Dr. Will Powers Interview [PFS / PAS / PSSD Summit 2026]

• 1:40–2:18Clinical origin: Powers treated ~4,000 transgender patients over 13 years; noticed post-drug syndromes, particularly PFS, appearing in his patient population far more often than expected for supposedly rare conditions; began treating PFS in 2019.
• 2:41–2:55Treatment unpredictability: Early PFS treatment was "literally a coin flip" whether an intervention would crash, window, or improve a patient — motivating his search for mechanism.
• 2:58–3:49Genomics approach: Used whole genome sequencing (100 GB per patient, vs ~17 MB for 23andMe) plus blood/specialized tests; describes himself as an "autistic pattern recognition machine"; ~100 PFS patients treated; invited ~a year prior by Dr. Peters, organizer of the World Congress on post-drug syndromes.
• 4:53–7:28Summit reception: Expected dismissal as "some random family doctor"; instead researchers were receptive. His model was built on their published work (e.g., androgen receptor upregulated ~1.7–1.8x in PFS cells; gene methylation findings from Melcangi's team). "Blind men and the elephant" — each lab had mapped one part; he proposed the unifying picture.
• 7:36–7:58Predictive value: Now has a "predictive index" of what will go poorly; notes the paradox that "the very things that will give somebody a window delay their recovery and make it worse."
• 8:30–8:43Next steps: Clinicians collaborating on a consensus document for the Journal of Sexual Medicine with collective findings and expert best recommendations.
• 8:47–9:03Scientific humility: "I guarantee you my theory is wrong. It's just probably less wrong than the ones that came before it."
• 9:24–11:07Core mechanism (androgen metabolism): PFS patients' androgen-metabolism genomes are "broken at baseline... before they ever took finasteride." Testosterone exits via multiple pathways (sulfation, hydroxylation, DHT 3α-metabolites, glucuronidation); most PFS patients lack glucuronidation capacity. "15-lane highway" analogy: finasteride removes ~5 lanes; fine if you had 15, catastrophic if you had 6–7. Selection bias: glucuronidation-deficient men run high DHT (relying on DHT metabolism to clear testosterone) → present with hair loss → prescribed finasteride → "Oh god, I had no redundancy pathways." Labs "maxing out the assays" (3α-androstanediol glucuronide unmeasurably high in one patient, near zero in another).
• 11:31–11:46Heterogeneity: Asked the summit "Is PFS one thing or is it multiple things?" — whole room: "It's multiple things." Three phenotypes proposed (names provisional).
• 11:46–12:16Phenotype 1 — neurosteroid phenotype: Elevated baseline pregnenolone, poor neurosteroid synthesis; 5α-reductase does "many jobs" (corticosteroid and neurosteroid metabolism, not just DHT); disabling it → brain-fog phenotype.
• 12:19–13:20Phenotype 2 — androgenic silencing: Intracellular buildup of weak androgen metabolites crowds out potent androgens ("musical chairs with Helen Keller" analogy); androgen receptor upregulates; signaling drops to near zero despite normal blood levels — an intracrine problem invisible to standard blood tests.
• 13:22–13:58Windows and crashes explained: Exogenous potent androgens briefly fix the potent:weak ratio ("injecting 200 healthy kids into the room") but convert into weak metabolites that can't be cleared — so each "window" requires a higher dose next time and delays recovery.
• 14:35–15:06Experimental approach: Trialing one-month chemical castration in "a few very brave soldiers" to fully clear sex-hormone metabolites — "unplug the router... and plug it back in, do they reboot?"
• 15:10–15:42Epigenetic layer: Recurring "glitches" in epigenetic monitoring genes — ARID1A, CHD8, HDAC10 appearing "more than they should" statistically; epigenetic flags (e.g., for AR upregulation) may fail to be removed after drug stop; mentions valproic acid/valproate/lithium as drugs involved in that biology (research context, not a recommendation).
• 16:04–16:33Prevention focus: "I don't know how to cure PFS" — but believes he has identified who is vulnerable; working on a pre-finasteride screening lab panel document: "at the very least, we don't have any new cases of PFS... Stop the flow."
• 16:38–17:01PSSD/PAS as same-but-different: "PSSD and PAS are basically the same but different... almost identical symptoms... just which metabolite problem, which gene." Intracellular testosterone could reach ~50,000 vs normal 350–1,000.
• 17:06–17:39Libido surge-then-crash: Initial 2–3 day libido surge on starting finasteride = ramp-up of intracellular accumulation ("Yeah, androgens... too many. Too many... the cell is going to pop"). Lecture titled "The Andro World Crowd Crush Disaster" (Astroworld analogy: too many coming in, not enough leaving).
• 17:47–18:15Falsifiability: Claims an experimentally verifiable mechanism matching labs, genetics, windows/crashes, initial reaction, and stop-triggered cases (epigenetic rewriting failure). Key gene classes: UGTs (glucuronidation), ABCC (intracellular transporters), ARID1A/CHD8/HDAC10 (epigenetics).
• 20:46–21:16Close: "No more suicides... We have a unified theory. We have research. We have grants... this is going to get solved."

Timestamps come from auto-captions and can be off by about five seconds.

This release lists transcript files (iWFDBRTgT3g.srt). They are not bundled with the site yet; drop them into corpus/transcripts/ to publish them.