PSSD question for the peanut gallery. How many of you were on hormone replacement at the time of developing it...

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

Labs are coming back on the theory that I had a few weeks ago on PSSD patients i've seen.

Some of my PSSD patients are reporting improvement from taking CDG (though some not or are worsened by it). In theory, at least for this phenotype of PSSD, it could help.

If you're not enlightened on this more recent theory of mine, here's some recent posts related to it:

https://www.reddit.com/r/DrWillPowers/comments/1v6nodd/definitive_phenotype_overlap_pfs_and_pssd_normal/

https://www.reddit.com/r/DrWillPowers/comments/1uu1arm/pssd_an_odd_signal_can_pssd_people_keep_an_eye/

If you've ever been to my practice, you know I'm a bit eccentric. I am assuredly a bit of a kook, but I've come to peace with it. I was hanging up some new aperture science art in the "portal" room yesterday after patients. This is not typical doctor behavior, but I've never been good at "typical" so I just keep doing my own thing.

I've got a bunch of schizophrenic relatives, and I assuredly have toed that line at certain points in my life. Part of schizophrenia is basically erroneous pattern recognition. Seeing things where there isn't really a pattern there. That being said, people like that can sometimes literally see things other people can't see, but they really are there. Its cranked up pattern recognition, and crank it up to 11 and it glitches out.

Pattern recognition is basically the thing my brain does best above all other cognitive abilities. One of the oddities I noticed about PFS dudes was that before PFS, a large amount of them were basically GI-Joe clones. They were hypermasculine men compared to your average men when it was a male patient. This was very curious to me, and was one heavily weighted datapoint in the training data for my brain of trying to solve "how does PFS work?".

I have noticed some different patterns in my PSSD patients, but I'm going to hold those cards for now until I'm more confident in them as I know a lot of what I say gets parroted elsewhere. I have learned my lesson on airing my "hrm I wonder" thoughts, as 95% of those are wrong. I'm keeping it now to "hrm, I'm pretty sure this might be".

That being said, I am starting to find consistent lab pattern anomalies in PSSD patients.

A lot (but not all) poisonous chemicals taste bad. For starving humans that thought hemlock didn't taste extremely bitter, they tended to not exist to have more kids. This is called selective pressure. Humans have many redundant pathways as evolution encouraged this to allow for both glitches to be tolerated as well as for them to sometimes be beneficial. Even ones not always directly beneficial for the person's own reproductive capacity can be beneficial for their family or village, so they are selected for anyway and carried on recessively.

This is how you get people who are "fine" but lack a redundancy pathway, but once challenged with a foreign substance, boom, catastrophe.

In the above linked posts, you can see how hormone synthesis and metabolism intersects with neurosteroid synthesis and metabolism. A glitch on one highway can result in traffic buildup on another. Not gridlock, but traffic. But add "an accident" and now no cars are moving.

Theoretically, if my idea on this is correct, an additional risk factor for the development of PSSD would be the same as PFS, overburdening a metabolism system.

How do you do that? Well, you use exogenous molecules. That molecule could be an SSRI that majorly upregulates neurosteroid synthesis until it hits a point of metabolite accumulation and lockout, in the same way that you inject a bunch of androgens (even if they give you a "window") that ends up increased metabolite load over what would normally be physiologically possible. Then the body's feedback loop mechanisms preserve the dysfunctional state, as they keep trying to correct for a problem that evolution never accounted for as it wasn't possible for it to exist without exogenous drugs/hormones.

Pair that problem with an inborn error of metabolism/excretion or transport, and you suddenly get a situation where the rate of neurosteroid/hormone/etc coming in exceeds the rate that it leaves. Once the concentration gets high enough, you get lock out. Signaling ceases. You've turned it up to 11 and the speakers blow out.

I don't think they blow out permanently, but, they will remain silenced until signaling is restored. If signaling is down for a prolonged timeframe, you'll start to see atrophy of the most distal and weak aspects of that system. Just like the collapse of rome, the most distant colonies go down first, and you get small fiber neuropathy, atrophy, and other more persistent symptoms. This could explain why some people "recover" but have some lasting damage that has to be dealt with medically in other means.

The osteoporosis cases with PFS highlight this pretty well. Even if I cure the PFS overnight with a magic wand that wipes out all metabolite build up and restores signaling to normal, the osteoporosis remains.

Alright, before this turns into a rambling rant that sounds more schizo than usual, simple question for the PSSD people here.

Were you using birth control, injectable T? Anything that would boost your overall hormone load at the time of the development of PSSD? If you were not, would you consider yourself pre-PSSD to be a particularly overly libidinous person compared to peers at baseline? Do you look like you have a "lot of hormones" for your gender?

Thanks to everyone who continues to work on this problem, including members like [username removed] for making tools to help the community look at their own genomes to save me time and help find patterns. For users like [username removed] who did something incredibly brave and shared their experience in detail with the community. And For really anyone who is helping with this project. I really deeply believe this is a solvable problem, but that the solution is going to be truly something counterintuitive and will require some outside the box thinking. If the solution was easy, it would have been found ages ago, but nothing good ever comes easy, so lets keep working hard at it okay?

Yes, I know I am supposed to be taking a break but I got this lab result this morning and was like holy fuck its real, so forgive my excited rant.

• Dr P