Calculate Free Testosterone with TruT by FPT

[DragonBits]

It's a great question.

Based on my reading of madman's post about the range, I believe it's the "16-31" range isn't a "95% of people fall into this" sort of range but rather the "therapeutic target" range. So it's something like, if you're in that 16-31 range, you may not have hypogonadal symptoms.

That's my reading at least.

@madman stated "Based on the new data on the distribution of free testosterone levels in healthy men the target range of free testosterone has been determined to be 164 to 314 pg/ml (mean+/−1SD)"

One problem I have with Trut is that it requires me to measure shbg each time I measure total T, that is if I want to know free T. I don't often order the shbg test.

I looked at those times I did measure both shbg and Free T, 5 out of 7 times the results when looking at their respective ranges were close enough. As an example, what I mean is when my free T measured by immunoassay was 24.7 (6.6-18.1 range), my calculated T by Trut was 48.64 (16-31 range). So both tests tell me I was over range, either by 36% or by 56% respectively. I didn't really need to know my exact free T, my total T of 1492 implied I would be well over.

Now 2 times the TruT gave more insight, once my total T was 690, free T 20.7 (6.6-18.1) and truT 21.5 (16-31. Based on my total T, i was inclined not to believe the free T number, and thought the trut result more realistic. My DHEA at 450 30-295) was significantly over range that day, perhaps that influenced the results of the immunoassay test.

BTW, the 16-31 range is NOT the really the "therapeutic target" range, its what was actually measured in "healthy men".

We know there has been a generational decline in total / free testosterone, so the distribution of free T now days is lower than the distribution of free T used to be 50 years ago. So is that range really therapeutic if it was much higher 50 years ago?

Just as average weight has gone up, if we take a distribution of normal, then average weight will be higher and BMI will be higher now.

 

[apsjiml]

I would stick with equilibrium dialysis for free testosterone. Free direct is not accurate at all. Alga rhythms you could try those as a back up but none of them are shown to necessarily be super accurate. Tru-t that is not shown to be accurate either. FDA registered means nothing. Doesn't mean it is more accurate- you could test it against equilibrium dialysis to see but nothing was proven that Tru T was necessarily accurate than any other method.

 

[Cataceous]

... Doesn't mean it is more accurate- you could test it against equilibrium dialysis to see but nothing was proven that Tru T was necessarily accurate than any other method.

This is contradicted by the research quoted by @madman earlier in this thread. If you have specific criticisms of the research then do share. Otherwise one must assume your opinion is without foundation.

 

[galaxy]

Hi All - Quick question. To build on DragonBits point made about the ranges.

While I agree that having the most accurate diagnostic testing is always the best case, my question is this: If the magnitude of the error in the direct Free Testosterone test is roughly the same in all (Big if and this is the crux of the question), then wouldn't having direct Free Testosterone numbers still be helpful. As long as all studies and clinical diagnostics are being done on the same tool, and IF the that tool has the same error rate isn't the outcome going to be the same?

I.E. if through helping thousands of patients a doctor notices in his clinical practice that direct Free T between 20 & 30 alleviates symptoms....then why does it matter if the absolute measurement is off? Unless the direct Free T error itself can vary substantially from individual to individual.

Similarly, if all the studies indicate TRT safety in the upper 20s using the direct Free T test, and once again there is no real difference in the error rate why do we really care about using the more accurate version?

 

[Cataceous]

...
I.E. if through helping thousands of patients a doctor notices in his clinical practice that direct Free T between 20 & 30 alleviates symptoms....then why does it matter if the absolute measurement is off? Unless the direct Free T error itself can vary substantially from individual to individual.

Similarly, if all the studies indicate TRT safety in the upper 20s using the direct Free T test, and once again there is no real difference in the error rate why do we really care about using the more accurate version?

Let me show you my lab results, and you'll see why I believe the direct free T test has limited value:

In terms of basic modeling, free testosterone should be proportional to dose. The Tru-T results illustrate this beautifully. But with an R-square of less than 0.5, the direct tests are clearly not accurate enough to be trusted.

 

[galaxy]

Right I see what you mean about the accuracy. My question is what do we do with the Tru T number.

