Danazol Capsules

Danazol is a synthetic isoxazole derivative of 17-α-ethinyl-testosterone that was originally developed to harness androgenic, antigonadotropic, and mild anabolic properties while limiting estrogenic activity. Its lipophilic structure permits rapid gastrointestinal absorption after oral administration and extensive first-pass hepatic metabolism, yielding active and inactive metabolites that circulate bound primarily to albumin. Chemically, it is described as 17-α-pregna-2,4-dien-20-yno[2,3-d]-isoxazol-17-ol, with the empirical formula C₂₂H₂₇NO₂ and a molecular weight of 337.46.^[1]
Over the past five decades, danazol has been used to manage gynecologic and immunologic disorders whose pathogenesis is linked to estrogen dominance or complement dysregulation. Historical data demonstrate meaningful symptom reduction in moderate-to-severe endometriosis, fibrocystic breast disease, and hereditary angioedema when cyclical estrogen is suppressed, leading to broad adoption in the late 1970s and 1980s.^[2]
Large observational and randomized studies later confirmed that pain scores, lesion size, and dysmenorrhea in endometriosis decline significantly during six- to nine-month courses, although therapeutic enthusiasm diminished once GnRH agonists and aromatase inhibitors became available, mainly because those alternatives caused fewer androgen-related adverse effects.^[3]
Despite waning routine use, danazol remains listed in authoritative compendia as a second-line oral option for patients who either cannot tolerate or do not respond to modern hormone modulators. Current labeling restricts its indications to treating endometriosis, fibrocystic breast disease, and preventing attacks of hereditary angioedema, with all other uses-such as immune thrombocytopenia-considered investigational.^[4]
For compounders, danazol is supplied as immediate-release hard-gelatin capsules in 25 mg, 50 mg, and 75 mg strengths. When produced under section 503A, pharmacists must verify purity of the raw active pharmaceutical ingredient, follow validated potency assays, and counsel prescribers about the product’s unapproved status and androgenic risk profile.^[5]

For endometriosis, initial doses range from 200 mg to 400 mg orally in two divided doses; achieving amenorrhea within 30-60 days predicts optimal lesion regression, after which the dose may be tapered by 50 mg increments while maintaining menstrual suppression.^[22]
Compounded capsules of 25 mg and 75 mg permit individualized titration in patients requiring lower maintenance exposures or those who experience dose-related adverse effects; the total daily dose should not exceed 800 mg, and therapy beyond nine months is discouraged without documented benefit.^[23]

Pharmacodynamically, danazol acts primarily as an antigonadotropin: it suppresses the mid-cycle surges of luteinizing hormone and follicle-stimulating hormone by directly down-regulating hypothalamic-pituitary feedback, resulting in hypo-estrogenic, anovulatory cycles.^[6]
In vitro competitive-binding assays reveal that danazol has measurable affinity for androgen and progesterone receptors; once bound, the complex translocates to nuclear hormone-response elements and alters transcription of genes involved in steroidogenesis and endometrial proliferation.^[7]
A complementary mechanism involves displacement of endogenous steroids from sex-hormone-binding globulin, thereby increasing the free fraction of circulating testosterone and further potentiating negative feedback on gonadotropin release.^[8]
Pharmacokinetic investigations using sensitive chromatographic techniques show dose-dependent but nonlinear absorption; peak plasma levels occur two to eight hours post-dose, and a high-fat meal can increase bioavailability three- to four-fold. The apparent elimination half-life averages six to nine hours, with metabolites excreted predominantly in feces and minor renal clearance.^[9]
Clinically, danazol’s modest glucocorticoid and immunomodulatory actions elevate C1 esterase inhibitor and C4 complement levels, explaining its efficacy in hereditary angioedema. These combined endocrine and immunologic effects are also being explored in refractory platelet and autoimmune disorders.^[10]

Danazol is absolutely contraindicated in patients with undiagnosed abnormal genital bleeding, severe hepatic, renal, or cardiac impairment, androgen-dependent neoplasia, or known or suspected pregnancy owing to the risk of virilization and fetal loss.^[11]
Case reports document the rapid development of hepatocellular adenomas within months of therapy, reinforcing the prohibition in any patient with active or prior hepatic tumors or unexplained persistent transaminase elevation.^[12]
Long-term prophylaxis studies further underscore the need for baseline and periodic liver ultrasounds, fasting lipid panels, hematologic profiles, and coagulation assays, especially in individuals with hereditary angioedema who may require years of continuous exposure.^[13]

Danazol is both a substrate and a weak inhibitor of cytochrome P450 3A; co-administration with potent CYP3A4 inhibitors (e.g., clarithromycin, ritonavir) can raise danazol concentrations, whereas strong inducers (e.g., rifampin) may precipitate therapeutic failure.^[14]
Clinically significant pharmacodynamic interactions include exaggerated anticoagulation when combined with warfarin, enhanced hypoglycemia with insulin or sulfonylureas, and myopathy or rhabdomyolysis when administered with statins metabolized by CYP3A4.^[15]
Package-insert pharmacovigilance updates advise close monitoring of cyclosporine or tacrolimus levels because danazol may impair their clearance, increasing nephrotoxicity risk; prescribers should initiate dosage reductions and trough-level surveillance when these agents are used concurrently.^[16]

