Never found a root cause to my Low T. Any ideas?

[WindFish1993]

Following up on this as I think I might have come across a possible cause for all of this why I suspect could be hypothyroidism.


Starting with all of the symptoms: I noticed my hands would get cold and stiff, my memory was shot, I had large weight fluctuations, poor libido, my hair was thinning, ED, muscle weakness. TRT helped with some of these, but I suspect it was only masking the issue.

I found some videos and pubmed articles that discuss what suppresses SHBG. Carbohydrate, sunflower oils, etc. What increases SHBG; your thyroid hormones and olive oil and some other things. As your SHBG goes down your androgens decrease too as it is all part of the feedback loop.

Less thyroid hormones, mean less SHBG production, so then cholesterol goes up, testosterone goes down and you get stuck in this negative loop.

I was only ever tested for TSH which has always been between 1.5-2 which is a normal healthy range, but TSH is just the signal for the thyroid to produce T3 and T4. It is possible to have normal TSH and deficient T3&4. In the same way we see men with normal LH and FSH but low testosterone.

Current theory is that T3/4 are deficient and that supplementing with thyroid medication could bring them into a normal range which could bring SHBG into a normal range which should bring Total T back into range. I will be requesting a lab test from my PCP soon to see if my theory is correct. If so, it could mean going from daily injections to a daily pill instead. Hopefully this also adds to the knowledge bank for others with low SHBG.

The video:

The pubmed article: Opposite effects of thyroid hormones on binding proteins for steroid hormones (sex hormone-binding globulin and corticosteroid-binding globulin) in humans - PubMed

Article which discusses what impacts SHBG:

SHBG – A Modulator to be Modulated | ZRT Laboratory

 

[Systemlord]

It is possible to have normal TSH and deficient T3&4.

Yes, however secondary hypothyroidism is exceeding rare and therefore unlikely. Your TSH is at the median level.

On TRT you have little control over SHBG.

 

[WindFish1993]

Yes, however secondary hypothyroidism is exceeding rare and therefore unlikely. Your TSH is at the median level.

On TRT you have little control over SHBG.

I still think it’s worth checking alongside my A1C again to rule out insulin resistance, especially if I can get insurance to do it. Also the labs shared were all pre-TRT where it was already in the teens. Now it’s almost single digits at 12. The end goal is not to be on thyroid medication and TRT but to find something that this all stems from and resolve it.

 

[Systemlord]

The end goal is not to be on thyroid medication and TRT but to find something that this all stems from and resolve it.

I’ve never seen anyone fix things from 266 ng/dL, you would be the first.

 

[Guided_by_Voices]

I still think it’s worth checking alongside my A1C again to rule out insulin resistance, especially if I can get insurance to do it. Also the labs shared were all pre-TRT where it was already in the teens. Now it’s almost single digits at 12. The end goal is not to be on thyroid medication and TRT but to find something that this all stems from and resolve it.

My two cents...I think you're going about it the right way. Even if you are unable to find or fix a root cause, you can be at peace with having tried, and things you do fix will be farther upstream which is likely to be a good thing. Chris Masterjohn is one of the most insightful resources you will find. If, for example, you grew up drinking flouridated water, that could account for thyroid issues and may or may not be fixable. You may also want to look into chelation therapy now that is is relatively cheap.

 

[Cataceous]

... As your SHBG goes down your androgens decrease too as it is all part of the feedback loop. ...

There's not exactly a feedback loop in this situation. SHBG is like a storage reservoir for testosterone, so when there's less SHBG there is less total testosterone. However, changing SHBG in isolation does not have much, if any effect on free testosterone. Free testosterone is what's regulated by the HPTA through feedback, and it is better correlated with the effects attributed to testosterone. Nonetheless, it may be worth trying to raise low SHBG because in addition to its other problematic correlations, there's speculation that it has a negative impact on androgen signaling relative to estrogen signaling.

