The Safest Form of Hormone Therapy

All right, so let's break down the different types of bioidentical hormone replacement therapy and how they can be used for the perimenopause, menopause, and beyond transition. So the first one I'm going to talk about today is specifically oral hormone replacement therapy in a bioidentical form. Now, if you listen to me for a long period of time, and especially a lot of my counterparts, that's not necessarily the first choice most people will use. However, there might be times and reasons why this may be valuable. For instance, if you can't remember to do your cream or your patch or your oil or any other form of topical estrogen, an oral bioidentical estradiol is an option. And I will say this is often used in women who might go through early hysterectomy or have other reasons why they might need to go on hormone replacement early. Now, let's talk about it. So when we're looking at oral estradiol, this is very important. The word estradiol stands for the exact composition of the ovarian hormone in made by our ovaries. So that is estradiol, and technically it's 17 beta estradiol. That is the exact same form. So this is synthesized in a lab, usually from vegetarian forms, but it is synthesized in a. Yeah, in a lab, usually from either yams or soy. And it is bioidentical or chemically exactly the same as what our body makes. Now, it's taken by the mouth. Now, here's the reason why I don't love it. Anytime we take a hormone, particularly estrogen, orally, it's going to go into the body, it's going to go all the way down into the gut, it's going to go straight to the liver and go through what we call first pass liver metabolism. And that's where our genetics and the overall load on the liver can take control. So depending on how we're wired genetically, we either process estrogens more cleanly or not. If we are on other medications that go through that pathway, we might have a more burdened pathway, like SSRIs, pain medications, anticoagulants. There's lots of things in this category that can affect affect those pathways. And let's say I have other health concerns. I might not want to load my liver with additional hormones. So when you take estrogen orally, it goes down into the liver, gets passed through first pass metabolism, then it hits the bloodstream and gets utilized. Now, where this is different from the synthetic forms and that are used in birth control is that it is actually bioidentical, right? It is 17 beta estradiol. So it is bioidentical to your body. The ethyl estradiol that we use and the many other forms that we use in synthetic birth control is different. Think of it as a key. It's not the exact same key. The other thing that birth control does that normal bio, bioidentical hormones do not do is it binds irreversibly to the receptor. And that's how it works to control fertility and keep you from being able to ovulate. But it also has a very different action. So the first thing to know is oral. 17 beta estradiol is not the same as birth control. It's not. It is bioidentical, but it is subject to first pass liver metabolism and therefore not usually the one that we want the most. Now, now for the micronized. So it is a micronized estradiol. So micronized means it's better absorbed and it metabolizes in a water soluble way. Now this dose is usually between 0.5 milligrams up to a 2 milligram tablet. And it's done daily. Obviously the active ingredient is 17 beta estradiol. Now it has other excipients or core ingredients that are part of its construction when it was a. It's generic. So these can vary a little bit from ransack. So that's the important thing. So we also have to understand that most of these medications are generic because they are not patentable. Right? Nobody's going to make a lot of money on it because it's bioidentical. So when it is generic, the active ingredient can vary up to 25% per batch. So one time it might be 0.5 and the next time it might be 0.25. And that's well within the the ingredients and well within the FDA's approval. So, so you can have variability up to 25% of the active ingredient on a generic. So if you're taking it and you feel like it's a little bit different, that could be part of it. The other thing is it's going to have a variety of inactive ingredients that are part of the construction of the tablet itself. Now most of these inactive ingredients are things like cornstarch, colloidal silicon dioxide, dibase, calcium phosphate, lactose monohydrate, magnesium stearate and sodium starch, glycolate. These are all things that help you make the actual tablet and hold the tablet together. Now this is where it Gets a little more interesting because these are pharmaceutical drugs, we don't want them to be boring looking. And so most of these drugs have dyes in them per chick. And what's interesting is the strength of the colorant depends on the dose. So the 1mg tablets often either have FD&C blue number one aluminum lake or DC red number 27. The 2mg palettes will have FD, D&C blue number one aluminum lake and FDC yellow number five. So it's going to have some colorants in it that most of us would choose not to do. So when we look at, you know, quality of product and what we want to put in our body, we may not want to put colorants in there every single day. Why would people do this, right? Why would, why would somebody want a pill knowing there's first pass liver metabolism, the convenience of a daily pill, right. A lot of people are like, hey, I just want to swallow a pill. I don't have to put on patch, I don't want to have to put on a cream, I don't want to have to go get a