The SHOCKING Connection Between Stress and Sex Hormones

Hey there, everybody, and welcome to today's presentation on sex, hormones and mental health. I'm your host, Dr. Donnelly Snipes. In today's presentation, we'll be discussing the effects of estrogen, progesterone, and testosterone levels on mood, cognition, and neurotransmitter levels. We'll explore the effect of cortisol, the stress hormone, on your sex hormones and your mood. And I identify causes of sex hormone imbalances, and we'll talk about some possible interventions. Let's start out with estrogen. It gets a bad reputation, but estrogen has a lot of beneficial properties to it when it's in balance. And with all of our hormones and neurotransmitters, they operate on the Goldilocks principle. Too little is bad, too much is bad. It needs to be just right. Not only that, but it needs to be just right for that person in balance with all of their other hormones and neurotransmitters. When one gets a little wonky, the other, the others tend to need to be adjusted. When I was little, my grandmother used to bake with me a lot. And one of the things that she taught me was when you're cooking, when you're baking, when you have sugar, if you add salt, if it. Salt actually enhances the flavor of the sugar, it makes it more robust or whatever you want to call it. So if it. Something tastes too salty, one thing you can do is add a little bit of sugar. If something tastes too sweet, you may be able to add a dash of salt. Now, the American Heart Association's probably freaking out about what I'm saying, but ultimately it's about balance because you don't want them to want to dominate the other. Our hormones and our neurotransmitters are very similar. Estrogen is linked to mood disruptions in women, including premenstrual syndrome, premenstrual dysphoric disorder, and postpartum depression. Now, I have asterisks after postpartum depression because men do get postpartum depression, too. Men do undergo hormone changes in the postpartum period as a result of psychological as well as physiological stress and genetic. Genetic programming. I. I don't know what you want to call it. That automatically reduces testosterone levels in the early postpartum period. And we can talk about all of the reasons why that might be beneficial for survival in other videos that are focused on testosterone. But suffice it to say, and I'm going to say it a couple of times today, people who are biologically male can get postpartum depression, too. Throughout this presentation, when I say male, I'm talking about someone who was assigned a male gender at birth. When I talk about female, I'm talking about someone who was assigned a female gender at birth. We are talking about their wiring, we're not talking about their gender identity. Estrogen levels in women with PMS or PMDD post. Pre. Pre menstrual dysphoric disorder are almost always normal. Right? We always thought that they were way high, but ultimately they're finding in a lot of these women, the estrogen levels are normal. The problem may instead lie in the way that estrogen talks to the parts of the brain involved in mood. Likewise, it may alter the way the estrogen talks to parts of the brain that are involved in mood, which impacts levels of other hormones like cortisol and serotonin. We know that when serotonin gets too high, people tend to experience more anxiety, more irritability. So saying that estrogen is the culprit greatly and grossly oversimplifies what we're talking about when we're talking about hormones and neurotransmitters. And I know I'm going to go off on a little diatribe here, it's important to remember that we can have not enough or too much of any of those things because our body can't make it, because our body's not releasing it. Because when our body releases it, it gets broken down too quickly. Because when our body releases it, the receptors on the other side don't pick it up. Or because somewhere down the line the receptors pick it up, but there's a blockage, so they can't communicate it to the next set of receptors. So there's a lot of reasons why somebody's hormones or neurotransmitters may be out of whack. And it oversimplifies it to say, oh, you don't have enough estrogen or serotonin, so let's give you a pill to increase it. No matter how much serotonin you give someone, if the problem is in this serotonergic system, the what I just talked about, if it's in one of those other four of the five areas, then increasing the level of serotonin may not do any good if it's not. If the body's not able to receive the impulses and communicate them down the line. So back to what we were talking about. Simply saying that someone has too little or too much estrogen oversimplifies it. And it could be a dysfunction in the estrogen system. During perimenopause, up to 10% of women experience depression that may be caused by unstable estrogen levels. As we age, regardless of your sex, as we age, the production of gonadal hormones decreases. And during perimenopause up to 10% of women may have really unstable estrogen levels. And I have another video that talks about estrogen in particular and explains the differences between the different types of estrogen. But for the purposes of this presentation, just recognize that as the ovaries start to shut down, there are going to be little spurts and fits of estrogen. Some days the ovaries will be like, okay, we can make it. And other days they're like, yeah, we're not going to work today. Some studies suggest that using a transdermal estrogen patch by itself may improve depression during perimenopause. Not everybody is down with hormone replacement therapy. I get it. Not everybody's down with psychotropics. It's an individualized decision. However, the research does indicate that as opposed to oral