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)