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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Cardiovascular mortality in patients with prostate cancer exposed to androgen deprivation therapy
J I Monzó-Gardiner1, F Herranz-Amo2
1Servicio Urología, Hospital Dr. Federico Abete, Buenos Aires, Argentina.
Insights
GnRH agonists may increase cardiovascular mortality in prostate cancer patients with prior heart conditions. Careful consideration of GnRH agonist appropriateness is advised for these patients.
Area of Science:
- Cardiovascular Medicine
- Oncology
- Endocrinology
Background:
- Observational studies suggest a link between GnRH agonists and acute myocardial infarction (AMI) risk in prostate cancer patients.
- No association was found between AMI and orchiectomy in these studies.
Purpose of the Study:
- Identify cardiovascular disease risk factors in patients receiving GnRH agonist therapy.
- Analyze the potential pathogenic mechanisms of cardiovascular events in the myocardium and peripheral vasculature.
Main Methods:
- Systematic review of English-language articles indexed in PubMed.
- Search conducted up to November 30, 2014, with no specified time period.
Main Results:
- Hormonal neoadjuvant therapy elevated cardiovascular mortality rates (HR: 1.96) and cardiovascular-specific mortality rates (AHR: 3.28) in patients with a history of AMI or congestive heart failure.
- Potential mechanisms include direct effects on myocardial GnRH receptors and indirect effects via metabolic disturbances.
Conclusions:
- Prostate cancer patients with a history of AMI or congestive heart failure may face increased mortality risk with GnRH agonist use.
- The appropriateness of GnRH agonist treatment should be carefully evaluated in these patients.
- Mechanisms involve direct myocardial/vascular effects and indirect metabolic alterations.
Introduction:
A relationship between the administration of GnRH agonists and the risk of acute myocardial infarction (AMC) in patients with prostate cancer has been showed in the third observational study published in April 2014. The association AMC-orchiectomy was not found in any of these studies.
Objective:
Define risk factors for cardiovascular disease in patients treated with GnRH agonist. Their probable underlying pathogenic mechanism in the myocardium and peripheral vascular tree was also analyzed.
Evidence Acquisition:
English articles cited in PubMed were reviewed. No time period is specified. The last search date was 11/30/14.
Evidence Synthesis:
In patients with coronary history of AMC or congestive heart failure, hormonal neoadjuvant therapy increased cardiovascular mortality rates (HR: 1.96, IC 95%: 1.04-3.71; P=.04) as well as cardiovascular-specific mortality rates (AHR: 3.28; IC 95%: 1.01-10.64; P=.048). Two possible mechanisms can be involved: a) direct mechanism through myocardial receptor for GnRH/PKA along with atherogenic plaques; and b) indirect mechanism related with metabolic disturbances.
Conclusions:
Patients with AMC or congestive heart failure history could present a higher risk of death related to the use of GnRH agonists. In these cases, should carefully consider appropriateness of such treatment. These effects can explained by a direct mechanism on myocardium and peripheral vascular tree and indirect ones related with modified metabolic syndrome.
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