You know, PSSD and PFS may actually be the same thing. Anyone got any data for me?

Original post by Powers — full self-text recovered from the r.genit.al mirror on 2026-10-07 (the export captured the title only):

I was thinking about PSSD the other night when talking to some sufferers about it. They asked me if there was any point in ordering the labs i'm currently looking into for PFS that seem to be abnormal a stupidly high amount of times in my PFS people. Those are:

A normal testosterone blood value

AND

A stupidly high, or stupidly low 3A-ADG or 11-Oxo-Androgen panel, or any other oddball androgen metabolism product (something on the chain on the way from T-synthesis to its excretion that is wildly out of place, indicating an inborn error of metabolism

OR

A stupidly high, or stupidly low urinary testosterone value.

AND FOR A TREAT AND BONUS POINTS:

major disruptive genetic mutations or stop codons or flat out deletions of any of the following (this is not an exhaustive list but seems to be the most common ones)

ABCC2, ABCC3, ABCC4, ABCG2, SLCO1B1, SLCO1B3, SLCO2B1, UGT2B17, UGT2B15, UGT2B7, UGDH, AKR1D1, H6PD, HSD11B1/2, STS

But this person wanted to know, would these be relevant for someone with PSSD. Initially, my gut response was like "nah" but then I actually put some thought into it, and I realized, PSSD may actually just be functioning exactly the same as PFS, just some slightly different inborn errors of metabolism + fuckery caused by various SSRIs.

This is my exact response to that person:

" But....

if you want me to go full tinfoil hat on this and will let me just randomly prognosticate? Fuck I love doing that shit, so here you go:

SSRIs are known to inhibit some of the critical big 4 for androgen metabolism. Those are UGT2B15 and UGT2B17, UGT2B7, and UGT1A4.

Fluoxetine inhibits UGT2B7 and UGT1A4, Sertraline inhibits UGT2B7, and Paroxetine inhibits UGT1A4.

Then, gluc'd steroids have to be exported from cells using MRP transporters, the relevant ones for my theory are ABCC2, 3 and 4.

Setraline inhibits ABCC2 (MRP2) and Fluoxetine does that to MRP 2 and 4.

THEN

There is another exit path, which is sulfation.

SSRIs can mess up sulfation, specifically SULT2A1, which could compound an inborn error as well.

And then fluox messes with CYP2d6, and CYP3A4, and parox 2d6, and sertraline 2c19 and I think maybe 3a4 as well but dont hold me to that one.

Those are the backup pathways, hydroxylation, and so if you're already fucked in another way, yeah that could worsen it.

So it is plausible that someone with an inborn error like the ones that finasteride fucks people up with (UGT2B17 in particular), could suffer from taking a SSRI by knocking out some of the other pathways that are not defective in that patient, creating a similar outcome.

however this is "on paper" and I have ZERO evidence to support that theory. But I only have zero because I don't treat much PSSD, and so data is limited.

In short, yeah, its possible, it works theoretically, but unlike the PFS guys, I have no data for this, and so you'd be the first if you did, which I would welcome.

• Will

Any explanation for PFS or PSSD has to explain why there are "windows" to the disease, and why some treatments initially cause improvement followed by yet another "Crash". I suspect the simplest answer here is that a "window" is when someone's metabolite 100 car pileup finally gets cleared out, and the androgen/estrogen/etc receptors can finally hear something again instead of just weak metabolites piled to the ceiling in terms of receptor noise. However, administering a powerful androgen can in theory briefly upregulate some of those clearance enzymes, but ultimately, that same molecule (like DHB or others people use) will get glucuronidated or otherwise "metabolite'd" and then stack in the corner like any other thing.

It also has to explain why males are disproportionately affected beyond just "exposed to fin more". The more severe cases I've seen are people who are male, and also have a non-stoppable testosterone source. Doing weekly injections or worse, testosterone pellets (which give no shits what your LH/FSH are, they just keep releasing T into a massively overcrowded system).

Mostly all of the female PFS cases I have seen aren't true PFS, they are masculinization after exposure to finasteride, or some sort of skin damage situation with stretch marks/striae and I suspect in most of those, the problem revolves around excretion of glucocorticoids and effectively the same thing as the guys with PFS, but instead of testosterone metabolites, they build up astronomical amounts of glucocorticoids in the skin cells, while maintaining normal serum levels. Another "the molecule checks in but doesn't check out" situation.

Some treatments at first are beneficial, and later harmful (what people report).

This is i suspect why HCG can improve someone, but simultaneously crash them. This is also why sometimes restoring the trigger of the crash can un-crash someone. It alters the enzyme dynamics and metabolite flow temporarily. This paradoxical behavior makes sense in the context of the buildup of ungodly amounts of intermediary molecules that are shifted around with enzyme modification/induction/inhibition, all caused by various other molecules these people are putting into their bodies seeking a cure.

This is also why a cure for one person crashes another. They have different enzyme deletions/failures at baseline.

I am absolutely certain that this situation that I am witnessing in clinical practice and in lab work and with matching genomic findings (like a UGT2B17 deletion) is absolutely ONE of the possible ways to get a PFS like syndrome. But I'm starting to wonder, is PSSD just the same pathophysiology, just reached via other molecules and enzyme knockouts?

So yeah, if anyone with PSSD has the above labs, and or glitches in the above genes. Comment below, because I'm starting to wonder if the thing that quacks like a duck is also a duck and not its own separate disorder, but the same pathophysiology of inborn error of metabolism + novel drug = failure to clear metabolites = crash.

Really though, if you've got PSSD and say have no urinary androgen metabolites on dutch testing, really really let me know that. I dont have enough PSSD cases yet to have enough data to begin my usual autistic pattern recognition machine rituals. That would help.

• Dr P