TRT Effect on 5 Alpha Reductase and Upstream Hormones- Cause of Low Mood and Anxiety?

[Cataceous]

... In fact if injecting more Testosterone would "burn 5 alpha reductase" we would see a drop in DHT as well, but not quite I believe.
...

As shown in this article, what happens is that the 5ar enzyme starts to saturate at higher doses of testosterone. DHT levels still increase with the higher doses, but less for each incremental increase in testosterone. What's interesting to consider is that there may be some competitive inhibition of other 5ar processes at higher T levels, leading to problems.

 

[Weasel]

I agree. In fact if injecting more Testosterone would "burn 5 alpha reductase" we would see a drop in DHT as well, but not quite I believe.






On TRT, Progesterone needs to be monitored, and supplemented to raise levels. I don't know why this is not common practice for practitioners out there. In fact many call Progesterone a "feminizing" hormone and don't give it to men, when in some cases it is desperately needed it, especially for people who worsen their anxiety/mental health, sleep and adrenal function while on TRT.

I believe allot are not successful with Progesterone supplementation due to the wrong delivery method used.

What method do you recommend? Dose?

 

[Gman86]

As shown in this article, what happens is that the 5ar enzyme starts to saturate at higher doses of testosterone. DHT levels still increase with the higher doses, but less for each incremental increase in testosterone. What's interesting to consider is that there may be some competitive inhibition of other 5ar processes at higher T levels, leading to problems.

View attachment 44843

When u say that 5ar enzymes start to saturate with higher levels of testosterone, does this only affect the conversion test into dht, or when higher test levels saturate 5ar enzymes, it could affect anything that uses 5ar enzymes in its conversion process? For example, could the 5ar enzymes that convert progesterone into dihydroprogesterone be affected from higher test levels?

 

[Cataceous]

When u say that 5ar enzymes start to saturate with higher levels of testosterone, does this only affect the conversion test into dht, or when higher test levels saturate 5ar enzymes, it could affect anything that uses 5ar enzymes in its conversion process? For example, could the 5ar enzymes that convert progesterone into dihydroprogesterone be affected from higher test levels?

That research showed the saturation effect with testosterone being converted to DHT. However, I was speculating that other processes using the 5ar enzyme could be similarly impaired at higher T levels, and yes, this would include progesterone's conversion. There are others too:

5a reductases convert testosterone, progesterone, deoxycorticosterone, aldosterone and corticosterone into their respective 5a-dihydro-derivatives, which serve as substrates for 3a-hydroxysteroid dehydrogenase enzymes. The latter transforms these 5a-reduced metabolites into a subclass of neuroactive steroid hormones with distinct physiological functions.​

[R]

If this hypothesis is true then it would be another reason to avoid excessive levels of testosterone. It's bizarre to consider that high doses of testosterone could have some finasteride-like effects.

 

[Gianluca]

As shown in this article, what happens is that the 5ar enzyme starts to saturate at higher doses of testosterone. DHT levels still increase with the higher doses, but less for each incremental increase in testosterone. What's interesting to consider is that there may be some competitive inhibition of other 5ar processes at higher T levels, leading to problems.

View attachment 44843

Interesting. I heard about the saturation for E2 and DHT with higher Test level before but never looked at the mechanism. The enzyme saturate, but doesn't "burn" as Mark Gordon mentions, perhaps in the brain it may be different.

It is interesting to note also the saturation of the 5 ar start to happen right about or before 1000 ng/dl of TT. if I'm reading the graph correctly,

 

[Gman86]

My prog level has been very high for years now, and now I’m wondering if running higher levels of androgens is the cause. I wonder if my higher level of androgens is saturating my 5ar enzymes, consequently preventing a good amount of the prog in my system from converting into dihydroprogesterone, and then allopregnenolone, and therefore prog levels then build up, and show high when I check my serum prog levels in my blood. @Cataceous do u think this could be plausible? Do u think if a hormone’s process of converting into another hormone is hindered, it could build up?

I guess we could look at testosterone levels, in guys using finasteride or dutasteride. Do we see their testosterone levels increase, when less of it is able to convert into DHT? Same with guys taking AI’s. Do we see their testosterone levels increase, since there’s less testosterone being converted into estrogen?

 

[Nelson Vergel]

I believe allot are not successful with Progesterone supplementation due to the wrong delivery method used.

Could you mind me again what you use? I think you mentioned micronized oral progesterone.

 

[Nelson Vergel]

My prog level has been very high for years now

What are you taking to increase your progesterone while on TRT?

 

[Gman86]

What are you taking to increase your progesterone while on TRT?

