to be on progesterone. We'll come back to IUDs and progesterone coded devices and things like that. And angel, let's just talk about the way you give progesterone. So progesterone's the easiest of the lot. Is there any reason when giving oral progesterone to use anything other than micronized FDA approved progesterone orally?
- [58:13]
Dr. Rachel Rubin
What's lovely is we need a toolbox because not everybody responds to the same thing. I love micronized progesterone. I think it's a fabulous product, is my go to first line. Sometimes we need to put it vaginally instead of orally to help with some of those sedating side effects. So you can avoid going to the brain if you put it vaginally. And so we do find that cuts down.
- [58:32]
Peter Attia
But you're going to start orally?
- [58:33]
Dr. Rachel Rubin
I typically start orally.
- [58:34]
Peter Attia
You're going to start at 100 milligrams.
- [58:35]
Dr. Rachel Rubin
Depending on the dose of estrogen. I typically start with a hundred milligrams. Some people say if you're going higher with your estrogen, you may need to do 200 milligrams of progesterone. That data is not very clear. And there's really two ways to give progesterone. You could do it every single day. So typically a hundred milligrams every day. And then some people in a lot of data shows if you do it cyclically, like 200 milligrams, 12 to 14 days out of the month is another way to do it. Both are fine. When we see many patients, they feel better doing it 100 every day because it can help with sleep and anxiety reduction.
- [59:07]
Peter Attia
Do we believe that a hundred systemically is sufficient to oppose estrogen?
- [59:13]
Dr. Rachel Rubin
I think there is not enough data there and we need more. I think if patients bleed, it's a nice tell that maybe they need more progesterone. I think there's some interesting that I've learned that some people say if you take it with fat or you take it with something to eat, it absorbs better because progesterone's not absorbed very well, which is why we always had synthetic progestins in the first place. And so we're still learning the capabilities of micronized progesterone. But according to most menopause specialists out there, they typically will use a hundred milligrams every day or 200 milligrams 12 to 14 days of the month.
- [59:46]
Peter Attia
So the only thing that we do, I would say different there is while we start women at 50 to 100, we will generally take them to 200 if tolerated, and if not, keep them where they are at 100. But we find women who are in that one third to one half group who are very positively selected towards progesterone. They feel fantastic at 200. The most notable improvement is sleep. So would you agree with that?
- [60:12]
Dr. Rachel Rubin
Totally agree.
- [60:12]
Peter Attia
Most women are just over the moon with how well they feel better.
- [60:16]
Dr. Rachel Rubin
Love you forever. It is so fun to get sleep.
- [60:18]
Peter Attia
Hair gets thicker and mood improves. So now let's talk about the other subset of women. I mean, this is a real subset, no question. It's, I would say in our population, it's about 10 to 20% for whom if you bring progesterone in the room, something goes wrong. Their mood really changes. Now, it can in some cases become depressive. But more commonly, what they tell me is, and I'm quoting them, this is not me saying it. I become a raging bitch. I'm worried I might kill my husband. So for those women, we think progesterone's a bad idea and we then use a progesterone coded iud. So are you doing that or are you using a suppository at that point?
- [61:03]
Dr. Rachel Rubin
You can do either. You can say, hey, try taking this vaginally and see if that goes away. See if you're no longer feeling anger or bloated or have irritability. And so vaginally can be an option. We love progestin coated IUDs. They're great in perimenopause. Why? Because people think that you just lightly dance into menopause. It is like bloody murder, hell seen. It can be terrible. You can bleed the whole month. You can bleed heavy, you can bleed when you're least expecting it. So the IUD is very nice because it will stop bleeding. And so you throw an estrogen patch on and some testosterone. And that's a really great perimenopause plan. Now you can still.
- [61:41]
Peter Attia
And you get birth control.
- [61:42]
Dr. Rachel Rubin
And you get birth control, which is very important. You can add micronized progesterone to the patient who gets good sleep, even if they have an iud that doesn't add danger. We love that. So we love IUDs for this population. There's another synthetic progestins which you can use as well. I've seen people do things like Slind, which is a birth control, a progestin only birth control pill. Add a patch in testosterone to that as well. Now, again, synthetic progestins sometimes can have mood side effects as well, so they're not completely benign for all people. There's another. I don't know if you've used this at all in your practice. It's called duvet. Have you heard of this? Yes, it's an oral estrogen, but it also has what's called basodoxifene, which protects the uterus but is not a progesterone based medicine. I wish they were separate. I wish we could just give bezodoxifene alone, any pharmaceutical reps so that you don't have to use oral estrogen if you don't have to. Oral estrogen is not evil. I'm a sex doctor and we know that transdermal is a little better for sexual function. So that's again, why I'm a big fan of transdermal products as well. But that's kind of another option. People get hysterectomies for lots of reasons. We've had patients do that who really don't tolerate progesterone and then you can just use estrogen only.
- [62:50]
Peter Attia
Are you referring women who are on what potentially might be a low dose of progesterone to their gyn for endometrial ultrasounds on some regular interval, just to look for hyperplasia or anything like that.
- [63:04]
Dr. Rachel Rubin
We really don't like to look for things. The nice thing about endometrial cancer, from what I understand, again, I'm putting my urology hat on. I am not a gynecologist. It bleeds now if you bleed, then if you bleed and you just started a new hormone therapy, it's probably okay now for me, I like to know if there's any structural things going on. Do you have a polyp? Do you have a fibroid? Is your lining super thick? If you're in perimenopause, you still should be bleeding. So it's that challenge. I don't go looking for things that aren't bleeding because I don't necessarily want to find things. So, no, at this point, there's not necessarily a reason for routine surveillance because if your lining is say 6 millimeters and you're not bleeding Are you really going to put that woman through a biopsy and through a hysteroscopy and those have significant pain and problems that go with that as well?
- [63:51]
Peter Attia
Okay. Anything else you want to say about progesterone? Do you start it concomitantly with the estrogen? Do you like to start one before the other?
- [63:59]
Dr. Rachel Rubin
I like to start one before the other in general because I like people to know what's doing what.
- [64:04]
Peter Attia
I agree.
- [64:04]
Dr. Rachel Rubin
When someone comes to see you, says, give it all to me, it's always a disaster every time. It's one time it worked well for me, but it's pretty much a disaster. So I like to stack it. And again, you're not gonna cause endometrial cancer in three months of using just estrogen. I mean, you're talking something that takes years and years and years to develop. And even that data is not that clear cut. So I'm not worried about me causing a uterine cancer. Now, often we'll start with the estrogen. Sometimes you'll start with progesterone if sleep is the major issue. But I find the vasomotor symptoms, it's such a big deal to get rid of those. So I do like often starting with estrogen and then slowly adding in the other ones.
- [64:41]
Peter Attia
I'm really happy to hear we're following your playbook already. So, yes, we almost always start with estradiol and we muck around for a while till we get it right. That's why I saved it for last, by the way, because it's the hardest, in my opinion, in my experience, to get right. Then we fiddle with progesterone and then testosterone if they're not already on it. But to your point, some women are coming into perimenopause already on testosterone. Okay, let's talk about estradiol. There are two other estrogens. Estradiol is E2, but there's estrone and there's estriol, E3. Now, the FDA only has a battery of approved products around the second estrogen, which is the dominant estrogen. There's no FDA approved product for estrone and there's no FDA approved product for estriol. But there are plenty of compounded opportunities around that. In fact, the most common of them is referred to as BioST BI Estrogen, which is an 8020 mix of estriol and estradiol. What is your take on why that product exists? Do you view that as a reaction to the whi? I mean, how do you think about it?
- [65:55]
Dr. Rachel Rubin
You said it right there I think that what happened is the Women's Health Initiative happened and hormone therapy all went into the underlying.
- [66:02]
Peter Attia
Went to the alley.
- [66:02]
Dr. Rachel Rubin
It went to the alley. And I think one of the ways that these back alley doctors did it was saying, oh, we're using the safer version, we're using this compound and we're going to make it 8020 and we're going to use the more safer option. By the way, I haven't seen that data and there is no data on biased in large trials. That's going to really tell me what it does. And we're going to just use this. And that's what got people through for a while. And I don't actually blame those people if they had no alternative. If I were in the middle of the desert and I had the options and I was having horrible symptoms and I had the options of nothing or a biased cream, I'd probably slather the biased cream on me. Where we are now, we have lots of options. We have FDA approved options and they're covered by insurance most of the time. So I don't prescribe it because I haven't needed to. Now if I have a patient who comes into me and they're feeling great and they have no problems, do I have to change them? Well, I'll say, well, do you want to save some money? Like, we could change you to a different formulation. That's an option. Sometimes I'll even check if, say, they're having symptoms, we'll check their levels. And I don't know if you find this, but their estradiol level is essentially zero. It's less than five. And I'm saying, listen, I think you're just using fancy lotion. I think you're paying a lot of money to put nice lotion on you. And I don't know that it's protecting your bones. And if we're using this to protect your bones or to stop your hot flashes or to help with your sexual health, maybe we use the formulations that are a little bit better studied and that I know are absorbing in your body because I can prove it. I know. What's your take on that?
