First post. Can’t get E2 under control, starting to worry

[Deleted member 43589]

It's called Androgen receptor sensitivity. Some men can't tolerate a lot and they can make a little bit go long ways and others take a lot to go a little ways. It's as simple as finding the dose that improves the symptoms of the deficiency while avoiding any unwanted side effects. It's not aiming for any specific level and men or so caught up in numbers that they just can't understand that simple fact. If a level of 700 improve symptoms then that's the number and if the level is 1500 to resolve symptoms that's the number. But whatever number it is it has to be balanced against any unwanted side effects. No one should have to add any additional chemical or drug to control side effects no different then we didn't need to take any chemicals or drugs when we were teenagers or in our 20s when we had excellent testosterone levels. And the receptor saturation is not a theory it's proven in the medical literature, and in medical physiology. People just want to ignore physiology, but this receptor saturation is fully understood. The one thing that we haven't found, though is the saturation point in muscle tissue that's why bodybuilders are as big as they are.

The saturation point for muscle hypertrophy may not exist, which may be why the top pros are getting bigger and bigger over time:

These mechanisms through the use of anabolic steroids and training include:

* Enhanced protein synthesis
* Enhanced growth factor activity (e.g. GH, IGF-1, etc.)
* Enhanced activation of myogenic stem cells (i.e. satellite cells)
* Enhanced myonuclear number (to maintain nuclear to cytoplasmic ratio)
* New myofibril formation

As training continues with the use of anabolic steroids more myogenic stem cells are activated as are myonuclear numbers and probably myofibril formation. Of course all of this is very dependent on requires consistent "effective" training, massive amounts of food, and most importantly, time.

 

[FunkOdyssey]

I’m a little confused. If they are at full saturation at 700tt. Why would they get side effects going higher then ?

Well, we haven't spoken about estrogen receptors here yet. Surely those are not saturated when your testosterone is at 700 ng/dL, leaving plenty of opportunity for higher dosing to stimulate more estrogen signaling.

Maybe this is a good time to talk about the relevance and effects of serum E2. The party line from the anti-AI crowd is that E2 is a paracrine hormone and serum E2 is a meaningless artifact of spillover from tissues, not worth measuring or being concerned with. It is the same logic that is being applied above to DHT.

Interestingly, some men have had superior results with TRT when they take estradiol valerate alongside it, either in the form of oral tablets or injections. When they do this, estradiol is introduced systemically, acts as an endocrine hormone, and improves their experience of TRT with better mood, libido, relief of joint pain, etc. In fact if I recall correctly, @RobRoy has himself experimented with estradiol valerate tablets.

Should we be surprised that estradiol can act as an endocrine hormone in humans? Of course not. That is how it operates in women. We can even perform gender transitions in men by administering anti-androgen drugs together with estradiol valerate at 2-4 mg daily.

Even in the naturally functioning male, circulating estradiol plays a key role as the primary regulator of gonadotropin secretion. Our HPTA system is set up to measure estradiol in the blood and then regulate output of gonadotropins to maintain a target level of estradiol in serum. Think about that when you hear people try to minimize the importance of serum estradiol. It is almost as if testosterone is just an incidental byproduct of the real mission of the HPT axis, which is to hit that level of serum estradiol it is looking for. Hence in obesity, the excessive aromatization in fat tissue allows you to hit the HPTA's estradiol target with much lower levels of testosterone, leaving you hypogonadal.

Between the easily observed effects created by raising serum E2 with exogenous estradiol, and the prime importance our own brain and biology places on maintaining serum estradiol at a given level, why do we continue to buy into this idea that serum E2 is meaningless in men on TRT? Just because the source of the E2 is spillover from tissues, we are to assume it exerts no systemic effects? The E2 spilling over from tissues acts magically different than E2 introduced via a pill or an injection? The logic falls apart upon closer examination.

Just to be clear, I am not advocating for any form of aromatase inhibition or estrogen blocking. I just want to open minds to the possibility that high serum levels of estradiol may actually be affecting you when they occur. Maybe those effects are all positive. Maybe they aren't.

