NEUROSTEROIDS & Their Often Overlooked Nuances (And other cool facts..)

The next thing is the application of the medications has to be a bit different, and sometimes this actually gets turned around in some of the lectures you see. In order for a neurosteroid to maximally impact the brain— Hey, it's Dr. Paul Anderson. Today I'm answering questions. One question was, I mentioned something called neurosteroids and people wondered what that was. Not everybody, but A number of people did. So I want to talk about neurosteroids here really quickly. Neurosteroids are obviously steroid. It's got that in the name and neuro, so they're used in your brain. They are the same steroid molecules as you use elsewhere in your body. So for purposes of today, we'll talk about what I like to call above the neck steroids and below the neck steroids. Neurosteroids specifically, Neurosteroids are a group of bioactive steroid hormones that have effects inside of your central nervous system. They have effects there that are very important to health and healing and some disorders and diseases. And they also are different often from the way that those hormones might be used in the rest of your body. So that's the idea with neurosteroids. The main ones that we talk about clinically are a couple of high-order steroids like pregnenolone and progesterone, and then there are things like testosterone and DHEA, and then there's some other hormones that we'll bring up as we go along. What do these things do? Well, if we think about pregnenolone, progesterone, DHEA, testosterone, those are used for reproductive hormone activity in the body. They're used as Precursor types of steroid hormones in the body, et cetera. Similarly, they might be used in the brain, but really the big picture is neurosteroids do a couple of very important things. One is some of them work on the healing end of the brain biochemistry and the brain maintenance in the body. And then some of them work towards helping to repair particular circuits. And then some of them work actually in some of the calming circuits in brain. So that's the big picture. Now, the world of neurosteroids. One of the most extreme examples of a neurosteroid imbalance is a type of epilepsy that's called catamenial epilepsy, which was sort of quantified. It was observed, but it was quantified by actually injecting people intravenously with different hormones and triggering seizures. Now, this research was not done in the United States. I had nothing to do with this research, but that's— Where was it done? That was some of the earlier research on neurosteroids. And what they found was that if they injected estrogen intravenously, they could trigger a seizure. And then if they injected progesterone, they could stop the seizure. And so they called an estrogenic-type seizure, and there's more to it than that, but basically an estrogenic-type seizure, catamenial epilepsy. And all of that to say, because we're not really talking about epilepsy here, although it has purpose there, Then they set about to figure out what is it that progesterone did that stopped the seizure. Well, this is a really good example. So if you think about the way that steroids are created in the body, they go from higher to lower order steroids. Pregnenolone comes from cholesterol, so it's the sort of the parent one steroid, and then it gets converted over to progesterone, and then all of the other steroids come after that in the process. So why would estrogen trigger something like a seizure? Now, what happens, and we know a lot more now than we used to in neurobiology, that estrogens can bind to particular receptors and make them more active, such as the glutamate class of receptors, like NMDA receptors that are very excitatory. And also they have a component of their metabolism, not the receptor, but the downstream metabolism that can be inflammatory. So you could trigger by glutamate triggering something like a seizure. Well, it turns out that progesterone and pregnenolone, through basically a similar pathway, work on a counterpoint to the excitatory glutamate receptor class. And that counterpoint is over at the GABA, gamma-aminobutyric acid class of receptors, which is a calming receptor. So glutamate Opens up ion channels and causes an increase in neuroelectrical activity. So you could see how maybe a seizure could get triggered there. And then GABA causes a calming effect by opening, in the case of the GABA-A receptor, the chloride channels. Well, as soon as you open a chloride channel, it sort of puts the brakes on the other excitatory receptor classes. Now, what else binds to GABA-A receptors? Well, a very famous drug category, the benzodiazepines, bind there, like Valium, and some of the non-benzodiazepine sleep aids bind there, etc. Alcohol has some activity there, for example. So it turns out that progesterone actually would stop the seizures because it would bind at the GABA-A receptors and it would actually enhance the activity of the GABA-A receptors. That would stop the glutamate-triggered seizure in catamenial epilepsy. Well, what if, what if you don't have Epilepsy, but you might have other things going on in your brain. Does this still work out? Well, there are things that we see in imbalances with hormones or certain pathologies, etc., where you might have a little too much estrogen activity. Now, this can happen in men and women, just so you know, but too much estrogen