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← Phenome Registry

PH014 — Hormonal Volatility

Stability of hormone-linked signalling patterns that influence mood, cognition, and physiological regulation.

How stable hormone-linked signalling feels over time — as distinct from a single hormone mechanism.

Therapeutic areas: TA001 ★TA002TA003TA004

Provenance: Core Version 1 registry phenome for hormone-linked signalling stability affecting mood and cognition. Cross-referenced to gut–estrobolome and insulin–estrogen biology from BRS-X Hormones workstream. (origin: BRAIN)

Related phenomes: PH003 — Emotional Regulation, PH004 — Cognitive Energy Stability

External framework cross-references

RDoC domains

  • Arousal and Regulatory Systems — endocrine / hormonal regulation

DSM / ICD context

  • Premenstrual dysphoric disorder
  • Perimenopause — mood and cognitive volatility

Foundational Evidence

Registry-level Phenome Evidence Confidence (below) is independent of Biology → Phenome Confidence and Evidence Confidence on individual mechanism pages. Use the scoring guide for definitions of all three scores.

These are three independent scores. They are not combined or averaged. A phenome can have Medium registry evidence while individual mechanism rows show different Biology → Phenome and Evidence scores.

1. Phenome Evidence Confidence (Phenome Registry only)

Question: How convincing is the foundational evidence that this phenome is a valid, well-defined functional construct — and that diet-relevant biology can plausibly connect to it?

Not a roll-up of Biology → Phenome Confidence or Evidence Confidence from Primary Mechanism page rows. Those are scored per mechanism; this score is assigned once per phenome at registry level.

Derived from foundational landmark evidence organised in up to three layers: construct validation, biology→phenome linkage, and nutrition→biology modulation. Each layer may include one or many landmark papers depending on registry review.

2. Biology → Phenome Confidence (Primary Mechanism page §3 rows)

Question: If this PM/FM biology were substantially impaired in isolation, how directly would that phenome be expected to suffer — within BRAIN architecture?

How it is derived: Reviewers read the PM/FM definition and biological function first — initially ignoring attached references and whether dietary intervention studies exist. References are reviewed only when scoring Evidence Confidence (below).

Score levels (the value shown on each row as Biology → Phenome Confidence):

  • High — primary biological determinant (e.g. noradrenergic signalling → attention; GABA synthesis → calming tone)
  • Medium — major contributory determinant, not the sole driver
  • Low–Medium — established but indirect, modulatory, or one integrative step removed
  • Low — distal, conditional, or weak biological coupling

“Not dietary treatment efficacy” means this score does not ask whether a diet or supplement treats the phenome. It asks whether the biology itself is architecturally relevant. Limited dietary RCT evidence belongs in Evidence Confidence, not here.

3. Evidence Confidence (Primary Mechanism page §3 rows)

Question: How convincing are the attached Key References on that specific row that this biology actually relates to this phenome?

How it is derived: Assigned after Biology → Phenome Confidence, by reviewing only the references on that PM/FM row. Judges whether refs support the relationship — not just mechanism or phenome in isolation.

  • High — strong convergent human evidence directly linking mechanism biology to phenome variation
  • Medium — multiple human lines supporting the relationship; may include one bridge study with an inferential step
  • Low–Medium — convergent translational stack without direct mechanism↔phenome measurement on the row
  • Low — mechanistic or preclinical only; mechanism and phenome supported separately but not bridged

Often equal to or lower than Biology → Phenome Confidence. Can occasionally be higher when outcome evidence is stronger than the mechanism's contributory role.

Phenome Evidence Confidence: Low–Medium

Estrobolome and sex-hormone signalling reviews are mechanistically strong; human dietary hormone-stability trials are not represented on the foundational stack.

Construct landmark papers

  • Hu et al. (2023) — Gut microbial beta-glucuronidase and estrogen recirculation — hormonal volatility biology.
  • Li et al. (2023) — Mitochondrial and neuroendocrine function intersecting mood and cognitive regulation.

Biology → phenome landmark papers

  • Depaoli et al. (2021) — Estrogen–insulin resistance coupling and neuropsychiatric endocrine volatility.
  • Ervin et al. (2019) — Estrobolome beta-glucuronidase activity and estrogen signalling stability.

Nutrition → biology landmark papers

  • Sui et al. (2021) — Dietary modulation of gut beta-glucuronidase and estrogen reactivation.
  • D'Afflitto et al. (2022) — Sex hormones, gut microbiota, and dietary signalling intersecting endocrine stability.

Connected mechanisms

BRS-X(Hormones)