4.2 Clinical evidence of arrhythmia in low testosterone states
Due to the inverse relation between testosterone levels and the length of the QT interval, testosterone deficient states can lead to QT interval prolongation, promoting arrhythmogenesis. In humans, testosterone deficient states can occur in the context of disease (e.g. CAH (19), hypogonadism (21), Cushing’s syndrome (28), decompensated cirrhosis (25), etc.) and androgen deprivation therapy for the treatment of prostate cancer (13,16,35,40). In all of these cases, testosterone administration and/or stopping ADT were able to return the QT interval back to normal levels. In animals, similarly to humans, testosterone deficient states such as after orchiectomy or by knocking out the cardiac androgen receptor (ARKO mice), prolong the QT interval and increase the risk of arrhythmogenesis and the effect of QT prolonging drugs (53,65,77) (Table 2 ).