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 ).