- [67:33]
Peter Attia
We don't use it at all. I have used it occasionally in the past, probably about 10 years ago, largely in women who were terrified of HRT. And to your point, it was viewed as, look, if you buy the argument, and this is a biochemical argument, there's no human data that demonstrate what I'm about to assert. And again, I say this because one can look at A whole bunch of biochemical charts and tables and talk themselves into anything being true. But there are biochemical arguments to be made that estrone, and in particular one of the metabolites of estrone, and I think it's four hydroxy estrone, is the estrogen that is driving breast cancer. So in an estrogen sensitive breast cancer, given that you have so many estrogens, is it more likely that one is responsible than another? And so the answer is, oh, you know, some of the data suggest it's four hydroxy estrone. Well, estriol has no biochemical path to even get there. In other words, there are no series of enzymes that can convert estriol into 4 hydroxy estrone. And of course there are pathways that will turn estriol weakly into estradiol. So maybe you get a little bit more. So in a. This is a long winded way of saying no reason at all from an evidence perspective to use it. We don't use it, have not used it in a decade. But that was my half baked argument in certain situations. And in fact I did use it once in a woman who had breast cancer, was adamant that she needed hormones symptomatically. She really seemed to wanted it very badly and I felt that this was a reasonable compromise. For what it's worth, she got insanely better on the biased. How much of that was from the estriol? How much of that was from the estradiol? I have no idea.
- [69:28]
Dr. Rachel Rubin
When I teach this, and I do a lot of teaching of physicians holding their hands saying, you can do this, you can write these prescriptions. And one of the things that I just keep coming back to is the sentence, what are you afraid of? And I love that because when someone says, well, can I do it in this patient? Well, what are you afraid of? Can I use this product? What are you afraid of? And it forces, I think in menopause medicine, the reason we're all struggling is we're not yet at an algorithm or a playbook, as you say, that it's a one size fits all. What's so sexy about this field is we actually have to use our brains. We have to use our brains, we have to talk to people, we have to get to know what's bothering them and we have to do the right tools for them, which may be different in each person. Because you have to also understand what are your patients afraid of? Because that is the only thing that matters. We take risks all the time. I took a risk taking a car to get here. We take risks if you ever drink alcohol, you are taking a risk. We all take these calculated risks and we all have different calculations. And so I love to push people of, well, if you were to use this. So patient comes in on biased, is that safe? Well, what are you afraid of? Am I afraid I'm going to hurt this patient? I don't think I'm going to hurt them necessarily. But I don't know what's in that compound. I don't know if the top of the bottle is the same as the bottom of the bottle. I don't know if it's good for her bones. I don't know if it's absorbing in the way that it should be. But I do have studies on FDA approved estradiol. And then it becomes what am I afraid of with the patients? Well, what are you afraid of about the estradiol? Are you afraid of cancer? Because you know that in the Women's Health Initiative, people who used estrogen had a decreased risk of getting and dying from breast cancer. Our patients don't know this.
- [71:06]
Peter Attia
Yeah, and you mentioned this earlier. I think this is one of the biggest limitations of how I talk about this thing, medicine 2.0, which is very few people are conditioned to ask the question what is the risk of not acting? We have a reasonable idea of what is the risk of doing X, what is the risk of doing Y. Although in this particular example we seem to get that patently wrong. But what's the risk of not doing something is very significant. So let's talk about all of the different ways in which a woman can get estradiol through an approved, tested, chemically.
- [71:44]
Dr. Rachel Rubin
Sound means a little bit of nomenclature here. There is systemic estrogen. So when we're talking about hormone therapy, whether you call it hormone replacement therapy, the new way we talk about it is menopause hormone therapy. Or if you want to just say hormone therapy is totally fine. We're talking about hormones for your whole body. Estrogen for your hot flashes, for your bone protection, for your skin, hair and nails. That's estrogen. That's systemic estrogen. But there's this whole other topic which I hope we talk about later because it's my favorite one, which is local vaginal hormones, which are to treat the genital and urinary symptoms of menopause. And those are pretty much safe. No, I'm going to say it. They are safe for every human on earth, including your 99 year old mother in law in the nursing home who potentially could die of a urinary tract infection. So this is Kind of the two separate areas. And I think the question you're asking me is let's talk about systemic estrogen.
- [72:39]
Peter Attia
Let's start with systemic. Let's come back to that as we talk about genitourinary syndrome, because I got.
- [72:46]
Dr. Rachel Rubin
A lot to say about that one. So systemic estrogen has a toolbox. We have patches, we have gels, we have rings which go vaginally. We have oral estradiol. Those are the big ones. There are injections that's kind of an old school way that I use sometimes injections of estradiol, valerate or cypionate. And so each one has pros and cons. And it's nice to have the toolbox because not every product works for every patient. And the key is, is getting it right for that patient because you need something that they're going to do and that they're going to do it for a long time because these are not things that you just due for a weekend.
- [73:24]
Peter Attia
Let's start with the oral. So we have an oral formulated estrogen. We don't use it that much. I'm trying to think used to use it a bit more than we did now, honestly, sometimes I would use it for women who we were struggling to get the dose right on something else and I just needed something to get them through the weekend and it was like, okay, I want you to just take a milligram of this estradiol tablet tonight while we readjust your cream or your patch or whatever. When are you using oral estradiol?
- [73:55]
Dr. Rachel Rubin
I don't use it much, but that's not to say that it isn't useful. I think it is actually very useful and I think it's underused. For example, people are used to taking birth control pills. They're used to taking pills they like pills doing for a healthy person with no major risk factors of cardiovascular issues, taking an oral estrogen really is not going to increase your risk of blood clots or heart attacks or anything like that at any significant worrisome level.
- [74:19]
Peter Attia
It's no more increase in risk of blood clot than a birth control pill.
- [74:22]
Dr. Rachel Rubin
Less. It's less, yeah.
- [74:23]
Peter Attia
So given the ubiquity with which women are on birth control pills, it shouldn't stay. We tend to blow this out. Proportion. Yeah. So what is your patient selection criteria on that? In other words, who are the women that you would say I don't want you on oral? Is this just factor 5 laden? Is this women who are obese? Where do you say, ah, the risk is a little too high I tend.
- [74:41]
Dr. Rachel Rubin
To always start transdermal. And again, this is my sex doctor hat, because we learned from this study called the Keeps trial, where they looked at oral estrogen versus transdermal dermal estrogen. And it's a fascinating trial. But in that trial they found that, yes, there's a slight increase of blood clots with oral estrogen, but sexual function is better in transdermal, and that's because of what happens to sex hormone binding globulin. So when you take oral estrogen, we talk a lot about first pass metabolism through the liver. It goes through the liver. The liver, lots of things go through the liver when you take medications. In this one in particular, it can pump out more clotting proteins. So if you're at any risk of blood clots, just like birth control pills, if you're a smoker, if you are overweight, if you have a genetic predisposition to blood clots, we're not going to use an oral hormone product. Now, I want to paint this because this is actually an area where I would love to see research. I was speaking at a Harvard testosterone course with Abe Morgan, Tyler and Mo Kara, who you've had on the show, and I was speaking about women's testosterone use. And the speaker who got up there to talk about a transgender hormone therapy, talked about sublingual estrogen. He kept referring to sublingual estrogen. And I ran to the microphone, I said, what are you talking about? I've never heard of sublingual estrogen. There's no product. What are you saying? And he says, oh, you just take an oral estrogen tablet and you put it under your tongue like a Tic Tac and you let it dissolve and it doesn't go through the liver and it works fabulously to increasing blood levels. And I said, oh, my God, this sounds amazing.
- [76:12]
Peter Attia
And it doesn't drive up shbg, presumably.
- [76:15]
Dr. Rachel Rubin
Presumably because it doesn't go through the liver. Which actually, if you think about it logically, I love logic here because we don't have a lot of data. So we love logic, is that, well, if you take an estrogen ring, a high dose estrogen ring, and you put it in the vagina, same thing, you absorb estrogen vaginally. What's the difference there? Right? A sublingual estradiol. So I think it's fascinating. I don't have many patients on it, but I would love to see data look in that direction. Because it's cheap. Oral estrogen is cheap. You get lots of doses, you can.
- [76:41]
Peter Attia
Dose it does that mean you can get away with a lower dose?
- [76:44]
Dr. Rachel Rubin
You can get away with a lower dose. Absolutely.
- [76:46]
Peter Attia
You must. Right. Because of that first pass effect. So how do you dose it again?
- [76:50]
Dr. Rachel Rubin
I don't have patients on this, and I haven't seen any studies on this.
- [76:53]
Peter Attia
Did you ask this guy?
- [76:54]
Dr. Rachel Rubin
Yeah, absolutely.
- [76:55]
Peter Attia
How does he dose it again?
