You somehow missed the boat on this one didn’t you? We are talking about specifically men that take testosterone and raise the DHT in the serum and the serum levels do not have any physiological effect. Testosterone enters the cell and is converted to DHT where it binds to the receptor. Once that receptor is fully saturated Testosterone or DHT has no further effect. The intracellular levels of DHT are not affected by what you measure in the serum. This is completely different than the studies where we give actual DHT to men. Giving just pure DHT to men decreases testosterone by 70 to 90% and therefore decreases estradiol and leads to a host of issues. The issues of raising DHT by giving pure DHT is the fact that it has a negative feedback on testosterone and estradiol production. But with that said, when we give pure DHT without testosterone, it will lower testosterone an Estradiol there for causing bad effects from the negative feedback loop but the intracellular levels of DHT are not affected by taking pure DHT and raising the DHT 10-20 times in some instances. Read the DHT article and learn somethingThe idea that serum DHT levels are meaningless and only DHT locally generated in tissues from T matters is contradicted by studies that administer pure DHT to men and observe all kinds of hormonal effects consistent with what you would expect DHT to do.
The effects of transdermal dihydrotestosterone in the aging male: a prospective, randomized, double blind study - PubMed
The objective of the study was to investigate the effects of dihydrotestosterone (DHT) gel on general well-being, sexual function, and the prostate in aging men. A total of 120 men participated in this randomized, placebo-controlled study (60 DHT and 60 placebo). All subjects had nocturnal...pubmed.ncbi.nlm.nih.gov
A double-blind, placebo-controlled, randomized clinical trial of transdermal dihydrotestosterone gel on muscular strength, mobility, and quality of life in older men with partial androgen deficiency - PubMed
The efficacy and safety of androgen supplementation in older men remains controversial. Despite biochemical evidence of partial androgen deficiency in older men, controlled studies using T demonstrate equivocal benefits. Furthermore, the importance of aromatization and 5alpha reduction in...
"..high levels of DHT in the blood will act as a hormone.."
Trans scrotal testosterone cream application is a game changer
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It's tissue-dependent, and it seems that even AR saturation in the prostate is not necessarily a done deal. DHT is an anti-estrogen, acting through competitive inhibition and also as an aromatase inhibitor. Raise T and DHT high enough and you can reduce relative estrogenic activity in various tissues, certainly leading to physiological effects.
I think this concept is a slippery slope that we throw around here. While some of the technical observations may be correct that DHT is regulated at the cellular level and serum levels don’t matter, one can argue that this is a very common phenomenon, and none of the stuff we measure in the serum matters.The idea that serum DHT levels are meaningless and only DHT locally generated in tissues from T matters is contradicted by studies that administer pure DHT to men and observe all kinds of hormonal effects consistent with what you would expect DHT to do.
The effects of transdermal dihydrotestosterone in the aging male: a prospective, randomized, double blind study - PubMed
The objective of the study was to investigate the effects of dihydrotestosterone (DHT) gel on general well-being, sexual function, and the prostate in aging men. A total of 120 men participated in this randomized, placebo-controlled study (60 DHT and 60 placebo). All subjects had nocturnal...A double-blind, placebo-controlled, randomized clinical trial of transdermal dihydrotestosterone gel on muscular strength, mobility, and quality of life in older men with partial androgen deficiency - PubMed
The efficacy and safety of androgen supplementation in older men remains controversial. Despite biochemical evidence of partial androgen deficiency in older men, controlled studies using T demonstrate equivocal benefits. Furthermore, the importance of aromatization and 5alpha reduction in...
"..high levels of DHT in the blood will act as a hormone.."
Also, while this phenomenon may be accurate, we don’t really know if full cellular saturation is safe and appropriate for us.
I’m not arguing for or against one side of the discussion. I am merely making comments.
Anecdote: I posted recently about getting labs while feeling shitty on cream. Still waiting on some results, but so far, labs demonstrate modestly, elevated DHT (99) and moderately low estradiol. For the first time in my TRT journey, I am contemplating that some of my negative experiences could be related to low estradiol. I have been a bit of an E2 hater. Is it possible I’ve been wrong all this time? Don’t know. I can fill in details, but want to wait until I have the rest of my labs.
