Peter Attia MD348 ‒ Women’s sexual health, menopause, and hormone replacement therapy (HRT)
EVERY SPOKEN WORD
145 min read · 28,566 words- 0:00 – 1:56
Intro
- PAPeter Attia
100% of people are heavily impacted by what we just discussed.
- RRRachel Rubin
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. 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. We saw a decrease in overall mortality, a decrease in cancer-specific mortality. The reality is this is half the population. This is not niche medicine. If a penis shriveled up at age 52, we'd probably have a vaccine sponsored by Pfizer, right? This is, this is-
- PAPeter Attia
[laughs]
- RRRachel Rubin
They created Viagra, they would create this, this vaccine. No one even tells women-
- PAPeter Attia
I, I love that analogy. There are two hormones we've talked a lot about, but there's a third that we haven't yet talked about. Doesn't get enough attention in women, and of course, that's testosterone.
- RRRachel Rubin
I, I don't know who said, who decided that men get testosterone and women have estrogen. Like, we have both of the hormones. We love to gaslight women and say, "Well, if you have your period, your hormones are normal." And the reality is, is that's not true.
- PAPeter Attia
I know there are people in the Medicare system-
- RRRachel Rubin
Mm-hmm
- PAPeter Attia
... who are gonna be interested to understand that.
- RRRachel Rubin
If everybody in Medicare eligibility used vaginal estrogen, we would save Medicare between $6 and $22 billion a year. They're going to their doctor for cultures. They're in the ICU with sepsis. Um, this is a huge economic and mortality problem that we are dealing with, and no one cares. 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.
- PAPeter Attia
[upbeat music] Hey, everyone, welcome to the Drive podcast. I'm your host, Peter Attia. Rachel,
- 1:56 – 4:55
Rachel’s training for sexual medicine & women’s health
- PAPeter Attia
thank you so much for making the trip out to Austin. I have been looking forward to this episode for a while, and I'm, uh, willing to go on record, uh, predicting that this will be a very popular episode given the nature of our, uh, of our discussion.
- RRRachel 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.
- PAPeter Attia
Um, I almost don't know where to begin, um, 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, um, and maybe help us understand how your training in urology led you to what you're doing today because most urologists, uh, wouldn't be doing exactly what you're doing. When we think of urology, we think about, you know, prostates, we think about kidneys, we think about bladders.
- RRRachel 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, right? We- we're board certified to take care of everybody's, uh, genital and urinary tracts. And so what the... 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, um, I trained in urology really because I was interested in women's health, but I also was interested in sexual health, sexual medicine. And, um, I didn't like delivering babies. I didn't like OBGYN. I, I... 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, and the magic of urology is also that you really can s- you get to know your patients. It's not like, you know, when you did surgery, you take out someone's appendix, and you never see them again.
- PAPeter Attia
Right.
- RRRachel Rubin
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 kind of gravitate towards what is easy, not what is hard. Um, and so it's just been a joy. Um, and really, I've 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, uh, to my colleagues about how we really need to care about the whole, you know, like everybody.
- PAPeter Attia
I really mostly wanna 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 and 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, um, you'll probably notice kind of a bias in what I wanna talk about, uh, vis-à-vis women specifically. So let's s- let's start with
- 4:55 – 14:34
Hormonal changes during ovulation, perimenopause, & menopause
- PAPeter Attia
perhaps the, the biggest and most obvious, uh, difference between men and women. Um, 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. Um, and that's, you know, to be contrasted with the way men's sex hormones kind of decline over time a little more slowly. So, um, I-- again, the listeners of this podcast are highly erudite, and they won't need, like, the lengthy, uh, dissertation, but just give us a quick overview of what the heck is happening in menopause. Why is it happening? Um, and, and, and, and, and then we can get into maybe what, what some of the symptoms are before women might really notice them.
- RRRachel Rubin
Yeah. Well, you know, I certainly did my research, and I am not a car person, but I know you are-
- PAPeter Attia
Hmm
- RRRachel Rubin
... a Formula 1 guy, and I got a, a very interesting email last week that said, "Dr. Rubin, my wife is seeing your practice, and she, her libido is now like an F1 Formula 1 race car, and I'm like a 1988 Honda Civic. What can you do for me?" And I think that really my analogy I really like to look at is sort of the gas tank analogy, this idea that men as they age, you know, 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 in the age, at age 52, their gas tank is empty, right? This is a castration event. We don't have many castration events in men's health.
- PAPeter Attia
Hmm.
- RRRachel Rubin
And so menopause is sort of a your gas tank is officially empty. There's not much i- 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.
- PAPeter Attia
Hmm.
- RRRachel Rubin
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.
- PAPeter 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-
- RRRachel Rubin
[chuckles]
- PAPeter Attia
... 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... You know, if, if we have kind of hormones running like this during premenopause, they're like this during menopause, but it's, this transition is nothing like linear. It's ch-ch-ch-ch-ch.
- RRRachel Rubin
It looks kind of like the stock market, actually.
- PAPeter Attia
Yeah.
- RRRachel Rubin
It goes up, it goes down, and even it's not even just checking it every three months. If you check it every 10 days-
- PAPeter Attia
Yeah
- RRRachel Rubin
... 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, right? We think of the... You talk a lot about continuous glucose monitors. I would love continuous hormo- uh, sex hormone monitors and, and unfortunately I know there'd be a lot of unintended consequences and bad things that would come of it.
- PAPeter Attia
Yeah.
- RRRachel Rubin
But I'd be very interested because the book says our low, so if you have your period that you are bleeding, that's day one, your low is not zero, right? In fact, it's probably somewhere 40, 50 is probably what the low should be of estradiol.
- PAPeter Attia
Of estradiol, yep.
- RRRachel Rubin
And that's, you know, uh, picograms per milliliter, um, as opposed to testosterone, which we do nanograms per deciliter, as you know. So, uh, so pi- let's say 50 is your low. Then you go and ovulate, and that's in your mid-cycle, and usually it's about 150, 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're 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 three quarters tank at 150, then down to a quarter tank. You can drive wherever you want to go, you know, during that time. What happens in perimenopause, and it is this chaos and erratic sort of 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. We've seen estro- I had a lady come in, you know, her, uh, b- her day one, her estrogen was 200, and her day 10 her estrogen was 900, right? So this is this wild fluctuation in perimenopause.
- PAPeter Attia
And, and what I'd like to do now just 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 l- l- let's also have you do an explanation now of the role of FSH and LH on the brain, 'cause you've already referred to that, and what the feedback cycle looks like with estrogen. I just want to make sure people are, are following the physiology you're describing.
- RRRachel 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 OBGYNs 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, and we think our doctors know everything, and unfortunately they don't. And so what happens is estrogen, you know, um, y- again, you have your period, your lining of your uterus is shedding. Your estrogen is kind of at its all-time low.
- PAPeter Attia
And, and again, just to make the obvious statement, it's because most of the time when a woman ovulates, she does not get pregnant.
- RRRachel Rubin
Right. Let's talk to the non-
- PAPeter Attia
So, so that's why it's shedding. Yep.
- RRRachel Rubin
Right. In this non-pregnancy state, right? 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, right? So this egg is developing, and then as your, you know, the LH is sort of your brain's c- uh, sort of marker of, 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, you know, 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, you know, sort of that's when progesterone is around. And so you get this surge of progesterone. When there is no fertilization, that, that shell of the egg sort of of, uh, evaporates, and then you lose your progesterone, and it is that withdrawal of progesterone that causes the uterine lining to shed. Now again, this is very confusing for people because hormones through that time, your estro- your progesterone goes from very, very low to, after you ovulate, very, very high, um, 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, right? They're sort of-
- PAPeter Attia
Yeah, a lot of my patients don't read the book about-
- RRRachel Rubin
It's called physiology
- PAPeter Attia
... what their physiology is supposed to do.
- RRRachel Rubin
[laughs]
- 14:34 – 17:55
Why women have such varied responses to the sharp drop in progesterone during the luteal phase & after menopause
- PAPeter Attia
do you buy the argument, which is, uh, the, 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, you know, progesterone levels are rising. We're building up the endometrial lining in preparation for, uh, pregnancy. Again, most of the times that's not going to happen. Lining sheds, progesterone crashes. This is what's referred to as, you know, obviously PMS, and some women are somewhat unfazed by that, you know? 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?
- RRRachel Rubin
I think it's a really important question, and we see this clinically all the time, right? In that if, uh, if you give somebody, say, micronized progesterone or a 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, right-
- PAPeter Attia
Hmm
- RRRachel Rubin
... and the metabolites of progesterone and how the body, you know, how the receptors, uh, in the brain, uh, sort of use these, uh, molecules. And so I think we just don't know enough about... I, 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. W- this is why I come on this, uh, 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. You give, you know, somebody, a- and I will pull up, put up that menstrual cycle, uh, 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 sort of hack the system to help you feel better, and how are you gonna 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. It helps their sleep. It reduces anxiety.
- PAPeter Attia
Oh my God.
- RRRachel Rubin
Magic.
- PAPeter Attia
Changes their life.
- RRRachel 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've got no s- you know, it's fine. Like, it protects my-"
- PAPeter Attia
Right, but if you tell me I need to take it, I'll take it.
- RRRachel Rubin
If you tell me I need to take it to protect my uterus-
- PAPeter Attia
Right
- RRRachel Rubin
... no problem. And then you've got a third of patients who are very sensitive, right? The progest- and even within that third, it is extreme. I mean, we see progesterone allergies where people have horrible reactions to, uh, it makes me too sleepy. It makes me feel bloated. I don't like this. And so I don't, as a, as a clinician and a interested researcher, like, I don't know exactly enough to be able to spot who those people are ahead of time.
- PAPeter Attia
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, 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. Um, and so, you know, 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 measurements, you know, and then estradiol and progesterone nonexistent.
