What Effect Does Exercise Have on Free Testosterone Blood Test Results?

This is a probably a VERY basic question for those that have a clear knowledge of how the hormone system works, but one that needs clarifying for those of us who are still learning.

If we assume (incorrectly) for the sake of debate, that when one is on TRT, all Testosterone comes from supplements. In my case, injected Testosterone Cypionate. The amount injected should therefore determine the total amount in the body … The size of the “Cake” or Total Testosterone.



As we know the “Cake” is then divided into three pieces: shown above.

My question is (following a recent blood test) what effect does exercise have on Free Testosterone?

I assume that as we exercise we use up the Free Testosterone and this can be seen in the measured blood test percentage, reducing as we exercise?

Why do I ask this? I have been on the same protocol for over a year. During the first six months I was physically very active. During the second six months I have been very busy at work and far less active. My recent blood test shows that my free testosterone percentage (%) is significantly higher (whilst on the same protocol). Is this to be expected, due to my more sedentary life style? Do I simply reduce my Cypionate protocol when less physically active?

What has confused me slightly, is that the total testosterone (ng/dL) is also elevated. Perhaps one would expect this to rise due to the increased amount of Free Testosterone circulating?

Perhaps my latest batch of Cypionate is stronger in mg terms per mL than advertised and I have inadvertently been taking a larger dose of Testosterone?

What effect on Total, Free & Bioavailable Testosterone does exercise have on blood test results?

jacb said:

The amount injected should therefore determine the total amount in the body … The size of the “Cake” or Total Testosterone.

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The amount injected determines the free testosterone (obligatory bow to Saint Cataceous). After 5 elimination half lives your blood levels will have a stable profile. Your Total Testosterone is set by your free T, SHBG, and HSA.

You are injecting free testosterone (once the carboxylic acid pops off fhe testosterone ester). What happened with your SHBG over time?

What did your free testosterone do over time? Post fT, SHBG, TT results you have all for the same protocol.

Your liver clearance of free testosterone (elimination rate) may have changed over time with activity level?

One more time....

Hi Aloetard

Yes you are technically correct we do inject “Free Testosterone” which then binds to Albumin (Human Serum Albumin or HSA) to give us Bioavailable & SHBG to give us SHBG-Bound testosterone. What remains is still Free Testosterone.

I understand what you are saying about the pining protocol employed coupled with the half life of particular testosterone ester combination selected. It will take a number of injections before levels stabilise hence the suggested 8 weeks on any protocol before testing. There are a number of good graphing tools available online that show this effect in graphic form. Like the one found here: LINK.

I have no idea who or what you are referring to with your “Saint Cataceous” reference? ….. (Note added later… would that be Cataceous the Super Moderator?)

Re my results:

6 months on Protocol then tested on 22/02/24
Protocol using hCG
Lots of exercise
TT 1015 ng/dl (too high) 114mg/week
SHBG 36 nmol/L
Albumin 46 g/L
FT 2.23%
BioT. 55.7%

23/02/24 - 23/08/24
Same protocol ….. but no hCG hence no reduction in testosterone.
Sedentary
TT 1343 ng/dL (way too high - but why?) 114mg/week
SHBG 35 nmol/L
Albumin 44 g/L
FT 2.51% (of a bigger Total Testosterone number)
BioT. 60.2%

I will now reduce TC to 96mg/week and try and get back to doing more exercise.

aloetard said:

The amount injected determines the free testosterone (obligatory bow to Saint Cataceous). After 5 elimination half lives your blood levels will have a stable profile. Your Total Testosterone is set by your free T, SHBG, and HSA.

You are injecting free testosterone (once the carboxylic acid pops off fhe testosterone ester). What happened with your SHBG over time?

What did your free testosterone do over time? Post fT, SHBG, TT results you have all for the same protocol.

Your liver clearance of free testosterone (elimination rate) may have changed over time with activity level?

One more time....