I’m currently trialing cream again, but this time, I added hCG back to my regimen to boost my estradiol levels. Very early, but so far, decent.
Please provide evidence of everything you just wrote because it's a bunch of nonsense. It's not based on any medical literature whatsoever or even physiology. Do you even take the time to read a study such a studies where they gave DHT to men for years and raised it 10 to 20 times normal? What happened did it lead to physiological effects in various tissues, including reducing estrogen activity directly by competitive inhibition or as an aromatase inhibitor? No, the DHT did not, but what it did do is suppress testosterone production, which will therefore lower estradiol since estradiol comes from testosterone. When you give DHT just by itself, it's similar to giving androgen deprivation therapy. Give DHT by itself and you will suppress testosterone by up to 90% therefore shutting down estradiol production as well. I guess we could call that anti-androgen and anti-estrogen affects but it's not through competitive inhibition. They don't compete for the same receptor either. You can do the same with estrogen, it used to be given to men that had prostate cancer as a form of androgen deprivation therapy. If you give estrogen to a man that is not on testosterone, it will shut down his production of testosterone. Same thing happens if you get pure DHT.
And by the way, here is Morgentalers rebuttal to Kims article you posted. The saturation model is fully excepted now, and it doesn't just occur in the prostate. It has been proven over and over again now.
You should really be careful not to continue to promote bro science as your previous statement is full of
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HCG doesn't boost estradiol levels while on testosterone. While on testosterone, it maintains intra-testicular testosterone levels there for maintaining spermatogenesis. It doesn't do anything for estradiol. When not on testosterone, it will raise testosterone levels, therefore, raising estradiol levels.
Actually, we been using testosterone 85 years and I think by now we realize that it's safe. This is nothing but simple physiology. There is actually a plateau affect with regard to taking testosterone. There's a point in which it's not going to make someone feel any better. That is the saturation point. There are a limited number of androgen receptors or estrogen receptors for that matter, and when they are saturated, they will have no further affect on the tissue. It just becomes excess. The reason this is confusing is because bodybuilders raise their levels of testosterone into the tens of thousands. They do that because testosterone acts directly on muscle tissue, and the androgen receptors are up regulated in muscle tissue. Therefore the more you take the bigger your muscles get. This doesn't happen and other tissues that are DHT or estradiol sensitive. There is also a saturation point with regard to testosterone being converted into DHT or estradiol. There comes a point where you can raise testosterone to the tens of thousands but DHT and estradiol will stable because they will plateau because the five alpha reductase and aromatase enzymes are fully saturated. So once you raise testosterone levels to the point that you have saturated the androgen receptors, and the estrogen receptors, you will get no further benefit as far as feeling good. You can continue to gain muscle mass with increasing testosterone, but I feel good effects, have a plateau and that's really based on estradiol. The majority of the feel good effects from testosterone come from it's aromatization into estradiol
"Also, while this phenomenon may be accurate, we don’t really know if full cellular saturation is safe and appropriate for us." Where do you come up with statements like this?
It's not safe to be below the saturation point. How do we know that?. Well, the saturation point for prostate tissue is around 250 ng/dL. Men with low testosterone levels have a higher risk of getting prostate cancer and aggressive prostate cancers. Low testosterone levels are a major risk factor for prostate cancer. We know that now. Testosterone is protective against prostate cancer and it is now being used to treat men with prostate cancer. So just keeping your testosterone levels above the saturation point of 250 is definitely healthy but keeping your levels below the saturation point is definitely harmful.
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Dammit. I hadn’t thought this through, apparently.
@RobRoy, in my situation assuming I want cream to be my primary TRT modality, but also need to raise my E2 levels (still a debatable concept), would you simply add testosterone injections?
I’m still evaluating past labs and current labs, but I am starting to wonder if some of my cream struggles are related to low E2, possibly mediated by high DHT?