pellet put in my butt, I don't want to put on an oil. So there's a convenience factor. However, it's going through first pass liver metabolism, which means it may have a slightly increased risk of blood clots compared to a topical form. But when we compare that to the Premarin, it's not as much as Premarin. Right. So Premarin, significant clotting risks when we get a lot older, estradiol pill, maybe a little increased risk, but not as much. And then topical forms, no increased risk of clotting risk. So when we look at that, the, we're treating clotting risk a little bit for convenience. And again, I see this more in women who are younger that maybe had a hysterectomy and they're just looking for convenience. You know, their lives are crazy. They got little kids, you know, they might be doing it for convenience, but I generally don't think it's the best choice for women who are in that perimenopause and menopause and beyond transition. And there's also potential digestive side effects, right? So when we look at the pill, there's going to be starches and excipients like magnesium stearate to help create the pill. And then there's usually colorants that are your non specific ingredients. Now one of the most common forms people use is the transdermal HRT patch and it is a 17 beta estradiol. It does not contain estriol. And I would make an argument in some cases genetically, it would be valuable to have an estriol because of its binding to the estrogen receptor B. Particularly in people who have the genetic mutations on CYP3A4 and CYP1B1. There could be reasons to do the estriol biased combination, but the patch is just 17 beta estradiol. So it's again, same thing. Now it contains in many cases bioidentical hormones. Right. There are a few forms that are synthetic and sometimes they will have a added progesterone. But the vast majority, like Dottie, the Vel Dot and a lot of your generics, if they say 17 beta estradiol on it and that's it, it's bioidentical. Now it's worn on the skin. So hormones that are absorbed through the skin gradually move through the skin into the bloodstream and then bypass the first pass of liver metabolism. And so what that means is it goes in, does its job and what little is left goes to the liver. So it carries less clotting risk and heart attack risk because it doesn't increase the clotting risk. Now here's where it gets a little interesting. The non hormonal components of these patches can vary by brand. But let me go through some of the common elements that are in it. So there's usually a backing film, that's a poly polyfin film, and then the relief liner, that's usually a polyester polyester combination that gets pulled off when you stick it to your body. And then there's a pressure sensitive adhesive and it's usually an acrylic or silicone adhesive. It's commonly used in sort of a drug delivery matrix. Right. The adhesive sticks really well, but it also helps with the delivery, delivery of the hormone over time. When we look at solvents and vehicles and excipients, these are all things that help move it into the bloodstream and help push it across the skin barrier. This is going to be the other ingredients in the adhesive. So there's a dipropylene glycol, which is a solvent or a vehicle, oleic acid, which is a permeation enhancer and a povedone polymer and a crystallization inhibitor. So what that is is that keeps it from junking up or crystallizing and keeping it at an even adhesion and also keeps the distribution of the drug even across the sticker. So as glycol, it solubilizes estradiol within the adhesive matrix and it helps the drug's thermal dynamic delivery while interacting with the lipids and the keratin to increase mobility and facilitation of diffusion. What does that mean? So the glycol helps make estrogen soluble, right? So makes it more absorbable and helps move it across the fatty tissue and the keratin, which is the proteins in the skin, to help mobilize it and move it across the skin barrier. Now what's interesting is some of the older style patches use an alcohol containing carrier which were implicated in higher irritation rates, particularly in hot humid conditions. So when we look at, at those, if you get a lot of irritation from your adhesive, it might be interesting to see if it's a alcohol excipient rather than a glycol excipient. When we look at experimen that has also looked at a thing called DMSO as a penetration enhancer as well. And that's used. DMSO is often used with the acrylic forms of adhesive. Now when we look at acrylic and silicone in the patch, again, that's the adhesive matrix and they're part of this sort of pressure sensitive, what they call polymer. The concerns about endocrine disruption really are usually on other ingredients kind of weight, what they call weight cyclical siloxans used in some consumer products, but generally are not used used in what they call high molecular weight silicone adhesives. So what that means is a lot of the other acrylic and silicone things that might be used in over the counter ingredient things are not the same as what's used in these pressure sensitive drug delivery patches. Now with that being said, so there are some chemicals on there, but they're, they're relatively safe and at very low doses, what does happen? So it's not uncommon to see itching, irritation, hives, dermatitis, which are often because of the delivery mechanism itself, adhesive allergies and can affect the transdermal delivery of estrogen. So when we're looking at the delivery, if you're, if you're getting sight irritation, then it's actually not the estradiol at all. It's the, it's