Who's currently on T propionate?

[DS3]

Yes, I am saying that almost all testosterone, exogenous or endogenous, must become free for it to be metabolized and/or excreted. There are some exceptions, such as when SHBG-bound testosterone binds to the megalin protein and is absorbed by cells. But the long half-life of SHBG suggests this activity is relatively small compared to the usual case of free T binding to androgen receptors.

The same principles apply to infrequent injections. In these cases steady state just means that each injection interval looks like the previous one. The only difference is that the rate of testosterone absorption declines more significantly over each interval, and this is reflected in free testosterone. This works because the rate of change in absorption is still slow compared to the half-life of testosterone in plasma.

Many factors influence subjective results. Some guys will be more sensitive to falling testosterone than others. Guys with low SHBG very likely do have problems with their levels of free estradiol compared to free testosterone. None of this suggests that absorption half-lives are very different.

That is interesting because this is a study providing evidence for the assertion that SHBG levels influence metabolic clearance rate.

Differences in the Apparent Metabolic Clearance Rate of Testosterone in Young and Older Men with Gonadotropin Suppression Receiving Graded Doses of Testosterone

"Body composition and SHBG were significant predictors of aMCR-T."

 

[Cataceous]

That is interesting because this is a study providing evidence for the assertion that SHBG levels influence metabolic clearance rate.

Differences in the Apparent Metabolic Clearance Rate of Testosterone in Young and Older Men with Gonadotropin Suppression Receiving Graded Doses of Testosterone

"Body composition and SHBG were significant predictors of aMCR-T."

The issue with this study is that they are basing MCR on total T rather than free T. The standard equation used is:

Production_rate = MCR * Hormone_concentration

But as I argued above, the proportionality applies to free testosterone, not total. So the equation should be:

Production_rate = MCR * Hormone_concentration = MCR * FT = MCR * f(SHBG, T)

The reason it might appear to work anyway is because at constant SHBG, free T is nearly proportional to total T. So you get:

Production_rate = MCR * f(SHBG, T) ~= MCR * f1(SHBG) * T = MCRx * T

The problem is that their measured clearance rate, MCRx, is actually dependent on both the underlying metabolism (MCR) and SHBG. Unfortunately they don't separate out the two, which potentially weakens their conclusions. The results are further muddied by the drop in SHBG—mainly in younger men—over the course of the experiment. It's frustrating, because they did measure free testosterone, apparently by an accurate method, along with baseline and final SHBG values—so they did have the raw data needed to separate out the various effects.

 

[DS3]

The issue with this study is that they are basing MCR on total T rather than free T. The standard equation used is:

Production_rate = MCR * Hormone_concentration

But as I argued above, the proportionality applies to free testosterone, not total. So the equation should be:

Production_rate = MCR * Hormone_concentration = MCR * FT = MCR * f(SHBG, T)

The reason it might appear to work anyway is because at constant SHBG, free T is nearly proportional to total T. So you get:

Production_rate = MCR * f(SHBG, T) ~= MCR * f1(SHBG) * T = MCRx * T

The problem is that their measured clearance rate, MCRx, is actually dependent on both the underlying metabolism (MCR) and SHBG. Unfortunately they don't separate out the two, which potentially weakens their conclusions. The results are further muddied by the drop in SHBG—mainly in younger men—over the course of the experiment. It's frustrating, because they did measure free testosterone, apparently by an accurate method, along with baseline and final SHBG values—so they did have the raw data needed to separate out the various effects.

All studies have weaknesses. Despite that fact, and the fact that this study's conclusions report that clearance rate is dependent on both underlying metabolism and SHBG, this provides evidence that you are incorrect in your theoretical assumption that clearance rates are independent of SHBG.

 

[Vince Carter]

All studies have weaknesses. Despite that fact, and the fact that this study's conclusions report that clearance rate is dependent on both underlying metabolism and SHBG, this provides evidence that you are incorrect in your theoretical assumption that clearance rates are independent of SHBG.

You'll get more satisfaction smashing your penis in a drawer than working on Cataceous and his goofy theories. He forget's this ain't that hot mess called PeakT forum.

 

[DS3]

The issue with this study is that they are basing MCR on total T rather than free T. The standard equation used is:

Production_rate = MCR * Hormone_concentration

But as I argued above, the proportionality applies to free testosterone, not total. So the equation should be:

Production_rate = MCR * Hormone_concentration = MCR * FT = MCR * f(SHBG, T)

The reason it might appear to work anyway is because at constant SHBG, free T is nearly proportional to total T. So you get:

Production_rate = MCR * f(SHBG, T) ~= MCR * f1(SHBG) * T = MCRx * T

The problem is that their measured clearance rate, MCRx, is actually dependent on both the underlying metabolism (MCR) and SHBG. Unfortunately they don't separate out the two, which potentially weakens their conclusions. The results are further muddied by the drop in SHBG—mainly in younger men—over the course of the experiment. It's frustrating, because they did measure free testosterone, apparently by an accurate method, along with baseline and final SHBG values—so they did have the raw data needed to separate out the various effects.

