3.1.1Conditions affecting testosterone levels and the QT interval
Different genetic, congenital and metabolic conditions can affect testosterone levels in men and women. For instance, men with congenital adrenal hyperplasia (CAH) present with longer QTcF (corrected with the Fridericia equation) and significantly lower serum total testosterone levels (19). In comparison women with CAH, were found to have a shorter QTcF compared to controls (404±2 msec vs. 413±2.1 msec, p<0.001) and these patients present with higher blood levels of total testosterone and significantly lower FSH levels (P<0.05) (19). Patients with Klinefelter syndrome (KS) receiving testosterone replacement therapy had shorter QTc compared to untreated KS patients and healthy controls (20). Hypogonadal men tend to have longer QT intervals and are almost twice as likely to suffer LQT than eugonadal men; this effect is further exacerbated in obese hypogonadal males (21–24). Men with decompensated cirrhosis exhibit significant QT interval prolongation as well as profoundly diminished free testosterone; likely secondary to increased levels of sex hormone binding globulin (25). Women with PCOS, which have higher levels of testosterone and estrogen present with QTc shortening (401±61ms vs 467±61ms in controls; p=0.007) and increased QT dispersion (the difference between the longest and shortest QT interval on an ECG) (26,27). Male patients with Cushing’s syndrome presented with QT prolongation (426.9 ± 9.27 vs. 389.7 ± 8.31, p < 0.05). The high level of cortisol in these patients causes a lowering in testosterone levels (28). In the case of testosterone deficiency, the QT prolongation and other physiologic changes were resolved by testosterone administration.
Negative Studies on QT interval in hypogonadal men
Several studies have failed to show an association between testosterone deficient states and QTc prolongation. Kirilmaz et al (29) andLa Fountaine et al (30) found no significant change in the QT interval of hypogonadal patients compared to healthy controls.Lubart et al (31) and Olsson et al (32), both did not find QT prolongation after ADT treatment. And Zhao et al (33), was not able to find an association between testosterone and QT, or a protective role for testosterone, in a large cohort of older Chinese men (4212 men).
Table 1. Biochemical effect of testosterone on humans and human derived tissue (34–42)