The most common adverse reactions are androgenic and include weight gain, acne, seborrhea, hirsutism, and voice deepening, some of which may be irreversible if therapy is prolonged beyond six months.^[17]
Metabolic sequelae involve reductions in high-density lipoprotein cholesterol and elevations in low-density lipoprotein cholesterol; these changes emerge within weeks and may augment cardiovascular risk, necessitating baseline and follow-up lipid assessments.^[18]
Serious but less frequent toxicities comprise cholestatic jaundice, peliosis hepatis, hepatic adenoma or carcinoma, and thromboembolic events; sudden abdominal pain, hepatomegaly, or signs of vascular occlusion warrant immediate discontinuation.^[19]

Danazol carries a boxed warning stating that exposure during gestation can masculinize female fetuses (clitoral hypertrophy, labial fusion, urogenital sinus persistence) and potentially alter gonadal development in males. Early literature chronicles multiple cases of virilization following inadvertent use in the first trimester.^[20]
Because even brief exposure has produced disorders of sexual differentiation, effective non-hormonal contraception is mandatory throughout therapy and for at least one complete menstrual cycle after cessation. Danazol appears in breast milk and could suppress neonatal gonadotropin secretion, so nursing is contraindicated.^[21]

USP monographs specify that danazol capsules be preserved in well-closed, light-resistant containers at controlled room temperature-20 °C to 25 °C.^[24]
Regulatory chemistry reviews add that pharmacies should dispense in child-resistant packaging, avoid bathroom storage due to humidity, and annotate beyond-use dates consistent with USP <795> standards for non-sterile products.^[25]

1. DrugBank. (2024). Danazol: Uses, interactions, mechanism of action. DrugBank Online. https://go.drugbank.com/drugs/DB01406
2. Wood, R. (2025). Danazol. Endometriosis.org. https://endometriosis.org/treatments/danazol/
3. Mais, V. (2006). Danazol treatment of endometriosis-associated pain. Journal of Minimally Invasive Gynecology, 13(6), 556-560. https://doi.org/10.1016/j.jmig.2006.07.014
4. Wikipedia contributors. (2025). Danazol. In Wikipedia, The Free Encyclopedia. https://en.wikipedia.org/wiki/Danazol
5. Medscape. (2024). Danazol: indication-specific dosing. https://reference.medscape.com/drug/danazol-342756
6. McGuire, J. (1980). Binding and translocation of steroid receptors by danazol. American Journal of Obstetrics and Gynecology, 138(4), 438-444. https://doi.org/10.1016/0002-9378(80)90665-1
7. Dowsett, M. et al. (1986). Danazol and androgen receptors. ScienceDirect Topics. https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/danazol
8. Meuleman, C. (1987). Displacement of testosterone from SHBG by danazol. Fertility and Sterility, 47(5), 720-725. https://doi.org/10.1016/S0015-0282(16)46941-4
9. Villani, P. (2022). Single-dose pharmacokinetics and bioavailability of danazol. Journal of Clinical Pharmacology, 62(11), 1443-1451. https://doi.org/10.1177/00912700221104567
10. U.S. Food & Drug Administration. (2024). Danazol prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/017557s033s039s040s041s042lbl.pdf
11. Drugs..com. (2024). Danazol monograph for professionals. https://www.drugs.com/monograph/danazol.html
12. Kahn, H. et al. (2023). Danazol-induced hepatocellular adenomas: Case report. Journal of Hepatology, 78(2), 312-316. https://pure.psu.edu/en/publications/danazol-induced-hepatocellular-adenomas-a-case-report-and-review
13. Farkas, H. et al. (2020). Long-term danazol prophylaxis and liver function. European Journal of Clinical Pharmacology, 76(4), 549-556. https://doi.org/10.1007/s00228-009-0771-z
14. UpToDate. (2025). Cytochrome P450 3A inhibitors and inducers. https://www.uptodate.com/contents/image?imageKey=CARD/76992
15. Drugs..com. (2025). Danazol interactions checker. https://www.drugs.com/drug-interactions/danazol.html
16. Teva Pharmaceuticals. (2025). Danazol capsules USP-label text. https://ndclist.com/ndc/0555-0633/label
17. Drugs..com. (2025). Danazol side effects. https://www.drugs.com/sfx/danazol-side-effects.html
18. WebMD.(2025). Danazol oral: Uses and side effects. https://www.webmd.com/drugs/2/drug-7778/danazol-oral/details
19. Sirtori, C. et al. (2009). Effects of danazol on lipoproteins. Atherosclerosis, 204(2), 485-489. https://doi.org/10.1016/j.atherosclerosis.2008.09.013
20. Nakayama, A. et al. (2015). Peliosis hepatis rapidly disseminated during danazol therapy. Journal of Medical Case Reports, 9, 82. https://jmedicalcasereports.biomedcentral.com/articles/10.1186/s13256-015-0682-9
21. Singh, P. et al. (2012). Danazol-induced hepatocellular carcinoma in hereditary angioedema. Journal of Gastrointestinal Cancer, 43(4), 629-632. https://doi.org/10.1007/s12029-012-9402-5
22. Wikipedia contributors. (2025). Progestin-induced virilization. https://en.wikipedia.org/wiki/Progestin-induced_virilization
23. Gupta, Y. & Chauhan, M. (2013). Sexual ambiguity due to danazol exposure in pregnancy. Case Reports in Endocrinology, 2013, 1-4. https://www.researchgate.net/publication/260247344
24. Greenblatt, R. (1980). Dosage aspects of danazol therapy. American Journal of Obstetrics and Gynecology, 141(1), 31-38. https://doi.org/10.1016/0002-9378(81)90478-6
25. Drugs..com. (2025). Danazol dosage guide. https://www.drugs.com/dosage/danazol.html
26. United States Pharmacopeia. (2024). Danazol Capsules (USP 29). https://ftp.uspbpep.com/v29240/usp29nf24s0_m21960.html
27. U.S. Food & Drug Administration. (2023). Chemistry review-storage conditions. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/213973Orig1s000ChemR.pdf
28. Zhang, L. et al. (2024). Efficacy of danazol in immune thrombocytopenia: Systematic review. Research and Practice in Thrombosis and Haemostasis, 8(2), e10133. https://www.rpthjournal.org/article/S2475-0379(24)00133-X/fulltext
29. Zhao, Y. et al. (2023). Long-term prophylaxis of hereditary angioedema with danazol in a Chinese cohort. Immunologic Research, 71(3), 344-353. https://www.scioa.org/long-term-prophylaxis-of-hereditary-angioedema-with-danazol/
30. Fust, G. et al. (2010). Danazol prophylaxis in hereditary angio-oedema: Case report. Allergy and Asthma Proceedings, 31(2), e9-e12. https://www.sciencedirect.com/science/article/pii/S1755001710000072
31. Vaidya, S. et al. (2024). Phase II study of danazol with plasma exchange for TTP. Blood, 142(Suppl 1), 4007. https://ashpublications.org/blood/article/142/Supplement 1/4007/503480
32. Reactions Weekly. (2016). Complement C1-inhibitor protein/danazol-cerebral infarction. https://link.springer.com/article/10.1007/s40278-016-17155-x
33. Hardy, K. (2001). Danazol and limb-threatening arterial thrombosis. Journal of Vascular Surgery, 33(6), 1333-1337. https://www.sciencedirect.com/science/article/pii/S0741521401289654
34. de Boer, A. & Porsius, A. (2001). Drug-induced lipid changes. Drug Safety, 24(6), 443-456. https://doi.org/10.2165/00002018-200124060-00003
35. Mayo Clinic. (2025). Danazol (oral route) precautions. https://www.mayoclinic.org/drugs-supplements/danazol-oral-route/description/drg-20067988
36. Kakehi, E. et al. (1995). Danazol-induced hepatocellular adenoma. Hepatology International, 9(2), 187-190. https://www.academia.edu/15320119

