Who's currently on T propionate?

[sh1973]

I agree, there’s no way a guy with single digit binding globulin should feel the same after 7 days with the same dose as someone like myself in the 70s. With this logic we should all only be 400-600ng to feel optimal which certainly could be correct considering 90% of the worlds population fall in this range and has for decades. Perhaps we all have it wrong which might explain why I feel better with low doses.

 

[Cataceous]

This study backs up that idea.

Serum levels of sex hormone‐binding globulin (SHBG) are not associated with lower levels of non‐SHBG‐bound testosterone in male newborns and healthy adult men

View attachment 8939

Is this the reasoning?: The HPTA is regulating for a fixed free testosterone. But if the underlying metabolic clearance rate varied with SHBG then non-SHBG-T would show some kind of (inverse) correlation with SHBG.

 

[sh1973]

I suppose but still can’t say it makes sense.

 

[Cataceous]

"Total testosterone adjusts to maintain free testosterone, which must be constant for a constant input rate."

This is the statement that you base your entire hypothesis on, that total T adjusts downward or upward in order to maintain free testosterone. ... Where in the literature does it demonstrate that Total T adjusts upward or downward depending on SHBG to maintain free T levels?

The adjustment by total testosterone in reaction to changes in free T or SHBG is actually one of the stronger parts of the hypothesis, supported by lots of research, including most recently that used to develop the Tru-T free testosterone calculator. I've been through the argument for maintenance of free T when testosterone input and output are matched at steady state. This does require a constant underlying MCR and a mass-action equation involving free testosterone rather than total.

... I, unfortunately, can't take you seriously.
...

In the absence of more useful or substantive criticism, the sentiment is, unfortunately, mutual.

 

[Cataceous]

...
However, I disagree with him that SHBG doesn’t matter when it comes to peak and trough levels
..

I can't even envision a mechanism by which SHBG could significantly affect the apparent half-lives of testosterone esters. It would have to be mind-bogglingly complex.

I agree, there’s no way a guy with single digit binding globulin should feel the same after 7 days with the same dose as someone like myself in the 70s. ...

This is straying well away from the points I'm making. I have little doubt that there can be a huge variability in the subjective experiences of guys whose SHBG levels differ by a factor of 10. I'm just trying to get people to focus on the more likely explanations rather than the myth of hormone levels falling faster.

 

[DS3]

The adjustment by total testosterone in reaction to changes in free T or SHBG is actually one of the stronger parts of the hypothesis, supported by lots of research, including most recently that used to develop the Tru-T free testosterone calculator. I've been through the argument for maintenance of free T when testosterone input and output are matched at steady state. This does require a constant underlying MCR and a mass-action equation involving free testosterone rather than total.

In the absence of more useful or substantive criticism, the sentiment is, unfortunately, mutual.

And the links to the peer-reviewed research is where?

 

[DS3]

The adjustment by total testosterone in reaction to changes in free T or SHBG is actually one of the stronger parts of the hypothesis, supported by lots of research, including most recently that used to develop the Tru-T free testosterone calculator. I've been through the argument for maintenance of free T when testosterone input and output are matched at steady state. This does require a constant underlying MCR and a mass-action equation involving free testosterone rather than total.

In the absence of more useful or substantive criticism, the sentiment is, unfortunately, mutual.

In cases such as this, the onus is not on me to find research to refute your hypothesis, rather challenge your logic. The onus is on you to in fact find peer-reviewed research that does support your bold statements. Posting interesting hypotheses based on self-assessments and somewhat of an understanding of biochemistry does not in fact prove anything. If you can post peer-reviewed research that supports what you are saying, then I will gladly review and if it does turn out that you are correct, I will be glad to say that you are correct.

But, until you provide actual evidence and not hypotheses with no research backing the idea, then the onus remains on you to actually prove yourself.

 

[DS3]

I can't even envision a mechanism by which SHBG could significantly affect the apparent half-lives of testosterone esters. It would have to be mind-bogglingly complex.


This is straying well away from the points I'm making. I have little doubt that there can be a huge variability in the subjective experiences of guys whose SHBG levels differ by a factor of 10. I'm just trying to get people to focus on the more likely explanations rather than the myth of hormone levels falling faster.

"I have little doubt that there can be a huge variability in the subjective experiences of guys whose SHBG levels differ by a factor of 10."

So you are saying that when lower SHBG guys crash around day 5 after a weekly Cypionate shot and higher SHBG guys remain stable even after day 7, these are just subjective differences? Nothing quantifiable? All mental?

 

[Cataceous]

And the links to the peer-reviewed research is where?

I've provided some links along the way. But here's a sampling dealing with the dynamics of free testosterone:

A critical evaluation of simple methods for the estimation of free testosterone in serum. - PubMed - NCBI
Calculation of free and bound fractions of testosterone and estradiol-17 beta to human plasma proteins at body temperature. - PubMed - NCBI
(PDF) An extraordinarily inaccurate assay for free testosterone is still with us
Calculation of Bioavailable and Free Testosterone in Men: A Comparison of 5 Published Algorithms
A multi-step, dynamic allosteric model of testosterone's binding to sex hormone binding globulin - ScienceDirect
Inverse relationship between hSHBG affinity for testosterone and hSHBG concentration revealed by surface plasmon resonance - ScienceDirect
https://pdfs.semanticscholar.org/7731/850422776511cb02bb538fe39578184dd785.pdf

 

[Gman86]

Explain how that works when the same amount of testosterone is being absorbed and used by each guy every day.

