Annals of Allergy, Asthma & Immunology
ArticlesHereditary angioedema: a current state-of-the-art review, V: attenuated androgens for the treatment of hereditary angioedema
Section snippets
INTRODUCTION
The management of hereditary angioedema (HAE) must address the abrogation of acute episodes of angioedema and short- and long-term prophylaxis.1, 2 Unfortunately, there are no drugs approved to date in the United States for the treatment of acute episodes,1 although many are in clinical trials and nearing Food and Drug Administration (FDA) approval. C1 inhibitor concentrate has been available for many years in Europe and Canada but is not yet available in the United States. Attenuated androgens
METHYLTESTOSTERONE
Methyltestosterone is one of the oldest available synthetic anabolic steroids and is derived from testosterone. Testosterone is an androgen but is not methylated and, therefore, has not been useful in preventing attacks of HAE.10 Methyltestosterone is responsible for the development and maintenance of primary and secondary male sex characteristics. Adverse effects include elevation of liver enzymes, acne, gynecomastia, increased aggression, and water retention. Methyltestosterone is sold in a
DANAZOL
Danazol is a synthetic analogue of ethinyltestosterone and was first developed in 1963. Danazol was first marketed as Danocrine but has since become available as a generic drug. It is available only as an oral capsule in doses of 50, 100, and 200 mg. It was the first drug the FDA approved for the treatment of endometriosis. Danazol is now also FDA approved for the treatment of fibrocystic disease of breast and HAE. Danazol is metabolized by the liver and should not be used by patients with
OXYMETHOLONE
Oxymetholone is an anabolic steroid first developed in 1960 and known to increase the production and excretion of erythropoietin and to stimulate erythropoiesis.20 Because of its effect on erythropoiesis, oxymetholone is currently FDA approved for the treatment of acquired aplastic anemia, anemia of chronic renal failure, Fanconi anemia, and pure red cell aplasia. Serious adverse effects have been reported, including cholestatic jaundice, hepatic necrosis, and malignancy. Also, there is
STANOZOLOL
Stanozolol, first developed in 1959, is an anabolic steroid also known by the brand name Winstrol. It is only FDA approved for the treatment of HAE. Stanozolol is supplied as 2-mg oral tablets. Stanozolol also has substantial fibrinolytic properties and has been effective in the treatment of Raynaud phenomenon and cryptofibrinogenemia.24 Stanozolol has also been used successfully in treatment of AIDS wasting syndrome.25 Several reports document abuse by athletes to help build muscle mass, boost
ATTENUATED ANDROGENS IN THE PEDIATRIC POPULATION
The adverse effects of the attenuated androgens, including virilization and decreased growth rates,29, 30 have led to their cautious use in the treatment of HAE in prepubescent children. Farkas et al31 recently published their experience treating children with HAE. Danazol was administered for short- and long-term prophylaxis in 11 children. Initial doses of 100 to 200 mg/d were used and titrated down to 100 mg every 2 to 3 days after 6 months only if the child was in clinical remission. The
CONCLUSIONS
Attenuated androgens have proven successful for the short- and long-term treatment of HAE. Adverse effects are still concerning, and their use in children and pregnant women must be undertaken with great caution. Scheduled monitoring of liver function test results and lipid profiles in patients treated with these medications is critical. Patients should be treated with the lowest dose of attenuated androgens needed to maintain symptom control. Pharmacies can compound attenuated androgenic
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Cited by (51)
Summary and future of medicine for hereditary angioedema
2024, Drug Discovery TodayAndrogen Physiology, Pharmacology, and Abuse
2015, Endocrinology: Adult and PediatricA phase 1 study investigating DX-2930 in healthy subjects
2014, Annals of Allergy, Asthma and ImmunologyCitation Excerpt :Existing preventative therapies are not consistently effective and patients continue to supplement long-term therapy with additional acute treatments for breakthrough attacks.14,15 Use of these prophylactic agents is not without risk of toxicity.16,17 Therefore, an unmet medical need exists for an effective, long-lasting, and easily administered prophylactic treatment for HAE with an improved risk-to-benefit profile.
Inhibition of plasma kallikrein by a highly specific active site blocking antibody
2014, Journal of Biological ChemistryCitation Excerpt :C1-INH therapy is also associated with a risk for serious thromboembolic events (31). Oral androgens are an alternative prophylactic option that are more convenient to administer but are associated with serious toxicities and morbidities from unwanted androgenizing effects, particularly in women, as well as hepatic adenomas with malignant potential (32, 33). Furthermore, despite chronic treatment with existing prophylactic agents, breakthrough attacks still occur (34).
Treatment of hereditary angioedema with nanofiltered C1-esterase inhibitor concentrate (Cetor®): Multi-center phase II and III studies to assess pharmacokinetics, clinical efficacy and safety
2012, Clinical ImmunologyCitation Excerpt :The concentrate is also used for long-term [11,27,30] and short-term prophylaxis [2,5,29,33,37]. Alternatively, reduction of the frequency and severity of angioedema attacks can be achieved by prophylactic treatment with attenuated androgens or anti-fibrinolytic agents [3,16,21,23,32,34–36]. Since 1972, C1-inhibitor concentrate purified from pooled human plasma by Sanquin Blood Supply Foundation (formerly the Central Laboratory of the Netherlands Red Cross Blood Transfusion Service (CLB)), has been used for treatment and prevention of HAE and AAE attacks in the Netherlands [41].
International consensus and practical guidelines on the gynecologic and obstetric management of female patients with hereditary angioedema caused by C1 inhibitor deficiency
2012, Journal of Allergy and Clinical ImmunologyCitation Excerpt :Specific side effects in women include hyperandrogenemia with possible virilization (clitoromegaly); hirsutism; hoarseness or deepening of the voice; weight gain; menstrual irregularities54; pseudomenopause55,56; postmenopausal bleeding; burning, dryness, or itching of the vagina; and breast hypotrophy.50,57 Most adverse effects are dose related and can be minimized by titrating the AA dose to the lowest effective level (evidence level III).45,47,58-62 However, AAs should be avoided in some patients because of secondary effects (evidence level III).
Disclosures: Dr Banerji is an investigator for Jerini. Dr Sloane is an investigator for Dyax. Dr Sheffer is an investigator for Dyax and a consultant for Pharming, Lev, Dyax, Jerini, and ZLB-Behring.