Prasterone

證據等級: L5

預測適應症: 10 個

Prasterone (DHEA): From No Approved Indication in Germany to Systemic Sclerosis

One-Sentence Summary

Prasterone (DHEA, DB01708) currently holds no marketing authorization in Germany, and its original indication and mechanism of action are not documented in this evidence pack. Among 10 TxGNN-predicted indications, only Systemic Sclerosis (Scleroderma) is supported by real-world evidence — 6 observational studies showing patients have consistently lower serum DHEA-S levels correlating with disease severity — while the other nine candidates have no clinical trial or literature support at all.

Quick Overview

Item	Content
Original Indication	Not available — no marketing authorization or documented original indication in this evidence pack
Predicted New Indication	Systemic Sclerosis (Scleroderma) — the only one of 10 candidates with supporting evidence
TxGNN Prediction Score	99.11% (rank 9169 of network predictions)
Evidence Level	L4 (observational biomarker/correlation studies, no interventional trials)
Germany Market Status	✗ Not marketed
Number of Authorizations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available for prasterone. Based on known pharmacology, DHEA is an endogenous adrenal androgen precursor with reported immunomodulatory activity (including inhibition of IL-6 production), and reduced circulating DHEA/DHEA-S has been observed in several autoimmune diseases.

Six independent cohort and case-control studies consistently report that patients with systemic sclerosis have significantly lower serum DHEA-S levels than matched controls, and that this deficit correlates with disease duration, severity, and organ involvement. This mirrors a pattern already studied more extensively in lupus (SLE), where adrenal androgen deficiency has been proposed to contribute to disease activity — offering a plausible hormone-replacement rationale for testing DHEA supplementation in SSc.

However, all six studies are correlational biomarker studies, not interventional trials of DHEA treatment — none test whether restoring DHEA-S levels improves clinical outcomes. This keeps the evidence at a mechanistic/hypothesis-generating level rather than a validated therapeutic signal.

Note on the other 9 candidates: Ranks 1–6, 8, 9 and 10 (heparin cofactor 2 deficiency, factor V excess, antithrombin deficiency, thrombophilia, diabetic retinopathy, protein S deficiency, complement C4a deficiency, pseudo-von Willebrand disease, platelet release disorder) have no supporting clinical trials or literature and are pure network-prediction artifacts (L5). One of them — thrombophilia (rank 4) — carries a potential safety signal in the opposite direction: the cited literature associates hyperandrogenic states with increased (not decreased) thrombotic risk, so this candidate should be treated as a caution flag rather than a repurposing lead.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
12073659	2002	Review	Orvosi Hetilap	DHEA/DHEA-S have immunosuppressive activity (inhibit IL-6); levels are reduced in most autoimmune diseases
25524921	2015	Cohort	Rheumatology (Oxford)	Androgen levels evaluated in post-menopausal systemic sclerosis patients
16855152	2006	Cohort	Ann NY Acad Sci	Testosterone and DHEA-S levels significantly altered in SSc patients vs. controls; related to disease duration/severity
17086608	2006	Case-control	J Rheumatol	Blunted adrenocortical/adrenomedullary responses to hypoglycemia in premenopausal SSc women, indicating HPA-axis dysfunction
9159534	1997	Case-control	Br J Rheumatol	High prolactin and low DHEA-S serum levels found in patients with severe SSc; correlated with organ involvement
11247320	2001	Case-control	Clin Exp Rheumatol	DHEA-S serum levels in an SSc cohort correlate with disease severity

Germany Market Information

Prasterone currently holds no marketing authorization in Germany (market status: not marketed; 0 authorizations on record).

Safety Considerations

Please refer to the package insert for safety information.

Additional caution: literature associated with a separate, unrelated candidate indication (thrombophilia) suggests androgen excess may be linked to increased thrombotic risk — this should be considered during any future safety workup for DHEA, though it is not derived from the drug's own DDI/warning data.

Conclusion and Next Steps

Decision: Hold

Rationale: Systemic sclerosis is the only predicted indication with any supporting evidence, but that evidence is limited to biomarker correlation studies (L4) with no interventional trials of DHEA treatment in SSc. Combined with the absence of German marketing authorization and complete gaps in MOA and safety data, this candidate is not ready to advance beyond a research hypothesis. The other nine predicted indications lack any supporting evidence (L5) and should not be pursued further.

To proceed, the following is needed:

TFDA/BfArM package-insert warnings and contraindications (currently Blocking data gap, DG001)
Mechanism of action data (currently High-priority data gap, DG002)
An interventional study testing DHEA supplementation specifically in systemic sclerosis patients
A formal safety/DDI profile before any clinical evaluation proceeds
Disclaimer

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