Good morning. Morning everybody. Welcome. Welcome. Lots of smiling, happy messages about the weather because we're good about talking about the weather. Um, so welcome to week eight and it's steroid hormone week. We're really really excited as usual. It's the last specialist topic of MPP and it's a big one. It's a popular one. Um and this week we are splitting um the session actually into three. Um so apologies for any confusion if you saw a scheduling uh message about the timing. Um but basically because the hormones report is split into three uh we are having three sessions this morning rather than making you sit here for an hour and a half desperate for a break. So we're going to cover steroid hormones first then have a short comfort break about quarter 2 11 224 to 11 then we'll do hormones then we'll have another short comfort break before we look at the HPA axis. So hopefully that will feel a little better paced um and and give you that uh that little break time in between. Okay. And this is where we are in the whole scheme of things. So next week is case study week two and it says focus on detox hormones and nervous. But actually those case studies can be on all of it or any part of it. Um it's an opportunity to tie lots of reports together and understand how we will do that in practice and on a support call. Um so we have room for one more case study um for case study week two. We've already identified one. And if you already submitted last time and you think yours is going to be a good uh a good candidate for week two, case study week two, then please do ping us another email back. Okay, so that's where we are in the big picture scheme of things. Yeah, well done for getting this far as well and sticking with it. We recognize a lot of your uh names and profiles now, which is really really nice. we're getting to know you. Um the whole scope as we've seen here um uh and this is where we're focusing today. As you will see today there are connections between lots of the reports. Um hopefully that sort of message is is coming across clearly. Um how to make the connections and how to think in a connected way as well. Um it's about digging down but also maintaining that perspective uh on everything. Okay. So hormones um I would start by saying so this is the connectedness um this is the hormones pathways and the hormones report was really evolved from our previous estrogen report which just focused on estrogen and that was quite a chunky report in its own right. Um but the reason we've gone beyond estrogen and extended the report to include more about the other steroid hormones and also the HPA axis which is more about the regulation of those hormones. Um lots of reasons but one one of those is hormones tend to be badged as a female thing. So it's like hormones it's it's women isn't it? um and we thought that that wasn't the right impression to give in terms of the scope of our text. So hopefully by the end of this you will agree that the hormones report is relevant to everybody um everybody and anybody and it is it is of course um of interest to women um but it is equally of interest to everybody. Okay. So the pathways this looks a little bit complicated but the the reason for it is to show in gloom these are the genes that are in the hormones report. Um we have things like um all this cluster here um that we're going to focus on today, but we also have some genes that you've seen before um in detox. example, we've got the CYPs, we've got comp um we've got some of these phase 2 detox uh pathways that we saw in the detoxification session that really really do come into their own uh in the context of hormones. Um and we've got some genes that we've seen in the nervous system report as well. So particularly this dopamine adrenaline pathway um think and we'll make you think that the the sex steroid hormones are regulated by the hypothalamus pituitary uh axes. Um and so all these chemicals, the neurotransmitters, things like vitamin D as well as the sex steroid hormones all are regulated uh by our brains and therefore there is this convergence between them. If one part of the process is disregulated or dominant then it can have a knock- on effect on other parts. So everything is connected from that regulatory perspective and there are also shared substrates as well. So hormones are made from cholesterol the sex steroid hormones as is vitamin D. Um tyrrosine is the substrate for dopamine but that's also involved in thyroid hormone uh systems. And so you get I'm sure the point um we can look at things in a particular context but we also should consider uh the bigger picture. Okay. So let's get into hormones. Um why would someone want to do a hormones report or why would you choose the hormones report for your clients? So all these potential uh symptoms uh aspects of someone's health um could be related to steroid hormone imbalance or imbalances as part or as whole of the reason. Um and you see there is a very very uh big set of of symptoms there and it goes way beyond that. Um so as well as the kind of stereotypical u people have estrogen uh estrogenic related symptoms or low testosterone