- 17:55 – 20:37
Health risks for postmenopausal women
- PAPeter Attia
Um, 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, uh, mental health, emotional health, the, the, the whole picture of her health, cognitive health, everything? What is, what is, what is she worse off for at that, uh, at that period of time?
- RRRachel 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 in that patient?
- PAPeter Attia
Yeah, and that's why I want to start like this.
- RRRachel Rubin
And so I think it's super interesting 'cause 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, um, she certainly will have the microbiome and genital and urinary changes of not having hormones. So as a urologist, this is the actually one of the things that, one of the couple things that will kill her, right? As the, you lose hormones in the genitals, which are very hormone sensitive. The bladder's very hormone sensitive. You change the microbiome. You increase, uh, 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, right, which we know more people die of hip fractures, uh, 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, your, your going back to the life that you lived is very challenging, right?
- PAPeter Attia
Yeah.
- RRRachel Rubin
Or you die. Um, and so there's also the risk of we know dementia and Alzheimer's much higher in, in women, and we can argue the data, and I don't think we actually have good data about, you know, whether hormones are, you know, when to start them and, 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 of me- 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.
- PAPeter Attia
Mm-hmm.
- RRRachel Rubin
But again, an empty gas tank is still an empty gas tank, and so we see a lot of challenges, you know, sort of in this time period.
- PAPeter Attia
We talked about obviously the risk of dementia. We talked about the risk of osteoporosis, cardiovascular disease, um, colon cancer, right? All of these are risks that are pretty clearly going up in the absence of hormones. Um, so
- 20:37 – 30:59
History of hormone replacement therapy (HRT)
- PAPeter Attia
h- do you want to talk about the history of HRT? I mean, you know, it was a largely normal practice, uh, in the 1960s. They, you know, certainly had some fits and starts, right? They initially were just replacing estrogen. Um, figured out pretty quickly, i.e. within a few years, that if you only gave a woman estrogen, you were gonna run the risk of endometrial cancer going up because the endometrial lining just continued to get bigger and bigger and bigger, and you eventually developed hyperplasia, which presumably became metaplasia and ultimately cancer. They figured out pretty quickly how to combat that if you just oppose the estrogen with progesterone. You keep the endometrial lining in check. And this largely became the, um, uh, the standard of care through the 1980s, uh, and into the 1990s, and this was largely validated by epidemiologic, uh, 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, right? 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, two components, a nutritional component, uh, that was asking a question about low-fat diets and then, um, a component that was looking at the HRT. So, um, would you like to pick up the story as to how the study was designed, maybe talk about some of the, the, the potential pitfalls of it, and, and ultimately how the results of that have been misunderstood and misinterpreted for so long?
- RRRachel Rubin
The fact that this story hasn't been made into a Hollywood, uh, biopic mega drama, I don't know, right? 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, um, and they did a press conference, okay? Before the study was published, they did a press conference. Have you ever seen the NIH do a press conference-
- PAPeter Attia
[laughs]
- RRRachel Rubin
... that Matt Lauer talked about or that was made it on you, you know, like Good Morning America? Like they did a press conference. It, I remember I was in medical school at the time. Like I remember sort of, uh, you know, this happening, and they said, "Okay, this, we had to stop the study early. It is increasing the risk of breast cancer and increasing the rid of, risk of blood clots and cardiovascular disease, and we have to stop the study." And everybody, it, this There's different statistics out there, but people say about 40% maybe of women were on hormone therapy at the time. Overnight it went-- it crashed to nothing. You're talking billions of dollars of an industry went to nothing. And the, the people who were prescribing the hormone therapy were like, "This doesn't make any sense. I, 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?" And then over the years, you know, then they published the paper and, and as we talked about ear- you know, before we did this podcast, is that they misinterpreted the data so drastically and scared everybody so, with so much fear that you actually have an entire generation that has forgotten how to prescribe hormone therapy. And this is where w- the nightmare that we're living in today because now we realize that the data was misinterpreted. So w- if we talk about... And again, and the 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 a, a progestin. It was not sort of the what we call, you know, more, um, 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're still practicing fear-based medicine 30 years later, whatever it is, saying like, like, 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 m-medicine, right? 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, right? We saw a decrease in overall mortality, a decrease in cancer-specific mortality. Um, 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, right? 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 'cause you can increase blood clots, right? 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 were on the estrogen alone, so they didn't have a uterus, so they didn't need the progestin therapy, had a decreased risk of getting and dying from breast cancer, right? And that didn't make the news. Estrogen was never this c- even in that study that put the box labeling on all the products, it's not true, right? 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. 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 'cause many of them had been on hormones in the past. And when you use a correct placebo group, the, 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.
- PAPeter 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, your, your vision into my carotid artery-
- RRRachel Rubin
I see it bulging.
- PAPeter Attia
Yeah. You'd, you'd notice that my, my blood pressure is up. It-- I'm probably at 180 over 120 right now. Um, first off, I think that was a remarkable, succinct summation of the WHI. I'm only going to repeat a few things be- 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.
- RRRachel Rubin
Shout it from every rooftop you can find.
- PAPeter Attia
Um, and truthfully, I have friends, female friends, and I have patients who to this day are paranoid about hormones, and I just, I, I want to offer yet another, uh, opportunity for them to, to sort of understand what's going on. So this was a study that had, you know, two parallel arms, right? One where women without a uterus were just randomized to either the synthetic, uh, 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, um, elephant in the room here was 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. Now, um, 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, right? So you had a 24% higher chance of getting breast cancer if you took the, um, 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, um, I have a treatment for you that is gonna 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, right? So the absolute risk increase for these women was 0.1%. So to put that in less technical terms, it meant that you w- 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-- 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 increased rate to the women who didn't get the hormone. This, to me, is... And I'd like you to push back on this, although I'm worried you won't be able to 'cause you share my bias. This is the greatest injustice imposed by the modern medical system in our lifetime.
- RRRachel Rubin
You are not gonna get pushback from me on that. I think women's-- I think that... This is a disaster.
- 30:59 – 36:52
Medical system’s failure to train doctors in HRT after the WHI study & its lasting impact on menopause care
- RRRachel Rubin
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. I was asked-- 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 sort of 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 GLP-1s or any of these lipid-lowering agents or all of the things that you've been pushing. The problem is you now have a, you have a brain drain, I think, because the doctors who prescribed hormone therapy either retired or died, right? 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 w- " People don't know how to do this. And it's not a small n- like it's, it's a huge problem. And the reality is this is half the population. This is not niche medicine.
- PAPeter Attia
Right.
- RRRachel Rubin
The fact that menopause medicine is the tiniest little, uh, room of off, of subset of gynecology, which it should not be under gynecology, right? This is whole body medicine, and yet nobody seems to care.
- PAPeter Attia
Yeah, it's really interesting to hear you say that because you're, you're highlighting something that's as dramatic and potentially more dramatic than the thing I've tended to focus on. I've, 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, and do this. I've tended to focus on the lost generation of women, right? 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. Like g- we just went through the entire list, right? Like so 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. Um, 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 endured. Didn't even try to quantify that 'cause I don't know how to. But, you know, 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, right? Like they're the ones that got absolutely screwed by this system. Um, you're highlighting something equally and potentia- 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.
- RRRachel Rubin
Yeah, I mean, the data's very clear on this, right? 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?
- PAPeter Attia
Zero.
- RRRachel Rubin
Zero, right?
- PAPeter Attia
Not one minute.
- RRRachel Rubin
I didn't learn one minute of it. And so here's the-
- PAPeter Attia
I did learn that hormones were bad.
- RRRachel Rubin
Oh, yeah, you learned-
- PAPeter Attia
Yeah, yeah. Not that I know of.
- RRRachel Rubin
Right, right. So, so there's this, this-- So, so because you are taught hormones are dangerous or the bodybuilders take the hormones, the snake oil salesmen take the hormones, right? Like we don't talk about this in real medicine, right? So you actually have everyone says, "It's not my, it's not-"
- PAPeter Attia
Yeah
- RRRachel Rubin
... "my i- industry. It's not my thing." I went to this internal medicine conference y- you know, yesterday, and all the internal medicine doctors were saying, "But this isn't, this isn't my field. Like 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. Like 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 i- we have to change this. We have to change this on a big level 'cause I need the ICU doctors and the pulmonologists and the card, and, and the, you know, uh, uh, the heart doctors and all the doctors to know that menopause affects their organs, right? Colon cancer. Why aren't, why aren't GI doctors talking to women that estrogen prevents colon cancer? Why are we checking DEXAs at 65? Like why are rheumatologists not prescribing hormone therapy? I found out recently that psychiatrists, 'cause 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, right? 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, of medicine. It is insanity. We're living in a nightmare.
- 36:52 – 49:45
Underappreciated role of testosterone in women’s sexual health
- PAPeter Attia
Yeah. So let's talk a little bit about how we go about doing things. Um, 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, um, very linked to these two hormones, uh, doesn't get enough attention in women, and of course, that's testosterone. So, uh, before we get into how one should think about replacing hormones, can you talk about the relationship, um, of testosterone to, to women’s sexual health and what's happening to testosterone levels during this transition from peri to menopause? Because of course, this, I want to bring this into the HRT discussion.
- RRRachel Rubin
So it's super interesting, and I'm very passionate about this topic. And so I think it comes from this idea that I do, uh, testosterone for men all the time, right? I'm very confident. I love prescribing testosterone for men's sexual health for, um, uh... And actually, very interestingly enough, when we prescribe testosterone for men, remember, their gas tank doesn't get empty. It gets low, right? It's off-label, right? We are doing off-label testosterone therapy in men. Unless they have Klinefelter or some, you know, significant medical problem, like 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, right? So the, the thing about women and 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, I don't know who said, who decided that men get testosterone and women have estrogen. Like, we both have all of the hor- Like, we, we have both of the hormones.