 

[WindFish1993]

There's not exactly a feedback loop in this situation. SHBG is like a storage reservoir for testosterone, so when there's less SHBG there is less total testosterone. However, changing SHBG in isolation does not have much, if any effect on free testosterone. Free testosterone is what's regulated by the HPTA through feedback, and it is better correlated with the effects attributed to testosterone. Nonetheless, it may be worth trying to raise low SHBG because in addition to its other problematic correlations, there's speculation that it has a negative impact on androgen signaling relative to estrogen signaling.

The way I understood it (may or may not be accurate) is that if SHBG is raised you would have less Free T and subsequently less Free Estrogen which is how the body determines to make more/less T. A normal person should see that their Hypothalamus sends a stronger signal to the pituitary which should send a stronger signal to the testes. I believe the body is always trying to achieve some form of homeostasis, but perhaps that level of what the body determines to be a good equilibrium can become distorted either through diet/medication/genetics/disease.

In any case, I’m just going to use this as a journal for any changes that happen or any interesting blood work results in hopes it might be helpful to someone else with the same problem.

 

[Systemlord]

perhaps that level of what the body determines to be a good equilibrium can become distorted either through diet/medication/genetics/disease.

You left out environment, which I believe is the biggest contributor to declining testosterone over the last 100 years. The industrial revolution started it all.

The places that have seen less decline are those less developed countries, like Africa.

 

[Cataceous]

The way I understood it (may or may not be accurate) is that if SHBG is raised you would have less Free T and subsequently less Free Estrogen which is how the body determines to make more/less T. ...

This is only a transient effect, which I have been neglecting for simplicity. Suppose you inject some SHBG. This new SHBG starts soaking up the free sex hormones, lowering their levels, though only temporarily. As time goes by the new SHBG becomes saturated and the free hormones return to their former levels. Total testosterone is now greater because now there's additional testosterone bound to the new SHBG. The body is still regulating to attain its desired level of free testosterone/estradiol, and this set point has not changed with the addition of SHBG.

 

[WindFish1993]

This is only a transient effect, which I have been neglecting for simplicity. Suppose you inject some SHBG. This new SHBG starts soaking up the free sex hormones, lowering their levels, though only temporarily. As time goes by the new SHBG becomes saturated and the free hormones return to their former levels. Total testosterone is now greater because now there's additional testosterone bound to the new SHBG. The body is still regulating to attain its desired level of free testosterone/estradiol, and this set point has not changed with the addition of SHBG.

Ok but do you think these people are both of equal health?

Person 1: Total T < 300, SHBG < 20
Person 2: Total T 550, SHBG 60

Free T will be roughly the same, but person 1 arguably has worse blood markers. Person 2 should also have an easier time with injection scheduling. Person 2 also has the ability to lower their SHBG if needed using known supplements. There is almost nothing that can be done for person 1 like that.

 

[Cataceous]

Ok but do you think these people are both of equal health?

Person 1: Total T < 300, SHBG < 20
Person 2: Total T 550, SHBG 60

Free T will be roughly the same, but person 1 arguably has worse blood markers. Person 2 should also have an easier time with injection scheduling. Person 2 also has the ability to lower their SHBG if needed using known supplements. There is almost nothing that can be done for person 1 like that.

It's pretty clear that low SHBG has more association with negative health markers than high SHBG. And anecdotally it seems as though guys with low SHBG tend to have more trouble dialing in their TRT. The claim about injection scheduling is speculative, and may be based on the erroneous notion that SHBG affects the pharmacokinetics of injected testosterone—i.e. changes the half-life. SHBG does play a role in androgen signaling, which may well be impaired by lower levels. Therefore, on average the guy with low SHBG is probably worse off than the one with it elevated. Even so, most hormones have U-shaped mortality associations, meaning you're better off having it in range.

If SHBG were available as an affordable pharmaceutical then low SHBG could be easily treated with twice-weekly injections. This would resolve issues directly caused by low levels. It wouldn't address any underlying problems, but some cases may just be genetically driven and otherwise benign.