Adverse health outcomes and patient and physician perspectives of attenuated androgen use in hereditary angioedema.

Attenuated androgens (AAs) historically have been used as long-term prophylaxis (LTP) for hereditary angioedema (HAE), and they continue to be used, especially in regions where access to newer therapies remains restricted. This systematic literature review assessed the adverse health outcomes associated with AAs, including adverse events (AEs), comorbidities, cardiovascular (CV) risk, as well as patient and physician perspectives. In total, 99 unique studies were identified through MEDLINE and EMBASE (searches up to March 2025), of which the majority were conducted in Europe (n = 57) and the United States (n = 26). Commonly reported adverse outcomes included weight gain, menstrual irregularities, virilization, myalgia, acne, and liver damage. Long-term use (≥5 years) of AAs, even at low doses, was associated with coagulation activation, hypertension, hypercholesterolemia, and hepatocellular carcinoma, a rare but serious AE. Studies also noted unfavorable changes in lipid profiles and markers of inflammation and endothelial dysfunction. Patients and physicians highlighted concerns over tolerability, AEs, and poor adherence. Notably, based on 3 serial surveys, physician reluctance to prescribe AAs rose from 18% in 2010 to 60% in 2019, likely reflecting the availability of alternative options. These findings underscore the need for improved access to targeted therapies for HAE and more research into the long-term CV risks of AAs.