- PAPeter Attia
Sorry to interrupt.
- RRRachel Rubin
Please.
- PAPeter Attia
You've probably heard me make this point before, 'cause 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.
- RRRachel Rubin
We... Way more, right?
- PAPeter Attia
Yeah.
- RRRachel Rubin
And I love sharing that, right? When you put everything in the same units, we are testosterone-driven beings. Both of us, right, are testosterone-driven beings. And so it's, you know, again, it, it... and, and we don't teach this to OBGYNs. No OBGYN knows... Well, some do, but, 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."
- PAPeter Attia
Mm-hmm.
- RRRachel Rubin
Drives me insane. This-- Women are told this all day, every day, is, "Well, you, you can't possibly have a hormone problem 'cause you're getting your period regularly." And the reality is, is that's not true. Why? 'Cause if no one taught... That, 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, right? That is nature's way of saying, "Let's make a baby." We know that. We know that your libido goes up around ovulation 'cause your testosterone goes up. And so there is this age-related decline in testosterone, and here's a- 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 in birth control, but as soon as you become menopause, everybody's afraid of hormone therapy. It makes no sense.
- PAPeter Attia
Hmm.
- RRRachel Rubin
So birth control is high dose, I would argue, you know, sort of the hormone therapy we were talking about in 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 ethinyl estradiol and a synthetic progestin. It doesn't add back testosterone. So we are botching testosterone for women sort of for 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 d- uh, there are some studies that indicate potentially depression and anxiety can increase because we do think there's a testosterone, uh, uh, effects on the brain. But we have global consensus, and I don't know if you've read the news lately, Peter, but, like, 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 on, uh, before that. So, but the, the consensus is it works. But everyone has emotions about testosterone. I don't know. 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, so people are... And there's no FDA-approved product for women, except in Australia. It's approved by their, their governing body. And so you have a lost art of knowing how to give people back testosterone when they are symptomatic.
- PAPeter Attia
And I think this is an area where women sometimes are also a bit concerned about what happens if I take testosterone, because testosterone understandably has, conjures up images of All sorts of things from large muscles, you know, big mustaches, uh, lots of, you know, other things. So, so how do you talk to women about this? Um, we, we enjoy having these discussions, and, um, and also acknowledging side effects, right? Like, the most common side effect we see in women is acne, right? And, and I, I don't think I've ever gotten to the point where I've seen any of the really dramatic side effects. Um, 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, that's, 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." Um, but h- how do you, how do you talk about the risks of testosterone therapy?
- RRRachel 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 testosterone therapy, and, uh, 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, 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-
- PAPeter Attia
Mm-hmm
- RRRachel Rubin
... than actually stop testosterone therapy because of the side effects. That's my-
- PAPeter Attia
Yeah
- RRRachel Rubin
... sort of 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, you know, um, but that's when you get really high with your doses. We really don't see it clinically. Yes, could you... I tell them to put the, I, I, I use FDA-approved testosterone for men, just at doses kind of one-tenth 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 hair, with leg hair. Um, I don't have that many patients stop for acne, oily skin. Um, again, I think there's that fear when you get really high in the dose. So I'm not a pellet, a promoter, or user because you get super physiologic levels.
- PAPeter Attia
Yeah.
- RRRachel Rubin
And I can't take it out if you get a pellet put in. And so if you have deepening voice or clitoromegaly or, you know, uh, uh, hair, uh, issues, these are the challenges with some of these super physiologic levels. But when we're using sort of, um, a reasonably dosed, uh, uh, uh, uh, level, like, um, uh, topicals, we really see magic happen. And, 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. 'Cause your ovary does three, it probably does more than three things, but at this point, estrogen, progesterone, and testosterone. When we add that testosterone piece, I, it's wild. All the, the patients come back, and they say me, "Wow, I feel like me again." It's wild, right? 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, right? I can't not want to give them that as an option on the menu.
- PAPeter Attia
Let's just finish the swing on, on testosterone. Do you prefer then to rely on the topical version of, which would be like an AndroGel-type product, um, and just dose it at a much smaller dose?
- RRRachel Rubin
Yeah, that's typically how we do it and how our guidelines sort of look at it. So ISSWSH, 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 sort of how-to practice guideline that they took from the global consensus. And they do recommend using sort of that FDA-approved testosterone for men and using it at appropriately, uh, doses for females. So, um, I like Testim, which is sort of the 1% generic testosterone gel. I brought, uh, I'll show it to you. I brought it for you to, to show you. It's a, it's a five-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. They, injections, orals, those are much better. Um, and so I tell my patients, use a blob or .5 mL, so they can put it in a syringe if they want to and dose out that .5 mLs. They take a blob. They rub it on their calf every day. Um, and so, um, just don't use, the whole tube should last you about a week or 10 days. That's kind of, it's an ish, right?
- PAPeter Attia
Yeah.
- RRRachel Rubin
Like, it's, it's not an exact, a, a precision science, but the patients can figure this out. It's not that challenging. And I, 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. Like, I will tell patients, like, "You need to do this regularly, and I think it's gonna be three, four, even five months before you're gonna really wake up and say, 'Wow, this is working. Oh my gosh,' like, 'Someone just walked across the street, and I did a cartoon-style head turn with my eyes popped out of my head.'"
- PAPeter Attia
[laughs]
- RRRachel Rubin
"Oh my gosh, I initiated sex. Wow, that orgasm was easier to have." Right? It's, these are the things that patients notice. I also get patients telling me their stress incontinence is slightly improved. Why? 'Cause the urethra has testosterone receptors in it. We know that for all genders. Um, a- and this, these are the kinds of things my patients will report. But I think it, I don't know, what do you think? I think it takes a while.
- PAPeter Attia
Hmm. That's an interesting question. Um, I, I, I mean, I definitely agree that that's true for some people. That said, I've also seen people who, within weeks, f- report feeling better. Now, the challenge here, of course, is the only way you could understand this is through blinding, right?
- RRRachel Rubin
Mm-hmm.
- PAPeter Attia
We just don't know how significant the placebo effect is. Um, and, and therefore, it's hard for me to, to discount or know whether-
- RRRachel Rubin
Well, we do. We do because we have studies on testosterone which show-
- 49:45 – 57:24
Bias against HRT—how institutional resistance is preventing meaningful progress in women’s health
- RRRachel Rubin
I talked about the labeling on testosterone being removed, that it doesn't worsen cardiovascular disease. Why? 'Cause they did the Traverse study that your listeners know about.
- PAPeter Attia
Yeah.
- RRRachel Rubin
That proved it. The box labeling on estrogen products which says that estrogen causes stroke, blood clots, heart attacks, probable dementia, like, 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.
- PAPeter Attia
Why do you think this is happening? If you, if you, if you try to steel man the case for the other side, w- where, where are they in their thinking on this?
- RRRachel Rubin
I think medicine has a humility problem, uh, and a, um, a deeply ability to say, "Hey, we d- 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 say, to evolve in their thinking. And for some reason, women's health comes with so much bias, and it is... The amount of money that goes into women's health research is, like, worse than it was 10 years ago, right? Like, like we are-
- PAPeter Attia
But is this a paternalistic... I mean, I hate to put sort of-
- RRRachel Rubin
I, I, I don't-
- PAPeter Attia
... sociology on top of this, but what... Like, w- again, when I, I, as you know, I've 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. Um, but I also can't even wrap my head around their thinking. Like, I can't steel man their case.
- RRRachel Rubin
I wake up in the morning, I'm like, "How is this real life?" Like, we met... Okay, I'll give you an example. We met with the chief before the administration changed. We met with the, um, the t- I think it was the, 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, um, which is basically microdosing hormones, and they prevent UTIs by more than half. When you use vaginal hormones, you treat the genitourinary sym- uh, syndrome of menopause. And we said to them, we said, "Your labeling, this should not have the same labeling of all estrogen products. You should remove the labeling." And they said, "Well, we're really gonna 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?" But 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 gonna look at allergy now." Uh, you have entire, uh, departments... We, we did a study once on pelvic pain. Uh, 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. We, it, it, it's true, and unfortunately, it's not getting any better.
- PAPeter Attia
I usually do not subscribe to, 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, right? Which is if the tables were turned and the WHI was really the, you know, MHI, right, 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"?
- RRRachel Rubin
To the Traverse trial, right?
- PAPeter Attia
Yeah.
- RRRachel Rubin
There were two bad studies that were done, horrible studies that made no sense, that showed testosterone had some dangers. So they, 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.
- PAPeter Attia
And by the way, the Traverse trial's not even a great trial. Like, I've been so critical of the Traverse trial.
- RRRachel Rubin
Amen, right?
- PAPeter Attia
I, 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.
- RRRachel Rubin
But that, that's the point, right?
- PAPeter Attia
Yeah, but that your point, yeah.
- RRRachel Rubin
Like, totally, 'cause you could look at data. Oh, there was an increase fr- 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 gonna do a study for five years. Why are you giving people gels? You know, is that the right thing? So why are we looking, why do we care what the people of the Women's Health Initiative said 20 years ago? Why is that even news, right? 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, 'cause they're not teaching it, right? You don't have the OBGYN saying this is wrong because they're delivering babies and women are dying in childbirth. Women's health, like menopause health in particular, is important to nobody, right? And when it's nobody's problem, nobody takes ownership of it.
- PAPeter Attia
Yeah, I mean, I do believe this is going to change, and I, and I don't know who said this, but it's, it's a, it's a great quote that said, uh, "Funeral by funeral, science makes progress." And so, you know, that's not a, that's not a pr- that's not a great explanation for what's about to happen temporally because, you know, it's gonna be a while before everybody who held that belief, you know, in their, in their, in their soul is, is no longer around. Um, but it, it does give me hope that, um, a new generation of, of women will come along and take ownership over their health. Um, and, and, and, and, and look, I've seen a change in 10 years. I mean-
- RRRachel Rubin
Did you?
