Danazol
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Danazol: From Endometriosis to Amenorrhea
One-Sentence Summary
Danazol is a synthetic androgen derivative historically used for endometriosis, benign fibrocystic breast disease, and hereditary angioedema. The TxGNN model predicts it may be effective for Amenorrhea (menstrual suppression), with 0 registered clinical trials but 20 supporting publications, including two Phase-comparable RCTs and a recent (2024) multi-site cohort study specifically on menstrual suppression.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Endometriosis, benign fibrocystic breast disease, hereditary angioedema (per literature record) |
| Predicted New Indication | Amenorrhea |
| TxGNN Prediction Score | 99.9995% |
| Evidence Level | L2 |
| Market Status (Taiwan) | Not marketed (Not marketed) |
| Number of Registrations | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed, drug-label-level mechanism of action data is not currently available for Danazol (data gap). Based on the literature contained in this evidence pack, Danazol is a synthetic derivative of 17α-ethinyl testosterone that suppresses hypothalamic-pituitary-ovarian axis LH/FSH secretion and exhibits antiestrogenic/antiprogestogenic activity. This directly produces endometrial atrophy and anovulation — the same pharmacological pathway used therapeutically to treat endometriosis.
Induction of amenorrhea is not a novel mechanism for Danazol; it is a well-documented, direct pharmacological consequence of its approved use in endometriosis and has been deliberately leveraged off-label for decades (e.g., menstrual suppression in military personnel, and more recently in transgender/nonbinary individuals). The TxGNN prediction therefore reflects an established secondary pharmacodynamic effect rather than a mechanistically distant repurposing hypothesis.
Because the drug’s original indications and new indication share the identical hormonal-suppression pathway, the biological plausibility is high even though dedicated “Danazol for amenorrhea” registrational trials do not exist — the supporting evidence largely comes from endometriosis trials that used amenorrhea as a treatment endpoint/marker.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 39051650 | 2024 | Cohort | Women’s Health (London) | Retrospective multi-site cohort on Danazol for menstrual suppression in transgender/nonbinary individuals; induces amenorrhea with reversible androgenic side effects |
| 1533675 | 1992 | Review | J Royal Army Medical Corps | Survey/review on therapeutic induction of amenorrhoea, comparing oral contraceptives and GnRH analogues |
| 2140996 | 1990 | RCT | Fertility and Sterility | Double-blind RCT: nafarelin vs. Danazol 600mg/day in 82 endometriosis patients; both produced significant disease regression via amenorrhea induction |
| 2523321 | 1989 | RCT | Fertility and Sterility | RCT: gestrinone vs. Danazol 600-800mg/day in 39 infertile endometriosis patients; amenorrhea used as treatment response marker |
| 6819580 | 1982 | Cohort | Prog Clin Biol Res | Danazol suppresses ovarian function/steroidogenesis in endometriosis and infertility treatment |
| 2404115 | 1990 | Review | J Reproductive Medicine | Review of Danazol’s diverse biologic effects, including central inhibition of gonadotropins |
| 16280355 | 2006 | Pending classification | Human Reproduction Update | Endometriosis management update noting lesion regression during amenorrhoea/menopause states |
| 36434439 | 2023 | Pending classification | Arch Gynecol Obstet | Systematic review/meta-analysis of gestrinone (antiestrogen inducing endometrial atrophy/amenorrhea) for endometriosis, contextualizing Danazol’s class effect |
| 21701432 | 2011 | Pending classification | Menopause (New York) | Evidence-based review of pharmacological therapy for abnormal uterine bleeding |
| 2013670 | 1991 | Pending classification | J Allergy Clin Immunol | 13-year survey of attenuated androgens (incl. Danazol) for hereditary angioedema; irregular menstruation/amenorrhea reported as common effect |
Taiwan Market Information
Danazol currently has no registered product license in Taiwan (market status: Not marketed, 0 registrations). No product/dosage-form/indication records are available to summarize.
Safety Considerations
Drug Interactions: 138 total interactions on record. Notably includes a Major-level interaction with Cisapride, and multiple Moderate-level interactions with antidiabetic agents (e.g., Acarbose, Albiglutide, Alogliptin, Canagliflozin, Dapagliflozin, Dulaglutide, Empagliflozin, Ertugliflozin, Exenatide, Glimepiride, Glipizide, Glyburide, insulin products), consistent with Danazol’s known effect of reducing glucose tolerance and requiring antidiabetic dose adjustment. Interactions are also noted with corticosteroids (Budesonide, Budesonide nasal) and Eliglustat.
Detailed key warnings and contraindications are not currently available in this evidence pack — please refer to the official package insert once obtained.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: The mechanistic link between Danazol’s established gonadotropin-suppressing/antiestrogenic action and amenorrhea induction is direct and well-supported by two RCTs, two cohort studies, and a 2024 dedicated cohort study on menstrual suppression (Evidence Level L2). However, no dedicated clinical trials target “amenorrhea” as a primary indication, and Danazol is currently unregistered/not marketed in Taiwan, and TFDA label warnings/contraindications data is a Blocking gap (DG001) that must be resolved before any safety sign-off.
To proceed, the following is needed:
- TFDA package insert (warnings/contraindications) — Blocking gap, required before S1 safety review can proceed
- Confirmed detailed mechanism of action (MOA) documentation from DrugBank or equivalent
- Regulatory pathway assessment given current “not marketed” status in Taiwan
- Clarification of target population and monitoring plan for androgenic side effects (given off-label menstrual-suppression use pattern)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.