 

[Cataceous]

It's because the cream will raise free testosterone levels better than injections for any given total in the same man. ...

I'm curious about the basis for this claim. An experimental determination seems challenging, given variable absorption of transdermal testosterone. On the theoretical side, if heightened conversion of testosterone to DHT effectively increases the underlying metabolic clearance rate constant for testosterone then downward pressure on free testosterone is the result. To increase free testosterone you'd need to instead decrease the effective metabolic clearance rate.

 

[Cataceous]

I would imagine it probably has to do with whether one was primary/secondary hypo as well when they started?

When I added in 500iu of HCG twice per week, my trough level on my protocol at the time increased from 950 to 1265, and E2 from 34 to 66 with no other changes. I'm pretty sensitive to it, I can go years without using it and within 2 shots I have a drastic difference in testicular size.

I did have secondary hypogonadism, with TT in the low 300s ng/dL and SHBG in the low 40s. I'm not surprised about low endogenous T production under ENC/GnRH, because the gonadotropins are not much over bottom-of-range — even so preventing testicular atrophy. But you'd think I'd have seen some endogenous T production with 300 IU hCG EOD.

 

[RobRoy]

I'm curious about the basis for this claim. An experimental determination seems challenging, given variable absorption of transdermal testosterone. On the theoretical side, if heightened conversion of testosterone to DHT effectively increases the underlying metabolic clearance rate constant for testosterone then downward pressure on free testosterone is the result. To increase free testosterone you'd need to instead decrease the effective metabolic clearance rate.

Well, I can let you spend 10 years discovering. Why like I did. I could send you all the medical literature to tell you why. But let me summarize it real quick for you. When you apply transdermal testosterone you do increase serum DHT levels because of the five alpha reductase enzyme in the skin. You will significantly increase DHT levels in the serum with a transdermal approach compared to injecting testosterone. DHT has five times the binding capacity to SHBG than testosterone. So when you increase that serum DHT level significantly, it's going to bind the SHBG therefore, freeing up testosterone. That's why for any given number in the same man the cream will raise free testosterone levels better than injections. We see it clinically every single day of every single week. And so funny that you guys try to make things so complicated. The variable absorption of men is why we adjust dosage to each individual. We raise free testosterone levels in each man when we use a transdermal method by adjusting dosage accordingly. When you make a statement like you just did to try to imply intelligence on the subject, it just shows that men don't understand true physiology, and how simple this all can really be

 

[RobRoy]

That's the current state of medical science. There are still many open questi

Well, we haven't spoken about estrogen receptors here yet. Surely those are not saturated when your testosterone is at 700 ng/dL, leaving plenty of opportunity for higher dosing to stimulate more estrogen signaling.

Maybe this is a good time to talk about the relevance and effects of serum E2. The party line from the anti-AI crowd is that E2 is a paracrine hormone and serum E2 is a meaningless artifact of spillover from tissues, not worth measuring or being concerned with. It is the same logic that is being applied above to DHT.

Interestingly, some men have had superior results with TRT when they take estradiol valerate alongside it, either in the form of oral tablets or injections. When they do this, estradiol is introduced systemically, acts as an endocrine hormone, and improves their experience of TRT with better mood, libido, relief of joint pain, etc. In fact if I recall correctly, @RobRoy has himself experimented with estradiol valerate tablets.

Should we be surprised that estradiol can act as an endocrine hormone in humans? Of course not. That is how it operates in women. We can even perform gender transitions in men by administering anti-androgen drugs together with estradiol valerate at 2-4 mg daily.

Even in the naturally functioning male, circulating estradiol plays a key role as the primary regulator of gonadotropin secretion. Our HPTA system is set up to measure estradiol in the blood and then regulate output of gonadotropins to maintain a target level of estradiol in serum. Think about that when you hear people try to minimize the importance of serum estradiol. It is almost as if testosterone is just an incidental byproduct of the real mission of the HPT axis, which is to hit that level of serum estradiol it is looking for. Hence in obesity, the excessive aromatization in fat tissue allows you to hit the HPTA's estradiol target with much lower levels of testosterone, leaving you hypogonadal.