testosterone related symptoms. Um there are behavioral things, there are mood things, there are memory related things, weight related symptoms, etc., etc., headaches. Um all of which could be at least partly due to dysregulation or differences in the hormone pathways. If you can't hear anything, it's difficult to say, maybe a could just type in that chat. um just refresh the browser. Sorry, I'm have difficulty multitasking in terms of talking, reading, and typing at the same time. So, just refresh the URL if someone could type that to help uh Sam out. Thank you. Okay, so beyond estrogen, these are the three sections. Um, we've got the steroid hormones, we've got the estrogen life cycle, and then we've got the HPA, HP axis. And as I said, it's applicable to everybody. a bit like we saw with the nervous system report. We have these multiple pathways um that we've used to summarize and present the results in to help you see at a glance where the reds and yellows are uh for that person. And when you get used to using the reports, some people can just use the the pathways as their clue, as their hints, as their I know what this means and what I'm going to tell my client and how I'm going to use it. Um, but don't forget about the rest of the report. Um, so the rest of the report, we've got the detailed results. Again, every single dot um color on the pathway summary has a corresponding entry behind the scenes with in some cases quite a detailed explanation. In other cases, it might be slightly shorter. Sometimes it's more simple and straightforward. Um but that detail is always there for you. So don't don't forget about that. I honestly go and look at the detailed results still very very often um to remind myself of the nuances or something uh that I might not remember. Okay. And the guide as well. So the guide is a static text in each report. It's just the same for everybody. But I'd really recommend that you read that guide uh or the guide in each report at least once um line by line and then you can know how the report is structured and you know what's there. I sometimes as well like if I just wanted a little reminder of how cortisol fitted into the picture, I'll just do control find on my keyboard look across the whole report for everywhere cortisol is mentioned and it will pop up in all these sections. Okay, so session one steroid hormones. This is the pathway. Um, and what we're going to see, I've split it into uh little subsections for ease. We've got this progesterone component here. Um, then in the middle, we've got cortisol and cortisone. Then we've got androgens in this little green loge here. And then how those androgens are processed. What is the fate of them? um do they go down this androgen pathway to make more potent uh DHT and another newer steroid or are they converted to estrogens? Well, the answer is both but the proportion of each will vary depending on the individual and that is partly genetic and partly environmental. Okay, so let's work our way through and let's start at the very beginning. So we know that cholesterol is the source of all steroids. So cholesterol gets bad rap. It's blamed for heart disease and all those things, but we know that it's got extremely important functions in the body, not least making all these steroid hormones um as well as vitamin D. Okay, so start with cholesterol. Then we've got next next down pregnenolone. And pregnenolone can go in a number of different directions. um across the top here. Um but first of all, we're going to explore the progesterone route going straight down. So progesterone known as the second uh main female sex hormone after estrogen. Also sometimes thought of as the pregnancy hormone. Um it is particularly high in pregnancy and important for sustaining pregnancy. But both men and women do have progesterone. So it has functions in everybody. Um not just women. Um and then we have progesterone being converted through firstly step one uh by five alpha reductase to five alpha dihydrop progesterone and then secondly to alo pragnolone. um which is a neuronactive steroid and we're going to look at these in detail don't worry I'm not just rushing through but alopanolone is a neuroststereroid it is involved in anti-depressant anti-anxiety type effects and it's neuroprotective and you might have spotted you might already know that it interacts with the GABA receptor which we talked about last week. Um, another connection going on there. So, let's let's break it down and look at the detail. So this gene five alpha reductase um it helps uh convert progesterone to 5 alpha DHP um which is the precursor to alop and actually the slow version of this five alpha reducttose gene is very common in Europeans but the frequency is quite different in Asians and I I like to point this out when it is a um that different populations, different heritage um of people can uh be associated with different frequencies of certain genetic variants. Um so more Europeans, majority of Europeans have a relatively slow five alpha reductase gene as conferred by this particular snip. Um, what's important to know here, not only the genotype, but the