The Peter Attia Drive - #348 ‒ Women's sexual health, menopause, and hormone replacement therapy (HRT)

00:00:00.000 Hey, everyone. Welcome to the Drive podcast. I'm your host, Peter Atiyah. This podcast,

00:00:16.540 my website, and my weekly newsletter all focus on the goal of translating the science of longevity

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00:00:53.200 of the subscription. If you want to learn more about the benefits of our premium membership,

00:00:57.980 head over to peteratiyahmd.com forward slash subscribe. My guest this week is Dr. Rachel

00:01:06.280 Rubin. Rachel is a board-certified urologist and one of the nation's leading experts in sexual health.

00:01:12.500 She is among a select group of physicians with fellowship training in sexual health for both

00:01:18.860 men and women, bringing a rare and deeply informed perspective to her clinical work.

00:01:24.280 In our conversation today, we focus on women's sexual health. We discuss why sexual medicine,

00:01:29.520 particularly for women, remains so neglected in traditional healthcare. The critical difference

00:01:34.540 in how men and women experience hormone decline with age, the physiology of the menstrual cycle,

00:01:40.000 including the role of estrogen, progesterone, FSH, and LH and why perimenopause is characterized

00:01:45.160 by extreme hormone fluctuations, the risks of menopause beyond just symptoms like hot flashes,

00:01:52.260 including the risk of osteoporosis, cardiovascular disease, dementia, and recurrent UTIs,

00:01:57.320 the long-standing controversy around HRT, and how a single study, the Women's Health Initiative study,

00:02:05.040 led to decades of fear-based medicine and an entire generation of women, by my calculation,

00:02:10.860 more than 20 million, deprived of the benefits of HRT, how to use estrogen, progesterone,

00:02:17.080 and testosterone therapy for women, including dosing, delivery method, such as oral transdermal

00:02:22.620 vaginal, and why personalized care is essential, the overlooked role of testosterone in women's

00:02:28.740 health both before and after menopause, the benefits of local vaginal hormonal therapy,

00:02:33.900 a safe, inexpensive, and underutilized treatment that prevents urinary tract infections,

00:02:38.480 improves sexual function, and dramatically enhances quality of life in post-menopausal women.

00:02:43.700 This is a podcast in which I learned a lot, even though I like to think I know quite a bit about

00:02:48.820 this already, but Rachel's expertise here is second to none, and I was feverishly taking notes

00:02:54.240 throughout and obviously can't wait to implement many of the things I learned into my own clinical

00:02:58.900 practice. So without further delay, please enjoy my conversation with Dr. Rachel Rubin.

00:03:08.480 Rachel, thank you so much for making the trip out to Austin. I have been looking forward to

00:03:13.200 this episode for a while, and I'm willing to go on record predicting that this will be a very

00:03:18.400 popular episode given the nature of our discussion. I am so thrilled to be here. I have been nervous for

00:03:23.880 quite a long time, but I'm super happy to be here. I almost don't know where to begin,

00:03:29.000 but it might not be a bad idea to just give people a little bit of a sense of your background.

00:03:34.240 You are a urologist by training, and maybe help us understand how your training in urology led you

00:03:40.960 to what you're doing today, because most urologists wouldn't be doing exactly what you're doing. When

00:03:46.840 we think of urology, we think about prostates, we think about kidneys, we think about bladders.

00:03:52.860 Yes, but what you forget, Peter, is that urologists are ultimately the quality of life doctors.

00:03:57.800 We deal with urination problems, and we deal with sexual medicine, right? No one cares about

00:04:02.920 erections and orgasm and libido quite the way that a urologist cares about. And when we're board

00:04:08.540 certified, actually, it's not a gender thing. We're not penis doctors only. We're board certified to

00:04:14.340 take care of everybody's genital and urinary tracts. Unfortunately, society has led us to know

00:04:20.200 a lot more about the men's sexual health and men's genitals than female genitals. And so my background,

00:04:26.280 I trained in urology really because I was interested in women's health, but I also was interested in sexual

00:04:31.800 health, sexual medicine. And I didn't like delivering babies. I didn't like OBGYN. It just

00:04:37.420 didn't fit well with my personality. And what I love about urology is that we can see everybody

00:04:42.720 and we can really dive deep on quality of life issues. And the magic of urology is also that

00:04:48.060 you really get to know your patients. It's not like when you did surgery, you take out someone's

00:04:53.040 appendix and you never see them again. Maybe you do one post-op visit. Urologists have deep

00:04:57.380 relationships. We're both surgeons, but we actually care about the medical side of these

00:05:02.320 quality of life issues. And so as I was going through medical school, I really realized that

00:05:07.600 talking about sexual health, quality of life issues, that was fun for me. I was good at that.

00:05:11.540 And in medicine, you gravitate towards what is easy, not what is hard. And so it's just been a joy.

00:05:17.120 And really, I've been working to further the field of urology to make us better at taking care

00:05:23.540 of women. And so really, I do a lot of educating and teaching to my colleagues about how we really

00:05:28.920 need to care about the whole, like everybody. Yeah. And I really mostly want to talk about it

00:05:34.460 from a female standpoint today, truthfully, because I think this is where there's just a

00:05:38.900 dearth of great information out there, where I think there's an abundance of garbage information

00:05:44.100 out there. So while I appreciate that your breadth of knowledge will cover both sexes, you'll probably

00:05:51.200 notice kind of a bias in what I want to talk about vis-a-vis women specifically. So let's start

00:05:56.800 with perhaps the biggest and most obvious difference between men and women. And that is

00:06:02.740 from an endocrine perspective, women go through this period called menopause, which is a rather

00:06:07.500 sudden and abrupt loss of their sex hormones. And that's to be contrasted with the way men's sex

00:06:13.740 hormones decline over time a little more slowly. So again, the listeners of this podcast are highly

00:06:19.680 erudite and they won't need the lengthy dissertation, but just give us a quick overview

00:06:25.140 of what the heck is happening in menopause. Why is it happening? And then we can get into maybe what

00:06:29.960 some of the symptoms are before women might really notice them. I certainly did my research and I am

00:06:35.260 not a car person, but I know you are a Formula One guy. And I got a very interesting email last week

00:06:41.040 that said, Dr. Rubin, my wife is seeing your practice. Her libido is now like an F1 Formula One race

00:06:48.020 car and I'm like a 1988 Honda Civic. What can you do for me? My analogy I really like to look at is

00:06:54.240 sort of the gas tank analogy. This idea that men, as they age, sometimes we see a decrease in their

00:07:00.420 gas tank. They're feeling low, they're feeling down, they've got erectile dysfunction, low libido.

00:07:05.060 Whereas women at age 52, their gas tank is empty. This is a castration event. We don't have many

00:07:11.200 castration events in men's health. And so menopause is sort of a, your gas tank is officially empty.

00:07:16.620 There's not much in the tank. Perimenopause is this time where it's very erratic. The gas tank is

00:07:23.180 over full and then it goes to empty really quickly without warning. And so I like that analogy because

00:07:28.480 I think it's helpful when we're talking to women about the reason you don't feel like yourself is

00:07:33.920 because there's just no gas in the tank. So we see the ovaries are no longer producing estrogen,

00:07:38.900 progesterone, and testosterone the way that they were during your reproductive years.

00:07:43.680 I love that analogy. I've never heard it before, but it absolutely replicates what of course we see

00:07:50.840 clinically, which is in perimenopause, why do we sometimes, when we're measuring a woman's labs,

00:07:57.140 say every three months, see periods where estradiol is through the roof, FSH and LH are low,

00:08:03.620 and three months later, it's completely flipped. And of course, with it go symptoms. So

00:08:08.660 can you explain why there's this, if we have hormones running like this during premenopause,

00:08:15.560 they're like this during menopause, but this transition is nothing linear.

00:08:20.320 It looks kind of like the stock market actually. It goes up, it goes down, and it's not even just

00:08:24.640 checking it every three months. If you check it every 10 days, you're going to see a fluctuation.

00:08:29.740 I'm obsessed with looking at the menstrual cycle. I'm obsessed with talking about numbers here

00:08:34.900 because it is so fascinating, and we are not taught to think this way. And so I have a lot

00:08:39.720 of curiosity about it. So for example, when you're in your, let's call it healthy reproductive years,

00:08:45.380 and by the way, nobody is the book. You talk a lot about continuous glucose monitors. I would love

00:08:50.720 continuous sex hormone monitors. And unfortunately, I know there'd be a lot of unintended consequences

00:08:54.860 and bad things that would come of it, but I'd be very interested because the book says,

00:08:58.640 our low, so if you have your period that you're bleeding, that's day one, your low is not zero.

00:09:04.600 In fact, it's probably somewhere 40, 50 is probably what the low should be of estradiol,

00:09:10.500 and that's picograms per milliliter, as opposed to testosterone, which we do nanograms per deciliter,

00:09:15.740 as you know. So probably, let's say 50 is your low. Then you go at ovulate, and that's in your

00:09:20.800 mid-cycle, and usually it's about 150. Let's say ish, maybe it's 200, 300, whatever it is.

00:09:26.340 Pregnancy, your level is 3,000 or higher, right? It's very high. And so if you're in your normal

00:09:32.280 reproductive cycle, you go from 50 to 150. So let's use the gas tank analogy. You're at a quarter

00:09:37.900 tank at 50, and you go to three quarters tank at 150, then down to a quarter tank. You can drive

00:09:43.580 wherever you want to go during that time. What happens in perimenopause, and it is this chaos and

00:09:49.440 erratic fluctuation where your body is just wanting more hormone than it has. Your brain,

00:09:55.360 your FSH is telling your eggs to do more than they can. Sometimes they overshoot. So now you

00:10:00.560 are overflowing gas. I had a lady come in. Her day one, her estrogen was 200, and her day 10,

00:10:07.320 her estrogen was 900. So this is this wild fluctuation in perimenopause.

00:10:13.100 And what I'd like to do now is make sure that anybody listening who wants a more nuanced overview

00:10:18.900 of this, we're going to link to a video that I made a couple of years ago where I walk through

00:10:24.140 the ovulatory cycle and I draw the graph of estrogen, progesterone, FSH, and LH according

00:10:31.040 to the nomenclature you're using by days. But let's also have you do an explanation now of the role of

00:10:38.980 FSH and LH on the brain because you've already referred to that and what the feedback cycle looks

00:10:43.820 like with estrogen. I just want to make sure people are following the physiology you're describing.

00:10:47.600 And that video is so fantastic. We actually were talking about it before doing this podcast about

00:10:51.900 that video. And I said, you know, if you asked most OBGYNs to draw the menstrual cycle, many of

00:10:57.260 them wouldn't be able to do so. It's incredibly complicated and it's so confusing and we think

00:11:02.020 our doctors know everything and unfortunately they don't. And so what happens is estrogen,

00:11:06.960 you have your period, your lining of your uterus is shedding, your estrogen is kind of at its all time

00:11:12.380 low. And again, just to make the obvious statement, it's because most of the time when a woman

00:11:17.440 ovulates, she does not get pregnant.

00:11:19.740 Right. In this non-pregnancy state, you didn't make a baby, you're shedding the lining,

00:11:24.040 your estrogen's about 50, let's say, to make it easy. Now it's starting to go up, up, up, up, up,

00:11:28.880 and you're developing this follicle. So this egg is developing and then the LH is sort of your brain's

00:11:35.340 marker of, okay, it's time to ovulate. So that's when you pee on a stick and you're trying to check

00:11:39.440 if you're ovulating, it's checking your LH levels. And so you're going to see this increase in LH.

00:11:44.700 That happens, again, everyone's a little bit different, but it happens kind of mid-cycle,

00:11:48.540 day 10 to 14, somewhere along the, again, urologist, not gynecologist. And so you get

00:11:53.820 this LH surge, the egg pops out and it is the shell of the egg that creates the progesterone surge.

00:12:00.560 So you actually don't make any progesterone really in that first half of your cycle.

00:12:04.940 And then after ovulation, we call the second half the luteal phase, which just means that's when

00:12:10.300 progesterone is around. And so you get this surge of progesterone when there is no fertilization,

00:12:15.660 that shell of the egg evaporates, and then you lose your progesterone. And it is that withdrawal

00:12:20.200 of progesterone that causes the uterine lining to shed. Now, again, this is very confusing for people

00:12:25.960 because hormones through that time, your progesterone goes from very, very low to after

00:12:31.300 you ovulate, very, very high. And it's that cycle every month. Now, estrogen, again, goes from 50 to

00:12:37.060 150 back down to 50. That's what the book says. I don't know about you, but my patients are not all

00:12:42.320 on the book. Yeah. A lot of my patients don't read the book about what their physiology is supposed to

00:12:47.760 do. It's very disappointing. I agree completely. And so we're super interested in this. We care about

00:12:52.740 how people are feeling. I may say this a lot during our conversation is there's the book answer,

00:12:57.500 there's the Instagram answer, and then my answer is somewhere in the middle is how we sort of talk

00:13:02.260 about it and understand it. Again, I think the numbers are helpful for people to see. When you're

00:13:07.000 pregnant, your estrogen's 3,000. When you're regularly ovulating, it's 50 to 150. Perimenopause,

00:13:13.740 it could be zero, it could be 1,000, and down to zero in two seconds flat.

00:13:19.120 So let's talk about why. So why is it that in perimenopause, the fluctuations in estradiol level

00:13:25.640 are so dramatic?

00:13:27.400 I think it has to do with the fact that you have a limited number of eggs. You're sort of getting to that

00:13:31.700 end of your bucket of eggs that you're born with. That's, again, controversial on the internet.

00:13:36.900 So your body is really trying to do what it has always done, and it's just having trouble. It's

00:13:43.140 having trouble recruiting the egg, ovulating. You don't ovulate every time. Sometimes you ovulate

00:13:48.120 twice, push out two eggs in this perimenopause cycle. So we can sometimes see really high elevations,

00:13:54.540 which can come with symptoms. And that's the challenge of perimenopause is sometimes you have

00:13:59.600 symptoms because you're too low. Sometimes you have symptoms because you're too high.

00:14:03.560 And sometimes it's that fluctuation. Like, again, we'll go to the car model. You're driving 100 miles

00:14:08.380 an hour on the highway, and you go to empty gas tank immediately. That is not good for a car.

00:14:13.740 That is inflammation. That is irritation. That is a lot of perimenopause symptoms.

00:14:17.980 So maybe to extend the analogy, part of the reason why a woman during this period of time can experience

00:14:22.200 these enormous surges of estradiol is, if you think that there's, say, a kink in the gas line,

00:14:29.200 and you really, really want to squeeze the lever to get as much gasoline as you can in the car,

00:14:34.080 sometimes you overshoot and just, you get a whole bunch extra in there because there's volatility in

00:14:39.340 the follicle release. I knew you would like this analogy.

00:14:42.440 Yeah, no, I love it. The one other thing I want to talk about, because it's going to come up later when

00:14:46.260 we get to HRT, is do you buy the argument, which is the argument I have found most appealing as to why

00:14:52.800 women have varying degrees of sensitivity to the dramatic reduction in progesterone that they

00:14:59.420 experience in the last quarter of the cycle once the lining sheds. So we talked about how, of course,

00:15:05.280 during the luteal phase, we're building up, progesterone levels are rising, we're building up

00:15:10.120 the endometrial lining in preparation for pregnancy. Most of the times that's not going to happen.

00:15:16.260 Lining sheds, progesterone crashes. This is what's referred to as PMS. And some women are

00:15:22.480 somewhat unfazed by that. And other women, that's a big deal. And so the question is,

00:15:27.660 is this about central receptors of progesterone and varying degrees of sensitivity?

00:15:33.320 I think it's a really important question. And we see this clinically all the time. If you give

00:15:37.340 somebody, say, micronized progesterone or a synthetic progestin, say, in birth control,

00:15:42.520 you will see a wide variety of reactions to these different medications. And so I would say it has

00:15:48.980 to probably do with the GABA receptor and the metabolites of progesterone and how the receptors

00:15:54.120 in the brain use these molecules. And so I think we just don't know enough. You know, I tell my

00:16:00.200 patients all the time, I wish, oh my gosh, we have so much work to do in women's health. We have so much

00:16:05.020 research we need done. This is why I come on this platform, not because I want to be on this platform,

00:16:10.080 but I need smart people to be listening to this, to ask the research questions and to do this

00:16:14.460 research. Because clinically, we see this all the time. I will put up that menstrual cycle with my

00:16:19.700 patients and say, when do you start to have symptoms? Are you having symptoms when your

00:16:23.000 estrogen is falling? Are you having symptoms when your progesterone is falling? And can we

00:16:26.820 hack this system to help you feel better? And how are you going to respond to it? Because when we give

00:16:31.780 someone micronized progesterone, I would say a third of the patients love it and guzzle it like it's

00:16:36.880 candy and they're the happiest people in the world. It helps their sleep, reduces anxiety.

00:16:39.680 Oh my God. Changes their life.

00:16:41.260 Oh, it's absolutely life-changing. A third of the patients are like, I don't really notice. It

00:16:45.280 doesn't bother me. It's fine.

00:16:46.680 Right. But if you tell me I need to take it, I'll take it.

00:16:48.720 If you tell me I need to take it to protect my uterus, no problem. And then you've got a third of

00:16:52.200 patients who are very sensitive. And even within that third, it is extreme. I mean, we see progesterone

00:16:58.140 allergies where people have horrible reactions to, it makes me too sleepy. It makes me feel bloated. I don't like

00:17:04.060 this. And so I don't, as a clinician and an interested researcher, like I don't know exactly

00:17:09.180 enough to be able to spot who those people are ahead of time.