Between the easily observed effects created by raising serum E2 with exogenous estradiol, and the prime importance our own brain and biology places on maintaining serum estradiol at a given level, why do we continue to buy into this idea that serum E2 is meaningless in men on TRT? Just because the source of the E2 is spillover from tissues, we are to assume it exerts no systemic effects? The E2 spilling over from tissues acts magically different than E2 introduced via a pill or an injection? The logic falls apart upon closer examination.

Just to be clear, I am not advocating for any form of aromatase inhibition or estrogen blocking. I just want to open minds to the possibility that high serum levels of estradiol may actually be affecting you when they occur. Maybe those effects are all positive. Maybe they aren't.

I don't believe a saturation occurs at 700 that would be Peter Attia

 

[RobRoy]

Well, we haven't spoken about estrogen receptors here yet. Surely those are not saturated when your testosterone is at 700 ng/dL, leaving plenty of opportunity for higher dosing to stimulate more estrogen signaling.

Maybe this is a good time to talk about the relevance and effects of serum E2. The party line from the anti-AI crowd is that E2 is a paracrine hormone and serum E2 is a meaningless artifact of spillover from tissues, not worth measuring or being concerned with. It is the same logic that is being applied above to DHT.

Interestingly, some men have had superior results with TRT when they take estradiol valerate alongside it, either in the form of oral tablets or injections. When they do this, estradiol is introduced systemically, acts as an endocrine hormone, and improves their experience of TRT with better mood, libido, relief of joint pain, etc. In fact if I recall correctly, @RobRoy has himself experimented with estradiol valerate tablets.

Should we be surprised that estradiol can act as an endocrine hormone in humans? Of course not. That is how it operates in women. We can even perform gender transitions in men by administering anti-androgen drugs together with estradiol valerate at 2-4 mg daily.

Even in the naturally functioning male, circulating estradiol plays a key role as the primary regulator of gonadotropin secretion. Our HPTA system is set up to measure estradiol in the blood and then regulate output of gonadotropins to maintain a target level of estradiol in serum. Think about that when you hear people try to minimize the importance of serum estradiol. It is almost as if testosterone is just an incidental byproduct of the real mission of the HPT axis, which is to hit that level of serum estradiol it is looking for. Hence in obesity, the excessive aromatization in fat tissue allows you to hit the HPTA's estradiol target with much lower levels of testosterone, leaving you hypogonadal.

Between the easily observed effects created by raising serum E2 with exogenous estradiol, and the prime importance our own brain and biology places on maintaining serum estradiol at a given level, why do we continue to buy into this idea that serum E2 is meaningless in men on TRT? Just because the source of the E2 is spillover from tissues, we are to assume it exerts no systemic effects? The E2 spilling over from tissues acts magically different than E2 introduced via a pill or an injection? The logic falls apart upon closer examination.

Just to be clear, I am not advocating for any form of aromatase inhibition or estrogen blocking. I just want to open minds to the possibility that high serum levels of estradiol may actually be affecting you when they occur. Maybe those effects are all positive. Maybe they aren't.