- PAPeter Attia
... 10 years ago when I was prescribing hormones to women, you c- you cannot believe the fights I would have with their other doctors. And I don't mean, like, you know, we weren't fist fighting, but they were scolding me. Like, "How dare you?" You know, and they... But, but, but it came with an arrogance of an, a, a lack of willingness to even look at the data. Now, which I found ironic, right? It's like if, if you wanna scold me, you better know as much as me, and hopefully more. But the, th- this, this sort of arrogance of I'm going to scold you but I know nothing, and I'm not actually willing to have a discussion with you. 'Cause I'd be like, "Great, let's, let's turn to figure two-
- RRRachel Rubin
Mm-hmm
- PAPeter Attia
... 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?"
- RRRachel Rubin
No, we can't. And it's so fascinating because I would never, I would never tell my... I do sexual medicine, so I look at the whole patient, I look at everything, and I would never say to them, "Hey, your, you have to stop this beta blocker right now because it's causing your erectile dysfunction," right? 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 kill-- it's, it's hurting you," right? 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, it is everywhere, right? We see this all the time.
- PAPeter Attia
Now let's talk about the flip side, because
- 57:24 – 1:01:43
How the medical system’s neglect of menopause care has opened the door for unregulated & potentially harmful hormone clinics
- PAPeter Attia
the unfortunate nature of everything we've just described is you create a fringe movement. And unfortunately, I've seen a lot of doc in a box hormone practices that are, I believe, putting women at risk.
- RRRachel Rubin
Mm-hmm.
- PAPeter Attia
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 are... I think they're ill-informed. I think they're just not that bright. Um, and, and maybe some of them are just actually charlatans, and they're seeing an enormous opportunity here. Um, as a general rule, I tell patients, "Be very, very suspicious of a doctor that is selling you hormones."
- RRRachel Rubin
Mm-hmm.
- PAPeter Attia
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 the, I don't wanna call it the dark side, but just kind of the fringe side of this world.
- RRRachel Rubin
So I would argue that people care about their pain points. People wanna feel better. People will go to anyone who tells them, "Here's..." You know, there's a whole supplement aisle at CVS that makes all these wildish claims that we're gonna help you with everything. And the reality is, is y- I just got done saying your d- 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, um, 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, people are... You know, they hear their friend did it. They hear their, their neighbor did it, and they say, "I want what she's having," right? This is why we call ourselves the Menopossy. 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 appr- approved products that work, you know, much better, that are more regulated, that are totally safe. You know, here's what they are. They should be covered by your insurance. You know, and giving them that knowledge, because the problem is, is when no one is sp- right? When 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 thing. You know what? We see this with men's health too, right?
- PAPeter Attia
Yeah.
- RRRachel Rubin
As a urologist, we see shot clinics and all these wild PRP clinics and, and, 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 wanna connect and get their answers, right? Which is why my colleagues and I are even loud about it on, you know, for everybody.
- PAPeter Attia
Yeah, the number of online testosterone clinics is mind-boggling. And, you know, a lot of them are prescribing I think second-tier drugs, right?
- RRRachel 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.
- PAPeter Attia
Yeah.
- RRRachel Rubin
Right? And that is true for hormones for everybody because w- they just-- I talked about this at the last menopause meeting. Less than 4% of women are on hormone therapy right now. Less than 4%. That's worse than 10-
- PAPeter Attia
4% of elig- of women who would-
- RRRachel Rubin
Yeah
- PAPeter Attia
... theoretically be required.
- RRRachel Rubin
Yeah, four-- less than 4%.
- PAPeter Attia
Wow.
- RRRachel Rubin
That's worse-
- PAPeter Attia
Wow
- RRRachel Rubin
... that's worse than 10 years ago.
- PAPeter Attia
That's worse than I would have guessed.
- RRRachel Rubin
It's worse than 10 years ago. It is so bad out there.
- PAPeter Attia
Hmm.
- RRRachel Rubin
I need... So I, 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 eighty-four million according to AI, right? And I said, "Okay, how..." And there are about three thousand 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 eighty-four million by three thousand, it's a big number, and we can't see patient panels of twenty-seven thousand people. Like, that does not-- the math doesn't math there. So we need people to step up and write the p- So who should be writing estrogen prescriptions? Who?
- PAPeter Attia
Every doctor who sees a woman of that age.
- RRRachel Rubin
Every doctor who sees a woman of that age. And so who actually does? Nobody.
- 1:01:43 – 1:10:20
The HRT playbook for women part 1: progesterone
- PAPeter Attia
Let's talk a little bit about the playbook. I wanna tell you how we do it, and, um, w- I don't, I d- I'm not saying we do it right 'cause I don't think there's a right way to do it, but I mostly wanna hear how you do it 'cause I bet you're way better than, than we are. Um, maybe we take a step back and explain. We've already alluded to it twice, but I just wanna make sure, um, 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. Um, we'll come back to IUDs and progesterone-coated devices and things like that. Nadia, let's just talk about the way you give progesterone. So the progesterone's the easiest of the lot here, right? Um, is there any reason when giving oral progesterone to use anything other than micronized FDA-approved progesterone orally?
- RRRachel Rubin
What's lovely is we need a toolbox because not everybody responds to the same thing.
- PAPeter Attia
Okay.
- RRRachel Rubin
I love micronized progesterone. I think it's a fabulous product. Um, so yes, I think it's, it 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.
- PAPeter Attia
Okay.
- RRRachel Rubin
So, um, you can avoid sort of going to the brain if you put it vaginally.
- PAPeter Attia
Yep.
- RRRachel Rubin
Um, and so we do find that cuts down a bit-
- PAPeter Attia
But you're gonna start orally.
- RRRachel Rubin
I typically start orally.
- PAPeter Attia
You're gonna start at 100 milligrams, 50 milligrams?
- RRRachel Rubin
Depending on your dose of estrogen, um, I typically start with 100 milligrams.
- PAPeter Attia
Mm-hmm.
- RRRachel Rubin
Some people say if you're going higher with your estrogen, you may need to do 200 milligrams of progesterone. That data's not very clear. And so-- and there's really two ways to give progesterone. You could do it every single day, right? So typically 100 milligrams every day. And then some people, and a lot of data shows if you do it cyclically, like 200 milligrams, you know, 12 to 14 days out of the month is another way to do it. Both are fine, but, uh, when we see many patients, right, they, they feel better doing it 100 every day 'cause it can help with sleep and anxiety reduction.
- PAPeter Attia
And do we believe that 100 systemically is sufficient to oppose estrogen?
- RRRachel Rubin
I think that's the way, um... I think there is not enough data there-
- PAPeter Attia
Okay
- RRRachel Rubin
... 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, uh, 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 my-- you know, progesterone's not absorbed very well, which is why we always had synthetic progestins, you know, in the first place. And so we're still learning sort of the capabilities of micronized progesterone. But, uh, according to most menopause specialists out there, they typically will use 100 milligrams every day or 200 milligrams 12 to 14 days of the month.
- PAPeter 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-
- RRRachel Rubin
Mm-hmm
- PAPeter Attia
... 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, uh, selected towards progesterone, they feel fantastic at 200. Uh, the most notable improvement is sleep.
- RRRachel Rubin
Mm-hmm.
- PAPeter Attia
So I, I-- Would you agree with that?
- RRRachel Rubin
Totally agree.
- PAPeter Attia
That that's the thing that most women-
- RRRachel Rubin
Mm-hmm
- PAPeter Attia
... are just over the moon with how well they sleep again.
- RRRachel Rubin
They love you forever.
- PAPeter Attia
Yeah.
- RRRachel Rubin
It is-- It's so fun to get to see.
- 1:10:20 – 1:19:35
The HRT playbook for women part 2: estradiol
- PAPeter Attia
testosterone.
- RRRachel Rubin
Mm-hmm.
- PAPeter Attia
Okay, let's talk about estradiol. Um, there are two other estrogens. Estradiol is E2, but there's estrone, E1, 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, um, and there's no FDA-approved product for estriol, but there are plenty of compounded, uh, opportunities around that. In fact, the most common of them is referred to as Bi-Est, bioestrogen, which is an 80/20 mix of estriol and estradiol. Um- What is your take on why that product exists? Do you view that as a reaction to the WHI? I mean, how, how do you think about it?
- RRRachel Rubin
Yeah, I think that you said it right there. I think that what happened, happened is the Women's Health Initiative happened and hormone therapy all went into the, to, to the underground-
- PAPeter Attia
It went to the alley
- RRRachel Rubin
... It went to the alley.
- PAPeter Attia
Yeah.
- RRRachel Rubin
And I think one of the ways that these alley doc- back alley doctors did it was saying, "Oh, we're using the safer version. We're using this compound, and we're gonna make it 80/20, and we're gonna use the more safer option." By the way, I haven't seen that data, uh, you know, and there is no data on Biest in, in large trials that's gonna really tell me what it does, and so, and we're gonna just use this. Um, and that's what got people through for a while, and I don't actually blame those people if they had no alternative, right? 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 Biest cream, like I'd probably slather the Biest cream on me. But we don't have, we're not in, you know, where we are now, we have lots of options. We have FDA-approved options, and they're covered by insurance, uh, most of the time. So I tend, 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 s- change them? Well, I'll say, "Well, do you wanna 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, you know, I know are absorbing in your body because I can prove it." So that's my ta- What's your take on that?
