Re: How does progesterone therapy work within the new PFS model of the disease?
u/drwillpowers
r/DrWillPowers2026-07-18T22:04:12Z
Dr Will Powers’ own statements and theorizing
Mentions treatments or doses — not guidance
Summary (paraphrased)
Powers names his three most common PFS subtypes: (1) androgenic signal loss, a metabolite pileup problem; (2) "melty," a glucocorticoid-related (rarely mineralocorticoid) metabolite buildup; (3) neurosteroid disruption — the traditional theory, which he considers true but covering only part of the symptoms, and the zone where PFS overlaps PSSD. The neurosteroid subtype generally responds to precursor therapy with pregnenolone and progesterone, sometimes plus mild NMDA antagonism. Separately, he notes progesterone acts as an antigonadotropin that can suppress the HPA axis; a mild pileup might be resolved by cutting testosterone synthesis for ~2 weeks — his first deliberate relugolix castration patient took 6 weeks to clear the metabolite pile on labs — suggesting earlier progesterone successes may have worked accidentally through this mechanism in patients without true neurosteroid deficit. He closes by admitting this could be completely wrong but is his best current model.
Key points (paraphrased)
- Three-subtype taxonomy: androgenic signal loss (pileup), melty (glucocorticoid buildup), neurosteroid disruption.
- Neurosteroid subtype = PFS/PSSD overlap zone; responds to pregnenolone/progesterone precursor therapy.
- Progesterone's antigonadotropic/HPA-suppressive effect may accidentally resolve mild pileups — dual mechanism proposed.
- Relugolix castration: 6 weeks to clear metabolite pile on labs.
Why it’s in the corpus
The clearest compact statement of Powers' three-subtype taxonomy and how progesterone therapy fits each — a key reference for the corpus's treatment/mechanism mapping, including the caveat that early progesterone successes may have been misattributed.
Context — the post Powers was replying toVerbatim third-party text, shown for context only — not Powers’ statement. Usernames removed.ShowHide
Powers' comment replies to the original post "How does progesterone therapy work within the new PFS model of the disease?" by [username removed]:
Many people report improvements -though not complete remission- from high-dose oral or rectal progesterone combined with pregnenolone and DHEA.
If the current model involves a buildup of metabolites inside cells, why would increasing progesterone help?
I wonder if this is similar to why a subset of people improve with TRT or DHT interventions, even though, according to the model, they should theoretically get worse.
Also, if progesterone somehow increases the clearance of these metabolites, why doesn't it lead to full remission? Why does it seem to produce only a partial recovery?
Just trying to make sense of all this. ;)
(Parent context recovered from the r.genit.al mirror on 2026-10-07; Powers' comment text itself is from John's user-provided export.)
Some fields on this page come from the release’s Markdown edition, which carries text the JSON edition omits.
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