Who's currently on T propionate?

[Cataceous]

" As noted, the rate of use and excretion of testosterone is proportional to free testosterone."
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Have I shamefully misinterpreted your statements?
...

Not shamefully, but you have misinterpreted the general idea. You assume that total testosterone doesn't change. But if underlying metabolism stays the same then free testosterone must be preserved to maintain the consumption/excretion rate. So it is total testosterone that adjusts to make it work.

...
"Suppose your SHBG suddenly changed dramatically. What happens at the new steady state? You must still be excreting the same amount of testosterone each week. Thus free testosterone must be unchanged after the transition, and total testosterone adjusts to preserve this level of free T at the new SHBG."

Is this a hypothesis or something that has been proven? This sounds highly theoretical.

Call it an informed hypothesis supported by anecdotal evidence. The primary assumption that might be questioned is that underlying metabolism, e.g. in the liver, does not change. I've observed mine to be static over several years and at various SHBG levels. I expect this is not unusual, but there are certainly going to be exceptions.

The point about testosterone intake matching use/excretion is straightforward. It assume no endogenous production. Therefore at steady state the average rate of testosterone being injected is matched by the average rate of testosterone being used/excreted. This is important, because with the rate of use/excretion proportional to free testosterone then average free testosterone is proportional to average dose. And here are some of my actual free testosterone values versus dose:

These points had to be acquired with frequent injections of longer esters—enanthate, cypionate—to avoid half-life effects.

In any case, taken together these arguments support the premise that in those on TRT injections, a sudden change in only SHBG would result in an adjustment to total testosterone, not free.

If you'd like to visualize what's happening with an analogy, I describe one involving tubs of water here.

 

[DS3]

Not shamefully, but you have misinterpreted the general idea. You assume that total testosterone doesn't change. But if underlying metabolism stays the same then free testosterone must be preserved to maintain the consumption/excretion rate. So it is total testosterone that adjusts to make it work.


Call it an informed hypothesis supported by anecdotal evidence. The primary assumption that might be questioned is that underlying metabolism, e.g. in the liver, does not change. I've observed mine to be static over several years and at various SHBG levels. I expect this is not unusual, but there are certainly going to be exceptions.

The point about testosterone intake matching use/excretion is straightforward. It assume no endogenous production. Therefore at steady state the average rate of testosterone being injected is matched by the average rate of testosterone being used/excreted. This is important, because with the rate of use/excretion proportional to free testosterone then average free testosterone is proportional to average dose. And here are some of my actual free testosterone values versus dose:
View attachment 8929
These points had to be acquired with frequent injections of longer esters—enanthate, cypionate—to avoid half-life effects.

In any case, taken together these arguments support the premise that in those on TRT injections, a sudden change in only SHBG would result in an adjustment to total testosterone, not free.

If you'd like to visualize what's happening with an analogy, I describe one involving tubs of water here.

"You assume that total testosterone doesn't change. But if underlying metabolism stays the same then free testosterone must be preserved to maintain the consumption/excretion rate. So it is total testosterone that adjusts to make it work."

According to what? Besides your anecdotal studies of yourself (wherein your hypothesized peaks using your trough values), where are you generating this information from? The current thought in medicine is that free testosterone is determined by binding globulins, namely Albumin and SHBG.

What evidence do you have that suggests different other than a few personal tests?

What evidence do you have that suggests changes in SHBG would decrease total T as opposed to affecting only Free T aside from a highly theoretical thought-process?

Also, where is your evidence that testosterone has to be 'free' in order to be excreted? Can you confidently state with evidence that the body cannot excrete bound testosterone (either by Albumin of SHBG) and that the testosterone must first be unbound before it can be excreted?

 

[Cataceous]

"You assume that total testosterone doesn't change. But if underlying metabolism stays the same then free testosterone must be preserved to maintain the consumption/excretion rate. So it is total testosterone that adjusts to make it work."

According to what? Besides your anecdotal studies of yourself (wherein your hypothesized peaks using your trough values), where are you generating this information from? The current thought in medicine is that free testosterone is determined by binding globulins, namely Albumin and SHBG.