activity without enough progesterone to balance it peripherally does different symptoms, but in your brain, it can actually cause a hyperexcitatory state. So, you might not get a seizure, but you may have trouble sleeping, You might trigger things like headaches, certain types of migraines, et cetera. You can trigger other sort of a neuroexcitatory, neuroinflammatory cascade if the estrogen is not balanced by the progesterone. And we're really simplifying it, but biochemically and neurochemically, estrogen's going to support the excitatory activity. Progesterone and pregnenolone indirectly is going to support the inhibitory activity. Now, the balance is what we really need, but what we see in a lot of people is that there might be a reasonable amount of estrogen being made, not enough pregnenolone and progesterone being produced. So that's one of the big neurosteroid things. What else do they do beyond this excitatory inhibitory thing? Well, neurosteroids are also involved in healing from the daily traumas we have from hitting our head or toxicities or other things that go on with the brain. And they're also involved in bigger things like traumatic brain injury. Post-surgical healing. Now we know that in a lot of post-COVID cases, the COVID— post-COVID brain is a lot like a traumatic brain injury brain, even though there was no direct concussive damage. It's a chemical brain injury. So pregnenolone and progesterone are used a lot in the healing end of that. It helps to repair what the blood-brain barrier has lost because of the trauma or inflammation, et cetera. It's It helps with the calming side of GABA reception, et cetera, and it helps with some of the other biochemical pathways that go on. Well, then you think of, well, what about some of the lower steroids? So we talked about estrogen, which is a lower-order steroid, and then there's DHEA, which is a precursor to some of your androgens and testosterone. Well, it turns out that DHEA and then testosterone are both also neurosteroids that are used more in the healing end of the spectrum. So, when we're working with people with any excitatory brain activity problem, from epilepsy over to mania, to sleep problems, to post-trauma, post-COVID injury of the brain, all of those sorts of things, certainly we're looking at this estrogen-progesterone balance, but also it's critically important regardless of being male or female brain, type. And of course, males are going to have more testosterone and females are going to have more estrogen, but we have receptors for both regardless. Very important in male and female to assess the androgens because they feed into the healing part of getting the blood-brain barrier working again, getting the circuits kind of to heal up after the trauma or inflammation, et cetera. And so in a female, we may measure those things. There's, there's slightly different tests for testosterone. In females, DHEA is usually about the same. And then in males, we'll test that as well. The other thing is in a male, we'll also test this balance, testosterone and estrogen, because males can make too much estrogen too. So all of this to say that this neurosteroid, this neurohormonal matrix that you have is critically important for the health of your brain. And it's important for excitatory inhibitory balances, It's important for healing of the blood-brain barrier and other brain tissues. It's important for recovery and is very important in either traumatic or inflammatory injuries of the brain, whether it be a typical traumatic brain injury or a post-infectious, like a COVID inflammatory traumatic brain injury that the neurology community is writing about a lot now. So these are the same Hormones that are used below the neck for different purposes, but they're used in your brain for very specific purposes. So, are they the same exactly? No, the structure is the same, but what progesterone or estrogen, testosterone, DHEA do below the neck and the rest of your body have more to do with either reproductive activity or other endocrine activity that goes on. In your brain, they're very, very specific. So what would be some clinical areas that we would use this assessment and treatment of the neurosteroid balance in? The first thing would be, as mentioned, any sort of inflammatory or concussive traumatic brain injury. So that would include all of your post-COVID and post-infectious inflammatory brain injury. It would include concussive trauma, mild to moderate to extreme traumatic brain injuries. Post, you know, accidents, healing, all of that sort of thing. The other place that it becomes important, especially if you see people not sleeping well, triggering migraines, triggering potentially epilepsy, triggering agitation, anxiety, et cetera, is in the chronically ill community. And so one of the things that happens there is you get injuries to the blood-brain barrier. You don't know about. And there are ways to test the blood-brain barrier to see if it's injured or not, but they're not terrifically available clinically outside of research. Now, there are some tests and they do a pretty good job, but the bottom line is if you have particular things going on, especially in the chronic illness space, in the post-infectious space like post-COVID, and in other spaces, you can assume that there's a level of inflammation and damage to the blood-brain barrier. So, that's a big area where we use those. The other thing is