Presumably we are all dosing to a dose based on a combination of factors:

1) doctor's clinical experience (I'm with defy)
2) a level that ameliorates symptoms
3) a level that has minimal to no negative side effects

which based on my understanding typically leads to a direct free T of ranging between 20-35.

While I understand Free T isn't as accurate what is the net immediate change we can make by having the True T number.

I'm not trying to be difficult I just am trying to understand what do we do with the Tru T number. Do we have enough clinical data to dose according to that number?

 

[Cataceous]

...
While I understand Free T isn't as accurate what is the net immediate change we can make by having the True T number.

I'm not trying to be difficult I just am trying to understand what do we do with the Tru T number. Do we have enough clinical data to dose according to that number?

The main issue is that if you're relying on direct free T to make clinical decisions then there's a greater chance of making mistakes. If you have enough SHBG and TT data then you can generate Tru-T numbers to compare to previous direct free T values, which is basically what I did with my lab results. The bare minimum usefulness to Tru-T is to compare your numbers to the healthy target range of 16-31 ng/dL. But I've been able to take things further, using Tru-T in reverse to predict my testosterone lab results so accurately that I almost don't need to test, and that's even while using a combination of testosterone esters.

You also don't touch on the the issue of consistency. You say direct free T should be 20-35. Which units? Presumably pg/mL. Which lab? Don't think for a second that LabCorp and Quest have interchangeable free T ranges. This creates another opportunity for significant misunderstandings and errors.

The point is that total testosterone and SHBG are more likely to be accurate and harmonious across different labs, making Tru-T a measure that is closer to universal.

 

[galaxy]

Gotcha thanks for explaining.

 

[sammmy]

My latest measurement, not using any androgens:
Total Testosterone 711 ng/dL
SHBG 58 nmol/L
Albumin 4.8 g/L

TruT Free Testosterone calculated: 19.84ng/dL = 198.4 pg/mL, with unspecified normal range?

Free Testosterone (Dialysis test by Quest Diagnostics): 78.2pg/mL with normal range 35-155.

The obvious issue is that if TruT has the same normal range, it turns out I have free testosterone above the normal range.
On the other hand, I have delayed ejaculation, not being able to put a lot of muscle by exercising, some flat around the navel, which contradicts any claim for "high free testosterone".

 

[sammmy]

The bare minimum usefulness to Tru-T is to compare your numbers to the healthy target range of 16-31 ng/dL.
Don't think for a second that LabCorp and Quest have interchangeable free T ranges. This creates another opportunity for significant misunderstandings and errors.

The point is that total testosterone and SHBG are more likely to be accurate and harmonious across different labs, making Tru-T a measure that is closer to universal.

16-31 ng/dL = 160 - 310 pg/mL

Normal range for Quest Diagnostics Free Testosterone (Dialysis) is 35 - 155 pg/mL

This is exactly the issue. Apparently the ranges between the calculator and the labs are not the same.

An attempt to account for that is to calculate where in the normal range you are:

For me TruT Free Testosterone calculated is 19.84 which is at position in the range: (19.84-16)/(31-16) = 0.256

Quest Diagnostics is 78.2 which is at position in the range: (78.2-35)/(155-35) = 0.36

The values are closer this way but obviously still do not match because selecting the lowest and highest normal range is subjective and depends on the data set used and the criteria for "normal".

 

[sammmy]

The best one can do is to plot a graph of the free testosterone values obtained by their Lab test (Dialysis) and the corresponding values calculated by TruT.

If these align along a straight line, one can do a linear regression to obtain the linear relationship between the Lab values and the calculator values. After that, one can just measure Total T, SHBG, and Albumin and calculate TruT after which can obtain the corresponding lab test value.

 

[Cataceous]

The best one can do is to plot a graph of the free testosterone values obtained by their Lab test (Dialysis) and the corresponding values calculated by TruT.

If these align along a straight line, one can do a linear regression to obtain the linear relationship between the Lab values and the calculator values. After that, one can just measure Total T, SHBG, and Albumin and calculate TruT after which can obtain the corresponding lab test value.

