Relationship Between Higher PSA and Higher SHBG

[ResearchIt]

I'm almost 43, have always been healthy, not on TRT or anything, my Total T is usually 600-800, somewhat lower Free T, SHBG is 48-58, and PSA is 1.7-1.8.

Doctors have never said much about my PSA when discussing labs, I guess because it was "within range" meaning less than 2.5.

However, the median PSA by age:
40 to 49: 0.7 ng/mL
50 to 59: 0.9 ng/mL

My PSA is double the median PSA of 50 year olds. Maybe they would say the absolute level is less relevant and whether it increases is the relevant factor.

I was thinking of reasons why my SHBG would be on the higher end and wondered if perhaps my body was producing extra SHBG to protect itself from cancer given my higher PSA? Does anyone have experience with this scenario? Perhaps our hypothalamus has a PSA sensor?

Higher sex hormone-binding globulin and lower bioavailable testosterone are related to prostate cancer detection on prostate biopsy - PubMed

Low bioavailable testosterone levels and high SHBG levels were related to a 4.9- and 3.2-fold risk of detection of PCa on prostate biopsy owing to PSA elevation or abnormal DRE. This fact may be useful in the clinical scenario in counselling patients at risk for PCa.

pubmed.ncbi.nlm.nih.gov

Prostate-specific antigen, testosterone, sex-hormone binding globulin and androgen receptor CAG repeat polymorphisms in subfertile and normal men

Abstract. The aim of this study was to understand the androgen-related factors which may regulate concentrations of the tumour marker, prostate-specific an

academic.oup.com

Baseline prostate-specific antigen compared with median prostate-specific antigen for age group as predictor of prostate cancer risk in men younger than 60 years old - PubMed

In men younger than 60, a baseline PSA value between the age-specific median and 2.5 ng/mL was a significant predictor of later CaP and was associated with a significantly greater PSA velocity. A young man's baseline PSA value was a stronger predictor of CaP than family history, race, or...

pubmed.ncbi.nlm.nih.gov

 

[hotdog]

" reasons why my SHBG would be on the higher end"

My notes tell me SHBG is driven up by cortisol, probably where I'd start.

 

[Vince]

Conclusions: Low bioavailable testosterone levels and high SHBG levels were related to a 4.9- and 3.2-fold risk of detection of PCa on prostate biopsy owing to PSA elevation or abnormal DRE. This fact may be useful in the clinical scenario in counselling patients at risk for PCa.

As men age their testosterone levels get lower, the shpg increases and of course their PSA increases.

 

[MIP1950]

My SHBG was 34. PSA over the past 3 to 4 months; 4.95>4.45>4.28, last week. 71,(72 in May) with mild BPH. Appointment with my urologist in two weeks.

 

[Dicky]

I'm almost 43, have always been healthy, not on TRT or anything, my Total T is usually 600-800, somewhat lower Free T, SHBG is 48-58, and PSA is 1.7-1.8.

Doctors have never said much about my PSA when discussing labs, I guess because it was "within range" meaning less than 2.5.

However, the median PSA by age:
40 to 49: 0.7 ng/mL
50 to 59: 0.9 ng/mL

My PSA is double the median PSA of 50 year olds. Maybe they would say the absolute level is less relevant and whether it increases is the relevant factor.

I was thinking of reasons why my SHBG would be on the higher end and wondered if perhaps my body was producing extra SHBG to protect itself from cancer given my higher PSA? Does anyone have experience with this scenario? Perhaps our hypothalamus has a PSA sensor?

Higher sex hormone-binding globulin and lower bioavailable testosterone are related to prostate cancer detection on prostate biopsy - PubMed

Low bioavailable testosterone levels and high SHBG levels were related to a 4.9- and 3.2-fold risk of detection of PCa on prostate biopsy owing to PSA elevation or abnormal DRE. This fact may be useful in the clinical scenario in counselling patients at risk for PCa.

pubmed.ncbi.nlm.nih.gov

Prostate-specific antigen, testosterone, sex-hormone binding globulin and androgen receptor CAG repeat polymorphisms in subfertile and normal men

