Dienogest for adenomyosis
Two meta-analyses indicate dienogest substantially alleviates dysmenorrhea and pelvic pain and reduces uterine volume in women with adenomyosis, with superiority over LNG-IUS for pain and uterine volume.
Hypothesized mechanism
As a progestin, dienogest may suppress adenomyotic tissue activity, reducing pelvic pain and uterine volume.
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 9 of 10 overall, a strong reading, from a direct rated strong 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 claim is provided, sourced from Open Targets noting DIENOGEST as a Phase 1 clinical candidate for adenomyosis. No mechanistic lines of evidence are described, so no independent convergence can be assessed.
Rigor
The claim is a database registry entry indicating clinical-candidate status, not a mechanistic model or study. No human-relevant or in-vitro mechanistic data are presented.
Specificity
The claim identifies DIENOGEST as a small molecule candidate but names no molecular target or mechanism of action. Without target information, drug-target specificity cannot be scored.
Plausibility
No target-phenotype relationship is described in the single claim. The entry only states clinical-candidate status, providing no basis to evaluate mechanistic plausibility.
Consistency
With only one registry claim and no mechanistic signals, there is nothing to compare for directional consistency.
Scored for women. Evidence generated in women (female population, ~100% female). (band F1, ×1.00).
Corroboration
Evidence comes from two independent systematic reviews/meta-analyses (Dienogest in-depth meta-analysis and the LNG-IUS comparison meta-analysis), both consistently finding dienogest effective for adenomyosis. Two distinct syntheses agreeing in direction supports a high score, though neither is a single large RCT.
Rigor
Both sources are explicitly meta-analyses (claims 1-12 cite 'meta-analysis' and 'systematic review and meta-analysis'), the highest study-design tier.
Specificity
Claims name both dienogest and adenomyosis directly (e.g., 'Dienogest substantially alleviates dysmenorrhea in women with adenomyosis' and 'more effective than LNG-IUS for the management of adenomyosis').
Plausibility
The claims describe outcomes (reduced pelvic pain, reduced uterine volume) consistent with a progestin acting on adenomyotic tissue, but no explicit mechanism is stated in the quotes. Mechanistic plausibility is implied rather than evidenced.
Consistency
Both independent meta-analyses agree dienogest is effective and reduces dysmenorrhea/pelvic pain; the comparison review further shows superiority over LNG-IUS for pain and uterine volume. The only negative (lower haemoglobin) is a safety signal, not a contradiction of efficacy.
Independent reading, reported beside the score
One outside model cross-reference is reported alongside the composite score. It is recorded separately and is not combined into the score.
MATRIX cross-reference
Every Cure’smachine-learned treatment-probability model, drawn from a biomedical knowledge graph. We read its public dataset release, which covers roughly 1,800 drugs and 22,000 diseases. It provides a model-based estimate of how plausible a drug-disease link is given the structure of biomedical knowledge, reported alongside the substrate’s own evidence.
For this pair. MATRIX maps this drug and disease in its graph but returned no treat-score for the pair, which can mean the predicted link fell below the model's publication threshold.
Scored over MATRIX’s own entities, confirming the same drug and disease: CHEBI:70708 (drug) and MONDO:0010888 (disease). Validate against the source: Every Cure’s MATRIX dataset ↗.
More on the MATRIX cross-reference and its provenance →Regulatory & development status
Where this candidate sits in the US regulatory landscape: whether the drug is already FDA-approved for adenomyosis (on-label) or approved for something else (off-label), whether the molecule is available as a generic or a single-source brand still under patent, and how far it has been studied as a therapy for this condition. Each fact is drawn from a public US source and reported beside the score; none of it is folded into the score.
This is descriptive context, not regulatory advice. It maps the landscape a 505(b)(2)route would build on (an already-approved active ingredient proposed for a new indication), but it is not a 505(b)(2) viability assessment, and says nothing about whether any particular development path is advisable. “Approved” means FDA-approved (US); approvals elsewhere are out of scope.
Approval relationship Off-label
Read from the drug’s FDA label via DailyMed, the US National Library of Medicine’s label repository. A label is only counted when it carries an FDA-approved marketing category (an NDA, ANDA, or biologic BLA); dietary supplements, homeopathics, and OTC-monograph products are not FDA-approved drugs and are excluded.
For this pair. The drug has an FDA-approved label, but for a different indication, so using it for this condition would be off-label.
Generic & patent supply Only in combination products
Read from the FDA Orange Book (Approved Drug Products with Therapeutic Equivalence Evaluations), using single-ingredient products only so that patents on novel branded combination formulations are never attributed to the base molecule.
For this molecule. Appears only inside combination products, not as a stand-alone single-ingredient product.
Clinical-trial stage, for this condition Phase 1
Read from ClinicalTrials.gov (US National Library of Medicine). A trial only counts when the drug appears as an experimental or active-comparator intervention in an interventional study of this condition; mechanistic, drug-interaction, post-marketing (Phase 4), and comparator-background uses are excluded, so this reflects the drug being tested as a therapy for adenomyosis.
For this pair. Studied in 2 qualifying interventional trials · highest stage reached Phase 1 · active trial(s).
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.
- 1dienogest was effective across varying severities of dysmenorrhea PubMed · PMID 39754909 ↗
- 2dienogest was effective across varying severities of dysmenorrhea and different treatment durations PubMed · PMID 39754909 ↗
- 3Dienogest has emerged as a promising drug for treating adenomyosis. PubMed · PMID 39754909 ↗
- 4CONCLUSION: Dienogest substantially alleviates dysmenorrhea in women with adenomyosis, particularly among those with severe baseline dysmenorrhea and extended treatment periods. PubMed · PMID 39754909 ↗
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 →