Diethylstilbestrol
| Evidence Level: L4 | Predicted Indications: 3 |
Table of Contents
Diethylstilbestrol: From Historical Oestrogen Therapy to Amenorrhoea
One-Sentence Summary
Diethylstilbestrol (DES) is a synthetic non-steroidal oestrogen with a long clinical history, though the evidence pack does not record a confirmed original indication or mechanism-of-action detail for this candidate. The TxGNN model predicts it may be effective for Amenorrhoea, with no registered clinical trials and 18 publications identified, most of which are older reviews and case reports describing safety signals (endometrial carcinoma, ovarian failure aetiology) rather than treatment efficacy.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | No approved-indication data recorded (drug not marketed in the UK) |
| Predicted New Indication | Amenorrhoea |
| TxGNN Prediction Score | 99.87% |
| Evidence Level | L4 |
| UK Market Status | Not Marketed |
| Number of Marketing Authorisations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism-of-action data is not available for this candidate. Based on known pharmacology, diethylstilbestrol is a synthetic non-steroidal oestrogen; oestrogen replacement can, in principle, induce endometrial proliferation and withdrawal bleeding, which offers a plausible physiological rationale for use in hypo-oestrogenic amenorrhoea (e.g. premature ovarian failure).
However, the literature retrieved for this candidate is overwhelmingly composed of retrospective reviews and case reports describing the consequences of oestrogen exposure — most notably endometrial carcinoma following long-term cyclical oestrogen-progestogen therapy, and premature ovarian failure/amenorrhoea arising as a complication of in-utero DES exposure — rather than prospective evidence of DES being used to treat amenorrhoea. In other words, the mechanistic direction is plausible, but the retrieved evidence base points more strongly to a safety signal than to a therapeutic effect.
No clinical trials (registered or ICTRP) were identified for this drug-disease pair, and no original indication or MOA data could be confirmed from the source registries used to build this evidence pack.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 24157186 | 2013 | Review | Presse médicale (Paris) | Review of premature ovarian failure (POF); notes in-utero DES exposure as a recognised cause of POF alongside chemotherapy, radiotherapy and ovarian surgery |
| 6141923 | 1984 | Review | Drug Intelligence & Clinical Pharmacy | Review of drug-induced infertility via hypothalamic-pituitary-gonadal axis or direct gonadal toxicity |
| 6764754 | 1982 | Review | Current Problems in Pediatrics | Review of menstrual disorders in adolescents |
| 545869 | 1979 | Review | The Western Journal of Medicine | Symposium review on secondary amenorrhoea and clinical consequences of in-utero stilbestrol exposure |
| 13117952 | 1953 | Case series/Review | Journal of Clinical Endocrinology and Metabolism | Early review of primary ovarian failure |
| 1137707 | 1975 | Case report | British Journal of Obstetrics and Gynaecology | Endometrial adenocarcinoma following long-term cyclical oestrogen-progestogen therapy for Turner’s syndrome (safety signal) |
| 1137706 | 1975 | Pending classification | British Journal of Obstetrics and Gynaecology | Oestrogen-induced endometrial carcinoma in a patient with gonadal dysgenesis after prolonged stilboestrol therapy |
| 4721406 | 1973 | Pending classification | Obstetrics and Gynecology | Turner’s syndrome with endometrial adenocarcinoma associated with stilbestrol therapy |
| 14227788 | 1964 | Pending classification | Thérapie | Treatment of endocrine sterility |
| 12305580 | 1940 | Case series | Human Fertility | Historical study of cyclic changes in cervical mucus and its relevance to fertility assessment |
UK Market Information
Diethylstilbestrol currently holds no MHRA marketing authorisations and is not marketed in the UK (0 licences recorded).
Safety Considerations
Please refer to the SmPC and BNF for safety information. Report suspected adverse reactions via the Yellow Card Scheme.
Conclusion and Next Steps
Decision: Hold
Rationale:
- The mechanistic rationale for oestrogen replacement in hypo-oestrogenic amenorrhoea is plausible, but the retrieved evidence base (L4, no clinical trials, predominantly older reviews and case reports) predominantly documents oestrogen-related harms — notably endometrial carcinoma — rather than therapeutic benefit, and safety/warning data needed for a formal S1 evaluation is currently missing (blocking data gap).
To proceed, the following is needed:
- SmPC-equivalent warnings and contraindications (currently a blocking data gap for safety evaluation)
- Confirmed mechanism-of-action documentation from DrugBank or an equivalent source
- Confirmation of the drug’s original approved indication(s), which are not currently recorded
- Prospective or controlled evidence specific to amenorrhoea, given the current evidence base is retrospective and safety-signal-dominated
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.