#275 - AMA #52: Hormone replacement therapy: practical applications and the role of compounding pharmacies

Hey everyone. Welcome to a Sneak Peek, Ask Me Anything or AMA episode of the Drive podcast. I'm your host, Peter Attia. At the end of this short episode, I'll explain how you can access the AMA episodes in full, along with a ton of other membership benefits we've created. Or you can learn more now by going to Peteratti md.com subscribe so without further delay, here's today's sneak peek of the Ask Me Anything episode. Welcome to Ask Me Anything episode number 52. I'm once again joined by my co host, Nick Stenson. In today's ama, we focus the entire conversation around hormone replacement therapy and testosterone replacement therapy as it relates to women. We've gathered many questions that have come through our recent podcasts with Joanne Manson, Sharon Parrish, and the Endocrine System video series that I did on this topic. These questions all focus around the practical application of HRT and TRT for women and how we do this in our practice with female patients. So this AMA is really centered around answering questions with the focus of helping people put into practice what we've talked about a lot in terms of theoretical application. So we've done so much work on the theory of HRT and trt. This is kind of the how to do it. Wrapped up in this conversation around HRT is the topic of compounding pharmacies. As it is almost impossible to disentangle the role of hormone replacement therapy of any form in compounding pharmacies. And if you don't know what a compounding pharmacy is, you're definitely going to want to pay attention. And certainly if you do know what it is, I think you're gonna wanna pay attention because compounding pharmacies are still a little bit the wild, wild west, and there's the good, the bad and the ugly associated with them. Even if you're not interested in hrt, this is probably an important discussion for anyone who falls within spitting distance of a compounding pharmacy. If you're a subscriber and you wanna watch the full video of this podcast, you can find it on the Show Notes page. And if you're not a subscriber, you can watch a sneak peek of the video on our YouTube page. So without further delay, I hope you enjoy.

52. Peter, welcome to another ama. How you doing?

Doing very well.

We got a topic you're really excited about.

I think today I am, yeah. I do find this topic to be simultaneously interesting and important. So glad we're doing it.

That's always a good overlap for today's Podcast. For those of you listening and watching, what we're going to do is answer questions that have come through from subscribers around recent topics covered on the podc. Specifically, questions around hormone replacement therapy and testosterone replacement therapy as it relates to women. So this is a topic that's been talked about on the Joanne Manson episode, Sharon Parrish, as well as the Endocrine System podcast where, Peter, you were drawing it on a whiteboard. And so from those episodes, we gathered a lot of questions. And these questions really focus around the practical application of HRT and TRT for women and how you use these in your practice with your female patients. So the hope is this is much more of a practical application as opposed to an educational one. Wrapped up in this conversation around HRT is the topic of compounding pharmacies, as many people who will need to get HRT and custom HRT prescriptions will use compound pharmacies. So even if you're not interested in hrt, if you ever think about or will have to use compound pharmacies, it will be a really good discussion. With all that said, anything you want to add before we get into it?

I think sometimes when you talk about something like sex hormones, there's a potential thinking that, oh, you're only speaking to half the population. But of course, while everything we're going to talk about is directly applicable to women, it's obviously applicable to men who sort of know or care about women. I know more about this topic than my wife, and that's going to, I think, help me help her as she goes through these transitions. And similarly, I think if you're listening to this and you're a guy, it's worth paying a lot of attention as though we're talking about male hormones as well, which, of course, we spend just as much time talking about. And the same argument would apply there as well.

Yeah, and I think that kind of leads to a good first question, which is, even though this is a topic we've covered somewhat extensively in the past, why did you kind of feel it was important to touch on hormone replacement therapy again as it relates to women and pull more questions around this?

You know, I just think that this is a very frustrating topic to me. I don't tend to get as animated about it as I used to or as angry about it. I still believe the sort of mainstream medical community has committed a gross injustice over the past 20 years in the misinterpretation of the Women's Health Initiative and the subsequent demonization of hormones in perimenopausal and postmenopausal therapy for women. And as a result of that, many women have been significantly harmed. The sum total of lives that have been saved due to less breast cancer as a result from the lack of HRT over the past 20 years is exactly zero. I say that a bit facetiously, but statistically that is true. Let's be clear. There were zero additional deaths due to HRT from breast cancer. There were more cases. One in a thousand women increase in case, but it translated to nothing in deaths. And yet I'm positive we could point to additional deaths due to hip fractures. I've discussed some of those elsewhere, and that says nothing about the quality of life that has been compromised. So we're not going to rehash all of that because it's been done elsewhere. And as you said, the purpose of this podcast is to talk about the logistics of how one goes about hormone replacement therapy and what all of the options are. And believe me, there are a lot of options, so a lot to cover.

Today we know there's a broad spectrum of the severity of symptoms that women will experience in menopausal transition. And because of that, we see a ton of questions come through from subscribers wanting to know, how will they know if it's time for them to start considering hrt? So do we know anything about what the tests are that can be done to confirm the onset of menopause?

