Danazol
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
Danazol: From Endometriosis to Amenorrhea
One-Sentence Summary
Danazol is a synthetic attenuated androgen historically used for endometriosis, benign fibrocystic breast disease and hereditary angioedema. The TxGNN model predicts it may be effective for amenorrhea (disease), with 0 registered clinical trials and 20 supporting publications, several of which describe its established amenorrhoea-inducing effect in clinical use.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not confirmed in UK marketing authorisation data; per supporting literature in this pack, historically endometriosis, benign fibrocystic breast disease and hereditary angioedema |
| Predicted New Indication | Amenorrhea |
| TxGNN Prediction Score | 99.9995% |
| Evidence Level | L3 |
| UK Market Status | Not marketed |
| Number of Marketing Authorisations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data for Danazol is not recorded in this evidence pack (structured MOA field is a data gap). However, the supporting literature consistently describes it as a synthetic steroid derived from 17-alpha-ethinyltestosterone that acts centrally to inhibit pituitary gonadotropin (LH/FSH) secretion, thereby suppressing ovarian steroidogenesis and gametogenesis (PMID 2404115).
This antigonadotropic mechanism is not incidental to Danazol’s established uses — it is the mechanism by which the drug produces its therapeutic effect in endometriosis: suppression of ovarian function induces a hypo-oestrogenic, amenorrhoeic state that causes regression of ectopic endometrial tissue (PMID 16280355). Several publications in this pack directly document Danazol being used specifically to induce amenorrhoea, including for menstrual suppression in transgender individuals (PMID 39051650) and in a paper explicitly titled “The induction of amenorrhoea” (PMID 1533675).
The TxGNN prediction therefore aligns closely with well-documented pharmacology: amenorrhoea is not a distant new indication but an established, mechanistically direct effect of Danazol that underlies several of its recognised uses. This strengthens biological plausibility, though clinical evidence remains observational/narrative rather than trial-based.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 2140996 | 1990 | RCT | Fertility and Sterility | Double-blind randomised comparison of nafarelin vs. danazol (600mg/day) in 82 endometriosis patients; both induced amenorrhoea and significant disease regression |
| 2523321 | 1989 | RCT | Fertility and Sterility | Randomised comparison of gestrinone vs. danazol (600–800mg/day) in 39 infertile endometriosis patients; time to amenorrhoea assessed as treatment endpoint |
| 36434439 | 2023 | Systematic Review | Archives of Gynecology and Obstetrics | Systematic review/meta-analysis noting antiestrogen agents (including danazol-class action) induce endometrial atrophy and/or amenorrhoea in endometriosis |
| 16280355 | 2006 | Review | Human Reproduction Update | Reviews endometriosis management; lesions regress during ovarian down-regulation states such as amenorrhoea induced by hormonal therapy |
| 21701432 | 2011 | Review | Menopause | Evidence-based review of pharmacological therapy for abnormal uterine bleeding, including hormonal agents that induce amenorrhoea |
| 6819580 | 1982 | Review | Progress in Clinical and Biological Research | Danazol suppresses ovarian function; describes its role in endometriosis and infertility treatment |
| 2404115 | 1990 | Review | The Journal of Reproductive Medicine | Describes Danazol’s mechanism: central inhibition of gonadotropins suppressing gametogenesis and steroidogenesis |
| 39051650 | 2024 | Cohort Study | Women’s Health (London) | Retrospective multi-site cohort study of danazol for menstrual suppression in transgender/nonbinary individuals; effective at inducing amenorrhoea with androgenic side effects |
| 2013670 | 1991 | Observational | J Allergy and Clinical Immunology | 13-year survey of hereditary angioedema prophylaxis with attenuated androgens; irregular menstruation/amenorrhoea reported as a treatment-related effect |
| 1533675 | 1992 | Review | Journal of the Royal Army Medical Corps | Discusses therapeutic induction of amenorrhoea as a clinical goal, referencing hormonal agents including GnRH analogues |
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:
- SmPC warnings/contraindications data for Danazol are marked as a Blocking data gap in this pack, which prevents even a preliminary (S1) safety assessment; combined with Danazol currently having no UK marketing authorisation (0 licences, “Not marketed”), progression cannot be responsibly recommended at this stage despite mechanistically plausible and literature-supported evidence for its amenorrhoea-inducing effect.
To proceed, the following is needed:
- SmPC/PIL safety data (warnings, contraindications, drug interactions) sourced from MHRA or an equivalent regulator
- Confirmation of UK market access route (licensing, import, or special licence supply) given current “Not marketed” status
- Formal study-type classification and relevance grading of the cited literature (currently unclassified/”pending”)
- Assessment of whether “induced amenorrhoea” as a treatment goal (vs. amenorrhoea as a primary disease) is the appropriate framing for further evaluation
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.