I’m trying not to post too much until I have more labs, but one observation I’ve made while on cream is that, despite having very high testosterone and DHT levels, I have no greasy skin or acne issues (minimal at best), and this has been a major issue for me in the past. Oily skin and acne are a hotly debated topic, but I am wondering, in my case, if estrogen is the driving factor, and that while on cream, my estrogen has been low.
All speculation right now.
FunkOdyssey
Seeker of Wisdom
I just posted studies proving that serum levels of DHT do affect tissues that do not have a robust amplification system. You sent an article about how serum DHT is irrelevant to tissues like the prostate that do have such an amplification system, which everyone understands already. In many other tissues, including at a minimum muscle, fat, and bone marrow, high serum DHT does exert hormonal effects. The authors commenting spell this out very clearly.
Until you understand the difference between giving pure DHT and raising DHT by giving testosterone you will not understand. There is a difference.
Ma ̊rin et al. compared the effects of transdermally applied T and DHT to a transdermal placebo treatment on changes in body composition and triglyceride uptake and release from adipose tissue in middle-aged eugonadal men with abdominal obesity who were treated daily with these androgens for 9 months. In response to DHT, circulating mean levels of DHT increased to 223 ng/dL at the end of the treatment whereas mean T levels declined to hypogonadal levels. Elevated DHT was not associated with statistically significant changes from baseline for body weight, body mass index, waist or hip circumference, lean body mass, total fat mass, and subcutaneous fat mass. There was a modest but statistically significant increase in visceral fat. DHT treatment was without effect on triglyceride uptake in abdominal and femoral sub- cutaneous adipose tissue and in lipoprotein lipase activity in abdominal fat.
Giving DHT will significantly reduce testosterone hi, up to 90% there for reducing estradiol as well. In other words, you lose all the wonderful beneficial effects of testosterone and estradiol when you give just DHT. But when you raise DHT by giving testosterone you maintain all the wonderful, beneficial effects of testosterone, estradiol, and DHT. You give testosterone and you raise free testosterone levels, which then enter the cells in DHT and estradiol, sensitive tissues, and then are converted to DHT and estradiol. Once those receptors are fully saturated, which occurs at a fairly low testosterone level, then the DHT and the estradiol are just excess. Once the receptors are saturated, what in the heck can they bind to to exert in a response? please answer me that? We are measuring excess at that point, and not what is at the cellular level.
And by the way what you provided was nothing more than abstract surfing, which is not good. Abstract surfing to try to make a point is not a good way to make a point because you obviously didn't read the articles themselves and understand the articles.
You increase estradiol by increasing free testosterone. That's how you do it. I don't see any reason why someone would need to add injections. In the right hands and utilizing a properly compounded cream the levels are at times equivalent to what one would have to inject 3 to 500 mg of testosterone cypionate a week to get. Also, remember what you're measuring in the serum with regard to estradiol is not what is occurring at the cellular level. It's what is aromatize peripherally, which doesn't represent what is occurring in the tissue. Making adjustments on serum levels of estradiol or DHT are incorrect. Instead of trying to follow surrogate numbers, why don't you just focus on how you actually feel. The problem is is that a lot of men want problems to be corrected that are not related to their hormones. So they'll make all these adjustments and measure all of the surrogate values on a continual basis, which is like a dog chasing its tail. If a person has symptoms of a deficiency, can you raise levels to overcome any deficiency, and then whatever improves was most likely related to the hormones and whatever doesn't was not. It will need to be addressed in another way. Also, nobody feels great all the time, no matter how great your hormones are. So many factors going to how we feel and function on a daily or weekly or even monthly basis besides hormones. Hormones, including testosterone do not make everyone feel good all the time. There's just so much miss information out there on what it does and doesn't do.
