Timeline

Retinoid whose enduring sexual dysfunction cases later joined the cross-drug syndrome literature, suggesting a shared downstream pathway with finasteride and SSRIs.

Opens the SSRI era; the drug class whose persistent post-discontinuation sexual effects became known as PSSD.

Second major SSRI; later among the most-reported drugs in persistent-dysfunction case series.

First 5-alpha-reductase inhibitor on the market; persistent sexual effects in this population were later documented alongside the hair-loss cohort.

Became the most deeply characterized SSRI in the corpus — four preclinical papers probe its neurosteroid, gut-microbiota, and transcriptomic effects.

Moved finasteride into a young, healthy population — the cohort in which persistent post-discontinuation symptoms (PFS) were first systematically described.

Dual 5-alpha-reductase inhibitor (types 1 and 2); included in PFS literature as a second 5-ARI trigger.

Early cases of sexual dysfunction persisting years after SSRI/SNRI discontinuation; first proposal of medication-induced gene-expression changes as the mechanism.

Conceptual umbrella for the entire corpus: lasting drug-induced epigenetic modifications as a general side-effect class, covering PFS and PSSD alike.

First regulatory acknowledgment that finasteride sexual effects can outlast treatment — a precursor to the broader 2012 label revision.

71 healthy young men; 94% low libido, 92% erectile dysfunction persisting ~40 months after stopping — established persistence, not just on-treatment effects, as the issue.

Propecia label adds persistent libido, ejaculation, and orgasm disorders; Proscar adds persistent decreased libido. The first major regulatory validation of PFS.

Patient-founded organization that funded the first clinical PFS studies (Brigham and Women's Hospital; Baylor College of Medicine), seeding the research literature.

54 men reassessed ~14 months later: 96% still symptomatic. Duration of use did not predict recovery — evidence for individual susceptibility over dose-response.

First direct biochemical evidence: persistent neurosteroid disruption in cerebrospinal fluid after finasteride discontinuation — the pharmacological mechanism at the heart of the corpus.

Early pharmacovigilance case series establishing the enduring-dysfunction signal across drug classes, before formal diagnostic criteria existed.

Replication in 7 patients: broad steroid-pathway disruption — precursors pile up while downstream calming neurosteroids stay depleted.

532 surveyed, 183 possible cases; genital anesthesia independent of depression; no dose-response — the best clinical characterization of PSSD to date.

Core genetic-susceptibility paper: AR (CAG)n/(GGN)n variants associated with different PFS symptom profiles — a precision-medicine angle for the corpus.

Melcangi's group reports pudendal nerve testing and CSF neurosteroids in 16 PFS patients (DISC-013, 2017) — the first objective peripheral-nerve evidence, abnormal in 4 of 16 — and in 2018 reviews PFS and PSSD together as possibly 'two sides of the same coin' (PFS-006).

Argues finasteride reprograms gene regulation (DNA methylation, histone modification, AR upregulation) — the theoretical origin of the epigenetic model.

300 cases across 37 countries spanning antidepressants, 5-alpha-reductase inhibitors, and isotretinoin with shared genital-numbness/anorgasmia phenotype — empirical basis for grouping the syndromes.

Standard definitional review of PSSD — genital anesthesia, pleasureless orgasm, persistent low libido — with epigenetic and 5-HT1A theories.

Start of the clinical experience that produced his evolving PFS/PSSD theories; he reports ~100 PFS patients treated by 2026.

Patient-reported dataset (~3,000 data points; 265+ PFS, 100+ post-SSRI, 50+ post-retinoid submissions) — one of the largest structured post-drug syndrome datasets available to researchers.

Foundational on-camera record of his endocrine reasoning — estrone, progesterone, androgen blockade — underlying his later neurosteroid commentary on post-drug syndromes.

Label sentence added for 10 substances (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, desvenlafaxine, duloxetine, milnacipran, venlafaxine): 'There have been reports of long-lasting sexual dysfunction where the symptoms have continued despite discontinuation.' First regulator-level recognition of PSSD.

Patient-led charity organizing scientific research, including the Institute of Human Genetics (Germany) study — a key funder of PFS genetics work. Exact founding date unverified; flag before citing.

250+ article review concluding PFS is a real persistent syndrome in a susceptible subset, framing finasteride as an endocrine disruptor — the foundational PFS review.

Foundational statement of his early model: a gene-drug interaction theory in which only carriers of decreased-function AKR1C variants develop PFS when 5AR is blocked; noted postpartum-depression parallels and reported 2 patients improving on rectal progesterone (N=2, self-flagged as weak).

Early-stage clinical-experience anchor: patients describing decade-long symptoms; captures his PFS work before the later model revisions.

Concluded it could neither confirm nor rule out causality but committed to updated warning language — the second major regulator to act after EMA.

Preclinical proof that SSRIs disrupt neurosteroid synthesis — a direct pharmacological bridge between PSSD and the PFS neurosteroid mechanism.

Operational definitions for PSSD, PGAD, PFS, and post-retinoid dysfunction: prior drug exposure, ≥3 months persistence, exclusion of other causes — the criteria the corpus's ICD mappings are built on.

Directly addresses genetic predisposition and cross-drug vulnerability as PSSD risk factors, with a symptom-by-symptom mechanism proposal.

First pharmacovigilance coding specific to PSSD — earlier reports were scattered under generic terms and not recoded, which had blocked database studies.

Argues PFS and PSSD share clinical features and likely common mechanisms — neuroactive steroids, neurotransmitter signaling, gut microbiota — justifying the single-corpus approach.

Latest major regulator action; six products needed updated warnings (citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine). The US FDA still has no equivalent warning.

Strongest preclinical evidence for lasting SSRI-induced transcriptional changes in nucleus accumbens — persistent molecular footprint after the drug is gone.

Potentially the key genetics-first post in his PFS work; full text not retrievable during collection — highest-priority gap. Exact date unverified; cited by secondary sources and the March 2026 SIDEfxHUB video.

Newest comprehensive review; implicates SSRIs in the same 5α-reductase/neurosteroid pathway as finasteride — the strongest pharmacological bridge between PSSD and PFS to date.

Translates Powers' theorizing into a community biomarker protocol: morning hormone panel + androstanediol glucuronide blood test + DUTCH urine test, with strict collection rules — the operational side of his research.

Richest primary source on his mature model: androgen-metabolism genomes 'broken at baseline,' glucuronidation-defect selection bias, three phenotypes (neurosteroid vs androgenic-silencing), window/crash dynamics, chemical-castration trials, epigenetic genes (ARID1A/CHD8/HDAC10), and a planned consensus paper for the Journal of Sexual Medicine.

Condensed public statements of the highway/selection-bias model and the whole-genome-sequencing approach (~100 PFS patients) — the most shareable artifacts of his 2026 model.

Major self-revision: the anhedonia/low-libido subtype is driven by pathological excess of GABA-A-modulating neurosteroids (THDOC, androsterone) causing network remodeling (benzodiazepine analogy). Splits PFS into androgenic-signal-loss vs neurosteroid-excess subtypes; implicates upregulated 3α-HSD, broken glucuronidation (UGT enzymes, gut beta-glucuronidase), and proposes CSF mass spectrometry to identify the overproduced molecule(s).