Yeah, so menopause is a clinical diagnosis, and technically it's really diagnosed retrospectively. It requires 12 months of amenorrhea. So 12 months of not having a period without any other obvious pathologic or physiologic cause. That said, there are a number of things that we can measure in the blood that tell us we're heading there. Or frankly, if you just happen to have difficulty or for other reasons have an inconsistent period, such as the use of an iud, which can interfere with a period. These blood tests can be particularly helpful. Really, the mainstay of looking at this is measuring follicle stimulating hormone and to a lesser extent, luteinizing hormone. But it's really fsh. That is perhaps the single most important hormone to look at to get a sense of where a woman is on her trajectory towards menopause. Now, we've covered this in great detail in the video that I made on the subject of hormones. And one of those videos people might recall was specifically on female reproductive hormones. I did one on male reproductive thyroid, et cetera. We'll link to the video of the female reproductive hormone systems in the show notes. This would be a great time to watch it if you did in the first place. And you'll get a sense of what FSH and LH are doing and how they're changing throughout a cycle. But I would say the gold standard is especially in the case of a woman who is still having a period. The reason I say that is there are women whose periods are very infrequent because of IUDs, but they're technically not still in menopause. But if you can measure FSH and LH and estradiol, just to round it out on day five, day one being the day the period begins. So five days in, that's a very good test. And boy, once that number starts to get to 20 or 25, that's really the surefire sign that a woman is in menopause. But it's important to understand that if a woman is sitting here and she's not in menopause yet and wondering, well, is that it? Is that the diagnosis? No, of course, again, it's. The diagnosis is based on amenorrhea. But for many women, they're going to be having symptoms even before they get there. And I think it's safe to say that the most common symptoms that women experience are the so called vasomotor symptoms of hot flashes and night sweats. Those tend to significantly precede other symptoms such as vaginal dryness, vaginal atrophy and things of that nature. And obviously more significant issues such as loss of bone mineral density. So, again, looking at the fsh, LH and estradiol level on that day five, you'll see FSH and LH go up, you'll see estradiol come down, and obviously we might start to see symptoms even before that diagnosis of menopause. And we would of course refer to those as perimenopausal symptoms.

Yeah, and that's a good transition because we also receive questions around if there are other tests that might be indicative of perimenopause. What do we know about that?

So the short answer is, yes, there is. We do not use this in our practice. But I think if you're chasing fertility, you may also be looking at the anti mullerian hormone or amh. So I think anybody listening to this who has thought about fertility, whether it be through IVF or other means, is probably familiar with this hormone. But it's a hormone that is produced by the granulosa cells of a growing follicle. So small follicles, sort of sub 8 millimeter follicles. Are making this hormone. And the more of this hormone you have, the more ovarian reserve you have. Now this is actually one of those examples where a figure is sometimes worth more than the words, because AMH declines precipitously before the onset of menopause. And so knowing your AMH level and knowing both the rate of decline and the absolute level can also be predictive. Again, I think this is not necessarily a valuable tool for predicting menopause. And I think the better use of this is actually around trying to get a better handle on ovarian reserve if reproduction is still in the cards. But if you pull up this figure, Nick, you'll get a sense of how fsh, LH and AMH are changing in the perimenopausal phase. So for people just listening to us, unfortunately, it's not as powerful. But you have a graph here that on the x axis shows you time. So time zero is the final menstrual period. Therefore, halfway between the zero and the one would be the definition of when you're in menopause, when you enter menopause. And you can see that this graph starts on the left. Five years before menopause and five years before menopause, you can see FSH and LH are very low. They're represented by the green line for fsh, the blue line for lh. By the way, the dotted lines on either side of the solid lines just show you the 95% confidence intervals. This is very, very tight. Five years prior to menopause, the anti Malarian hormone, the AMH, is very high. So the FSH and LH concentrations are shown on the left Y axis and the right Y axis shows the AMH concentration. So 5 years premenopause, the AMH concentration is 0.6. The units are nanograms per milliliter, but most people would just say 0.6 because those are the only units they're typically measured in. The FSH and LH are very low. They're going to be somewhere between 2 and 5. And just watch what happens as you move from basically five years prior to menopause towards menopause. The AMH drops very suddenly within a period of about a year or two. It goes from 0.6 to 0.1 and certainly less than that. Whereas the FSH and LH rise and you'll notice that fsh, LH again. Remember I said the FSH was the thing I care most about. You can sort of see if you look at that green curve, that FSH is hitting 25 right around menopause, maybe even a little bit before. So there are a couple of studies and we'll link to at least one that do look at the rate of change of AMH as a predictor of menopause. Again, we don't do this clinically in our practice. I don't think that means it's not valuable, but there are certain predictors that come out. So for example, if your AMH is below 0.2 and you're more than 40, then the probability that you're going to go through menopause in the next five years is very high. But again, the FSH is still valuable. In fact, it's probably necessary to determine how earlier late you are in it. I think where the AMH is helpful is when it's high. So if your AMH is above 1.5, you're likely not perimenopausal. In fact, even if you're over 40, but your AMH is over 1.5, menopause is probably at least six years away. So anyway, I think those are kind of examples of where the AMH can be helpful, again, especially if you're still considering fertility.

Peter, earlier you mentioned vasomotor symptoms and this is something that we see a lot of questions come through on from people. So maybe start with what are the underlying hormonal changes that cause menopausal symptoms like hot flashes? And then from there maybe discuss what are some hormone replacement therapies that can be used to alleviate those symptoms?

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Sam.