We use it to improve dyslipidemia because it is metabolized in the liver and improves our lipid profile. That's why we use it. But we're also all saying is that what you're measuring the serum is no reflection of what's at the tissue level. It's a meaningless measurement. And don't extrapolate what happens to obese men that have high estradiol that are not on testosterone what happens when we give obese men testosterone and then raise their estradiol. And maybe those men that are injecting estradiol to get the improvement in the areas that you're mentioning should try increasing estradiol by raising their free testosterone level. And when we give estradiol to men that want to transition it chemically castrates them. Its negative feedback shuts down testosterone production. In fact, medicine has utilized estrogen to chemically castrate men with prostate cancer. So what you're doing is trying to look at baseline observations of high estradiol and men, and apply that to raising estradiol in men by giving them testosterone. Yes we can agree that high estradiol in obese men will decrease testosterone production. But we also have to agree that when we give men testosterone and raise estradiol in men that already have high estradiol it doesn't cause any harm, but instead benefit. I can literally provide you with dozens of studies, giving testosterone to morbidly obese man that had high estradiol levels because they were morbidly obese, and provided them with nothing but benefit. But then, when we give men testosterone and block estradiol with an aromatase inhibitor, they get fatter. It's because what you're measuring the serum is spill over as well as what's produced peripherally, and we try to block what we are measuring in the serum, we cause damage at the tissue level. So, when we raise estradiol with testosterone, or we take estradiol, it has a positive effect on our lipid profile and provides us with cardiovascular protection. And that's due to How estradiol is metabolized. And a whole other topic is the non-genomic effects of testosterone and estradiol, etc. But we're talking about is the genomic effects
And as far as spill over goes once again, you're not understanding that what's in the serum is in the serum and not doing anything because you can measure it in the serum. Where estradiol is exerting his actions is in the tissues. Testosterone is converted into estradiol in the tissues where it binds to its receptor. You can't measure that.

 

[jmbb]

I did have secondary hypogonadism, with TT in the low 300s ng/dL and SHBG in the low 40s. I'm not surprised about low endogenous T production under ENC/GnRH, because the gonadotropins are not much over bottom-of-range — even so preventing testicular atrophy. But you'd think I'd have seen some endogenous T production with 300 IU hCG EOD.

Individual response strikes again. I've definitely seen people get no response, some response, or a high response based on labs.

One thing I haven't really seen is HCG "backfill" by boosting the pregenolone/dhea levels as strongly as people claim it does...or at all, really. It may, but I've personally never seen anyone post before/after bloodwork to prove it.

 

[Charliebizz]

We use it to improve dyslipidemia because it is metabolized in the liver and improves our lipid profile. That's why we use it. But we're also all saying is that what you're measuring the serum is no reflection of what's at the tissue level. It's a meaningless measurement. And don't extrapolate what happens to obese men that have high estradiol that are not on testosterone what happens when we give obese men testosterone and then raise their estradiol. And maybe those men that are injecting estradiol to get the improvement in the areas that you're mentioning should try increasing estradiol by raising their free testosterone level. And when we give estradiol to men that want to transition it chemically castrates them. Its negative feedback shuts down testosterone production. In fact, medicine has utilized estrogen to chemically castrate men with prostate cancer. So what you're doing is trying to look at baseline observations of high estradiol and men, and apply that to raising estradiol in men by giving them testosterone. Yes we can agree that high estradiol in obese men will decrease testosterone production. But we also have to agree that when we give men testosterone and raise estradiol in men that already have high estradiol it doesn't cause any harm, but instead benefit. I can literally provide you with dozens of studies, giving testosterone to morbidly obese man that had high estradiol levels because they were morbidly obese, and provided them with nothing but benefit. But then, when we give men testosterone and block estradiol with an aromatase inhibitor, they get fatter. It's because what you're measuring the serum is spill over as well as what's produced peripherally, and we try to block what we are measuring in the serum, we cause damage at the tissue level. So, when we raise estradiol with testosterone, or we take estradiol, it has a positive effect on our lipid profile and provides us with cardiovascular protection. And that's due to How estradiol is metabolized. And a whole other topic is the non-genomic effects of testosterone and estradiol, etc. But we're talking about is the genomic effects
And as far as spill over goes once again, you're not understanding that what's in the serum is in the serum and not doing anything because you can measure it in the serum. Where estradiol is exerting his actions is in the tissues. Testosterone is converted into estradiol in the tissues where it binds to its receptor. You can't measure that.

so what is happening when a man doesn’t get much symptom relief at say 700tt but boosts it slowly overtime. Starts to get symptom relief but also side effects ?