00:17:12.360 Okay. So we've established now what's happening. We've established that during the period of

00:17:19.680 perimenopause, the one consistent thing that's happening is inconsistency. At some point, we get

00:17:26.560 to the place where the consistency returns, but now it's a new norm. And that new norm is you don't

00:17:33.740 make estrogen. You don't make progesterone. The signal from your pituitary FSH and LH begin

00:17:39.380 monotonically rising, rising, rising. And so if you were to do the blood work of a woman in her

00:17:45.300 sixties who had never been placed on HRT, you would see a very high FSH, a very high LH, usually above

00:17:51.320 the lab's cutoff for measurements and then estradiol and progesterone non-existent. Let's talk about

00:17:58.620 all the reasons why that woman that I just described in her sixties, who is now 10 years

00:18:05.760 out of any hormones, what are the risks to her physical health, mental health, emotional health,

00:18:11.600 the whole picture of her health, cognitive health, everything. What is she worse off for

00:18:15.300 at that period of time?

00:18:16.260 So I think there's a really important question in the sense of what is the risk of taking hormone

00:18:21.680 therapy in that patient? And what is the risk of not taking hormone therapy in that patient?

00:18:25.080 Yeah, and that's why I want to start with this.

00:18:26.740 And so I think it's super interesting because we love talking about the risks of medication,

00:18:30.500 but we don't spend a lot of time talking about the risks of not taking medication. So if we think

00:18:35.640 about that woman as she gets older, she certainly will have the microbiome and genital and urinary

00:18:41.320 changes of not having hormones. So as a urologist, this is actually one of the couple things that

00:18:46.220 will kill her. As you lose hormones in the genitals, which are very hormone sensitive,

00:18:50.440 the bladder is very hormone sensitive, you change the microbiome, you decrease the acidity of the

00:18:55.160 tissue, the bad bacteria grow, your risk of urinary tract infections increase drastically.

00:19:00.360 So she may get recurrent urinary tract infections or pelvic pain. She may develop osteoporosis,

00:19:06.120 which we know more people die of hip fractures, about the same die of hip fractures as die of breast

00:19:10.640 cancer. So the risk of not taking hormone therapy when you get a hip fracture, as all of your

00:19:15.480 listeners know, going back to the life that you lived is very challenging, or you die.

00:19:20.740 There's also the risk of dementia and Alzheimer's much higher in women, and we can argue the data,

00:19:26.260 and I don't think we actually have good data about whether hormones, when to start them,

00:19:30.620 and if they're actually protective and how they're protective. But we also know that heart disease

00:19:34.840 is the number one killer of women, and we know that things get worse as you get older. So I think

00:19:39.460 there are significant risks to that person. And from the mental health perspective,

00:19:43.680 I think there's no question that we see worsening. Now, I will say perimenopause,

00:19:48.680 from what I understand of the data, is actually worse on mental health and can actually level out

00:19:53.120 a little bit once there's less erratic hormones. But again, an empty gas tank is still an empty gas

00:19:58.060 tank. And so we see a lot of challenges in this time period.

00:20:01.240 We talked about, obviously, the risk of dementia. We talked about the risk of osteoporosis,

00:20:07.560 cardiovascular disease, colon cancer. All of these are risks that are pretty clearly going up in the

00:20:13.660 absence of hormones. So do you want to talk about the history of HRT? I mean, it was a largely normal

00:20:21.120 practice in the 1960s. They certainly had some fits and starts. They initially were just replacing

00:20:27.060 estrogen. Figured out pretty quickly, i.e. within a few years, that if you only gave a woman estrogen,

00:20:33.400 you were going to run the risk of endometrial cancer going up because the endometrial lining

00:20:38.780 just continued to get bigger and bigger and bigger, and you eventually developed hyperplasia,

00:20:42.780 which presumably became metaplasia and ultimately cancer. We figured out pretty quickly how to combat

00:20:47.780 that. If you just oppose the estrogen with progesterone, keep the endometrial lining in check.

00:20:52.820 And this largely became the standard of care through the 1980s and into the 1990s. And this

00:21:03.520 was largely validated by epidemiologic observations, which showed that women who took hormones did

00:21:11.520 significantly better. Now, people who listen to this podcast are well aware of how critical I am of

00:21:16.780 epidemiology. And it's certainly very easy to make the case that in the 1980s, women who were taking

00:21:24.600 hormones had a healthy user bias. These are women that probably had better access to healthcare.

00:21:30.120 They were probably more health conscious. And as a result, they were probably doing many more things

00:21:34.400 to improve the quality of their health. So the NIH did something that I think made a lot of sense.

00:21:40.300 It was the right thing to do, which was they said, look, we can't rely on this epidemiology.

00:21:44.300 We need to do a randomized control trial. And they did it through something called the Women's Health

00:21:48.620 Initiative, which had two components, a nutritional component that was asking a question about low

00:21:53.220 fat diets, and then a component that was looking at the HRT. So would you like to pick up the story

00:21:58.220 as to how the study was designed, maybe talk about some of the potential pitfalls of it, and ultimately

00:22:05.220 how the results of that have been misunderstood and misinterpreted for so long?

00:22:08.920 The fact that this story hasn't been made into a Hollywood biopic megadrama, I don't know.

00:22:15.240 This is a big deal. A billion dollars of our resources went into doing this study. And there

00:22:21.280 are many things that we learned that were helpful and useful. And this huge set of data that we're

00:22:25.720 still using today to extrapolate information from, and there was a lot of good that came from it.

00:22:30.340 But there was a lot of misinformation and just really bad marketing or really effective marketing,

00:22:36.400 you could argue. Because what is so wild, Peter, is that when this study came out,

00:22:42.160 they did a press conference. Before the study was published, they did a press conference. Have you

00:22:47.240 ever seen the NIH do a press conference that Matt Lauer talked about or that was made it on Good

00:22:52.340 Morning America? Like, they did a press conference. I remember I was in medical school at the time.

00:22:57.020 Like, I remember this happening. And they said, okay, we had to stop the study early. It is increasing

00:23:04.160 the risk of breast cancer and increasing the risk of blood clots and cardiovascular disease. And we

00:23:08.780 have to stop the study. There's different statistics out there. But people will say about 40% maybe of

00:23:14.020 women were on hormone therapy at the time. Overnight, it crashed to nothing. You're talking billions of

00:23:19.360 dollars of an industry went to nothing. And the people who are prescribing the hormone therapy were

00:23:25.160 like, this doesn't make any sense. I do this. I've been doing this for 20 years, 30 years. I don't have a

00:23:30.060 clinic full of people who are dying of blood clots or heart attacks or who get breast cancer. Like,

00:23:34.680 this is not my clinic. Whose clinic is this? Then they published the paper. And as we talked

00:23:39.860 about before we did this podcast, is that they misinterpreted the data so drastically and scared

00:23:46.000 everybody with so much fear that you actually have an entire generation that has forgotten how to

00:23:52.660 prescribe hormone therapy. And this is the nightmare that we're living in today because

00:23:56.800 now we realize that the data was misinterpreted. So the WHI was one medication, one dose. That's it.

00:24:05.320 And it was a sort of birth control pill style kind of hormone therapy. So a synthetic estrogen and

00:24:11.780 progestin. It was not the, what we call more, and we can talk about the marketing term bioidentical,

00:24:16.900 but the FDA approved products that we use today, like estradiol and progesterone,

00:24:21.100 they're different medications that we use today. And so you're talking one medication,

00:24:25.040 one dose, and we're still practicing fear-based medicine 30 years later, whatever it is,

00:24:31.400 saying like, we don't practice any other medicine like this. We're like, well, there was one study

00:24:35.200 about surgery 30 years ago, and that's the way we practice medicine. We evolve, we learn new things.

00:24:40.240 So what did it show? Let's talk about the good. When you took estrogen and progestin or estrogen

00:24:45.960 alone, you had a decreased risk of colon cancer. You had decreased risk of fractures, like significant

00:24:51.160 decrease of fractures. Decrease of diabetes, okay, that seems like a good, those seem like all good

00:24:55.900 things. This is in the hormones we don't even really prescribe anymore. We saw a decrease in

00:24:59.940 overall mortality, a decrease in cancer-specific mortality. And then when you looked at the

00:25:05.100 cardiovascular data over time, and again, I'm a urologist, I'm not a heart expert, but you saw

00:25:09.380 there was actually no difference. It actually wasn't so scary. Now, as you get older, we know birth

00:25:13.800 control pills can cause blood clots. So we do worry about giving a birth control pill to grandma

00:25:18.360 because you can increase blood clots. That's true. I agree with that. When it comes to breast

00:25:22.580 cancer, the most fascinating data that didn't make the press conference, women who are on the

00:25:27.340 estrogen alone, so they didn't have a uterus, so they didn't need the progestin therapy,

00:25:30.820 had a decreased risk of getting and dying from breast cancer. And it didn't make the news.

00:25:35.960 Even in that study that put the box labeling on all the products, it's not true. So then when you

00:25:40.760 looked at the estrogen and the progestin groups, there was a fear that there was an increased risk of

00:25:45.160 incidence but not mortality from breast cancer. And even when you look at that data, there is

00:25:50.320 questioning of the fact that the placebo group actually was more protected by breast cancer

00:25:56.180 because many of them had been on hormones in the past. And when you use a correct placebo group,

00:26:00.680 the lines actually go together. And so you're more of a statistics nerd than I am, but the reality is

00:26:05.520 there was no difference. And so we scared an entire generation of people away from hormones because

00:26:11.020 of a bad misinterpretation of statistics. So Rachel, I don't know how good you are at sensing a person's

00:26:18.060 blood pressure from across the room, but if you were able to sort of project your vision into my

00:26:24.860 carotid artery... I see it bulging. Yeah, you'd notice that my blood pressure is up. I'm probably at 180

00:26:31.440 over 120 right now. First off, I think that was a remarkable, succinct summation of the WHI. I'm only

00:26:40.980 going to repeat a few things, not because I didn't think you did a great job, you did, but because

00:26:46.120 sometimes hearing it twice highlights the egregiousness of this study. Shout it from every

00:26:52.300 rooftop you can find. Truthfully, I have friends, female friends, and I have patients who to this day

00:26:59.300 are paranoid about hormones, and I just want to offer yet another opportunity for them to sort of

00:27:06.500 understand what's going on. So this was a study that had two parallel arms, one where women without

00:27:13.180 a uterus were just randomized to either the synthetic or equine-based estrogen versus a placebo, and then

00:27:19.980 one where if you had a uterus, you got MPA, a synthetic progesterone, and the estrogen. As you pointed out,

00:27:26.740 the elephant in the room here, the one finding that got all of the attention was that in the

00:27:33.840 women with uterus group, if you got the synthetic progesterone and estrogen, you had an increase in

00:27:43.160 your incidence of breast cancer. It turned out it didn't actually lead to any change in mortality

00:27:49.240 from breast cancer, but there was an increase in the incidence. The number is really scary if it's given

00:27:56.100 in relative terms. It was a 24% increase in the incidence. Incidence, for the listener, meaning

00:28:03.520 getting breast cancer. You had a 24% higher chance of getting breast cancer if you took the two

00:28:11.660 hormones. On the surface, that sounds devastating, but again, as people who listen to this podcast know,

00:28:16.560 we always need to think in terms of absolute risk. And relative risk doesn't mean that much if you

00:28:22.900 don't understand absolute risk. So if I said to you, Rachel, I have a treatment for you that is

00:28:28.940 going to fix a hundred problems, but it increases your risk by 100% of getting hit by an asteroid,

00:28:37.520 would you take the medicine or not? Well, you'd have to know what your base level risk of getting

00:28:42.460 hit by an asteroid is. And given that it's almost zero, doubling it doesn't mean anything.

00:28:48.580 So the absolute risk increase for these women was 0.1%. So to put that in less technical terms,

00:28:58.840 it meant even if you believe the results of that study, and you've offered a great explanation for

00:29:04.000 why the actual results should be questioned, but even if you take them at face value, for every

00:29:10.640 1,000 women who were put on HRT, an additional one got breast cancer, though she didn't die from it

00:29:20.460 at any increased rate to the women who didn't get the hormone. This to me, and I'd like you to push

00:29:27.300 back on this, although I'm worried you won't be able to because you share my bias. This is the greatest

00:29:32.800 injustice imposed by the modern medical system in our lifetime.

00:29:37.860 You are not going to get pushback from me on that. This is a disaster. I just got back

00:29:43.160 yesterday from teaching at the largest internal medicine conference, ACP, the American College of

00:29:47.680 Physicians, and you're talking more than 20,000 internal medicine physicians. What a wonderful

00:29:52.320 thing. I was asked to give a course on female sexual dysfunction, and it was wonderful. I talked a lot

00:29:56.940 about menopause. There was no other menopause content at this course. There was no courses how to

00:30:02.940 prescribe. Given everything you've done, my colleagues and myself have done to bring it into

00:30:07.780 just popularity. Patients are coming in asking questions, and there wasn't even a course to

00:30:16.100 learn. I can't say that's true for GLP-1s or any of these lipid-lowering agents or all of the things

00:30:22.600 that you've been pushing. The problem is you now have a brain drain, I think, because the doctors who

00:30:28.140 prescribed hormone therapy either retired or died, and there was no one they taught ahead of them.

00:30:35.200 Now, I was very lucky. I had very good mentorship and incredible experience, but we are now trying

00:30:40.780 to make up for lost time to train people how to write prescriptions. So it's not enough to say,

00:30:46.720 hey, the WHI was misinterpreted, and we've done a bad thing for women. People don't know how to do

00:30:51.920 this. It's a huge problem. And the reality is this is half the population. This is not niche medicine.

00:30:59.900 The fact that menopause medicine is the tiniest little room of subset of gynecology, which it should

00:31:07.080 not be under gynecology. This is whole body medicine, and yet nobody seems to care.

00:31:13.420 Yeah, it's really interesting to hear you say that because you're highlighting something that's as

00:31:19.280 dramatic and potentially more dramatic than the thing I've tended to focus on. I've focused more so,

00:31:25.540 maybe I just take for granted that I got lucky and I had amazing mentors and they taught me how to do

00:31:30.240 this stuff, but it's also the nature of my personality to just be endlessly curious and

00:31:35.980 show up in somebody's clinic for two weeks and do this. I've tended to focus on the lost generation

00:31:42.420 of women. So I had my analysts do this analysis two years ago, and I don't remember the exact numbers,

00:31:48.320 but the analysis was calculate for me or estimate for me the number of women who were deprived of HRT

00:31:55.820 because of the WHI and calculate the excess mortality that was achieved through that injustice,

00:32:03.240 through hip fractures, cardiovascular disease. We just went through the entire list. Calculate the

00:32:10.400 number of lives that were lost, the amount of disability that was incurred, because to your point,

00:32:15.920 even if you don't die from a hip fracture, 50% of survivors never regained the same level of

00:32:20.840 function. And I didn't even know how to quantify all of the sexual side effects that women unnecessarily

00:32:27.000 endured, all of the vasomotor side effects that they unnecessarily didn't even try to quantify that

00:32:32.080 because I don't know how to, but that's the thing that I focus on. And again, it's personal to

00:32:37.040 someone my age because my mother and my mother-in-law are in that category. They're the ones that got

00:32:43.360 absolutely screwed by this system. You're highlighting something equally catastrophic

00:32:49.360 with potentially a greater impact, which is we failed to train a generation of doctors to do

00:32:54.640 anything about it. And if that's not reversed, the problem doesn't get much better.

00:32:59.480 Yeah. I mean, the data is very clear on this. Less than 6% of internal medicine, OBGYN or family

00:33:05.560 practice doctors get even an hour of menopause education in their training. Do you remember

00:33:11.600 learning about menopause in your medical school? Zero. Zero. Not one minute.

00:33:15.040 I didn't learn one minute of it. I did learn that hormones were bad.

00:33:18.660 Oh, yeah. You learned, right, right. So because you are taught hormones are dangerous or the

00:33:23.420 bodybuilders take the hormones, the snake oil salesmen take the hormones. We don't talk about

00:33:27.720 this in real medicine. Everyone says, it's not my industry. It's not my thing. I went to this

00:33:33.600 internal medicine conference yesterday and all the internal medicine doctors were saying, but this isn't

00:33:37.840 my field. I don't feel comfortable, right? An endocrinologist was standing there saying,

00:33:41.740 I don't feel comfortable doing this. I said, you're a hormone doctor. That is what you do.

00:33:46.660 It is so embarrassing. I've been asked to speak at multiple academic centers to teach on hormone

00:33:51.480 therapy. And every time I'm like, is this real life? I am a urologist teaching hormone doctors about

00:33:58.120 how to prescribe hormone therapy. And it is real life. And this is why I'm so loud about it, because

00:34:03.520 we have to change this. We have to change this on a big level, because I need the ICU doctors

00:34:09.900 and the pulmonologists and the heart doctors and all the doctors to know that menopause affects their

00:34:16.100 organs. Colon cancer. Why aren't GI doctors talking to women that estrogen prevents colon cancer?

00:34:22.260 Why are we checking DEXAs at 65? Why are rheumatologists not prescribing hormone therapy? I found out

00:34:28.700 recently that psychiatrists, because I do a lot of teaching about how to prescribe hormone therapy,

00:34:33.000 a few of us are very passionate about it. And I was like, sit with me. I will teach you how to

00:34:36.440 write the prescriptions. I've had psychiatrists tell me their malpractice insurance will not cover

00:34:41.540 them if they prescribe hormone therapy. And I said, wait a minute, you prescribe postpartum

00:34:47.580 depression drugs, which are progestin based. You do reproductive psychiatry, which means birth

00:34:52.900 control is a part of what you do. And you're being told you're not allowed to prescribe hormone therapy

00:34:57.720 when hormone therapy is one of the greatest antidepressants in the history of medicine.

00:35:02.780 It is insanity. We're living in a nightmare.

