Sub Q injections quit working

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ivkonst2017

Active Member
We've been through this before. If you want any credibility in contradicting legitimate studies then you must measure the areas under the curves, not to mention demonstrate that you've eliminated all the other confounding variables, such as SHBG changes, injection site leakage, etc. Anything else falls well short of being "rigorous and clear". Which is more likely: You've stumbled across some heretofore undiscovered bizarre medical phenomenon, or you simply jumped to the wrong conclusion based on very limited data?
If you read carefully my posts where Ive described the case you will see all confounding variables have been eliminated and the result is more than clear
 

Cataceous

Super Moderator
If you read carefully my posts where Ive described the case you will see all confounding variables have been eliminated and the result is more than clear
I must have missed your AUC plots and the SHBG values measured simultaneously. If you'd link to them then we can compare your IM and SC absorption. Without these I'll favor the more prosaic explanations for your results.
 

Cataceous

Super Moderator

Vince

Super Moderator
I use both Sub-Q and shallow IM injections. I posted my last labs.

 

ivkonst2017

Active Member
If your SHBG happened to be lower while doing subcutaneous injections then total testosterone would also be lower at the same dose. Here's the analogy I use to explain it:

So far Ive never heard or seen scientific evidence that SHBG value can affect total testosterone value in men on exogenous test? I would agree that can be the case on exogenous production

As much as I have been told by the doctors Ive worked with so far total testosterone in the serum is a function of only what we inject(dose, frequency etc).

For what is worth my SHBG is always fluctuating within 10 units, even while Im on IM but Ive never experienced such a a drop in total t levels since I started doing IM injections. Since Im doing IM my levels always make sense - Ive been on EOD sustanon, daily sustanon(Im daily sucks too much), bi weekly enanthate and now again EOD sustanon. On a protocol that has achieved steady state on IM injections my total t was never below 1100, and I never have injected more than 140mg per week on IM.

On sub q on steady protocol on 160mg per week daily sustanon my total t was 700-800 and it was not lab error, because I also felt like shit, like Im supposed to feel on such levels when Im used to be at around 1200-1300 since I started TRT.

I never mention free t to not overcomplicate thingsnin the context of that discussion, but I always test SHBG as well and it has been moving between 20 and 30 since I started TRT.
 

ivkonst2017

Active Member
I use both Sub-Q and shallow IM injections. I posted my last labs.

Seems you have been mixing them together so I dont see how this contributes to the debate :) To me it seems you are one of the guys that absorbs sub q well and Ive never argued that there are such guys, but NOT EVRYBODY is like that
 

Cataceous

Super Moderator
So far Ive never heard or seen scientific evidence that SHBG value can affect total testosterone value in men on exogenous test? I would agree that can be the case on exogenous production

As much as I have been told by the doctors Ive worked with so far total testosterone in the serum is a function of only what we inject(dose, frequency etc).
...
I should be qualifying it as a hypothesis, but it pretty much falls out of the law of mass action. The primary assumption is that underlying steroid metabolism is basically static over the time frame of interest. Another interesting feature is that the rate at which—exogenous or endogenous—testosterone enters our system directly drives free testosterone, not total. If SHBG isn't changing much then the proportionality can appear to apply to total testosterone also.

Consider a thought experiment: We can infuse a test subject with testosterone at a fixed rate. Assume no endogenous production. At steady state we know that however much testosterone we're putting in, the same amount is being metabolized and eliminated. For example, if we're infusing at a rate of 10 mg T per day then the subject is also metabolizing 10 mg T per day. In accordance with the law of mass action, the rate of metabolism is proportional to the concentration of free testosterone; bound testosterone cannot be metabolized directly. Therefore free testosterone is proportional to the dose rate.
 

ivkonst2017

Active Member
As much as the scientific part of my mind finds all this interesting we know in the practice of TRT its not exactly how it works. At least with me and everyone I observed and have read about it works this way...

I mean if you raise your dose with 20mg weekly your total will rise, right? No matter what happens to the SHBG and free test which can vary in different folks
 

Cataceous

Super Moderator
As much as the scientific part of my mind finds all this interesting we know in the practice of TRT its not exactly how it works. At least with me and everyone I observed and have read about it works this way...