We actually did that for someone's results with Quest:

We're also wondering about the quality of Quest's purported equilibrium dialysis test, because it is so much less expensive than at other labs.

 

[sammmy]

Let me show you my lab results, and you'll see why I believe the direct free T test has limited value:
View attachment 9667
View attachment 9668
In terms of basic modeling, free testosterone should be proportional to dose. The Tru-T results illustrate this beautifully. But with an R-square of less than 0.5, the direct tests are clearly not accurate enough to be trusted.

Free testosterone depends also on SHBG (which depends on injectable dose) and other factors so getting a perfect straight line between TruT and your injectable dose probably reflects the linear formula used by TruT, not the actual values of free testosterone.

It is highly suspect for any medical measurement (assuming TruT is the actual value of free testosterone) to get such a perfect linear linear fit with another variable.

 

[Cataceous]

Free testosterone depends also on SHBG (which depends on injectable dose) and other factors so getting a perfect straight line between TruT and your injectable dose probably reflects the linear formula used by TruT, not the actual values of free testosterone.

It is highly suspect for any medical measurement (assuming TruT is the actual value of free testosterone) to get such a perfect linear linear fit with another variable.

I admit the data look too good to be true, but they are the real deal. The only small fudge is that there are a couple other data points not used in this graph that are just off the line. They only reduce R-squared a little, and were trending away from an origin intercept. I wanted to get the best dose-response estimate to use for future predictions. The graph with all seven data points is in another thread somewhere.

The linearity is because free testosterone should basically be proportional to dose, not because of anything to do with Tru-T. It's just that Tru-T is giving a better estimate of free T than Vermeulen, the direct measurement, etc. The reasoning on proportionality is this: The rate of testosterone absorption in TRT is proportional to dose. The law of mass action says that the production rate (absorption rate in TRT) is proportional to the hormone concentration, free testosterone in this case. So:

k * dose = production_rate = MCR * free_T = MCR * f(T, SHBG)

where MCR is a metabolic clearance rate constant. This means:

free_T = constant * dose

I've noted that there aren't guarantees that MCR won't change over time. But my results show that mine has been stable over a period of five years, and with SHBG values ranging from 20s to 40s nMol/L.

 

[sammmy]

In that model, freeT will be proportional to dose only if k/MCR remains constant, irrespective of dose and other factors.

The absorption rate after an injection is probably not constant - it is due to diffusion and probably diminishes with the dose concentration, so it matters at what time you measure the total testosterone after injection.

If looks like what you are doing is proving that total circulating testosterone measured at fixed time after injection is proportional to the dose.

If that is the case, and the calculator uses a formula highly linear with respect to the total testosterone and not very dependent on the other variables, you will get a near perfect straight line between dose and free testosterone from the calculator.

However, the relation
freeT (at what time after injetion?) = constant * dose
needs to be verified with a highly precise actual measurement of free testosterone, not calculators. I do not believe in that relationship at all.

 

[Cataceous]

The slowly changing absorption rate of an injected testosterone ester is just a distraction here. The theory is better understood by thinking of the limit, in which identical tiny amounts of the ester are injected at such frequent intervals that the absorption rate is effectively constant, and of course is proportional to the individual doses. The proportionality constant is the "k" above; it doesn't change. MCR, the metabolic clearance rate, is generally considered to be a constant, even though it is dependent on many underlying factors. The fact that mine hasn't changed over a significant time period is at least suggestive that it can be fairly stable.

What I'm showing is that average free testosterone is proportional to dose if the same dose is administered at constant intervals. In the limiting case where the inter-dose interval goes to zero then free testosterone becomes constant. It doesn't take anything extreme to create these conditions: Every-other-day dosing of cypionate or enathate leads to nearly constant testosterone levels.

If that is the case, and the calculator uses a formula highly linear with respect to the total testosterone and not very dependent on the other variables, you will get a near perfect straight line between dose and free testosterone from the calculator.​

This only describes a case with unchanging SHBG. One of the points of this exercise is to show that changes in SHBG lead to changes in total testosterone, not changes in free testosterone, at least after stabilization. The concept is intuitively better understood with reference to a fluid flow analogy, which I presented here.

