Danazol
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
Danazol: From Endometriosis to Amenorrhea (Menstrual Suppression)
One-Sentence Summary
Danazol is an oral synthetic steroid approved by the FDA for endometriosis, benign fibrocystic breast disease and hereditary angioedema. The TxGNN model predicts it may be useful for amenorrhea, which is better understood as menstrual suppression than as a disease to treat. There are 0 registered clinical trials and 20 publications, mostly older studies, reviews and one 2024 retrospective cohort.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not listed in the license records. Literature states FDA approval for endometriosis, benign fibrocystic breast disease and hereditary angioedema (PMID 39051650) |
| Predicted New Indication | Amenorrhea |
| TxGNN Prediction Score | 99.9995% |
| Evidence Level | L3 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 11 (the authorizations listed are all ANDA generics) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the Evidence Pack. General pharmacology from the literature applies instead. Danazol inhibits gonadotropins, suppresses gametogenesis and steroidogenesis, and has direct effects on ovarian and adrenal enzyme systems (PMID 2404115). It is also androgenic, and it suppresses ovarian function (PMID 6819580).
Amenorrhea is therefore an expected pharmacologic effect of danazol, not a separate disease target. In endometriosis, lesions become inactive and regress during amenorrhea (PMID 16280355). This is why the knowledge-graph link probably appears. A 2024 retrospective cohort reports danazol used for menstrual suppression in transgender and nonbinary individuals (PMID 39051650). The prediction is plausible, but it is best treated as a therapeutic endpoint. Examples are menstrual suppression, endometriosis and abnormal uterine bleeding.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 2140996 | 1990 | Double-blind randomized study | Fertil Steril | Nafarelin vs danazol 600 mg/day for 6 months in 82 women with endometriosis. Both significantly reduced active disease, but not adhesions |
| 2523321 | 1989 | Randomized comparison | Fertil Steril | Gestrinone vs danazol 600 mg/day for 6 months in 39 infertile women with endometriosis. Doses were raised if amenorrhea was not reached after 1 month |
| 6210867 | 1982 | Double-blind dose study | Obstet Gynecol | 100, 200, 400 or 600 mg/day for 6 months in 27 women with endometriosis. Clinical improvement varied with dose |
| 39051650 | 2024 | Retrospective cohort | Women’s Health (London) | Danazol used for menstrual suppression in transgender and nonbinary individuals. It can induce amenorrhea but causes androgenic side effects |
| 3680485 | 1987 | Clinical study | Hum Reprod | 24 women on 300-400 mg/day for 6 months. Serum progesterone fell significantly |
| 2404115 | 1990 | Review | J Reprod Med | Danazol inhibits gonadotropins and suppresses gametogenesis and steroidogenesis. It also has immunoregulatory effects |
| 6819580 | 1982 | Clinical study/Review | Prog Clin Biol Res | Danazol suppresses ovarian function. Treating endometriosis improves the chance of conception |
| 16280355 | 2006 | Review | Hum Reprod Update | Endometriosis lesions regress during states of ovarian down-regulation, such as amenorrhea or menopause |
| 21701432 | 2011 | Review | Menopause | Evidence-based review of drug therapy for abnormal uterine bleeding. The choice of agent depends on cause, contraception needs and adverse effects |
| 1533675 | 1992 | Review | J R Army Med Corps | Review of inducing amenorrhea in female military personnel. The excerpt in the pack covers the oral contraceptive pill and goserelin, and danazol is not shown |
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ANDA078214 | Danazol (Lannett Company, Inc.) | Capsule | Not listed in the license record |
| ANDA074582 | Danazol (Teva Pharmaceuticals USA, Inc.) | Capsule | Not listed in the license record |
| ANDA077246 | Danazol (Chartwell RX, LLC.) | Capsule | Not listed in the license record |
| ANDA078214 | Danazol (Proficient Rx LP) | Capsule | Not listed in the license record |
The pack lists 5 authorization records, and the fifth is a second Chartwell record under ANDA077246. The only route of administration is oral.
Safety Considerations
Please refer to the package insert for safety information. The Evidence Pack has no label warnings or contraindications, and the drug interaction query found nothing.
Two signals appear in the literature only and are not from the label. Danazol has androgenic side effects, such as pigmentation of vellus hairs and voice changes (PMID 39051650). A case report describes rhabdomyolysis and pancreatitis when danazol 600 mg/day was combined with lovastatin 40 mg/day (PMID 18691993).
Conclusion and Next Steps
Decision: Hold
Rationale: Amenorrhea is an expected pharmacologic effect, so the prediction confirms danazol’s known hormonal suppression and does not point to a new disease. There are no registered trials and no completed Phase 3 RCTs, so evidence is L3. The package insert safety data is missing, which blocks the safety screening step.
To proceed, the following is needed:
- The package insert warnings and contraindications for the US danazol products
- Mechanism of action data, for example from DrugBank
- A decision on whether to pursue menstrual suppression, endometriosis or abnormal uterine bleeding as the indication. Benign mammary dysplasia (rank 2) has a randomized double-blind trial of 80 women (PMID 3074777) and may be the stronger repurposing candidate.
- A benefit-risk assessment of androgenic adverse effects for any menstrual suppression use
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.