17yr female with confirmed HAE dx and recent ICU admission due to sudden onset of laryngeal edema requring 6 FFP (no new HAE therapies tried). Mom (also my patient) has + HAE and doing well on Danazol. Pt. and mother very resistant to try attenuated androgens but also can't afford co-payments for Cinryme or Berinert or other biological HAE meds. She is not pregnant, can Danazol be tried but keep option to Rx her acute symptoms with Berinert or Cinryze? Will appreciate your thoughts for androgens use in a young adolescent females.


Thank you for your inquiry.

I do not think in your case there is any option other than to use a modified androgen or perhaps epsilon-aminocaproic acid. I think, of the two choices, a modified androgen would be, at least in my opinion, preferred. I have used both danazol and oxandrolone in cases of pediatric or adolescent hereditary angioedema in females. Copied below is an abstract of an excellent review article on the management of pediatric angioedema which contains a very helpful discussion on the use of danazol. I have also copied below abstracts pertaining to the use of oxandrolone in the pediatric population. There is a link to a very helpful report by Barakat describing the use of oxandrolone in a 14 year-old girl. The full article can be accessed using this link.

In summary, in view of the obstacles you have to using C1 inhibitor replacement therapy or anti-kinin therapy, I believe a modified androgen would be the treatment of choice. When managing adolescent females with a modified androgen, I think you have two choices - oxandrolone and danazol. The references copied below will help you employ either should you choose to do so.

Finally, we usually have female adolescents on modified androgens also followed simultaneously by an obstetrician/gynecologist.

Thank you again for your inquiry and we hope this response is helpful to you.

Ann Allergy Asthma Immunol. 2004 Mar;92(3):377-8.
Oxandrolone treatment of childhood hereditary angioedema.
Church JA.
Division of Clinical Immunology and Allergy, Department of Pediatrics, Childrens Hospital Los Angeles and Keck of School of Medicine, The University of Southern California, Los Angeles, California 90027, USA.
Background: The virilizing effects of danazol, stanozolol, and methyltestosterone significantly restrict the usefulness of these agents in the treatment of children with hereditary angioedema (HAE). Oxandrolone is a synthetic anabolic steroid with limited virilizing effects that has been used in a variety of pediatric conditions and has an acceptable safety profile.
Objective: To report the effective use of oxandrolone in a 6-year-old boy with recurrent, life-threatening episodes of angioedema.
Methods: Oxandrolone was administered at a dose of 0.1 mg/kg per day. Symptoms and laboratory findings were evaluated by parental report and laboratory analysis of serum C1 esterase inhibitor and C4 levels, respectively.
Results: Oxandrolone therapy resulted in a marked reduction in clinical episodes and normalization of serum complement levels; cessation of oxandrolone therapy resulted in recurrence of symptoms and decreased complement levels. However, early signs of virilization were noted.
Conclusions: Oxandrolone treatment was associated with significant clinical and laboratory evidence of a therapeutic effect in a prepuberal boy with HAE. It is imperative to treat HAE with the lowest dose of oxandrolone that controls life-threatening episodes of angioedema.

Successful Use of Oxandrolone in the Prophylaxis of Hereditary Angioedema: A Case Report
Amin J. Barakat, M.D, Anthony J. Castaldo, M.P.A.
Pediatric Asthma, Allergy and Immunology, 1999, 13 (4) 189-193.
Hereditary angioedema (HAE) is a rare autosomal dominant disorder typified by a deficiency or dysfunction of C1-esterase inhibitor (C1-INH), and characterized clinically by swelling of the extremities, severe episodic abdominal pain, and sometimes upper airway obstruction. This paper reports for the first time the successful use of oxandrolone in the prophylaxis of HAE in a 14-year-old girl. Oxandrolone has comparatively milder side effects and less potential for hepatotoxicity and virilization than other attenuated androgens used in the prophylaxis of this disease. We believe oxandrolone should be considered as an alternative androgen therapy for children and adults with HAE, particularly females experiencing untoward side effects from danazol or stanozolol, and patients who are not adequately controlled on maximum doses of androgens currently prescribed for HAE.

Pediatr Allergy Immunol. 2002 Jun;13(3):153-61.
Clinical management of hereditary angio-oedema in children.
Farkas H, Harmat G, Füst G, Varga L, Visy B.
Semmelweis University, Kútvölgyi Directory, ENT Allergology and Angioedema Outpatient Clinic, Budapest, Hungary.
Hereditary angio-oedema (HAE) results from the deficiency of C1-esterase inhibitor (C1-INH). The clinical picture of this autosomal dominant disorder is characterized by recurrent attacks of subcutaneous oedema and/or potentially life-threatening swelling of the submucosa. This review discusses the authors' decade-long experience obtained in the treatment and follow-up of pediatric patients with HAE. Twenty-six children with HAE were reviewed. Pedigree analysis was performed in all cases to identify afflicted relatives. C1-INH concentrate was reserved for the emergency treatment of acute oedematous attacks, whereas tranexamic acid and danazol were administered for short- or long-term prophylaxis. Follow-up care included laboratory tests and abdominal ultrasound, which was repeated at regular intervals. Twenty-one children had Type I HAE and five suffered from Type II HAE. Clinical manifestations of the disease first occured in children when 2.5-12 years of age. Oedema formation primarily afflicted subcutaneous tissues. Mechanical trauma was identified as a precipitating factor in 20 patients. Pedigree analysis revealed 24 patients with relatives who suffered from HAE. Long-term prophylaxis with tranexamic acid or danazol was initiated in 11 patients; two children required short-term prophylaxis. No drug-related adverse effects were observed, except for one case of delayed menarche. Therapy improved serum complement parameters significantly and substantially reduced the frequency and severity of clinical episodes. Adequate prophylaxis and follow-up care can spare pediatric patients from oedematous attacks caused by HAE. Undesirable adverse effects can be avoided and the patient's quality of life enhanced considerably by administering the lowest effective drug dose.

Phil Lieberman, M.D.

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