PFS metabolite theory, and initial chemical castration cure trial patient update. Also research update.
u/drwillpowers
r/DrWillPowers2026-06-06T22:40:19Z
Dr Will Powers’ own statements and theorizing
Mentions treatments or doses — not guidance
Summary (paraphrased)
The export-captured text of this post presents Powers' observations on hormones and sexuality drawn from 15 years and nearly 5,000 patients: he estimates human sexuality is about 75% hard-coded and 25% hormone-state influenced, citing transgender patients whose orientations and copulatory preferences shifted over years of HRT, and androgen megadosers whose aromatization produced unexpected estrogenic effects. He argued that because PFS eliminates androgenic signaling in some phenotypes, only estrogenic signaling remains, producing shifts in copulatory preference that typically drift back toward baseline on resolution. He drew a parallel with women with 21-hydroxylase deficiency, whose stress-driven cortisol demand increases androgen synthesis and can shift attraction patterns, and framed orientation as a gradient set by in-utero hormone exposure with adult hormones modulating expression only where the "code" exists. Note: the post's title indicates it also covered the PFS metabolite theory, an initial chemical-castration cure-trial patient update, and a general research update — sections not represented in the captured text.
Key points (paraphrased)
- Sexuality estimated ~75% hard-coded, ~25% hormone-state influenced (clinical observation, n≈5,000).
- Trans HRT and androgen-megadose cases cited as evidence of hormone-driven preference shifts.
- PFS's androgenic-signal loss leaves estrogenic signaling dominant → copulatory preference shifts, usually reversible.
- 21-hydroxylase-deficiency parallel: stress-driven androgen synthesis shifting attraction in AFAB individuals.
- Orientation as in-utero-coded gradient; adult hormones modulate only existing code.
- Title signals additional content (metabolite theory, castration-trial update, research update) not captured in export text.
Why it’s in the corpus
Documents Powers' clinical model of hormone-driven sexuality changes in PFS — a distinctive part of his phenotype descriptions — and, via its title, marks a milestone post combining metabolite theory with the first chemical-castration cure-trial patient update. The missing sections should be recovered when the mirror is reachable.
Original post textVerbatim text recovered via the r.genit.al mirror; other users’ names removed.ShowHide
Original post by Powers — self-text as served by the r.genit.al mirror on 2026-10-07 (consistent with the text captured in John's export):
I keep being asked this all over reddit so I'm making a brief update.
On the GNRH drugs, it took this patient approximately 2 weeks to reach a level of T and DHT that could be considered "chemically castrated". Effectively, what could be considered an adrenal level of production.
Patient zero's weirdest baseline metabolite value was a 3A-ADG that was astronomical. So high it could not be measured. Just, something over 5000ng/dl could have been 5001, could have been 100,000ng/dl. no idea. Assay got maxed out.
Despite T and DHT being wiped, that value hung out in the average male range for weeks after that point.
Its now been almost 6 weeks since we started this journey, and his 3A-ADG has finally dropped below 100ng/dl, which means as far as I know, he's clean of androgenic metabolite build up.
During this time, we also did a brief course of daily hydrocortisone replacement at slightly supraphysiological dosing in order to wipe out a potential middle glucocorticoid metabolite build up. In most "melty" patients, this is 11DOC, but it can vary in my experience. Disable ACTH and CRH, and the body stops making these precursors to cortisol, and they can wash out. This was done just to make sure there was no occult metabolite pile up there.
At this point, we're just waiting for his system to wash out the GNRH drug and reboot. I expect he will start to come online by the end of June and produce his own natural hormones again. I imagine it will take him a few weeks from that point to decide if he feels normal and cured or partially so or not at all, and based on that, there are plans of what to do next. But I do hope this is all that's required for most patients of the "androgenic signal loss" Post Finasteride Syndrome phenotype due to metabolite buildup.
non-seq, I did meet with people from corewell about them funding and starting a research study, and we have more meetings to do about this as well, but it does seem like the plan is to put my theory of exactly how PFS works and what genetic mutations cause someone to be vulnerable to it to the test with formal and funded academic research.
This is a glacially slow process sort of thing, as academia always is, so I will continue to do my own thing with my own patients while that process is underway, but I figured I should mention that it will be happening.
That's all for now, please stop asking on unrelated threads every time I comment on literally anything. PFS cure project test #1, "have you tried unplugging it and plugging it back in again?" is still underway. This is all the information I have until he reboots naturally, and even then, I expect a few weeks of time from that point for him to really know if he feels right or not. If you ask in a comment thread, I will be linking this post until I have more information to offer.
-Dr. P
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