Prasterone
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Prasterone: From Systemic Lupus Erythematosus to Heparin Cofactor 2 Deficiency
One-Sentence Summary
Prasterone (DHEA) is a sex-steroid precursor whose original indications in the data compiled for this report are systemic lupus erythematosus, pediatric systemic lupus erythematosus, and psychologic dyspareunia. The TxGNN model predicts it may be effective for heparin cofactor 2 deficiency, but this is a model-only prediction with 0 clinical trials and 0 publications supporting it.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Systemic lupus erythematosus; pediatric systemic lupus erythematosus; psychologic dyspareunia (US labeling for the vaginal insert covers dyspareunia due to vulvar and vaginal atrophy) |
| Predicted New Indication | Heparin cofactor 2 deficiency |
| TxGNN Prediction Score | 99.99% |
| Evidence Level | L5 |
| US Market Status | Cancelled only (no currently valid authorizations) |
| Number of NDAs | 2 (both cancelled) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, prasterone (DHEA) is an endogenous steroid precursor that is converted in the body into androgens and estrogens. It has reported immunomodulatory properties, which is consistent with its use in lupus.
For heparin cofactor 2 deficiency, no mechanistic link has been established. This is a rare inherited serpin deficiency, and prasterone has no known effect on heparin cofactor II levels or function. The prediction is a graph-based score only.
The high score therefore should not be read as biological support. Sex steroids may raise rather than lower thrombotic risk, so the prediction is of doubtful plausibility and carries a safety caveat.
Other top predictions show the same pattern. Most are coagulation or platelet disorders (factor V excess, antithrombin type 2 deficiency, thrombophilia, protein S deficiency, pseudo-von Willebrand disease, platelet release disorder), none with supporting evidence. Two have a loose indirect rationale:
- Scleroderma: an autoimmune connective tissue disease like lupus, and DHEA has immunomodulatory properties.
- Complement C4A deficiency: linked to lupus susceptibility.
- Severe nonproliferative diabetic retinopathy: only a speculative link through DHEA’s anti-inflammatory and metabolic effects in preclinical models.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available.
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| NDA208470 | Intrarosa (Millicent US, Inc.) | Insert | Status: cancelled |
| Not available | DHEA (Deseret Biologicals, Inc.) | Liquid | Status: cancelled |
Pharmacology data indicate that prasterone (Intrarosa) was FDA approved for moderate to severe pain during sexual intercourse (dyspareunia) as a symptom of vulvar and vaginal atrophy in women. Both authorizations are now cancelled.
Safety Considerations
- Thrombotic risk: Prasterone is converted to androgens and estrogens, and sex steroids may raise thrombotic risk and can lower free protein S. This is a concern for the predicted coagulation-related indications.
- Pharmacological target: Pharmacology data list the glycine receptor (all subtypes) as a target of DHEA. No other interaction data are available.
Please refer to the package insert for other safety information, including warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests only on a model score, with no trials, no literature, and no plausible mechanism. The coagulation-related predictions also raise a safety concern, since sex-steroid precursors may increase rather than reduce thrombotic risk. Both US authorizations are cancelled.
To proceed, the following is needed:
- Package insert warnings and contraindications (FDA label)
- Mechanism of action data (e.g., from DrugBank)
- Preclinical or mechanistic evidence linking prasterone to heparin cofactor II function
- Thrombotic risk assessment for sex-steroid precursors in patients with coagulation disorders
- Route and formulation compatibility analysis
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.