What evidence do you have that suggests different other than a few personal tests?

What evidence do you have that suggests changes in SHBG would decrease total T as opposed to affecting only Free T aside from a highly theoretical thought-process?

Also, where is your evidence that testosterone has to be 'free' in order to be excreted? Can you confidently state with evidence that the body cannot excrete bound testosterone (either by Albumin of SHBG) and that the testosterone must first be unbound before it can be excreted?

Expand your thinking on the free T computation. Basically there are four variables: SHBG, albumin, free T and total T. If you know any three then you can compute the fourth. My assumptions lead to specifying the first three. If you accept these assumptions then it's ok to think of total T as a dependent variable, a function of the other three, and my other statements are a logical result. So which particular underlying assumption do you disagree with and why? Here they are:

• On average the exogenous testosterone taken in matches the amount metabolized and/or excreted.
• The metabolic clearance rate is linear in free testosterone, so the rate of loss is k * FT. See Law of Mass Action.
• The underlying metabolism doesn't change, so the constant "k" does not change appreciably. This is the best avenue for criticism, but I see no reason to believe that my numbers are unique. And indeed, articles like this one generally treat MCR as a fixed constant.

Your question about excreting bound testosterone is fair. But the binding proteins are used to prevent early excretion, and a couple facts show that loss via this route, if it exists, is negligible. First "In the healthy kidney, albumin's size and negative electric charge exclude it from excretion in the glomerulus."[1] And second, the half-life of SHBG is several days.[2] This must be contrasted with the half-life of free testosterone in serum, which is on the order of minutes. In other words, even if SHBG-bound testosterone were escaping, the rate of loss would be very low.

 

[DS3]

Expand your thinking on the free T computation. Basically there are four variables: SHBG, albumin, free T and total T. If you know any three then you can compute the fourth. My assumptions lead to specifying the first three. If you accept these assumptions then it's ok to think of total T as a dependent variable, a function of the other three, and my other statements are a logical result. So which particular underlying assumption do you disagree with and why? Here they are:

• On average the exogenous testosterone taken in matches the amount metabolized and/or excreted.
• The metabolic clearance rate is linear in free testosterone, so the rate of loss is k * FT. See Law of Mass Action.
• The underlying metabolism doesn't change, so the constant "k" does not change appreciably. This is the best avenue for criticism, but I see no reason to believe that my numbers are unique. And indeed, articles like this one generally treat MCR as a fixed constant.

Your question about excreting bound testosterone is fair. But the binding proteins are used to prevent early excretion, and a couple facts show that loss via this route, if it exists, is negligible. First "In the healthy kidney, albumin's size and negative electric charge exclude it from excretion in the glomerulus."[1] And second, the half-life of SHBG is several days.[2] This must be contrasted with the half-life of free testosterone in serum, which is on the order of minutes. In other words, even if SHBG-bound testosterone were escaping, the rate of loss would be very low.

In spite of the complex rhetoric aimed at dissuading me from finding argument due to your obvious need to prove yourself more adept in the subject, you have stated previously that SHBG and free T are independent. From your statement, "Expand your thinking on the free T computation. Basically there are four variables: SHBG, albumin, free T and total T. If you know any three then you can compute the fourth. My assumptions lead to specifying the first three. If you accept these assumptions then it's ok to think of total T as a dependent variable, a function of the other three, and my other statements are a logical result," it is clear that you are in agreement that SHBG, Albumin, Total T, and Free T have an interdependent relationship and thus affect the outcome of one another regardless of whether it is upstream or downstream.

Your logic is indeed interesting, however, none of its theoretical components prove or disprove that an individual with lower SHBG would or would not excrete testosterone faster than their converse counterparts. Your constructs suggest that the amount of T an individual ingests would match the amount excreted, however, it does not provide evidence for making assumptions among individual differences (i.e. whether or not individuals with lower SHBG indeed excrete faster, regardless of an equal proportion of ingestion and excretion).

 

[equel]

I consistently have low SHBG at 20 mnol/L and I love EOD propionate shots. No crazy hormonal or mood swings. Peak (tested) is at 1100 ng/dL and trough is at 700-800 ng/dL (again, no crazy swings). Your issue with rapidly metabolizing propionate runs deeper than mere SHBG levels.