- [76:57]
Dr. Rachel Rubin
Transgender hormone therapy uses much higher doses, so my guess is 1 or 2mg bid is probably what they do. If I were playing with it, I would probably be nervous, and I'd probably do 0.5 check levels, and I'd do twice a day. Again, this is not what I do in my clinic. But just as we think through. What are you afraid of? What are you afraid of with this? It's pretty fascinating stuff.
- [77:17]
Peter Attia
Okay, let's talk about the panoply of topical ways you can do this. Creams, patches. What are the challenges of using these things? How do they limit women's activity levels? I mean, I used to have this whole talk I would give women about what I thought was the best way to maximize the absorption of the cream and what I wanted them to do before they put it on. And I wanted them to have a shower, and I wanted them to exfoliate their inner thigh. And I just had this thing, whole, whole routine that was probably so elaborate that it decreased compliance because, like, it's not that serious. All right, talk to me about it.
- [77:51]
Dr. Rachel Rubin
But it is true for men in testosterone, we often find the topicals do not Some. They absorb beautifully, and you get these beautiful levels and they feel great. And then you do have a population that just doesn't absorb well through the skin. And unfortunately, we don't know who those people are. I always tell patients, here's the menu, and we're going to tinker. We have to tinker to get it right for you, because you're not like anybody. And so patches. A lot of people have heard of patches. They like patches. They make twice weekly patches, and they make once weekly patches. I find the twice weekly patches are much better tolerated, and my patients like them better. What's nice about patches is you have a wide variety of doses that you can play around with. When I start patients on hormones, I typically choose, like, a medium to medium low version because if you go too high initially, they get breast tenderness and they get really annoyed with you, and then you have to backtrack. So I always like to titrate up a little bit as we need to. So patches are nice, but for some people, they don't stick well. For some people, they don't absorb well. For some people, they feel that they kind of drop off if you change it twice a week, they feel like they're getting a little lower.
- [78:53]
Peter Attia
We also notice women who use the sauna who are very, very athletic and exercising like crazy. You just have an adherence physically. An adherence problem.
- [79:02]
Dr. Rachel Rubin
Yeah. And there are people who are allergic to the adhesives. We see that as well. So some people, they love patches. Again, you have to have a menu if you're going to a doctor. And they give you one type of hormone therapy, and that's the only type, please run. They need to know the menu because it's not a one size fits all. So there's gels, and there are number of different gels. There's gels like the brand name is Diva. Gel goes on your thigh. There's Estrogel, which goes on your arm. There's Eva mist, which is a spray, sort of an aerosolized spray that goes on your arm. Gels can be really nice because it's every day. So it's dosing every day. The challenge is sometimes they take a little bit to dry. So if you're a busy person and you want to rub something on and you want to run out of there, I find gels. Not everybody wants to do something every day. You got to get to know the people of what do you like to do? What's your routine? You have to get it into their routine. And sometimes you got to work up to it. And sometimes I have patients, they'll use patches, but when the summertime hits and it's hot and muggy, they'll switch to the ring or they'll switch to a gel.
- [80:03]
Peter Attia
What's the case for not just using the ring all the time?
- [80:06]
Dr. Rachel Rubin
Ugh. So I love the ring. There's two types of ring. Now, this is important because your pharmacist sometimes messes this up. So there are two FDA approved rings. Now, a ring, just like a birth control ring, you set it and forget it. You put it in the vagina. The vagina does not feel it like a tampon. You don't feel it and it just stays in for three months at a time.
- [80:24]
Peter Attia
And it's sitting right up against the cervix.
- [80:26]
Dr. Rachel Rubin
You just kind of push it in there and it just settles in and finds a place. By the way, if you have penetrative sex, most people don't take it out. They don't feel it. Nobody's bothered by this thing. So this ring goes in there, stays in for about three months. Now there is a FEM ring, which is a high dose ring, which means if you have a uterus, you need progesterone to protect the uterus. And it comes in two doses, 0.05 and 0.1. Then there's an E string, which is a 2 milligram localized estrogen ring. You do not need progesterone if you have a uterus because it's just treating the genitourinary syndrome of menopause. So it's not treating your hot flashes, it's not protecting your bones, it's not going to help your night sweats, but it's going to prevent UTIs. It's important that you know the difference because the pharmacist sometimes won't and he'll give you the wrong ring, which could be catastrophic if they think they have a systemic ring, but they have a local ring.
- [81:16]
Peter Attia
And it's just dose is the only difference between the two.
- [81:19]
Dr. Rachel Rubin
Yeah, they look a little different.
- [81:20]
Peter Attia
Yeah, yeah. The reason one is systemic is a.
- [81:23]
Dr. Rachel Rubin
High dose and one is a low dose.
- [81:25]
Peter Attia
But it's this that you change them at the same frequency.
- [81:26]
Dr. Rachel Rubin
Yeah, both three months.
- [81:27]
Peter Attia
Okay. I thought you changed the Easter ring more frequently. But good to know.
- [81:30]
Dr. Rachel Rubin
Both three months. Now, there's a company right now studying a product. I'm not at all affiliated, but it is a one month ring that has both estrogen and progesterone in it, which is very interesting and I'm curious to see where the research goes with that. And it's a one month ring. So the issue with the ring, I love the ring. Now there are women who you show them and they're like, no, I don't want that. There are women who've used rings for birth control. They love the idea. I will tell you. And we've been hoping to publish on this clinically. Again, I don't know about you, but my patients don't listen to the book, they don't read the book and they don't follow the FDA curves. But my patients, it peters out. It literally stops working. That last month.
- [82:06]
Peter Attia
How long?
- [82:07]
Dr. Rachel Rubin
Everyone's a little different. But I have patients where that last month they are dragging, their hot flashes dragged.
- [82:11]
Peter Attia
So why not just swap it every two months?
- [82:13]
Dr. Rachel Rubin
It's expensive. So a lot of times insurance doesn't cover the ring. It's about $180 cash price. When you use an online pharmacy called Transition, it's expensive. Sometimes they'll slap a patch on or a gel at the time to sort of overlap. So they'll change it early, or they'll add a different therapy, or they'll stop using the ring altogether. It is perfect for like two months. And we'll check levels again. There's the book answer, the Instagram answer, and the Dr. Rubin answer. This is where checking levels is actually helpful.
- [82:40]
Peter Attia
I'm sure there are a couple of my patients that would actually volunteer to do this, where we just do twice a week levels for three months while they're on a product, while they're on a ring, and just watch the clinic.
- [82:51]
Dr. Rachel Rubin
It's incredible because you will see it, you'll check it. You have a 0.1 ring in, and you should expect estrogen levels of 60, 70, something like that. And you'll see an estrogen level of 13, and you'll be like, oh, my God, this is not working right. And they'll complain of hot flashes, night sweats. Their symptoms will come back. And so we see a lot of ring issues with dosing for that purpose. And then another problem is if you have any kind of prolapse, so as people have babies, things can kind of prolapse. And so the ring can fall out during bowel movements, other things like that, if there's not enough space in there. So I had an ultra marathon run.
- [83:24]
Peter Attia
That can get expensive.
- [83:25]
Dr. Rachel Rubin
It gets expensive. This is where checking levels is beautiful. Marathon runner comes to me, she loves her ring, she's doing great. She messages me, oh, my God, I feel awful. Something's not right. I don't feel like myself again. I said, oh, where are you in your ring? Where are you in the cycle of your ring? We talk about it. I said, let's just check a level, see what's happening. Sure. Estrogen was undetectable. I said, okay, we need to change this ring. And she messaged me, I can't find it. She can't find the ring. It's not there. She probably had a bowel movement. It fell out, she didn't notice, and then her levels dropped. So it's where that detective work helps you kind of figure out what's going on with your patient. So the ring is not perfect for everybody, but I love the ring. If you're in perimenopause and you have an iud, a ring, you put a little testosterone every morning. It's really a set it and forget it. You get vaginal estrogen, systemic estrogen, you get your progestin from the iud, you add a little topical testosterone.
- [84:17]
Peter Attia
Very low maintenance and very low maintenance solution.
- [84:20]
Dr. Rachel Rubin
Yeah. And not expensive like you can do it relatively inexpensively.
- [84:25]
Peter Attia
Two things I want to talk about on the lab front. We've talked a lot about labs, so not sure if you share our view on this. We are really fastidious about using LC Ms. For estradiol. We do not want to use the ELISA based assays at all. Are you pretty meticulous about that or do you find that you're just happy checking any estradiol?
- [84:41]
Dr. Rachel Rubin
I typically get the sensitive estradiol level. Yeah, that's what we get for everybody. And same with the testosterone as well.
- [84:46]
Peter Attia
So. So let's maybe make that a PSA for people, both physicians who are out there and patients. We have seen that if you do not use the LC M S assay, which is the very sensitive, the liquid chromatography assays, the results can be meaningless, and I mean truly meaningless. And the reason is that the ELISA based assays are so susceptible to interference from other molecules. And there are some really known obvious supplements that completely obscure the findings. So biotin, which is in a lot of things will render a non LC Ms. Test irrelevant. But I think there are other things that we're just not fully aware of. So it is worth splurging and paying the extra. Maybe it's 5 or $10 would be the cash price difference on that test. But absolutely make sure when testosterone and estradiol are being measured. If you're the physician, you actually have to go through the hoops and make sure you're ordering the LC Ms. Test. And if you're a patient, you should be asking for it.
