T Nation

SHBG Upregulation

SHBG upregulation

Does an increase of free testosterone causes an SHBG upregulation as an homeostatic response?

If one subject genetically has high SHBG that will led him to have low free testosterone. This will be his homeostatic set point.
Then this subject decides to go into TRT or blasting. At first there’s a honeymoon period when the effects of extra testosterone are notable. Then things feel the same as they were at the start.
Most steroid users have reported a loss of effects after some time (hence the Androgen Receptor down regulation theory).
Also Proviron users report a honeymoon period that fades as time goes, given that mesterolone binds to SHBG the body tends to produce more of it to restore its own free test balance.

Is it possible that the improvements that TRT guys need rely on an increase in free test (which they were deficient), but this improvement fades as the body increases SHBG production in an homeostatic quest?

May be of interest. See plot linked therein.

Big difference between endogenous T production with an intact HPTGA vs using exogenous T where one uncouples negative feedback loop between T/E2 and hypothalamus/pituitary.

With endogenous T production there is typically strong correlation between TT and SHBG. With exogenous T use you see SHBG decrease over time with TRT/AAS usage [usually dose dependent].

Also usually misunderstood…your T dose sets your free T level and then SHBG sets your Total T. That is fT level set by mass action (how much T you inject) then SHBG binds some fT to TT by dynamic equilibrium (storage). At steady state for same injection amount per unit time, the amount of fT leaving body is proportional to amount entering body. At steady state there is no accumulation hence SHBG can’t change fT level for a constant T dosage per unit time (only the storage amount). Also ignoring downstream conversion, E2, etc.

You can try this experiment yourself by keeping your TRT dose constant and drop SHBG with another medication like oxandrolone/etc. Now compare your pre and post TT/ fT levels using accurate TT/fT methods.

I’d argue (if SHBG does play a role) that more realistically the honeymoon period fades for many due to T/AAS abuse which erodes SHBG over time (there’s probably a bunch of factors in the erosion of that honeymoon phase). You don’t see SHBG increase over time with with exogenous T use. We still don’t understand the full roles of fT/TT and relative impacts which are coupled with SHBG.

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Yeah I see it much clearer now.

Are you being serious or joking? Glad it’s clearer to you than to me! :smiley:

Too bad we don’t have access to high quality fT measurements in the literature from which to draw meaningful conclusions. Many times hypothesis testing gets clouded by TT numbers which are coupled to fT and SHBG. I’m still waiting to see which free T calc is accurate as there’s still no consensus on Vermeulen vs Tru-T.

Also standardized fT numbers will help since I still don’t know if we are really measuring fT today. Waiting with anticipation …

My assumption was that at first they notice the increase in neurotransmitter activity, but that eventually becomes their new set point, so they stop noticing that big surge they felt in the beginning. When they up their dose, or change frequency, or whatever, DA/SA changes and they “feel” it again, but eventually that will balance again and they’ll be back to their new normal.

Agreed. I was just pointing out if SHBG is involved, it’s not because SHBG increases with TRT over time and hence rendering fT lower. It’s the opposite once you understand the effect of androgens on the liver and SHBG production. Neurotransmitter effects and “burn out” over time seem very plausible in this “honeymoon” stuff.

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I was not joking, you explained it very clear and that insight has been of great value

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That theory is more plausible