the polymers, the adhesives, the acrylic, the silicone and the adhesive itself that you're reacting to. Now the, both the acrylic silicone pressure sensitive patch are standard and approved patches. Right? So those are all standardized. They have gone through human clinical trial trials. They are utilized in Human clinical trials to prove efficacy and are generally overall well tolerated. Right. Have I worn a patch? Yeah, I have. Sometimes it's easier when I'm traveling to have a patch because it's one less bottle of something I need to take. It's not my favorite, right? It's not my favorite, but I do use it and in the grand scheme of things, it's better than taking estrogen orally. Now the permeation enhancers, right? So these things help get it across the skin barrier. Oleic acid and dipropylene glycol, they facilitate the actual absorption itself and it's, they're considered inactive ingredients. Now oleic acid naturally exists in things like olive oil, right? So, so we have to understand that that's a carrier that helps push it across the skin. And like I said, there's a DMSO patch that, that are not standardly marketed, not particularly here in the United States, and they help to increase the flux of estrogen across the skin. But they're not really utilized as often. Now the other reason why someone might choose a patch is it's less frequent, right? You change it twice week, you slap it on, you go do your thing. And as long as you're not in a really humid, hot, sticky situation, it sticks usually pretty well. Now I'm in Texas and when it gets to 105 and I'm exercising outside in the middle of the day, I might have issues with it staying stuck. The other thing is it's got a lower risk profile than oral estrogen clotting risk. So the studies, particularly the 10 million women study that looked at long term mortality risk, the women who were on topical forms of estrogen, including the patch, did not show increased risk of stroke, heart attack or blood clot. So a patch is going to be a better choice than an oral estrogen for that stroke and heart attack risk, particularly if you are older. So that's your patch. Now let's look at creams and gels. So compounding pharmacies are basically the most common places where you're going to find a bioidentical estradiol or biased, which is combination of estradiol and estriol, again, another ovarian hormone that is produced after your body biotransforms or detoxifies estrogen off the CYP3A4 pathway. And so it's produced by the body. It's generally not high unless you're pregnant, but it has physiological action. So it's not like your body doesn't make it for a reason. It's just not as strong as estradiol. Now, when we look at the creams, those are made by, by compounding pharmacies based on an individual prescription. Now what I will tell you is those are usually based on some standards, right. It's not like somebody's making some nuance changed. There is some standardization that's commonly used for bioidentical hormones, particularly in the beginning when you're going to a compound pharmacy and then it might get tweaked over time to get it right to you. But generally speaking, there's doses that most people end up on. Typically we're going to be using either a biased or an estradiol. And then you can also have cream forms of progesterone. Right. I personally am not a fan of topical progesterone. It is a big molecule. It doesn't cross the skin in the same way estradiol does. And it hasn't been shown in studies to protect the uterine lining against cell proliferation and blood supply, which is what estrogen does. So I don't like the topical progesterone because of what the research shows. I think it's, it's, you know, potentially valuable for other reasons. But if you are, if you have a uterus, you need oral progesterone or vaginal micronized progesterone and oral micronized progesterone. So let's go back to the topical creams and then you could also have a bioidentical form of, to testosterone as a cream. Now sometimes people put all those things together, I think in the beginning when you're trying to figure out your dose, my 20 year history with the clinicians in my office who prescribe, it's always best to kind of start with things separated because then you can get individualized on each individual hormone to figure out what you want. But when we look at the absorption. So the creams usually are applied to the inner thigh, the wrist, the inner arm, sometimes the back of the calf. Places where the skin is very thin and more easily absorbed. Like you don't want it on your hands because this is very, very dense tissue. We've got calluses. You want it in very thin skin area. The idea again being that it can be personalized and it's, you know, potentially a lot of times what we do is it's easier to give to those people who are highly sensitive when we look at the creams. Here's where it becomes difficult is most of the creams have a, a base, right? And these bases can vary significantly by the companies that make them. Right. So one compounding pharmacy could be using a CoQ10 based cream that's got you, let's say shea butter and other delivery mechanisms. Another one will have a different cream base. And what I have seen over 20 years working with women in my clinic, with our clinicians that prescribe is some women will absorb it really well, other women may not. Sometimes you switch from one pharmacy to the next and you get a completely different absorption. So the challenge with bioidentical creams is it varies based on the woman, the cream and where you're getting. It doesn't mean that they're not valid, it doesn't