 

[Cataceous]

Well, I can let you spend 10 years discovering. Why like I did. I could send you all the medical literature to tell you why. But let me summarize it real quick for you. When you apply transdermal testosterone you do increase serum DHT levels because of the five alpha reductase enzyme in the skin. You will significantly increase DHT levels in the serum with a transdermal approach compared to injecting testosterone. DHT has five times the binding capacity to SHBG than testosterone. So when you increase that serum DHT level significantly, it's going to bind the SHBG therefore, freeing up testosterone. That's why for any given number in the same man the cream will raise free testosterone levels better than injections. We see it clinically every single day of every single week. And so funny that you guys try to make things so complicated. The variable absorption of men is why we adjust dosage to each individual. We raise free testosterone levels in each man when we use a transdermal method by adjusting dosage accordingly. When you make a statement like you just did to try to imply intelligence on the subject, it just shows that men don't understand true physiology, and how simple this all can really be

If you had been following the discussions on ExcelMale then you would know that it is dated thinking to believe that an effective reduction in SHBG raises free testosterone. Here's a thought experiment for you: Imagine a guy with a normal HPTA that is regulating for its desired level of free testosterone. In order to use the Vermeulen calculator, assume that free testosterone is 15.1 ng/dL, TT is 650 ng/dL, ALB is 4.3 g/dL and SHBG is 30 nMol/L. The calculator tells us that 295 ng/dL of the total testosterone is bound to SHBG. Now imagine removing half of the guy's SHBG, including what's bound to it. What is the result? For one thing, SHBG is reduced to 15 nMol/L. My question for you: what pressure is there on free testosterone to change? The answer is none. The HPTA is still happy because it is seeing the desired 15.1 ng/dL of free T. With the SHBG we removed we have also removed 295/2 = 147.5 ng/dL of total testosterone, leaving 650 - 147.5 = 502.5 ng/dL. Is this a stable equilibrium? Yes, according to Vermeulen these new values for SHBG and TT result in the same 15.1 ng/dL of free testosterone.

 

[Charliebizz]

If you had been following the discussions on ExcelMale then you would know that it is dated thinking to believe that an effective reduction in SHBG raises free testosterone. Here's a thought experiment for you: Imagine a guy with a normal HPTA that is regulating for its desired level of free testosterone. In order to use the Vermeulen calculator, assume that free testosterone is 15.1 ng/dL, TT is 650 ng/dL, ALB is 4.3 g/dL and SHBG is 30 nMol/L. The calculator tells us that 295 ng/dL of the total testosterone is bound to SHBG. Now imagine removing half of the guy's SHBG, including what's bound to it. What is the result? For one thing, SHBG is reduced to 15 nMol/L. My question for you: what pressure is there on free testosterone to change? The answer is none. The HPTA is still happy because it is seeing the desired 15.1 ng/dL of free T. With the SHBG we removed we have also removed 295/2 = 147.5 ng/dL of total testosterone, leaving 650 - 147.5 = 502.5 ng/dL. Is this a stable equilibrium? Yes, according to Vermeulen these new values for SHBG and TT result in the same 15.1 ng/dL of free testosterone.

In my case @RobRoy theory doesn’t seem correct. First labs are on injections. Second is on cream.

 

[Cataceous]

In my case @RobRoy theory doesn’t seem correct. First labs are on injections. Second is on cream.

The problem is that you don't have a very accurate idea of the transdermal absorption. He will claim that you're getting less testosterone with the cream. It's not a simple experiment when done this way. But one might be able to demonstrate the principle by injecting X mg of a testosterone ester for a period and comparing it to injecting both Y mg of the same ester of DHT and X - Y mg of the testosterone ester — ignoring the minor difference in the weights of T and DHT. In this case you have effectively pre-converted the T to DHT and don't need to rely on the skin and its uncertain absorption. Clearly by increasing the fraction of DHT in the combined dose you could force free testosterone to be as low as you like, mimicking the skin being highly efficient at the conversion. This is going in the opposite direction of the original dubious claim.

