Androgenic Effects on Ventricular Repolarization

August 2019 in “ Circulation ”

Joe-Elie Salem, Tao Yang, Javid Moslehi, Xavier Waintraub, Estelle Gandjbakhch, Anne Bachelot, Françoise Hidden-Lucet, Jean-Sébastien Hulot, Bjorn C. Knollmann, Bénédicte Lebrun-Vignes, Christian Funck-Brentano, Andrew M. Glazer, Dan M. Roden

androgen deprivation therapy ADT long-QT syndrome aLQTS torsades de pointes TdP sudden death enzalutamide dihydrotestosterone cardiomyocytes induced pluripotent stem cells QT prolongation hormone therapy heart rhythm disorder sudden cardiac death Xtandi DHT heart cells iPS cells

TLDR ADT, especially enzalutamide, may increase the risk of heart rhythm problems and sudden death in men.

The study explored the link between androgen deprivation therapy (ADT) and the risk of acquired long-QT syndrome (aLQTS), torsades de pointes (TdP), and sudden death. Analyzing data from VigiBase, which contained 6,560,565 individual case safety reports, researchers found 184 cases of aLQTS and/or TdP and 99 cases of sudden death associated with ADT. Seven out of ten ADT drugs showed a significant association with these conditions. Enzalutamide, an ADT drug, was linked to a higher percentage of deaths (17%) compared to other ADTs (8.1%). In vitro studies on cardiomyocytes from induced pluripotent stem cells indicated that enzalutamide disrupted cardiac electrophysiology, an effect that could be reversed by dihydrotestosterone. The study concluded that ADTs, particularly enzalutamide, pose a risk of QT prolongation and TdP in men.

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