mean that they don't have the right dose. It's just creams can, can adjust the absorption. So when we're looking at estrogen, the creams can change. So if you're on a bioidentical cream form of estrogen and especially if your labs don't seem to be changing or you don't seem to see symptom resolution, I recommend changing the base it's in and then also changing potentially the pharmacy. Now, testosterone. The FDA has not approved testosterone for the treatment of hormone related conditions other than libido for women. And we do not have an FDA approved dose for women. However, lots of women are getting prescribed and we've been prescribing it since the 40s. So testosterone is absolutely important. And in most cases if you're on a testosterone, you're on a compounding pharmacies version of testosterone because again, you can't go to a traditional pharmacy and get it. Some doctors prescribe Androgel which is dosed for men and then try and tell you to take a little tiny bit and rub it on the back of your calf, which makes it very hard to manage right to because again, it's, it's dosed and also concentrated at a level which is 10 times what a woman would take. So testosterone is almost always going to be a compounding pharmacy dose and again, usually a cream. And again, the creams can be absorbed in different ways. I would love to give you a million ingredients, but literally when I started pulling apart the compounding pharmacies, they're all different and there's a lot of different bases. Now let's talk about one last form that doesn't get its fair due and it's actually the hormone that we commonly use within our clinic and that we are starting to use with our telemedicine company. We spent the last year researching it, studying it Utilizing it with women, which is a bioidentical hormone, 17 beta estradiol and or 17 beta estradiol and estriol bioidentical form of testosterone in jojoba oil. One pharmaceutical company in the world is patented to deliver hormones and oil. And this particular company has pharmaceutical grade pharmaceutical dosing hormones in jojoba oil, which means it's just hormones and jojoba oil. And we've utilized that. And what's interesting, and this is kind of anecdotal, I haven't done a, you know, randomized controlled trial, but I can tell you my own experience. I have tried every hormone, including sublingual troches. And what I found is that the jojoba oil hormones absorb very well. They, they absorb into the skin much better than a cream. The creams can kind of feel like you're sort of slathering yourself up and they get utilized very easily. And so jojoba oil based hormones are my particular favorite. And then we always use micronized oral progesterone. So that's another choice for a top. And again, topical forms, whether it's the patch, topical cream or topical oil, do not carry the clotting risk that is seen with oral forms of either synthetic or thioidentical. Now there's also oral troches. Now troches are either going to be a gel like substance that you put behind the tongue and underneath the tongue. You let it absorb in the mouth or in some cases it's almost like a consolidated powdered, sort of like a sweet tart that you put under the tongue and let it absorb. Those absorbs very, very well. They absorb in the mucosal area of the mouth and, and absorb into the bloodstream. And my experience when I tried the testosterone is I absorbed very, very well. So I got too high very quickly. And so if I wanted to stay on that, we would have needed to adjust the available dose in that oral sublingual form to a much lower dose than what it would have been equivalent to the cream or the topical oil that I was using. That may not be true for everybody, but it absorbs very well. You don't swallow it. So it goes through the permeability of the tissue inside the mouth to the bloodstream. But again, it can become, you know, higher just because of that oral mucosal absorption. And so and also in those, that varies a lot by compounding pharmacy. And so if you're looking at all these different hormone replacement therapies, you know, the first thing we need to remember is bioidentical, is safer and better. Right. They match the same hormones or body identical to what you make and the delivery mechanism. The rule generally of thumb that most functional medicine people recommend and also even conventional providers is a topical form for estradiol or abiest, which is estradiol, estriol and or a topical form of testosterone. You don't really want to take those orally just because we get just the great absorption without first pass liver metabolism. Now, progesterone, micronized only oral, has been shown to protect the uterine lining and also gets metabolized into a byproduct that actually helps with sleep and relaxation. Now, some women will get so sleepy on that that they can't handle it. And in some cases you can actually use that same one vaginally and have it absorbed into the system that way. But generally, topical progesterone do not provide the uterine protection that you're looking for. And it's not that estradiol is bad for the uterus. It's not that progesterone is good or bad for the uterus. It's that they're supposed to be together to balance out what your uterine lining is up to. Both hormones are both there in relative balance to each other when you are fertile. And so they need to be balanced when we go to replace them. So we don't do synthetics, right? Premarin, prempro, no longer things to do. And I'm also not a fan of using birth control to transition through the menopausal transition, particularly if you're in that sort of end