Paradox TRT results, very low SHBG

A few points to consider: Your T is fake. No offense, but looks legit and seems reputable doesn’t make it so. It’s a risk with UGL and you lost this time. Even with low SHBG, 3x weekly would be enough to see a serum T increase. Your PRL is a bit high. Your SHBG was low before TRT. Very, very...

www.excelmale.com

SHBG and Free Testosterone - Everything You Need to Know

Table of Contents Testosterone Fractions in Men How SHBG Influences Free Testosterone What Factors Influence Your SHBG Levels? How Do You Know if Your SHBG Levels Are High? How to Lower SHBG and Automatically Increase Free Testosterone Levels? Raise Your Total Testosterone Level Lower Your...

www.excelmale.com

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Biophysics while assuming stable boundary conditions.
I agree with Jacob's experience. Might be 'just' liver clearance depending on metabolism. No idea. I gave up on digging into theoretical details and follow an empirical approach.

jacb said:

Hi Aloetard

Yes you are technically correct we do inject “Free Testosterone” which then binds to Albumin (Human Serum Albumin or HSA) to give us Bioavailable & SHBG to give us SHBG-Bound testosterone. What remains is still Free Testosterone.

I understand what you are saying about the pining protocol employed coupled with the half life of particular testosterone ester combination selected. It will take a number of injections before levels stabilise hence the suggested 8 weeks on any protocol before testing. There are a number of good graphing tools available online that show this effect in graphic form. Like the one found here: LINK.

I have no idea who or what you are referring to with your “Saint Cataceous” reference? ….. (Note added later… would that be Cataceous the Super Moderator?)

Re my results:

6 months on Protocol then tested on 22/02/24
Protocol using hCG
Lots of exercise
TT 1015 ng/dl (too high) 114mg/week
SHBG 36 nmol/L
Albumin 46 g/L
FT 2.23%
BioT. 55.7%

23/02/24 - 23/08/24
Same protocol ….. but no hCG hence no reduction in testosterone.
Sedentary
TT 1343 ng/dL (way too high - but why?) 114mg/week
SHBG 35 nmol/L
Albumin 44 g/L
FT 2.51% (of a bigger Total Testosterone number)
BioT. 60.2%

I will now reduce TC to 96mg/week and try and get back to doing more exercise.

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Thanks. So timing of blood draw relative to injection same for both results? Same injection frequency?

Seagal said:

I gave up on digging into theoretical details and follow an empirical approach.

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Good approach. Too much work for too little return. I have learned the hard way but enjoy math models and fitting data.

aloetard said:

Thanks. So timing of blood draw relative to injection same for both results? Same injection frequency?

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Yes same test time (09:40 hrs give or take the odd minute)
Yes same injection frequency (every other day)

jacb said:

Yes same test time (09:40 hrs give or take the odd minute)
Yes same injection frequency (every other day)

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Wow, very cool. If what you were injecting was same for both time points above and same injection location, then I would think your liver clearance changed. Thanks for sharing!

Back to your hypothesis:

Exercise--->Liver blood flow increases, upregulation enzymes--->increased clearance

aloetard said:

If what you were injecting was same for both time points above and same injection location, then I would think your liver clearance changed.

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Thanks again.

“Liver clearance” change … a factor I hadn’t considered, but that makes sense. Your linked article will take some studying.

I am not sure if my changed liver clearance is positive or negative (perhaps just a change?) on one hand I seem to be getting more total and free T for the same input (more effective striping of the ester) if this is done in the liver it would seem to be more efficient (positive) …. Then again if the liver is a consumer of free T etc, it doesn’t seem to be mopping up (using) the available testosterone (negative) ….. I simply don’t know enough about how the body works.

jacb said:

Thanks again.

“Liver clearance” change … a factor I hadn’t considered, but that makes sense. Your linked article will take some studying.

I am not sure if my changed liver clearance is positive or negative (perhaps just a change?) on one hand I seem to be getting more total and free T for the same input (more effective striping of the ester) if this is done in the liver it would seem to be more efficient (positive) …. Then again if the liver is a consumer of free T etc, it doesn’t seem to be mopping up (using) the available testosterone (negative) ….. I simply don’t know enough about how the body works.

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Here's the theory (very hard to find my old stuff on here; only have myself to blame):


You only have single points in time. What you would like to know is area under curve (AUC). In the absence of additional info you know that AUC for fT is proportional to dose. It is probably pretty close for both cases (you are going through the same mg of testosterone each week). But there is some variation in your serum concentrations over the week (exercise vs no exercise) as your single data points show; your liver clears the T faster or slower which changes your elimination rate constant. There is also the term called distribution volume.

