conjugated equine estrogen for menopause
CEE (with or without MPA) is associated with an increased risk of stroke and venous thromboembolism, on the order of about 1 excess event per 1000 person-years.
Hypothesized mechanism
Estrogen-induced procoagulant changes may increase thrombotic and stroke risk.
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 7 of 10 overall, a moderate reading, from a direct rated moderate 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. Evidence generated in women (female population). (band F1, ×1.00).
Corroboration
Both claims derive from a single source, 'Management of Menopausal Symptoms: A Review,' a review article rather than multiple independent studies. A single synthesis scores 1, not higher, since there is no independent replication shown.
Rigor
The source is a review article summarizing risk estimates with quantitative excess-event rates per 1000 person-years, consistent with synthesis of randomized data (e.g., WHI-type trials of CEE). A review/meta-analysis-level source scores 2.
Specificity
Both the drug (CEE, conjugated equine estrogen with or without MPA) and the context (menopausal symptom management) are named directly. The safety outcomes (stroke, VTE) are explicitly tied to CEE.
Plausibility
Estrogen's prothrombotic effects on coagulation factors plausibly underlie increased stroke and VTE risk, but the claims assert the association without spelling out the mechanism. This is a plausible but not explicitly evidenced mechanism in the quotes.
Consistency
Only a single source is provided, so cross-study directional agreement cannot be assessed. Per rules, a single source is scored 1 (n/a, not penalized).
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, Direct research. 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.
- 1the increased risk of stroke and venous thromboembolism associated with CEE (with or without MPA) PubMed · PMID 36749328 ↗
- 2the increased risk of stroke and venous thromboembolism associated with CEE (with or without MPA) PubMed · PMID 36749328 ↗
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 →