estrogen, transdermal estrogen patches seem to keep the estrogen levels a little bit more stable. So let's talk about the mood related functions of estrogen. We assume that estrogen is the bad guy and it may make us feel irritable and anxious. Well, it can, but. Or when our estrogen levels go up, it can. Within our normal range. When our estrogen starts to starts communicating with those parts of the brain differently during different phases of our cycle, we may have some irritability. Estrogen increases serotonin and the number of serotonin receptors in the brain. Remember I said high levels of serotonin we know is associated with anxiety and irritability and all of those things modifying the production and effect of endorphins, our feel good chemicals is another aspect of estrogen. Estrogen is actually also neuroprotective in in our body. It can help buffer against some stress related damage that may occur when we're under chronic stress. I digress. Estradiol, the predominant form of estrogen, is essential for modulating libido, erectile function and spermatogenesis or the creation of sperm in men. When I talk to people and I talk about estrogen, the responses they give me and even when I do Google searches and stuff, the responses I get are always for biological females. And it's so important to understand that men and women, people of both assigned sexes, have estrogen, have progesterone and have testosterone. And if you think that it is irrelevant, the estrogen in Men is irrelevant. You're wrong. Now estrogen does seem to have a greater impact on women and testosterone tends to have a greater changes tend to have a greater impact on men. Why? Because in both, in each gender, in each sex, they are wired for that particular hormone to be the dominant hormone. And again, when testosterone changes in a female, it's only a small change. Here, when testosterone levels change in a male, it can have, it can be big because there's a lot of testosterone. As testosterone decreases with age, porn use or illness, chronic or, or even chronic stress, estrogen levels tend to increase, which can make older men more vulnerable to mood disorders like depression. And, and I know it, you're like, we're talking about estrogen, but now you're talking about testosterone because they go hand in hand and you can't separate one from the other. We're going to a lot of what we talk about today, you're going to see the bi directional nature and it's important to pay attention to that. When we get down to testosterone, we'll talk more about porn use and in a minute we're going to talk some about chronic stress and trauma. There are some disorders that mimic premenstrual syndrome or premenstrual dysphoric disorder, mood and anxiety disorders. Someone may have generalized anxiety that gets worse when they're in certain phases of their cycle because either their estrogen levels are increasing but still within the normal range, or the estrogen is communicating differently with the serotonin system. We don't exactly know why, but it is important not to dismiss someone as just having PMS because that's invalidating and a horrible thing to do. We need to acknowledge the impact and the intensity of these symptoms and how it, how these symptoms impact all areas of their life. But also look outside of that cycle window and say, are there other times during the month when this person also has anxiety? Because there's going to likely be a different treatment protocol if the person has generalized anxiety versus PMS or pmdd. Postpartum is another time when hormones are just in flux and can be all over the place. And, and that's because the body's healing and the body's adjusting to not growing a little peanut anymore. Also, when people quit breastfeeding, it's important to recognize again that there are significant hormone changes that happen when the mammary glands don't have to produce milk anymore. And for a lot of people, there is an upsurgence of their PMS or PMDD or even postpartum depression during those times. So immediately after the baby is born, as well as when the mother finishes. Lactating is important during menopausal transition. We've already talked about that one. Thyroid disorders. Thyroid disorders will alter levels of estrogen in the body and estrogen availability. They also alter levels of serotonin and cortisol. All of those things can contribute to symptoms similar to PMS or PMDD. By the way, I believe the stat is like 20%, but don't quote me on that, but I think it's about 20% of women may develop hypothyroid in the postpartum period. It's important if you're seeing someone who is in that postpartum period. And, and I use that term pretty liberally to six months after they discontinue lactating. And that's not the traditional definition, I realize, but, but postpartum depression can set in during, you know, a pretty wide range. And the American College of Obstetrics and Gynecology is finally starting to recognize that. We need to look at the first two years. So if someone has given birth within the first two years, we must consider not only postpartum and generalized moot, moot and anxiety disorders. And one thing I don't have on here is trauma, but I'll get to that in a minute. We also need to consider thyroid disorders because the person may have developed postpartum hypothyroid. That is going to explain a lot of symptoms and no amount of talk therapy. It's going to make that top, make that thyroid kick in again. Substance use is another thing. If someone is abusing stimulants, they're going to be more agitated when they're withdrawing, they're going to be more flat and depressed when they are abusing stimulants, they are more likely to experience psychotic symptoms when they are withdrawing from alcohol or depressants. They're a lot more