Progesterone is why we're resistant to androgens

General Discussion
#1

Cholesterol -> Pregnenolone -> Progesterone -> Allopregnanolone

Finasteride users have low allopregnanolone, implying the conversion process is inhibited.

This causes a blockade of its precursors, that then pool in the serum with nowhere else to go. Hence why many have high progesterone (and in my case high cholesterol).

High levels of progesterone ‘can block the androgen receptor’. This is why I believe we’re resistant to androgens, in spite of high serum levels and the ineffectiveness of TRT.

So why would supplementing progesterone help? In the short-term it should make things worse as you push serum levels even higher. But if it stimulates the conversion process, maybe this brings serum levels back to normality once you stop supplementing. This is all wild speculation, but is the only theoretical reason I can see how people are getting better from it.

Here’s an interesting (depressing) article regarding the conversion process; bio.net/mm/neur-sci/2004-August/058929.html

It then goes on to discuss environmental factors that influence DHT, such as high insulin diets and a natural DHT antibody that resides in the guy.

#2

Well, I can tell you this. After five just a few days of use I got very bad, penis numbness that I hadn’t had in 6 months, bright red and dry face, so stimulating the estrogen receptors is doing something here. Let’s see how I bounce back from this. It is very interesting what has happened. It’s like I created my own crash…in the past, after every mini crash I had I wound have improvements that held

#3

from day one after i got pfs, i didn’t understand how it is possible that my hairloss increased ? it shoud had be the other way around.
and this could explain this perfectlly.
if it is true , i should see decrease of the hairloss and improvment of my symptoms.

#4

The only time I’ve ‘crashed’ (sensitive nipples, numbness, emotional/anxious) since the first week of PFS, was following use of progesterone.

Sorry i don’t understand that either. Unless your hairloss is induced by something other than DHT.

#5

Did you rebound? I rebound and feel better

#6

I improved, but was no better than I was before supplementing.

#7

If you have high progesterone it is just a symptom of pFs.

#8

What is PFS? Sexual dysfunction. What is sexual dysfunction? Resistance to androgens. What blockades androgen receptors? High progesterone.

What makes you think it’s purely a symptom and not a cause, anyone with above range levels regardless of whether they’d taken propecia or not would have similar problems. It’s administrated to inmates purely to remove their libido, disregarding it as being insignificant doesnt make any sense to me whatsoever.

#9

Dannyfc- this is a fantastic article if you get a chance to read it

sciencedirect.com/science/ar … 821300097X

#10

viewtopic.php?f=9&t=8214&start=20#p78491
FYI Progesterone and other neurosteroid levels in plasma and csf of post-fin patients. PROG levels are considered normal in plasma.

Also, don’t post spam rubbish about gut bacteria. thanks.

#11

Is plasma more relevant than serum? Blood tests are used to diagnose hormonal imbalances, so I don’t see how you can disregard high serum progesterone levels even if they’re normal within plasma.

In fact, given that the progesterone metabolites in the study are extremely low in the CFS re-enforces the implication that conversion from progesterone is inhibited. Where does that progesterone go? It pools and causes anti-androgenic effects.

And I wasn’t ‘spamming’ anything so no need for the snark. It was just an addendum to the article I linked that I thought may be interesting.

#12

I had better results using pregnelone

#13

How good were your results?

#14

That’s the same thing?

You answer your own point. Also, only one patient actually had levels higher than controls. It is also up to you to show at what level progesterone is an antiandrogen. I would guess this isn’t even remotely close.

Yeah that’s obvious. Although 3adiol was MUCH higher in plasma than controls, for 2 patients. This is a marker of 5a-reductase activity. So thats a bit funny.

Where does it go??? It converts into another hormone or gets excreted from the body. Pooling??? If it was ‘pooling’ that would also be in the blood test result?!

#15

Where are blood test results in that study? All I see are spinal fluid and plasma results. Results on the forum imply that most members have above average progesterone levels though.

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?

It’s anti-androgenic effects of progesterone are fairly renowned. The side-effects of Deca will verify that given it’s progesteronic properties.

#16

@Finatruth That link you just sent is very interesting. Particularly “Figure 4)”.

These guys are saying that mice with PR haploinsuficiency don’t get all the promyelinating and neuroprotective effects of progesterone they should be getting.
Even when treated with Nestorone (a Progesterone receptor agonist), after having suffered demyeliation through exposure to lysolecithin, myelin repair was not stimulated.

Haploinsuficiency happens in diploids, like mammals, when you have only one functional copy of a gene, being that the other is deactivated by a mutation, and that single functional copy doesn’t produce enough of a gene product, in this case a protein, to bring about a wild-type condition, leading to an abnormal or diseased state.

In mice PR+/-, PR expression is decreased 50-60%!!!

This could be what happened:
A)
Finasteride induced demyelination, like lysolecithin:

  • Maybe the people on this board are PR+/-, which means they didn’t have much neuroprotective and myelin protection from their Progesterone, and also means once damage is done, they can’t recover easily because they have reduced PR expression. Hence the time frame for recovery being so large. Maybe some people are even PR-/-!!
  • “Progesterone treatment does not significantly accelerate myelination in PR+/− mice with reduced PR expression…” -> But it did accelarate it a bit?

B)
Finasteride destroyed progesterone receptors:
-> hence why so much progestorone floating around in serum. Does everyone has medium->high levels?
-> Hence why so little in CFS.

What about now:

  • Find out which gene is this? Haven’t some people done 23andme? If we find out which gene and mutation it is we can just check if
    we have it!
  • Maybe try nestorone, as it may increase sensitivity to the existing progesterone in CFS! even if it doesn’t significantly accelarate myelination!
  • analyzing myelin basic protein (MBP) ? Is this possible? Or how could one try to find if demyelination is occurring?
  • why would it destroy progesterone receptors? maybe it blocks progesterone and the body down-regulates the number of those receptors, adapting, and creates extra number of receptors for other things that got increased by blocking progesterone?If that’s the case, this would be the reason why exogenous progesterone works, as the body feels the need to create MORE progesterone receptors, and then when you cut the exogenous progesterone, he still has those receptors that he just created. Would this make any sense at all?

Someone has access to the whole article and can post it here??

#17

And now I’m reading this:

And I just saw in the study, in the plasma, propeciahelp.com/forum/viewt … =20#p78491, DHP is undetectable in PFS and detected in control.
Same for THP but I don’t know what is THP and now I need to get back to work.

#18

I like where your head is at. Remember, in the most basic scientific equation, less progesterone receptors means less to offset estrogen, even if people have regular estrogen levels.

#19

LOW DHP could be another sign for reduced 5aRII activity. Someone who did 23andme should search the results for mutations of this gene ghr.nlm.nih.gov/gene/SRD5A2. There’s 50 mutations identified that cause 5ARII deficiency… Maybe finasteride triggered that mutant gene expression?

If we have low DHP it means our body doesn’t need as many PR receptors as before. Can someone please check 23andme results??

#20

@Finatruth what you are basically saying is we could all estrogen dominant even if estrogen is within normal boundaries…this is very interesting