I also don't know of anyone with cream struggles. I don't even know what that means. I just don't see it. Look 90 to 95% of men that are on injections are fine with it but there's going to be five or 10% that hate it and don't like it and it just doesn't work for them and the same is going to hold true for cream. If one way doesn't work just use the other. It doesn't matter how you take testosterone. It's the free testosterone level that matters. It's what is converted into DHT and estradiol in the target tissues. It's all about the free testosterone. And the compare apples to apples you would have to inject daily to really be able to compare to daily cream. There are no significant peaks and troughs, but instead just a nice little sine wave, when utilizing a daily injection or cream. And then it's just simply finding the level that improves your symptoms and avoids any unwanted side effects. It's just a simple, balancing act. The problem is a lot of men want testosterone to improve symptoms that are unrelated to it.
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And also, you do realize that when you measure estradiol, you're measuring a snapshot in time. If you were to measure it eight hours after you did, it would've been a different number. Trying to compare and estradiol level doing injections and then comparing it to cream is futile. The number is always going to be different depending on the timing of when you test it. Do men really think that their estradiol levels stay constant day in and day out when they're on testosterone? It doesn't work that way. Even if you're on injections in measuring your estradiol, that number is going to change depending on when you test it relative to your injection. When you are on cream, the estradiol levels are going to change, depending on when you test it relative to your application. So trying to compare your estradiol levels while on injections, and then on cream is not comparing apples to apples. You are better off looking at one number and one number only for the most part and that is your free testosterone level and then you're symptomatic improvement. Find a free testosterone level that improves your symptoms and allows you to avoid any unwanted side effects. A stable and fairly consistent free Testosterone level tends to work best when you can avoid any significant peaks and troughs. Just a simple little sine wave with regard to levels.
Charliebizz
Well-Known Member
I think most guys like @Fortunate just do not give things time to level out when the switch to cream. I know I was one of them. I had a rough start with it. But I also made it a lot worse from all the overthinking and constantly messing with the dose. I also think guys pay way too much attention to serum levels of testosterone. @RobRoy might be able to explain this way better than me. But I just don’t think because you serum levels dip you’re going to feel it like guys think they will. I’ve been on vacation and my timing of application has been all over. I’ve missed my evening dose. I’ve went swimming 1 hour after application. And I feel completely fine. i think these “crashes“ people speak about are just what happens to normal people. And they like to act like it didn’t happen on injections or off trt. So why did you get on trt in first place. And why are a lot of guys looking to switch to creams.
love or hate @RobRoy since I’ve followed his line of thinking in regards to trt Its Been the best I’ve felt in years. My only problem is when I feel good I want more and start fucking around With other things lol.
Good to hear, but just understand there is a plateau to the feel good effects of testosterone. That plateau is whenever the androgen, receptors, and more importantly, the estrogen receptors are fully saturated. Raising testosterone past that point will only result in excess, but yes, it will increase lean muscle mass as I've already explain, because testosterone ask directly on the muscle tissue, and there is an up regulation of androgen receptors with increasing levels of androgens. Also, the plateau will occur no matter what because you can only make so much DHT and estradiol from testosterone, because the five alpha reductase enzyme, and the aromatase enzyme also have a saturation point. So there are two saturation points and the first is the receptors, and the second is the enzymes that create testosterone's active metabolites. These are things that nobody talks about because so many want to ignore the real physiology of how testosterone works. And if everyone likes you, then you're doing something wrong if you understand what I mean by that statement.
And I'm going to take it a step further, but not get into too much detail on this forum, but I will leave you with this question.
Could it possibly be that we are more sensitive and responsive to our own production based on the complexity of the physiologic events involved in steroidogenesis, how it is released, and how it exerts its biological effects? When we bypass these complex physiologic events does it have an effect on our response to testosterone? Do we need more when given exogenously to exert the same physiologic effect as when we produce it endogenously?
When we see dozens of studies where testosterone doesn't work, the common denominator is that they only raised it a little bit. They aim for a physiologic number such as 450 to 700 for instance. Did this number come from any medical data that shows this is the right way to do it or that it is the best way to do it for it to work? The answer is no. So why do we keep doing it that way? Well that's because it's the way it's always been done because someone thought that that would be a good idea. Was it a good idea and has it proven to be the best most effective way to give testosterone?
