Danazol
| Evidence Level: L5 | Predicted Indications: 9 |
Table of Contents
Danazol: From Endometriosis to amenorrhea (disease)
One-Sentence Summary
Danazol is a synthetic androgen with antigonadotropin activity, originally used to treat endometriosis and fibrocystic breast disease. The TxGNN model predicts it may be effective for amenorrhea (therapeutic induction of amenorrhea), with no registered clinical trials and 20 publications (mostly dated reviews and small clinical studies) currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Endometriosis; endometriosis of uterus; breast fibrocystic disease |
| Predicted New Indication | Amenorrhea (disease) |
| TxGNN Prediction Score | 1.0000 |
| Evidence Level | L5 |
| India Market Status | Listed in a compiled Indian medicine price dataset (at least 20) – CDSCO approval status is not included in this data |
| Number of Listed Products | at least 20 |
| Recommended Decision | Hold |
Note: The approved-indication text was not available in the India licence records, so the original indications above are not taken from licence records. Predictions and scores on this page come from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence.
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on the published literature, danazol is an antigonadotropin synthetic steroid derived from 17α-ethinyltestosterone. It suppresses the pituitary-ovarian axis (reduced LH/FSH), suppresses gonadal and adrenal steroidogenesis, and binds steroid receptors in target tissues. These effects lead to endometrial atrophy and amenorrhea.
Amenorrhea is already the mechanism through which danazol treats endometriosis: lesions become inactive and regress when the ovaries are down-regulated. Inducing amenorrhea is therefore a direct pharmacological effect rather than a distant extrapolation. A 2024 retrospective multi-site cohort study also reports danazol being used for menstrual suppression in transgender and nonbinary individuals.
Caution is needed in how the indication is read. The model’s label “amenorrhea” most plausibly represents a therapeutic effect (menstrual suppression), which differs from a disease to be corrected. Androgenic side effects also limit how widely this use can be adopted.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 39051650 | 2024 | Retrospective multi-site cohort | Women’s Health (London) | Danazol used for menstrual suppression in transgender and nonbinary individuals; induces amenorrhea with reversible androgenic effects |
| 2523321 | 1989 | Randomized comparative study | Fertil Steril | Gestrinone vs danazol 600 mg/day for 6 months in 39 infertile women with endometriosis |
| 2140996 | 1990 | Double-blind randomized | Fertil Steril | Nafarelin vs danazol in 82 women with endometriosis; both produced significant disease regression |
| 6210867 | 1982 | Double-blind dose study | Obstet Gynecol | Danazol 100–600 mg/day for 6 months in 27 women; clinical improvement varied with dose |
| 2404115 | 1990 | Review | J Reprod Med | Danazol inhibits gonadotropins and suppresses gametogenesis and steroidogenesis |
| 16280355 | 2006 | Review | Hum Reprod Update | Endometriosis lesions regress during amenorrhea or menopause; update on management |
| 21701432 | 2011 | Review | Menopause | Evidence-based review of drug therapy for abnormal uterine bleeding |
| 1533675 | 1992 | Review | J R Army Med Corps | Methods for induced amenorrhoea in female personnel (continuous pill, GnRH analogue) |
| 36434439 | 2023 | Systematic review and meta-analysis (gestrinone; indirect) | Arch Gynecol Obstet | Gestrinone induces endometrial atrophy and/or amenorrhea in endometriosis |
| 6819580 | 1982 | Review/clinical | Prog Clin Biol Res | Danazol suppresses ovarian function in endometriosis and infertility |
India Market Information
The approved-indication text was not recorded for any licence. Twenty valid single-ingredient registrations exist; the main ones are:
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 124467 | Ladogal 50mg Capsule (Sanofi India Ltd) | Strip of 10 capsules | Not recorded |
| 123026 | Ladogal 100mg Capsule (Sanofi India Ltd) | Strip of 10 capsules | Not recorded |
| 58574 | Danogen 200 Capsule (Cipla Ltd) | Strip of 10 capsules | Not recorded |
| 94655 | Gynazol 200mg Capsule (Sun Pharmaceutical Industries Ltd) | Strip of 10 capsules | Not recorded |
| 247045 | Zendol 200mg Capsule (Serum Institute of India Ltd) | Strip of 10 capsules | Not recorded |
Safety Considerations
Contraindication signals (from knowledge-graph disease associations, not label text): epilepsy, porphyria (including inherited porphyria and porphyrin metabolism disease), kidney disease, liver disease, gallbladder disease, female breast carcinoma, migraine disorders, pyoureter, and familial combined hyperlipidemia.
Drug Interactions: 138 interactions were identified in total. Examples:
- Major: Cisapride
- Moderate: Antidiabetic agents, including acarbose, alogliptin, canagliflozin, dapagliflozin, empagliflozin, glimepiride, glipizide, glyburide, human insulin and GLP-1 agonists (albiglutide, dulaglutide, exenatide); also budesonide and eliglustat
- Literature reports also describe increased carbamazepine levels with danazol and rhabdomyolysis/pancreatitis when combined with lovastatin.
Androgenic adverse effects (e.g., voice changes, hair pigmentation) are described in the literature. Please also refer to the package insert, as label warnings were not available in the data compiled for this report.
Conclusion and Next Steps
Decision: Hold
Rationale: The mechanistic link is direct, since amenorrhea is the known pharmacological effect of danazol in endometriosis. However, the evidence is L3 only: there are no registered trials, the supporting studies are largely dated or indirect, and the one recent study is a retrospective cohort. The indication is also an intentional drug effect rather than a disease, and the safety profile (many contraindication signals and interactions) calls for caution. It is best treated as a research question at this stage.
To proceed, the following is needed:
- Clear definition of the target use (e.g., menstrual suppression in specific populations versus a disease indication)
- Prospective or controlled data on danazol for menstrual suppression, including dose, duration and contraception requirements
- Package insert warnings and contraindications from India licence holders
- Mechanism of action data (MOA) from DrugBank
- Comparison with established alternatives (continuous hormonal contraception, GnRH analogues)
- A safety-monitoring plan addressing androgenic effects, liver function, lipids and the interactions listed above
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.