SHBG Changes after Keto

[Gus80]

The myth that won't die. Changing SHBG in isolation does not affect free testosterone in normal situations, except transiently. It is total testosterone that responds to such changes. SHBG binds testosterone, so more SHBG means more total testosterone, not more free testosterone.

This is not what my unsuccessful experience of 7 years with TRT, performing exams every 3 months approximately, shows me.
Whenever my SHBG levels went down, estradiol and free testosterone went up a lot. The higher the dose of T, the greater the drop in shbg.

More SHBG = less free testosterone and less estradiol. ((men who respond well to higher doses of TRT).
Less SHBG = more free testosterone and more estradiol. (men who respond badly even to small doses of Testosterone, like me).

So much so that it is possible to increase free testosterone just by manipulating shbg with dht derivatives, even in the absence of extra exogenous testosterone.

But if you have any scientific article that says the opposite, I would like to read it.

 

[Systemlord]

More SHBG = less free testosterone and less estradiol. ((men who respond well to higher doses of TRT).
Less SHBG = more free testosterone and more estradiol. (men who respond badly even to small doses of Testosterone, like me).

So much so that it is possible to increase free testosterone just by manipulating shbg with dht derivatives, even in the absence of extra exogenous testosterone.

This seems to be a commonly held belief, however once your SHBG is fully saturated, Free T rebounds and therefore Free T can no longer be affected by SHBG. SHBG doesn’t affect testosterone production because there’s no mechanism for that, SHBG doesn’t increase or decrease testosterone production, not without changes in LH.

Also E-2 is weakly bound to SHBG, much less than Free T, and again once fully saturated, E-2 is no longer affected. If your have a guy with a Total T at 533 ng/dL, SHBG at 71 and he has low Free T, decreasing the SHBG in isolation will lead to a Total T value <300 and Free T remains unchanged.

So changes in SHBG doesn’t change Free T values. There are some medical conditions which raise the SHBG while also decreasing testosterone production, like starvation. So reducing SHBG isn’t going to do anything for your testosterone production.

 

[Cataceous]

...
But if you have any scientific article that says the opposite, I would like to read it.

Consider it a strong hypothesis, almost to the point of being a theory. @readalot points to support in the mechanistic literature, e.g. here.

I have also argued directly for it like this:

The working hypothesis is that in steady state conditions free testosterone is directly proportional to the production rate of endogenous testosterone, or to the dose rate of exogenous testosterone. Only two primary assumptions are necessary: 1) The rate of testosterone entering the system is matched by the rate of testosterone being metabolized and eliminated. 2) The rate of metabolism and elimination is proportional to the level of free testosterone, following the law of mass action. A secondary assumption is that the underlying rate constant for metabolic clearance is relatively static. There are situations in which this constant changes dramatically, presumably including damage to the liver. But we'd hope these would not be common.​

If the hypothesis is correct then it's clear that SHBG has little effect on free testosterone. ...​

In your case I'd first ask if you are using an accurate test for free testosterone? An immunoassay-based test is inaccurate and unusable. Calculated free testosterone can be viable if SHBG isn't extreme. What is the biological basis for your view? Is it tied to the notion that testosterone production or dosing drives total testosterone? This is probably incorrect unless you can find a flaw in the above reasoning.

 

[Nelson Vergel]

https://onlinelibrary.wiley.com/doi/10.1155/2024/9301369

Three months of keto reduced free testosterone

 

[aloetard]

But if you have any scientific article that says the opposite, I would like to read it

Permanent crash of estrogen?

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Great post by @Cataceous. Get the papers and read them if interested. Well understood phenomena. Clouded in the TRT space by inaccurate testing and lots of youtube misinformation.

 

[Seagal]

https://onlinelibrary.wiley.com/doi/10.1155/2024/9301369

Three months of keto reduced free testosterone

Interesting results but not so good study set-up.

Their results support the hypothesis of decrease in fT with constant TT and increased SHBG.

 

[aloetard]

Interesting results but not so good study set-up.

Their results support the hypothesis of decrease in fT with constant TT and increased SHBG.

I don't see any record of FT measurement in the article. But eyeballing the data I would gather that calculated FT (cFTV) would show lower based on the TT/SHBG data given? I agree with your comment on the set-up.

 

[Seagal]

I don't see any record of FT measurement in the article. But eyeballing the data I would gather that calculated FT (cFTV) would show lower based on the TT/SHBG data given. I agree with your comment on the set-up.

You are right, they write free androgen index and I state fT.
Not a reliable comparison and low power.

"
Study II. Total testosterone was unaffected after the KD compared to the SDD in men (20.2 ± 1.23 nmol/l vs. 18.2 ± 1.23 nmol/l (p = 0.1)) and was lower after KD in women (0.87 ± 0.06 vs. 1.1 ± 0.06 nmol/l (p < 0.0001)).

Sex hormone-binding globulin (SHBG) increased in men after KD compared with SDD (31.2 ± 2.6 nmol/l vs 25.0 ± 2.6 nmol/l, p < 0.0001) and women (26.5 ± 3.05 nmol/l vs 24.2 ± 3.05 nmol/l, p = 0.003).

The free androgen index decreased after KD in men (ratio: 0.65 ± 0.05 vs. ratio: 0.74 ± 0.05, p = 0.04) and in women (ratio: 0.036 ± 0.006 vs. SDD 0.05 ± 0.006, p = 0.0001). Free estradiol index was also found lower after KD in men (ratio: 3.1 ± 0.8 vs. ratio: 4.8 ± 0.8, p = 0.0003) and in women (ratio: 1.2 ± 2.2 vs. 9.8 ± 2.2, p = 0.0001).
"

The study II reference:

https://onlinelibrary.wiley.com/doi/10.1002/oby.23967

Typical salami slicing tactics...

 

[Seagal]

I'm waiting for @Nelson Vergel to ask his AI

 

[Cataceous]

... Their results support the hypothesis of decrease in fT with constant TT and increased SHBG.

... But eyeballing the data I would gather that calculated FT (cFTV) would show lower based on the TT/SHBG data given. ...

I see essentially no change in cFTV based on averages, using 4.3 g/dL for albumin.
Order: Baseline -> KD
SHBG: 25.0 -> 31.2 nMol/L
TT: 18.2 -> 20.2 nMol/L
cFTV: 0.449 -> 0.452 nMol/L
FAI: 72.8 -> 64.7

Using FAI as a proxy for free testosterone seems like a poor choice in 2024.

 

[aloetard]

I see essentially no change in cFTV based on averages, using 4.3 g/dL for albumin.
Order: Baseline -> KD
SHBG: 25.0 -> 31.2 nMol/L
TT: 18.2 -> 20.2 nMol/L
cFTV: 0.449 -> 0.452 nMol/L
FAI: 72.8 -> 64.7

Using FAI as a proxy for free testosterone seems like a poor choice in 2024.

Thanks for running the numbers. Even better confirmation. So the title is not consistent with the data presented. Cataceous masterclass as usual. I hope people don't ever take this person for granted.

 

[Seagal]

Thanks for checking the numbers. Even better confirmation. So the title is not consistent with the data presented. Cataceous masterclass as usual. I hope people don't ever take this person for granted.

Indeed, thank you Cataceous!

And good news for the keto diet