Humor me and follow this thought-process for a minute:

In order for testosterone to be metabolized and subsequently excreted in any appreciable amount, testosterone has to be converted into free testosterone. Low SHBG guys have higher free/unbound testosterone than their converse counterparts. Low SHBG guys would have higher clearance rates than high SHBG guys due to the fact that the amount of free/unbound T is higher at any given time that a high SHBG guy. Thus, with higher amount of free/unbound T, low SHBG guys will have a larger amount of readily excretable testosterone given its unbound state, and will subsequently 'run through' a single dosage of T faster than their converse counterparts.

Where is this flawed?

 

[Vince Carter]

Oh you're not flawed, at all in that logical thought process. Dr Crisler had stated it as such that we guys piss it out but on the flip side, don't get that same rate of clearance with the Estrogen component. The low SHBG can sometimes tolerate almost no E also from Dr C.

 

[Cataceous]

All studies have weaknesses. Despite that fact, and the fact that this study's conclusions report that clearance rate is dependent on both underlying metabolism and SHBG, this provides evidence that you are incorrect in your theoretical assumption that clearance rates are independent of SHBG.

On the contrary, I demonstrated exactly why the study incorrectly concludes that MCR depends on SHBG.

 

[sh1973]

Release from the depot is the same no matter what the shbg number. The only variables that affect release are activity, blood flow etc.... Once it’s released and in circulation someone with lower binding globulin will absolutely clear the testosterone molecule from their system faster. Case in point mine is high and I can do a single shot and still have elevated t levels two weeks later whereas someone with single digit shbg would be at the bottom of the range in that time. Me and the low shbg guy are releasing the drug from the depot at the same rate but I have more bound in circulation than the low shbg guy. I might have 3 days worth of bound testosterone still in circulation whereas the low shbg guy might have 12 hours worth, hence lower total and free t. Cat I normally see your reasoning with some things but this isn’t one of those times.

 

[Cataceous]

Humor me and follow this thought-process for a minute:

In order for testosterone to be metabolized and subsequently excreted in any appreciable amount, testosterone has to be converted into free testosterone. Low SHBG guys have higher free/unbound testosterone than their converse counterparts. Low SHBG guys would have higher clearance rates than high SHBG guys due to the fact that the amount of free/unbound T is higher at any given time that a high SHBG guy. Thus, with higher amount of free/unbound T, low SHBG guys will have a larger amount of readily excretable testosterone given its unbound state, and will subsequently 'run through' a single dosage of T faster than their converse counterparts.

Where is this flawed?

Low SHBG guys have higher free/unbound testosterone than their converse counterparts. Low SHBG guys would have higher clearance rates than high SHBG guys due to the fact that the amount of free/unbound T is higher at any given time that a high SHBG guy.

Only when total testosterone is forced to be the same.

Thus, with higher amount of free/unbound T, low SHBG guys will have a larger amount of readily excretable testosterone given its unbound state, and will subsequently 'run through' a single dosage of T faster than their converse counterparts.

You seem to be appealing to intuition, which doesn't work in this case. The point you keep ignoring is that with constant testosterone production or absorption the total level of testosterone is not the same for different SHBG and the same underlying metabolism. Total testosterone adjusts to maintain free testosterone, which must be constant for a constant input rate.

 

[Cataceous]

Release from the depot is the same no matter what the shbg number. The only variables that affect release are activity, blood flow etc....

Yes!

... Once it’s released and in circulation someone with lower binding globulin will absolutely clear the testosterone molecule from their system faster. ...

Only if free testosterone is higher, which it's not when testosterone inputs are constant and only SHBG is different.

...
Case in point mine is high and I can do a single shot and still have elevated t levels two weeks later whereas someone with single digit shbg would be at the bottom of the range in that time. ...

Serum levels for the low-SHBG guy drop at the same rate as yours, governed by the changing amount absorbed. But the lower-SHBG has proportionally lower total testosterone throughout, all else being equal.

...
Me and the low shbg guy are releasing the drug from the depot at the same rate but I have more bound in circulation than the low shbg guy. I might have 3 days worth of bound testosterone still in circulation whereas the low shbg guy might have 12 hours worth, hence lower total and free t. ...