 

[Mastodont]

It's called Androgen receptor sensitivity. Some men can't tolerate a lot and they can make a little bit go long ways and others take a lot to go a little ways. It's as simple as finding the dose that improves the symptoms of the deficiency while avoiding any unwanted side effects. It's not aiming for any specific level and men or so caught up in numbers that they just can't understand that simple fact. If a level of 700 improve symptoms then that's the number and if the level is 1500 to resolve symptoms that's the number. But whatever number it is it has to be balanced against any unwanted side effects. No one should have to add any additional chemical or drug to control side effects no different then we didn't need to take any chemicals or drugs when we were teenagers or in our 20s when we had excellent testosterone levels. And the receptor saturation is not a theory it's proven in the medical literature, and in medical physiology. People just want to ignore physiology, but this receptor saturation is fully understood. The one thing that we haven't found, though is the saturation point in muscle tissue that's why bodybuilders are as big as they are.

Now this is making much more sense than the message usually coming through that excess does not matter because receptors are full.

I don't believe a saturation occurs at 700 that would be Peter Attia

which is to hit that level of serum estradiol it is looking for. Hence in obesity, the excessive aromatization in fat tissue allows you to hit the HPTA's estradiol target with much lower levels of testosterone, leaving you hypogonadal.

That target would often seem to be much too low, probably due to EDCs fooling the e2 receptors.

I have gotten the adverse effects, primarily much increased anxiety on estradiol valerate orally on top of T.

 

[Seagal]

If you had been following the discussions on ExcelMale then you would know that it is dated thinking to believe that an effective reduction in SHBG raises free testosterone. Here's a thought experiment for you: Imagine a guy with a normal HPTA that is regulating for its desired level of free testosterone. In order to use the Vermeulen calculator, assume that free testosterone is 15.1 ng/dL, TT is 650 ng/dL, ALB is 4.3 g/dL and SHBG is 30 nMol/L. The calculator tells us that 295 ng/dL of the total testosterone is bound to SHBG. Now imagine removing half of the guy's SHBG, including what's bound to it. What is the result? For one thing, SHBG is reduced to 15 nMol/L. My question for you: what pressure is there on free testosterone to change? The answer is none. The HPTA is still happy because it is seeing the desired 15.1 ng/dL of free T. With the SHBG we removed we have also removed 295/2 = 147.5 ng/dL of total testosterone, leaving 650 - 147.5 = 502.5 ng/dL. Is this a stable equilibrium? Yes, according to Vermeulen these new values for SHBG and TT result in the same 15.1 ng/dL of free testosterone.

It's not about reducing SHBG. DHT or proviron has higher affinity to SHBG than T and E. Proviron is a popular add-on to release T/AAS from SHBG.

This experiment were men were given transdermal DHT. I understand it had no negative effect, but I believe it should have an effect. Yes, if you just use enough of T, saturation of receptors, enzymes etc will occur and homeostasis achieved.
To understand effects on mood, mental performance one has to look into the brain.

 

[Seagal]

Dihydrotestosterone: Biochemistry, Physiology, and Clinical Implications of Elevated Blood Levels - PMC

Benefits associated with lowered serum DHT levels after 5α-reductase inhibitor (5AR-I) therapy in men have contributed to a misconception that circulating DHT levels are an important stimulus for androgenic action in target tissues (e.g., prostate). ...

www.ncbi.nlm.nih.gov

That's worth reading. I think BigTex has already posted it.

 

[Cataceous]

It's not about reducing SHBG. DHT or proviron has higher affinity to SHBG than T and E. Proviron is a popular add-on to release T/AAS from SHBG.
...

But it is exactly about reducing — available — SHBG. And the increase in free testosterone is a myth that doesn't want to die. Sure, in the short run if you start administering DHT then *transiently* this displacement occurs and free T briefly increases. But a steady state is soon reached and free testosterone returns to its original level, thus ensuring that the rate of testosterone metabolism matches the rate of production or dosing.

 

[jmbb]

But it is exactly about reducing — available — SHBG. And the increase in free testosterone is a myth that doesn't want to die. Sure, in the short run if you start administering DHT then *transiently* this displacement occurs and free T briefly increases. But a steady state is soon reached and free testosterone returns to its original level, thus ensuring that the rate of testosterone metabolism matches the rate of production or dosing.

