Does SHBG affect the apparent half-lives of testosterone esters?

[Cataceous]

The relative level of SHBG has a pronounced effect on serum levels of testosterone delivered via TRT. This is through the influence of SHBG on the metabolic clearance rate of testosterone. But as far as I can tell the effect on the apparent half-lives of testosterone esters is subtle at best. Is there some evidence or theory to the contrary?

 

[Vince Carter]

Just the personal experience, a low SHBG guy is going to piss it all out rather quickly, in Dr Crisler's words. I've long held the thought that the half-life of the ester is that in which it's in an ideal, or "normal" environment, or even in a lab environment, but you add in low (or high) SHBG and I think that it does negate the half-life.

 

[Cataceous]

Just the personal experience, a low SHBG guy is going to piss it all out rather quickly, in Dr Crisler's words. I've long held the thought that the half-life of the ester is that in which it's in an ideal, or "normal" environment, or even in a lab environment, but you add in low (or high) SHBG and I think that it does negate the half-life.

Ok, I can see how this might be reconciled with what the basic model is saying. See if you agree: Some guys with SHBG around 50 nmol/L are injecting 100 mg of T cypionate weekly and have trough T values averaging 500 ng/dL. Another group of guys has SHBG more like 10 nmol/L and follows the same protocol, yet their average trough T value is 250 ng/dL. So the natural conclusion is that the low-SHBG guys have excreted "it all out rather quickly". And they have, relatively, because their excretion rate is double that of the higher SHBG guys.

But here's the part where I got tripped up: I was assuming the low-SHBG guys would have equal or higher peaks than the high-SHBG guys. But I don't think this is the case. It looks as though the serum testosterone curves are proportionally smaller the whole time. In this example the high-SHBG guys might peak at 1000 ng/dL while the low SHBG guys would peak at only 500 ng/dL. Thus the half lives remain the same.

 

[Vince Carter]

I don't know if the two are the same, I might read the half-lives are how they reach a serum concentration over time but the rate of clearance is something else.

 

[Cataceous]

I don't know if the two are the same, I might read the half-lives are how they reach a serum concentration over time but the rate of clearance is something else.

Yes, there are really two apparent half-lives at work, one for the absorption from the injected depot, which is different for different esters and formulations. The other half-life is associated with the clearance of testosterone, and is short, from minutes to hours. What can be confusing is that the two half-lives together create the serum testosterone levels we measure. My point with this thread is that SHBG can influence the clearance half-life pretty strongly, but in our serum measurements the longer ester half-life is dominant and controls the relative amplitudes, while the clearance half-life can scale serum measurements up or down by a constant amount.