SHBG cause or consequence of hypogonadism?

[arsenio7]

Dear all,

I'm pretty amazed by this website and the quality of all the discussions in that forum.

I recently did some tests because I had the feeling that something was wrong with my T level, and also because I had a shock down there while doing sport a few months ago.

My result is 720 ng/dL for full T and 71 for nmol/L (I'm not under TRT)

The lab page report contains something a bit scary, like if high SHBG is a consequence of hypogonadism

(http://admed.ne.ch/files/flhn/flhn-info/042_2008_09_12_AdmedInfo_SHBG.pdf).

In my understanding, the consequence of high SHBG can be lack of T, if total T is not compensating. But not the consequence, or is it the other way around?

I'd redo the test,
I'll add LH, albumine, and prolactine, is there something else to add?

Best regards!

 

[Systemlord]

In my understanding, the consequence of high SHBG can be lack of T, if total T is not compensating.

The high SHBG will increase your Total T and decrease your Free T, the most potent active form of T.

Normally when a person has very high SHBG, high Total T, low Free T and high LH, this isn't secondary hypogonadism, but SHBG production out of control, for which the pituitary cannot compensate for.

So add Free T to your list using the more accurate method LC/MS and not the direct method.

 

[FunkOdyssey]

The cause or consequence question is interesting because androgens do reduce SHBG. Your SHBG will usually come down if you start TRT for example. Mine has already dropped from 50-56 to 43 nmol/L after just a month at a low dose. So, you could argue it is a consequence, at least in some cases -- if your body were making more testosterone the ShBG would be lower.

 

[arsenio7]

So add Free T to your list using the more accurate method LC/MS and not the direct method.

do estradiol and growth hormone test make sense as well?

thanks so much

 

[Cataceous]

The high SHBG will increase your Total T ...

Yes.

... and decrease your Free T...

No. The hypothalamus and pituitary regulate free testosterone; at steady state they are minimally influenced by total testosterone or SHBG. There's no evidence that elevated SHBG causes low free testosterone—except transiently if you happened to inject a bunch.

The cause or consequence question is interesting because androgens do reduce SHBG. ...

Yes, so it is likely that hypogonadism, aka low free testosterone, contributes to higher SHBG. This yields the observed inverse correlation.

 

[arsenio7]

thanks @Cataceous for this complete answer.

when shbg becomes high for other reasons, the pituitary gland is then supposed to adapt LH in order to higher T generation to keep an acceptable free T. is that roughly the idea?

 

[savefoxes]

Yes.

No. The hypothalamus and pituitary regulate free testosterone; at steady state they are minimally influenced by total testosterone or SHBG. There's no evidence that elevated SHBG causes low free testosterone—except transiently if you happened to inject a bunch.


Yes, so it is likely that hypogonadism, aka low free testosterone, contributes to higher SHBG. This yields the observed inverse correlation.

You're saying that low free T is caused by low T production no matter what SHBG level is, but why when injecting trt doses of T that provide a flow of free T it still gets bound by the shbg leaving a person with low free T levels?

 

[Systemlord]

Yes, so it is likely that hypogonadism, aka low free testosterone, contributes to higher SHBG.

So a low level of androgens has less of a suppressive effect on SHBG. Got it.

 

[FunkOdyssey]

You're saying that low free T is caused by low T production no matter what SHBG level is, but why when injecting trt doses of T that provide a flow of free T it still gets bound by the shbg leaving a person with low free T levels?

Does it though? I would say it raises their free T proportionately to the dose and leaves with them high total T levels. If you adjusted the dose to reach a certain target total T value, you would hit the total T at a lower dose than average and the free T would be lower than average, only because the dose was lower.

People's responses vary but I think if you give a high SHBG guy a certain dose and a lower SHBG guy the same dose, and everything else was equal, they'd probably have comparable free T but the high SHBG guy's total would be high and the low SHBG guy's total would be low.

 

[Cataceous]

...
when shbg becomes high for other reasons, the pituitary gland is then supposed to adapt LH in order to higher T generation to keep an acceptable free T. is that roughly the idea?

There's no need for higher testosterone production. Think of production as equaling free testosterone. At steady state the amount of SHBG is basically irrelevant. Someone recently suggested a sponge analogy: SHBG is likened to a sponge, with testosterone being the water. Testosterone—water—is dripped onto the sponge. This represents production. When the sponge is saturated the testosterone drips off the bottom of the sponge—this represents free testosterone being used. At steady state the flow of testosterone leaving the sponge equals the production entering the sponge. You can double the size of the sponge—the amount of SHBG—which temporarily reduces the flow, but the sponge soon saturates again so that outflow again equals inflow. A larger sponge means more total testosterone is contained within the sponge. But that testosterone within the sponge isn't doing much of anything, and so is largely irrelevant. For the sake of simplicity this ignores the possible benefits in having testosterone buffered this way.

A little more detail on the transient effect: Think of the body as regulating production to attain its desired outflow. If you could instantly enlarge the sponge—increase SHBG—then the body detects the reduced outflow and increases production. But the sponge soon saturates and outflow even goes too high, leading to reduced production. There could even be damped oscillations. But over time the flow rates return to where they started.

