Androgenic Effects on Ventricular Repolarization: A Translational Study from Pharmacovigilance Databases to iPSC-Cardiomyocytes

    October 2019 in “ European heart journal ”
    Joe‐Elie Salem, Tao Yang, Javid Moslehi, Xavier Waintraub, Estelle Gandjbakhch, Anne Bachelot, Françoise Hidden‐Lucet, Jean‐Sébastien Hulot, Björn C. Knollmann, Bénédicte Lebrun‐Vignes, Christian Funck‐Brentano, Andrew M. Glazer, Dan M. Roden
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    TLDR Androgen-deprivation therapies increase the risk of certain heart conditions, but testosterone treatment may help.
    The study investigated the association between androgen-deprivation therapies (ADT) and the risk of acquired long-QT syndrome (aLQT), Torsades de Pointes (TdP), and sudden death (SD) in men. Analyzing data from the WHO pharmacovigilance database, which included 6,560,565 men, researchers found 184 cases of aLQT and/or TdP (11% fatal) and 99 cases of SD associated with ADT. Seven out of ten ADTs examined showed a significant association with these conditions. Enzalutamide, an androgen antagonist, was linked to a higher percentage of deaths (17%) compared to other ADTs. In vitro studies using cardiomyocytes derived from induced pluripotent stem cells (IPS-CMs) from men showed that enzalutamide prolonged action potential durations and caused early/delayed afterdepolarizations and/or triggered activity, effects that were reversed by dihydrotestosterone (DHT). In seven men with aLQT and hypogonadism, ECGs indicated low amplitude, bifid T-waves typical of IKr block, which resolved with testosterone treatment. The study concluded that ADT is a risk factor for aLQT and TdP, and androgens may be beneficial in treating TdP in hypogonadic men.
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