Lower total T, the same free T, all else being equal.

... Cat I normally see your reasoning with some things but this isn’t one of those times.

Sorry I am not conveying the ideas more clearly. Nonetheless, if the assumptions outlined previously are correct then what I'm saying follows naturally.

 

[Cataceous]

This illustration may help with visualizing the dynamics of testosterone flow with injections. It relies on the simplified model, in which Production/Absorption Rate = MCR * f(SHBG) * T. The containers in this analogy are not quite like real-life containers, in that they can never empty entirely due to the flow rate out being proportional to fluid level.

 

[sh1973]

I sorta get what you're trying to say but if I inject 100mg Monday and a low shbg injects the same he will be hypogonadal on Friday whereas I will be 950-1000ng on day 7. If he's at 220ng with a shbg of 7 then his free t is 8.18ng. Mine at 70 for shbg would be a free t of 31.30ng. How in the world can you say that's the same? Its simple mathematics and this is using the Tru T calculator. You can't surely state that we're going to feel the same symptomatically! Mine,being more tightly bound, whether usable or not, will ABSOLUTELY be in circulation longer and excreted at a lower rate than the guy with a 7 shbg value. You surely can't think he's going to feel the same effect having 8ng vs 31ng. There's zero proof anywhere to date, that can demonstrate how bound testosterone acts upon the bodies cells but one thing is for certain and that is someone with high shbg will keep released testosterone in circulation longer than someone with low shbg.

 

[Cataceous]

I sorta get what you're trying to say but if I inject 100mg Monday and a low shbg injects the same he will be hypogonadal on Friday whereas I will be 950-1000ng on day 7. If he's at 220ng with a shbg of 7 then his free t is 8.18ng. Mine at 70 for shbg would be a free t of 31.30ng. How in the world can you say that's the same? Its simple mathematics and this is using the Tru T calculator. You can't surely state that we're going to feel the same symptomatically! Mine,being more tightly bound, whether usable or not, will ABSOLUTELY be in circulation longer and excreted at a lower rate than the guy with a 7 shbg value. You surely can't think he's going to feel the same effect having 8ng vs 31ng. ...

Let's say that low-SHBG guy is identical to you in all regards except SHBG. You both inject inject 100 mg TC every Monday, and after steady state you measure serum levels on Friday. You, with SHBG 70 nMol/L, measure total T as 950-1000 ng/dL. In this case low-SHBG twin, with SHBG of 7, measures about 800 ng/dL. Basically, his total testosterone is always going to be around 20% lower than yours. You do not and cannot metabolize/excrete at a lower rate. We've agreed that you're each absorbing the same amount of testosterone over any time interval. Therefore, at steady state, over any reasonable time interval, you must both be using/excreting the same amount. Furthermore, applying the law of mass action, Absorption_rate = MCR * free_T, means you both have the same free testosterone over any reasonable interval. This is how you work backwards to determine low-SHBG twin's total testosterone—we know he must have about the same free T as you.

... There's zero proof anywhere to date, that can demonstrate how bound testosterone acts upon the bodies cells...

As I mentioned above, there are some known uses for SHBG-bound testosterone, and they may contribute to suboptimal results by low-SHBG guys. However, the evidence so far seems to be saying that this activity plays a relatively small role in the consumption and elimination of testosterone.

...but one thing is for certain and that is someone with high shbg will keep released testosterone in circulation longer than someone with low shbg.

No, free testosterone is what drives this. If you and your low-SHBG twin have the same free testosterone levels then you will both be metabolizing and excreting testosterone at close to the same rate.

 

[Gman86]

Let's say that low-SHBG guy is identical to you in all regards except SHBG. You both inject inject 100 mg TC every Monday, and after steady state you measure serum levels on Friday. You, with SHBG 70 nMol/L, measure total T as 950-1000 ng/dL. In this case low-SHBG twin, with SHBG of 7, measures about 800 ng/dL. Basically, his total testosterone is always going to be around 20% lower than yours. You do not and cannot metabolize/excrete at a lower rate. We've agreed that you're each absorbing the same amount of testosterone over any time interval. Therefore, at steady state, over any reasonable time interval, you must both be using/excreting the same amount. Furthermore, applying the law of mass action, Absorption_rate = MCR * free_T, means you both have the same free testosterone over any reasonable interval. This is how you work backwards to determine low-SHBG twin's total testosterone—we know he must have about the same free T as you.

... There's zero proof anywhere to date, that can demonstrate how bound testosterone acts upon the bodies cells...

