Progesterone

Evidence Level: L5 Predicted Indications: 10

Table of Contents

  1. Progesterone
  2. Progesterone: From an Undocumented Original Indication to Amenorrhea
    1. One-Sentence Summary
    2. Quick Overview
    3. Why is This Prediction Reasonable?
    4. Clinical Trial Evidence
    5. Literature Evidence
    6. Safety Considerations
    7. Conclusion and Next Steps
    8. Disclaimer

## Pharmacist Assessment Report

Progesterone: From an Undocumented Original Indication to Amenorrhea

One-Sentence Summary

Progesterone (DrugBank ID: DB00396) is an endogenous steroid hormone; however, this evidence pack contains no record of an original approved indication or India market registration for it. The TxGNN model predicts it may be effective for Amenorrhea, with an extremely high confidence score (99.9996%), but currently 0 clinical trials and 0 publications in this dataset directly support this specific prediction — meaning the prediction is mechanistically compelling but evidentially untested.


Quick Overview

Item Content
Original Indication Not documented — Progesterone has no registered license or approved indication text in this evidence pack
Predicted New Indication Amenorrhea
TxGNN Prediction Score 99.9996%
Evidence Level L5
India Market Status ✗ Not Marketed
Number of Registrations 0
Recommended Decision Hold

Why is This Prediction Reasonable?

Detailed mechanism of action data for Progesterone is not available from DrugBank in this evidence pack (data gap, High severity — DG002). Based on established pharmacology, Progesterone is the key hormone of the luteal phase of the menstrual cycle: its physiological decline (“withdrawal”) triggers endometrial shedding and menstrual bleeding.

This is directly relevant to the predicted indication. Clinically, the “progesterone withdrawal test” is a standard diagnostic and therapeutic maneuver for secondary amenorrhea — administering progesterone and then stopping it is used both to confirm adequate estrogen priming of the endometrium and to induce a withdrawal bleed. This gives the TxGNN prediction (score 0.99999, the highest-ranked candidate in this dataset) a strong mechanistic rationale.

That said, the mechanistic strength is not matched by empirical evidence: the query log shows the ClinicalTrials.gov, ICTRP, and PubMed searches for “Progesterone” + “amenorrhea (disease)” all returned zero results. Given how well-established progesterone use is for amenorrhea in real-world practice, this is most plausibly a search/indexing gap in the data collection pipeline (e.g., query terms not matching how this indication is coded in trial registries or literature databases) rather than a true absence of evidence. This should be verified before the evidence level is treated as final.


Clinical Trial Evidence

Currently no related clinical trials registered.


Literature Evidence

Currently no related literature available.


Safety Considerations

Drug Interactions: A completed DDI query identified 163 total interactions for Progesterone. The interactions sampled in this evidence pack are predominantly rated Moderate severity and are concentrated among antidiabetic agents, including:

  • Metformin, Acarbose, Chlorpropamide, Glimepiride, Repaglinide, Pioglitazone
  • DPP-4 inhibitors: Alogliptin, Saxagliptin
  • SGLT2 inhibitors: Canagliflozin, Dapagliflozin, Empagliflozin
  • GLP-1 agonists: Albiglutide, Dulaglutide, Liraglutide, Semaglutide
  • Insulins: Insulin aspart, Insulin degludec, Insulin detemir
  • Also: Aprepitant, Clarithromycin

This pattern is consistent with progesterone’s known tendency to reduce insulin sensitivity and antagonize glycemic control — patients on antidiabetic therapy would need blood glucose monitoring if progesterone is co-administered. With 163 total interactions on file and only a subset reviewed here, a full interaction screen against the patient’s medication list is recommended before use.

No key warnings or contraindications data are currently available for Progesterone in this evidence pack (Blocking data gap — DG001: TFDA/local label warnings and contraindications have not yet been retrieved).


Conclusion and Next Steps

Decision: Hold

Rationale: The prediction for amenorrhea carries the highest TxGNN confidence score in the entire candidate set and a credible mechanistic basis, but it is currently backed by zero clinical trials and zero publications (Evidence Level L5), and a Blocking-severity data gap (missing local label warnings/contraindications) prevents this candidate from entering safety pre-screening (S1). Under the current evidence base, this does not meet the bar to proceed.

To proceed, the following is needed:

  • Retrieve TFDA/India label warnings and contraindications (resolves Blocking gap DG001) to enable S1 safety screening
  • Confirm mechanism of action via DrugBank API (resolves High-severity gap DG002)
  • Re-run the ClinicalTrials.gov/ICTRP/PubMed searches for “amenorrhea” with expanded synonyms (e.g., “secondary amenorrhea,” “progesterone withdrawal test,” “oligomenorrhea”) to rule out a false-negative search result before finalizing the L5 rating
  • Confirm original indication and regulatory status, since no license or approved indication text exists for this drug in the current dataset
  • As a lower-risk alternative, consider prioritizing benign mammary dysplasia (rank 3, Evidence Level L3, S2) or cervix endometriosis (rank 5, Evidence Level L3, S2) from this same evidence pack — both have at least one completed clinical trial and multiple literature sources, offering a stronger near-term evidentiary base than amenorrhea while the above gaps are resolved

    Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.



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