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Volume 23, Issue 1 (January 2021) 23, 3–10; 10.4103/aja.aja_22_20

Androgen deprivation therapy and side effects: are GnRH antagonists safer?

Stephen J Freedland1,2, Per-Anders Abrahamsson3

1 Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
2 Section of Urology, Durham VA Medical Center, Durham, NC 27705, USA
3 Department of Urology, Skåne University Hospital, Lund University, Malmö 20502, Sweden

Correspondence: Dr. SJ Freedland (stephen.freedland@cshs.org)

Date of Submission 16-Oct-2019 Date of Acceptance 27-Mar-2020 Date of Web Publication 10-Jul-2020


Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists and antagonists is the mainstay of advanced prostate cancer treatment. Both drug classes decrease levels of luteinizing hormone and follicle-stimulating hormones (FSH), thereby lowering testosterone to castrate levels. This is associated with adverse events (AEs), including cardiovascular (CV) disorders, bone fractures, metabolic dysfunction, and impaired cognitive function. This literature review discusses these AEs, with a focus on CV and bone-related events. A hypothesis-generating meta-analysis of six clinical trials showed a potentially increased risk for CV disorders with GnRH agonists versus the GnRH antagonist degarelix. While no study has directly compared GnRH agonists versus antagonists with a primary CV outcome, one hypothesis for this observation is that GnRH agonists lead to initial surges in FSH that may negatively impact CV health, whereas antagonists do not. GnRH agonists are associated with metabolic and cognitive AEs and while data are lacking for GnRH antagonists, no differences in risk are predicted. Other common AEs with ADT include injection site reactions, which are much more common with degarelix than with GnRH agonists, which may reflect differing administration and injection techniques. Future studies are needed to further evaluate and compare the safety profiles of GnRH agonists and antagonists, especially in patients with pre-existing CV disease and other co-morbidities. Physicians should carefully evaluate benefits and risks when prescribing ADT and ensure that side effects are well managed.

Keywords: androgen antagonists; metabolic syndrome; prostate cancer; safety

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