As I mentioned above, there are some known uses for SHBG-bound testosterone, and they may contribute to suboptimal results by low-SHBG guys. However, the evidence so far seems to be saying that this activity plays a relatively small role in the consumption and elimination of testosterone.

...but one thing is for certain and that is someone with high shbg will keep released testosterone in circulation longer than someone with low shbg.

No, free testosterone is what drives this. If you and your low-SHBG twin have the same free testosterone levels then you will both be metabolizing and excreting testosterone at close to the same rate.

I can guarantee that a guy with a SHBG of 7 will absolutely not have a total of 800 by Friday, if he injects 100mg that previous Monday. The science can say whatever it wants. I’ve seen enough blood work to know that if two guys inject 100mg on a Monday, one having a SHBG of 70, and one of 7, the high SHBG guy will hold his level much much much better than the low SHBG guy.

 

[Cataceous]

I can guarantee that a guy with a SHBG of 7 will absolutely not have a total of 800 by Friday, if he injects 100mg that previous Monday. The science can say whatever it wants. I’ve seen enough blood work to know that if two guys inject 100mg on a Monday, one having a SHBG of 70, and one of 7, the high SHBG guy will hold his level much much much better than the low SHBG guy.

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

 

[HarryCat2]

... Furthermore, applying the law of mass action, Absorption_rate = MCR * free_T, means you both have the same free testosterone over any reasonable interval. This is how you work backwards to determine low-SHBG twin's total testosterone—we know he must have about the same free T as you.

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

 

[DS3]

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

Low SHBG guys have higher free/unbound testosterone than their converse counterparts. Low SHBG guys would have higher clearance rates than high SHBG guys due to the fact that the amount of free/unbound T is higher at any given time that a high SHBG guy.

Only when total testosterone is forced to be the same.

Thus, with higher amount of free/unbound T, low SHBG guys will have a larger amount of readily excretable testosterone given its unbound state, and will subsequently 'run through' a single dosage of T faster than their converse counterparts.

You seem to be appealing to intuition, which doesn't work in this case. The point you keep ignoring is that with constant testosterone production or absorption the total level of testosterone is not the same for different SHBG and the same underlying metabolism. Total testosterone adjusts to maintain free testosterone, which must be constant for a constant input rate.

"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. Unfortunately, Cataceous, your views are highly theoretical and based on anecdotal evidence of self-testing and theoretical mathematical components, as opposed to research-based evidence. For that reason, I, unfortunately, can't take you seriously.

Everything you state for evidence begins with, "Let's say...". Let's not say something theoretical based on a hypothesis of yours, and let's defer to research. Where in the literature does it demonstrate that Total T adjusts upward or downward depending on SHBG to maintain free T levels?

 

[HarryCat2]

Where in the literature does it demonstrate that Total T adjusts upward or downward depending on SHBG to maintain free T levels?

That is shown in the study I just posted.

 

[Gman86]

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

No idea. I’m just saying what happens. How it happens beats me

 

[Gman86]

"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. Unfortunately, Cataceous, your views are highly theoretical and based on anecdotal evidence of self-testing and theoretical mathematical components, as opposed to research-based evidence. For that reason, I, unfortunately, can't take you seriously.

Everything you state for evidence begins with, "Let's say...". Let's not say something theoretical based on a hypothesis of yours, and let's defer to research. Where in the literature does it demonstrate that Total T adjusts upward or downward depending on SHBG to maintain free T levels?

I think Cataceous definitely knows what he’s talking about. We’ve had a discussion on this topic before. Here’s two sets of blood work that backs up his theory where the body will adjust total T to maintain free T values at a certain level. There’s other labs that I’ve had back to back that back his theory up as well, just can’t find them at the moment.

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

8-15-17 labs were while on this protocol:
Test- 90mg split into EOD dosing
HCG - 600IU split into EOD dosing (Pregnyl HCG)
Arimidex - 0.25mg EOD
Total -1299 (250-1100 ng/dL)
Free - 146.6 (46.0-224.0)
Bio- 307.8 (110.0-575.0 ng/dL)
SHBG 51 (10-50)
E2 Sensitive - 8
E2 NOT Sensitive - 13
E2 Free - 0.28 (0.2-1.5)

12-13-17 labs were while on this protocol:
Test- 90mg split into EOD dosing
HCG- 800iu split into EOD dosing (Pregnyl HCG)
Exemestane - 6.25mg EOD
Total - 974 (250-1100 ng/dL)
Free - 142.6 (46.0-224.0)
Bio - 287.0 (110.0-575.0 ng/dL) SHBG 36 (10-50)
E2 Sensitive - 9
E2 NOT Sensitive - 13
E2 Free - 0.28 (0.2-1.5)