Dr. Will Powers' theory on PFS

General Discussion
#1

Hey guys,

I ran into a comment from Dr. Will Powers on reddit regarding PFS affecting trans woman. I didn’t post it in the science section, because it is a very loosely formulated theory.

However, it is interesting he’s on the 23andme & allo path as well. I am almost confident he has read up on this forum. Can we reach out to him as the foundation? He may be willing to assist us in certain ways.

Has anyone here taken finasteride or dutasteride and gotten post finasteride syndrome (PFS) from them? I have a theory as to why this seems to happen in transgender women more than cis men (which may just be my selection bias anyways).

I have a theory about why this happens, and PFS seems to be reported a lot in transgender women more than the genpop. it at least appears that way to me, but then again, my population of people who have taken finasteride is mostly transgender women.

I have this one theory that single nucleotide polymorphisms in the AKR1C(whatever) enzyme family result in some human sex hormone weirdness that precipitates the development of neural architecture that does not always match the genitals the patient is born with. AKA, those could be a potential Target for genes that cause people to turn out transgender. I collect 23andMe data and I have noticed this as a potential trend but I lack the resources and the data to confirm this at the current time. I have previously put it out there on the internet for people smarter than me to look into.

5-alpha reductase inhibitors can block the conversion of progesterone to 5-alpha-dihydroprogesterone which in turn is processed by the AKR1C genes into a allopregnenolone.

I believe a deficiency in this neurocorticoid (allopregnanolone) is the cause of post finasteride syndrome, as we do know that treatment with a synthetic form of it given via IV infusion (brexanolone) to women with incredibly severe postpartum depression is like an overnight cure. many of the described symptoms of post finasteride syndrome are nearly identical to severe postpartum depression. I think they are effectively the same condition, a depletion of allopregnanolone.

However I think that the overwhelming majority of people never have this problem with 5 alpha reductase inhibitors because they do not have a decrease of function mutation downstream in one of these AKR1C genes as well which I believe is necessary to see the problem happen when blocking 5AR.

Because I think these genes are mutated statistically more often in transgender people, I am asking here if anybody has gotten post finasteride syndrome and additionally has a point mutation in any one of those AKR1C genes.

My reasoning being that we could utilize rectal progesterone or simply 5-a-DHP as a treatment for these people as a much cheaper option than the tens of thousands of dollars per dose brexanolone which isn’t even approved for this indication.

I will disclose I have had two patients with post finasteride symptoms and both responded to rectal progesterone positively. However, N=2 is pretty weak and unimpressive and I need more data beyond what I will ever get in terms of patients that are suffering from this. those two patients lead me to believe that my theory might be correct, but I have a lot of theories, and many of them end up in the trash can after having been tested.

Being as I do not prescribe these drugs (5ARI) I don’t basically create a population group for me to test this theory on. I do not give people post finasteride syndrome by accident for me to experiment with curing it.

That being said, there are forums online of tons of people suffering horrible lives after having taken these drugs even if they are only a small percentage of the population, a solution for them would improve a lot of lives of people who are suffering.

So if you’re out there and you have this data, as always, I would appreciate you sharing it with me.

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#2

Everybody on this forum likely has a form of PFS from taking either of those two drugs.

Do you have any evidence for this?

Proof??

Perhaps for their postpartum depression. PFS is to many so much more than just depression.

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#3

I would imagine that we’d have more trans people here if that was the case.

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#5

This is where I stopped reading #bullshittheory

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#6

I don’t even think this theory even warrants a discussion and I don’t believe this doc remotely understands PFS.

#7

Regardless of whether this notion on prevalance among trans/cis is wrong, I do think it’s interesting to talk about.
Is transgenderism indeed gene related? Do we as PFS sufferers perhaps have gene setups with similar qualities that make us more vulnerable to the effects of 5ari?

I can imagine quite a few transgenders take Finasteride to combat hair loss. Surely there must be PFS sufferers among them too. But since it is already rare among us regular men, it is probably even more rare among them. I mean… Are they here on this forum? If not, why aren’t they here? Do they discuss PFS inside their own transgender community hubs? Would it benefit our goals if more transgender people were present here with us trying to fight this disease and get recognition and research done?

We honestly really don’t know how many of this forums members are potentially transgenders, my guess based on the average poster here is… very very few. But being transgender usually isn’t something you scream off the rooftops given the stigma so we don’t really know.

Is there any statistic on how many people are lurkers on this forum? Could they potentially be transgender people who are a bit fearful to mingle with our predominantly cis-hetero men community?

I have no connections with any transgender communities so I have no idea how prevalent PFS discussions are among them.
My guess is that the average transgender person that takes Finasteride is a man transitioning into a woman… but since they are trying to distance themselves from their manhood I don’t know how much they care about for example their erectile function. I mean it’s still a pleasureable part of their bodies I imagine a transgender person would freak out over loss of genital function just as much as a normal person would?

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#8

The doctor has done some observations and throw out the question if some have a decreased function mutation in acr1s gene. He will not get an answer though…
He is even humble and honest when he admit he hasnt the best data bank and i dont think we should take it against him. Seems to play with open cards and i like that.

Possibly even this theory is going to the trash can but it comes from a doctor and then he has atleast a sporting chance to be on the right way.
I think its great this doctor tries to turn around every stone and comes with new angles. And when he focuses on the brain through normalized allopregnalone levels its even in line with what the science and pfs doctors speak about.
The brain is even a very important player in the hormonal game so going the backway through increased allopregnalone levels with the rectal progesterone can very well get the hormones back and many other pfs symptoms if lucky, even if the brain is the first target. For me the topic is very worth to discuss.

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#9

“5-alpha reductase inhibitors can block the conversion of progesterone to 5-alpha-dihydroprogesterone which in turn is processed by the AKR1C genes into a allopregnenolone”

5a-DHP is in turn processed by the 3a-HSD enzyme into Alleopregnenolone.

Does the AKR1C gene encode the 3a-HSD enzyme?

Could you ask this person on Reddit to provide the AKR1C 23andme data that shows what you say it shows ?

For the record my urine allopregnenolone is high. This does not show what my allopregnenolone levels are in my CNS. But it does probably show that I’m producing ample allopregnenolone via the 3a-HSD enzyme. But I don’t want to assume this means that my 3a-HSD enzyme is working correctly. Maybe it’s converting more 5a-DHP to Allopregnanolone then it should be. So a mutation of a gene related to the 3a-HSD enzyme interests me

Something appears to be “off” with my GABAa receptors and allopregnenolone is a positive allosteric modulator of the GABAa receptors