00:35:06.900 Let's talk a little bit about how we go about doing things. So there are two hormones we've

00:35:12.280 talked a lot about, but there's a third that we haven't yet talked about that is very linked

00:35:18.140 to these two hormones, doesn't get enough attention in women. And of course, that's testosterone.

00:35:23.320 So before we get into how one should think about replacing hormones, can you talk about the

00:35:29.440 relationship of testosterone to women's sexual health and what's happening to testosterone levels

00:35:34.920 during this transition from peri to menopause? Because of course, I want to bring this into

00:35:38.960 the HRT discussion. Super interesting. And I'm very passionate about this topic. And so I think it

00:35:43.760 comes from this idea that I do testosterone for men all the time. I'm very confident. I love

00:35:49.220 prescribing testosterone for men's sexual health. And actually, very interestingly enough,

00:35:53.820 when we prescribe testosterone for men, remember, their gas tank doesn't get empty. It gets low.

00:35:58.340 It's off-label. We are doing off-label testosterone therapy in men. Unless they have

00:36:02.320 Klinefelter's or some significant medical problem, we're doing off-label testosterone for men. And it's

00:36:07.700 very understood. It's talked about. The FDA just three weeks ago removed the labeling on testosterone

00:36:13.660 therapy, saying it no longer is a cardiovascular disease risk. So that's great news.

00:36:18.080 So the thing about women and testosterone is it's actually not a menopause thing. Testosterone is an

00:36:24.280 age-related decline. So in your 30s, you're starting to drop your testosterone. And testosterone,

00:36:31.200 I don't know who decided that men get testosterone and women have estrogen. Like we both have both of

00:36:36.280 the hormones. You've probably heard me make this point before because you alluded to it a few minutes

00:36:41.260 ago. We measure testosterone in nanograms per deciliter. We measure estradiol in picograms per

00:36:47.000 milliliter. If you normalize those to the same level, women are shocked to learn that they have

00:36:53.980 10 times the amount of testosterone in their body that they do estradiol at peak estradiol.

00:37:00.640 Way more. And I love sharing that. When you put everything in the same units,

00:37:05.300 we are testosterone-driven beings. Both of us, right, are testosterone-driven beings.

00:37:09.620 We don't teach this to OB-GYNs. No OB-GYN knows, some do, but very few know about the role of

00:37:16.140 testosterone in women's health. And so we love to gaslight women and say, well, if you have your

00:37:21.600 period, your hormones are normal. Drives me insane. Women are told this all day every day is, well,

00:37:27.100 you can't possibly have a hormone problem because you're getting your period regularly.

00:37:31.640 And the reality is, is that's not true. Why? That curve, that curve we were just talking about,

00:37:36.240 testosterone is nowhere on that curve. And so we know there's a peak of testosterone around

00:37:40.560 ovulation. That is nature's way of saying, let's make a baby. We know that. We know that your libido

00:37:46.180 goes up around ovulation because your testosterone goes up. And so there is this age-related decline

00:37:52.420 in testosterone. And here's another big problem. We give women birth control pills all the time.

00:37:58.060 How does birth control work? By the way, birth control is high-dose hormone therapy. We love hormone

00:38:03.980 therapy in birth control, but as soon as you become menopause, everybody's afraid of hormone therapy.

00:38:07.880 It makes no sense. So birth control is high-dose, I would argue, the hormone therapy we're talking

00:38:14.320 about in the WHI that is more synthetic, that has side effects, that have issues like that. So birth

00:38:18.980 control turns off your ovaries, and it adds back a final estradiol and a synthetic progestin. It

00:38:25.440 doesn't add back testosterone. So we are botching testosterone for women along the life cycle, to be

00:38:31.600 honest. But if you take someone who's never been on birth control, their testosterone starts to drop in

00:38:35.840 their 30s. So what are they complaining about? It's not just a libido thing. We know there are

00:38:40.340 testosterone receptors all throughout the genitals and the urinary tract. So we see women have an

00:38:44.960 increased risk of UTIs. We see an increased risk of pain with intercourse or pelvic pain conditions.

00:38:50.840 We see there are some studies that indicate potentially depression and anxiety can increase

00:38:55.340 because we do think there's a testosterone effects on the brain. But we have global consensus. And I don't

00:39:01.220 know if you've read the news lately, Peter, but we don't agree on too much as a globe. But there is

00:39:05.220 global consensus that testosterone in women works for low libido. And so specifically, the data is on

00:39:11.220 postmenopausal women. That's where the global consensus is. But there is data in perimenopause

00:39:16.080 and much smaller studies before that. The consensus is it works. But everyone has emotions about testosterone.

00:39:23.320 I didn't think testosterone was a feeling, but apparently it is a feeling for people because people hate

00:39:28.220 talking about it. And again, nobody taught you how to prescribe it. And there's no FDA-approved

00:39:33.280 product for women, except in Australia, it's approved by their governing body. And so you have

00:39:38.380 a lost art of knowing how to give people back testosterone when they are symptomatic.

00:39:45.240 I think this is an area where women sometimes are also a bit concerned about what happens if I take

00:39:51.440 testosterone because testosterone, understandably, conjures up images of all sorts of things from

00:39:59.700 large muscles, big mustaches, lots of other things. So how do you talk to women about this?

00:40:07.340 We enjoy having these discussions and also acknowledging side effects. The most common

00:40:12.160 side effect we see in women is acne. I don't think I've ever gotten to the point where I've seen

00:40:17.040 any of the really dramatic side effects. But I do tell women, I say, look, there's a decent chance

00:40:22.600 if you were shaving your legs every five days, you're going to be shaving them every three days.

00:40:27.460 That's a chance. If you were kind of susceptible to acne growing up, you might get a little bit more

00:40:31.580 of it and we'll have to back off. How do you talk about the risks of testosterone therapy?

00:40:35.100 I love talking about this. And I'm actually grateful for celebrities because just in the news in the past

00:40:39.300 few weeks, Halle Berry says she's on testosterone. Kate Winslet says she's on testosterone therapy.

00:40:43.840 They look pretty amazing to me and they don't look androgenized at all.

00:40:47.360 And so I actually want to do this study. It's something my research team's working on

00:40:51.520 is I think I have more patients who never start testosterone therapy because of the fear of

00:40:56.460 side effects than actually stop testosterone therapy because of the side effects. That's my

00:41:01.080 observation in doing a lot of this. Now, when we talk about side effects, I tell them,

00:41:05.760 think about a horny teenager. They have these great libidos, but they have some oily skin,

00:41:09.800 acne, but that's when you get really high with your doses. We really don't see it clinically.

00:41:14.400 Yes. I use FDA approved testosterone for men, just a doses, one 10th a dose in a way. They rub

00:41:20.380 it on their leg because if they do get hair on their leg, people are used to having hair on their

00:41:24.280 leg. And so they shave it, they wax it, they laser it, whatever it is that they do with leg hair.

00:41:29.280 I don't have that many patients stop for acne, oily skin. I think there's that fear when you get

00:41:34.080 really high in the dose. So I'm not a pellet promoter or user because you get super physiologic

00:41:38.840 levels and I can't take it out if you get a pellet put in. And so if you have deepening voice

00:41:43.900 or clitoromegaly, hair issues, these are the challenges with some of these super physiologic

00:41:49.240 levels. But when we're using reasonably dosed topicals, we really see magic happen. And I

00:41:56.020 can't tell you when we get estrogen and progesterone right for our patients, it is by adding that third

00:42:01.740 piece, that testosterone, because your ovary probably does more than three things, but at this point,

00:42:05.720 estrogen, progesterone, and testosterone, when we add that testosterone piece, it's wild. All the

00:42:11.240 patients come back and they say to me, wow, I feel like me again. It's wild. That's the piece. Wow.

00:42:17.300 I didn't realize how badly I felt. Wow. That was the missing piece. I hear it over and over and over

00:42:23.200 again. I can't not want that for all women. I can't not want to give them that as an option

00:42:28.600 on the menu.

00:42:29.620 So let's just finish the swing on testosterone. Do you prefer then to rely on the topical version

00:42:37.980 of, which would be like an androgel type product and just dose it at a much smaller dose?

00:42:44.080 Yeah, that's typically how we do it and how our guidelines look at it. So ISWISH,

00:42:47.860 the International Society for the Study of Women's Sexual Health, fabulous organization. You can find

00:42:52.640 any doctor to help you with menopause and sexual health by going to their website. They came out with

00:42:56.640 a really lovely how-to practice guideline that they took from the Global Consensus. And they

00:43:02.020 do recommend using that FDA-approved testosterone for men and using it at appropriately doses for

00:43:08.560 females. So I like Testim, which is sort of the 1% generic testosterone gel. I'll show it to you.

00:43:14.760 I brought it for you to show you. It's a 5-milliliter tube of gel. Our male patients would use the whole

00:43:20.400 tube of gel, rub it on their chest every day. I have very few men who do that, by the way. Injections,

00:43:24.820 orals, those are much better. And so I tell my patients, use a blob or 0.5 ml so they can put it

00:43:30.720 in a syringe if they want to and dose out that 0.5 ml. They take a blob, they rub it on their calf

00:43:35.980 every day. And so just don't use the whole tube should last you about a week or 10 days. It's an

00:43:41.340 ish. It's not an exact precision science, but the patients can figure this out. It's not that

00:43:46.640 challenging. I will say this, and I think I have colleagues who disagree with me on this, and I would

00:43:50.820 love to know your experience. I think testosterone, I think for men too, but that's my bias, it takes a

00:43:56.960 while to kick in. I will tell patients, you need to do this regularly, and I think it's going to be

00:44:03.100 three, four, even five months before you're going to really wake up and say, wow, this is working.

00:44:09.760 Oh my gosh, someone just walked across the street and I did a cartoon-style head turn when my eyes

00:44:14.720 popped out of my head. Oh my gosh, I initiated sex. Wow, that orgasm was easier to have. These

00:44:20.420 are the things that patients notice. I also get patients telling me their stress incontinence

00:44:24.280 is slightly improved. Why? Because the urethra has testosterone receptors in it. We know that for

00:44:29.060 all genders. These are the kinds of things my patients will report. I don't know. What do you

00:44:32.820 think? I think it takes a while. That's an interesting question. I mean, I definitely agree that that's true

00:44:38.240 for some people. That said, I've also seen people who within weeks report feeling better. Now, the

00:44:45.120 challenge here, of course, is the only way you could understand this is through blinding. We just don't

00:44:49.980 know how significant the placebo effect is. And therefore, it's hard for me to discount or know.

00:44:56.280 We have studies on testosterone, which show- Oh, sorry. I mean, within my observation.

00:44:59.700 Got it. I hear you. Yes. I want to ask you another question about Natesto. So Natesto,

00:45:05.280 for the listener, is a nasal formulation. It's an FDA-approved formulation. In theory,

00:45:11.220 it seems like a great idea. In practice, it has not really panned out just based on its messiness.

00:45:17.580 It's a gel, a nasal gel. We've had women use it vaginally, nasally. What's your experience been

00:45:24.180 with it? It's getting harder and harder to find these days. And so I think similarly, we've been

00:45:29.360 interested in it and people have played with it before. This idea, can you do one squirt into your-

00:45:34.400 Nobody likes to squirt things in their nose, it turns out. It's a challenge. Now, any of these

00:45:38.760 topical testosterone formulations, a lot of them have alcohol in them, so I don't recommend putting

00:45:43.000 them on your genitals directly. But I do think it needs to be studied. It's challenging finding the

00:45:48.700 formulation of testosterone that is low enough, like from the male side, because we have lots of

00:45:52.820 formulations for men, that is low enough to kind of give an appropriate dose.

00:45:56.560 Why isn't a female formulation being made?

00:45:59.480 Buckle up, buttercup. So here we go. We had a billion dollars that was put into it. A billion

00:46:04.240 dollars and a five-year study that was done at the FDA. And it showed it was safe. It showed that

00:46:09.380 it was effective. It showed that it was- The TLDR on testosterone is it's not that serious.

00:46:14.320 We want it to be serious. Again, not a feeling. We want it to be like all about aggression. It's not

00:46:19.080 a feeling. It truly isn't. So they did five years of study. A billion dollars went into it.

00:46:23.920 And the FDA came back and they said, ooh, women have breast tissue. So we're going to need five

00:46:29.780 more years of data and another billion-dollar study. And every company was like, I'm out.

00:46:35.060 The benchmark was different for women. Men, six months-

00:46:38.280 And this was a real goalpost move.

00:46:40.160 Yeah. They just keep moving the goalpost. Everywhere they move the damn goalpost. Okay,

00:46:44.680 I talked about the labeling on testosterone being removed, that it doesn't worsen cardiovascular

00:46:48.740 disease. Why? Because they did the Traverse study that your listeners know about that proved it.

00:46:53.560 The box labeling on estrogen products, which says that estrogen causes stroke, blood clots,

00:46:58.440 heart attacks, probable dementia. We just got done saying that that study didn't show that.

00:47:03.400 So why is that box labeling still there? We're killing women by trying to protect them.

00:47:09.920 Why do you think this is happening? If you try to steel man the case for the other side,

00:47:17.700 where are they in their thinking on this?

00:47:20.480 I think medicine has a humility problem and a deeply ability to say, hey, we didn't know what

00:47:28.040 we didn't know back then. We're learning and we're adjusting. They don't like to say, I don't know.

00:47:33.580 They don't like to evolve in their thinking. And for some reason, women's health comes with so much

00:47:39.640 bias. The amount of money that goes into women's health research is worse than it was 10 years ago.

00:47:45.940 But is this a paternalistic, I mean, I hate to put sociology on top of this. As you know,

00:47:51.400 I've spoken with one of the PIs from the WHI and I think she is by far the most honest broker of that

00:47:57.780 group. And I don't have good things to say about that group. I really don't. But I also can't even

00:48:05.120 wrap my head around their thinking. Like I can't steel man their case.

00:48:09.360 I wake up in the morning. I'm like, how is this real life? Okay. I'll give you an example. We met

00:48:14.440 with the chief before the administration chain. We met with the, I think it was the chief medical

00:48:19.460 officer of the FDA. We met with someone high up at the FDA. It was a room full of perimenopausal

00:48:23.260 women. I was like, yeah, we got this. It's a room full of perimenopausal women. And we presented

00:48:27.160 our case about vaginal hormones, which is basically microdosing hormones. And they prevent UTIs by more

00:48:33.360 than half. When you use vaginal hormones, you treat the genitourinary syndrome of menopause.

00:48:37.800 And we said to them, we said, your labeling, this should not have the same labeling of all

00:48:42.220 estrogen products. You should remove the labeling. And they said, well, we're really going to need

00:48:47.760 industry to come at us to remove the labeling. I said, you didn't need industry to put the box on.

00:48:52.880 Why do you need industry to remove the box? We no longer have industry in this field in any

00:48:57.660 significant way because the WHI destroyed that industry. So we have a huge problem where you actually

00:49:03.660 don't have any money to women's health. I think Pfizer completely fired their women's health

00:49:08.200 division saying, yeah, we're going to look at allergy now. You have entire departments. We did

00:49:12.760 a study once on pelvic pain. We were looking at botulinum toxin in pelvic pain. And I was on the

00:49:17.500 call where they said, ooh, we have a new CEO now and women's health is no longer a priority. Like I

00:49:22.600 heard those words. So we do have a paternalistic problem. It's true. And unfortunately, it's not getting

00:49:30.160 any better. I usually do not subscribe to theories like that. I usually find myself thinking there

00:49:38.840 are alternative explanations and we're just pointing to the most sensational ones, but it gets hard to

00:49:46.100 dismiss an argument as follows, which is if the tables were turned and the WHI was really the MHI,

00:49:55.560 the Men's Health Initiative, and it produced equally idiotic results, would we be in the same place we

00:50:01.640 are today? Or would men have said, oh, hell no? The Traverse trial, right? There were two bad studies

00:50:07.820 that were done, horrible studies that made no sense that showed testosterone had some dangers. The FDA

00:50:13.820 threw that box labeling on, said, oh my gosh, within minutes, they created the Traverse trial. It got done

00:50:19.100 in five years. And within minutes when it was finished and it got published in the New England Journal of

00:50:23.300 Medicine, the box was removed. And by the way, the Traverse trial's not even a great trial. I've been

00:50:28.600 so critical of the Traverse trial. Amen, right? I think you could have come to the same conclusion

00:50:32.760 of the Traverse trial if you knew how to read all of the data before it. I actually don't think the

00:50:37.100 Traverse trial added much, but anyway. Totally. Look at data. Oh, there was an increased fractures from

00:50:41.980 the, oh, testosterone causes fractures. That makes no sense. We know that's not true. We know testosterone

00:50:46.800 helps bone mineral density. And so you can make the same arguments of how you look at these studies,

00:50:51.440 how these studies are designed, the flaws of them. You're going to do a study for five years.

00:50:55.240 Why are you giving people gels? Is that the right thing? So why do we care what the people of the

00:51:00.940 Women's Health Initiative said 20 years ago? Why is that even news? And why can't it die? And because

00:51:07.800 you don't have enough people like you standing up, you don't have the internal medicine doctor standing

00:51:13.540 up and saying this is wrong because they're not teaching it. You don't have the OBGYN saying this is

00:51:17.960 wrong because they're delivering babies and women are dying in childbirth. Women's health,

00:51:23.080 menopause health in particular, is important to nobody. When it's nobody's problem, nobody takes

00:51:28.960 ownership of it. I mean, I do believe this is going to change. And I don't know who said this,

00:51:33.900 but it's a great quote that said, funeral by funeral science makes progress. That's not a great

00:51:39.420 explanation for what's about to happen temporally because it's going to be a while before everybody

00:51:45.060 who held that belief in their soul is no longer around. But it does give me hope that a new

00:51:51.980 generation of women will come along and take ownership over their health. And look, I've seen

00:51:56.320 a change in 10 years. 10 years ago, when I was prescribing hormones to women, you cannot believe

00:52:03.900 the fights I would have with their other doctors. And I don't mean like we weren't fist fighting,

00:52:08.780 but they were scolding me like, how dare you? But it came with an arrogance, a lack of willingness to

00:52:18.260 even look at the data, which I found ironic. If you want to scold me, you better know as much as me

00:52:24.680 and hopefully more. But this arrogance of I'm going to scold you, but I know nothing. And I'm not

00:52:30.600 actually willing to have a discussion with you because I'd be like, great, turn to figure two

00:52:34.960 in the JAMA paper and let's look at this. And look at the appendix and look at the supplemental

00:52:41.340 data. Like, are you seeing the same thing I'm seeing? Can we at least agree on the facts?

