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Hereditary angioedema: a current state-of-the-art review, V: attenuated androgens for the treatment of hereditary angioedema

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Objective

To provide a summary of the literature regarding the use of attenuated androgens during the past 40 to 50 years for the treatment of hereditary angioedema (HAE).

Data Sources

MEDLINE and PubMed were searched to identify studies involving the treatment of HAE with androgens.

Study Selection

Studies were selected based on their relevance to the use of androgens for the treatment of HAE.

Results

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 tests and lipid profiles in patients treated with these medications is critical.

Conclusions

Attenuated androgens have been successful in the short- and long-term treatment of HAE, and they are still the most frequently used medications in the United States for the treatment of this disease. There is a lack of readily available options for the treatment of acute HAE attacks apart from the administration of fresh frozen plasma or safe prophylactic therapies; however, several appropriate agents currently in clinical trials in the United States appear promising.

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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    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.

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