likely to be very agitated, irritable, have low energy. So we need to recognize the symptoms of substance abuse. And some medical disorders can worsen before menes, including migraines, irritable bowel syndrome, and myoencephalitis. We, we need to recognize that chronic fatigue, chronic fatigue syndrome, cfs, is an autoimmune condition. And a lot of autoimmune conditions also worsen before men because as irritability goes up, irritability is a sign of stress. And we know that stress is a trigger for autoimmune issues. There are some things that we can do biologically or that the person can work with their doctor to do biologically to address these things. But then there are other things we can help them work on cognitively, environmentally, interpersonally. During this time, estrogen can increase serotonin synthesis and release as well as enhance serotonin receptor sensitivity and function. Remember I said the estrogen levels may be in the normal range, but during certain times of the month, that estrogen may actually do something to irritate or make the serotonin receptors even more sensitive. Serotonergic neurons in the brain also have been found to contain estrogen inducible progestin receptors. So we need to recognize as well that estrogen, as estrogen goes up, it can trigger the development of or development release of other hormones. Estrogen modulates serotonin transmission, binding and metabolism in the brain regions involved in regulating mood and cognition. Remember, our serotonin availability is dependent not only on how much our body makes, but how quickly it is metabolized, how quickly it's broken down in that synapse and how effectively it binds to the receptors. Is it a problem with not enough serotonin? And this is where I get frustrated, where doctors just start throwing SSRIs at people because that oversimplifies. That's really first order thinking. Some of the physical effects attributed to estrogen include changes in pain perception. Serotonin is very well known to help regulate our pain perception. And when people have low serotonin, they have more pain, they feel more pain, their pain threshold is lower. However you want to say it, estrogen also in high in inhibits the enzyme monoamine oxidase or maoi. And the first generation, I think antidepressants were MAOI inhibitors. These were drugs that people took that when the serotonin was released into that synaptic space, they went in there and prevented that drug, prevented the MAOI from being released and breaking down the serotonin. So it could be reabsorbed. Phenylzine or nardal are two examples. Most people, because of all the side effects, most people are not on maois anymore. However, it is interesting to recognize how estrogen serves the same function, if you will it. It inhibits the maoi, so it prevents the breakdown of serotonin. Chronically elevated levels of estrogen can induce depression by causing functional high hypothyroidism. Not only can that happen during the postpartum period, but anytime. If somebody has chronically elevated levels of est estrogen, this can be genetic. This can be due to some other physiological issue. This can be due to taking supplements that increase Estrogen levels over the counter supplements. Estrogen increases tbg, which decreases the amount of free thyroid hormone available to the body, triggering symptoms of underactive thyroid or hypothyroidism. And I just put that in there. So you have the clinical explanation, the take home message. Too much estrogen can suppress the thyroid. Chronically elevated levels of estrogen and low progesterone can contribute to anxiety. Progesterone is your buffer. It is sort of like GABA to glutamate. Progesterone buffers the stress response or buffers against the estrogen. And estrogen tends to be more associated with the stress response. Estrogen enhances the release of cortisol, our main stress hormone, dopamine, our main motivation, and norepinephrine, our main attention. Go back to that Goldilocks principle. Not enough estrogen, then you're not going to have as much stimulation and release of cortisol, dopamine and norepinephrine. So you're going to feel pretty crappy right in that sweet spot. You're going to feel good. Too much estrogen or too much activity of the estrogen system in whatever way it's communicating can cause the release of too much cortisol, releasing our stress hormones certainly going to make us feel anxious. Dopamine, which motivates us to try to make that stressor stop. So we're in fight or flee and we are really focused on getting the heck out of there. Estrogen decreases the release of gaba, our main calming hormone, and promotes increased glutamate, our main excitatory hormone and dopamine transmission. So as we stop relaxing and get more excitable and more motivated to do something again in the perfect combination and the perfect ratio. That's great. And I don't want to be unmotivated and sitting on the couch all day long, but I don't want to be so excited, so stressed out and so, you know, focused in that fight or flight stage that I can't function. Estrogen reduces the fear response. And I know you're like, excuse me, haven't we been saying that it increases irritability? Yeah, it increases stress, it increases motivation and focus. When we are trying to fight or flee from that angry lion, being scared is not going to be really productive. We need to fight, we need to move, we need to get out. When estrogen is low, people may be more likely to startle and have an exaggerated fear response and increased anxiety. Causes of low estrogen Age. I said it declines as we age. Just the way it is premature ovarian failure, which can happen in people in their 20s, in their 30s. That's why they call it premature postpartum. I mentioned that before. Stress as a result