3.1 Effects of testosterone on the QT interval of humans
In men, testosterone ranges from 9-38 nmol/L and has QT shortening
effects in a dose dependent manner, which become evident as testosterone
rises with puberty (1). In different patient populations high
testosterone levels (exogenous and endogenous) resulted in significant
QT interval shortening in both men and women (8–10). For instance,Schwartz et al (8), showed that older men and women exposed to
testosterone for 12 weeks presented with significant QT interval
shortening (for men: 385 ± 28ms to 382 ± 28ms, p < 0.002; and
for women: 400 ± 25ms to 397 ± 23ms, p = 0.06), when compared to
placebo. Additionally, testosterone increases the repolarization reserve
(redundancy of repolarization currents in cardiac cells) which protects
the heart against the effects of QT prolonging drugs such as Quinidine
(11). Women taking Drospirenone – an anti-androgenic pill, have higher
incidences of drug induced QT prolongation (12). In comparison, prostate
cancer therapy which involves the use of androgen depravation therapy is
associated with considerable cardiovascular risk and QT lengthening
(12–17). In a comparable fashion breast cancer therapy can also modify
the QT interval. For instance, aromatase inhibitors (AIs), cause the
accumulation of testosterone resulting in QT shortening (12,18). AsTable 1 shows, research conducted on testosterone in humans
explains that the shortening of the QTc interval occurs through the
upregulation and downregulation of ion channel expression and function
in the presence of testosterone.