- [85:49]
Dr. Rachel Rubin
So we're gonna get a lot of hate. There's a lot of disagreements when it comes to hormone therapy, how to properly do hormone therapy, how to check for hormone therapy. And one of the places, and it's funny because I truly believe, and for anyone who's gonna say mean things about me on the Internet from this podcast, because I truly believe that actually most of us agree on like 98% of this. Truly we want women feeling better. Most of us believe the data that hormones, the benefits outweigh the risk. And So I think 98% we agree there's the 2% where there is disagreement. And part of it is also in the what we don't know yet, the unknown and the curiosity and sort of things. And lab testing is one of those issues. The book says never check labs. If your doctor checks labs, they are really doing something wrong. You should only care about symptoms. And then you have sort of the fringe that are doing all saliva based testing every Minute check labs. Do all these expensive labs, which I do not agree with again, the Instagram answer, the book answer, the Dr. Rubin answer of sort of. There are reasons to check labs and I do find labs similar to you. My curiosity with labs is so fascinating when you can capture this perimenopausal fluctuations and show the patient the reason you feel so terrible is because your estrogen was 1000 and now it's zero and that hurts. Now do I need numbers to know that that's what's happening? It actually helps patients quite a lot for them to look at this and see the data. What is your take on that?
- [87:17]
Peter Attia
I'm actually surprised, but you have to understand I don't spend any time paying attention to the buffoons in the periphery on this topic. I don't like the whole terminology around functional medicine. I don't buy into the idea that you need to be spending an inordinate amount of money on esoteric, non validated labs. You can go to LabCorp, you can go to Quest, you can go like any CLIA approved lab that knows how to do an assay correctly is all you need. Our view and what we tell patients is the symptoms are the most important things, but the numbers help direct my thinking. This is how we manage thyroid, this is how we manage sex hormones. And to be clear, there's a caricature of the Dunning Kruger curve that I just find so helpful. So for the folks who aren't familiar, on the X axis you have experience and on the Y axis you have confidence in the sort of character version of the representation of this curve. You initially have a huge spike which then falls into a valley and then a slow rise. And of course the huge spike is referred to as the peak of Mount Stupid, followed by the Valley of Despair and the Slope of Enlightenment. And it's just important for people to understand that when you are on Instagram and YouTube, disproportionately, you are seeing people at the peak of Mount Stupid, which is to say they have very low experience, insanely high confidence, and these are the ones that are telling you that TSH, I'm making this up. As one example, TSH must be between 0.4 and 1.9 and if it is any bit above 1.9, you have hypothyroidism and you need to be on armour thyroid or nature throid or whatever. And it's sort of like, no, none of that is correct. And you just have to take care of enough patients for enough years to get humbled enough to Know that whatever you think you know with rigidity is probably wrong.
- [89:24]
Dr. Rachel Rubin
You've seen all my gray hair that I've grown. It's true. I find again that humility of medicine is I am famous and my patients love me because I spend a lot of my day saying, we don't actually know. This is a data free zone. Here's what I think, here's how we're going to use logic, here's the tools in our toolbox. But there is that ability to really know the data so well, to truly understand. There's a lot we need to figure out. And that's why I have a research group and that's why we're trying to answer these questions, because we have more questions than we have answers. But I also need to get my patients feeling as good as possible. And that is addicting, to be honest.
- [90:02]
Peter Attia
Yeah. So here's what we do. We focus relentlessly on the symptoms and we care what the estradiol level is. We also think the FSH is a very helpful marker. So if a woman's FSH is 78 and her estradiol is 40, I'm inclined to believe she needs more estrogen. Especially if she's saying, I think I feel a bit better. I'm just not sure. Like, to me, that says I'm going to go more. And by the way, with the labs being where they are, I'm more inclined to push a little bit. But again, nothing tells me I've given her too much estrogen more than her saying her breasts hurt. And that's the advantage of doing it with these short term estrogens because I can pull it back really quickly. So I don't know if that answers your question, but I would consider myself an essentialist on labs, kind of a minimalist essentialist, but not an absolutist in either direction.
- [90:56]
Dr. Rachel Rubin
I love that and I think it's such a reasonable and logical the logic there. It makes so much sense to me. So we're totally in line with that. And that's why again, it's very confusing for our patients on social media because they want the exact answer. And you're not going to find your exact answer from one doctor on social media. Oh my gosh. You said that I have to use an estrogen gel, but I use a patch. Should I switch to a gel? Again, it's not that serious. There is a menu. If it's working for you and you feel like you're getting what you need now, it's good to get educated and learn about all the different options so that you can see what's right for you. But I think expecting that one doctor gives you all the answers is not going to happen.
- [91:36]
Peter Attia
Anything else you want to say about systemic therapy before we go and talk about local therapy in the context of genitourinary symptoms of menopause?
- [91:44]
Dr. Rachel Rubin
We haven't spent a lot of time really talking about the symptoms of menopause. What are we treating? Why do people need systemic therapy? I'm often saying that menopause has the worst PR campaign in the history of the universe. Why? Because we think it's for old people and we think it's just hot flashes, and we think hot flashes go away. There's actually not enough education. Like, we can argue about E1, E2 and E3, but the reality is doctors don't even know the symptoms of menopause. Patients don't even know the symptoms of menopause. The person who was doing my makeup this morning, she's like, I just feel awful. I feel like an old person. I'm not sleeping. I'm not fun anymore. I can't drink. Joints are achy. And I said, welcome to. You need hormone therapy. I'm always teaching. No matter who I'm, whether it's a cab driver, a hairstylist, I'm always teaching. But this idea of you have hormone receptors throughout your whole body, it is a whole body experience. So, yes, there's hot flashes and night sweats. And by the way, hot flashes are not just a nuisance. That is a neurologic vasculogenic probably. Eventually. The worse your hot flash is, the worse your risk of cardiovascular issues and things like that. Joint pain is a huge one. I never thought as a urologist, I would treat so much joint pain. Never in a million years did I think I cared about joint pain. And yet patients come in all the time and say, oh, my God, I don't get out of bed feeling old. I don't feel creaky. My joints recover again after I exercise again, empty gas tank inflammation. I think hormones are nature's joint fluid, if you will. So almost like brake fluid. Go back to the car analogy.
- [93:17]
Peter Attia
We are going to milk the heck out of this, right?
- [93:19]
Dr. Rachel Rubin
So it's really cool. So your eyes need lubrication, your ears need wax, your vagina needs lubrication, your joints actually need lubrication. And so think of horny teenager. You've got oils, oily skin. So hormones create these oils, vaginal lubrication, oil for your skin. There are androgen receptors in Your eyeballs right in these myobian glands. So I think of hormones like fluid. So as you lose the hormones or the hormones go too high or too low, it dries everything out. And so you get joint pain, you get frozen shoulder, you get plantar fasciitis. And now it was recently published on by my colleague Vonda Wright, the musculoskeletal syndrome of menopause. This idea that so many women in their 40s and 50s, everything starts to break down, it's because the gas tank is empty and that inflammation increases. It's such a simple analogy. So what are the symptoms? You get musculoskeletal symptoms, sleep issues, mood issues, bleeding changes, obviously low libido, orgasm problems, arousal problems. Pain with sex increases like crazy. I sent you a list here. What am I missing? You've got a list there.
- [94:27]
Peter Attia
Irritability, very common one. One that I was going to ask you about is brain fog and depression. This is one where I think this is a very unique one because it's one that gets easily dismissed as something unrelated. Say more about those.
- [94:42]
Dr. Rachel Rubin
It's one of the most common symptoms. All women start going to doctors in their 40s, like, doctors, I know you're listening. And you get so many people. And every day you say, oh, it's probably hormonal. But you're not giving them the solution. You're just telling them it's not cancer. So the neurologists are seeing all these patients to rule out cognitive decline or all these other issues, but really it's that brain fog because your brain is filled with estrogen receptors. This is crazy research. Okay, I don't know if you've had Lisa Moscone on, but here's this researcher from Cornell neuroscience researcher who says, hey, I want to study Alzheimer's. I want to do this. This is just in the last couple years. And she goes to her lab manager and says, okay, what's the assay for estradiol in the brain? I need to look at estradiol receptors in the brain. And the people at Cornell was like, that doesn't exist. She's like, what do you mean that doesn't exist? She's like, how can we not look at estrogen receptors in the brain? So she gets Maria Shriver to give her a giant amount of money, who gives her a huge amount of money. So she now develops this assay. This is only within the last couple of years. She just published in Nature very early findings. What would you expect? Your body is efficient. It's not going to do Things it doesn't need to do. So the hypothesis was that as menopause gets later and later, the estrogen receptors in your brain are going to downregulate. Why have receptors around when there's no estrogen to feed the brain? What did she find? The exact opposite. That actually even up to 65, she stopped looking past 65 because she's like, there's no way that's gonna matter. They increase in receptor density the older you get and it correlates to brain fog, correlates to all these symptoms.