- PAPeter Attia
We don't use it at all. Um, I have used it occasionally in the past, probably about 10 years ago, um, 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, there's no human data that, that, that demonstrate what I'm about to assert. But if you, and, and, 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's, there are biochemical arguments to be made that estrone, and in particular one of the metabolites of estrone, and I think it's 4-hydroxyestrone, is the, the, is the, 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, and so the answer is, oh, you know, some of the data suggest it's 4-hydroxyestrone. Well, estriol has no biochemical path to even get there. In other words, the, there, there are no series of enzymes that can convert estriol into 4-hydroxyestrone. And, um, of course, there are, uh, pathways that will turn estriol weakly into estradiol, so maybe you get a little bit more. So in a way, all, this is a long-winded way of saying, you know, no, no, no reason at all from an evidence perspective to use it. Uh, we don't use it, have not used it in a decade. Uh, but that, that was my half-baked argument in certain situations. And in fact, I th- I, I did use it once in a woman who, um, had breast cancer, um, was adamant that she needed hormones. Symptomatically, she really seemed to. Um, wanted it very badly, and I felt that this was a reasonable compromise. For what it's worth, she got insanely better on the Biest. So how much of that was from the estriol, how much of that was from the estradiol, I have no idea.
- RRRachel Rubin
When I teach this, and I, I do a lot of teaching of physicians, holding their hands, saying, "You can do this. You can write these prescriptions."
- PAPeter Attia
Hmm.
- RRRachel Rubin
And one of the things that I just keep coming back to is the sentence, what are you afraid of, right? 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. And so then it becomes you have to also understand what are your patients afraid of, right? Because that is the only thing that matters is what your... We take risks all the time. I took a risk taking a car to get here, right?
- PAPeter Attia
Yeah.
- RRRachel Rubin
We take risks. I, if you ever drink alcohol, you are taking a risk, right? 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, so patient comes in on Biest, uh, 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 gonna hurt them necessarily, but I don't know what's in that compound. I don't know if the top of the bottle's 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, right? And, and then it becomes what am I afraid of with the, with the patients? Well, what are you afraid of about the estradiol? Are you afraid of cancer? 'Cause 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, right?
- PAPeter Attia
Yeah. And you, you mentioned this earlier. Uh, I think this is one of the biggest limitations of, you know, 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? Uh, you, you know, we, we, we, we, 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, you know, patently wrong. But the what's the risk of not doing something is, um, is, is very significant. So, um, let's talk about all of the different ways in which a woman can get estradiol through an approved, tested, chemically sound means.
- RRRachel Rubin
Yeah. So, um, a little bit of nomenclature here, right? There is systemic estrogen, right? 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, right? Uh, estrogen for your hot flashes, for your bone protection, um, uh, for your skin, hair, and nails, right? Uh, that's estrogen. That's systemic estrogen. But there's this whole other topic which I hope we talk about later 'cause 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 gonna say it. They are safe for every human on Earth, including your ninety-nine-year-old mother-in-law in the nursing home who is 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.
- PAPeter Attia
Let's start with systemic. I-- And we can-- Let's come back to that as we talk about geno- genitourinary, uh, syndrome.
- RRRachel Rubin
Yeah, because I got a lot to say about that one.
- PAPeter Attia
Yes.
- RRRachel Rubin
So systemic estrogen has a toolbox, right? We have patches, we have gels, we have rings, uh, which go vaginally. Um, we have oral, uh, estradiol, right? Um, we have, um... Those are the big ones. There are injections. That's kind of an old school way that I kind of use sometimes, injections of estradiol valerate or cipionate. Um, and so each one has pros and cons, um, and it's nice to have the toolbox because not every, uh, product works for every patient. And the key is, is getting it right for that patient 'cause you need something that they're going to do and that they're gonna do it for a long time. 'Cause these are not things that you just, you know-
- PAPeter Attia
Yep
- RRRachel Rubin
... do for a weekend.
- PAPeter Attia
Uh,
- 1:19:35 – 1:23:52
Oral formulated estrogen for systemic administration: risks & benefits
- PAPeter Attia
let's start with the oral. So we have an oral formulated estrogen. Um, we don't use it that much. I'm trying to think. Used to use it a bit more than, than we did now. Honestly, sometimes I would use it for women who were-- 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, just, I want you to just take a milligram of, of, of, of this estradiol tablet tonight while we readjust your cream or your patch or whatever." When are you using oral estradiol?
- RRRachel Rubin
So I don't use it much.
- PAPeter Attia
Okay.
- RRRachel Rubin
Um, but that's not to say that it is, there isn't useful.
- PAPeter Attia
Yeah.
- RRRachel Rubin
I think it is actually very useful, and I think it's underused, right? Uh, uh, for example, people are used to taking birth control pills. They're used to taking pills. They like pills. Um, you doing for a, a healthy person, uh, uh, with no major risk factors of cardiovascular issues, taking an oral estrogen really is not gonna increase your risk of blood clots or heart attacks or anything like that at any significant worrisome level.
- PAPeter Attia
It's no more increase in risk of blood clot than a b- birth control pill.
- RRRachel Rubin
Less. It's less.
- PAPeter Attia
Yeah.
- RRRachel Rubin
Yeah.
- PAPeter Attia
So given the ubiquity with which women are on birth control pills, we're, we're, we-
- RRRachel Rubin
It shouldn't scare you
- PAPeter Attia
... we tend to blow this out of proportion. Yeah.
- RRRachel Rubin
Mm-hmm.
- PAPeter Attia
So what is your, what is your advice to, or, uh, what is your patient selection criteria on that? In other words, who are the women that you would say, [clicks tongue] "I don't want you on oral"? Is this just factor V laden? Is this women who-
- RRRachel Rubin
Yeah
- PAPeter Attia
... are obese? Like, where do you sort of say, "Ah, the risk is a little too high"?
- RRRachel Rubin
So I tend to always start transdermal, and again, this is my sex doctor hat because we n- learned from this study called the KEEPS trial where they looked at oral estrogen versus transdermal estrogen. Um, and, uh, it's a fascinating trial, but in that trial, they found that, um, uh, yes, there's a slight increase of blood clots, right, with, 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. Um, and this one in particular, it can pump out more clotting proteins, so if you're at any risk of blood clots, uh, just like birth control pills, right? If you're at any risk of, if you're a smoker, if you are overweight, if you have a genetic predisposition to blood clots, we're not gonna use an oral hormone product. Does that make se-- Is that helpful?
- PAPeter Attia
Absolutely. Yep.
- RRRachel Rubin
Um, now I wanna paint this because this is actually an area where I would love to see research. Uh, I was speaking at a Harvard testosterone course with Abe Morgan, Tyler, uh, and Mo Khera, who you've had on the show, and, and I was speaking about w- women's testosterone use. And, um, the speaker who got up there, um, to talk about, uh, transgender hormone therapy talked about sublingual estrogen. He kept referring to sublingual estrogen, and I got up to the micro-- I ran to the microphone. I said, "What are you talking about? I've never heard of sublingual estrogen. There's no product. Who, 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 is, this sounds amazing."
- PAPeter Attia
And it doesn't drive up SHBG presumably-
- RRRachel Rubin
Pre- presumably-
- PAPeter Attia
... because it's not going through the liver
- RRRachel Rubin
... because it doesn't go through the liver, which actually, if you think about it logically, I love logic here 'cause we don't have a lot of data, so we love logic, is that, well, if you take an estrogen ring and put it in the va-- a high dose estrogen ring, and you put it in the vagina, same thing. You absorb estrogen vaginally, so how-- 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 sort of look in that direction 'cause it's cheap. Oral estrogen is cheap. Uh, you get lots of doses. You can dose it, you know-
- PAPeter Attia
Does that mean you can get away with a lower dose?
- RRRachel Rubin
You can get away with a lower dose, absolutely.
- PAPeter Attia
You must, right?
- RRRachel Rubin
Yeah.
- PAPeter Attia
Because of that first pass effect.
- RRRachel Rubin
'Cause it's gonna absorb. Mm-hmm.
- 1:23:52 – 1:31:52
Topical & vaginal estrogen delivery options: benefits & limitations, & how to personalize treatment for each patient
- PAPeter Attia
Okay. Um, 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 whole, like, routine that was probably so elaborate that it, it decreased compliance 'cause, like-
- RRRachel Rubin
It's not that serious, Peter
- PAPeter Attia
... yeah. So talk, talk-
- RRRachel Rubin
It's not that, it's not that serious, Peter
- PAPeter Attia
... all right. Talk to me about it.
- RRRachel Rubin
Um, no, it, it, but it is true, right? For men and testosterone, like, we af- 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.
- PAPeter Attia
Yes.
- RRRachel Rubin
Right? So it is, I always tell patients that, like, "I'm gonna, here's the menu, and we're gonna tinker. We have to tinker to get it right for you 'cause 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. Um, and so a- I always, 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-
- PAPeter Attia
Yep
- RRRachel Rubin
... and they get really annoyed with you, and then you have to backtrack. So I always like to kinda 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, uh, don't absorb well. For some people, they feel that they kinda drop off. If you change it twice a week, they feel like they're getting a little lower.
- PAPeter Attia
We also notice women who use the sauna, who are very, very athletic and exercising like crazy, you just have an adherence, uh, physically an adherence problem.
- RRRachel Rubin
Yeah, and there are people who are allergic to the adhesives, right?
- PAPeter Attia
Yep.
