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.
Regulatory & development status
Where this candidate sits in the US regulatory landscape: whether the drug is already FDA-approved for pmdd (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: “use by females of reproductive potential to: Prevent pregnancy. ( 1.1 ) Treat symptoms of premenstrual dysphoric disorder (PMDD) for females of reproductive potential who choose to use an oral contrac”, VESTURA (DROSPIRENONE AND ETHINYL ESTRADIOL) KIT [TEVA PHARMACEUTICALS, INC.] · view label ↗
Generic & patent supply Brand-only, patent-protected
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. Single-source brand with at least one unexpired Orange Book patent (latest listed expiry Jun 2031).
Latest listed Orange Book patent expiry: Jun 2031. Patent listings can change and do not by themselves determine when a generic may launch.
Clinical-trial stage, for this condition Phase 2
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 pmdd.
For this pair. Studied in 1 qualifying interventional trial · highest stage reached Phase 2 · halted or terminated.
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 →