co-actors. So, we've got NADH, a form of B3, vitamin B3 as a co-actor, a helper. And then we've got this little symbol here, an I, stands for inhibitor um, next to the pathway. And that's there as an eye because there are quite a large number of inhibitors and it would be too busy to put it there. But that's shown on the pathway at the bottom there, a little key to show you what those inhibitors are. Um, and we've spelled it out for you here as well. And you might be thinking, well, why am I interested in inhibiting a five alpha reducttose if it makes this amazing like amazingly good neuroid? Um well, you can have too much of a good thing. We know that. Um most of these chemicals aren't inherently bad or good. Um they've got a function or set of functions, but it's possible to have too much of a good thing. Um and also as we're going to see five alpha reducttose is involved in testosterone conversion as well as progesterone conversion. Okay. So let's just keep on going. Um the next step is a gene called AC R1C4. Doesn't really roll off the tongue. Uh this is the long name for it. Um, its other name is 3 alpha hydroxystereroid dehydrogenase. Doesn't really roll off my tongue either. Um, but 3A HSD is a bit easier to say. Okay. It shouldn't be fuzzy. It shouldn't be fuzzy. The quality of the uh of the slides is pretty good. Okay. and a snip on a R1C4 actually has potentially a very big effect. So this is the quirk about this particular snip. Um its magnitude of impact is quite dramatic or it can be. So if you have a red result on AC R1C4 um that can mean that there is up to 80% less activity or ability to convert uh 5A DHP to AOP. Okay. And because of the neuroststereroid function of alop then this particular snip has strong associations with risk of mood uh disorders uh lots a big range that you see there depression anxiety bipolar etc. Okay so yeah sorry I'm being a little bit distracted by all the technical chat. Um, if you've got technical problems, can you just um refresh the browser and then I can hopefully try and focus on the chat about the content. Much appreciated. Thank you. Um, so the hetrazy it could be about the 60% uh range in terms of percentage hit on activity. But the whole point of this is that we can push that activity up the scale and it's the co-actor power that is within us to to actually do that and manipulate it. So again because there are quite a lot of co-actors that can be helpful in this conversion step. We've just put a little symbol there um activators. Uh that stands for and the the listing is still on the page but it's in smaller letters at the bottom and it's basically all these things here. So omega-3 fatty acids uh PA um the fatty acid version is really really helpful as is evening primrose oil. Hey, haven't you heard about some of these things in the in connection with menopause for example? Um saffron again we've seen saffron haven't we in the context of serotonin uh as well and actually SSRIs at a very low dose um directly help support this pathway. Um, so if progesterone is low, your starting point is low. Your substrate that all of these products come from, if that is low, then the the products will be lower. And that happens in different life stages such as menopause, but also cyclically. Um during a menstrual cycle, a cycling woman will have points in that cycle when progesterone is relatively low and other times when it's relatively high. Um so these are the things that you can do to help support that pathway and also be conscious of the things that inhibit it as well. So stress, chronic stress again, insulin resistance again um can impact that. I've got a little poll for you as well about that particular gene that I'm just going to put up there. Pop up there. Um the R1C4. If you know your genotype, have a little play. Pop it in the poll and see how you compare to other people. Um, haven't got any reds yet, but we've got quite a lot of ambers, which is interesting. Oh, we got one red. Yeah. See, all these variances do happen. They're not all uber rare. Um, so you will encounter clients who have these variances. Okay. Emma, just to double check. Um, we are recording, correct? Yes. Amazing. Why do we think not? Um, just someone pointed it out and I started panicking. So, no. Technically, we're all good as far as I can tell. Sorry about that. No, that's okay. That's cool. It's good to check. Um, right. I'm going to try and get rid of that poll. So it's out of my line of sight though. Very interesting though. Okay. So the whole point of knowing this is obviously so that we can put the pieces together in terms of what clients are experiencing and decide if we want to help support it um in one way or the other with these co-actors. um and inhibitors in terms of encouraging or trying to support uh people to reduce them if this is a problem. And this is the mechanism of action. It's via the GABA receptor um which we've seen and we discussed at length last week. So the GABA receptor as we've seen if there is a snip then that means the receptor is genetically less sensitive and it's not only less sensitive to GABA but it's less sensitive to ALOP. So ALOP