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 originally used to treat endometriosis and fibrocystic breast disease. The TxGNN model predicts it may be effective for amenorrhea (menstrual suppression), with no registered clinical trials but 20 publications (mostly reviews and observational reports) currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Endometriosis; endometriosis of uterus; breast fibrocystic disease (the Singapore licence text does not list an approved indication) |
| Predicted New Indication | Amenorrhea (disease) |
| TxGNN Prediction Score | 99.9995% |
| Evidence Level | L3 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold (research question) |
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 suppresses the pituitary-ovarian axis. It reduces gonadotropin (GnRH/LH/FSH) signalling and ovarian steroid production, and it produces an atrophic endometrium. These pharmacological effects underlie its use in endometriosis.
Amenorrhea is a direct consequence of this same action. Endometriosis lesions regress when the ovaries are down-regulated, as in amenorrhea or menopause, so inducing amenorrhea is part of how danazol treats the disease. The new indication is therefore closely tied to the original one and is a plausible extension rather than a distant mechanistic leap.
A 2024 retrospective multi-site cohort study supports danazol for menstrual suppression in transgender and nonbinary individuals. The evidence remains observational and indirect. Androgenic adverse effects, liver toxicity, thromboembolic risk and teratogenicity limit its use compared with newer options such as progestins and GnRH antagonists.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
The data compiled for this report contain no RCT for this indication. The table shows the most relevant publications, prioritising comparative studies and cohorts, then reviews.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 39051650 | 2024 | Retrospective cohort | Women's Health (London) | Danazol used for menstrual suppression in transgender and nonbinary individuals; amenorrhea induced, with reversible androgenic side effects such as voice changes |
| 2523321 | 1989 | Randomised comparison | Fertil Steril | Gestrinone vs danazol (600 mg/day) in 39 infertile women with endometriosis, with dose escalation if amenorrhea was not achieved |
| 2140996 | 1990 | Double-blind randomised study | Fertil Steril | Nafarelin vs danazol in 82 endometriosis patients; both significantly reduced active disease |
| 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 steroidogenesis and has immunoregulatory effects |
| 16280355 | 2006 | Review | Hum Reprod Update | Endometriosis lesions regress during amenorrhoea or menopause |
| 21701432 | 2011 | Review | Menopause | Evidence-based medical therapy for abnormal uterine bleeding |
| 1533675 | 1992 | Review | J R Army Med Corps | Therapeutic induction of amenorrhoea; GnRH analogue and continuous pill approaches |
| 6819580 | 1982 | Review | Prog Clin Biol Res | Danazol suppresses ovarian function and improves conception chances in endometriosis |
| 6798763 | 1981 | Clinical experience | Wien Klin Wochenschr | Danazol 400 mg/day for 3–6 months in endometriosis and cystic mastopathy |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN03932P | NAZOL CAPSULE 200 mg (Duopharma (M) Sdn Bhd) | Capsule (oral) | Not stated in the licence data |
Safety Considerations
- Disease-level contraindications (from the knowledge graph, not label text): epilepsy, porphyria (including inherited porphyria and other porphyrin metabolism disorders), kidney disease, liver disease, gallbladder disease, female breast carcinoma, migraine disorder, and familial combined hyperlipidemia. Pyoureter is also listed.
- Drug Interactions: 100 interactions were found. The sample reviewed includes one major interaction, with cisapride. Most others are moderate, including antidiabetic agents (acarbose, SGLT2 inhibitors such as canagliflozin and dapagliflozin, GLP-1 agonists such as exenatide and dulaglutide, sulfonylureas such as glimepiride and glipizide, and insulins), budesonide, and eliglustat.
- Other risks from the literature: androgenic effects (hirsutism, voice changes, acne, weight gain), hepatotoxicity, thromboembolic risk and teratogenicity. A published case report describes rhabdomyolysis and pancreatitis when danazol was given with lovastatin.
Please also refer to the package insert for the official warnings and contraindications.
Conclusion and Next Steps
Decision: Hold (research question)
Rationale: The mechanism for inducing amenorrhea is well established and a 2024 cohort supports menstrual suppression. However, there are no registered trials, no RCT, and the evidence is observational or indirect (L3). Safety concerns and newer alternatives also weigh against prioritising danazol for this use.
To proceed, the following is needed:
- Singapore package insert warnings and contraindications from HSA, which are required for safety screening
- Detailed mechanism of action data from DrugBank
- Prospective or comparative studies of danazol against current agents (progestins, GnRH antagonists) for menstrual suppression
- A risk-benefit assessment for hepatic, thromboembolic, androgenic and teratogenic risks, with pregnancy exclusion measures
Other Predicted Indications (for reference)
| Predicted Indication | TxGNN Score | Evidence Level | Suggested Decision | Note | |------|------|------|------|------| | Benign mammary dysplasia | 99.9990% | L3 | Proceed with Guardrails | Closely related to the existing fibrocystic breast disease use; several 1980s clinical studies, including a double-blind randomised trial in 80 women (PMID 3074777) and a double-blind crossover study against placebo (PMID 6373293). Reserve for severe, refractory symptoms. | | Breast adenosis | 99.9960% | L3 | Research Question | Evidence concerns fibrocystic change in general; low-dose danazol reports exist. | | Apocrine adenosis of breast | 99.9987% | L4 | Hold | Indirect evidence through the parent condition only. | | Breast abscess | 99.9966% | L4 | Hold | Two 1986 letters on periareolar abscess; anecdotal. | | Lactation disease | 99.9964% | L4 | Hold | Evidence indirect; danazol is generally avoided during lactation. | | Blunt duct adenosis of breast | 99.9987% | L5 | Hold | Model prediction only. | | Fat necrosis of breast | 99.9966% | L5 | Hold | Weak mechanistic rationale; no evidence. | | Vulvovaginitis | 99.9568% | L5 | Hold | Only an in vitro murine study (progesterone); not tested with danazol. | | Vulvitis | 99.9519% | L5 | Hold | Same preclinical study; no danazol-specific evidence. |
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.