of not getting enough sleep, as a result of hormone changes, whatever's going on during that postpartum period can contribute to reduced estrogen levels. And when the woman is pregnant, the main source of estrogen for that pregnancy is in the placenta. So when the placenta is delivered, after the baby is born, there's a dramatic drop in estrogen, which can be really shocking for people who are sensitive to alterations. Congenital conditions like Turner syndrome, thyroid disorders. So estrogen can cause thyroid disorders, and thyroid disorders can cause low estrogen. If someone is presenting with pmdd, pms, depression, get their thyroid screened. It really, it's not difficult for a doctor to do. Being severely underweight, having poor nutrition or poor nutritional absorption. For example, people who've had bypasses, who have leaky gut, or who are under chronic stress, and they're pretty much whatever they eat just kind of shoots through their system without getting absorbed very well. Those people don't have the nutrients needed for their body to make the hormones. And one of the things that the body needs in order to make your gonadal hormones and any of your steroid hormones is cholesterol. Again, whoa, wait a minute. We've been told cholesterol is bad. Not all cholesterol is bad. We need some in order for our body to be able to manufacture the steroid hormones. And then chemotherapy. Chemotherapy just really screws up the entire system, including the gut microbiome. Let's talk about trauma for a second. Someone who has experienced chronic trauma, Somebody who's experienced trauma and it's gone unresolved. Even if it was an acute trauma and they have now have PTSD or cptsd, they are in a chronic state of stress. We've talked in other videos about how stress is not just mental. Stress is physical. When you over exercise, when you don't get enough sleep, when you're malnourished, when you're sick, when there's inflammation, when you are cognitively overwhelmed or emotionally stressed or overwhelmed, all of those are stressors. And stress triggers the HPA axis. It triggers the stress response and which is good. I mean, it's our body saying, hey, I want to protect you, I want to give you some energy so you can do what you need to do to get safe. Under conditions of chronic stress, though, just like the receptors in the brain become resistant to dopamine in addictions, the receptors in the brain start becoming resistant to cortisol over time. Eventually the brain goes, there's no point in getting upset over anything right now, which is when people go from being stressed out and irritable to just flat there. We talk about the stress response. There's fight, flight, fawn, do whatever you can to make it stop, freeze, and forget about it, or the other F word. And when people experience glucocorticoid resistance, they're at that forget about it stage. They just. They don't have the energy. It has to be something big for their body to actually respond. Glucocorticoid resistance can also extend to other hormones like the thyroid hormone and progesterone gen. Progesterone, estrogen, and testosterone. Why? Because the hypothalamic pituitary areas of the brain have three axes of importance in this the hypothalamic pituitary adrenal axis, the HPA axis. That's our stress response, the HPG axis, which is the hypothalamic pituitary gonadal axis, and that's what we're talking about today. And then there's the hypothalamic pituitary, thyroid or the HPT axis. Whenever one of those is activated, the other two are always activated. Whenever one starts getting out of whack, the other two start also becoming resistant and out of whack. When estrogen sensitivity is reduced as a result of glucocorticoid resistance, so your body's resistant to cortisol as well as estrogen. Adding estrogen therapy may not alleviate estrogen deficiency syndrome symptoms. Instead, it can lead to side effects like weight gain, water retention, and mood swings, which are signs of estrogen excess. Remember what I said earlier, it's not always about your body not having enough or not making enough. In this particular situation, there's plenty of estrogen there, but. But the receptors aren't receptive. They're like, no, we're not opening the door to move this along. So when you add more estrogen, that just floods the synapse and you start getting side effects. Low functioning pituitary gland is also associated in decreased production of sex hormones like estrogen and testosterone and gut microbiome D function. Gut microbes can build hormones like estrogen, progesterone and testosterone through the action of various enzymes, just like how they build neurotransmitters. And when we don't have the right enzymes, when we don't have the right worker crew in our gut to break down what we're eating, we're not going to produce the stuff that we need. Disruptions to the gut microbiome, such as through antibiotic use have also been linked to alterations in estrogen levels. Why is this important? If somebody has Lyme disease or has just taken a two week course of some antibiotic and their mood has been altered, this could be part of the reason. Until their gut microbiome gets back in sync, they may have more symptoms. I in here in Tennessee, Lyme disease is a big issue and I've been on a course of doxycycline more than once to as a preventative measure and that just when you take doxy, a lot of people, my experience and, and my daughter's experience is you are exhausted. You've kind of felt feel like you've got the flu and like it been hit by a Mack truck. And that goes on for actually a couple weeks after you finish the doxy. Why? Because it takes that long for your gut microbiome to get back in sync. High estrogen can be caused by leaky gut thyroid dysfunction. Thyroid can be too low, too