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Understanding and managing the cardiovascular risks of androgen deprivation therapy for prostate cancer

Nature Reviews Urology volume 20, pages 3–4 (2023)Cite this article

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Androgen deprivation therapy potentiates cardiovascular morbidity and mortality, which is the most common cause of non-cancer-related death in patients with prostate cancer. Whether the mode of testosterone suppression affects the risk of cardiovascular adverse events is unclear, especially as the 2021 PRONOUNCE trial — which aimed to compare the cardiovascular risks of gonadotropin-releasing hormone (GnRH) antagonists with GnRH agonists — was prematurely terminated.

Androgen deprivation therapy (ADT) has been known for several decades to increase the risk of cardiovascular events in patients with prostate cancer: in the mid-twentieth century, oestrogens such as diethylstilbestrol and oestradiol were introduced to suppress testosterone for the treatment of metastatic prostate cancer1; however, by the late 1960s, data consistently showed a substantial increase in the rate of cardiovascular complications and deaths following treatment with diethylstilbestrol compared with surgical castration2. Mounting concerns about these risks led to a reduction in the use of exogenous oestrogens in prostate cancer management and the introduction of gonadotrophin-releasing hormone (GnRH) agonists, which were first developed in the 1970s. Prolonged administration of GnRH agonists reduces serum testosterone to castration levels without the adverse effects associated with exogenous oestrogens3. GnRH antagonists were subsequently developed, and early studies demonstrated a faster reduction in testosterone and PSA than was observed with GnRH agonists4.

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Authors and Affiliations

  1. Department of Urology, Barts Health NHS Trust, Whipps Cross University Hospital, London, UK

    Kerem Atalar

  2. Barts Cancer Institute, Queen Mary University of London, London, UK

    Prabhakar Rajan

  3. Department of Urology, Barts Health NHS Trust, The Royal London Hospital, London, UK

    Prabhakar Rajan

Authors
  1. Kerem Atalar
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  2. Prabhakar Rajan
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Correspondence to Kerem Atalar.

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Competing interests

P.R. declares research grant support from Ferring Pharmaceuticals. K.A. declares no competing interests.

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Atalar, K., Rajan, P. Understanding and managing the cardiovascular risks of androgen deprivation therapy for prostate cancer. Nat Rev Urol 20, 3–4 (2023). https://doi.org/10.1038/s41585-022-00671-5

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  • DOI: https://doi.org/10.1038/s41585-022-00671-5

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