- [96:16]
Peter Attia
My reading of that was estrogen is so important in the brain that it has to upregulate the receptors as the estrogen level goes down and down and down, every morsel. In other words, it's a lot like the way the brain is treated for glucose. The body will, if you are fasting, the muscles will within days become completely insulin resistant. It's their way of saying every molecule of glucose that that liver spits out better not go into the muscle, it better go to the brain. And so you look like you have diabetes in an effort to save glucose for the brain. And I think that's what's happening with estrogen.
- [96:54]
Dr. Rachel Rubin
And could you argue that weight gain in menopause is evolutionary so that you make more estrone or whatever? Right. That then goes to the brain because it wants every morsel that it can get. So this idea of hormones matter for the brain deeply. This is very important. So it's fascinating research, but you're going to see a lot of. Again, think of a receptor as perimenopause is happening. The receptors are full, now they're empty. Then they're full, now they're empty. Now they're half full, now they're empty. This is why we see ADHD pop up in perimenopause. All these women are saying, I have now new diagnosed adhd. It's real. Why? Because your brain is having a panic attack. Because it's just trying to figure out some stability here, which is why actually in empty gas tanks. So in menopause where you are totally empty, the brain fog gets better, the.
- [97:41]
Peter Attia
Volatility of hormone gets less. Yep.
- [97:43]
Dr. Rachel Rubin
But if we just. All I'm saying is just add some estrogen to just keep the receptors happy.
- [97:48]
Peter Attia
The other one that we didn't talk about was the urinary symptoms. So both urinary incontinence and then the higher prevalence of UTIs. You've alluded to it a little bit, but just maybe finish the swing on that.
- [97:59]
Dr. Rachel Rubin
Okay, so this is my favorite topic in the history of topics. Because we used to call this problem. Initially it was called senile vagina. That was the initial, yes. There was papers written on the senile vagina.
- [98:12]
Peter Attia
I don't even understand what that means.
- [98:14]
Dr. Rachel Rubin
An old vagina, I suppose, but then it got changed to vulvovaginal atrophy or atrophic vaginitis. That was the terminology that was used. I'm familiar with that up until 24. Before that, it was senile vagina.
- [98:24]
Peter Attia
I totally missed that.
- [98:25]
Dr. Rachel Rubin
Check the history books. Very fascinating. So vulvovaginal atrophy was sort of the common name of this. Of. Okay. As you get older, the vagina atrophies, it shrivels up, it shrinks up again. If a penis shriveled up at age 52, we'd probably have a vaccine sponsored by Pfizer. This is. They created Viagra, they would create this vaccine.
- [98:45]
Peter Attia
I love that analogy. So you're saying if by the time a man became 50, his penis became a shriveled up, useless organ, you're saying that the medical system would have probably done something about this.
- [98:56]
Dr. Rachel Rubin
What do you think? Right. Tell me what you think.
- [98:59]
Peter Attia
You might be onto something, Rachel.
- [99:01]
Dr. Rachel Rubin
This is the thing. We just called it vulvovaginal atrophy. And we said, well, if you have pain with sex or a little vaginal dryness, here's some moisturizers, here's some lubricants. Here you go. If you're really bothered, really bothered, you gotta be really bothered. Then there's this thing called vaginal estrogen that we could give you. Now, here's the crazy part of this. It's not just a little vaginal dryness. The vagina and the bladder need hormones. Babies don't have hormones. And that's why, you see, it's red, it's irritated. There are these small little labia minora. Diaper cream was invented because it looks so painful. They pee their diapers all the time. The genitals morph and change with hormones. Puberty happens, and you have a change of the genital and urinary system. What happens is, as you lose hormones, it goes in reverse. It changes the microbiome. The hormones keep the tissue acidic. It grows the healthy lactobacilli. It is. The vagina is supposed to be acidic. It's supposed to be able to fight infection. And without proper hormones, you lose that ability to fight infection. So you see urinary frequency, urinary urgency, vaginal dryness, increase in leakage, increase in urge Incontinence and recurrent urinary tract infections, which can and do kill people. We've known this since the 90s in the New England Journal of Medicine. Actually, this was on Estriol. They looked you could reduce the risk of urinary tract infections by well over 50%. We have known this all along.
- [100:24]
Peter Attia
And that was with topical Estriol. Interesting. Yeah, I was not aware of that. And yet there is no FDA approved Estriol formulation, despite that fact.
- [100:32]
Dr. Rachel Rubin
Yeah, correct. I think it's available in Europe. So the name got changed in 2014. 2014, a bunch of people got in a room and they said, you know what, this vulvovaginal atrophy thing, that's kind of a bad name because it doesn't describe what's really happening to people. So they changed the name to genitourinary Syndrome of Menopause, gsm. Now, there was one urologist, my mentor was in the room, and they almost didn't put the word urinary in it. And he fought and he yelled and he screamed. This is the power of one person to be able to change the whole world. And they said, okay, we'll listen to you. We'll put the word urinary in it. And I'm so glad they did, because the urinary problems are the things that kill people. People are dying of urinary tract infection. In fact, a large amount of money goes to Medicare expenditures when it comes to urinary tract infections. And we published last year that if Medicare patients used vaginal estrogen, which is safe for everybody, and $13 a tube, we would save Medicare between 6 and 22 billion dollars a year. Billion.
- [101:29]
Peter Attia
Just say that again, please, because I know there are people that are in the Medicare system who are going to be interested to understand that when you.
- [101:38]
Dr. Rachel Rubin
Do a low dose local vaginal estrogen or DHEA product, you can reduce your risk of urinary tract infections by more than half. They are safe to use if you've had a history of blood clots, breast cancer, whatever medical problem, you can come at me. I can tell you that it's safe. It will not only help with lubrication, help with pain, with sex, help with urinary frequency, urgency, leakage, but it will reduce your risk of urinary tract infections by more than half. It's also inexpensive and covered by your insurance. If everybody in Medicare eligibility used vaginal estrogen, we would save Medicare between 6 and $22 billion a year. And in my opinion, that is a conservative estimate because of how Many patients are getting urinary tract infections. They're going to their doctor for cultures. They're in the ICU with sepsis. This is a huge economic morbid and mortality problem that we are dealing with, and no one cares.
- [102:35]
Peter Attia
I mean, again, I always try to come up with this steel man and say, is it that they don't care, or is it that they're unaware, or is it that they feel that it just needs to fall on the shoulders of somebody other than themselves?
- [102:52]
Dr. Rachel Rubin
I think we have a marketing problem. I truly believe this is a marketing problem.
- [102:56]
Peter Attia
Okay, let me push back. Not because I don't agree with you, but I'm just gonna put my hat on that says the opposite. So maybe I am too attuned to this, but I feel like there is nothing more talked about right now. I mean, look at what Halle Berry's doing. Look what Oprah's doing. Look what Gwyneth is doing. I mean, there are so many very powerful, very influential women that are talking about this. Is this not in the zeitgeist right now?
- [103:26]
Dr. Rachel Rubin
It's getting better, but again, they don't know how to write the prescriptions.
- [103:31]
Peter Attia
So you're saying there's not enough physicians talking about this?
- [103:33]
Dr. Rachel Rubin
Yeah.
- [103:34]
Peter Attia
If it really comes down to prescriptions, yeah.
- [103:35]
Dr. Rachel Rubin
If you can't get the. It's not over the counter. If you can't get the prescription, or if you don't go to your doctor saying that you need it. We had an Instagram reel just yesterday that the patient said, my friend went to her doctor, said she was having pain with sex, asked for vaginal estrogen, and her gynecologist said, and I quote, you need to think of other ways to change your relationship from now on. It's not in the cards for you.
- [103:56]
Peter Attia
What does that mean?
- [103:57]
Dr. Rachel Rubin
Meaning you can't have sex anymore. You can't have sex anymore. And the fact is, it's not about sex. It's about urinary tract infections.
- [104:02]
Peter Attia
Wait a minute. Wait a minute. This is impossible for me to fathom. A woman went to her gynecologist and said, I'm having pain with intercourse?
- [104:09]
Dr. Rachel Rubin
Yep.
- [104:10]
Peter Attia
Any idea how old this woman is?
- [104:11]
Dr. Rachel Rubin
In her 60s.
- [104:12]
Peter Attia
Okay, and you think this gynecologist doesn't know about estrogen?
- [104:17]
Dr. Rachel Rubin
Honestly, I don't know anymore. It's incredible. It's incredible. So we could argue Viagra, 1998, Viagra comes out. Viagra changed the world billions of dollars. What is Viagra? It is a PD5 inhibitor. It relaxes smooth muscles of the penis, increase blood Flow gives you a rigid erection, so it helps with arousal for men. Okay. If you take it microdose, low doses, it can also help with BPH or urinary problems. We love Viagra. We love Cialis. Wish it was in the water. We should study it in women.