These ideas are based on currently accepted models, so I am fairly confident in the general principles, but acknowledge that I'd like to see other guys collecting data to verify the linearity. In fact, I think this kind of calibration should be a first step in TRT for anyone. It's very useful to establish a dose-response relationship that can be used to predict testosterone levels from any dose.

 

[sammmy]

If your total testosterone remains constant in between frequent doses can easily be checked with several measurements between two doses. If you inject every day or every other day, that will require several measurements on the same day.

Even if that is true, the theory that your free testosterone remains constant between doses and is proportional to the doses in a steady state has to be verified with an actual precise measurement of free testosterone. An online calculator doesn't prove that just because it fits a simplistic model.

It is also puzzling why a test by Quest diagnostics that purports to measure the full amount of free testosterone and the online calculator that purports to estimate the same have completely different normal ranges in the same units and most importantly they have centers of normal ranges that differ by a factor of 2. Even if their definition of "normal range" is different, I expect the center to be approximately the same, not differ by a huge scale factor.

 

[Cataceous]

If your total testosterone remains constant in between frequent doses can easily be checked with several measurements between two doses. If you inject every day or every other day, that will require several measurements on the same day.
...

In fact I do expect a little rise post-injection in these cases, but it's not enough to affect the results. I did measure consistent values pre-injection and day-after injection on the EOD schedule.

...
Even if that is true, the theory that your free testosterone remains constant between doses and is proportional to the doses in a steady state has to be verified with an actual precise measurement of free testosterone. An online calculator doesn't prove that just because it fits a simplistic model.
...

The literature on TRT does not support the notion of arbitrary variations in T or free T. The creators of free T calculations believe that it's possible to obtain a fairly accurate value for free testosterone based on total testosterone, SHBG, etc. If you prefer to reject that then it's beyond my purview. But the calculation of free T is not essential to the underlying principles; it just allows a nice demonstration of them. The Law of Mass Action is accepted theory, and harder to reject.

There are two basic principles: 1) If we're putting testosterone in at a steady rate then at steady state it's being used up at the same rate. 2) The rate of use is proportional to the free hormone concentration. Therefore, free testosterone is proportional to the amount of testosterone we're putting in.

Is there additional complexity beyond this model? Most likely. Does it matter in most cases? Probably not.

...
It is also puzzling why a test by Quest diagnostics that purports to measure the full amount of free testosterone and the online calculator that purports to estimate the same have completely different normal ranges in the same units and most importantly they have centers of normal ranges that differ by a factor of 2. Even if their definition of "normal range" is different, I expect the center to be approximately the same, not differ by a huge scale factor.

This is par for the course. Different assays produce very different results. The direct assays are typically giving results around 10-30 pg/mL, which is off by a factor of 10 from the true concentrations. It would be ok if they correlated well with more accurate tests, but they don't do that either. The point of the Tru-T calculator is attain better correlation with the most accurate testing method, which it does.

 

[sammmy]

The main problem why I don't believe free testosterone is simply proportional to the dose in steady state is the negative feedback in the body that will try to regulate it, probably by adjusting SHBG etc. It seems too good to be true that you put twice the dose and voila you get twice the free testosterone.

 

[Cataceous]

The main problem why I don't believe free testosterone is simply proportional to the dose in steady state is the negative feedback in the body that will try to regulate it, probably by adjusting SHBG etc. It seems too good to be true that you put twice the dose and voila you get twice the free testosterone.

On TRT, testosterone regulation is disabled due to HPTA shutdown. It's true that excess androgens typically reduce SHBG, though this takes place over weeks to months, and the phenomenon doesn't affect the argument that free testosterone is proportional to dose. The consequence of falling SHBG is falling total testosterone. This then maintains free testosterone as it was.

If the idea is too simple to be true then one of the two points I listed above must be wrong. The idea of testosterone consumption equaling testosterone input at steady state seems almost self-evident and hard to attack. It's a little easier to criticize the concept of hormone usage being proportional to concentration, though the idea is widely accepted. The model probably isn't perfect over all forms of testosterone metabolism. Nonetheless, it seems likely that any errors are small enough to ignore.