Pregnenalone and TRT

[Gman86]

Ya a separate thread for those PSA supplements would probably be good. I’m sure there are other guys struggling with the same issue.

I guess it’s debatable whether older men should have the hormone levels of a younger guy. I personally think that it’s ok, but I obviously could be wrong. Most TRT doctors like to see DHEA at the top of the range, regardless of age, or an age adjusted reference range. So the top of the range would be around 450-500. So that’s why I said your level was pretty much perfect. Have you ever tried using low dose sublingual DHEA from a compounding pharmacy? If I were to start using DHEA, that’s what I would try, and I would personally only trust pharmacy grade DHEA.

I would also never mess with any medication that lowers DHT. That’s just not the right way to lower PSA. You’re doing more harm than good by lowering DHT. Seems like those supplements are helping though. So keep doing what you’re doing. Hopefully your PSA continues to decrease.

 

[Cataceous]

Is it true that DHEA raises estrogen in men?
...

If by "estrogen" you mean estrone, then yes, DHEA supplementation raises it significantly. However, various studies have shown no effect on estradiol in men with functioning HPTAs, i.e. not on TRT. This makes sense, because if DHEA raised estradiol independently of testosterone then it would be highly suppressive and testosterone would go down. It's more plausible that DHEA supplementation could raise estradiol in men on TRT due to the lack of regulation. However, as far as I know this has not been studied rigorously.

 

[DragonBits]

If by "estrogen" you mean estrone, then yes, DHEA supplementation raises it significantly. However, various studies have shown no effect on estradiol in men with functioning HPTAs, i.e. not on TRT. This makes sense, because if DHEA raised estradiol independently of testosterone then it would be highly suppressive and testosterone would go down. It's more plausible that DHEA supplementation could raise estradiol in men on TRT due to the lack of regulation. However, as far as I know this has not been studied rigorously.

The article in your link says that Dhea increased free T from 17 to 29 pg/ml, BUT only had a minor effect of lowering SHBG by 10% and no effect on Total T.

So how is this possible, I thought Free T was derived by total T, and there are online calculators that use SHBG and Albumin to calculate Free T from Total T. Using an online calculator if I reduce SHBG from 45 to 35 with Total T being constant at 690 ng/dl, free T only changes from 12.7 > 14.9 ng/dl.

So what is going on to have a big effect on free T with no change in Total T and a minor drop in shbg?

If true, this also tells me that calculated Free T is a very poor predictor of actual values. (which I always suspected was true)

Anyone have any comments on this?

 

[Cataceous]

The article in your link says that Dhea increased free T from 17 to 29 pg/ml, BUT only had a minor effect of lowering SHBG by 10% and no effect on Total T.

So how is this possible, I thought Free T was derived by total T, and there are online calculators that use SHBG and Albumin to calculate Free T from Total T. Using an online calculator if I reduce SHBG from 45 to 35 with Total T being constant at 690 ng/dl, free T only changes from 12.7 > 14.9 ng/dl.

So what is going on to have a big effect on free T with no change in Total T and a minor drop in shbg?

If true, this also tells me that calculated Free T is a very poor predictor of actual values. (which I always suspected was true)

Anyone have any comments on this?

Usually it's measured free testosterone that is suspect, and calculated is the one to rely on. Here's a paper on the subject. As for the DHEA paper, it would be better to calculate the change in calculated free testosterone for each member of the cohort, and then average. But I don't have that data, so I must use cFT of the average numbers. This yields a more modest increase of 20% in free testosterone, driven by the significant increase in DHT and the decrease in SHBG.

 

[DragonBits]

Usually it's measured free testosterone that is suspect, and calculated is the one to rely on. Here's a paper on the subject. As for the DHEA paper, it would be better to calculate the change in calculated free testosterone for each member of the cohort, and then average. But I don't have that data, so I must use cFT of the average numbers. This yields a more modest increase of 20% in free testosterone, driven by the significant increase in DHT and the decrease in SHBG.

I agree with you that measured Free T is more suspect, likely it's better but much more expensive to use the Free T LC/MS test. I used to research that, but have given up getting definitive answers, and it's just too expensive only to satisfy my curiosity.

