Norethindrone for menopause
Per Open Targets, NORETHINDRONE is a Phase 3 clinical candidate for menopause acting as a progesterone receptor agonist.
Hypothesized mechanism
NORETHINDRONE agonizes the progesterone receptor, supplying progestational activity relevant to menopausal hormone therapy.
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 3.8 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 line of evidence is present: one Open Targets annotation stating NORETHINDRONE is a progesterone receptor agonist clinical candidate for menopause. No independent mechanistic lines converge.
Rigor
The claim is a curated database annotation reporting a PHASE_3 clinical stage for menopause, implying human-relevant development, but no actual study model, data, or experimental result is described. This is registry/annotation-level evidence rather than a strong mechanistic or clinical model.
Specificity
The claim names a specific molecular action: progesterone receptor agonist acting on the progesterone receptor target. This is a clearly specified drug-target relationship.
Plausibility
Progesterone receptor agonism fits the menopausal hormone therapy context where a progestin is used, but the claim does not articulate how this action addresses a menopausal phenotype. The target-phenotype link is implied but not demonstrated by the single annotation.
Consistency
There is only one signal, so there is nothing to contradict, but also no convergence to confirm directional consistency. A lone annotation cannot establish that multiple mechanistic signals agree.
Regulatory & development status
Where this candidate sits in the US regulatory landscape: whether the drug is already FDA-approved for menopause (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 On-label (FDA-approved for this use)
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. This condition appears in the drug's FDA-approved label (Indications & Usage), so using it here is an approved, on-label use.
From the label’s Indications & Usage section: “estin combination indicated in a woman with a uterus for: Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause ( 1.1 ) Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atr”, ESTRADIOL AND NORETHINDRONE ACETATE TABLET [INGENUS PHARMACEUTICALS, LLC] · view label ↗
Generic & patent supply Generic available
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. A live ANDA lists this active ingredient, so the basic molecule is available as a generic (off-patent in its basic form).
Clinical-trial stage, for this condition Phase 3
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 menopause.
For this pair. Studied in 1 qualifying interventional trial · highest stage reached Phase 3 · completed.
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), NORETHINDRONE (a Small molecule) is a clinical candidate for menopause (maximum clinical stage PHASE_3); its mechanism of action is Progesterone receptor agonist on target progesterone receptor. Open Targets · mechanistic ↗
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 →