high or just right. Stress can disrupt the balance between estrogen and other hormones. Pregnolone, which is a precursor to cortisol, is also a precursor to progesterone. Remember, progesterone buffers against estrogen. Well, if you're under too much stress and your body's going well, I need to use the pregnolone to make the cortisol to survive from this angry lion, then there's not enough pregnolone left over to make the progesterone. So estrogen is just running off and not being reined in by anybody. Pharmaceutical drug use can change gut flora and digestive function and obesity, especially in the abdominal area. And this is true for all of the hormones. Obesity in the abdominal area is associated with higher cortisol. But we also know that visceral obesity and fat cells in general increase the production of estrogen. People who are clinically obese have more systemic inflammation than people who are not. I'm not fat shaming, I'm just saying stating a fact. Progesterone has anti anxiety and neuroprotective effects in the brain. It can influence cognitive function, mood and behavior. When you're stressed out, when you're in fight or flee, your brain is not using those higher order cognitive processes that just ain't happening. So in order to get into your wise mind, the serotonin has to go down a little bit. The estrogen, the norepinephrine, we need to get into our wise mind. We need to down regulate so we can think clearly. And it actually buffers progesterone, can help buffer against the damage that glutamate does when the brain is exposed to it for too long. Progesterone can antagonize the effects of the stress hormone cortisol so that it works against cortisol, helping to mitigate the negative impacts of stress. When people's progesterone is too low, they may experience more anxiety, more irritability. Aha. So let's go back to that men's cycle. When people are in that phase of their cycle where they develop pms, it's often because their progesterone levels are dropping, their estrogen levels are increasing. So when somebody starts feeling irritable, it could be not serotonin, it could be not estrogen, it could be that progesterone dropped too low. So the ratio of progesterone to estrogen to serotonin is out of balance for that person and GABA and glutamate. Progesterone activates the GABA receptors, our natural calming receptors in the brain, and can modulate glutamate, the major excitatory neurotransmitter. Actually GABA is made from glutamate. So when someone gets stressed, their body releases glutamate. When it's time to relax, the glutamate is broken down into gaba, which is great, it's great recycling. But it's important to maintain a balance. Too much GABA and you're going to feel depressed, unmotivated. In addition to having physiological symptoms, too much glutamate, you're going to feel very, very anxious. Progesterone can be converted to testosterone. Can't get rid of the interaction. Progesterone may also modulate the effects of testosterone in the brain and body. And notice I'm not identifying any sex here because it impacts both sexes. Cortisol and progesterone are both made from pregnolone. Progesterone is generally anti anxiety in nature. Estrogen is generally antidepressant. Estrogen generally because it stimulates norepinephrine. Dopamine and cortisol tends to give us more energy when, when it's not, when it's not too much in out of balance. Progesterone typically helps us calm down. Too much of either, however, can produce an on edge feeling. The higher estrogen levels go, the more cortisol is released, making us less able to adapt to stress. That is a statement from one of the articles that's cited on here. But it's also important again to realize that it may not be the estrogen itself. It may be the way the estrogen is communicating or the other hormones and neurotransmitters the estrogen is triggering to be released. High estrogen levels can contribute to subclinical hypothyroidism. So somebody starts feeling depressed, which decreases GABA release. Gabas are natural calming. Now you've got somebody who has no energy, no motivation and they're anxious. Wow. In terms of the stress response, estrogen can activate the HPA axis, our main stress response, and increase cortisol release. It increases dopamine synthesis. Well, when we're in fight or flight, we need some dopamine in order to get motivated to get away from that angry lion. Progesterone modulates the effects of estrogen on the dopaminergic system. We when it is time to relax, when you're safe, progesterone comes in and goes, okay, dopamine, you can, you can go away now. Everything's cool, we can all just relax for a minute. Testosterone can have a significant impact on mood. Low dose testosterone has been shown to improve depression symptoms including fatigue, anxiety and sexual function in both sexes. Testosterone administration in people who are biologically female, in women is still a very debated topic. However, there are a lot of doctors now that are recognizing the importance of bioidentical hormone replacement therapy. And these studies have proven that for some people with treatment resistant depression, low dose testosterone can be a game changer. Depression and anxiety are well known symptoms of low testosterone in adolescent males, but not females. Remember, in people who are male, testosterone is the dominant hormone. So when the dominant hormone has changes, it's going to be more profound than when some of this sub hormones have some changes. So in adolescent males, so they're going through puberty, their hormones are all over the place. Oh wow. There's a decline in salivary testosterone throughout the day due to circadian flux. And this is correlated with an increase in anxiety and depressive like measures in the evening. The adolescent