- RRRachel Rubin
We see that as well. So that's, so some people are patch, you know, 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, right? They need to know the menu because you are not a, you know, it's not a one-size-fits-all, right? So there's gels, and there are a number of different gels. There's gels, like, uh, the brand name is Divigel, goes on your thigh. There's Estrogel, which goes on your arm. There's EvaMist, which is a spray, sort of an aerosolized spray that goes on your arm. Um, gels can be really nice because it's every day, um, so it's dosing every day. Um, the challenge is sometimes they take a little bit to dry, so if you're a busy person and you wanna rub something on and you wanna run out of there, um, uh, I find gels, um, not everybody wants to do something every day. So again, it's you gotta get to know the people of, like, what do you, what do you, what do you like to do? What's your routine? Um, you have to get it into their routine, and sometimes you gotta work up to it. And sometimes I have patients, right, they'll, they'll use patches. Uh, uh, but when the summertime hits and it's hot and muggy, they'll switch to the ring, right? Or they'll switch to a gel. Like, they'll, they'll kind of-
- PAPeter Attia
What's the case for not just using the ring all the time?
- RRRachel Rubin
Ugh. So I love the ring.
- PAPeter Attia
Yeah.
- RRRachel Rubin
So there's, there's two types of ring. Now, this is important.
- PAPeter Attia
Can you explain? Yeah, yeah.
- RRRachel Rubin
Yeah, it's really important because your pharmacist sometimes messes this up. Uh, 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.
- PAPeter Attia
And it's sitting right up against the cervix?
- RRRachel Rubin
Yeah. It's not like a diaphragm where you have to place it or a, or a menstrual cup or anything like that. You just kinda 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. Like, they're, nobody's bothered by this thing. So this ring goes in there, stays in for about three months. Now, there is a Femring, 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, .05 and .1. Then there's an Estring, which is a two milligram, like, localized estrogen ring that is, 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 gonna help your night sweats, but it's gonna prevent UTIs. It's important that you know the difference 'cause 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 l- a local ring. So the ring is lovely.
- PAPeter Attia
And it's just dose is the only difference between the two, right?
- RRRachel Rubin
Yeah, they look a little different.
- PAPeter Attia
Yeah, yeah. But I'm, but I mean-
- RRRachel Rubin
They're, they're, they're... But yes. It's just, right
- PAPeter Attia
... like, the reason one is systemic is-
- RRRachel Rubin
It's just a dose. One is a high dose-
- PAPeter Attia
Yeah, yeah
- RRRachel Rubin
... and one is a low dose.
- 1:31:52 – 1:39:48
How to navigate hormone lab testing without getting misled
- PAPeter Attia
Two things I want to talk about on the lab front. We've talked a lot about labs. Um, [clicks tongue] so I'm not sure if you share our, 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?
- RRRachel Rubin
I typically get the sensitive estradiol level.
- PAPeter Attia
Yeah, yeah.
- RRRachel Rubin
Yeah, that's what we give for everybody, and same with the te- the testosterone as well.
- PAPeter Attia
Yes, 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, uh, the LC-MS assay, right, 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, um, there are some really known obvious supplements that completely obscure the findings, so biotin, [swallows] which is in a lot of things, will, I mean, render, uh, a non-LC-MS test, uh, irrelevant. Um, but I think there are other things that we're just not fully aware of. So, you know, it is worth splurging and paying the extra, maybe it's $5 or $10, it'd 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.
- RRRachel Rubin
So we're gonna get a lot of hate, uh, just so you know. We get a lot of ha- there's a lot of, um, there's a lot of disagreements, uh, 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, I truly believe that actually most of us agree on, like, 98% of this. Like, truly, we want women feeling better. Many of us, most of us believe the data that hormones, the benefits outweigh the risk. Um, and so I think 98% we agree. There's the 2% where there is, uh, disagreement, and part of it is also in the what we don't know yet, right? Like the, 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.
- PAPeter Attia
Mm-hmm.
- RRRachel Rubin
And then you have sort of the fringe that are doing all saliva-based testing, every minute check labs, do, you know, 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, um, 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 1,000 and now it's zero and that hurts. Now, do I need numbers to, to, to, 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. Um, what is your take on that? Because it is a very controversial issue.
- PAPeter Attia
I'm actually surprised, but this is... You have to understand, I don't spend any time paying attention to the buffoons in the periphery on this topic. So, uh, you know, I, I don't like the term even... I, I don't, 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. Um, I, again, I, I think you can, 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. Um, our view and what we tell patients is the symptoms are the most important things, but the numbers help direct my thinking.
- RRRachel Rubin
Mm-hmm.
- PAPeter Attia
This is how we manage thyroid. This is how we manage sex hormones, you know. And, and, and, and to be clear, like, there's, again, I, y- y- you know, there's a caricature of the Dunning-Kruger curve that I just find so helpful, right? So for the folks who aren't familiar, on the x-axis, you have experience, right? And on the y-axis, you have confidence. And in the, 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 Armor Thyroid or Nature-Throid or whatever. And, and it, and it's sort of like, no, none of that is correct, okay? 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.
- RRRachel Rubin
You've seen all my gray hair-
- PAPeter Attia
Yeah
- RRRachel Rubin
... that I've grown. It, it's true, right? And, and I find, you know, what's so, again, that humility of medicine is I have made a ca- 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 gonna 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. Um, but I also need to get my patients feeling as good as possible, and that is, it's addicting, to be honest.
- PAPeter Attia
Yeah. So here's what we do. We, we, 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, 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 gonna 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.
- RRRachel Rubin
[chuckles]
- PAPeter Attia
Like, and that's the advantage of doing it with these short-term estrogens 'cause I can pull it back really quickly. So I don't know if that answers your question, but I, I would consider myself an essentialist on labs, kind of a minimalist essentialist, uh, but, but neither, not an absolutist in either direction.
- RRRachel Rubin
And I love that, and I think it's so re- it's such a reasonable and logical, like the logic there, it makes so much sense to me. So we're totally in line with that. Um, and that's why, again, it's very confusing for our patients on social media because they want the exact answer, right? And you're not gonna find your exact answer from one doctor on social media, right? "Oh my gosh, you said that I have to use an estrogen gel, but I use a patch. Should I switch to a gel?" And it's not, 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. Um, 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 gonna happen.
- PAPeter Attia
So
- 1:39:48 – 1:46:33
Wide-ranging symptoms of menopause—joint pain, brain fog, mood issues
- PAPeter Attia
anything else you wanna say about systemic therapy before we go and talk about local therapy in the context of genitourinary symptoms of menopause?
- RRRachel Rubin
Yeah, I think we haven't spent a lot of time really talking about the symptoms of menopause, right?
- PAPeter Attia
Yeah.
- RRRachel Rubin
What are we treating? Why do people have, why do people need systemic therapy? And I think, you know, I, I'm often saying that menopause has the worst PR campaign in the history-
- PAPeter Attia
Hmm
- RRRachel Rubin
... 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, right? 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. I can't, you know, my joints are achy." And I said, "Welcome to you need hormone therapy, right?" Like I'm always teaching, no matter who I'm, whether it's a cab driver, a, a hairstylist, I'm always teaching. But this idea of, of, 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 event, right?
- PAPeter Attia
Hmm.
- RRRachel Rubin
The, the worse your hot flashes, the worse your risk of cardiovascular issues and things like that. Um, joint pain is a huge one. I never thought as a urologist I would treat so much joint pain. Uh, never in a million years-
- PAPeter Attia
Mm-hmm
- RRRachel Rubin
... 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. Um, my joints recover again after I exercise." And the, again, empty gas tank inflammation. When you, uh, I think hormones are, um, nature's, uh, joint fluid, if you will. So, so almost like brake fluid, right? Go back to the car analogy. So-
- PAPeter Attia
I love I- we are gonna milk the heck out of this, and I love it
- RRRachel Rubin
... we're gonna... Right? So, 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, so hormones create these oils, vaginal lubrication, oil for your skin. There are androgen receptors in your eyeballs, right, in these Meibomian glands. So, so I think of hormones like fluid. So as you lose the hormones or the hormones go, uh, 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 our, my colleague Vonda Wright, the musculoskeletal syndrome of menopause, right? 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 an- it, it's such a simple analogy. So what are the symptoms? You've got musculoskeletal symptoms, sleep issues, mood issues, um, uh, bleeding changes, um, obviously low libido, orgasm problems, arousal problems, pain with sex increases like crazy. Um, I sent you a list here. What am I missing? You've got a, you've got a list there.
- PAPeter Attia
Uh, irritability, very common one. Um, I think the, the one that I was gonna ask you about is brain fog and depression. Um, this is one where... I think this is a, I think this is a very unique one because it's one that gets easily dismissed as something unrelated.
- RRRachel Rubin
Mm-hmm.
- PAPeter Attia
Say, say more about those.
- RRRachel Rubin
It, it's, it's one of the most common symptoms, and all women start going to doctors in their 40s. Like, like, doctors, you're, 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, um, you know, a cognitive decline or all, all these other issues. But really, it's that brain fog because your brain is filled with estrogen receptors. I- this is crazy research, okay? I don't know if you've had Lisa Mosconi on, but here's this researcher from Cornell, neuroscience researcher, who says, "Hey, I wanna study Alzheimer's. I wanna 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, um, uh, 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 that what would you expect, right? Your body is efficient. It's not gonna 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?
- PAPeter Attia
The opposite.
- RRRachel Rubin
The exact opposite.
- PAPeter Attia
Yeah.
- RRRachel Rubin
Right? That actually, even up to 65, she stopped looking past 65 'cause she's like, "There's no way that's gonna matter." The increase in receptor density the older you get, and it correlates to brain fog and irritabili- you know, sort of correlates to all these symptoms.
- PAPeter 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, and it ac-
- RRRachel Rubin
To get every morsel
- PAPeter Attia
... in other words, it's a lot like the way the brain is treated for glucose. The body will, if you, 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.
- RRRachel 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, the brain because it wants every morsel that it can get, right? So this idea of hormones matter for the brain deeply, right? This is very important. So it's fascinating research.
- PAPeter Attia
Mm-hmm.