This makes complete sense in someone with natural function, but I'm hoping you can explain how this works in someone using exogenous hormones so that I can understand it better, because I'm a little confused. Wouldn't this just depend on when you measured it?

Lets say 100mg of T was administered vs 100mg was administered with some method of boosting DHT to lower and/or bind to SHBG. There would still be the same amount of testosterone administered, but metabolizing faster since its unbound - so at the very least if you measured the initial peak it would have to be higher, even if its metabolizing extremely quickly - resulting in at least some time with higher free testosterone in the serum?

 

[Seagal]

But it is exactly about reducing — available — SHBG. And the increase in free testosterone is a myth that doesn't want to die. Sure, in the short run if you start administering DHT then *transiently* this displacement occurs and free T briefly increases. But a steady state is soon reached and free testosterone returns to its original level, thus ensuring that the rate of testosterone metabolism matches the rate of production or dosing.

Never used it consistently for longer periods, thus it might has been then a transient effect. I guess you have your experience with it.

 

[Cataceous]

This makes complete sense in someone with natural function, but I'm hoping you can explain how this works in someone using exogenous hormones so that I can understand it better, because I'm a little confused. Wouldn't this just depend on when you measured it?

Lets say 100mg of T was administered vs 100mg was administered with some method of boosting DHT to lower and/or bind to SHBG. There would still be the same amount of testosterone administered, but metabolizing faster since its unbound - so at the very least if you measured the initial peak it would have to be higher, even if its metabolizing extremely quickly - resulting in at least some time with higher free testosterone in the serum?

The principle is the same with exogenous testosterone. Instead of internal HPTA regulation of free testosterone there is external regulation via our control of the dose rate. Your example would get complicated if you're talking about injecting pure testosterone and DHT. But typically these hormones are injected as long-acting esters, which lead to a slow and steady introduction of the base hormones into circulation. The DHT does effectively make less SHBG available to bind testosterone. I illustrated above that this does not affect free testosterone when T and DHT are being introduced at constant rates.

Another point about your example is that overall metabolism of testosterone is limited by the rate of production or dosing. If testosterone is slowly being absorbed from a depot then you cannot on average metabolize testosterone at a faster rate than it is coming in. If you provide a sudden spike of pure DHT then you would have a brief surge in free T and its metabolism. But as the DHT declines things go the other way, with a short-lived excess of available SHBG causing free T to fall below baseline. If you take the average of free testosterone over the transient period then you'd find that it's the same as during the original steady state.

Somebody proposed a sponge analogy for SHBG, which is fleshed-out here. I find it useful for getting a sense of SHBG's role as a storage buffer for testosterone. It also highlights that the main action we care about is the "flow" of free testosterone from production/dosing to eventual metabolism and elimination.

 

[RobRoy]

In my case @RobRoy theory doesn’t seem correct. First labs are on injections. Second is on cream. View attachment 42234View attachment 42235

Laugh out loud. What was your dosage of cream? How often did you apply it? When did you get your labs measured? How many hours after application for your labs measured? How long were you on it before you got labs done? Reading your nonsense makes me nauseated.How often were you injecting? How much were you injecting? When did you get your labs measured? How long were you on each before you got labs ? I can show you a spot lab and make it say anything I want you to see. Your post is absolutely meaningless. Absolutely meaningless. You are super moderator of miss information. Please, as a moderator ban me from this forum. It's so easy to see now why read a lot left. It is absolute morons like yourself don't want to argue with someone that has 20 years of experience and tens of thousands of lives in different men on different method of delivery and you're going to tell me that you know better. Ridiculous please band me It is absolute morons like yourself don't want to argue with someone that has 20 years of experience and tens of thousands of lives in different men on different method of delivery and you're going to tell me that you know better. Ridiculous please ban me from the cesspool of miss information. It's best I just use your post to make videos which I'll be doing.