male may wake up in the morning and be attentive and focused and in a decent mood and whatever. And as the day goes on, they lose their attention. They have more difficulty tolerating life on life's terms. They may become more irritable and depressed or have lower energy. We want to recognize that, that testosterone follows a very similar path to our cortisol levels. In the morning our cortisol levels are highest. Get out of bed, do your daily stuff. As it go through the day, it decreases. Same thing is true with testosterone. If you're working with adolescent males, remember that's up to age 24, but especially in that high school age when the hormones are really just starting to figure out what's going on. Some of the mood symptoms, especially if they are in sync with circadian flux, may be due to those circadian rhythms. And the youth will have to figure out how can they work their day in a way that's meaningful based on what their body's doing? They're not going to be able to fight the circadian rhythms very much. They may be able to alter their circadian clock a little bit, but ultimately getting the brunt of their thinking stuff done earlier in the day is going to be more important because later in the day it's going to be harder to learn. Surgical removal of the ovaries increased mood disturbances and depression in females. Obviously because only females have ovaries. This is an effect reversed by testosterone. So you think ovaries, you think estrogen, but testosterone is also made in the ovaries. Androgen, including testosterone, are essential for the production of estradiol by the ovaries. And for people who have premature ovarian failure, that means not only are they not making estrogen to the same level that they need to, they're not making testosterone. And that throws multiple systems out of whack. Testosterone has organizing effects on brain development and several psychological traits and behaviors in both sexes at proper levels. It helps with one's sense of well being and self confidence, which are important aspects of mood. Numerous clinical studies in postmenopausal women and men in andropause showed improvements of learning and memory after testosterone supplementation. Let's think about this. We've got estrogen that tends to increase norepinephrine and dopamine, which are important for learning. But if you have too much dopamine and norepinephinephrine, too much activity in that estrogen system, then it's going to be hard to focus because you're in stress, you're in fight or flight. If you've got too little progesterone, then that's not going to balance or buffer the estrogen. Now we bring in testosterone. If you have too little testosterone, this is also going to make it harder to learn and remember things. Thinking about again, those adolescent males and even adolescent females, hormones all over the place. It makes sense why some days they just have difficulty learning things and remembering things. High cortisol can have a direct inhibitory effect on testosterone production which impacts learning, memory and aggression. And this is another one that I made sure to hyperlink because there are some people that are going to say, well, when men are under stress, their toss testosterone goes up so they can fight or flee. Well, that's actually not what they're finding. So much high cortisol can impact testosterone production. Testosterone is also a reproductive hormone. And when someone is under a lot of stress, the brain goes, yeah, now is not the time to reproduce. It's just not practical to reproduce. So testosterone levels may actually drop. There's a positive relationship between cortisol and free testosterone during exercise recovery. So during this particular event, as cortisol goes up, free testosterone also goes up. That's a head scratcher. This may be due to the concurrent production of both hormones from the same precursor in the adrenal gland. And, and they're thinking that there's also growth hormone that is being created to help the body recover from exercise, which also may impact the cortisol testosterone relationship in the body. There are so many different functions and so many different interactions that we can't make super sweeping statements. We need to recognize and say in most cases, just like with human beings, in different scenarios, when I am interacting with my husband, I act a certain way. When I'm interacting with a stranger, I interact a certain way in different settings, in different contexts. I will act and react in different ways. And our bodies the same way. Our serotonin system, our dopamine system, our stress response is going to react differently under different conditions. Acute stress can temporarily suppress testosterone levels, While chronic stress can have long term negative impacts on testosterone production. What they found is that acute stress temporarily says, okay, not the time to reproduce. When it's when we're all clear, then we'll ramp up testosterone again. Under chronic stress, the body says, you might as well just not worry about making that testosterone anymore because it ain't never going to be safe to reproduce anymore. Over generalized. I know, but ultimately that's what they believe is going on. People also develop glucocorticoid resistance under those conditions of chronic stress. We talked about that earlier, where they start becoming resistant to cortisol, the stress hormone. So cortisol's not coming out to inhibit the testosterone, but testosterone is also not there. The person's going to start feeling pretty crappy. The relationship between testosterone and status seeking behaviors, what we identify as leadership and aggression, is moderated by, by cortisol levels. H Now this is especially true in men because Testosterone is their dominant hormone. So