Abstract. The aim of this study was to understand the androgen-related factors which may regulate concentrations of the tumour marker, prostate-specific an

academic.oup.com

Baseline prostate-specific antigen compared with median prostate-specific antigen for age group as predictor of prostate cancer risk in men younger than 60 years old - PubMed

In men younger than 60, a baseline PSA value between the age-specific median and 2.5 ng/mL was a significant predictor of later CaP and was associated with a significantly greater PSA velocity. A young man's baseline PSA value was a stronger predictor of CaP than family history, race, or...

pubmed.ncbi.nlm.nih.gov

Are you a fairly lean person? I know of 2 people who have pretty high SHBG and they are both very lean and active. I know of another 2 people who are more plump and they have low SHBG. It's a pretty low N. But that's what I know.

 

[ajax31]

Are you a fairly lean person? I know of 2 people who have pretty high SHBG and they are both very lean and active. I know of another 2 people who are more plump and they have low SHBG. It's a pretty low N. But that's what I know.

Could be fatty liver. There is an inverse or negative association between NAFLD and SHBG.

 

[Dicky]

Could be fatty liver. There is an inverse or negative association between NAFLD and SHBG.

So if you have fatty liver, you might have low SHBG?

 

[ajax31]

So if you have fatty liver, you might have low SHBG?

Yes.

 

[Dicky]

Yes.

I guess that's good news for OP. He has high SHBG, so likely no NAFLD

 

[ResearchIt]

Are you a fairly lean person? I know of 2 people who have pretty high SHBG and they are both very lean and active. I know of another 2 people who are more plump and they have low SHBG. It's a pretty low N. But that's what I know.

Yes I am a lean healthy active person. I am 6'1" and weight 185lbs. My body fat percentage is usually between 12% and 14%.

 

[Match]

Befitting the result here. Also thin and active, 57 years, SHBG 63 nmol/l. From what they said, obesity, etc., reduces SHBG, but do not know to what extent High SHBG is good, the ideal point what would it be?

 

[ResearchIt]

Befitting the result here. Also thin and active, 57 years, SHBG 63 nmol/l. From what they said, obesity, etc., reduces SHBG, but do not know to what extent High SHBG is good, the ideal point what would it be?

I am new here and others can correct me if I am off, but from what I have read SHBG in the realm of 30-35 nmol/L is "ideal". You see this in the Free T calculators that are available:

Free & Bioavailable Testosterone calculator

TruT Free Testosterone Calculator by FPT

Free testosterone calculator by FPT. Improved accuracy of free T calculations.

tru-t.org

Plug in a normal Total T value and higher range SHBG value and you get a lower range Free T number. Here are a few examples:

As you can see, Free T is quite a bit higher in the example with lower SHBG. I think these calculators are where people get the idea that higher range SHBG is a problem in that it causes lower Free T. Even on the homepage of this website there is an article about lowering your SHBG to increase Free T.

That being said, there are other threads you can read on here that say higher SHBG isn't the culprit and the real culprit to lower range Free T is the hypothalmus setting a lower range Free T target and your SHBG level is just along for the ride and trying to fight your higher SHBG is useless.

Also, a point has been made in other threads that SHBG is simply a reservoir for testosterone and having higher SHBG is just a bigger reservoir and, once it gets filled up, it's all about the continuing production or flow into and out of the reservoir that matters.

What I do know is if my SHBG were 30 instead of 50, that my Free T would come out higher in the calculators. Whether that would make a difference in how I feel, I have no idea.

 

[ResearchIt]

57 years, SHBG 63 nmol/l

Have you had your PSA checked? Do you mind me asking what the level is?

 

[Match]

ResearchIt,​

It was in this Forum that I read, not which post member, that TLivre controls TTotal, so that TTotal increases or decreases porporcionalmente at the level of SHBG. That's about it.
The formula leads to more Free T if Low SHBG, but low SHBG also causes bad symptoms, as they said.
So it's pretty complicated

PSA 1.90

 

[Cataceous]

...
What I do know is if my SHBG were 30 instead of 50, that my Free T would come out higher in the calculators. Whether that would make a difference in how I feel, I have no idea.

