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

Freedland, Stephen and Abrahamsson, Per Anders LU (2021) In Asian Journal of Andrology 23(1). p.3-10
Abstract

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... (More)

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.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
androgen antagonists, metabolic syndrome, prostate cancer, safety
in
Asian Journal of Andrology
volume
23
issue
1
pages
8 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85099448679
  • pmid:32655041
ISSN
1008-682X
DOI
10.4103/aja.aja_22_20
language
English
LU publication?
yes
id
80c88486-1c0c-4b1a-9a0a-f515b667d00c
date added to LUP
2021-01-28 11:29:50
date last changed
2024-03-05 20:26:48
@article{80c88486-1c0c-4b1a-9a0a-f515b667d00c,
  abstract     = {{<p>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.</p>}},
  author       = {{Freedland, Stephen and Abrahamsson, Per Anders}},
  issn         = {{1008-682X}},
  keywords     = {{androgen antagonists; metabolic syndrome; prostate cancer; safety}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{3--10}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Asian Journal of Andrology}},
  title        = {{Androgen deprivation therapy and side effects : Are GnRH antagonists safer?}},
  url          = {{http://dx.doi.org/10.4103/aja.aja_22_20}},
  doi          = {{10.4103/aja.aja_22_20}},
  volume       = {{23}},
  year         = {{2021}},
}