- RRRachel Rubin
But you're gonna 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. It is, 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, 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 when you are totally empty, the brain fog gets better, right? Because there's stabili-
- PAPeter Attia
The volatility of hormones gets less, yeah
- RRRachel Rubin
... yeah, it's not volatile anymore. But if we just, all I'm saying is just add some estrogen, right, to just keep the receptors happy.
- PAPeter Attia
The other one that we didn't talk about was the urinary
- 1:46:33 – 1:50:15
Evolution of medical terminology & the underrecognized importance of local estrogen therapy for urinary & vaginal health in menopausal women
- PAPeter Attia
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.
- RRRachel Rubin
Okay, so this is my favorite topic in the history of topics, uh, because we used to call this problem, initially it was called senile vagina. That was the initial, uh, yes, there was, uh, uh, papers written on the senile vagina. Then it got updated-
- PAPeter Attia
I don't even understand what that means
- RRRachel Rubin
... i-i, an old vagina, I suppose. But the, the, then it got changed to vulvovaginal atrophy or atrophic vaginitis.
- PAPeter Attia
Okay.
- RRRachel Rubin
That was the terminology that was used just-
- PAPeter Attia
That, I'm familiar with that term
- RRRachel Rubin
... up until '24. Before that it was senile-
- PAPeter Attia
Yeah, yeah, yeah
- RRRachel Rubin
... senile vagina. To-
- PAPeter Attia
That I, I totally missed that
- RRRachel Rubin
... check the, uh, check the history books. Very fascinating. So vulvovaginal atrophy was sort of the common, uh, name of this, of, okay, as you get older, the vagina atrophies. It shrivels up. It shrinks up. Uh, you know, again, if a penis shriveled up at age 52, we'd probably have a vaccine sponsored by Pfizer, right? This is, this is-
- PAPeter Attia
[laughs]
- RRRachel Rubin
They created Viagra. They would create this, this vaccine. No one even tells women-
- PAPeter Attia
I, 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, you, you're, you're saying that the medical system would have probably done something about this?
- RRRachel Rubin
What do you think, right?
- PAPeter Attia
[laughs]
- RRRachel Rubin
Like, tell me what you think.
- PAPeter Attia
You might be onto something, Rachel.
- RRRachel Rubin
I, I, I, I know what I'm talking about. So this is, right, so-
- PAPeter Attia
[laughs]
- RRRachel Rubin
... so, so this is the thing. We just told w- 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, is it's not just a little vaginal dryness. The vagina and the bladder need hormones, right? Babies don't have hormones, and that's why you see it's red. It's irritated. There are these small little labia minora. Uh, diaper cream was invented, right, to, 'cause it looks so painful. Then hormones h- they pee their diapers all the time. The genitals morph and change with hormones, right? Puberty happens, and you have a change of the genital and urinary system. And, um, a- and so what happens is as you lose hormones, it goes in reverse. And so it changes the microbiome. Uh, the, the hormones keep the tissue acidic. It grows the healthy lactobacilli. It is, uh, the vagina's 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, okay? 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. And yet-
- PAPeter Attia
And that was with topical estriol?
- RRRachel Rubin
Yeah
- PAPeter Attia
Interesting.
- RRRachel Rubin
Yeah.
- PAPeter Attia
I was not aware of that. And yet there is no FDA-approved estriol formulation despite that fact?
- RRRachel Rubin
Yeah. Correct. I think it's available in Europe. Um, so-
- PAPeter Attia
Hmm
- RRRachel Rubin
... we-- So the name got changed in 2014. Okay, 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 'cause 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, right? People are dying of urinary tract infection.
- 1:50:15 – 2:00:30
Benefits of vaginal estrogen (or DHEA) for preventing UTIs & improving sexual health
- RRRachel Rubin
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 six and $22 billion a year. Billions.
- PAPeter Attia
J- just say that again, please, because-
- RRRachel Rubin
Okay
- PAPeter Attia
... I know there are people that are in the Medicare system-
- RRRachel Rubin
Mm-hmm
- PAPeter Attia
... who are gonna be interested to understand that.
- RRRachel Rubin
Okay. So when you, when you 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, okay? It will not only a- help with lubrication, help with pain with sex, uh, uh, 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 six 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. Um, this is a huge economic, uh, morbid, uh, uh, mortality problem that we are dealing with, and no one cares.
- PAPeter Attia
I mean, again, I always try to come up with the 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?
- RRRachel Rubin
So I think we have a marketing problem. I, I truly believe this is a marketing problem. 'Cause let me tell you-
- PAPeter Attia
But how... Okay, let me push back, not because I don't agree with you, but I, I'm just gonna put, put my, my hat on that says the opposite, right? 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. Why is... I- is this not in the zeitgeist right now?
- RRRachel Rubin
It's getting better, but again, they don't know how to write the prescriptions, okay? So let me tell you. So-
- PAPeter Attia
Okay, so you're saying there's not enough physicians talking about this, then.
- RRRachel Rubin
Yeah. They really can't.
- PAPeter Attia
If it really comes down to prescri-
- RRRachel Rubin
Yeah
- PAPeter Attia
... if it-
- RRRachel 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... Uh, we had an Instagram Reel just yesterday that the patient said, "I sent my f- 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, uh, to, to change your relationship from now on. It's not in the cards for you.'"
- PAPeter Attia
What does that mean?
- RRRachel Rubin
Meaning you-
- PAPeter Attia
You can't have sex anymore?
- RRRachel Rubin
You can't have sex anymore, right? And the fact is, it's not about sex, it's about urinary tract infections.
- PAPeter Attia
Wait a minute.
- RRRachel Rubin
So-
- PAPeter Attia
Wait a minute. Yeah. Uh, this is impossible for me to fathom. A woman went to her gynecologist and said, "I'm having pain with intercourse."
- RRRachel Rubin
Yep.
- PAPeter Attia
This wom- Any idea how old this woman is?
- RRRachel Rubin
In her 60s.
- PAPeter Attia
Okay. And the gynecologist said... Didn't, didn't, didn't... You think this gynecologist doesn't know about estrogen?
- RRRachel Rubin
Honestly, I don't know anymore.
- PAPeter Attia
That's incredible.
- 2:00:30 – 2:07:13
Use of DHEA & testosterone in treating hormone-sensitive genital tissues
- RRRachel Rubin
know, and we just published a study that DHEA does the same thing. It reduces the risk of UTIs by more than half.
- PAPeter Attia
Why is DHEA doing it?
- RRRachel Rubin
So DHEA is a fascinating, uh... 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, right? 'Cause your, uh, adrenals are pumping out-
- PAPeter Attia
Adrenal production of testosterone, yeah
- RRRachel Rubin
... a lot of DHEA. So but when you put DHEA vaginally, it is this, 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 probably, we do have patients that benefit from having an androgen in the tissue as well, and the only FDA-approved product we have is, uh, uh, um, Intrarosa, which is vaginal DHEA. Now, it's often hard to get for patients. Um, if I could get it for everybody, I, I would. It's fabulous because the tissue needs D, it needs androgens. Um, so-
- PAPeter Attia
Hmm
- RRRachel Rubin
... i- it's, it's, um, it, it, the data's very good. It's just-
- PAPeter Attia
We've just started using it-
- RRRachel Rubin
Oh
- PAPeter Attia
... so I don't have a lot of experience with it.
- RRRachel Rubin
Oh, it's gonna change. So there is some data, not a lot, but there's data that shows someone with urgency.
- PAPeter Attia
Yeah.
- RRRachel Rubin
Um, you give them vaginal estrogen, switch them to DHEA. It'll, it'll help those people who still have urgency. Um-
- PAPeter Attia
Do you think it gives you the same UTI protection?
- RRRachel Rubin
Uh, we, we published on this. So we just published in the Menopause journal that it, it shows the same, uh, decreased risk of UTIs by more than half. So that was a very proud publication that we just put out. Um, and so, um, 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?
- PAPeter Attia
Well, I know what the vulva is, and I know what a vestibule is, but I, I don't think I know what the vulvar vestibule is.
- RRRachel Rubin
It's okay. So I'm obsessed with homologs. Homologs are sort of this idea of how one part, you know... I'll give you an example. The penis and the clitoris are exactly the same thing.
- PAPeter Attia
Yes, yes, sorry. That-
- RRRachel Rubin
No, no, they're the same.
- PAPeter Attia
Yeah, yeah, yeah.
- RRRachel Rubin
They're homologs of each other, right? The head of the penis and the head of the clitoris, homologs. The, um, uh, urethra, right? They're ho- So, so it's what part of the body in one is the same in the other. So the homolog, okay, of, of, of the labia-- sorry, of the scrotal skin is the labia majora.
- PAPeter Attia
Majora, yeah.
- RRRachel Rubin
Okay, you're with me? The prepuce or the hood, right? They, every, every, the clitoris and the penis both have a prepuce or a hood to it.
- PAPeter Attia
Yep, yep.
- RRRachel Rubin
Um, the... So okay, so there's a line that goes down a penis, that goes down the, the penis and the scrotum. Do you remember what that's called? Median ra-
- PAPeter Attia
The ra- raf, uh-
- RRRachel Rubin
Yeah, you got it, raphe.
- PAPeter Attia
Yeah, yeah.
- RRRachel Rubin
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.
- PAPeter Attia
Oh, well, it must be the vestibule.
- 2:07:13 – 2:09:24
Is it too late to start HRT after menopause?
- PAPeter Attia
three other questions that I want to ask you going back to hormones post-menopause. Um, and these are, I'm saving the three most contentious questions for, for last on this topic. Question one: I buy your argument. This is, 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?
- RRRachel Rubin
Yeah. So we have this idea in menopause medicine called the timing hypothesis.
- PAPeter Attia
Or the window idea, right?
- RRRachel Rubin
So the question of the timing hypothesis is what are you afraid of? What are we worried about?
- PAPeter Attia
Mm-hmm.