You're saying that low free T is caused by low T production no matter what SHBG level is, but why when injecting trt doses of T that provide a flow of free T it still gets bound by the shbg leaving a person with low free T levels?

As illustrated in the above analogy, once the SHBG is "saturated" by the flow of testosterone the amount of SHBG and total testosterone doesn't much matter.

 

[savefoxes]

There's no need for higher testosterone production. Think of production as equaling free testosterone. At steady state the amount of SHBG is basically irrelevant. Someone recently suggested a sponge analogy: SHBG is likened to a sponge, with testosterone being the water. Testosterone—water—is dripped onto the sponge. This represents production. When the sponge is saturated the testosterone drips off the bottom of the sponge—this represents free testosterone being used. At steady state the flow of testosterone leaving the sponge equals the production entering the sponge. You can double the size of the sponge—the amount of SHBG—which temporarily reduces the flow, but the sponge soon saturates again so that outflow again equals inflow. A larger sponge means more total testosterone is contained within the sponge. But that testosterone within the sponge isn't doing much of anything, and so is largely irrelevant. For the sake of simplicity this ignores the possible benefits in having testosterone buffered this way.

A little more detail on the transient effect: Think of the body as regulating production to attain its desired outflow. If you could instantly enlarge the sponge—increase SHBG—then the body detects the reduced outflow and increases production. But the sponge soon saturates and outflow even goes too high, leading to reduced production. There could even be damped oscillations. But over time the flow rates return to where they started.


As illustrated in the above analogy, once the SHBG is "saturated" by the flow of testosterone the amount of SHBG and total testosterone doesn't much matter.

So having 2000+ total T is not harmful for health if the free T is in range?

 

[savefoxes]

Does it though? I would say it raises their free T proportionately to the dose and leaves with them high total T levels. If you adjusted the dose to reach a certain target total T value, you would hit the total T at a lower dose than average and the free T would be lower than average, only because the dose was lower.

People's responses vary but I think if you give a high SHBG guy a certain dose and a lower SHBG guy the same dose, and everything else was equal, they'd probably have comparable free T but the high SHBG guy's total would be high and the low SHBG guy's total would be low.

Usually high SHBG guys need large doses once or twice a week while people with low SHBG can inject like 70 mg a week and still have high free T

 

[Systemlord]

So having 2000+ total T is not harmful for health if the free T is in range?

Free T is what influences changes inside the body.

 

[tareload]

Usually high SHBG guys need large doses once or twice a week while people with low SHBG can inject like 70 mg a week and still have high free T

First Cycle Questions for 46Y/O

The most concise way I can explain it: The fundamental roles of fT and TT are typically explained backwards. Dose sets fT (your body eliminates fT not TT). fT + SHBG then set your TT on a very rapidly attained chemical equilibrium between fT and SHBG. Reaction of fT + SHBG —> TT much...

forums.t-nation.com

Here and posts below it from "tareload" which largely summarizes all of @Cataceous 's greatest hits!

 

[Cataceous]

So having 2000+ total T is not harmful for health if the free T is in range?

I wouldn't go so far as to say that something this far outside of normal physiology is necessarily benign, even if the bound testosterone is relatively inert. SHBG does have some other functions, which could be overdriven by the implied high levels. There's also the question of whether there's an underlying pathology driving the excess SHBG.

 

[tareload]

So having 2000+ total T is not harmful for health if the free T is in range?

An example if I spot you 25 ng/dl fT as "in range":

 

[savefoxes]

An example if I spot your 25 ng/dl fT as "in range":


View attachment 24455

Would that be too high level of total T to be at long-term in your opinion, or only the free T matters? People with low SHBG can achieve the same level of free T while keeping their total T under 1000

 

[FunkOdyssey]

Would that be too high level of total T to be at long-term in your opinion, or only the free T matters? People with low SHBG can achieve the same level of free T while keeping their total T under 1000

25 ng/dL would land between the 97.5 - 99th percentile among young, healthy, non-obese men in the FHS Gen 3 reference sample. It's basically the tippity-top of the physiological range. Hoping to check out what that feels like in the near future.

Reference Ranges for Testosterone in Men Generated Using Liquid Chromatography Tandem Mass Spectrometry in a Community-Based Sample of Healthy Nonobese Young Men in the Framingham Heart Study and Applied to Three Geographically Distinct Cohorts

 

[savefoxes]

25 ng/dL would land between the 97.5 - 99th percentile among young, healthy, non-obese men in the FHS Gen 3 reference sample. It's basically the tippity-top of the physiological range. Hoping to check out what that feels like in the near future.

View attachment 24461
Reference Ranges for Testosterone in Men Generated Using Liquid Chromatography Tandem Mass Spectrometry in a Community-Based Sample of Healthy Nonobese Young Men in the Framingham Heart Study and Applied to Three Geographically Distinct Cohorts

I'm young healthy and not obese yet only at 10 ng/dl. Total T is over 1000 though

 

[tareload]

I'm young healthy and not obese yet only at 10 ng/dl. Total T is over 1000 though

Looking good you stud!