Though I have read about variations on total t from the same lab sample, any problems with total T will ripple into the calc of FT.

It's all a lot more amorphous than I would like it to be.

Are you saying an increase in DHT will drive FT up beyond what is indicated by calculating FT from Total T / SHBP?

 

[DragonBits]

Ya a separate thread for those PSA supplements would probably be good. I’m sure there are other guys struggling with the same issue.

I guess it’s debatable whether older men should have the hormone levels of a younger guy. I personally think that it’s ok, but I obviously could be wrong. Most TRT doctors like to see DHEA at the top of the range, regardless of age, or an age adjusted reference range. So the top of the range would be around 450-500. So that’s why I said your level was pretty much perfect. Have you ever tried using low dose sublingual DHEA from a compounding pharmacy? If I were to start using DHEA, that’s what I would try, and I would personally only trust pharmacy grade DHEA.

I would also never mess with any medication that lowers DHT. That’s just not the right way to lower PSA. You’re doing more harm than good by lowering DHT. Seems like those supplements are helping though. So keep doing what you’re doing. Hopefully your PSA continues to decrease.

I don't know of any other non-surgical way to shrink prostate other than to reduce DHT. Maybe you can lower your PSA level,but is that making the level just look better or actually shrinking the prostate? Most of what I have read about what you eat and exercise is about preventing BPH, not shrinking BPH.

In any case, I don't think of DHT as sacrosanct, as long as it can go back up, a temporary lowering isn't going to concern me.

 

[Gman86]

I don't know of any other non-surgical way to shrink prostate other than to reduce DHT. Maybe you can lower your PSA level,but is that making the level just look better or actually shrinking the prostate? Most of what I have read about what you eat and exercise is about preventing BPH, not shrinking BPH.

In any case, I don't think of DHT as sacrosanct, as long as it can go back up, a temporary lowering isn't going to concern me.

Just be careful, there are a vast number of men that report permanent side effects after lowering their DHT with finasteride, even years after discontinuing. I think it’s called post finasteride syndrome.

 

[Cataceous]

I agree with you that measured Free T is more suspect, likely it's better but much more expensive to use the Free T LC/MS test. I used to research that, but have given up getting definitive answers, and it's just too expensive only to satisfy my curiosity.

Though I have read about variations on total t from the same lab sample, any problems with total T will ripple into the calc of FT.

It's all a lot more amorphous than I would like it to be.

Are you saying an increase in DHT will drive FT up beyond what is indicated by calculating FT from Total T / SHBP?

We did have somebody at the PeakTestosterone forum say he had good agreement between calculated free testosterone and the mass spectrometry-based measurement. But the mass spectrometry tests are complex and easier to mess up, which I've found out the hard way via botched estradiol tests.

A more sophisticated free testosterone calculator, such as the spreadsheet you can download here, takes DHT as an input rather than using a default value. DHT does have the highest binding affinity for SHBG and can displace testosterone as it increases. However, in the usual physiological range the effect isn't so large. But in the DHEA paper DHT increased from 64 ng/dL to 339!

 

[DragonBits]

We did have somebody at the PeakTestosterone forum say he had good agreement between calculated free testosterone and the mass spectrometry-based measurement. But the mass spectrometry tests are complex and easier to mess up, which I've found out the hard way via botched estradiol tests.

A more sophisticated free testosterone calculator, such as the spreadsheet you can download here, takes DHT as an input rather than using a default value. DHT does have the highest binding affinity for SHBG and can displace testosterone as it increases. However, in the usual physiological range the effect isn't so large. But in the DHEA paper DHT increased from 64 ng/dL to 339!

THanks, that makes sense to me about the role DHT can have.

BTW, what is cbg in the spreadsheet? Corticosteroid Binding Globulin (CBG)? or something to do with glucose?

B

 

[DragonBits]

Just be careful, there are a vast number of men that report permanent side effects after lowering their DHT with finasteride, even years after discontinuing. I think it’s called post finasteride syndrome.

I think post finasteride syndrome is rare but real.

Though I don't see any reason I would take finasteride and I have doubts any doctor would prescribe if I don't have LUTS.