What is your dosage?

 

[Cataceous]

In spite of the complex rhetoric aimed at dissuading me from finding argument due to your obvious need to prove yourself more adept in the subject,...

If you think I view this as some kind of competitive situation then you are misguided. To me this is about peer review, along with sharing and receiving new ideas.

...
Your logic is indeed interesting, however, none of its theoretical components prove or disprove that an individual with lower SHBG would or would not excrete testosterone faster than their converse counterparts. Your constructs suggest that the amount of T an individual ingests would match the amount excreted, however, it does not provide evidence for making assumptions among individual differences (i.e. whether or not individuals with lower SHBG indeed excrete faster, regardless of an equal proportion of ingestion and excretion).

This is a different, though related topic: What predictions can be made about different individuals? However, you muddle the situation by seeming to contradict something I find to be obvious: If I am setting exogenous testosterone doses for guys then I am unequivocally controlling their use/excretion rate, no matter what SHBG they have. If I inject you with 10 mg T cypionate daily then after some time you will be using/excreting 7 mg testosterone every day, regardless of whether your SHBG is 10 nMol/L or 100, and also independent of your underlying metabolism. Agreed?

 

[Gman86]

Your deca dick comment is interesting. I personally have experienced ED side effects of nandrolone at 100 mg per week while taking 200 mg T. I have even done a 3:1 ratio of T to N and still had the issue. I think the deca dick train of thought that it only occurs in users who go above therapeutic levels is rudimentary, frequently leaving neurotransmitters out of the conversation and the effect that nandrolone can have on upregulating dopamine in brain structures such as the hypothalamus. Decreased dopamine in the CNS can certainly create ED issues, and could help explain why some users experience deca dick even when they are within therapeutic ranges. Note: I am not referring to increased prolactin as the root cause of decreased dopamine in the CNS. I am referring to a direct effect on the CNS from nandrolone, aside from any effects on prolactin.

So you’re saying that since nandrolone upregulates dopamine in the brain, that this causes down-regulation of dopamine in the CNS?

 

[DS3]

What is your dosage?

75 mg Test Prop EOD

 

[Gman86]

75 mg Test Prop EOD

Thats a whopper of a dose. 262mg/ week, which is the equivalent of 310mg/week of cypionate. Why so high?

 

[DS3]

So you’re saying that since nandrolone upregulates dopamine in the brain, that this causes down-regulation of dopamine in the CNS?

I meant to state that nandrolone has been demonstrated to increase the reuptake of dopamine in the CNS. However, as I go back and read the study I was referring to, I stand corrected. The study actually demonstrated an increase of dopamine in the hypothalamus. The Impact of Nandrolone Decanoate on the Central Nervous System

From my experience using nandrolone, after about 6 weeks at 100 mg/week I begin to feel extremely depressed and apathetic. Neuroscience is a very complex topic and is certainly multi-faceted in regard to cause and effect. However, I did indeed experience 'deca dick' after 6 weeks of nandrolone at that dosage, and my prolactin had not increased, nor had my estrogen. Interestingly, my depression set it a week or so before my ED issues, and cleared 2 weeks after discontinuing use of nandrolone.

 

[DS3]

Thats a whopper of a dose. 262mg/ week, which is the equivalent of 310mg/week of cypionate. Why so high?

I agree it is a high dose for TRT. But, as my blood tests show, my peaks are at 1100 and troughs are 700-800 at this dosage. So for my body, this dosage is the effective dosage. Lower than that any my levels obviously drop and so does my energy and mood. I'm not sure why I need such as high dosage. Perhaps previous bodybuilding pursuits when I was younger damaged my androgen receptors. Not sure.

 

[DS3]

Thats a whopper of a dose. 262mg/ week, which is the equivalent of 310mg/week of cypionate. Why so high?

Also, my testosterone levels stay around 1200 with EOD injections of 50 mg of Cypionate (175 per week). There is a major difference in the dosage, for me, needed to maintain T equivalent T levels when using propionate versus cypionate. I have no explanation as to why.