00:52:45.740 No, we can't. And it's so fascinating because I would never, I do sexual medicine. So I look at

00:52:51.620 the whole patient, I look at everything and I would never say to them, hey, you have to stop this beta

00:52:57.380 blocker right now because it's causing your erectile dysfunction. I would never tell a patient that,

00:53:02.240 though, the beta blocker may be worsening his erectile dysfunction. But I would never say,

00:53:07.300 stop this medicine. It's hurting you. I would talk to their doctor. I would have a conversation.

00:53:11.580 But there's something about hormones that doctors who know nothing feel very confident in saying,

00:53:17.840 you can't be on this. You must stop this without even having that curiosity of, huh, I wonder if the

00:53:25.140 person who prescribed it actually knew what they were talking about. And it is everywhere. We see this all

00:53:30.060 the time. Now let's talk about the flip side because the unfortunate nature of everything

00:53:36.120 we've just described is you create a fringe movement. And unfortunately, I've seen a lot of

00:53:43.340 doc on a box hormone practices that are, I believe, putting women at risk. And I believe are doing bad

00:53:51.040 things to women in the name of doing good. And I don't believe that these are inherently bad

00:53:56.900 individuals. I think they're ill-informed. I think they're just not that bright. And maybe some of

00:54:02.660 them are just actually charlatans. And they're seeing an enormous opportunity here. As a general

00:54:07.000 rule, I tell patients, be very, very suspicious of a doctor that is selling you hormones. Be incredibly

00:54:16.120 suspicious of any physician who has their own compounding pharmacy within the practice and is

00:54:24.020 giving you compounded formulations and also making money on it. Talk a little bit about,

00:54:29.600 I don't want to call it the dark side, but just the fringe side of this world.

00:54:33.540 So I would argue that people care about their pain points. People want to feel better. People will go

00:54:39.780 to anyone who tells them there's a whole supplement aisle at CVS that makes all these wildish claims

00:54:44.920 that we're going to help you with everything. And the reality is, is I just got done saying your

00:54:49.660 gynecologist and your internal medicine doctors are going to, in that 10-minute visit, tell you that

00:54:54.880 you don't need this. This is not going to help you. And so enter the fringe people, the snake oil

00:54:59.460 salesmen, the people who are doing wildly inappropriate things. That doesn't mean the

00:55:04.120 hormones themselves are bad. It just means we have a marketing problem here. If we're not doing it and

00:55:09.420 helping people, they hear their friend did it, they hear their neighbor did it, and they said,

00:55:13.100 I want what she's having. This is why we call ourselves the menopause. This is why we teach so

00:55:18.720 loudly, is because we're trying to bring it back into medicine and evidence-based medicine and say,

00:55:24.880 you can actually do this quite reasonably. In fact, there are many FDA-approved products that work

00:55:30.320 much better, that are more regulated, that are totally safe. Here's what they are. They should

00:55:34.760 be covered by your insurance and giving them that knowledge. Because the problem is, is it's too quiet.

00:55:39.900 No one is giving people answers. No one's even looking at the questions. So then the fringe people

00:55:45.260 take over and are unfortunately doing a very inappropriate thing. You know what? Men's health

00:55:49.780 too. As a urologist, we see shot clinics and all these wild PRP clinics and testosterone pellet clinics

00:55:56.720 and compounded pellets and all of these things because my colleagues, we are not doing enough to

00:56:02.000 take care of men's sexual health. And so these clinics exist to prey on those patients who deeply want

00:56:07.400 to connect and get their answers, which is why my colleagues and I are even loud about it for

00:56:12.620 everybody. Yeah. The number of online testosterone clinics is mind-boggling. And a lot of them are

00:56:20.020 prescribing, I think, second-tier drugs. And you know what I say? I say, you know, with these things

00:56:25.280 is the people who need it are not being offered it. And the people who don't need it are abusing it.

00:56:30.560 And that is true for hormones for everybody. I talked about this at the last menopause meeting.

00:56:35.160 Less than 4% of women are on hormone therapy right now. Less than 4%.

00:56:39.660 4% of women who would theoretically be required?

00:56:42.980 Yeah. Less than 4%. That's worse.

00:56:45.260 That's worse than I would have guessed.

00:56:46.700 It's worse than 10 years ago. It is so bad out there. I did the same calculations you did when I

00:56:52.080 was on my Uber on the way over. I said, how many women are over 40? It was something like 84 million,

00:56:56.600 according to AI. And there are about 3,000 people on the Menopause Society website. That doesn't mean

00:57:02.120 everybody knows what they're doing or that they all do the same thing. But divide 84 million by

00:57:06.680 3,000, it's a big number. And we can't see patient panels of 27,000 people. The math doesn't math

00:57:12.640 there. So we need people to step up. So who should be writing estrogen prescriptions? Who?

00:57:20.620 Every doctor who sees a woman of that age.

00:57:22.620 Every doctor who sees a woman of that age. And so who actually does? Nobody.

00:57:26.520 Yeah. Let's talk a little bit about the playbook. I want to tell you how we do it. I'm not saying we

00:57:32.200 do it right because I don't think there's a right way to do it. But I mostly want to hear how you do

00:57:35.460 it because I bet you're way better than we are. Maybe we take a step back and explain. We've already

00:57:39.840 alluded to it twice, but I just want to make sure people are understanding this. If a woman has a

00:57:44.440 uterus, you have to protect that endometrial lining. So even if she's in the camp of women who don't

00:57:50.600 notice being on progesterone, you have to be on progesterone. We'll come back to IUDs and

00:57:56.660 progesterone-coded devices and things like that, Nigel, let's just talk about the way you give

00:58:00.200 progesterone. So progesterone is the easiest of the lot. Is there any reason when giving oral

00:58:05.940 progesterone to use anything other than micronized FDA-approved progesterone orally?

00:58:12.580 What's lovely is we need a toolbox because not everybody responds to the same thing. I love micronized

00:58:17.460 progesterone. I think it's a fabulous product. It's my go-to first line. Sometimes we need to

00:58:21.960 put it vaginally instead of orally to help with some of those sedating side effects. So you can

00:58:27.200 avoid going to the brain if you put it vaginally. And so we do find that cuts down. But you're going

00:58:32.120 to start orally? I typically start orally. You're going to start at 100 milligrams, 50 milligrams?

00:58:36.100 Depending on your dose of estrogen, I typically start with 100 milligrams. Some people say if you're

00:58:40.360 going higher with your estrogen, you may need to do 200 milligrams of progesterone. That data is not

00:58:44.880 very clear. And there's really two ways to give progesterone. You could do it every single day.

00:58:49.720 So typically 100 milligrams every day. And then some people in a lot of data shows if you do it

00:58:54.400 cyclically, like 200 milligrams 12 to 14 days out of the month is another way to do it. Both are fine.

00:59:00.380 When we see many patients, they feel better doing it 100 every day because it can help with sleep and

00:59:05.220 anxiety reduction. Do we believe that 100 systemically is sufficient to oppose estrogen?

00:59:12.920 I think there is not enough data there and we need more. I think if patients bleed,

00:59:18.340 it's a nice tell that maybe they need more progesterone. I think there's some interesting

00:59:22.220 that I've learned that some people say if you take it with fat or you take it with something to eat,

00:59:27.200 it absorbs better because progesterone is not absorbed very well, which is why we always had

00:59:31.000 synthetic progestins in the first place. And so we're still learning the capabilities of

00:59:36.220 micronized progesterone. But according to most menopause specialists out there,

00:59:40.020 they typically will use 100 milligrams every day or 200 milligrams 12 to 14 days of the month.

00:59:46.180 So the only thing that we do, I would say different there is while we start women at 50

00:59:49.580 to 100, we will generally take them to 200 if tolerated. And if not, keep them where they are

00:59:56.000 at 100. But we find women who are in that one third to one half group who are very positively

01:00:03.120 selected towards progesterone and they feel fantastic at 200. The most notable improvement

01:00:08.880 is sleep. So would you agree with that? Totally agree. Most women are just over the moon with how

01:00:15.360 well they sleep again. They love you forever. It is so fun to get to see. Hair gets thicker and mood

01:00:19.660 improves. So now let's talk about the other subset of women. I mean, this is a real subset.

01:00:24.280 No question. It's, I would say in our population, it's about 10 to 20% for whom, if you bring

01:00:30.780 progesterone in the room, something goes wrong. Their mood really changes. Now it can in some cases

01:00:38.500 become depressive, but more commonly what they tell me is, and I'm quoting them, this is not me saying

01:00:44.140 it, I become a raging bitch. I'm worried I might kill my husband. So for those women, we think

01:00:51.960 progesterone's a bad idea. And we then use a progesterone-coded IUD. So are you doing that or

01:01:00.820 are you using a suppository at that point? You can do either. You can say, hey, try taking this

01:01:05.740 vaginally and see if that goes away. See if you're no longer feeling anger or bloated or have irritability.

01:01:12.940 And so vaginally can be an option. We love progesterone-coded IUDs. They're great in perimenopause.

01:01:18.700 Why? Because people think that you just lightly dance into menopause. It is like bloody murder

01:01:25.200 hell scene. It can be terrible. You can bleed the whole month. You can bleed heavy. You can bleed

01:01:30.640 when you're least expecting it. So the IUD is very nice because it will stop bleeding. And so you throw

01:01:35.860 an estrogen patch on and some testosterone, and that's a really great perimenopause plan.

01:01:40.640 Now you can still take-

01:01:41.280 And you get birth control.

01:01:42.060 And you get birth control, which is very important. You can add micronized progesterone to the patient who

01:01:46.740 gets good sleep, even if they have an IUD. That doesn't add danger. We love that.

01:01:50.700 So we love IUDs for this population. There's another synthetic progestins, which you can use

01:01:55.580 as well. I've seen people do things like SLIND, which is a birth control, a progestin-only birth

01:02:00.320 control pill, add a patch and testosterone to that as well. Now, again, synthetic progestins sometimes can

01:02:06.220 have mood side effects as well. So they're not completely benign for all people. There's another,

01:02:10.740 I don't know if you've used this at all in your practice, it's called DUAVE. Have you heard of this?

01:02:14.640 Yes.

01:02:15.340 It's an oral estrogen, but it also has what's called basodoxyphine, which protects the uterus,

01:02:21.100 but is not a progesterone-based medicine. I wish they were separate. I wish we could just give

01:02:25.220 basodoxyphine alone, any pharmaceutical reps, so that you don't have to use oral estrogen if you

01:02:30.000 don't have to. Oral estrogen is not evil. I'm a sex doctor, and we know that transdermal is a little

01:02:35.420 better for sexual function. So that's, again, why I'm a big fan of transdermal products as well.

01:02:39.560 But that's kind of another option. People get hysterectomies for lots of reasons. We've had

01:02:44.960 patients do that who really don't tolerate progesterone, and then you can just use estrogen

01:02:48.340 only.

01:02:49.680 Are you referring women who are on what potentially might be a low dose of progesterone to their GYN

01:02:58.160 for endometrial ultrasounds on some regular interval just to look for hyperplasia or anything like that?

01:03:03.900 We really don't like to look for things. The nice thing about endometrial cancer,

01:03:08.640 from what I understand, again, I'm putting my urology hat on. I am not a gynecologist.

01:03:12.400 It bleeds. Now, if you bleed, then if you bleed and you just started a new hormone therapy,

01:03:17.640 it's probably okay. Now, for me, I like to know if there's any structural things going on. Do you

01:03:21.820 have a polyp? Do you have a fibroid? Is your lining super thick? If you're in perimenopause,

01:03:26.400 you still should be bleeding. So it's that challenge. I don't go looking for things that aren't

01:03:31.160 bleeding because I don't necessarily want to find things. So no, at this point, there's not

01:03:35.700 necessarily a reason for routine surveillance because if your lining is, say, six millimeters

01:03:41.400 and you're not bleeding, are you really going to put that woman through a biopsy and through

01:03:45.500 a hysteroscopy? And those have significant pain and problems that go with that as well.

01:03:51.080 Okay. Anything else you want to say about progesterone? Do you start it concomitantly

01:03:56.020 with the estrogen? Do you like to start one before the other?

01:03:58.520 I like to start one before the other in general because I like people to know what's doing what.

01:04:03.800 I agree.

01:04:04.460 When someone comes to see who says, give it all to me, it's always a disaster. Every time. One time,

01:04:09.360 it worked well for me, but it's pretty much a disaster. So I like to stack it. And again,

01:04:14.140 you're not going to cause endometrial cancer in three months of using just estrogen. I mean,

01:04:18.580 you're talking something that takes years and years and years to develop. And even that data is not

01:04:22.640 that clear cut. So I'm not worried about me causing a uterine cancer. Now, often, we'll start with

01:04:28.040 the estrogen. Sometimes you'll start with progesterone if sleep is the major issue,

01:04:32.100 but I find the vasomotor symptoms, it's such a big deal to get rid of those. So I do like often

01:04:36.880 starting with estrogen and then slowly adding in the other ones.

01:04:40.860 I'm really happy to hear. We're following your playbook already. So yes, we almost always start

01:04:45.920 with estradiol and we muck around for a while till we get it right. That's why I saved it for last,

01:04:52.260 by the way, because it's the hardest, in my opinion, in my experience to get right.

01:04:55.920 Then we fiddle with progesterone and then testosterone if they're not already on it.

01:05:01.440 But to your point, some women are coming into perimenopause already on testosterone.

01:05:05.880 Okay, let's talk about estradiol. There are two other estrogens. Estradiol is E2,

01:05:12.580 but there's estrone, E1, and there's estriol, E3. Now, the FDA only has a battery of approved

01:05:21.220 products around the second estrogen, which is the dominant estrogen. There's no FDA-approved

01:05:27.640 product for estrone and there's no FDA-approved product for estriol, but there are plenty of

01:05:34.280 compounded opportunities around that. In fact, the most common of them is referred to as bi-est,

01:05:40.200 bi-estrogen, which is an 80-20 mix of estriol and estradiol. What is your take on why that product

01:05:49.000 exists? Do you view that as a reaction to the WHI? I mean, how do you think about it?

01:05:54.920 You said it right there. I think that what happened is the Women's Health Initiative happened

01:05:59.560 and hormone therapy all went into the underground.

01:06:01.680 Went to the alley.

01:06:02.500 It went to the alley.

01:06:03.220 Yeah.

01:06:03.680 And I think one of the ways that these back alley doctors did it was saying, oh,

01:06:08.500 we're using the safer version. We're using this compound and we're going to make it 80-20

01:06:13.540 and we're going to use the more safer option. By the way, I haven't seen that data and there is no

01:06:18.720 data on bi-est in large trials that's going to really tell me what it does and we're going to just

01:06:23.540 use this. And that's what got people through for a while. And I don't actually blame those people

01:06:28.540 if they had no alternative. If I were in the middle of the desert and I had the options and I

01:06:34.220 was having horrible symptoms and I had the options of nothing or a bi-est cream, I'd probably slather

01:06:39.140 the bi-est cream on me. Where we are now, we have lots of options. We have FDA-approved options

01:06:43.640 and they're covered by insurance most of the time. So I don't prescribe it because I haven't

01:06:48.400 needed to. Now, if I have a patient who comes into me and they're feeling great and they have no

01:06:52.940 problems, do I have to change them? Well, I'll say, well, do you want to save some money? Like we could

01:06:57.100 change you to a different formulation. That's an option. Sometimes I'll even check if, say,

01:07:02.300 they're having symptoms. We'll check their levels. And I don't know if you find this, but their

01:07:06.500 estradiol level is essentially zero. It's less than five. And I'm saying, listen,

01:07:11.120 I think you're just using fancy lotion. I think you're paying a lot of money to put nice lotion

01:07:15.860 on you. And I don't know that it's protecting your bones. And if we're using this to protect

01:07:20.560 your bones or to stop your hot flashes or to help with your sexual health, maybe we use the

01:07:25.260 formulations that are a little bit better studied and that I know are absorbing in your body because I

01:07:30.800 can prove it. And what's your take on that? We don't use it at all. I have used it

01:07:35.780 occasionally in the past, probably about 10 years ago, largely in women who were terrified of HRT.

01:07:44.440 And to your point, it was viewed as, look, if you buy the argument, and this is a biochemical

01:07:53.040 argument, there's no human data that demonstrate what I'm about to assert. And again, I say this

01:07:58.240 because one can look at a whole bunch of biochemical charts and tables and talk themselves into anything

01:08:03.520 being true. But there are biochemical arguments to be made that estrone, and in particular,

01:08:09.480 one of the metabolites of estrone, and I think it's 4-hydroxyestrone, is the estrogen that is

01:08:16.960 driving breast cancer. So in an estrogen-sensitive breast cancer, given that you have so many estrogens,

01:08:23.940 is it more likely that one is responsible than another? And so the answer is, oh, you know,

01:08:29.020 some of the data suggests it's 4-hydroxyestrone. Well, estriol has no biochemical path to even get

01:08:37.260 there. In other words, there are no series of enzymes that can convert estriol into 4-hydroxyestrone.