- [104:45]
Peter Attia
I did in medical school.
- [104:46]
Dr. Rachel Rubin
Oh, I'm going to talk about that. But I will argue. We have had Viagra for women long before we've had Viagra for men, and we've known about it since the 1970s. And Viagra for women is vaginal hormones. What do vaginal hormones do? They relax the tissue, they increase arousal, they increase lubrication, they increase orgasm, they help with urinary symptoms. So they do everything Viagra does, and they prevent urinary tract infections. Viagra doesn't do that. So you're talking about better than Viagra. It's inexpensive. Now, it didn't used to be. So when I got out of my training, a tube of estrase was $500. Now, because of people like Mark Cuban and Goodrx, and I've talked to Mark Cuban on my DMs and Twitter, and he knows more about vaginal estrogen than 90% of doctors. But this idea of it's not expensive. A tube of estrogen is $13.
- [105:33]
Peter Attia
And you're saying that the reason that this price has come down is. I know Mark is a very hardliner against the PBMs. Did Mark basically take a sledgehammer to that?
- [105:41]
Dr. Rachel Rubin
Yeah. Yeah. They changed the game. And so it's incredible. Oh, my gosh. It's incredible. And he understands this. He literally understands the nuances of why vaginal estrogen is so important. I can't get doctors to do that. I think he's incredible. So we have a marketing problem. We have a product that is better than Viagra for women. It's been around longer than Viagra. It's inexpensive. What are we missing? It's marketing. We're not telling the patients, we're not telling the doctors. And we have a box labeling that says, this product causes stroke, heart attacks, blood clots, probable dementia, breast cancer, and needs to be taken with progesterone. Not one of those statements is true. Not one. Okay, so we went to the FDA and says, you got to remove the box. You're killing people. And the FDA said, nah, we're going to leave the box on. This is a nightmare. Can I just tell a very personal story? I promise it won't take long. My mother just died in November. We spent six months in the icu. In Houston, Texas, six months. My mother, nobody should be in an ICU for six months. It was absolutely gut wrenching, horrible time for me. My mother had been on vaginal estrogen because want her to prevent UTIs for many, many years. You know, she's a 70 year old woman, many years. So she gets into the hospital, has a transplant, has a catheter and isn't doing well, is on ECMO and very sick for a very long time. And I said to the doctors, I said, I know this isn't the most important thing in the world, but I'd like to restart her vaginal hormones because having a catheter, being in an ICU and being immunocompromised, my mother's risks of a urinary tract infection are incredibly high. And a urinary tract infection is going to kill this woman. So I would like to restart her vaginal estrogen. And because menopause medicine is a tiny little field in a tiny little corner, they looked at me like I was an insane person. They said, what do you mean your mother's very sick right now? I said, I know my mother's very sick right now and this is one thing I can control. I sort of did a. Do you know who I am? Because I'm on the guidelines committee for GSM for the American Urologic Association. So for the transplant team, I had to write up a whole S bar of like, here's why it's important, here's the research, here's all the literature, here's the citations. And they said, but it'll increase her risk of blood clots. I said, no, it won't. Vaginal hormones don't increase your risk of blood clots. It's like hydrocortisone cream compared to Solu Medrol. Those are very different things. So then they went to the ICU team, they said, no, we can't give this to her. To increase her risk or blood clots had to convince them. Then the pharmacy, they finally got them to write the prescription. I had to teach them how to write the prescription. Pharmacy wouldn't dispense it. Why? It increases the risk of blood clots. It says so right on the box. So I had to call and yell, right, I'm trying to run a practice in Washington D.C. my brother and father are trying to advocate with me because they know, they also follow me on social media. They know this is important. Finally, the pharmacy dispenses the tube of Estrase. There's no applicator. The nurses don't know how to give it. I had to show them and teach them how to give. My mother, who was on ECMO and ultimately passed not from a uti, thank goodness, but had to show them how to dispense. I had to do all this, being one of the leading educators on this topic. What does everybody else do? And guess what? The teams changed every week. We had to do this every week and to teach them why this was important and how to do this. Vaginal hormones should not be gynecology. It should not be a small subset of menopause medicine. We could save Medicare between 6 and $22 billion a year if people understood this, if the box labeling weren't on there. I mean, it is so personal at this point, and yet it is horrible.
- [109:08]
Peter Attia
Well, I'm very sorry to hear that story, both at the personal level, but also at the meta level of what is implied. I want to clarify one thing, Rachel. If a woman is on a high enough systemic dose of estradiol, does she also need, later in life local estrogen.
- [109:28]
Dr. Rachel Rubin
Maybe even not later in life? So we find that systemic hormones are not often enough to help with the genital and urinary symptoms. Most doctors don't know this. Again, what are you afraid of? You're not adding any systemic risk. It doesn't increase. If Your estrogen level's 70 on your patch and you add a vaginal estrogen, her estrogen level is going to stay 70. You're not going to get that systemic absorption, but you are going to reduce your UTI rate significantly.
- [109:53]
Peter Attia
Has that study been done? That would be a super interesting study. Think of how easy it would be to do a study where you took a group of women that were all at systemic target of estradiol and you randomized them to a placebo vaginal cream versus an estradiol vaginal cream. You could follow these women for a year if they were in a susceptible enough population, and you would get a very clear answer as to whether or not you're getting additional UTI protection. And if the answer to that is yes, just imagine the implications there. At that point, it becomes malpractice.
- [110:23]
Dr. Rachel Rubin
We just published a study that DHEA does the same thing. It reduces the risk of UTIs by more than half.
- [110:28]
Peter Attia
Why is DHEA doing it?
- [110:30]
Dr. Rachel Rubin
So they've looked at a lot of oral. You probably know this data better than I do. Oral dhea. The data's all over the place. Because your adrenals are coming out of testosterone. Yeah, but when you put DHEA vaginally, the idea is that your vaginal enzymes convert it into both estrogen and androgens. And what's so fascinating is we know that the vagina, the vulvar vestibule, the clitoris, the bladder have androgen receptors. So us using just estrogen in this tissue may be missing the whole point. We do have patients that benefit from having an androgen in the tissue as well. And the only FDA approved product we have is intrarosa, which is vaginal dhea. Now, it's often hard to get for patients. If I could get it for everybody, I would. It's fabulous because the tissue needs androgens. The data is very good.
- [111:16]
Peter Attia
We've just started using it, so I don't have a lot of experience with it.
- [111:19]
Dr. Rachel Rubin
So there is some data. Not a lot, but there's data that shows someone with urgency, give them vaginal estrogen, switch them to dhea. It'll help those people who still have urgency.
- [111:27]
Peter Attia
Do you think it gives you the same UTI protection we published on this?
- [111:31]
Dr. Rachel Rubin
So we just published in the Menopause Journal that it shows the same decreased risk of UTIs by more than half. So that was a very proud publication that we just put out. We use it frequently. What's nice about the product, it's a nightly product. It's DHEA and palm oil. So it's very moisturizing, very lubricating. And my mentor, Irwin Goldstein published that, actually. It also helps the tissue called the vulvar vestibule. Do you know what the vulvar vestibule is?
- [111:54]
Peter Attia
Well, I know what the vulva is and I know what a vestibule is. I don't think I know what the vulvar vestibule is.
- [112:01]
Dr. Rachel Rubin
So I'm obsessed with homologs. Homologs are sort of this idea of. I'll give you an example. The penis and the clitoris are exactly the same thing.
- [112:09]
Peter Attia
Yes, yes. Sorry.
- [112:09]
Dr. Rachel Rubin
No, no, no. They're homologs of each other. Right. The head penis and the head of the clitoris, homologs. So it's what part of the body in one is the same in the other? So the homolog of the scrotal skin is the labia majora labora. Okay, you're with me. The prepuce or the hood? The clitoris and the penis both have a prepuce or a hood to it. So there's a line that goes down a penis, that goes down the penis and the scrotum. Do you remember what that's called? Median. Raphe.
- [112:34]
Peter Attia
Raph.
- [112:35]
Dr. Rachel Rubin
Yeah. You got it. Raphe. Yeah. Okay. So the median raphe is the line that goes down the penis and the scrotum straight line right in the middle. What's the homolog in the vulva? I just learned this.
- [112:45]
Peter Attia
Oh, well, it must be the vestibule.
- [112:47]
Dr. Rachel Rubin
No, No.
- [112:48]
Peter Attia
I don't know.
- [112:48]
Dr. Rachel Rubin
Close. Labia minora. Okay, so it's skin. It's ectoderm. So it is skin and we're split open. So if you take the median raphae and you split it, that's your labia minora, which very hormone sensitive. I'm not on TikTok, but I am trending on TikTok because I talk about the labia minora shrinking and disappearing in menopause and the Internet has broken because of it. So the labia minor is very hormone sensitive tissue that we do not study and we know almost nothing about, but it resorbs in menopause inside the labia minor. So if we cut into the median raphae in a man and we do this, when we put in penile implants or we do urethral surgeries, we get to the male urethra. So, Peter, your outside of your cheek is skin. The inside of your cheek is different tissue. One's more sensitive, one's thicker. So the skin of the median raphae is very different than the skin of the tube of your urethra. You agree?