Supplements can also lower DHT, how do you feel about those?

 

[Gman86]

I think post finasteride syndrome is rare but real.

Though I don't see any reason I would take finasteride and I have doubts any doctor would prescribe if I don't have LUTS.

Supplements can also lower DHT, how do you feel about those?

I never really thought much about supplements that lower DHT, mostly because I’ve never personally had a reason to lower DHT. But I would imagine those would be mostly safe. It’s just the lowering of DHT to a large degree that you want to avoid. I’ve just heard too many horror stories. And post finasteride syndrome is not rare at all. There’s tons of posts online about it, on many different websites and forums. There’s even whole websites dedicated specifically to it.
Home - Welcome to the Post-Finasteride Foundation - The Post-Finasteride Syndrome Foundation. And it’s not just with finasteride. It can happen from taking any of the main medications to lower DHT, from my understanding. All I’m saying is just be careful, and proceed with caution, when trying to actively lower DHT, or lower any hormone, for that matter.

Is science even positive that lowering DHT lowers PSA? Because not too long ago, science told us that we needed to lower testosterone and estrogen, in order to reduce PSA, and we know now that just simply isn’t true. To me, it just doesn’t make sense that having a healthy level of any hormone could be bad for us. It’s hard to believe that blunting a hormone could make you healthier. Common sense tells me that having an optimal level of DHT would be beneficial for all functions in the body. For your sake, I wish there was more things you could do to lower your PSA. But sounds like you’re having pretty good success with the supplements you’re using, so I would at least continue using those

 

[Cataceous]

...
BTW, what is cbg in the spreadsheet? Corticosteroid Binding Globulin (CBG)? ...

Yes. Apparently it binds a few percent of serum testosterone.

 

[DragonBits]

I never really thought much about supplements that lower DHT, mostly because I’ve never personally had a reason to lower DHT. But I would imagine those would be mostly safe. It’s just the lowering of DHT to a large degree that you want to avoid. I’ve just heard too many horror stories. And post finasteride syndrome is not rare at all. There’s tons of posts online about it, on many different websites and forums. There’s even whole websites dedicated specifically to it.
Home - Welcome to the Post-Finasteride Foundation - The Post-Finasteride Syndrome Foundation. And it’s not just with finasteride. It can happen from taking any of the main medications to lower DHT, from my understanding. All I’m saying is just be careful, and proceed with caution, when trying to actively lower DHT, or lower any hormone, for that matter.

Is science even positive that lowering DHT lowers PSA? Because not too long ago, science told us that we needed to lower testosterone and estrogen, in order to reduce PSA, and we know now that just simply isn’t true. To me, it just doesn’t make sense that having a healthy level of any hormone could be bad for us. It’s hard to believe that blunting a hormone could make you healthier. Common sense tells me that having an optimal level of DHT would be beneficial for all functions in the body. For your sake, I wish there was more things you could do to lower your PSA. But sounds like you’re having pretty good success with the supplements you’re using, so I would at least continue using those

I have been using the Internet since 1981. By which I mean, I have seen tons of posts on totally ridiculous theories. One guy posted 10 times a day for 2 years about a penny junk stock he lost his ass on. In the early years people used to use their real names, once in a while I would call someone just to see what the basis was for their posts and if they were otherwise rational.

I think it's well established that lowering DHT lowers PSA for prostate volumes > 30 cm, even better for >50 cm. it doesn't work as well on smaller prostates.

The most common side effects included decreased libido, ejaculatory disorder, and erectile dysfunction, with rates of 3.4%, 2.7%, and 1.7% in the 5 mg finasteride group

And from what I have read, high serum levels of DHT don't have an adverse effect on the prostate either.

But typically you have to keep DHT lower forever, you can reduce the dose to 2.5 mg but once you stop something like finasteride in a few months you are back to where you started. And I am not sure if the effect lasts forever, rarely it may slightly increase the risk of developing a very serious form of prostate cancer, and if it's cancer you are trying to fight then often no therapy last forever.

But, but I have no intention of using finasteride, out of curiosity I was going to ask the urologist if he would even prescribe it if I don't have any symptoms, only an elevated PSA. Not to mention, my PSA now it's even considered elevated for my age.