01:08:44.200 And of course, there are pathways that will turn estriol weakly into estradiol. So maybe you get a

01:08:52.300 little bit more. So this is a long-winded way of saying no reason at all from an evidence perspective

01:08:57.460 to use it. We don't use it, have not used it in a decade, but that was my half-baked argument in

01:09:05.000 certain situations. And in fact, I did use it once in a woman who had breast cancer, was adamant that

01:09:11.720 she needed hormones. Symptomatically, she really seemed to, wanted it very badly, and I felt that

01:09:17.940 this was a reasonable compromise. For what it's worth, she got insanely better on the biest. How

01:09:23.140 much of that was from the estriol? How much of that was from the estradiol? I have no idea.

01:09:27.660 When I teach this, and I do a lot of teaching of physicians holding their hands saying, you can do

01:09:32.760 this, you can write these prescriptions. And one of the things that I just keep coming back to is the

01:09:37.480 sentence, what are you afraid of? And I love that because when someone says, well, can I do it in this

01:09:43.060 patient? Well, what are you afraid of? Can I use this product? What are you afraid of?

01:09:48.100 And it forces, I think in menopause medicine, the reason we're all struggling is we're not yet at

01:09:53.640 an algorithm or a playbook, as you say, that it's a one-size-fits-all. What's so sexy about this field

01:10:00.060 is we actually have to use our brains. We have to use our brains. We have to talk to people. We have

01:10:05.060 to get to know what's bothering them. And we have to do the right tools for them, which may be different

01:10:10.480 in each person. Because you have to also understand what your patient's afraid of. Because that is the only

01:10:15.560 thing that matters. We take risks all the time. I took a risk taking a car to get here. We take

01:10:21.400 risks. If you ever drink alcohol, you are taking a risk. We all take these calculated risks and we

01:10:26.860 all have different calculations. And so I love to push people of, well, if you were to use this,

01:10:32.820 so patient comes in unbiased, is that safe? Well, what are you afraid of? Am I afraid I'm going to

01:10:37.980 hurt this patient? I don't think I'm going to hurt them necessarily, but I don't know what's in

01:10:42.140 that compound. I don't know if the top of the bottle is the same as the bottom of the bottle.

01:10:45.900 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

01:10:49.720 be. But I do have studies on FDA-approved estradiol. And then it becomes, what am I

01:10:54.400 afraid of with the patients? Well, what are you afraid of about the estradiol? Are you afraid of

01:10:57.620 cancer? Because you know that in the Women's Health Initiative, people who used estrogen had a

01:11:02.020 decreased risk of getting and dying from breast cancer. Our patients don't know this.

01:11:05.900 Yeah. And you mentioned this earlier. I think this is one of the biggest

01:11:09.480 limitations of how I talk about this thing, Medicine 2.0, which is very few people are

01:11:16.380 conditioned to ask the question, what is the risk of not acting? We have a reasonable idea of what is

01:11:22.300 the risk of doing X? What is the risk of doing Y? Although in this particular example, we seem to

01:11:26.360 get that patently wrong. But what's the risk of not doing something is very significant. So let's talk

01:11:33.120 about all of the different ways in which a woman can get estradiol through an approved, tested,

01:11:43.580 chemically sound means. A little bit of nomenclature here. There is systemic estrogen. So when we're

01:11:50.980 talking about hormone therapy, whether you call it hormone replacement therapy, the new way we talk

01:11:55.960 about it is menopause hormone therapy. Or if you want to just say hormone therapy is totally fine.

01:12:00.660 We're talking about hormones for your whole body. Estrogen for your hot flashes, for your bone

01:12:05.820 protection, for your skin, hair, and nails. That's estrogen. That's systemic estrogen.

01:12:11.480 But there's this whole other topic, which I hope we talk about later because it's my favorite one,

01:12:15.560 which is local vaginal hormones, which are to treat the genital and urinary symptoms of menopause.

01:12:21.960 And those are pretty much safe. No, I'm going to say it. They are safe for every human on earth,

01:12:27.180 including your 99-year-old mother-in-law in the nursing home who potentially could die of a

01:12:32.020 urinary tract infection. So this is kind of the two separate areas. And I think the question you're

01:12:36.300 asking me is let's talk about systemic estrogen. Let's start with systemic. Let's come back to that

01:12:42.620 as we talk about genitourinary syndrome. Because I got a lot to say about that one. So systemic

01:12:47.800 estrogen has a toolbox. We have patches. We have gels. We have rings, which go vaginally. We have oral

01:12:56.460 estradiol. Those are the big ones. There are injections. That's kind of an old school way that

01:13:01.480 I use sometimes. Injections of estradiol valerate or cipionate. And so each one has pros and cons.

01:13:08.040 And it's nice to have the toolbox because not every product works for every patient. And the key is,

01:13:13.940 is getting it right for that patient because you need something that they're going to do and that

01:13:18.660 they're going to do it for a long time. Because these are not things that you just do for a weekend.

01:13:23.200 Let's start with the oral. So we have an oral formulated estrogen. We don't use it that much.

01:13:30.500 I'm trying to think, used to use it a bit more than we did now. Honestly, sometimes I would use it

01:13:36.660 for women who we were struggling to get the dose right on something else. And I just needed something

01:13:42.620 to get them through the weekend. And it was like, okay, I want you to just take a milligram of this

01:13:47.880 estradiol tablet tonight while we readjust your cream or your patch or whatever. When are you using

01:13:53.880 oral estradiol?

01:13:55.040 I don't use it much. But that's not to say that it isn't useful. I think it is actually very useful.

01:14:00.380 And I think it's underused. For example, people are used to taking birth control pills. They're used

01:14:04.700 to taking pills. They like pills. Doing for a healthy person with no major risk factors of cardiovascular

01:14:11.080 issues, taking an oral estrogen really is not going to increase your risk of blood clots or heart

01:14:15.260 attacks or anything like that at any significant worrisome level.

01:14:18.780 It's no more increase in risk of blood clot than a birth control pill.

01:14:21.600 Less. It's less.

01:14:22.360 Yeah. So given the ubiquity with which women are on birth control pills-

01:14:25.940 It shouldn't scare you.

01:14:26.800 We tend to blow this out of proportion. Yeah. So what is your patient selection criteria on that?

01:14:30.520 In other words, who are the women that you would say, I don't want you on oral? Is this just

01:14:35.000 factor five laden? Is this women who are obese? Where do you say, ah, the risk is a little too high?

01:14:40.780 I tend to always start transdermal. And again, this is my sex doctor hat because we,

01:14:45.260 learned from this study called the KEEPS trial where they looked at oral estrogen versus

01:14:48.740 transdermal estrogen. And it's a fascinating trial, but in that trial, they found that yes,

01:14:54.700 there's a slight increase of blood clots with oral estrogen, but sexual function is better in

01:14:59.480 transdermal. And that's because of what happens to sex hormone binding globulin.

01:15:03.660 So when you take oral estrogen, we talk a lot about first pass metabolism through the liver.

01:15:08.320 It goes through the liver, the liver, lots of things go through the liver when you take medications.

01:15:12.540 And this one in particular, it can pump out more clotting proteins. So if you're at any risk of

01:15:17.620 blood clots, just like birth control pills, if you're a smoker, if you are overweight, if you

01:15:22.840 have a genetic predisposition to blood clots, we're not going to use an oral hormone product.

01:15:28.220 Now, I want to paint this because this is actually an area where I would love to see research.

01:15:33.500 I was speaking at a Harvard testosterone course with Abe Morgan Tyler and Mo Cara,

01:15:38.460 who you've had on the show, and I was speaking about women's testosterone use. And the speaker

01:15:43.540 who got up there to talk about a transgender hormone therapy talked about sublingual estrogen.

01:15:49.760 He kept referring to sublingual estrogen. And I ran to the microphone. I said,

01:15:53.580 what are you talking about? I've never heard of sublingual estrogen. There's no product.

01:15:57.340 What are you saying? And he says, oh, you just take an oral estrogen tablet and you put it under

01:16:02.280 your tongue like a tic-tac and you let it dissolve. And it doesn't go through the liver. And it works

01:16:07.500 fabulously to increasing blood levels. And I said, oh, my God, this sounds amazing.

01:16:12.220 And it doesn't drive up SHBG, presumably?

01:16:15.120 Presumably, because it doesn't go through the liver, which actually, if you think about it

01:16:18.780 logically, I love logic here because we don't have a lot of data, so we love logic.

01:16:21.960 Is it, well, if you take an estrogen ring, a high dose estrogen ring, and you put it in the vagina,

01:16:26.320 same thing. You absorb estrogen vaginally. What's the difference there,

01:16:29.980 a sublingual estradiol? So I think it's fascinating. I don't have many patients on it,

01:16:35.080 but I would love to see data look in that direction because it's cheap. Oral estrogen

01:16:38.760 is cheap. You get lots of doses. You can dose it.

01:16:41.900 Does that mean you can get away with a lower dose?

01:16:43.980 You can get away with a lower dose. Absolutely.

01:16:45.720 You must, right? Because of that first pass effect. So how do you dose it?

01:16:49.700 Again, I don't have patients on this and I haven't seen any studies on this.

01:16:53.020 Did you ask this guy?

01:16:54.160 Yeah, absolutely.

01:16:54.960 How does he dose it?

01:16:55.980 Again, transgender hormone therapy is just much higher doses. So my guess is,

01:16:59.780 one or two milligrams BID is probably what they do. If I were playing with it,

01:17:04.100 I would probably be nervous and I'd probably do 0.5 check levels and I'd do twice a day. Again,

01:17:08.300 this is not what I do in my clinic, but just as we think through, what are you afraid of?

01:17:13.600 What are you afraid of with this? It's pretty fascinating stuff.

01:17:16.940 Okay. Let's talk about the panoply of topical ways you can do this. Creams, patches.

01:17:23.760 What are the challenges of using these things? How do they limit women's activity levels? I mean,

01:17:29.640 I used to have this whole talk I would give women about what I thought was the best way to maximize

01:17:35.220 the absorption of the cream and what I wanted them to do before they put it on. And I wanted them to

01:17:40.300 have a shower and I wanted them to exfoliate their inner thigh. And I just had this whole routine that

01:17:45.000 was probably so elaborate that it decreased compliance because like...

01:17:48.560 It's not that serious.

01:17:49.440 All right. Talk to me about it.

01:17:50.660 But it is true. For men in testosterone, we often find the topicals do not... Some,

01:17:55.640 they absorb beautifully and you get these beautiful levels and they feel great. And then you do have

01:17:59.840 a population that just doesn't absorb well through the skin. And unfortunately, we don't know who those

01:18:04.000 people are. I always tell patients, here's the menu and we're going to tinker. We have to tinker to get

01:18:09.380 it right for you because you're not like anybody. And so patches, a lot of people have heard of

01:18:13.840 patches. They like patches. They make twice-weekly patches and they make once-weekly patches. I find

01:18:19.120 the twice-weekly patches are much better tolerated and my patients like them better. What's nice about

01:18:24.240 patches is you have a wide variety of doses that you can play around with. When I start patients on

01:18:29.360 hormones, I typically choose like a medium to medium-low version because if you go too high

01:18:34.840 initially, they get breast tenderness and they get really annoyed with you and then you have to

01:18:38.860 backtrack. So I always like titrate up a little bit as we need to. So patches are

01:18:43.680 nice, but for some people, they don't stick well. For some people, they don't absorb well. For some

01:18:48.840 people, they feel that they kind of drop off. If you change it twice a week, they feel like they're

01:18:52.320 getting a little lower. We also notice women who use the sauna, who are very, very athletic and

01:18:57.980 exercising like crazy. You just have an adherence, physically an adherence problem.

01:19:01.560 Yeah. And there are people who are allergic to the adhesives. We see that as well. So some people,

01:19:05.960 they love patches. Again, you have to have a menu. If you're going to a doctor and they give you

01:19:10.900 one type of hormone therapy and that's the only type, please run. They need to know the menu because

01:19:16.900 it's not a one-size-fits-all. So there's gels and there are a number of different gels. There's gels

01:19:22.640 like the brand name is DiviGel goes on your thigh. There's Estrogel, which goes on your arm. There's

01:19:27.760 EvaMist, which is a spray, sort of an aerosolized spray that goes on your arm. Gels can be really nice

01:19:34.140 because it's every day. So it's dosing every day. The challenge is sometimes they take a little bit

01:19:39.880 to dry. So if you're a busy person and you want to rub something on and you want to run out of

01:19:44.200 there, I find gels, not everybody wants to do something every day. You got to get to know the

01:19:49.160 people. What do you like to do? What's your routine? You have to get it into their routine.

01:19:53.920 And sometimes you got to work up to it. And sometimes I have patients, they'll use patches,

01:19:57.720 but when the summertime hits and it's hot and muggy, they'll switch to the ring or they'll switch to a gel.

01:20:02.820 So what's the case for not just using the ring all the time?

01:20:05.960 Oh, so I love the ring. There's two types of ring. Now this is important because your pharmacist

01:20:11.220 sometimes messes this up. So there are two FDA approved rings. Now a ring, just like a birth

01:20:16.240 control ring, you set it and forget it. You put it in the vagina. The vagina does not feel it like

01:20:20.120 a tampon. You don't feel it. And it just stays in for three months at a time.

01:20:23.880 And it's sitting right up against the cervix.

01:20:25.900 You just kind of push it in there and it just settles in and finds a place. By the way,

01:20:30.060 if you have penetrative sex, most people don't take it out. They don't feel it.

01:20:33.880 Nobody's bothered by this thing. So this ring goes in there, stays in for about three months.

01:20:38.200 Now there is a fem ring, which is a high dose ring, which means if you have a uterus,

01:20:43.140 you need progesterone to protect the uterus. And it comes in two doses, 0.05 and 0.1.

01:20:48.760 Then there's an E string, which is a two milligram localized estrogen ring.

01:20:55.060 You do not need progesterone if you have a uterus because it's just treating the genitourinary

01:20:59.700 syndrome of menopause. So it's not treating your hot flashes. It's not protecting your bones. It's

01:21:03.920 not going to help your night sweats, but it's going to prevent UTIs. It's important that you

01:21:07.780 know the difference because the pharmacist sometimes won't and he'll give you the wrong ring, which could

01:21:11.900 be catastrophic if they think they have a systemic ring, but they have a local ring.

01:21:16.300 And it's just dose is the only difference between the two.

01:21:19.220 Yeah, they look a little different.

01:21:20.420 Yeah, yeah, yeah. The reason one is systemic is...

01:21:22.660 High dose and one is a low dose.

01:21:24.700 But it's the same you change them at the same frequency?

01:21:26.400 Yeah, both three months.

01:21:27.280 Okay. I thought you changed the E string more frequently, but good to know.

01:21:29.860 Both three months. Now there's a company right now studying a product. I'm not at all affiliated,

01:21:34.320 but it is a one month ring that has both estrogen and progesterone in it, which is

01:21:38.620 very interesting. And I'm curious to see where the research goes with that. It's a one month ring.

01:21:43.080 So the issue with the ring, I love the ring. Now there are women who you show them and they're like,

01:21:47.440 no, I don't want that. There are women who've used rings for birth control. They love the idea.

01:21:51.820 I will tell you, and we've been hoping to publish on this clinically. Again,

01:21:56.840 I don't know about you, but my patients don't listen to the book. They don't read the book and

01:21:59.900 they don't follow the FDA curves. But my patients, it peters out. It literally stops working that

01:22:05.760 last month.

01:22:06.320 How long?

01:22:06.760 Everyone's a little different, but I have patients where that last month,

01:22:09.680 they are dragging. Their hot flashes come back.

01:22:11.080 So why not just swap it every two months?

01:22:12.780 It's expensive. So a lot of times insurance doesn't cover the ring. It's about $180 cash price

01:22:17.600 when you use an online pharmacy called Transition. It's expensive. Sometimes they'll slap a patch on

01:22:22.420 or a gel at the time to sort of overlap. So they'll change it early or they'll add a different

01:22:27.620 therapy or they'll stop using the ring altogether. It is perfect for like two months. And we'll check

01:22:33.220 levels. Again, there's the book answer, the Instagram answer, and the Dr. Rubin answer.

01:22:37.580 This is where checking levels is actually helpful.

01:22:39.460 I'm sure there are a couple of my patients that would actually volunteer to do this,

01:22:43.120 where we just do twice a week levels for three months while they're on a product,

01:22:48.680 while they're on a ring and just watch the curve.

01:22:51.100 It's incredible because you will see it. You'll check it. You have a 0.1 ring in and you should

01:22:55.480 expect estrogen levels of 60, 70, something like that. And you'll see an estrogen level of 13.

01:23:00.940 And you'll be like, oh my God, this is not working, right? And they'll complain of hot flashes,

01:23:05.340 night sweats, their symptoms will come back.

01:23:07.320 And so we see a lot of ring issues with dosing for that purpose. And then another problem is if

01:23:12.940 you have any kind of prolapse. So as people have babies, things can kind of prolapse. And so

01:23:17.740 the ring can fall out during bowel movements, other things like that, if there's not enough

01:23:21.720 space in there. So I had an ultra marathon runner.

01:23:24.120 That can get expensive.

01:23:25.200 It gets expensive. This is where checking levels is beautiful. Marathon runner comes to me. She loves

01:23:30.540 her ring. She's doing great. She messages me, oh my God, I feel awful. Something's not right. I don't

01:23:35.300 feel like myself again. I said, oh, where are you in your ring? Where are you in the cycle of your

01:23:39.700 ring? We talk about it. I said, let's just check a level, see what's happening. Sure. Estrogen was

01:23:43.580 undetectable. I said, okay, we need to change this ring. And she messaged me, I can't find it.