- [113:43]
Peter Attia
For sure.
- [113:44]
Dr. Rachel Rubin
So if you split open the labia minora, you get to the urethra and that is the vulvar vestibule. So the tissue that surrounds the urethra in a woman, that goes all the way around. And I will show you nerdy anatomical diagrams when we're done here because I need you to know this. That is the female urethra. It's called the vulvar vestibule. It is made up of endoderm. So we think of the cervix as a transition point. But the most important transition point that affects sexual health in a woman is when you go from ectoderm of the labia minora to endoderm of the vulvar vestibule. And then past the hymen is mesoderm. It's fascinating anatomy. Why is this important?
- [114:23]
Peter Attia
Super compressed.
- [114:24]
Dr. Rachel Rubin
It's so important because if you push with a Q tip on the labia minora, they'll have no pain. If you push them on their vulvar vestibule, they'll say, that's my uti, that's my interstitial cystitis. That's the pain that I have with sex. It is rich in hormone receptors. This is why 50% of women go off their endocrine therapy for breast cancer. Because they have urinary symptoms, pelvic pain symptoms. And it is all sourced in a body part that no one taught you in medical school. And I did that on purpose because I knew you wouldn't know it because no one is taught how to examine it. They put a speculum in and they bypass it completely. And they are missing the problem. Back to the dhea. This tissue has estrogen and testosterone receptors in it. So sometimes estrogen is not enough to help this vulvar vestibule tissue. And so dhea, there's some data, there's one paper to suggest that DHEA is enough. And this is the one time that I will compound a product for a woman. Otherwise I use FDA approved products in my practice and I compound basically the amount of estrogen and estrogen. Vaginal topical cream, the 01%. And I will use a topical testosterone. 0.1% different than the 1% we talked about for libido, but a 0.1%. They rub it topically on this vulvar vestibule. You cure pain with sex. You help these UTI symptoms. Interstitial cystitis goes away in so many patients, it's miraculous.
- [115:47]
Peter Attia
Sorry, tell me again. 0.1% T. And what was the percentage?
- [115:51]
Dr. Rachel Rubin
0.01% estradiol. And we typically use Aversabase or a methylcellulose base. No, but I would love to see that studied.
- [115:59]
Peter Attia
And what's the base?
- [116:00]
Dr. Rachel Rubin
It can be usually a methylcellulose or a Versa base. There's a base called Ellage that a lot of people are using right now. Again, I am not a compounding junkie in any way. This is a miraculous compound that literally will. If you have a patient who's on vaginal estrogen, Systemic estrogen, systemic testosterone. They say, peter, I still have pain with sex. It still kind of hurts. It's always the vestibule.
- [116:20]
Peter Attia
This is super interesting.
- [116:21]
Dr. Rachel Rubin
Isn't it fun?
- [116:22]
Peter Attia
There are three other questions that I want to ask you. Going back to hormones post menopause. I'm saving the three most contentious questions for last on this topic. Question one. Someone's posing this question to you, not me. I buy your argument that hormones are safe. But I am now 56 years old. I finished menopause at 49. Isn't it too late to do anything about it?
- [116:47]
Dr. Rachel Rubin
So we have this idea in menopause medicine called the timing hypothesis or the window idea. The Window or the timing hypothesis. So the question of the timing hypothesis is, what are you afraid of? What are we worried about? Worried about blood clots. We don't want to hurt people. We're worried about cancer, we're worried about blood clots, we're worried about heart disease. But the question is, is, does the hormone therapy that we use apply to the data that we have? And I would argue it doesn't. And so there is a level of we don't know what we don't know. But even the timing hypothesis using Prempro, which was the medicine used in the whi, is under question. So Susan Davis from Australia just wrote a big paper questioning the timing hypothesis and say, actually, when you look at the data really closely, it doesn't really hold muster. We shouldn't really be forcing people to say, you cannot start hormone therapy after 60. So I think this is where shared decision making really comes into play of what are we treating? Do you care about your bones? Do you care about your sexual health? Do you care about your mental health? And do you wanna see if hormone therapy helps with these things? Now, hormone therapy is indicated for three reasons. Vasomotor symptoms, hot flashes, night sweats, that sort of thing. Prevention of osteoporosis, which to me is a green light. So anyone should be offered hormone therapy, because who wouldn't want to prevent osteoporosis? And the thing I just talked about a lot is the genital and urinary syndrome of menopause. So anybody of any age, and I'm talking even perimenopause and premenopause, vaginal estrogen or DHEA, is safe and really helpful to prevent UTIs and should be used absolutely everywhere throughout life. Throughout life.
- [118:22]
Peter Attia
Okay, now I'm going to ask another question that is the extension of that question, but I think your logic is going to hold the same, which is the hedging strategy, which says not only use as little as possible for as short a duration as possible, says you really need to stop this after 10 years. So even if you were lucky enough to catch a woman through perimenopause, you got her on hormones by the age of 49. Now that she's 69, you gotta stop it, right?
- [118:51]
Dr. Rachel Rubin
Definitely not. So that's really. There is no data to suggest stopping it. In fact, stopping it. All of your bone gains go away. They all go away quickly.
- [118:59]
Peter Attia
By the way. That was the argument put forth to me with one of the authors of the whi, who is by far the most willing to concede that mistakes Were made, which was okay. Yes. I will concede that the estradiol is doing amazing things for the woman's bones. But remember, they're gonna go away when you stop the hormones, as though that was a necessary thing to do.
- [119:21]
Dr. Rachel Rubin
So keep them on again. This idea of, if it's not broke, don't fix it. By taking a woman off of hormone therapy, you actually potentially could be disrupting any plaques that are there. You could be causing vasospasm. Like, there are all these things that could happen. We really don't wanna take women off their hormone therapy unless there is a reason to. And the only reason I honestly see is if a woman has an active cancer, that you are going to target hormones as a target for your treatment of cancer. That's not to say the hormones cause the cancer, but we have a target sometimes because all body parts have hormone receptors, and we have used hormones as a target for our breast cancer therapies and some other cancer therapies. Is that helpful? Does that make sense?
- [120:02]
Peter Attia
Yes. And it actually dovetails perfectly into my third critical situation, which is how do we manage hormones in women who are at risk of breast cancer from a familial standpoint, who have been diagnosed with dcis, which is not cancer, but increases the risk of cancer. So that's kind of a subset of the first group. And then in women who actually have breast cancer or have a history of treated breast cancer. So I would imagine you see women that fit into all four of those buckets. How do you handle it?
- [120:38]
Dr. Rachel Rubin
So first, we take a long time at my clinic and we get to know each other, and we really try to dive into the data and say, what do we know? What do we not know? And I always tell people, you can't take hormone therapy because Rachel Rubin tells you to take hormone therapy. You have to do your own research, figure out what you're interested. And so I have a lot of colleagues who are talking about this. You had Avram Blooming on your show, and he has a great book called Estrogen Matters. He's an oncologist who's questioning a lot of this research. We have amazing colleagues of mine, like Corinne Men, who is a gynecologist who had breast cancer as a young person in her 20s and now takes hormone therapy and talks a lot about hormone therapy and teaches courses on hormone therapy and breast cancer. So I am always learning. So I don't like fear. I don't like telling women they can't do things with their body. I like understanding, well, what are we Afraid of. So when it comes to the BRCA patients, if you do surgical menopause on someone and they don't have cancer and you do not give them back hormone therapy, you are trading one problem for another. You may give them extra life from a breast cancer perspective, but you are shortening their life from a bone health and a cardiovascular disease perspective. That is very clear. So the other problem is the dcis. If you are not going to give someone endocrine therapy of any kind and they're done, they have surgery, they're done, there is no reason why they can't take hormone therapy. And then when it comes to active breast cancer, there is a lot of emerging questioning in this patient population. And again, the question is, if you're allowed to get pregnant, are you allowed to take hormone therapy? And that's really the pushback that we give some people. And I think there's a lot of data that we need here, but we need to be asking these questions. I'm a urologist. When I came out of my training, it was testosterone fuels prostate cancer. Now 10 years later, it's, you have prostate cancer, sure, we can give you testosterone, no problem. If you have metastatic disease, we target testosterone, so we're going to use castration level androgen blockers. But that doesn't mean if you have localized disease, that you can't have testosterone therapy. So we think of testosterone and prostate cancer as a saturation model concept. And I actually think we need to be using that model potentially when it comes to breast cancer and have more logic and understanding and less fear. It's marketing. All prostate cancer is testosterone sensitive prostate cancer. But we don't cut off testicles for the fear that an abnormal cell will happen in a prostate. A lot of breast cancer is estrogen receptive breast cancer. Not all of it. Right. But some of it is. That doesn't mean estrogen causes cancer.