Again, have no clue why it happens, just know that it happens. Maybe the low SHBG guy is still getting all that same testosterone in his system, but he still will be left with much lower T levels by the end of the week, compared to the high SHBG, and will need to inject more frequently if he wants to avoid the roller coaster effect.

 

[Cataceous]

...
But, until you provide actual evidence and not hypotheses with no research backing the idea, then the onus remains on you to actually prove yourself.

As you might imagine, proving these ideas to your satisfaction is not a high priority. Maybe if you were one of the reviewers for a journal submission of mine. In any case, the ideas are largely derivative and deductive in nature. As I have neither the desire nor current university affiliation from which to seek research grants, I am more interested in exposing weaknesses in the assumptions and logic, or in examining additional existing research that supports or contradicts the hypotheses.

...
So you are saying that when lower SHBG guys crash around day 5 after a weekly Cypionate shot and higher SHBG guys remain stable even after day 7, these are just subjective differences? Nothing quantifiable? All mental?

Don't put words in my mouth. I've already discussed some of the alternative ideas. And the level of free estradiol relative to that of free testosterone is certainly quantifiable.

Speaking of burdens of proof, if you are one of the ones believing that SHBG affects ester half-lives then where is that proof? This is a misguided idea that through repetition has gained widespread acceptance. Yet it makes no sense in light of what's known about testosterone ester pharmacokinetics.

 

[DS3]

As you might imagine, proving these ideas to your satisfaction is not a high priority. Maybe if you were one of the reviewers for a journal submission of mine. In any case, the ideas are largely derivative and deductive in nature. As I have neither the desire nor current university affiliation from which to seek research grants, I am more interested in exposing weaknesses in the assumptions and logic, or in examining additional existing research that supports or contradicts the hypotheses.


Don't put words in my mouth. I've already discussed some of the alternative ideas. And the level of free estradiol relative to that of free testosterone is certainly quantifiable.

Speaking of burdens of proof, if you are one of the ones believing that SHBG affects ester half-lives then where is that proof? This is a misguided idea that through repetition has gained widespread acceptance. Yet it makes no sense in light of what's known about testosterone ester pharmacokinetics.

"As you might imagine, proving these ideas to your satisfaction is not a high priority. Maybe if you were one of the reviewers for a journal submission of mine. In any case, the ideas are largely derivative and deductive in nature."

In other words, this says, "I've taken studies conducted on theoretical mathematical components and my own understanding of pharmacokinetics and extrapolated that information to make bold statements that are not actually validated in current literature." So basically you speak over people's heads and have lofty hypotheses that you've deduced from research on theoretical computations, but we should believe you because, well, you seem to understand pharmacokinetics at a higher level, so even if what you are saying at this point still pseudoscience, we should just accept your hypotheses as fact because, well, you sound smart, so it must be true. Right?

 

[Cataceous]

...
In other words, this says, "I've taken studies conducted on theoretical mathematical components and my own understanding of pharmacokinetics and extrapolated that information to make bold statements that are not actually validated in current literature." So basically you speak over people's heads and have lofty hypotheses that you've deduced from research on theoretical computations, but we should believe you because, well, you seem to understand pharmacokinetics at a higher level, so even if what you are saying at this point still pseudoscience, we should just accept your hypotheses as fact because, well, you sound smart, so it must be true. Right?

In other words, it's too much effort to learn the concepts, but you want to criticize anyway.

 

[DS3]

In other words, it's too much effort to learn the concepts, but you want to criticize anyway.

Pseudoscientists are all the same.

 

[Vince Carter]

"As you might imagine, proving these ideas to your satisfaction is not a high priority. Maybe if you were one of the reviewers for a journal submission of mine. In any case, the ideas are largely derivative and deductive in nature."

In other words, this says, "I've taken studies conducted on theoretical mathematical components and my own understanding of pharmacokinetics and extrapolated that information to make bold statements that are not actually validated in current literature." So basically you speak over people's heads and have lofty hypotheses that you've deduced from research on theoretical computations, but we should believe you because, well, you seem to understand pharmacokinetics at a higher level, so even if what you are saying at this point still pseudoscience, we should just accept your hypotheses as fact because, well, you sound smart, so it must be true. Right?

Just put him on ignore/block and go with your life.

 

[DS3]

Just put him on ignore/block and go with your life.

Will do. Thank you Vince.

 

[Cataceous]

Pseudoscientists are all the same.

Ad hominem attacks, the last resort when one lacks logical arguments. Since this is the best you have please do follow VC's suggestion.

 

[Tokumei]

Cataceous wins.

 

[Tokumei]

Will do. Thank you Vince.

There is no way in hell someone taking 75mg test p eod is peaking at just 1100.

 

[Cataceous]

Cataceous wins.

The support is appreciated. Nonetheless, the goal here is to improve our knowledge. That can only occur when new ideas face close scrutiny and survive informed criticism. @DS3 was on point to bring up the subject of direct metabolism of bound testosterone. But his other comments are mainly vague skepticism, which is hard to address.