let's think about this. As testosterone goes, as cortisol goes up, testosterone goes down. As testosterone goes up, cortisol goes down. When people have more testosterone, they tend to have less stress, they tend to be less anxious about going into these environments. They feel more empowered. So that testosterone goes up as the cortisol goes down makes sense in terms of serotonin. Testosterone is associated with improved serotonin receptor binding and a reduction of depression and anxiety in people. Estrogen increases serotonin receptor sensitivity, serotonin binding and production. We know this in both sexes. And testosterone does the same thing. Testosterone has to do it as the predominant gonadal hormone in men, and estrogen, being the predominant in women, kind of takes that role. So we see how testosterone and estrogen have very similar roles in the different sexes. And then, you know, when testosterone, when we're talking about testosterone in women, it also has some similar factors, but it is not as much of a driving feature, just like estrogen is, is not as much of a driving hormone in men. Testosterone modulates serotonin receptor activity in a way that directly affects aggression, fear and anxiety. It impacts the emotion processing areas of the brain just like estrogen does, and it can increase fear and anxiety and by increasing serotonin. The central fatigue hypothesis suggests that an increase in the ratio of serotonin to dopamine is linked to fatigue and reduced performance. And, and that's important because as serotonin goes up and dopamine goes down, people are going to feel more fatigued. Think about people who are on antipsychotic medications. They struggle with fatigue. Dopamine helps us have energy. So as serotonin goes up and dopamine goes down, people may start experiencing more fatigue. Therefore, high levels of testosterone may also be associated with depression because the high levels of testosterone are stimulating that serotonin system, which is also potentially reducing dopamine. GABA function and transmission is also enhanced by testosterone. GABA is our main calming hormone, so that's a good thing. Glutamate is reduced. So our main stress hormone, reduced good thing. Low testosterone is associated with decreased GABA levels and function, which may contribute to symptoms of anxiety and depression. Low testosterone, and we're talking out of the range, will means that less serotonin is binding because testosterone increases serotonin binding. So we don't have enough serotonin binding to help us feel okay, and we don't have enough gaba. So we don't have either one of our, you know, predominant calming hormones. Higher Testosterone levels may increase dopamine, which is associated with reward and motivation. Testosterone can affect dopamine receptor density and sensitivity just like estrogen does in women, resulting in increased mood, motivation and cognition. Increased dopamine can also increase cause increases in testosterone and possibly aggression. When people are engaging in addictive behaviors, what do we generally attribute to what's going on in their brain? Dopamine. They're flooding their brain with dopamine. So if somebody is engaging in addictive behaviors, whether it's drug addiction, gambling, porn, whatever, their dopamine levels are just being through the roof, which may also increase testosterone and possibly aggression, which may explain part of the disinhibition hypothesis. When people get are under the influence, they're more likely to do stuff that they wouldn't do if they were sober. Adolescent males have an increased risk of developing psychotic disorders. And again, remember, testosterone is primarily predominant in males, which is why this is male focus, not both genders. This implicates testosterone, basically testosterone overload in the precipitation of dopamine related psychopathology. And this is a really interesting article that talks about how as adolescents go into puberty and the body starts producing copious amounts of testosterone and it's kind of all over the place, sometimes it can over basically overwhelm the brain circuitry, which may lead to damage in the dopaminergic system, which can in some cases contribute to psychotic symptoms. Norepinephrine can be increased by testosterone. Remember, norepinephrine is our focus chemical and can stimulate the conversion of testosterone into estradiol. Well, there we go. Now the estrogen is coming back full circle. Low testosterone levels trigger symptoms such as anorexia, fatigue, decreased libido, which also impact mood. Testosterone has been shown to have antidepressant effects in women with dysfunctional pituitary glands and low testosterone. And again that people with SSRI or treatment resistant depression. This is another avenue that we can explore instead of just kind of throwing up our hands. Here's an example. A 55 year old man named John has been experiencing fatigue, low mood, decreased libido for several months due to low testosterone levels. We don't test blood, we're not going to be making these calls about whether it's too low. But for the purposes of this, he came to your clinic, he had these symptoms, you said, hey John, you know, I'd love to see you. Let's get a blood workup done on you. Go see your doctor to make sure there's nothing going on underlying that can be addressed. Found out his Testosterone levels are low. As a result, low testosterone led to high serotonin, which was contributing to his fatigue and mood changes. They hypothesized that low testosterone levels lead to an increase in serotonin levels as a compensatory mechanism. So when testosterone goes low, the brain says, well, we need to put something in its place. Increased GABA may further exacerbate his fatigue and low energy. As his