 

[DS3]

If you think I view this as some kind of competitive situation then you are misguided. To me this is about peer review, along with sharing and receiving new ideas.

This is a different, though related topic: What predictions can be made about different individuals? However, you muddle the situation by seeming to contradict something I find to be obvious: If I am setting exogenous testosterone doses for guys then I am unequivocally controlling their use/excretion rate, no matter what SHBG they have. If I inject you with 10 mg T cypionate daily then after some time you will be using/excreting 7 mg testosterone every day, regardless of whether your SHBG is 10 nMol/L or 100, and also independent of your underlying metabolism. Agreed?

That would make sense, but that would also have to mean that your body was excreting bound testosterone at a rate that isn't insignificant. Unless you are proposing that ALL/MOST exogenously ingested testosterone must become free/unbound before it can become excreted.

If you are using it daily then yes that would make sense. But if using Cypionate as a once per week shot, can you still conclude that individuals with high SHBG or low SHBG would excrete the exogenous T at the same rate? And if you can, then how would you explain how some guys feel a massive 'comedown' accompanied by a significant reduction in T around day 4 or 5, while others can maintain higher levels all the way until day 7 or even 8 or 9?

 

[Gman86]

Also, my testosterone levels stay around 1200 with EOD injections of 50 mg of Cypionate (175 per week). There is a major difference in the dosage, for me, needed to maintain T equivalent T levels when using propionate versus cypionate. I have no explanation as to why.

Interesting. One of the reasons I stopped using propionate was that i just couldn’t get my free T to budge past mid point in the range, no matter how high I upped my dose. It was taking way too much propionate to get to much lower levels than I had on cypionate. My E2 was much higher proportionate to the level of T on propionate, compared to cypionate, which I didn’t like.

 

[HarryCat2]

This paper seems to say that lower SHBG results in higher apparent testosterone metabolic clearance rates.

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

Abstract

Background: Recently we found that testosterone levels are higher in older men than young men receiving exogenous testosterone. We hypothesized that older men have lower apparent testosterone metabolic clearance rates (aMCR-T) that contribute to higher testosterone levels.

Objective: The objective of the study was to compare aMCR-T in older and young men and identify predictors of aMCR-T.

Methods: Sixty-one younger (19–35 yr) and 60 older (59–75 yr) men were given a monthly GnRH agonist and weekly testosterone enanthate (TE) (25, 50, 125, 300, or 600 mg) for 5 months. Estimated aMCR-T was calculated from the amount of TE delivered weekly and trough serum testosterone concentrations, corrected for real-time absorption kinetics from the im testosterone depot.

Results: Older men had lower total (316 ± 13 vs. 585 ± 26 ng/dl, P < 0.00001) and free testosterone (4 ± 0.1 vs. 6 ± 0.3 ng/dl, P < 0.00001) and higher SHBG (52 ± 3 vs. 33 ± 2 nmol/liter, P < 0.00001) than younger men at baseline. Total and free testosterones increased with TE dose and were higher in older men than young men in the 125-, 300-, and 600-mg dose groups. aMCR-T was lower in older men than young men (1390 ± 69 vs. 1821 ± 102 liter/d, P = 0.006). aMCR-T correlated negatively with age (P = 0.0007), SHBG (P = 0.046), and total testosterone during treatment (P = 0.02) and percent body fat at baseline (P = 0.01) and during treatment (P = 0.004). aMCR-T correlated positively with lean body mass at baseline (P = 0.03) and during treatment (P = 0.01). In multiple regression models, significant predictors of aMCR-T included lean body mass (P = 0.008), percent fat mass (P = 0.009), and SHBG (P = 0.001).

Conclusions: Higher testosterone levels in older men receiving TE were associated with an age-related decrease in apparent testosterone metabolic clearance rates. Body composition and SHBG were significant predictors of aMCR-T.

 

[DS3]

This paper seems to say that lower SHBG results in higher apparent testosterone metabolic clearance rates.

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

Abstract

Background: Recently we found that testosterone levels are higher in older men than young men receiving exogenous testosterone. We hypothesized that older men have lower apparent testosterone metabolic clearance rates (aMCR-T) that contribute to higher testosterone levels.