binds with the GABA receptor in a similar way to how GABA binds with the receptor and it has GABA like effects. So hence the connection with the anti-anxiety calm uh effects. Okay. Now we also saw last week that there are herbs particularly that can help to support GABA receptors as well. So again, these can be useful for women who lack or have uh snips or environmental factors that are disrupting the alop pool and synthesis um to support GABA in a broader way as well. Now there are also connections through the mood uh effects with things like PMDD. Um so um PMS, PMD, PMDD kind of scale of um negative effects in terms of mood that relate to alterations in hormones. Um and PMDD is related to ALOP. um but it is supposedly not about the absolute levels of alop. So there has been lots and lots of research that's gone, oh we think it's connected to alop and GABA, but it's not been shown to be connected to the absolute level. It's about the altering levels. It's about the shifts. It's about the cycling. And it's thought to be due to tolerance. So when we have a high amount of substrate binding with a receptor, that receptor can adjust and downregulate itself um in order to protect the the system from overload. And that's the tolerance um principle that Gaga that AA presented last week. Um and that applies to most receptors. Um so it is now believed that during parts of a cycle when progesterone is high the the GABA receptors downregulate and do that as an adjustment uh in order to tolerate the high progesterone making more LOP. But what that can mean is when the progesterone falls at the towards the end of the cycle around here and at the beginning actually it's this fall this plummeting that um that that causes those mood uh effects because the receptor isn't plastic enough to bounce back and become ever so sensitive straight away again and respond. respond to that NOP. So it's become downregulated. It's become tolerant to the progesterone. When the progesterone falls, uh then that receptor is less plastic. So that is thought to be the mechanism behind PMDD, but it could also be a mechanism for mood issues that aren't quite as severe as PMDD. um PMS that it's experienced by many many many women for example a similar similar mechanism could well be in play and if you want to look more at that particular topic here are some links to papers um so some of them are really recent as well it is an emerging uh area of research okay yeah exactly na That's a really really good point in terms of the pregnancy effect and post-natal depression as well can be a thing. So, so yeah, that's that's a a a really really good example of another case when people might experience alterations in mood um due to shifts in progesterone and alop. I'm not having this plasticity of receptor to bounce back. And also remember that other environmental factors could reduce the plasticity of that receptor um like alcohol use for example as we discussed last week. We would hope that a pregnant woman is not using alcohol. Um, but actually I've come across cases of PMDD where people are using alcohol as a coping mechanism and it's quite possibly one of the worst things they could be doing um to cope because it's it's it's basically interacting with that receptor and uh making it even less plastic and less responsive. Okay, so that is the progesterone bit. Um hopefully you're all following it. looks like you are from the questions. Um so moving on a little bit to the middle of this page one uh pathway one section to look at cortisol. Um so some progesterone I'm going to zoom in a little. some progesterone um gets converted to 17 hydroxy progesterone and some of it we've seen some of the pregnenolone gets converted to 17 hydroxypnolone and either of these these substrates um can then be made into cortisol and cortisone and support this pathway. Okay. Um there's a gene involved early on um which is 17A1 and you can see that here we're showing an upregulated uh genotype red dot two up arrows. Um it's following the same rule as the other CYP genes that we saw in detox. So CYP genes, we don't really want them to be upregulated um because that can present more toxic intermediaries. We want them to be doing their thing but not excessively. Um so this person has more risk of upregulation and that is added to if there are environmental factors uh like stress, blood sugar dysregulation and alcohol again can push up that activity and force this pathway away from the progesterone route away from the alop and more towards these other uh steroid synthesis. So, it's good to be aware that someone has that potential and then obviously to consider what is going on with them and what's the environment that might be adding to that and what they're able to do to reduce it and work the other way if that's particular area of risk for them. And even if they've got a green result, the environment could be pushing up that uh particular enzyme activity as well. Okay. And then we've got um the 11 beta hydroxy steroid dehydrogenase HSD 11B1. Um and this is involved in cortisone to cortisol conversion. And similarly as with the 17 if it is upregulated that if