I wouldn't worry about it. But if the single time point is concerning then do what makes you comfortable.

aloetard said:

I wouldn't worry about it. But if the single time point is concerning then do what makes you comfortable.

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Yes this is only a single test and the lab’ may have changed the test method .. there are many variables.

As a guy of 230 lbs/6 1” in reasonable shape for a 64 year old the amount of Testosterone Cypionate I have been talking was not excessive at 114mg per week. I felt ok on it, but TT 1343 ng/dL is way too high.

I will therefore reduce my protocol to 0.11mL x EOD and retest in the future.
(0.11mL of 250mg/1mL = 27.5mg) (27.5mg x 3.5 = 96.25mg per week).

jacb said:

Yes this is only a single test and the lab’ may have changed the test method .. there are many variables.

As a guy of 230 lbs/6 1” in reasonable shape for a 64 year old the amount of Testosterone Cypionate I have been talking was not excessive at 114mg per week. I felt ok on it, but TT 1343 ng/dL is way too high.

I will therefore reduce my protocol to 0.11mL x EOD and retest in the future.
(0.11mL of 250mg/1mL = 27.5mg) (27.5mg x 3.5 = 96.25mg per week).

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That does seem high for that dose. What is your injection frequency? When was the blood drawn with respect to injection (elapsed hours)?

I did a dose response graph a ways back.


Your response is quite high on that last data set.

jacb said:

I have no idea who or what you are referring to with your “Saint Cataceous” reference? ….. (Note added later… would that be Cataceous the Super Moderator?)

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Yes. Meant to be a nice hat tip.

aloetard said:

What is your injection frequency?
When was the blood drawn with respect to injection (elapsed hours)?

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EOD = Every Other Day (3.5 times a week).
The blood was drawn 24 hours after the last injection. (Immediately prior to the next one).

Yes according to the chart your link took me to … my response to 114mg/week would be quite exceptional.

jacb said:

EOD = Every Other Day (3.5 times a week).
The blood was drawn 24 hours after the last injection. (Immediately prior to the next one).

Yes according to the chart your link took me to … my response to 114mg/week would be quite exceptional.

View attachment 47091

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Wow, thanks. So your weekly profile is pretty stable on that frequency. Both of your data points shared above show exceptional response on the chart (>= 97.5 percentile). Your SHBG is mid range. Hence, your results are indicative of a very low end "volume of distribution" to explain such high serum levels at that dose. Your frequent injections cancel out the "liver clearance" being the major driver of what's observed. By injecting so frequently you have largely nullified any pharmacokinetic artifacts of blood sample timing vs injection.

Approximate peak to trough ratio for EOD timing ~1.15 (see assimptions below)


Appreciate you sharing your details..

More details on Vd...

jacb said:

… my response to 114mg/week would be quite exceptional.

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Making it seem even more likely to be a lab error or some dosing issue instead of a 50% increase in free testosterone caused by a very large change in liver metabolism.

Cataceous said:

Making it seem even more likely to be a lab error or some dosing issue instead of a 50% increase in free testosterone caused by a very large change in liver metabolism.

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Or that, LOL!

I felt something was odd when I got the results … hence my initial question and trying to see if I had done anything differently. I am fairly certain (no one can ever be 100%) that I have been consistent in my timing, dosage etc. so the new batch of Cypionate may be stronger than advertised or the test itself may have changed. I don’t know, but I will reduce to just less than 100mg/week and retest in the future.

I did find myself thinking about the Liver Clearance issue and that led me to think about liver health in general. What tests are available that might be worth monitoring if any?

The internet shows that there are a broad spectrum of laboratory tests available to evaluate liver function/possible liver damage. Liver testing generally seems to include: alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), serum bilirubin, prothrombin time (PT), and albumin tests. ALT and AST are markers of hepatocellular damage, ALP and GGT are markers of cholestasis, PT and albumin are indicators of synthetic function, and bilirubin is a nonspecific marker of liver function.

Regarding a “clearance test” to evaluate the functional mass of the liver, which reflects the volume of a given substance removed per unit of time. It seems that a practical test of hepatic clearance as a diagnostic measure began with the introduction of sulfobromophthalein (AKA bromsulphthalein & BSP). It was first used in 1924 to estimate hepatic clearance. Due to severe anaphylactic reactions in some patients, it is rarely used today.

Is there a modern-day equivalent to the BSP liver clearance test?