Does aiming for a specific number work better than actually treating with pharmacologic dosing for a physiologic response? Insulin is a hormone. Should we not treat patients with testosterone like we do with insulin. We give the patient enough insulin to normalize their blood glucose. Should we not treat men with testosterone in the same way and give them a dosage of testosterone that improves their symptoms and not stop at a specific number such as 700 for instance, and say well this is all you get and if you're not better it's because it's not testosterone etc.? There is no medical data to support the way we presently treat men with testosterone in that aiming for that specific number that all the guidelines recommend is the best way. From a clinical standpoint you see, over and over again that levels outside the normal range work the best. I'll ask again is it because that when we make it ourselves we don't need as much because we are more sensitive and responsive to it based on the complex physiologic mechanisms involved. When we bypass all of that and just give the end product testosterone, it tends to take more to get the same effect.
Every man has his own number. Some men make a little bit go a long way, and some take a lot to go a little ways. It has to do with multiple factors which we can't go into now, but one being of course their androgen receptor sensitivity level. And yes, outside the normal range means super physiologic for a lot of men. There's no harm in that what so ever.
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Charliebizz
Well-Known Member
Well for me personally the last 3 years on trt I tried to stay some what conservative with my numbers. my assumption is switching to cream keeps me closer to where I need to be more of the time. Where injections give me too high peaks and lower valleys.
Appreciate the feedback.
I actually do understand how much these levels can vary throughout the day. I have a very specific and relatively new phenomenon that I’ve been experiencing for about six months. I have been extremely deliberate and have worked through a process of elimination to try to figure out what is causing it.
I experienced a daily, recurrent and episodic fatigue that is fairly strong and significant. It starts around the same time every day, and it tapers off within a few hours, but it makes those several hours very difficult to function.
I fully get it. I know hormones are not the source of all struggles, nor are they the solution. However, it has been a head scratcher for me, and I’ve been trying to figure out what’s going on.
When I got those estradiol levels recently, I did it specifically while I was experiencing one of these fatigue episodes.
Again, appreciate your input.
Charliebizz
Well-Known Member
I understand what you’re saying. But you based off your postings and our conversations I think you’re still changing things way too fast. I’m telling you from personal experience it took me a few months to adjust to cream. And now that it works well for me I can play with the dosage and it doesn’t really effect me to much. But it took a 2-3 months of staying on a decent dose to get to this point. I’m not trying to give you shit at all. I just want to see you feel good. You need to pick a dose of the cream that gets you good levels and just ride it out. At first. I was having anxiety and Fatigue. but Now I’m pretty stable. Especially when I stop blaming everything on my trt protocol
If your free testosterone is optimal, which I doubt that it actually is, then you need to be looking at thyroid. That's the real problem. Everybody wants to attribute everything to testosterone and then when it's not going right for them, blame it on estradiol. You do realize that most of the fatigue that a lot of men attribute to testosterone is actually their thyroid. It's one of the most common things that I see is that men thinking that their testosterone is not working, because it didn't improve their fatigue because their fatigue was actually their thyroid needed to be optimized. It's not estradiol. Let me repeat. It is not estradiol. In fact, from a personal standpoint, when my testosterone was fully optimal. I still had persistent significant fatigue, especially early afternoon that lasted for several hours, making it difficult to even work and stay awake. It was thyroid. The symptoms of suboptimal thyroid are not any different than suboptimal testosterone symptoms. They look the same and most areas that's why men need both of them optimized in many instances. It's not estradiol I will assure you of that. From from an observational standpoint, then that would mean that every woman that we know that's pre-menopausal, would have quite severe fatigue for two weeks out of every month because for two weeks their estrogen is low and the other two weeks it is high. What were your thyroid levels specifically your free T3 level during one of these episodes? What was it? Why did you just measure your estradiol? What is the mechanism behind low estradiol causing fatigue? It's your thyroid until proven, otherwise. Another mechanism that a lot of men miss is, they have undiagnosed and untreated, sleep apnea. But it's never estradiol causing the symptoms that you were describing. You can blame it on it all day long but that's not what it is.
Charliebizz
Well-Known Member
What happens when you’ve tried to optimize thyroid and only leaves you feeling worse ?
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