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.