I mean if you raise your dose with 20mg weekly your total will rise, right? No matter what happens to the SHBG and free test which can vary in different folks
Biological systems may result in noisy data, but it's still possible to support or refute hypotheses with well run studies.

At least one large study has shown that free testosterone is proportional to dose. This principle should apply to anyone on TRT. It's easiest to observe with frequent injections where testosterone levels are not changing much between doses. If someone is only injecting once or twice a week then there's a lot more noise in the measurements, and ideally you'd average areas under the curves for a few weeks to get good data. This is impractical for the vast majority of individuals. However, on EOD enanthate I was able to obtain very linear data involving several different doses.

If you raise your dose by 20 mg/week then free testosterone increases in proportion to the extra testosterone. If at the same time you independently lower your SHBG by a sufficient amount then it is possible to have total testosterone go lower. Of course this would be somewhat unusual. Here's an example relying on the Vermeulen free T calculator:

Joe Average takes in 6.5 mg testosterone per day and has a total testosterone of 650 ng/dL. His SHBG is 30 nMol/L and his free testosterone is 15 ng/dL. From this and the free T calculator we infer that his free testosterone in ng/mL may be computed as 15/6.5 * daily_T_intake. Now add 20 mg per week of testosterone cypionate to his intake. This is an extra 2 mg/day of testosterone. His new free T is 15/6.5 * 8.5 = 19.6 ng/dL. What if he halves his SHBG to 15 nMol/L at the same time? Using the free T calculator we find that total testosterone has dropped to 632 ng/dL.
 

Vince

Super Moderator
Seems you have been mixing them together so I dont see how this contributes to the debate :) To me it seems you are one of the guys that absorbs sub q well and Ive never argued that there are such guys, but NOT EVRYBODY is like that
That is my first set of labs, which I was also using sub q. Before that I only did shallow IM. My testosterone panel did not change.

I'm adding my information into this thread.
 

ivkonst2017

Active Member
@Cataceous I get your point and to summarize it in one sentence the idea is that:
It is possible on higher dose to drive down SHBG which will increase the rate of excretion and this can reduce the total t levels build up in the serum.

I think it is a very unlikely scenario even if possible from what Ive seen. In most cases the increase in test income will outweigh the possible reduced SHBG and increased excretion. I mean we see people who up their doses get higher serum concentrations :)

For sure the case with me was not that. My SHBG has stayed relatively stable. In fact it decreased by 20(from 50 to 30) only on starting TRT the first two months(I had no problem with unexpected drop in levels then) and when I have already started IM injections and I cut my metformin dose in half the SHBG went down to 20, but after a while bounced back to around 25, currently its around 30.
Especially when the issue with sub q drop of levels occured it was stable, and on sub q I was doing daily injections.
Also as I mentioned again on sub q Ive been relativy short period of time - 4-5 months and the drop in test levels was big and all comfounding variables and factors were under control. Even after I continued on IM injections and restored the expected high levels I continued using the same vial of testosterone, so a bad batch is out of the question as well. On the other hand on IM injections Ive been over a year now and never had unexpected such drop in total test levels and I test the quite often, cause its cheap and the lab is close to me

So the issue with sub q is either absorbtion or too prolonged half life that doesnt allow build up of proper levels(I think the key is the build up of nodules which by the way sucks too much on its own), whatever it is I dont care and I dont see how I can find out, I just know its not reliable for me to use sub q and I see that in many other people
 