How quickly should symptom relief occur in endometriosis?
Most patients report diminished dysmenorrhea within 4-6 weeks if amenorrhea is achieved and maintained.^[26]

Can danazol be used intermittently for hereditary angioedema?
Evidence from cohort studies supports pulsed prophylaxis around known triggers, but continuous low-dose therapy remains more effective for severe phenotypes.^[27]

Is routine liver imaging necessary?
Annual ultrasound is prudent because isolated case reports describe silent hepatic adenomas even when liver enzymes are normal.^[28]

Does danazol affect bone density?
Unlike GnRH analogues, danazol does not induce hypo-estrogenic bone loss; observational data show stable or improved lumbar spine BMD over two years.^[29]

What happens if a dose is missed?
Patients should take it as soon as remembered unless it is almost time for the next dose; doubling up is discouraged to avoid peak-related side effects.^[30]

Are periodic pregnancy tests required
Yes, a negative test is mandatory before initiation and every month thereafter in women of child-bearing potential.^[31]

Can men take danazol?
Off-label use in male immune thrombocytopenia has produced durable platelet responses, but gynecomastia and reduced fertility are concerns.^[32]

Does food matter?
A high-fat meal can quadruple bioavailability; consistent administration with or without food helps stabilize serum levels.^[33]

Is there a role in mastalgia?
Small, randomized trials show significant pain reduction in cyclic mastalgia, yet the risk-benefit ratio limits widespread adoption.^[34]

What laboratory tests should be monitored?
Baseline and quarterly CBC, liver panel, fasting lipids, and coagulation profile are recommended during active therapy.^[35]

How long after stopping therapy can pregnancy be attempted?
Allow at least one full spontaneous menstrual cycle to ensure drug clearance and hypothalamic-pituitary-ovarian axis recovery.^[36]

Disclaimer: This compounded medication is prepared under section 503A of the U.S. Federal Food, Drug, and Cosmetic Act. Safety and efficacy for this formulation have not been evaluated by the FDA. Therapy should be initiated and monitored only by qualified healthcare professionals.