LEVONORGESTREL for PMDD
Per Open Targets, levonorgestrel is a Phase 3 clinical candidate for PMDD acting as a progesterone receptor agonist.
Hypothesized mechanism
Levonorgestrel acts as an agonist at the progesterone receptor, potentially modulating luteal-phase progesterone signaling implicated in PMDD.
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 — an Open Targets database entry stating LEVONORGESTREL is a progesterone receptor agonist clinical candidate for PMDD. No independent mechanistic lines converge to support the claim.
Rigor
The claim cites a curated database (Open Targets) reporting a PHASE_3 clinical stage, implying human-relevant clinical development, but no actual study data, models, or outcomes are presented. The evidence is purely a target-annotation reference rather than experimental results.
Specificity
The mechanism is precisely named: levonorgestrel acts as a progesterone receptor agonist on the progesterone receptor target, a specific and well-defined molecular action per the Open Targets annotation.
Plausibility
Progesterone receptor modulation is mechanistically relevant to PMDD given the condition's link to the luteal phase and progesterone/allopregnanolone fluctuations, and the PHASE_3 stage suggests target-phenotype fit. However, the single claim provides no direct phenotypic data linking PR agonism to symptom improvement.
Consistency
With only one claim there is no contradictory signal, but neither is there corroborating direction from multiple sources. Internal consistency cannot be meaningfully assessed from a single database annotation.
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), LEVONORGESTREL (a Small molecule) is a clinical candidate for PMDD (maximum clinical stage PHASE_3); its mechanism of action is Progesterone receptor agonist on target progesterone receptor. Open Targets · mechanistic ↗
- 2In FDA AEMS (the FDA Adverse Event Reporting System, formerly FAERS; retrieved 2026-06-16), 5394 report(s) of FATIGUE were recorded for LEVONORGESTREL among female patients (of 201815 female reports for LEVONORGESTREL 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 LEVONORGESTREL acts on a system relevant to PMDD — as a mechanistic lead for further investigation, not evidence of benefit. AEMS · adverse-event report ↗
- 3In FDA AEMS (the FDA Adverse Event Reporting System, formerly FAERS; retrieved 2026-06-16), 4949 report(s) of ANXIETY were recorded for LEVONORGESTREL among female patients (of 201815 female reports for LEVONORGESTREL 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 LEVONORGESTREL acts on a system relevant to PMDD — as a mechanistic lead for further investigation, not evidence of benefit. AEMS · adverse-event report ↗
- 4In FDA AEMS (the FDA Adverse Event Reporting System, formerly FAERS; retrieved 2026-06-16), 4918 report(s) of DEPRESSION were recorded for LEVONORGESTREL among female patients (of 201815 female reports for LEVONORGESTREL 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 LEVONORGESTREL acts on a system relevant to PMDD — 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 →