testosterone goes low, his GABA goes up. Decreased dopamine, low dopamine, low testosterone, low testosterone, low drive, low motivation. You can think about it that way. Also, when our dopamine is low, we have low energy and low cognitive functioning. That doesn't mean our IQ drops. It means it's harder to think we've got more brain fog. And the low testosterone is was also associated with increased norepinephrine, one of our focus chemicals. But it's also a stimulatory or excitatory chemical which also contributed to his anxiety and other mood disturbances. Just low Testosterone in this 55 year old man, which his testosterone may have been low to begin with because of his age or other factors like gambling or something else. Whatever the case, his T is low and it caused all of these other things to get out of whack. The same thing is true in females. When one gets one of the hormones gets out of whack, all of his buddies follow suit. Causes of low T Just like with estrogen, obesity, fat cells make estrogen. The more estrogen in ratio to the testosterone, the the less healthy testosterone signals are sent. So it's important to recognize the obesity increases stress, obesity increases estrogen, obesity increases systemic inflammation and obesity may cause a reduction in testosterone. When testosterone levels decline in men, so does estrogen. All right, well since your body converts some free testosterone to estrogen, we also may see low testosterone. When testosterone levels are declining. Even though the body can convert free testosterone to estrogen, the testosterone is is declining and the estrogen isn't declining as quickly. Insulin resistance and diabetes Elevated insulin and blood sugar create issues with testosterone signaling. This is true in both sexes. Low testosterone levels correspond with higher insulin resistance. More problems with diabetes in men in particular because testosterone is their dominant hormone. Porn, just like other addictions, can disrupt testosterone levels, partly because the body develops a tolerance or a resistance to the testosterone and the dopamine, leading to a lack of stimulation or arousal by women in real life. They found that it's called the andro accelerator hypothesis in sex and porn addiction with when the addiction is related to sex, the combination of dopamine with testosterone intensifies exponentially the impact of the reward and the damage on the dopaminergic system. Sick guts, gut microbiome not healthy, then it's going to impact the level gut impact the body levels of all your hormones and all your neurotransmitters, endocrine disruptors. And this is true again for all of the hormones, especially your gonadal hormones. But we're just talking about it under tea. Chemicals in our air, food and water can act as anti androgenic compounds that can damage testosterone receptors. Bpa we all have heard about getting stuff that's BPA free. Thiolates which are used to make plastic more flexible and pfas which used to be used in non stick cookware are all endocrine disruptors. And fluoride, which is in a lot of our toothpaste and a lot of our water in excessive levels can also be an endocrine disruptor. And it was actually declared. So it's not just me coming off some fringe site with that. Hypertension also can cause low testosterone. The thought is that mental stress might suppress the HPA gonadal axis to decrease testosterone levels. When someone is under chronic stress, they may develop hypertension. We already talked about how chronic stress leads to glucocorticoid resistance and the body reducing testosterone levels. Cortisol's high, testosterone's low. Estrobolo is a collection of microbes capable of metabolizing estrogens. Hormone production takes place in your gut among other places. So when your gut is leaky, when your body's not able to metabolize these estrogens and these other products, you can start to get systemic inflammation. And a leaky gut means that the stuff is being made in the digestive system, but it's actually able to leak out of the walls a little bit, which causes an inflammatory response and an increase in cortisol. Both men and women have testosterone and estrogen and progesterone. Estrogen, testosterone and progesterone impact serotonin, gaba, dopamine, norepinephrine levels. You can't extricate the gonadal hormones from the neurotransmitters. They work in concert. Cortisol reduces the amount of sex hormones because your body says a not not it. It isn't the time to use energy for sex or reproduction. Too much estrogen or testosterone can contribute to anxiety. Too little can contribute to depression. That is grossly oversimplified. It could be that it's poor functioning in one of those symptoms in systems where you have plenty of estrogen or plenty of testosterone, but the system itself is not working. Progesterone balances estrogen. Cortisol is made from pregnolone, which is the same hormone that progesterone. Progesterone is made from. If you're too busy making cortisol, you're going to use up all the pregnolone and then you're not going to have enough basically to make the progesterone to balance out the estrogen. Too much cortisol means too little progesterone and estrogen dominance. Leaky gut also contributes to estrogen dominance and excessive cortisol and systemic inflammation and hypertension, obesity, diabetes and stress all impact the leaky gut as well as hormone levels. The take home message is a lot of our mood and cognitive symptoms can be caused by or exacerbated by hormone imbalances. And a lot of our mood and cognitive symptoms can also exacerbate those hormone imbalances. So it's essential that we work in tangent with a medical doctor in order to make sure we're addressing the mind and body to help people reach their maximal level of recovery.