it is snipped that means it regulated or tendency to upregulate and generate more cortisol. Um now cortisol isn't bad. It's not evil per se. Again a bit like cholesterol. Um, anecdotally and colloally, um, cortisol is often talked about as if it's a really terrible thing. Oh, my cortisol's through the roof. Um, I use that phrase quite often. Um, but cortisol has many, many important functions. So, we want to be supporting cortisol uh production, but we don't want it to be excessive. Um, and so depending on the context of the person who owns this gene, um, we might want to try and slow that down if the cortisol is through the roof. Lots and lots of ways to do that, um, through stress management and things like that, but green tea is a inhibitor of that particular pathway. Whereas licorice could support someone if there is a low cortisol picture. And if you want to gently support that cortisol, um if their cortisol is on the floor and you want to give them a little nudge, you could use licorice. Um not the um not the sweets. I can't remember the name of them now. Um all sorts. Licorice. All sorts. good licorice or medicinal or you know good grade licorice um but with care um because you could you you don't want to do too much um strongly uh for someone in this way. Okay. Um would people need to be more careful with corticosteroid medications? Potentially yes. I mean it's a complicated area um but potentially yes. Um the green tea um EC EGCG cortisol and alop um can it drop al. Yeah, it could. So now think about these things carefully. Green tea in particular, we're going to see it again in part two today in detail. Um but it affects many many things. So think carefully about what you're doing. My personal belief is it's a pretty good thing on the whole. Um but it depends what your objectives are. Yeah. And the same with licorice, you know, be careful, think about um think about the effect and think about what you're trying to do. Um so, thanks very much to those of you who are commenting on that point. Um Cassim and Kaye, much appreciated. Don't just throw things at people um certainly not just off the back of genetics um without a proper console and understanding that person. And that is why we always want a practitioner in the mix with our genetic reports. We don't want people just seeing something and thinking they can go and take a load of licorice uh without proper guidance. Okay. Um, so I'll let you carry on the discussion about that as people with a lot of knowledge um here. So then what happens next? If we carry on across the pathway um we then have SIP 17A1 still pushing further um towards the androgen part of the picture. And this can also all be upregulated obviously when people are under a lot of stress. It's fight or flight. It can be stress. It can be blood sugar. It's a whole vicious cycle. Um which means that someone is being diverted or all these resources are being diverted to some extent away from the rest repair and reproduce part of the picture and towards a fight or flight um set of compounds. Okay. And that can be partly genetic but of course the environmental factors are massive uh in this respect. Okay. Um we want it balanced. We don't want it all in one place or the other. It's about supporting the whole. Okay. So now we're moving over to the androgen pathway. Um which looks very similar to the progesterone one. And here we've got the same genes involved in testosterone to five alpha DHT, a much more potent androgen. Uh and then five alpha DHT to adol. Now Adole is also a neuroststeroid similar to LOP. Um it has gabaogenic effects. Um and so it's important for anti-anxiety. low testosterone, anxiety issues in men. Makes sense, right? Um so it's a parallel pathway. Um women have this pathway too, just like men have the progesterone pathway, but we would expect the the emphasis to be different in males and females. Okay. So we've seen that the five alpha reductase gene performed that progesterone to five alpha DHP and it also performs this testosterone to 5 alpha DHT. Um this is the same result um as we saw. It's the same genotype behind the scenes but we've presented it as green um in this pathway. Is it good? Is it bad? For women, it might be considered to be a good thing to have less five alpha DHT. Um, excess DHT in women is associated with excess hair. Um, her suitism. It's also associated with peacos. Um, in men, um, having too much of that really potent form of testosterone has associations with, um, prostatic hypertrophy and prostate cancer. Um, and at hair loss in men and women. So, we don't want it to be too quick. So again, be careful what you're doing if you're trying to promote that five alpha reductase activity to support the progesterone alop pathway because it's very very difficult to control um the activity in different places. It's the same inhibitors and the same co-actors um that are involved wherever that five alpha reductase uh is. So take care with it whereas I think um the AKR1C4 is a little bit more straightforward that we do want it to be functioning nicely. We do want it to be helping to make these new steroids uh both the alop and