Objective: The objective of the study was to compare aMCR-T in older and young men and identify predictors of aMCR-T.

Methods: Sixty-one younger (19–35 yr) and 60 older (59–75 yr) men were given a monthly GnRH agonist and weekly testosterone enanthate (TE) (25, 50, 125, 300, or 600 mg) for 5 months. Estimated aMCR-T was calculated from the amount of TE delivered weekly and trough serum testosterone concentrations, corrected for real-time absorption kinetics from the im testosterone depot.

Results: Older men had lower total (316 ± 13 vs. 585 ± 26 ng/dl, P < 0.00001) and free testosterone (4 ± 0.1 vs. 6 ± 0.3 ng/dl, P < 0.00001) and higher SHBG (52 ± 3 vs. 33 ± 2 nmol/liter, P < 0.00001) than younger men at baseline. Total and free testosterones increased with TE dose and were higher in older men than young men in the 125-, 300-, and 600-mg dose groups. aMCR-T was lower in older men than young men (1390 ± 69 vs. 1821 ± 102 liter/d, P = 0.006). aMCR-T correlated negatively with age (P = 0.0007), SHBG (P = 0.046), and total testosterone during treatment (P = 0.02) and percent body fat at baseline (P = 0.01) and during treatment (P = 0.004). aMCR-T correlated positively with lean body mass at baseline (P = 0.03) and during treatment (P = 0.01). In multiple regression models, significant predictors of aMCR-T included lean body mass (P = 0.008), percent fat mass (P = 0.009), and SHBG (P = 0.001).

Conclusions: Higher testosterone levels in older men receiving TE were associated with an age-related decrease in apparent testosterone metabolic clearance rates. Body composition and SHBG were significant predictors of aMCR-T.

Pretty cool study. Thanks for sharing. So this study is actually showing evidence that SHBG does indeed play a role in metabolic clearance rate. "Body composition and SHBG were significant predictors of aMCR-T."

Side note: That's crazy they gave some participants 600 mg TE weekly. I would be insane on that dosage.

 

[DS3]

Interesting. One of the reasons I stopped using propionate was that i just couldn’t get my free T to budge past mid point in the range, no matter how high I upped my dose. It was taking way too much propionate to get to much lower levels than I had on cypionate. My E2 was much higher proportionate to the level of T on propionate, compared to cypionate, which I didn’t like.

Very interesting. Crazy how different we all respond to things. My E2 is much easier for me to keep in a good range with Test Prop and my free T is double the reference range. Just adds more fuel to the fire for the thought process that every man's HRT should be tailored specifically to him and his individual response.

 

[Gman86]

Very interesting. Crazy how different we all respond to things. My E2 is much easier for me to keep in a good range with Test Prop and my free T is double the reference range. Just adds more fuel to the fire for the thought process that every man's HRT should be tailored specifically to him and his individual response.

Exactly. We are all very unique. How are you getting a doctor to prescribe that high of a dose? Are you using UGL?

 

[DS3]

Exactly. We are all very unique. How are you getting a doctor to prescribe that high of a dose? Are you using UGL?

My doctor is okay with prescribing T as high is as needed to reach optimal levels. If I was taking that much prop and my total T tested at 2000 ng/dL then he would titrate the dosage. But, given that my total T is where we want it to be, he is okay with it.

I wouldn't use UGL... too much anxiety on my end about getting tainted product.

 

[Cataceous]

That would make sense, but that would also have to mean that your body was excreting bound testosterone at a rate that isn't insignificant. Unless you are proposing that ALL/MOST exogenously ingested testosterone must become free/unbound before it can become excreted.
...

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.

...
If you are using it daily then yes that would make sense. But if using Cypionate as a once per week shot, can you still conclude that individuals with high SHBG or low SHBG would excrete the exogenous T at the same rate? And if you can, then how would you explain how some guys feel a massive 'comedown' accompanied by a significant reduction in T around day 4 or 5, while others can maintain higher levels all the way until day 7 or even 8 or 9?

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.