Progesterone is why we're resistant to androgens

[xptriado]

Please read here:
http://www.ncbi.nlm.nih.gov/pubmed/16758493

“Progesterone increased the levels of DHP and THP in plasma and hippocampus and prevented kainic-acid-induced neuronal loss.”

“The administration of the 5alpha-reductase inhibitor finasteride prevented the increase in the levels of DHP and THP in plasma and hippocampus as a result of progesterone administration and abolished the neuroprotective effect of progesterone.”

"Both DHP and THP were neuroprotective against kainic acid. "

"the administration of indomethacin, a 3alpha-hydroxysteroid dehydrogenase inhibitor, blocked the neuroprotective effect of both DHP and THP, suggesting that both metabolites are necessary for the neuroprotective effect of progesterone. "

So something happened to us during finasteride use that consumed/destroyed something. And unfortunately, it keeps happening even after we took finasteride out, as we can see in those 3 subjects in the study!!!

Those 3 guys don’t have DHP nor THP… Of course if you don’t have DHP, you can’t metabolise it into THP… And we still don’t know if once we have DHP we’ll be able to metabolise the THP …

Now…why don’t we have DHP? 5aRII gene mutation? Suggestions?

We also seem to be missing the whole 5a-reductase III thing… and that we can’t do anything about it

[no_hope]

@xptriado

Or how could one try to find if demyelination is occurring?

iirc this is done with a mri. quite a few people on this board have had one to check for ms and other demyelination diseases, and i think only mario has come up positive?

[xptriado]

ok, I thought only Mario had done it.

If Mario tested positive for it, could mean that in fact this is what is happening. But not eveyrone will get demyelination I suppose…maybe it takes a bigger reduction in PR expression to see demyelination. I wonder if Mario is one of the users with more severe symptoms? Or with more altered Progesterone values (higher values)?

I just found this:
sciencedirect.com/science/ar … 8213000683

Highlights
• Nervous system adapts its local levels of pregnenolone, progesterone and its metabolites in response to changes in gonadal hormones.
• Progesterone and its metabolites act as physiological modulators and protective agents in the nervous system.
• Levels of progesterone and its metabolites are affected in neurodegenerative diseases.
• Levels of progesterone and its metabolites in the nervous system are sex-dimorphic.
• It is possible to increase locally the levels of progesterone and its metabolites by pharmacological approaches.

Does someone have access to these articles?

EDIT: I just saw MarioVitali has taken his last finasteride pill more than 12 years ago so he must be one of the users with more pronouced PR expression reduction! Maybe such a dramatic thing like demyelination only occurs when you have very low PR expression… PR expression could be reduced for some more than others. I think this makes sense. Now to find out why there is no DHP…

1. PR gene mutation expression changes after finasteride?
2. Reduction of PR expression leads to less need for DHP and system is downregulated?
3. Down regulated 5ARII enzyme?
   3.1) Due to change in gene mutation expression?
4. Some vitamins being needed for production of NADPH or NADP+ ?

[Oscar]

@dannyfc

Where are blood test results in that study? All I see are spinal fluid and plasma results.

Blood = Plasma

@dannyfc

It’s not unreasonable suggest it should be elevated when conversion is inhibited. We know for a fact the same happens to testosterone when it can’t convert to DHT, found to be 20% higher than before propecia use while on the drug. So why not progesterone as well?

Its not unreasonable. It the only reason I posted. But this study proves that its not true. In fact one of the patients has very low progesterone. There is actually a high amount of variance amongst the patients. (Also, progesterone can be converted into more hormones than testosterone.)

@dannyfc

It’s anti-androgenic effects of progesterone are fairly renowned.

Is there a single source saying Progesterone effects the androgen receptor?

@dannyfc

The side-effects of Deca will verify that given it’s progesteronic properties.

In no way shape or form does Deca in any way support anything you are saying or trying to say in any way. This thread is full of jibberish, but just understand the study proves the title of this thread is wrong. Simple as that.

[xptriado]

@Oscar

In fact one of the patients has very low progesterone.

Yes but he also has very low levels of Pregnenolone. All their Pregnenolone to Progesterone ratio are similar and lower than in Control (except for Control Subject 5).

Basically it’s very diificult to conclude something with such a low sample

Maybe we should look at ratios instead of direct measures

[xptriado]

Sorry to be posting jibberish again, but I found something potentially interesting…
I decided to put these study values of plasma and cfs in a stylesheet and calculate the ratios of substrates to direct metabolytes and between related metabolytes.
I know this is a very small small sample, but this is what we’ve got…
I observed that on average:

• Plasma values of DHEA:PROG are the same for PFS and for Control.
• Plasma values of PREG:PROG are the same for PFS and for Control.
• Plasma values of PREG:DHEA are the same for PFS and for Control.
• CFS values of DHEA:PROG are the same for PFS and for Control.
• CFS values of PREG:PROG are 2,2 points lower in PFS than Control. Average(PFS) = 3.166;Average(Control)=5.351
• CFS values of PREG:DHEA are 2,5 points lower in PFS than Control. Average(PFS) = 3.004;Average(Control)=5.519

How relevant is this I don’t know, but I leave it here…
If it were a big sample, this would suggest that there’s a problem in CFS on the PREG to PROG and PREG to DHEA, while the ratio of DHEA to PROG is maintained.

How about supplementing pregnanolone?

EDIT: Regarding demyelination: alex.miller on hairlosshelp forum has 20 posts on it. Do a search, they are veyr interesting since he seems to be studying biology -> specialization track: neurology and neurological sciences, and he’s very dedicated in helping his friend suffering from PFS. He even refers 2 cases of people diagnosed with Multiple Sclerosis from Finasteride use. He says, though, that it’s not full blown MS since you don’t have 5ArII on the brain, but in fact there is a specific region of the spinal cord which has 5aRII, and it just so coincides that is the region responsible for sexual impulses. So the brain shouldn’t be affected but the spinal cord should.
He also says that most probably this will only occur in long-term (years) fina users.
So long term users could be looking at spinal cord demyelation and short-medium term users at something else…

[Finatruth]

The problem is some people take 1mg to 1/2mg once and have symptoms identical to me and I took it 9 years. Therefore I think the degree of symptoms is more with regards to what levels of prog/neurosteroids in the brain and less to do with the time taking it. It’s has an insidious affect