01:23:48.140 She can't find the ring. It's not there. She probably had a bowel movement. It fell out. She

01:23:52.360 didn't notice. And then her levels dropped. So it's where the detective work helps you kind of figure

01:23:57.160 out what's going on with your patient. So the ring is not perfect for everybody, but I love

01:24:00.960 the ring. If you're in perimenopause and you have an IUD, a ring, you put a little testosterone

01:24:07.460 every morning. It's really a set it and forget it. If you get vaginal estrogen, systemic estrogen,

01:24:13.140 you get your progestin from the IUD. You add a little topical testosterone.

01:24:17.400 Very low maintenance and complete solution.

01:24:19.920 Yeah. And not expensive. Like you can do it relatively inexpensively.

01:24:24.400 Two things I want to talk about on the lab front. We've talked a lot about labs.

01:24:27.480 So not sure if you share our view on this. We are really fastidious about using LC-MS

01:24:32.880 for estradiol. We do not want to use the ELISA-based assays at all. Are you pretty meticulous about

01:24:38.680 that? Or do you find that you're just happy checking any estradiol?

01:24:40.840 I typically get the sensitive estradiol level. Yeah, that's what we get for everybody. Same

01:24:44.560 with the testosterone as well.

01:24:45.840 So let's maybe make that a PSA for people, both physicians who are out there and patients.

01:24:51.120 We have seen that if you do not use the LC-MS assay, which is the very sensitive, the liquid

01:24:58.580 chromatography assays, the results can be meaningless. And I mean truly meaningless. And

01:25:05.740 the reason is that the ELISA-based assays are so susceptible to interference from other molecules.

01:25:12.880 And there are some really known obvious supplements that completely obscure the findings. So biotin,

01:25:20.080 which is in a lot of things, will render a non-LC-MS test irrelevant. But I think there

01:25:25.960 are other things that we're just not fully aware of. So it is worth splurging and paying the extra,

01:25:31.480 maybe it's $5 or $10. It would be the cash price difference on that test. But absolutely make

01:25:37.080 sure when testosterone and estradiol are being measured, if you're the physician, you actually have

01:25:42.540 to go through the hoops and make sure you're ordering the LC-MS test. And if you're a patient,

01:25:47.080 you should be asking for it.

01:25:48.740 So we're going to get a lot of hate. There's a lot of disagreements when it comes to hormone

01:25:53.260 therapy, how to properly do hormone therapy, how to check for hormone therapy. And one of the

01:25:58.020 places, and it's funny because I truly believe, and for anyone who's going to say mean things about

01:26:02.940 me on the internet from this podcast, I truly believe that actually most of us agree on like 98%

01:26:08.680 of this. Truly, we want women feeling better. Most of us believe the data that hormones,

01:26:13.180 the benefits outweigh the risk. And so I think 98% we agree. There's the 2% where there is

01:26:19.080 disagreement. And part of it is also in the, what we don't know yet, the unknown and the curiosity

01:26:24.860 and sort of things. And lab testing is one of those issues. The book says, never check labs.

01:26:31.440 If your doctor checks labs, they are really doing something wrong. You should only care about

01:26:36.140 symptoms. And then you have sort of the fringe that are doing all saliva-based testing. Every

01:26:42.140 minute check labs do all these expensive labs, which I do not agree with. Again, the Instagram

01:26:47.640 answer, the book answer, the Dr. Rubin answer of sort of there are reasons to check labs. And I do

01:26:52.420 find labs similar to you. My curiosity with labs is so fascinating. When you can capture this

01:26:58.860 perimenopausal fluctuations and show the patient the reason you feel so terrible is because your

01:27:04.600 estrogen was a thousand and now it's zero and that hurts. Now, do I need numbers to know that

01:27:09.580 that's what's happening? It actually helps patients quite a lot for them to look at this and see the

01:27:14.320 data. What is your take on that? I'm actually surprised, but you have to understand, I don't

01:27:19.540 spend any time paying attention to the buffoons in the periphery on this topic. I don't like the whole

01:27:27.520 terminology around functional medicine. I don't buy into the idea that you need to be spending an

01:27:32.980 inordinate amount of money on esoteric non-validated labs. You can go to LabCorp, you can go to Quest,

01:27:40.600 you can go like any CLIA approved lab that knows how to do an assay correctly is all you need.

01:27:48.940 Our view and what we tell patients is the symptoms are the most important things, but the numbers help

01:27:57.420 direct my thinking. This is how we manage thyroid. This is how we manage sex hormones. And to be clear,

01:28:04.960 there's a caricature of the Dunning-Kruger curve that I just find so helpful. So for the folks who

01:28:09.840 aren't familiar, on the x-axis, you have experience. And on the y-axis, you have confidence. In this sort

01:28:17.940 of character version of the representation of this curve, you initially have a huge spike,

01:28:23.520 which then falls into a valley and then a slow rise. And of course, the huge spike is referred

01:28:29.420 to as the peak of Mount Stupid, followed by the valley of despair and the slope of enlightenment.

01:28:35.900 And it's just important for people to understand that when you are on Instagram and YouTube,

01:28:41.720 disproportionately, you are seeing people at the peak of Mount Stupid, which is to say they have

01:28:46.580 very low experience, insanely high confidence. And these are the ones that are telling you that

01:28:53.100 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

01:29:05.060 1.9, you have hypothyroidism and you need to be on armor thyroid or naturethroid or whatever.

01:29:11.580 And it's sort of like, no, none of that is correct. And you just have to take care of enough patients

01:29:16.920 for enough years to get humbled enough to know that whatever you think you know with rigidity

01:29:22.620 is probably wrong.

01:29:24.260 You've seen all my gray hair that I've grown. It's true. I find, again, that humility of medicine

01:29:29.660 is I am famous and my patients love me because I spend a lot of my day saying,

01:29:35.680 we don't actually know. This is a data-free zone. Here's what I think. Here's how we're going to use

01:29:40.820 logic. Here's the tools in our toolbox. But there is that ability to really know the data so well,

01:29:46.740 to truly understand. There's a lot we need to figure out. And that's why I have a research group.

01:29:51.580 And that's why we're trying to answer these questions because we have more questions than

01:29:54.960 we have answers. But I also need to get my patients feeling as good as possible. And that is,

01:30:00.440 it's addicting to be honest. Yeah. So here's what we do. We focus

01:30:04.600 relentlessly on the symptoms and we care what the estradiol level is. We also think the FSH is a very

01:30:11.980 helpful marker. So if a woman's FSH is 78 and her estradiol is 40, I'm inclined to believe she needs

01:30:20.820 more estrogen, especially if she's saying, I think I feel a bit better. I'm just not sure. Like to me,

01:30:26.800 that says I'm going to go more. And by the way, with the labs being where they are, I'm more inclined

01:30:32.760 to push a little bit. But again, nothing tells me I've given her too much estrogen more than her

01:30:38.140 saying her breasts hurt. And that's the advantage of doing it with these short-term estrogens because

01:30:42.840 I can pull it back really quickly. So I don't know if that answers your question, but I would

01:30:47.500 consider myself an essentialist on labs, kind of a minimalist essentialist, but not an absolutist in

01:30:54.480 either direction. I love that. And I think it's such a reasonable and logical, the logic there,

01:31:00.540 it makes so much sense to me. So we're totally in line with that. And that's why, again,

01:31:04.120 it's very confusing for our patients on social media because they want the exact answer. And

01:31:10.460 you're not going to find your exact answer from one doctor on social media. Oh my gosh, you said

01:31:16.260 that I have to use an estrogen gel, but I use a patch. Should I switch to a gel? Again, it's not

01:31:20.800 that serious. There is a menu if it's working for you and you feel like you're getting what you need.

01:31:26.240 Now it's good to get educated and learn about all the different options so that you can see what's

01:31:30.660 right for you. But I think expecting that one doctor gives you all the answers is not going to

01:31:35.300 happen. Anything else you want to say about systemic therapy before we go and talk about

01:31:39.460 local therapy in the context of genitourinary symptoms of menopause?

01:31:44.260 We haven't spent a lot of time really talking about the symptoms of menopause. What are we treating?

01:31:49.080 Why do people need systemic therapy? I'm often saying that menopause has the worst PR campaign in the

01:31:54.720 history of the universe. Why? Because we think it's for old people and we think it's just hot flashes.

01:32:00.060 And we think hot flashes go away. There's actually not enough education. We can argue about E1, E2,

01:32:06.720 and E3, but the reality is doctors don't even know the symptoms of menopause. Patients don't even know

01:32:11.880 the symptoms of menopause. The person who was doing my makeup this morning, she's like,

01:32:16.160 I just feel awful. I feel like an old person. I'm not sleeping. I'm not fun anymore. I can't drink.

01:32:22.640 Joints are achy. And I said, welcome to You Need Hormone Therapy. I'm always teaching,

01:32:27.560 no matter who I'm, whether it's a cab driver, a hairstylist, I'm always teaching. But this idea

01:32:31.960 of you have hormone receptors throughout your whole body. It is a whole body experience. So yes,

01:32:37.940 there's hot flashes and night sweats. And by the way, hot flashes are not just a nuisance.

01:32:41.940 That is a neurologic, vasculogenic, probably, event. The worse your hot flashes, the worse your

01:32:48.160 risk of cardiovascular issues and things like that. Joint pain is a huge one. I never thought as a

01:32:53.120 urologist, I would treat so much joint pain. Never in a million years did I think I cared about

01:32:57.420 joint pain. And yet patients come in all the time and say, oh my God, I don't get out of bed feeling

01:33:02.120 old. I don't feel creaky. My joints recover again after I exercise. Again, empty gas tank inflammation.

01:33:09.600 I think hormones are nature's joint fluid, if you will. So almost like brake fluid. Go back to the car

01:33:16.140 analogy. We are going to milk the heck out of this and I love it.

01:33:18.640 So it's really cool. So your eyes need lubrication. Your ears need wax. Your vagina

01:33:22.760 needs lubrication. Your joints actually need lubrication. And so think of horny teenager.

01:33:28.740 You've got oils, oily skin. So hormones create these oils, vaginal lubrication,

01:33:34.160 oil for your skin. There are androgen receptors in your eyeballs, right, in these myobian glands.

01:33:40.220 So I think of hormones like fluid. So as you lose the hormones or the hormones go too high or too low,

01:33:46.760 it dries everything out. And so you get joint pain. You get frozen shoulder. You get plantar

01:33:52.360 fasciitis. And now it was recently published on by my colleague Vonda Wright, the musculoskeletal

01:33:57.820 syndrome of menopause. This idea that so many women in their 40s and 50s, everything starts to break

01:34:04.500 down. It's because the gas tank is empty and that inflammation increases. It's such a simple analogy.

01:34:10.880 So what are the symptoms? You've got musculoskeletal symptoms, sleep issues, mood issues,

01:34:16.660 bleeding changes, obviously low libido, orgasm problems, arousal problems, pain with sex increases

01:34:23.020 like crazy. I sent you a list here. What am I missing? You've got a list there.

01:34:27.440 Irritability, very common one. One that I was going to ask you about is brain fog and depression.

01:34:32.780 This is one where I think this is a very unique one because it's one that gets easily dismissed as

01:34:39.500 something unrelated. Say more about those. It's one of the most common symptoms. All women start

01:34:45.540 going to doctors in their 40s. Like doctors, I know you're listening and you get so many people

01:34:50.940 and every day you say, oh, it's probably hormonal, but you're not giving them the solution. You're just

01:34:55.640 telling them it's not cancer. So the neurologists are seeing all these patients to rule out cognitive

01:35:00.560 decline or all these other issues. But really, it's that brain fog because your brain is filled

01:35:05.840 with estrogen receptors. This is crazy research. Okay. I don't know if you've had Lisa Moscone on,

01:35:10.480 but here's this researcher from Cornell, neuroscience researcher who says, hey, I want to study

01:35:15.640 Alzheimer's. I want to do this. This is just in the last couple of years. And she goes to her lab

01:35:19.980 manager and says, okay, what's the assay for estradiol in the brain? I need to look at estradiol

01:35:24.760 receptors in the brain. And the people at Cornell was like, that doesn't exist. She's like, what do you

01:35:29.220 mean that doesn't exist? She's like, how can we not look at estrogen receptors in the brain?

01:35:32.540 So she gets Maria Shriver to give her a giant amount of money who gives her a huge amount of

01:35:37.360 money. So she now develops this assay. This is only within the last couple of years. She just

01:35:42.060 published in Nature, very early findings. What would you expect? Your body is efficient. It's not

01:35:46.820 going to do things it doesn't need to do. So the hypothesis was that as menopause gets later and

01:35:52.280 later, the estrogen receptors in your brain are going to downregulate. Why have receptors around when

01:35:57.800 there's no estrogen to feed the brain? What did she find? The exact opposite. That actually,

01:36:03.280 even up to 65, she stopped looking past 65 because she's like, there's no way that's going to matter.

01:36:08.400 They increase in receptor density the older you get and it correlates to brain fog, correlates to all

01:36:14.800 these symptoms. My reading of that was estrogen is so important in the brain that it has to upregulate

01:36:21.940 the receptors as the estrogen level goes down and down and down. To get every morsel. In other words,

01:36:27.140 it's a lot like the way the brain is treated for glucose. The body will, if you are fasting,

01:36:33.980 the muscles will within days become completely insulin resistant. It's their way of saying every

01:36:41.460 molecule of glucose that that liver spits out better not go into the muscle. It better go to the brain.

01:36:47.680 And so you look like you have diabetes in an effort to save glucose for the brain. And I think that's

01:36:52.900 what's happening with estrogen. And could you argue that weight gain in menopause is evolutionary so

01:36:58.520 that you make more estrone or whatever, right? That goes to the brain because it wants every morsel that

01:37:04.080 it can get. So this idea of hormones matter for the brain deeply. This is very important. So it's

01:37:10.180 fascinating research, but you're going to see a lot of, again, think of a receptor. As perimenopause

01:37:16.220 is happening, the receptors are full. Now they're empty. Then they're full. Now they're empty. Now

01:37:20.320 they're half full. Now they're empty. This is why we see ADHD pop up in perimenopause. All these women

01:37:24.980 are saying, I have now new diagnosed ADHD. It's real. Why? Because your brain is having a panic attack

01:37:30.900 because it's just trying to figure out some stability here, which is why actually in empty gas

01:37:37.200 tanks, so in menopause, when you are totally empty, the brain fog gets better.

01:37:40.880 The volatility of hormone gets less, yeah. But if we just, all I'm saying is just add

01:37:44.780 some estrogen to just keep the receptors happy. The other one that we didn't talk about was

01:37:50.180 the urinary symptoms. So both urinary incontinence and then the higher prevalence of UTIs. You've

01:37:56.760 alluded to it a little bit, but just maybe finish the swing on that. Okay. So this is my favorite

01:38:01.000 topic in the history of topics because we used to call this problem, initially it was called senile

01:38:07.340 vagina. That was the initial, yes, there was papers written on the senile vagina.

01:38:12.180 I don't even understand what that means.

01:38:14.200 An old vagina, I suppose, but then it got changed to vulvovaginal atrophy or atrophic

01:38:19.140 vaginitis. That was the terminology that was used up until 24. Before that, it was senile vagina.

01:38:24.020 I totally missed that.

01:38:25.100 Check the history books. Very fascinating. So vulvovaginal atrophy was sort of the common

01:38:29.900 name of this of, okay, as you get older, the vagina atrophies, it shrivels up, it shrinks up.

01:38:35.840 Again, if a penis shriveled up at age 52, we'd probably have a vaccine sponsored by Pfizer.

01:38:40.920 This is, they created Viagra, they would create this vaccine.

01:38:44.940 I love that analogy. So you're saying if by the time a man became 50, his penis became a

01:38:50.800 shriveled up useless organ, you're saying that the medical system would have probably done

01:38:55.140 something about this?

01:38:56.160 What do you think, right? Tell me what you think.

01:38:58.600 You might be onto something, Rachel.

01:39:01.020 This is the thing. We just call it vulvovaginal atrophy. And we say, well,

01:39:04.500 if you have pain with sex or a little vaginal dryness, here's some moisturizers, here's

01:39:09.420 some lubricants, here you go. If you're really bothered, really bothered, you got to be really

01:39:13.820 bothered, then there's this thing called vaginal estrogen that we could give you.

01:39:17.760 Now, here's the crazy part of this. It's not just a little vaginal dryness. The vagina and

01:39:23.860 the bladder need hormones. Babies don't have hormones. And that's why you see it's red.

01:39:29.440 It's irritated. There are these small little labia minora. Diaper cream was invented because

01:39:34.340 it looks so painful. They pee their diapers all the time. The genitals morph and change

01:39:39.480 with hormones. Puberty happens and you have a change of the genital and urinary system.

01:39:44.440 What happens is as you lose hormones, it goes in reverse. It changes the microbiome. The hormones

01:39:50.860 keep the tissue acidic. It grows the healthy lactobacilli. The vagina is supposed to be acidic.

01:39:55.820 It's supposed to be able to fight infection. And without proper hormones, you lose that

01:39:59.920 ability to fight infection. So you see urinary frequency, urinary urgency, vaginal dryness,

01:40:05.840 increase in leakage, increase in urge incontinence, and recurrent urinary tract infections, which

01:40:11.080 can and do kill people. We've known this since the 90s in the New England Journal of Medicine.

01:40:16.860 Actually, this was on estriol. You could reduce the risk of urinary tract infections by well over

01:40:21.800 50%. We have known this all along.

01:40:23.940 And that was with topical estriol. Interesting. I was not aware of that. And yet there is no FDA

01:40:29.460 approved estriol formulation, despite that fact?

01:40:32.340 Yeah, correct. I think it's available in Europe. So the name got changed in 2014.

01:40:37.380 2014, a bunch of people got in a room and they said, you know what, this vulvovaginal atrophy

01:40:41.340 thing, that's kind of a bad name because it doesn't describe what's really happening to people.