Correction: If your SHBG were 30 instead of 50 and you demanded total testosterone remain unchanged then free testosterone would have to be increased to make this happen. But the reality is that your body regulates for its preferred level of free testosterone, so there's no pressure to increase it; if you simply remove 20 nMol/L of your SHBG then your free testosterone doesn't change and total testosterone drops by the amount that was bound to the SHBG you removed.

This explanation is slightly simplified. The nitty-gritty is that reducing SHBG affects the equilibrium with free testosterone. This means that total testosterone ends up a little different than if you only subtract the amount that was bound to the removed SHBG.

 

[Match]

Right, but then the result of the TF by the formulas are always false, in that it directly changes the TF more or less, according to the value that I consider as SHBG. Would this be a very rough estimate?
A person with TT 800 and SHBG 40 would have the same FT as someone with TT 1000 and SHBG 60.

 

[Cataceous]

Right, but then the result of the TF by the formulas are always false, in that it directly changes the TF more or less, according to the value that I consider as SHBG. Would this be a very rough estimate?
A person with TT 800 and SHBG 40 would have the same FT as someone with TT 1000 and SHBG 60.

The formulas are not producing false results. The confusion arises because they are given in the form

FT = f(TT, SHBG, ALB)

This makes sense when you want to estimate free testosterone and the three function parameters are relatively easy to measure. However, this form creates the perception that total testosterone drives free testosterone, and also encourages the misperception that total testosterone can be treated as constant and directly under our control in the case of TRT. Instead, consider rearranging the formula to

TT = f1(FT, SHBG, ALB)

I've been arguing that this form is more natural with respect to physiology. Free testosterone is driven proportionally by the production rate of testosterone, or by the testosterone dose rate in those on TRT. The relative constancy of free testosterone allows for your observation above that "[Free testosterone] controls TTotal, so that TTotal increases or decreases porporcionalmente at the level of SHBG." If you invert the Vermeulen calculation and ignore albumin then the equation looks something like this:

TT = (a + b * FT + SHBG) * FT / (c * FT + d)

This does imply that total testosterone increases monotonically with SHBG when free testosterone is fixed.

 

[Match]

I understood more or less. Very complex this theme

 

[ResearchIt]

Correction: If your SHBG were 30 instead of 50 and you demanded total testosterone remain unchanged then free testosterone would have to be increased to make this happen. But the reality is that your body regulates for its preferred level of free testosterone, so there's no pressure to increase it; if you simply remove 20 nMol/L of your SHBG then your free testosterone doesn't change and total testosterone drops by the amount that was bound to the SHBG you removed.

This explanation is slightly simplified. The nitty-gritty is that reducing SHBG affects the equilibrium with free testosterone. This means that total testosterone ends up a little different than if you only subtract the amount that was bound to the removed SHBG.

That's a good point, I neglected to include the "and". I meant that if my SHBG were 30 instead of 50 and my total testosterone remained constant, then the calculators would produce a higher Free T number.

I think you are right that the body regulates for its preferred level of Free T. Are there solid studies you have seen that show this as well?

Also, have you seen any research that tells us how the body decides what mix of Total T, SHBG, and Albumin to combine to generate its desired Free T level?

As always, thank you for your feedback. It's good stuff.

 

[Cataceous]

...
I think you are right that the body regulates for its preferred level of Free T. Are there solid studies you have seen that show this as well?
...

I don't recall seeing this stated explicitly, though it probably is. It's a pretty straightforward deduction from what's known about HPTA feedback. Estrogen and androgen receptors in the hypothalamus and pituitary respond to free testosterone and its free metabolites to regulate testosterone production. There's additional regulation at the hypothalamus—For example, calorie deprivation reduces testosterone production; sex becomes a lower priority when there's not enough food.

...
Also, have you seen any research that tells us how the body decides what mix of Total T, SHBG, and Albumin to combine to generate its desired Free T level?
...

To reiterate: The body is not measuring and manipulating total testosterone. The body increases or decreases the production rate of testosterone to attain the desired level of free testosterone. SHBG does not have much effect on free testosterone, so its regulation is not intended for that, as opposed to it's buffering ability and other independent functions. We know that androgens tend to reduce SHBG while estrogens tend to increase it. T3 increases it. Albumin, as a general transporter protein, is even more independent.