Chronic illness, whether it's chronic infectious, chronic inflammatory illness, autoimmunity. There's a lot of crossover with toxicity pictures like mycotoxins from mold do a very good job of inflaming your whole body, especially your brain. Certain chemical insults, chemical toxins, and some of the metals will create this problem up there. The other thing is that just the general feeling of optimizing the brain chemistry. with neurosteroid activity. So, uh, diminishing the estrogen excess and putting in, say, some progesterone, maybe pregnenolone, and balancing up the androgens, DHEA and testosterone, can be very, very efficacious in bringing the brain balance back. So it can take the edge off of anxiety, certain headache syndromes. I've seen it You know, postpartum depression in some people. I've seen it with catamenial epilepsy in a number of patients and a number of other things that go on too. So to kind of put a point on this in this quick little talk here about neurosteroids, because it was a really good set of questions I got online, just keep in mind that these are balanced. They're a way for your brain to maintain and sort of perpetuate the balance of the neurotransmitters in the brain, which we don't usually think of hormones doing, but they do it. It's also one of the ways that your brain tries to heal when it's either been inflammatorily injured through autoimmunity, infections, et cetera, or concussively injured in an accident like a traumatic brain injury. And they're critically important for that. Now, your healthcare provider, some do a lot with neurosteroids, some know about it and do some with it. And then some, I've given lectures at medical conferences and a lot of people that don't deal with this particular end of chronic illness or potentially the neurology community, if it's outside of that area, they may say, a neurosteroid, what do you mean? And they'll think, well, you mean like anabolic steroids or cortisone or something like that. It's not the same. The next thing is the application of the medications has to be a bit different, and sometimes this actually gets turned around in some of the lectures you see. In order for a neurosteroid to maximally impact the brain, because they have so many uses in the rest of your body— think about progesterone, male or female, there's going to be a whole bunch of uses outside your brain for progesterone, testosterone, all these things we're talking about. So for the more calming ones like progesterone and pregnenolone, we try and do them in a lipophilic form. So that could be a capsule where the progesterone is actually in an oil or a troche, which dissolves, you know, kind of in your cheek area or sublingual drops. And why are we doing this? We're doing this because the lipid or the sublingual application goes around the first-pass effect in the liver. What we want is the brain to get the brunt of this Sudden increase in blood pregnenolone or progesterone so that it can go and it can be metabolized in your brain. The same enzymes exist in your liver, but what'll happen is if you use a non— if you use a high first-pass effect drug like dry progesterone, non-lipid form pregnenolone, etc., it's going to absorb, it's going to go through your liver first pass, the liver will metabolize it, and then your reproductive organs will Kind of preferentially get that progesterone or pregnenolone. So, we tend to do micronized progesterone in oil. That's a real common type of a prescription, or drops, or troches, and that works better for the brain. Now, people always say, well, do I have to take that forever? And usually with neurosteroids, you don't unless you have certain types of epilepsy and a few other neurological conditions. What I usually tell people is let's get your brain working and calmed down healing, and we might do this for 6 months, maybe longer, and then we can try either tapering you off or doing a lower dose of a different type because your blood levels will be up and your brain levels will be up too. Well, I'm Dr. Paul Anderson for Medicine to Health, and it's been a talk based on your questions about neurosteroids. I hope I got deeply enough into it. If not, leave a comment below and I'll try again. I'll go deeper into any area that you would like. This is an area, neurosteroids, where I have seen some quasi-miraculous changes in patients when we'd worked on everything else and the brain was still not healing or the neurochemistry was still all over the place and had some very, very good clinical outcomes and clinical outputs with using neurosteroids with patients. So I really want to talk about this. I want to bring it out, etc. This is the Medicine Health Podcast. I'm Dr. Paul. Please, whatever platform you're on, like, share, subscribe, comment, all of those things. Hit the notifications. And if you're wondering how to get to all these platforms, because you might be listening to this on iTunes or Apple Podcasts or YouTube or whatever, just go to my hub website, which is dranow.com. There are links there to the YouTube community, which we're growing. I really love you there. to join there on the YouTube side. There's links to all of the pod burners, and there's links to cool stuff like our newsletters and all that other stuff. So, dranow.com, go over there, check us out. Thank you very much for listening. Thank you all very much for your questions, and I will see you on the next one. Thank you.