01:40:45.600 So they changed the name to genitourinary syndrome of menopause, GSM. Now there was one urologist,

01:40:51.880 my mentor was in the room, and they almost didn't put the word urinary in it. And he fought and he

01:40:56.440 yelled and he screamed, this is the power of one person to be able to change the whole world.

01:40:59.960 And they said, okay, we'll listen to you. We'll put the word urinary in it. And I'm so glad they

01:41:04.500 did because the urinary problems are the things that kill people. People are dying of urinary

01:41:09.220 tract infection. In fact, a large amount of money goes to Medicare expenditures when it comes to

01:41:14.900 urinary tract infections. And we published last year that if Medicare patients used vaginal estrogen,

01:41:21.540 which is safe for everybody, and $13 a tube, we would save Medicare between $6 and $22 billion a

01:41:28.320 year. Billion.

01:41:29.280 Just say that again, please, because I know there are people that are in the Medicare system who are

01:41:35.300 going to be interested to understand that.

01:41:36.940 When you do a low dose local vaginal estrogen or DHEA product, you can reduce your risk of

01:41:44.440 urinary tract infections by more than half. They are safe to use if you've had a history of blood

01:41:49.260 clots, breast cancer, whatever medical problem you can come at me, I can tell you that it's safe.

01:41:54.440 It will not only help with lubrication, help with pain with sex, help with urinary frequency,

01:41:59.940 urgency, leakage, but it will reduce your risk of urinary tract infections by more than half.

01:42:04.460 It's also inexpensive and covered by your insurance. If everybody in Medicare eligibility used vaginal

01:42:11.240 estrogen, we would save Medicare between $6 and $22 billion a year. And in my opinion,

01:42:17.660 that is a conservative estimate because of how many patients are getting urinary tract infections.

01:42:23.160 They're going to their doctor for cultures. They're in the ICU with sepsis. This is a huge

01:42:28.760 economic morbid and mortality problem that we are dealing with and no one cares.

01:42:35.540 I mean, again, I always try to come up with the steel man and say,

01:42:40.220 is it that they don't care or is it that they're unaware or is it that they feel that it just needs

01:42:48.300 to fall on the shoulders of somebody other than themselves?

01:42:51.500 I think we have a marketing problem. I truly believe this is a marketing problem.

01:42:56.320 Okay. Let me push back. Not because I don't agree with you, but I'm just going to put my hat on that

01:43:01.760 says the opposite. So maybe I am too attuned to this, but I feel like there is nothing more talked

01:43:09.840 about right now. I mean, look at what Halle Berry is doing. Look what Oprah is doing. Look what

01:43:15.060 Gwyneth is doing. I mean, there are so many very powerful, very influential women that are talking

01:43:22.300 about this. Is this not in the zeitgeist right now?

01:43:25.980 It's getting better, but again, they don't know how to write the prescriptions.

01:43:30.760 So you're saying there's not enough physicians talking about this?

01:43:33.520 Yeah.

01:43:33.720 If it really comes down to prescriptions.

01:43:35.160 Yeah. If you can't get them, it's not over the counter. If you can't get the prescription or if

01:43:38.380 you don't go to your doctor saying that you need it. We had an Instagram reel just yesterday that

01:43:42.840 the patient said, my friend went to her doctor, said she was having pain with sex, asked for vaginal

01:43:47.840 estrogen, and her gynecologist said, and I quote, you need to think of other ways to change your

01:43:53.800 relationship from now on. It's not in the cards for you.

01:43:56.320 What does that mean?

01:43:56.920 Meaning you can't have sex anymore?

01:43:58.160 You can't have sex anymore. And the fact is, it's not about sex. It's about urinary tract infections.

01:44:02.220 Wait a minute. Wait a minute. This is impossible for me to fathom. A woman went to her

01:44:06.220 gynecologist and said, I'm having pain with intercourse.

01:44:09.280 Yeah.

01:44:09.560 Any idea how old this woman is?

01:44:10.800 In her 60s.

01:44:11.520 Okay. And you think this gynecologist doesn't know about estrogen?

01:44:16.420 Honestly, I don't know anymore. It's incredible. So we could argue Viagra. 1998, Viagra comes out.

01:44:23.180 Viagra changed the world. Billions of dollars. What is Viagra? It is a PD5 inhibitor. It relaxes

01:44:28.620 smooth muscles of the penis, increased blood flow, gives you a rigid erection. So it helps with arousal

01:44:33.500 for men. Okay. If you take it microdose, low doses, it can also help with BPH or urinary problems.

01:44:40.260 We love Viagra. We love Cialis. Wish it was in the water. We should study it in women.

01:44:44.740 I did in medical school.

01:44:46.140 Oh, I'm going to talk about that. But I will argue we've had Viagra for women long before

01:44:51.980 we've had Viagra for men. And we've known about it since the 1970s. And Viagra for women is vaginal

01:44:57.900 hormones. What do vaginal hormones do? They relax the tissue. They increase arousal. They increase

01:45:02.980 lubrication. They increase orgasm. They help with urinary symptoms. So they do everything Viagra does.

01:45:08.240 And they prevent urinary tract infections. Viagra doesn't do that. So you're talking

01:45:12.680 about better than Viagra. It's inexpensive. Now, it didn't used to be. So when I got out

01:45:17.380 of my training, a tube of estrase was $500. Now, because of people like Mark Cuban and

01:45:22.160 GoodRx, and I've talked to Mark Cuban on my DMs and Twitter, and he knows more about vaginal

01:45:26.220 estrogen than 90% of doctors. But this idea of it's not expensive. A tube of estrogen is $13.

01:45:32.480 And you're saying that the reason that this price has come down is, I know Mark is a very

01:45:36.440 hard liner against the PBMs. Did Mark basically take a sledgehammer to that?

01:45:40.860 Yeah. Yeah. They changed the game.

01:45:42.240 Awesome.

01:45:42.780 And so it's incredible. Oh my gosh. It's incredible. And he understands this. He literally

01:45:46.360 understands the nuances of why vaginal estrogen is so important. I can't get doctors to do that.

01:45:50.540 I think he's incredible. So we have a marketing problem. We have a product that is better than

01:45:55.180 Viagra for women. It's been around longer than Viagra. It's inexpensive. What are we missing?

01:46:00.720 It's marketing. We're not telling the patients. We're not telling the doctors. And we have a box

01:46:05.600 labeling that says this product causes stroke, heart attacks, blood clots, probable dementia,

01:46:11.820 breast cancer, and needs to be taken with progesterone. Not one of those statements is

01:46:16.640 true. Not one. Okay. So we went to the FDA and says, you got to remove the box. You're killing people.

01:46:21.980 And the FDA said, nah, we're going to leave the box on. This is a nightmare. Can I just tell a very

01:46:27.440 personal story? I promise it won't take long. My mother just died in November. We spent six months

01:46:32.180 in the ICU in Houston, Texas. Six months, my mother. Nobody should be in an ICU for six months.

01:46:37.120 It was absolutely gut-wrenching, horrible time for me. My mother had been on vaginal estrogen because

01:46:41.840 I want her to prevent UTIs for many, many years. You know, she's a 70-year-old woman, many years.

01:46:47.440 So she gets into the hospital, has a transplant, has a catheter, and isn't doing well. Is on ECMO and

01:46:53.060 very sick for a very long time. And I said to the doctors, I said, I know this isn't the most

01:46:57.440 important thing in the world, but I'd like to restart her vaginal hormones because having a

01:47:01.780 catheter, being in an ICU, and being immunocompromised, my mother's risks of a

01:47:06.300 urinary tract infection are incredibly high, and a urinary tract infection is going to kill this

01:47:10.440 woman. So I would like to restart her vaginal estrogen. And because menopause medicine is a

01:47:15.500 tiny little field in a tiny little corner, they looked at me like I was an insane person.

01:47:20.940 I said, what do you mean? Your mother's very sick right now. I said, I know my mother's

01:47:24.340 very sick right now. And this is one thing I can control. I sort of did a, do you know

01:47:27.780 who I am? Because I'm on the guidelines committee for GSM for the American Urologic Association.

01:47:33.340 So for the transplant team, I had to write up a whole S-bar of like, here's why it's important.

01:47:37.280 Here's the research. Here's all the literature. Here's the citations. And they said, but it'll

01:47:40.660 increase her risk of blood clots. I said, no, it won't. Vaginal hormones don't increase your

01:47:45.280 risk of blood clots. It's like a hydrocortisone cream compared to a solumedrol. Those are very

01:47:49.940 different things. So then they went to the ICU team. They said, no, we can't give this

01:47:53.480 to her to increase her risk of blood clots. Had to convince them. Then the pharmacy, they

01:47:57.720 finally got them to write the prescription. I had to teach them how to write the prescription.

01:48:01.640 Pharmacy wouldn't dispense it. Why? It increases the risk of blood clots. It says so right on

01:48:06.080 the box. So I had to call and yell, right? I'm trying to run a practice in Washington,

01:48:10.600 D.C. My brother and father are trying to advocate with me because they know, they also follow

01:48:15.120 me on social media. They know this is important. Finally, the pharmacy dispenses the tube of

01:48:19.560 estrase. There's no applicator. The nurses don't know how to give it. I had to show them

01:48:24.080 and teach them how to give my mother, who was on ECMO and ultimately passed, not from a

01:48:29.340 UTI, thank goodness, but had to show them how to dispense. I had to do all this being one

01:48:34.660 of the leading educators on this topic. What does everybody else do? And guess what? The

01:48:40.440 teams changed every week. We had to do this every week and to teach them why this was important

01:48:46.540 and how to do this. Vaginal hormones should not be gynecology. It should not be a small

01:48:53.140 subset of menopause medicine. We could save Medicare between $6 and $22 billion a year

01:48:59.140 if people understood this, if the box labeling weren't on there. I mean, it is so personal

01:49:05.000 at this point, and yet it is horrible.

01:49:08.620 Well, I'm very sorry to hear that story, both at the personal level, but also at the meta

01:49:12.520 level of what is implied. I want to clarify one thing, Rachel. If a woman is on a high

01:49:19.100 enough systemic dose of estradiol, does she also need later in life local estrogen?

01:49:27.580 Maybe even not later in life. So we find that systemic hormones are not often enough to help

01:49:33.380 with the genital and urinary symptoms. Most doctors don't know this. Again, what are you

01:49:37.700 afraid of? You're not adding any systemic risk. It doesn't increase. If your estrogen level

01:49:42.300 is 70 on your patch and you add a vaginal estrogen, her estrogen level is going to stay

01:49:47.220 70. You're not going to get that systemic absorption, but you are going to reduce your

01:49:51.160 UTI rate significantly.

01:49:53.500 Has that study been done? That would be a super interesting study. Think of how easy it would

01:49:57.580 be to do a study where you took a group of women that were all at systemic target of estradiol

01:50:03.140 and you randomized them to a placebo vaginal cream versus an estradiol vaginal cream. You could

01:50:09.080 follow these women for a year if they were in a susceptible enough population and you

01:50:13.280 would get a very clear answer as to whether or not you're getting additional UTI protection.

01:50:17.940 And if the answer to that is yes, just imagine the implications there. At that point, it becomes

01:50:22.260 malpractice.

01:50:23.560 We just published a study that DHEA does the same thing. It reduces the risk of UTIs by more

01:50:27.720 than half.

01:50:28.460 Why is DHEA doing it?

01:50:30.080 So they've looked at a lot of oral, you probably know this data better than I do. Oral DHEA,

01:50:34.040 the data's all over the place because your adrenals are pumping out a lot of DHEA.

01:50:39.380 But when you put DHEA vaginally, the idea is that your vaginal enzymes convert it into both

01:50:46.220 estrogen and androgens. And what's so fascinating is we know that the vagina, the vulvar vestibule,

01:50:51.780 the clitoris, the bladder have androgen receptors. So us using just estrogen in this tissue may be

01:50:57.700 missing the whole point. We do have patients that benefit from having an androgen in the tissue as

01:51:03.100 well. And the only FDA approved product we have is Intrarosa, which is vaginal DHEA. Now it's often

01:51:08.020 hard to get for patients. If I could get it for everybody, I would. It's fabulous because the

01:51:12.740 tissue needs dandrogens. The data is very good.

01:51:15.780 We've just started using it, so I don't have a lot of experience with it.

01:51:18.940 So there is some data, not a lot, but there's data that shows someone with urgency,

01:51:22.800 give them vaginal estrogen, switch them to DHEA. It'll help those people who still have urgency.

01:51:27.540 Do you think it gives you the same UTI protection?

01:51:29.380 We published on this. So we just published in the Menopause Journal that it shows the same

01:51:33.400 decreased risk of UTIs by more than half. So that was a very proud publication that we just put out.

01:51:38.060 We use it frequently. What's nice about the product, it's a nightly product. It's DHEA in palm oil,

01:51:43.360 so it's very moisturizing, very lubricating. And my mentor, Erwin Goldstein, published that actually

01:51:48.020 it also helps the tissue called the vulvar vestibule. Do you know what the vulvar vestibule is?

01:51:53.540 Well, I know what the vulva is, and I know what a vestibule is. I don't think I know what the

01:51:59.680 vulvar vestibule is.

01:52:01.040 So I'm obsessed with homologues. Homologues are sort of this idea of, I'll give you an example,

01:52:06.240 the penis and the clitoris are exactly the same thing.

01:52:08.620 Yes, yes, sorry.

01:52:09.460 No, no, no, that's okay. They're homologues of each other, right? The head of the penis and the head of

01:52:13.380 the clitoris, homologues. So it's what part of the body in one is the same in the other.

01:52:17.340 So the homologues of the scrotal skin is the labia majora. Okay, you're with me? The prepuce or the

01:52:24.440 hood, the clitoris and the penis both have a prepuce or a hood to it. So there's a line that

01:52:28.860 goes down a penis that goes down the penis and the scrotum. Do you remember what that's called?

01:52:33.500 Median, raff.

01:52:34.300 Raff.

01:52:34.920 Yeah, you got it, raffae.

01:52:36.360 Yeah.

01:52:36.740 Okay, so the median raffae is the line that goes down the penis and the scrotum,

01:52:40.740 straight line right in the middle. What's the homologues in the vulva? I just learned this.

01:52:45.640 Well, it must be the vestibule.

01:52:46.920 No.

01:52:47.520 No, I don't know.

01:52:48.340 Close. Labia minora.

01:52:49.640 Okay.

01:52:50.220 So it's skin. It's ectoderm. So it is skin and we're split open. So if you take the median raffae

01:52:57.140 and you split it, that's your labia minora, which very hormone sensitive. I'm not on TikTok,

01:53:02.860 but I am trending on TikTok because I talk about the labia minora shrinking and disappearing in

01:53:07.360 menopause and the internet has broken because of it. So the labia minora is very hormone sensitive

01:53:12.480 tissue that we do not study and we know almost nothing about, but it resorbs in menopause.

01:53:17.540 Inside the labia minora. So if we cut into the median raffae in a man, and we do this when

01:53:22.520 we put in penile implants or we do urethral surgeries, we get to the male urethra. So Peter,

01:53:28.500 your outside of your cheek is skin. The inside of your cheek is different tissue. One's more

01:53:34.580 sensitive, one's thicker. So the skin of the median raffae is very different than the skin of the tube of

01:53:41.660 your urethra. You agree? So if you split open the labia minora, you get to the urethra and that is

01:53:49.580 the vulvar vestibule. So the tissue that surrounds the urethra in a woman that goes all the way around,

01:53:55.820 and I will show you nerdy anatomical diagrams when we're done here because I need you to know this,

01:54:00.140 that is the female urethra. It's called the vulvar vestibule. It is made up of endoderm. So we think of

01:54:06.280 the cervix as a transition point. But the most important transition point that affects sexual

01:54:10.900 health in a woman is when you go from ectoderm of the labia minora to endoderm of the vulvar

01:54:16.800 vestibule, and then past the hymen is mesoderm. It's fascinating anatomy. Why is this important?

01:54:23.000 It's super compressed.

01:54:23.640 It's so important because if you push with a Q-tip on the labia minora, they'll have no pain. If you push

01:54:29.320 them on their vulvar vestibule, they'll say, that's my UTI. That's my interstitial cystitis. That's

01:54:34.560 the pain that I have with sex. It is rich in hormone receptors. This is why 50% of women go

01:54:39.960 off their endocrine therapy for breast cancer because they have urinary symptoms, pelvic pain

01:54:45.620 symptoms, and it is all sourced in a body part that no one taught you in medical school. And I

01:54:50.960 did that on purpose because I knew you wouldn't know it because no one is taught how to examine it.

01:54:55.520 They put a speculum in and they bypass it completely and they are missing the problem.

01:55:00.560 Back to the DHEA, this tissue has estrogen and testosterone receptors in it. So sometimes

01:55:07.560 estrogen is not enough to help this vulvar vestibule tissue. And so DHEA, there's some data.

01:55:13.820 There's one paper to suggest that DHEA is enough. And this is the one time that I will compound a

01:55:19.400 product for a woman. Otherwise, I use FDA-approved products in my practice. And I compound basically

01:55:24.600 the amount of estrogen and estrogen vaginal topical cream, the 0.01%. And I will use a topical

01:55:30.680 testosterone 0.1%, different than the 1% we talked about for libido, but a 0.1%, they rub it topically

01:55:38.220 on this vulvar vestibule. You cure pain with sex. You help these UTI symptoms. Interstitial cystitis

01:55:43.760 goes away in so many patients. It's miraculous.

01:55:46.580 Sorry, tell me again, 0.1% T and what was the percent DHEA?

01:55:50.820 0.01% estradiol. And we typically use a VersaBase or a methylcellulose base.

01:55:55.420 And no DHEA in that.

01:55:56.480 No, but I would love to see that studied.

01:55:58.700 And what's the base?