- RRRachel Rubin
We're worried about blood clots. We're-- We don't want to hurt people. We're worried about cancer. We're worried about bl- 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. Um, but even the timing hypothesis using Prempro, which was the medicine used in the WHI, is under question. So Suven- Susan Davis from Australia just wrote a big paper questioning the timing hypothesis and say, "Actually, when you look at the data really closely, even it doesn't really hold muster." We shouldn't really be forcing people to, like, say, "You cannot start hormone therapy after sixty." So I think this is where shared decision-making really comes into play of what are we treating? What are we try-- Do you care about your bones? Do you care about your sexual health? Do you care about, you know, sort of your mental health, and do you want to 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.
- PAPeter Attia
Right.
- RRRachel Rubin
Because who wouldn't want to prevent osteoporosis? And the thing I just talked about a lot is the genitourinary 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.
- PAPeter Attia
Throughout life.
- RRRachel Rubin
Throughout life.
- 2:09:24 – 2:11:19
Should women stop hormone therapy after 10 years?
- PAPeter Attia
Um, okay. Now I'm gonna ask another, uh, question that is the extension of that question, but I think your logic is gonna 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 ten years, right? I mean, so even if you were lucky enough to catch a woman through perimenopause, and, you know, you got her on hormones by the age of forty-nine, now that she's sixty-nine, you gotta stop it, right?
- RRRachel Rubin
Definitely not.
- PAPeter Attia
[laughs]
- RRRachel Rubin
So that's really the, the-- There is no data to suggest stopping it. In fact, stopping it, all of your bone gains go away.
- PAPeter Attia
That's right.
- RRRachel Rubin
They all go away quickly.
- PAPeter 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, right? 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.
- RRRachel Rubin
So keep them on, right?
- PAPeter Attia
Yeah.
- RRRachel Rubin
And again, this idea of if hormones-- If y- 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 vasospas. Like, there are all these things that could happen. And so it, we really don't want to 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, is that helpful? Does that, does that make sense?
- PAPeter Attia
Yes, and it actually dovetails perfectly into my third critical situation, which is
- 2:11:19 – 2:17:39
How to manage hormone therapy in women with BRCA mutations, DCIS, or a history of breast cancer
- PAPeter Attia
how do we manage hormones in women who are at risk of breast cancer from a familial standpoint, who, uh, 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 three or four of those buckets. How do you handle it?
- RRRachel Rubin
Yeah. 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 'cause Rachel Rubin tells you to take hormone therapy. You have to do your own research, figure out what you, you know, what you're interested." And so I have a lot of colleagues who are, who are talking about this. You had Avrum Bluming, uh, 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 Menn, who is a gynecologist who had breast cancer, uh, as a young person in her twenties.
- PAPeter Attia
Mm.
- RRRachel Rubin
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 about, well, what data-- 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? And 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 gonna 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. To stop-- When I came out of my training, it was testosterone fuels prostate cancer.
- PAPeter Attia
Mm-hmm.
- RRRachel Rubin
Now, ten 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. Um, it's marketing. All prostate cancer is testosterone sensitive prostate cancer, but we don't cut off testicles for the fear that a, a, an abnormal cell will happen in a prostate. All-- A lot of breast cancer is estrogen, uh, uh, uh, receptive breast ca- Not all of it, right? But some of it is. That doesn't mean that estrogen causes cancer. Is that helpful? Like, I think it's a-
- PAPeter Attia
It's insanely helpful. And of course, it echoes exactly what Ted Schaeffer 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 three plus three," means he has prostate cancer, and we are going to follow this, and if it becomes a three plus four, he's-- we're gonna actually have to take this thing out. Um, 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-
- RRRachel Rubin
Correct
- PAPeter 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?
- RRRachel 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 that 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 don't tell you. They give you advice. They are-- So the... It's like a pit crew. Let's go back to our car model.
- PAPeter Attia
Hmm.
- RRRachel Rubin
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, you know, a heart doctor. So you need to collect your pit crew, but when one doctor says, "No, you can't do this with your body," I don't like that termina- 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, uh, osteoporosis. Listen, my grandma died." No. Sorry. "My grandma broke a bunch of ribs, right? She had Alzheimer's and osteoporosis, and my grandpa hugged her, and she broke a bunch of ribs. Like, that's not how I wanna age, right? So what do I care about? I don't wanna get osteoporosis. I don't wanna get dementia, and I've seen all the literature. Hormone therapy sounds pretty good to me," right? Like, a- and that's really the key. I think there's a lot of people on social media maybe negative about hormone therapy, but if you look, they are on hormone therapy themselves. They will say they have an estrogen patch on.
- PAPeter Attia
Wait, I'm sorry. I don't... I... Because I don't pay any attention-
- RRRachel Rubin
[laughs]
- PAPeter Attia
... to social media, there are people out there saying they're b- they're anti-HRT, but they use-
- RRRachel Rubin
Use HRT
- PAPeter Attia
... So I don't... What's their argument? What are they talking about?
- RRRachel Rubin
This idea that we are overselling HRT, that not every woman needs HRT.
- PAPeter Attia
Got it.
- RRRachel Rubin
And I'm not suggesting every woman needs HRT. But I want every woman to be offered the menu, right? I want them to know what they are, like, like, uh, uh, 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. Uh, does that make
- 2:17:39 – 2:24:37
How women can identify good menopause care providers
- RRRachel Rubin
sense?
- PAPeter Attia
Sure. Um, what do women need to be aware of? So n- not every woman can come and see you, right? 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, that they need to be, uh, mindful of and not get duped into sort of sub, you know, either dangerous therapies or, you know, just, uh, you know, overly extractive therapies?
- RRRachel 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 wanna do this," right? 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 you need... I like, um, being somewhere in the middle and getting a few opinions here, right? So this is where opinions can be, uh, following the, uh, 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, right? There are-
- PAPeter Attia
What are some of your favorites?
- RRRachel Rubin
So I mean, you've got, um, Mary Claire Haver has the most popular book called The New Menopause.
- PAPeter Attia
Yep.
- RRRachel Rubin
Heather Hirsch has a great book called Pick Your Menopause Type. Um, there's been, uh, uh, uh, Hot and Bothered. A journalist wrote a great book on perimenopause, uh, Jancee Dunn. Um, Tamsen Fadal just wrote a book, um, about menopause who's also a reporter. So you're getting a l- Estrogen Matters is a great book-
- PAPeter Attia
Right
- RRRachel Rubin
... right, a really great book. So this is-- There's a lot of books now, thank goodness. Um, you know, there's one called The Menopause Manifesto. There's great books on menopause. There's also podcasts now. There's great podcasts out there. There's great, um, Oprah just did a special on, uh, uh, uh, you know, there's, 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. There are telemedicine companies.
- PAPeter Attia
And what's a, what's that website you referred to?
- RRRachel 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, um, I'm on that website, but ISSWSH, I-S-S-W-S-H.org is the Women's Sexual Health Society. So people who we care about menopause and sexual health.
- PAPeter Attia
Mm-hmm.
- RRRachel Rubin
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 gonna fill that gas tank and get you where you wanna go.
- PAPeter Attia
Do you feel that there are too many women that are still getting their hormone therapy in the, in the sort of dark alley with-
- RRRachel Rubin
Yeah
- PAPeter Attia
... with sort of highly sus individuals? And if so, what would be, what would be a clue that you're in that camp? 'Cause there's nobody that's in that camp that knows it, right? So what, what, who are, w- what are the... I want s- I want a woman who's watching this who's not getting great medical care but thinks she is to maybe get a c- a bit of a hint as to what that might look like.
- RRRachel Rubin
I think this is a, a problem. When your doctor only has one t- type of med-- But when your doctor says, "No, you can't have anything," that's s-suspect. If your doctor says, "You can only have this really expensive product that has to be, uh, uh, uh, inserted into your butt, uh, four times a year, and you have to pay me thousands of dollars," that's extremely suspect. Um
- PAPeter Attia
Or compounded by me or, yeah
- RRRachel Rubin
... if they're, if y- they say you have to pay lots of money for this special compounded product that's safer and more effective, I, 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. Um, I think the pellet industry, we-- I have a big problem. We have an FDA-approved pellet for men, okay? It can be FDA approved. I'm 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's safe. If you believe it's billion-dollar industry, if you believe that it's the greatest thing in the world, show me so that I have that, so that I can start using it, because I'm gonna-- because the FDA is a pretty good compounding pharmacy.
- PAPeter Attia
Hmm.
- RRRachel Rubin
So do the work. Go-- 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. That, everyone takes advantage of women. All the supplement companies, all of these, 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, is just do the work.
- PAPeter Attia
Rachel, as expected, this was, this was a fantastic discussion, and I think it adds to what we're trying to do in this podcast, which is really, um, have nuanced and deep discussions about important topics. You know, not every podcast I do gets to impact that many people. Um, some of them impact nobody. They're just really esoteric, but they're, they, they, they fit into my curiosity window. Um, but, but this is, 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 a-again, the, 100% of people are, are heavily impacted by what we just discussed.
- RRRachel Rubin
Can I say one thing real quick, is that I'm a, 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, how do you-- You, 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-
- PAPeter Attia
Hmm
- RRRachel Rubin
... because it changes their marriages, and it leads to divorce, which leads to death. So I, I, I give this lecture of if, if men's health doctors-
- PAPeter Attia
Hmm
- RRRachel Rubin
... if doctors truly cared about keeping men alive, they would do menopause medicine because that is the most im- 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'm just-- I can't thank you enough for this platform, um, because it is everybody's problem.
- PAPeter Attia
Rachel, thank you very much for the work you're doing, and thanks for coming today.
- RRRachel Rubin
Thanks for having me. [upbeat music]
Episode duration: 2:24:37
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