I can see from Cataceous posts that lowering DHT will lower Free T, and too low a level of Free T would likely cause problems with libedo / sexual funcition.

This is all sort of connected to DHEA, because DHEA said to increase DHT which binds to shbg and then creates more Free T.

 

[madman]

Usually it's measured free testosterone that is suspect, and calculated is the one to rely on. Here's a paper on the subject. As for the DHEA paper, it would be better to calculate the change in calculated free testosterone for each member of the cohort, and then average. But I don't have that data, so I must use cFT of the average numbers. This yields a more modest increase of 20% in free testosterone, driven by the significant increase in DHT and the decrease in SHBG.

That paper is from 1999.

This is where we stand on measuring free testosterone.


Direct vs Equilibrium

 

[madman]

Usually it's measured free testosterone that is suspect, and calculated is the one to rely on. Here's a paper on the subject. As for the DHEA paper, it would be better to calculate the change in calculated free testosterone for each member of the cohort, and then average. But I don't have that data, so I must use cFT of the average numbers. This yields a more modest increase of 20% in free testosterone, driven by the significant increase in DHT and the decrease in SHBG.

Only a matter of time now until we finally have the CDC (HoSt) PROGRAM for FREE TESTOSTERONE

How the CDC Clinical Standardization Programs Are Improving Hormone Tests

 

[Cataceous]

That paper is from 1999.

This is where we stand on measuring free testosterone.


Direct vs Equilibrium

Nice post there, which I'd view as supporting my argument in favor of calculated free testosterone. The cheap tests that most people use are lousy:

... these direct immunoassays are inaccurate and should not be used

- if equilibrium dialysis is not available for measuring FT, clinicians should estimate FT concentration using a formula that accurately calculates FT concentrations using TT, SHBG, and albumin concentrations

But why spend the extra money on a fancier test when you should still be testing total T and SHBG, which already give you a reliable free T estimate? Equilibrium is going to set you back $99 at Discounted Labs, versus $30 for the regular. Admittedly the extra money is going to get you a more accurate total T test too, but I'd suggest the expense isn't justified.

That's interesting about SHBG circulating as a dimer. It would be useful to know if the differences from older models are significant.

- estimates of FT that use an allosteric model provide close approximations of measures using equilibrium dialysis

 

[madman]

Nice post there, which I'd view as supporting my argument in favor of calculated free testosterone. The cheap tests that most people use are lousy:





But why spend the extra money on a fancier test when you should still be testing total T and SHBG, which already give you a reliable free T estimate? Equilibrium is going to set you back $99 at Discounted Labs, versus $30 for the regular. Admittedly the extra money is going to get you a more accurate total T test too, but I'd suggest the expense isn't justified.

That's interesting about SHBG circulating as a dimer. It would be useful to know if the differences from older models are significant.

Reassessing Free-Testosterone Calculation by Liquid Chromatography–Tandem Mass Spectrometry Direct Equilibrium Dialysis

 

[Cataceous]

That paper is from 1999.

This is where we stand on measuring free testosterone.


Direct vs Equilibrium

The newer ZBJ free testosterone model is described in this paper. The authors say the older Vermeulen model differs "substantially" from equilibrium dialysis. The graphs in the paper show that results differ systematically, and not-quite-linearly. The implication may be that the older model is still useful as its own standard, but less so for direct comparison to measurements. The issue also begs the question of whether any online calculators are using the new model yet.

 

[madman]

The newer ZBJ free testosterone model is described in this paper. The authors say the older Vermeulen model differs "substantially" from equilibrium dialysis. The graphs in the paper show that results differ systematically, and not-quite-linearly. The implication may be that the older model is still useful as its own standard, but less so for direct comparison to measurements. The issue also begs the question of whether any online calculators are using the new model yet.

I did a post regarding that paper last year.

This one: May 18/2018
A Reappraisal of Testosterones's Binding In Circulation: Physiological and Clinical Implications




June 23/2018
Hope for an accurate method to determine Free Testosterone

 

[madman]

Ravi Jasuja, Ph.D. (Chief Scientific Officer of Function Promoting Therapies)



Function Promoting Therapies