game. With that being said, if you are in the early transition of perimenopause and still potentially have fertility, which most people do, again, your egg carton is not completely empty. It may just have a few left. And you want to control whether you have a baby or not. Bioidentical forms do not provide that level of protection. So it becomes, how are you going to handle this? Are you going to use the rhythm method which works? But you know, I was a baby that was a rhythm method baby, like, oh, I don't think I'm ovulating right now. So it's not 100%, it's not even 95%, especially when you get into perimenopause, you can't follow cervical mucus like you used to before. So that could be a case for using birth control for what it's meant a very, very low dose to control your fertility. So you can decide whether you want to have a child or not. But as you go into menopause and you go into hormone replacement therapy for the long term and for the support of cognitive decline, osteoporosis, heart disease, breast cancer, all those things to reduce those risks, then a bioidentical form is the right thing to do. And obviously all of those things are up to you and how you want to manage your own care. But that's a little bit about all of those, all of those risks and all of those choices. So I want you to think about when you look at hormone replacement therapy and the efficacy of what it really is and what's important. And last but not least, let's talk about the effective treatment for not only alleviating symptoms such as hot flashes, night sweats, mood swings, genital urinary syndrome, and also protects against osteoporosis, cardiovascular disease, depression and cognition. We have to also remember that we're trying to hit a particular dose, dose and dose. Individualization is really important here. So if you're seeing a clinician that's prescribing based on symptoms but never checks your labs, we need to know that, because the consensus among menopause specialists and major guidelines is that we need to individualize it, that not every woman requires the same amount to get to an effective dose. And the reality is, if you look at the menopause society and a lot of the other groups, they don't recommend routine testing to see if your hormones are at adequate levels. However, you know there is variability day to day, hour to hour, when you're in perimenopause on blood levels. But once you're on the other side, it's very easy to test for. And the optimal blood levels for relief of symptoms is not always rigorously defined and doesn't necessarily indicate whether you're actually protecting against the things that we're worried about. So what does that mean? So if you are working with a practitioner that doesn't think about the different forms of hormone and how they work, and they aren't testing your labor, you may actually not be getting enough or be getting too much. A recent large scale study showed that about 25% of women have sub therapeutic estradiol levels based on the current standards of treatments, even on the highest dose of transdermal estrogen. Right. So we're talking about patches A for symptom control, but B, also to protect the brain, the heart, the bone. So despite this variation, the primary indication for dose adjustment is the persistent resolution of symptoms such as hot flashes or joint pain. And here's the reason why there's absorption differences between different forms and different women. And when Dr. Louise Newsom and her team looked at it, her clinic has has really led this study. And what they found was 50% of women would be under treated using hot flashes, night sweats and just symptoms alone and 25% would be over treated. And so when we do treatment, we got to look not only at treatment level and whether they're in the ranges to affect your symptoms, but are they also in a therapeutic range which we have blood levels for to protect the brain, the heart, the bone. So some people could be higher than what is usually listed on the the normal patch, cream, oil or some people can have a much lower dose and get the same effective rate. So dose efficiency is better monitored first for symptoms relief, then labs to check levels and then I would argue also checking how you metabolize it through the first pass liver metabolism and how you get rid of it it. So this approach prevents under treatment, over treatment and appropriate treatment and also will help you understand which form of estrogen works best for you. Some people work better like I do well on a transdermal patch or the oils, but I don't do well on the creams and testing was the only way for me to see that. So for you, if you've got a provider that's providing hormone replacement therapy, you want to ask yourself, are my symptoms better? If not, am I getting an adjustment to my dose and have I had labs to confirm effective dose? If I haven't, I need to know that. And if those those things are not true, you need to change the form, the method and how you take them to see if you need to change that and potentially the dose. And if your clinician or physician is not willing to do that, you probably need to find a new one. So I hope you found this to be helpful and really helped you kind of understand the different forms of bioidentical hormones to help yourself make a better choice. I want to thank you for listening and watching Menopause Mastery. If you happen to be watching this on YouTube, please subscribe and like. And if you're listening to us on the podcast, please leave a comment, give us a thumbs up or a five star review that really helps and we'll be back together next week.