DROSPIRENONE for PMDD
Drospirenone is a Phase 2 clinical candidate for PMDD whose annotated mechanism is mineralocorticoid receptor (NR3C2) antagonism.
Hypothesized mechanism
By antagonizing the mineralocorticoid receptor (NR3C2), drospirenone may counteract aldosterone-mediated fluid retention and related premenstrual symptoms 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 of 10 overall, a exploratory reading, from a pathway rated exploratory 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: drospirenone acting as a mineralocorticoid receptor antagonist on NR3C2 (claim 1). No independent converging lines (e.g., progesterone receptor activity, anti-androgenic action, GABAergic effects) are cited.
Rigor
The evidence is a database (Open Targets) annotation citing a Phase 2 clinical stage for PMDD (claim 1), which is human-relevant context, but no actual study design, model, or outcome data are presented. This is a curated target-mechanism statement rather than experimental rigor.
Specificity
The claim names a specific molecular target and action—mineralocorticoid receptor (NR3C2) antagonism (claim 1)—but drospirenone is known to be pharmacologically promiscuous (progestogenic, anti-androgenic), and only one target is documented here, limiting demonstrated specificity.
Plausibility
The single annotated mechanism (mineralocorticoid receptor antagonism, claim 1) plausibly relates to fluid retention/bloating symptoms in PMDD and is consistent with a Phase 2 clinical candidacy, but the claim does not link the target directly to core mood/affective phenotypes of PMDD.
Consistency
With only one mechanistic claim there is no internal contradiction, but neither is there convergence among multiple signals (claim 1). Consistency cannot be strongly affirmed from a single data point.
Cycle-phase dependence
Why it matters. Some treatments work differently depending on where someone is in the menstrual cycle, and for a cyclical condition like PMDD the timing can be the whole point. A drug that helps in the luteal phase, the roughly two weeks before menstruation, can look weaker than it is when its effect is averaged across the entire cycle.
What tracking the phase adds. Holding the phase as structured data lets a luteal-phase result be read in its phase rather than averaged across the cycle, and records the dosing pattern, taking the drug only in the luteal phase, that a phase-blind record does not capture.
What the literature says. For PMDD this is well established: intermittent luteal-phase SSRI dosing is an accepted first-line regimen (ACOG 2023), and it works within days, which is itself a clue that the drug acts through a faster route here than in depression. The standard outcome instrument for measuring it is the Daily Record of Severity of Problems (DRSP).
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 →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), DROSPIRENONE (a Small molecule) is a clinical candidate for PMDD (maximum clinical stage PHASE_2); its mechanism of action is Mineralocorticoid receptor antagonist on target nuclear receptor subfamily 3 group C member 2. Open Targets · mechanistic ↗
- 2In FDA AEMS (the FDA Adverse Event Reporting System, formerly FAERS; retrieved 2026-06-16), 7113 report(s) of ANXIETY were recorded for DROSPIRENONE among female patients (of 47699 female reports for DROSPIRENONE 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 DROSPIRENONE 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), 1957 report(s) of DEPRESSION were recorded for DROSPIRENONE among female patients (of 47699 female reports for DROSPIRENONE 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 DROSPIRENONE 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), 1244 report(s) of FATIGUE were recorded for DROSPIRENONE among female patients (of 47699 female reports for DROSPIRENONE 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 DROSPIRENONE 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 →