Tolerability and Effectiveness of 17-α-Alkylated Androgen Therapy for Hereditary Angioedema: A Re-examination.

Background: Hereditary angioedema (HAE) is a genetic disorder clinically characterized by recurrent attacks of subcutaneous and mucosal swelling. 17-α-Alkylated androgens (AA) have been used prophylactically to reduce HAE severity, but there are many questions about the efficacy and tolerability of AA.

Objective: The objective of this study was to investigate the tolerability and effectiveness of AA therapy in a large cohort of patients with HAE.

Methods: We performed a retrospective cross-sectional study on 650 subjects with HAE utilizing a one time, anonymous, web-based survey. Based on an initial questionnaire, patients were routed to one of the following questionnaires: currently using AA, previously used but discontinued AA, or never used AA.

Results: Statistical analysis revealed that androgens decreased attack frequency and severity in previous AA users (P < .0001) and current AA users (P < .0001). Substantial variability in the effectiveness was observed. Users who discontinued AA reported significantly lesser benefit. No dose effect was seen for the beneficial effect of AA; however, almost all users reported frequent side effects that were dose related and often severe.

Conclusions: AA therapy is usually effective for the treatment of HAE although a substantial fraction of patients with HAE do not achieve adequate benefit. In contrast, the side effects of AA are seen in almost all subjects who take the medicines. If used, AA should only be recommended in the lowest effective and tolerated dose for carefully selected patients.