That’s the thing, I’m taking nothing to increase prog directly, and for around 2-3 years now it has come back around 1.4-1.6 (0.0-0.5). I eliminated everything that could possibly increase prog, at one point, and it still came back around 1.4-1.6. Cannot figure out for the life of me why it keeps coming back so high

 

[FunkOdyssey]

That’s the thing, I’m taking nothing to increase prog directly, and for around 2-3 years now it has come back around 1.4-1.6 (0.0-0.5). I eliminated everything that could possibly increase prog, at one point, and it still came back around 1.4-1.6. Cannot figure out for the life of me why it keeps coming back so high

Have you tested PROG and seen a high result when you were not taking nandrolone or only when taking nandrolone?

 

[Nelson Vergel]

Have you used the LC/MS test?

Quest Diagnostics: Test Directory

testdirectory.questdiagnostics.com

Quest Diagnostics: Test Directory

testdirectory.questdiagnostics.com

 

[FunkOdyssey]

Have you used the LC/MS test?

Quest Diagnostics: Test Directory

testdirectory.questdiagnostics.com

Quest Diagnostics: Test Directory

testdirectory.questdiagnostics.com

That's a great suggestion for Gman's case. The regular test picks up other things besides progesterone and isn't necessarily accurate. The LC/MS test, which is truly specific for progesterone, has a normal range that includes zero for adult men. That's always one of my talking points when arguing that progesterone just isn't that important for men.

 

[Gman86]

Have you tested PROG and seen a high result when you were not taking nandrolone or only when taking nandrolone?

Ya I took nandrolone out for quite a while, and prog didn’t budge. Was still high

 

[Gman86]

Have you used the LC/MS test?

Quest Diagnostics: Test Directory

testdirectory.questdiagnostics.com

Quest Diagnostics: Test Directory

testdirectory.questdiagnostics.com

So I did back in July 2022. But I didn’t use the sensitive version ever again due to the reference range being different. Here were my results

7-14-22
Progesterone - <0.1 (<0.3ng/ml)

The thing is, my prog level started coming back elevated during my next set of labs in November 2022.

11-22-22
Progesterone - 1.6 (0.0-0.5ng/ml)

I never got prog tested with the sensitive version once my prog level started to continuously come back very high. But what I’ll do next time I have labs done, is have it tested with both the sensitive, and non sensitive versions that quest offers

 

[Gianluca]

Could you mind me again what you use? I think you mentioned micronized oral progesterone.

I’m currently use an injectable, which I find it works the best, more physiologic as it doesn’t make that first pass in the liver.

I tried oral micronized IR and SR, cream or forearm and scrotum, I felt too moody with this and groggy at times, likely due to excess allopregnenolone.

There is out there a solution made with Progesterone dissolved in vitamin E and MCT oil, the vitamin E it thought to by pass the first metabolism in the liver and give Progesterone a 48hr half life, that might be something to try

 

[FunkOdyssey]

So I did back in July 2022. But I didn’t use the sensitive version ever again due to the reference range being different. Here were my results

7-14-22
Progesterone - <0.1 (<0.3ng/ml)

The thing is, my prog level started coming back elevated during my next set of labs in November 2022.

11-22-22
Progesterone - 1.6 (0.0-0.5ng/ml)

I never got prog tested with the sensitive version once my prog level started to continuously come back very high. But what I’ll do next time I have labs done, is have it tested with both the sensitive, and non sensitive versions that quest offers

My interpretation of these results is that your actual progesterone level is below the limit of detection. The less specific, standard progesterone test can pick up other things as progesterone, the same way a standard testosterone test will count nandrolone as testosterone for example.

 

[Nelson Vergel]

I’m currently use an injectable, which I find it works the best, more physiologic as it doesn’t make that first pass in the liver.

Thanks. What benefits have you experienced?

 

[Gman86]

My interpretation of these results is that your actual progesterone level is below the limit of detection. The less specific, standard progesterone test can pick up other things as progesterone, the same way a standard testosterone test will count nandrolone as testosterone for example.

Interesting. That would be very ironic if these past couple years I’ve thought I had an excess of prog in my system, when in reality I probably should have been supplementing with prog this whole time lol

 

[Gianluca]

Thanks. What benefits have you experienced?

anxiety and mood improved, some sort of fear of heights improved, I believe it improved my thyroid and adrenal function, better skin, erections sex drive and libido. I was hoping to see improvements in my sleep like other experienced in here, but I don't think I noticed anything in that regard

 

[Gianluca]

Interesting. That would be very ironic if these past couple years I’ve thought I had an excess of prog in my system, when in reality I probably should have been supplementing with prog this whole time lol

keep us posted, I may actually take the LC/MS as well, I think there has been some inconsistency with my Progesterone testing since the beginning as well