Cataceous

Super Moderator
@Cataceous I get your point and to summarize it in one sentence the idea is that:
It is possible on higher dose to drive down SHBG which will increase the rate of excretion and this can reduce the total t levels build up in the serum.
...
Let me clarify this: At steady state the rate of excretion is determined by the dose. So even after a large change in SHBG, when a new equilibrium is reached the rate of excretion must be the same as before the change. The rate of excretion is driven directly by free testosterone, so free testosterone must also return to its previous value. Because of these effects it is total testosterone that becomes the dependent variable. A sudden decrease in SHBG transiently pushes up free testosterone, which acts to lower total testosterone until free testosterone is forced back to the level needed for excretion to match the rate of testosterone input.
...
So the issue with sub q is either absorbtion or too prolonged half life that doesnt allow build up of proper levels(I think the key is the build up of nodules which by the way sucks too much on its own), whatever it is I dont care and I dont see how I can find out, I just know its not reliable for me to use sub q and I see that in many other people
Regarding other possible explanations for your results, incomplete absorption is very improbable. Aside from the controlled studies showing no such problems, there's the lack of a plausible mechanism for the testosterone to seemingly disappear. Injection site leakage is possible, though it would need to be a regular occurrence, which would make it harder to miss. You suggest unusually slow absorption as a possibility, but unusually fast absorption is a better fit. In the case of slow absorption it is still going to raise your levels eventually. With fast absorption your high peaks pass before you take your measurements. This is why I emphasize that multiple measurements are needed to evaluate area under the curve.
 

bixt

Well-Known Member
The testing Ive done is absolutely rigorous and clear - sub q was causing absurdly low levels of serum concentrations in me, my friends, Im 150 percent sure in that and I would bet all my material assets on that

Its pointless trying to talk sense to these guys @madman and @Cataceous

If they get a study that says the sky is red, its red. Doesnt matter what everyones eyes are seeing.
 

ivkonst2017

Active Member
If they get a study that says the sky is red, its red. Doesnt matter what everyones eyes are seeing.

If I remember correctly it turned out the main study they rely upon is with testosterone without alcohol(correct me if Im wrong). 90 percent of the TRT users use testosterone with alcohol so this study becomes absolutelly IRRELEVANT
 

Cataceous

Super Moderator
If I remember correctly it turned out the main study they rely upon is with testosterone without alcohol(correct me if Im wrong). 90 percent of the TRT users use testosterone with alcohol so this study becomes absolutelly IRRELEVANT
So your new claim is that the presence of benzyl alcohol in testosterone products makes them unusable for subcutaneous injections? It's a peculiar idea, to say the least, with zero supporting evidence. Here's an older study for you that used a standard commercial product with good results:

Conclusion: Therapy with weekly subcutaneous testosterone produced serum levels that were within the normal range in 100% of patients for both peak and trough levels. This is the first report, which demonstrated the efficacy of delivering weekly testosterone using this cheap, safe, and less painful subcutaneous route.
 

bixt

Well-Known Member
100% correct. It was the autoinjector study. There is no BA, no BB and no other preservatives in that sterile injector.

The SAME guys also correctly point out how these excipients affect values in other threads.

Therefore this autoinjector study cannot be used. Also check the scatterbox in that study, theres plenty of outliers all over the chart.

This subq vs IM issue has nothing to do with areas under the curve. Its some other issue causing low levels over long periods of time.
 

bixt

Well-Known Member
So your new claim is that the presence of benzyl alcohol in testosterone products makes them unusable for subcutaneous injections? It's a peculiar idea, to say the least, with zero supporting evidence. Here's an older study for you that used a standard commercial product with good results:

Conclusion: Therapy with weekly subcutaneous testosterone produced serum levels that were within the normal range in 100% of patients for both peak and trough levels. This is the first report, which demonstrated the efficacy of delivering weekly testosterone using this cheap, safe, and less painful subcutaneous route.

Thats not a study! Your paper is a joke.

I have given it a 5 second glance and the following glaring omisions in methodology come to light:

1. Poor sample size. 22 is too small a sample size for producing statistically significant results.

2. No placebo, OR at the least no comparison to IM amongst the sample.

3. Results are vague and meaningless. "Subq produces levels that are 100% in the normal range" is meaningless for the debate at hand. So all these 22 guys could have had levels of 350ng/dl and yay, the study was a success. Its a joke actually. No IM same to compare levels with, at the same dose.
 

bixt

Well-Known Member
So your new claim is that the presence of benzyl alcohol in testosterone products makes them unusable for subcutaneous injections? It's a peculiar idea, to say the least, with zero supporting evidence.
Nobody said that. Find me the proof someone here said that. Quote it.

What we did say is that benzyl alcohol affects absorbtion, and perhaps is responsible for the differences in subq vs IM levels. A hypothesis.

Do not twist words, perhaps your estrogen is at PMS levels and you need some AI?
 
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