01:55:59.700 It can be usually a methylcellulose or a VersaBase. There's a base called Elage that a lot of people

01:56:04.360 are using right now. Again, I am not a compounding junkie in any way. This is a miraculous compound

01:56:10.480 that literally will, if you have a patient who's on vaginal estrogen, systemic estrogen,

01:56:15.060 systemic testosterone. I said, Peter, I still have pain with sex. It still kind of hurts.

01:56:18.720 It's always the vestibule.

01:56:20.260 This is super interesting.

01:56:21.160 Isn't it fun?

01:56:22.160 There are three other questions that I want to ask you going back to hormones post-menopause.

01:56:27.740 I'm saving the three most contentious questions for last on this topic.

01:56:32.200 Question one. Someone's posing this question to you, not me. I buy your argument that hormones

01:56:36.240 are safe, but I am now 56 years old. I finished menopause at 49. Isn't it too late?

01:56:45.060 To do anything about it?

01:56:46.740 So we have this idea in menopause medicine called the timing hypothesis.

01:56:50.460 Or the window idea, right?

01:56:51.620 The window or the timing hypothesis. So the question of the timing hypothesis is what are

01:56:55.800 you afraid of? What are we worried about? We're worried about blood clots. We don't

01:56:59.100 want to hurt people. We're worried about cancer. We're worried about blood clots. We're worried

01:57:02.380 about heart disease. But the question is, is does the hormone therapy that we use apply to the

01:57:07.960 data that we have? And I would argue it doesn't. And so there is a level of we don't know

01:57:12.780 what we don't know. But even the timing hypothesis using PremPro, which was the medicine used in the

01:57:18.340 WHI, is under question. So Susan Davis from Australia just wrote a big paper questioning

01:57:23.620 the timing hypothesis and say, actually, when you look at the data really closely, it doesn't

01:57:28.280 really hold muster. We shouldn't really be forcing people to say you cannot start hormone

01:57:33.220 therapy after 60. So I think this is where shared decision-making really comes into play

01:57:39.180 of what are we treating? Do you care about your bones? Do you care about your sexual health? Do

01:57:44.560 you care about your mental health? And do you want to see if hormone therapy helps with these things?

01:57:49.940 Now, hormone therapy is indicated for three reasons. Vasomotor symptoms, hot flashes, night

01:57:54.680 sweats, that sort of thing. Prevention of osteoporosis, which to me is a green light. So anyone should

01:57:59.920 be offered hormone therapy because who wouldn't want to prevent osteoporosis? And the thing I just

01:58:04.540 talked about a lot is the genital and urinary syndrome of menopause. So anybody of any age,

01:58:09.700 and I'm talking even perimenopause and premenopause, vaginal estrogen or DHEA is safe and really helpful

01:58:16.980 to prevent UTIs and should be used absolutely everywhere. Throughout life. Throughout life.

01:58:22.420 Okay. Now I'm going to ask another question that is the extension of that question, but I think your

01:58:28.360 logic is going to hold the same, which is the hedging strategy, which says not only use as little

01:58:34.820 as possible for as short a duration as possible, says you really need to stop this after 10 years.

01:58:40.040 So even if you were lucky enough to catch a woman through perimenopause, you got her on hormones by

01:58:46.020 the age of 49. Now that she's 69, you got to stop it, right? Definitely not. So that's really,

01:58:52.320 there is no data to suggest stopping it. In fact, stopping it, all of your bone gains go away.

01:58:57.540 They all go away quickly. By the way, that was the argument put forth to me with one of the authors

01:59:03.080 of the WHI, who is by far the most willing to concede that mistakes were made, which was, okay,

01:59:10.760 yes, I will concede that the estradiol is doing amazing things for the woman's bones, but remember,

01:59:16.760 they're going to go away when you stop the hormones as though that was a necessary thing to do.

01:59:21.000 So keep them on. Again, this idea of if it's not broke, don't fix it. By taking a woman off of

01:59:26.420 hormone therapy, you actually potentially could be disrupting any plaques that are there. You could

01:59:31.120 be causing vasospasm. Like there are all these things that could happen. We really don't want

01:59:35.060 to take women off their hormone therapy unless there is a reason to. And the only reason I honestly see

01:59:40.840 is if a woman has an active cancer that you are going to target hormones as a target for your

01:59:47.560 treatment of cancer. That's not to say the hormones cause the cancer, but we have a target sometimes

01:59:52.600 because all body parts have hormone receptors and we have used hormones as a target for our breast

01:59:58.080 cancer therapies and some other cancer therapies. Is that helpful? Does that make sense?

02:00:02.300 Yes. And it actually dovetails perfectly into my third critical situation, which is how do we manage

02:00:09.500 hormones in women who are at risk of breast cancer from a familial standpoint, who have been diagnosed

02:00:18.240 with DCIS, which is not cancer, but increases the risk of cancer. So that's kind of a subset of the

02:00:24.480 first group. And then in women who actually have breast cancer or have a history of treated breast

02:00:31.620 cancer. So I would imagine you see women that fit into all four of those buckets. How do you handle it?

02:00:38.060 So first, we take a long time at my clinic and we get to know each other and we really try to dive

02:00:42.860 into the data and say, what do we know? What do we not know? And I always tell people,

02:00:46.740 you can't take hormone therapy because Rachel Rubin tells you to take hormone therapy.

02:00:50.640 You have to do your own research, figure out what you're interested. And so I have a lot of

02:00:54.580 colleagues who are talking about this. You had Avram Blooming on your show and he has a great book

02:00:59.380 called Estrogen Matters. He's an oncologist who's questioning a lot of this research.

02:01:04.000 We have amazing colleagues of mine like Corinne Mann, who is a gynecologist who had breast cancer

02:01:08.280 as a young person in her 20s and now takes hormone therapy and talks a lot about hormone therapy

02:01:13.260 and teaches courses on hormone therapy and breast cancer. So I am always learning. So I don't like

02:01:18.620 fear. I don't like telling women they can't do things with their body. I like understanding,

02:01:23.340 well, what are we afraid of? So when it comes to the BRCA patients, if you do surgical menopause

02:01:28.820 on someone and they don't have cancer and you do not give them back hormone therapy, you are trading

02:01:33.440 one problem for another. You may give them extra life from a breast cancer perspective, but you are

02:01:38.100 shortening their life from a bone health and a cardiovascular disease perspective. That is very

02:01:42.220 clear. So the other problem is the DCIS. If you are not going to give someone endocrine therapy of any

02:01:48.000 kind and they're done, they have surgery, they're done, there is no reason why they can't take hormone

02:01:52.440 therapy. And then when it comes to active breast cancer, there is a lot of emerging questioning in

02:01:59.540 this patient population. And again, the question is, if you're allowed to get pregnant, are you allowed to

02:02:04.900 take hormone therapy? And that's really the pushback that we give some people. And I think there's a lot

02:02:09.580 of data that we need here, but we need to be asking these questions. I'm a urologist. When I came out of

02:02:15.260 my training, it was testosterone fuels prostate cancer. Now, 10 years later, it's, you have prostate

02:02:22.280 cancer? Sure, we can give you testosterone. No problem. If you have metastatic disease, we target

02:02:27.160 testosterone. So we're going to use castration level androgen blockers. But that doesn't mean if you have

02:02:33.460 localized disease that you can't have testosterone therapy. So we think of testosterone and prostate

02:02:39.300 cancer as a saturation model concept. And I actually think we need to be using that model

02:02:44.240 potentially when it comes to breast cancer and have more logic and understanding and less fear.

02:02:49.900 It's marketing. All prostate cancer is testosterone-sensitive prostate cancer, but we don't cut off

02:02:55.720 testicles for the fear that an abnormal cell will happen in a prostate. A lot of breast cancer is

02:03:01.720 estrogen-receptive breast cancer. Not all of it, right? But some of it is. That doesn't mean

02:03:06.760 estrogen causes cancer. It's insanely helpful. And of course, it echoes exactly what Ted Schaefer

02:03:12.660 said when we spoke about this after discussing the TRAVERSE trial, which was, I think, to me,

02:03:18.200 the most telling thing that Ted said was, look, if I have a man who's got a Gleason 3 plus 3,

02:03:23.560 means he has prostate cancer and we are going to follow this. And if it becomes a 3 plus 4,

02:03:29.780 we're going to actually have to take this thing out, we'd put him on TRT if he needed it. And his

02:03:34.160 argument was exactly your argument on the pregnancy side, which is the reason we would happily give him

02:03:39.920 TRT is, let's just assume he's a man replete with testosterone. Would we castrate him during that

02:03:46.280 period of time of observation? Of course not. So why would I not give him testosterone if he needs it,

02:03:52.140 even though he actually has prostate cancer?

02:03:54.060 And this is, again, where that patriarchal divide happens is we're willing to take those risks and

02:03:59.720 focus on quality of life when it comes to men's health. We castrate women with the mere thought

02:04:05.540 that they may develop an abnormal cell in their body and completely ignore their quality of life

02:04:10.660 and all of those things that go with it. And women are more than breast tissue. They are so much more

02:04:16.020 than their cancer risk. And we have to understand and actually have these reasonable conversations

02:04:21.060 with women. And what I say is your oncologist is not in charge of you. They give you advice.

02:04:26.440 It's like a pit crew. Let's go back to our car model. You have a pit crew, but you get to decide

02:04:31.600 who's on your pit crew and who fits into your pit crew. But it can't be just one doctor. You may need

02:04:37.020 someone to talk about your sexual health. You may need someone to talk about your menopause hormones.

02:04:40.840 You may need a bone doctor. You may need a heart doctor. So you need to collect your pit crew.

02:04:45.840 But with one doctor says, no, you can't do this with your body. I don't like that terminal. I don't

02:04:50.840 think it's fair anymore. And when you give women information about how their bodies work, they make

02:04:56.320 great decisions for themselves. They can look at the menu and say, listen, I'm most worried about

02:05:01.620 Alzheimer's and I've looked at the data and this is what I choose to do. Or, hey, I'm more worried about

02:05:07.220 osteoporosis. Listen, my grandma broke a bunch of ribs. She had Alzheimer's and osteoporosis and my

02:05:13.360 grandpa hugged her and she broke a bunch of ribs. That's not how I want to age. So what do I care

02:05:18.000 about? I don't want to get osteoporosis. I don't want to get dementia. And I've seen all the

02:05:22.180 literature. Hormone therapy sounds pretty good to me. And that's really the key. I think there's a lot

02:05:26.560 of people on social media, maybe negative about hormone therapy, but if you look, they are on hormone

02:05:31.660 therapy themselves. They will say they have an estrogen patch on. Because I don't pay any attention to

02:05:36.440 social media, there are people out there saying they're anti-HRT, but they- Use HRT.

02:05:42.420 What's their argument? What are they talking about?

02:05:43.920 This idea that we are overselling HRT, that not every woman needs HRT. And I'm not suggesting

02:05:48.940 every woman needs HRT, but I want every woman to be offered the menu. I want them to know what they

02:05:56.200 are. Just like I want people to know how to exercise and lift weights and eat healthy. Here's

02:06:01.400 the menu. If you choose to smoke and drink and do drugs, that is your choice. But I want you to know

02:06:06.540 that the menu exists.

02:06:08.200 What do women need to be aware of? Not every woman can come and see you.

02:06:11.420 Not every woman has access to a doctor who has the breadth of knowledge that a select few

02:06:19.800 do in this space. So A, how can women find practitioners near them? And what do they need

02:06:28.620 to be aware of? What are the exploitative practices out there that they need to be mindful of and not

02:06:35.220 get duped into either dangerous therapies or overly extractive therapies?

02:06:40.420 I think there's danger on both sides. There's danger going to the doctor for 10 minutes and

02:06:44.100 saying, oh, that's not safe. You don't want to do this. And there's dangers of going to the very

02:06:48.320 expensive pellet clinic that is going to overdose you and charge you lots and lots of money.

02:06:53.460 So I like being somewhere in the middle and getting a few opinions here. So this is where opinions can be

02:06:58.820 a bunch of people on Instagram. Don't just follow one people, follow a bunch of people.

02:07:02.780 If you like books, there's tons of books now on menopause.

02:07:05.780 What are some of your favorites?

02:07:07.040 You've got Mary Claire Haver has the most popular book called The New Menopause.

02:07:11.000 Heather Hirsch has a great book called Pick Your Menopause Type. There's been a hot and bothered,

02:07:15.520 a journalist wrote a great book on perimenopause, Jan C. Dunn. Tamsin Fidal just wrote a book about

02:07:21.260 menopause, who's also a reporter. Estrogen Matters is a great book, a really great book.

02:07:25.540 There's a lot of books now, thank goodness. There's one called The Menopause Manifesto.

02:07:29.700 There's great books on menopause. There's also podcasts now. There's great podcasts out there.

02:07:34.300 Oprah just did a special. There's documentaries on PBS now. So menopause is having a movement.

02:07:39.420 So you can't have this excuse anymore of, oh, my doctor doesn't do this. Go find a different

02:07:44.480 doctor. They're telemedicine companies.

02:07:46.360 And what's the website?

02:07:47.100 So menopause.org is the Menopause Society website. That doesn't guarantee you have someone who knows

02:07:52.240 everything. But menopause.org means somebody took a test and put some effort into saying,

02:07:56.900 I care about menopause. I'm on that website. But iswish, I-S-S-W-S-H.org is the Women's Sexual

02:08:03.080 Health Society. So people who we care about menopause and sexual health. So that's a great

02:08:07.700 place to find a provider. So those are two websites that can help you find someone. Again,

02:08:12.840 you have to advocate for yourself because no one will do that other than you. And so I think the more

02:08:19.160 you educate yourself, the more you can find the right people in your pit crew who are going to

02:08:23.900 fill that gas tank and get you to where you want to go.

02:08:26.940 Do you feel that there are too many women that are still getting their hormone therapy in the

02:08:31.960 dark alley with highly sus individuals? And if so, what would be a clue that you're in that camp?

02:08:37.740 Because there's nobody that's in that camp that knows it. I want a woman who's watching this,

02:08:41.300 who's not getting great medical care, but thinks she is to maybe get a bit of a hint as to what that

02:08:46.420 might look like. I think this is a problem. When your doctor says, no, you can't have anything,

02:08:52.260 that's suspect. If your doctor says you can only have this really expensive product that has to be

02:08:57.740 inserted into your butt four times a year and you have to pay me thousands of dollars,

02:09:01.980 that's extremely suspect. If they say you have to pay lots of money for this special compounded

02:09:07.180 product that's safer and more effective, I call red flag on that situation. If you have to give very

02:09:12.200 expensive saliva testing labs and they're making you pay a lot of money, very suspect. Again,

02:09:17.660 that doesn't mean you can't do it. If it's working for you and you're happy, you have body autonomy,

02:09:21.820 you do what you want, but know that there's red flags there. I think the pellet industry,

02:09:26.980 I have a big problem. We have an FDA approved pellet for men. It can be FDA approved. I'm not upset

02:09:32.380 with a pellet as a concept. If the pellet companies cared about women, do the studies,

02:09:38.940 go through the FDA, show me it's safe. It's a billion-dollar industry. If you believe that

02:09:43.600 it's the greatest thing in the world, show me so that I can start using it because the FDA is a

02:09:48.940 pretty good compounding pharmacy. So do the work. I have my beef with the FDA. Hello, you need to take

02:09:54.080 that box labeling off estrogen products, especially vaginal estrogen. But if the pellet companies

02:09:59.160 deeply cared about women, which they say they do, do the work. Everyone takes advantage of women.

02:10:04.100 All the supplement companies, they take advantage by promising these things to women,

02:10:09.260 but they don't do the work of science. So that's what I ask is just do the work.

02:10:13.840 Rachel, as expected, this was a fantastic discussion. And I think it adds to what we're

02:10:20.060 trying to do in this podcast, which is really have nuanced and deep discussions about important topics.

02:10:27.780 Not every podcast I do gets to impact that many people. Some of them impact nobody. They're

02:10:33.880 just really esoteric, but they fit into my curiosity window. But this is kind of a topic

02:10:38.660 that really impacts almost 100% of the population because 50% of the population is who we just talked

02:10:47.780 about. But the other 50% of the population would be hard-pressed to say that they don't care about

02:10:52.500 at least one person in that other group. So 100% of people are heavily impacted by what we just discussed.

02:11:00.860 Can I say one thing real quick? I'm also a men's health doctor and I lecture my urology colleagues

02:11:06.340 and I say, and you talk about longevity and here are the things you can do for longevity. I think

02:11:10.640 you're missing one point. And that is that men who are divorced, single, or widowed have horrible

02:11:17.340 health outcomes. Horrible. Whether you look at mental health, prostate cancer, cancer outcomes,

02:11:22.720 horrible. They die sooner. So if you want longevity, if you want to keep living,

02:11:26.960 you have to keep people partnered. And when do people get divorced? Between 40 and 60.

02:11:32.480 That is the age of perimenopause and menopause. Menopause is killing men. It is killing men

02:11:38.280 because it changes their marriages and it leads to divorce, which leads to death. I'd give this

02:11:44.080 lecture of if men's health doctors, if doctors truly cared about keeping men alive, they would do

02:11:50.440 menopause medicine because that is one of the most important ways to keep men alive. So that's my

02:11:55.900 other argument for you to focus on this and really make change here. And I'm just can't thank you

02:12:00.880 enough for this platform because it is everybody's problem. Rachel, thank you very much for the work

02:12:06.420 you're doing and thanks for coming today. Thanks for having me. Thank you for listening to this

02:12:11.140 week's episode of The Drive. Head over to peteratiamd.com forward slash show notes if you want to dig deeper

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The Peter Attia Drive - May 12, 2025

#348 ‒ Women's sexual health, menopause, and hormone replacement therapy (HRT) ｜ Rachel Rubin, M.D.

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