ESTRADIOL VALERATE for menopause
Estradiol valerate is an approved clinical agent for menopause acting as an estrogen receptor alpha (ESR1) agonist.
Hypothesized mechanism
Estradiol valerate replaces declining endogenous estrogen by agonizing estrogen receptor alpha (ESR1), restoring estrogen-dependent signaling in menopause.
This is the model’s proposed mechanism from the sources on file, not a demonstrated causal pathway. How well the published record supports it is reflected in the rigor and plausibility dimensions of the score, and traced to the verbatim sources at the foot of the page.
How the score was reached, for this pair
The composite score is the sum of five dimensions, each scored 0 to 2 by the model from the evidence on file. Below is the sub-score this specific pair received on each, with what that dimension measures. It scored 5.3 of 10 overall, a emerging reading, from a pathway rated emerging in strength.
The model’s overall reasoning for this pair is the summary at the top of the page, and the mechanism it proposed is in the section above.
Scored for women. Female representation not stated — applicability to women uncertain (flagged for full text). (band F4, ×0.75).
Corroboration
Only a single mechanistic line is provided: Open Targets linking estradiol valerate to ESR1 as an ERα agonist. There are no independent converging sources or pathways, so corroboration is limited to one annotation.
Rigor
The claim is drawn from a curated database (Open Targets) reflecting clinical approval status rather than a specific human or in-vitro experiment. It is human-relevant in that it reflects an approved indication, but no primary study model or data is described, limiting rigor.
Specificity
The mechanism is precisely named: ERα agonism on the specific target estrogen receptor 1 (ESR1). This is a clearly specified drug-target action.
Plausibility
Estrogen receptor agonism is a well-established and biologically coherent mechanism for treating menopause, which involves declining estrogen. The target-phenotype fit is strong and the drug is approved for this indication.
Consistency
There is only one mechanistic signal (ERα agonism), so there is nothing to be inconsistent with; the single signal aligns with the menopause phenotype but consistency cannot be evaluated across multiple lines.
Layers not covered for this pair
Not covered for this pair. This layer holds documented sex-specific pharmacokinetics for a limited set of drugs, and this compound is not among them yet. A blank here means the drug is not covered by the layer, not that no sex difference exists.
More on the sex-specific pharmacokinetics layer and its sources →Not covered for this pair. The cycle-phase layer is seeded for the strongest-evidence cases so far (PMDD), and this pair is not among them yet. A blank here means the pair is not covered by the layer, not that the effect was found to be phase-independent.
More on the cycle-phase layer and its sources →Source evidence · what the pipeline ingested
These are the sources the pipeline ingested to detect and score this signal, the published literature the model actually read, each tagged by study type. Where the model combined findings the claim is marked as a synthesis (S), and where the literature disagrees the contradiction is shown (!).
Every source below belongs to this signal’s evidence arm, Pathway insights. Whel reads each drug-condition pair through four such arms, each held to its own inclusion bar; a signal is surfaced through one of them.
- 1Per Open Targets (retrieved 2026-06-16), ESTRADIOL VALERATE (a Small molecule) is a clinical candidate for menopause (maximum clinical stage APPROVAL); its mechanism of action is Estrogen receptor alpha agonist on target estrogen receptor 1. Open Targets · mechanistic ↗
- 2In FDA AEMS (the FDA Adverse Event Reporting System, formerly FAERS; retrieved 2026-06-16), 13 report(s) of INSOMNIA were recorded for ESTRADIOL VALERATE among female patients (of 863 female reports for ESTRADIOL VALERATE in the analysed sample). This is a raw adverse-event report count, not a disproportionality statistic or evidence of causation, and is subject to reporting bias and confounding. Read two ways: as a safety consideration, and — because it suggests ESTRADIOL VALERATE acts on a system relevant to menopause — as a mechanistic lead for further investigation, not evidence of benefit. AEMS · adverse-event report ↗
These are the verbatim sources the pipeline surfaced and read; they may not be the full published record for a pair, and the score reflects the strength and agreement of the evidence rather than its volume. The strength of these source types is what the rigor dimension of the score reads off. MATRIX, sex-specific pharmacokinetics, and cycle phase are separate layers the pipeline does not ingest, external cross-references reported beside the score, and they link to their own sources in their sections above.
The primary sources and pipelines this evidence is drawn from →