Anti-Androgenic Therapy with Finasteride Attenuates Cardiac Hypertrophy and Left Ventricular Dysfunction
Background—Compared to men, women have a better prognosis when suffering from aortic valve stenosis, hypertrophic cardiomyopathy or heart failure. Recent data suggest that androgens like testosterone or the more potent dihydrotestosterone (DHT) contribute to the development of cardiac hypertrophy and failure. Therefore, we analyzed whether anti-androgenic therapy with finasteride, which inhibits the generation of DHT by the enzyme 5-α-reductase, improves pathological ventricular remodeling and heart failure.
Methods and Results—We found a strongly induced expression of all three isoforms of the 5-α-reductase (Srd5a1-3) in human and mouse hearts with pathological hypertrophy, which was associated with increased myocardial accumulation of DHT. Starting one week after the induction of pressure overload by transaortic constriction, mice were treated with finasteride for two weeks. Cardiac function, hypertrophy, dilation and fibrosis were markedly improved in response to finasteride treatment in male, but also in female mice. In addition, finasteride also very effectively improved cardiac function and mortality after long-term pressure overload and prevented disease progression in cardiomyopathic mice with myocardial Gαq overexpression. Mechanistically, finasteride by decreasing DHT potently inhibited hypertrophy and Akt dependent pro-hypertrophic signaling in isolated cardiac myocytes, while introduction of constitutively active Akt blunted these effects of finasteride.
Conclusions—Finasteride, which is currently used in patients to treat prostate disease, potently reverses pathological cardiac hypertrophy and dysfunction in mice, and might be a therapeutic option for heart failure.
- Received July 1, 2014.
- Revision received December 15, 2014.
- Accepted January 16, 2015.