- [123:09]
Peter Attia
It's insanely helpful. And of course, it echoes exactly what Ted Schaefer said when we spoke about this after discussing the Traverse trial, which was, I think, to me the most telling thing that Ted said was, look, if I have a man who's got a Gleason 3, 3 means he has prostate cancer. And we are going to follow this and if it becomes a 3, 4, we're gonna actually have to take this thing out. We'd put him on TRT if he needed it. And his argument was exactly your argument on the pregnancy side, which is the reason we would happily give him TRT is let's just assume he's a man replete with testosterone. Would we castrate him?
- [123:45]
Dr. Rachel Rubin
Correct.
- [123:46]
Peter Attia
During that period of time of observation? Of course not. So why would I not give him testosterone if he needs it, even though he actually has prostate cancer?
- [123:54]
Dr. Rachel Rubin
And this is, again, where that patriarchal divide happens, is we're willing to take those risks and focus on quality of life when it comes to men's health. We castrate women with the mere thought that they may develop an abnormal cell in their body and completely ignore their quality of life and all of those things that go with it. And women are more than breast tissue. They are so much more than their cancer risk. And we have to understand and actually have these reasonable conversations with women. And what I say is, your oncologist is not in charge of you. They give you advice. It's like a pit crew. Let's go back to our car model. You have a pit crew, but you get to decide who's on your pit crew and who fits into your pit crew. But it can't be just one doctor. You may need someone to talk about your sexual health. You may need someone to talk about your menopause hormones. You may need a bone doctor, you may need a heart doctor. So you need to collect your pit crew. But with one doctor says, no, you can't do this with your body. I don't like that terminal. I don't think it's fair anymore. And when you give women information about how their bodies work, they make great decisions for themselves. They can look at the menu and say, listen, I'm most worried about Alzheimer's, and I've looked at the data and this is what I choose to do. Or, hey, I'm more worried about osteoporosis. Listen, my grandma broke a bunch of ribs. She had Alzheimer's and osteoporosis, and my grandpa hugged her and she broke a bunch of ribs. That's not how I want to age. So what do I care about? I don't want to get osteoporosis. I don't want to get dementia. And I've seen all the literature. Hormone therapy sounds pretty good to me. And that's really the key. I think there's a lot of people on social media may be negative about hormone therapy, but if you look, they are on hormone therapy themselves. They will say they have an estrogen.
- [125:34]
Peter Attia
Patch on, because I don't pay any attention to social media. There are people out there saying they're anti hrt, but they use hrt. What's their argument? What are they talking about?
- [125:44]
Dr. Rachel Rubin
This idea that we are overselling hrt, that not every woman needs hrt, and I'm not suggesting every woman needs hrt, but I want every woman to be offered the menu. I want them to know what they are. Just like I want people to know how to exercise and lift weights and eat healthy. Here's the menu. If you choose to smoke and drink and do drugs, that is your choice. But I want you to know that the menu exists.
- [126:08]
Peter Attia
What do women need to be aware of? Not every woman can come and see you. Not every woman has access to a doctor who has the breadth of knowledge that a select few do in this space. So a how can women find practitioners near them and what do they need to be aware of? What are the exploitative practices out there that they need to be mindful of and not get duped into either dangerous therapies or overly extractive therapies?
- [126:40]
Dr. Rachel Rubin
I think there's danger on both sides. There's danger going to the doctor for 10 minutes and saying, oh, that's not safe. You don't want to do this. And there's dangers of going to the very expensive pellet clinic that is going to overdose you and charge you lots and lots of money. So I like being somewhere in the middle and getting a few opinions here. So this is where opinions can be. A bunch of people on Instagram, don't just follow one people, follow a bunch of people. If you like books, there's tons of books now on menopause.
- [127:06]
Peter Attia
What are some of your favorites?
- [127:07]
Dr. Rachel Rubin
You've got Mary Claire Haver is the most popular book called the new Menopause. Heather Hirsch has a great book called pick your menopause type. There's been a hot and bothered. A journalist wrote a great book on perimenopause. Jancy Dunn. Tamsin Fadal just wrote a book about menopause, who's also a reporter. Estrogen Matters is a great book, a really great book. There's a lot of books now, thank goodness. There's one called the Menopause Manifesto. There's great books on menopause. There's also podcasts now. There's great podcasts out there. Oprah just did a special. There's documentaries on PBS now. So menopause is having a movement. So you can't have this excuse anymore of, oh, my doctor doesn't do this. Go find a different doctor. They're telemedicine companies.
- [127:46]
Peter Attia
And what's their website?
- [127:47]
Dr. Rachel Rubin
So menopause.org is the menopause society website that doesn't guarantee you have Someone who knows everything. But menopause.org means somebody took a test and put some effort into saying I care about menopause. I'm on that website. But isswish, isswsh.org is the women's sexual health society. So people who we care about menopause and sexual health. So that's a great place to find a provider. So those are two websites that can help you find someone. Again, you have to advocate for yourself because no one will do that other than you. And so I think the more you educate yourself, the more you can find the right people in your pit crew who are going to fill that gas tank and get you to where you want to go.
- [128:27]
Peter Attia
Do you feel that there are too many women that are still getting their hormone therapy in the dark alley with highly sus individuals? And if so, what would be a clue that you're in that camp? Because there's nobody that's in that camp that knows it. I want a woman who's watching this, who's not getting great medical care but thinks she is to maybe get a bit of a hint as to what that might look like.
- [128:48]
Dr. Rachel Rubin
I think this is a problem. When your doctor says no, you can't have anything that's suspect. If your doctor says you can only have this really expensive product that has to be inserted into your butt four times a year and you have to pay me thousands of dollars, that's extremely suspect. If they say you have to pay lots of money for this special compounded product that's safer and more effective, I call red flag on that situation. If you have to give very expensive saliva testing labs and they're making you pay a lot of money, very suspect. Again, that doesn't mean you can't do it. If it's working for you and you're happy you have body autonomy, you do what you want. But know that there's red flags there. I think the pellet industry. I have a big problem. We have an FDA approved pellet for men. It can be FDA approved. I don't not upset with a pellet as a concept. If the pellet companies cared about women, do the studies go through the fda? Show me. It saves billion dollar industry. If you believe that it's the greatest thing in the world, show me so that I can start using it. Because the FDA is a pretty good compounding pharmacy. So do the work. I have my beef with the fda. Hello. You need to take that box labeling off estrogen products, especially vaginal estrogen. But if the pellet companies deeply cared about women, which they say they do do the work. Everyone takes advantage of women. All the supplement companies, they take advantage by promising these things to women. But they don't do the work of science. So that's what I ask is just do the work.
- [130:13]
Peter Attia
Rachel, as expected, this was a fantastic discussion and I think it adds to what we are trying to do in this podcast, which is really have nuanced and deep discussions about important topics. Not every podcast I do gets to impact that many people. Some of them impact nobody. They're just really esoteric, but they fit into my curiosity window. But this is kind of a topic that really impacts almost 100% of the population because 50% of the population is who we just talked about. But the other 50% of the population would be hard pressed to say that they don't care about at least one person in that other group. So 100% of people are heavily impacted by what we just discussed.
- [131:01]
Dr. Rachel Rubin
Can I say one thing real quick? I'm also a men's health doctor and I lecture my urology colleagues and I say, and you talk about longevity and here are the things you can do for longevity. I think you're missing one point and that is that men who are divorced, single or widowed have horrible health outcomes. Horrible. Whether you look at mental health, prostate cancer, cancer outcomes, horrible. They die sooner. So if you want longevity, if you want to keep living, you have to keep people partnered. And when do people get divorced? Between 40 and 60. That is the age of perimenopause and menopause. Menopause is killing men. It is killing men because it changes their marriages and it leads to divorce, which leads to death. I give this lecture if men's health doctors, if doctors truly cared about keeping men alive, they would do menopause medicine because that is one of the most important ways to keep men alive. So that's my other argument for you to focus on this and really make change here. And I just can't thank you enough for this platform because it is everybody's problem.
- [132:05]
Peter Attia
Rachel, thank you very much for the work you're doing and thanks for coming today.
- [132:08]
Dr. Rachel Rubin
Thanks for having me.
- [132:09]
Peter Attia
Thank you for listening to this week's episode of the Drive. Head over to Peteratti md.com shownotes if you want to dig deeper into this episode. You can also find me on YouTube, Instagram and Twitter, all with the handle Peteratti MD. You can also leave us review on Apple Podcasts or whatever podcast player you use. This podcast is for general informational purposes only and does not constitute the practice of medicine, nursing, or other professional healthcare services, including the giving of medical advice. No doctor patient relationship is formed. The use of this information and the materials linked to this podcast is at the user's own risk. The content on this podcast is not intended to be a substitute for professional medical advice, diagnosis or treatment. Users should not disregard or delay in obtaining medical advice from any medical condition they have, and they should seek the assistance of their healthcare professionals for any such conditions. Finally, I take all conflicts of interest very seriously. For all of my disclosures and the companies I invest in or advise, please visit Peter Attia, where I keep an up to date and active list of all disclosures.