Person:

Basaria, Shehzad

The numbers of testosterone prescriptions written have increased several-fold worldwide, but the incidence of pathological hypogonadism due to hypothalamic, pituitary, and testicular disease has remained unchanged. Most of these prescriptions are being dispensed to middle-aged and older men who have experienced age-related decline in serum testosterone levels; a subset of the population in which benefits of testosterone replacement is at best, modest. Recently, some randomized controlled trials have reported increased cardiovascular events in men (mainly older men and those with prevalent cardiovascular disease) with testosterone use, and a few recent meta-analyses have confirmed these findings. In this review, we discuss trials of testosterone therapy that have reported higher cardiovascular events, relevant trials that have not reported increased cardiovascular events and large trials that have focused on cardiovascular risk (mainly atherosclerosis progression) as their main outcome. We also review findings from meta-analyses that have evaluated cardiovascular events in various testosterone trials. Finally, we discuss some potential mechanisms by which testosterone use might result in an increased cardiovascular risk. As none of the trials conducted to date were adequately powered to evaluate cardiovascular events, no firm conclusions can be drawn regarding the cardiovascular safety of testosterone therapy at this time. In the interim, we hope that this review will help practitioners make informed decisions regarding the care of their patients.

Abstract Context Androgen deprivation therapy (ADT) for prostate cancer (PCa) is associated with increased cardiovascular mortality and sudden cardiac death, with some events occurring early after initiation of ADT. Testosterone levels are inversely associated with corrected QT (QTc) interval duration; therefore, prolongation of QTc duration could be responsible for some of these events during ADT. Objective: To evaluate changes in QTc duration during ADT. Design and Interventions A 6-month prospective cohort study that enrolled men with PCa about to undergo ADT (ADT group) and a control group of men who previously underwent prostatectomy for PCa and never received ADT (non-ADT group). Patients At study entry, all participants were eugonadal and had no history of cardiac arrhythmias or complete bundle branch block. Outcomes Difference in change in QTc duration from baseline on a 12-lead electrocardiogram at 6, 12, and 24 weeks after initiation of ADT compared with electrocardiograms performed at the same intervals in the non-ADT group. PR, QRS, and QT interval durations were also evaluated. Results: Seventy-one participants formed the analytical sample (33 ADT and 38 non-ADT). ADT was associated with prolongation of the QTc by 7.4 ms compared with the non-ADT group [95% confidence interval (CI) 0.08 to 14.7 ms; P = 0.048]. ADT was also associated with shortening of the QRS interval by 2.4 ms (95% CI −4.64 to −0.23; P = 0.031). Electrolytes did not change. Conclusions: Men undergoing ADT for PCa experienced prolongation of the QTc. These findings might explain the increased risk of sudden cardiac death seen in these patients.