the adon. Okay. So interesting can red. So red would be normal activity relatively high of five alpha reductase um and making a robust amount of uh five alpha DHT but it depends on the environmental factors in your life as well. Um you know do you have any of these inhibitors? Do you drink green tea for example? Um what about queretin? um lots of lots of things that can contribute and combine with a genotype to have one effect or another. Okay. So yeah, it's all about the mix. Absolutely. So hopefully that makes sense. Um and the you know the I think the power is in understanding what you can use to adjust adjust fine-tune these pathways uh to help your client it really is about tuning the systems I think rather than hammering in a huge high dose of something or another neuroseroids are pretty delicate things. Um so treat with respect and care. Um in terms of it's it's better to start slow and low and titrate these things up and see what the difference uh is made. Okay. Interesting about the finasteride. So that is a five alpha reductase blocker. Um so it's used to reduce this this pathway as a medication. Um and so yeah, it it could absolutely impact anxiety and mood. That is a potential side effect. Thanks for uh the person who asked that now. So yeah. Okay, good. So looking at both of these together, we're now moving on just about to segue into the next section. So we've looked at how testosterone can be used to make five alpha DHT. Um but testosterone also is the substrate for estrogens. And the gene that is involved in converting testosterone to estrogens is CYP19A1 or SIP 19A1 or aromatodes. Those are all different ways of saying it. Um so testosterone is aromatized um to estrogen and we can see that there is a gene involved in this that can alter uh the rate of that change. it can upregulate it just like the other sips that we've seen and that can mean someone may have more of a tendency to send testosterone to estrogens. Um, is that good or bad? Well, just like we said about the five alpha reducttose, it depends. It's not categorically good or bad to have more or less uh five alpha reductase activity. It depends on the context and sip 19a1 generally we don't want it to be too active. Um we probably or a male client would probably be more concerned than a female client if their profile looked like this and it was weighted towards estrogens. Um but actually we don't want that sick 1901 to be upregulated too much for anyone um because it could result in excess estrogen. So the key message is nothing is good or bad categorically. It's about the relative uh unto amounts and it's about the context of the person. Um, but we can certainly see some patterns and we can certainly connect uh some of these genotypes with certain symptoms in order to then work out what we want to try and do environmentally um to adjust and rebalance and fine-tune these pathways. Okay, so this is a summary from a slightly different perspective in terms of for the progesterone little section. Um, these are the key points. Um, this is what happens to the progesterone. It can make alop interacts with GABA. Here are some of the possible symptoms that someone might experience or some of the considerations to have. And the same goes for when we think about the pull away from progesterone towards cortisol or to androgens or to estrogens. Um, one thing that I didn't cover in detail because in these specialist sessions, we can't cover absolutely every single snip. Um but I will just mention this salt 2A1 um which is associated with higher androgens as well um and that is also a poss risk in women. We know that excess androgens um can be a factor in peacos polycystic ovarian syndrome um and the salt A1 salt 2 A1 gene um can be a factor in that as well. Okay, so that is the end of session one for today. I'm going to have a quick look at the questions. Um just see if there's anything that I think we didn't cover. So I think I've covered the five alpha reductase. The fact that you would see as we see here actually this is the same actual genotype for this person. It's down reggulated. You see there it is in the progesterone context. There it is. In the testosterone context, the down arrows tell you that it's down regulated. In the progesterone context, we would pretty usually consider that to be not a good thing. Um whereas in the testosterone context, it could be considered uh a good or better thing to have a relatively slow five alpha reductase step there. So that's why the color coding is different. But if you were to go to the personalized result for this, it would be the same letters and the description would provide that explanation. So hopefully that's answered CLA's uh question. Um and with respect to the co-actors and inhibitors depends what the context is as to whether you want to use those, you're trying to slow it down or not. um and EGCG. AA is going to discuss that in more detail in session two. So, please bear with us. Okay. So, thanks everybody. Um we're going to end this session, have a little break. We'll call you back into the next one in about 3 minutes at 10 two and we will see you there for estrogen.