Quantifying Observational Evidence for Risk of Fatal and Nonfatal Cardiovascular Disease Following Androgen Deprivation Therapy for Prostate Cancer: A Meta-analysis

Abstract

We investigated all the available data from observational studies on hormonal treatment for prostate cancer and its possible cardiovascular adverse effects. We found consistent evidence that this treatment may increase the risk of cardiovascular disease.

Differences in Hypercholesterolemia and Atherogenesis Induced by Common Androgen Deprivation Therapies in Male Mice

“…However, even though LDL particles fuel the atherosclerotic disease process and it is well known that changes in LDL levels upon statin treatment can exert relatively rapid effects on CVD end points,27 the ADT‐associated LDL increase is modest (<10%),3 and it is doubtful whether the combined metabolic changes associated with testosterone deficiency can provide a comprehensive explanation for the acutely increased CVD risk associated with ADT initiation. Interestingly, recent observational studies and a meta‐analysis of randomized controlled trials suggested that non–testosterone‐mediated effects of GnRH agonists may be important for the increased risk of atherosclerotic CVD 4, 5. Bosco et al, using registry data, found that GnRH agonist‐based ADT was associated with a higher risk of CVD than surgical orchiectomy 5.…”

“…Interestingly, recent observational studies and a meta‐analysis of randomized controlled trials suggested that non–testosterone‐mediated effects of GnRH agonists may be important for the increased risk of atherosclerotic CVD 4, 5. Bosco et al, using registry data, found that GnRH agonist‐based ADT was associated with a higher risk of CVD than surgical orchiectomy 5. Furthermore, Albertsen et al, in a meta‐analysis of trials comparing the GnRH agonists leuprolide and goserelin to the GnRH antagonist degarelix, found that agonist treatment was associated with a higher cardiovascular event rate in the subgroup of men with preexisting CVD 4…”

“…Recent studies, however, have suggested that the number of CVD events in PCa patients differs between different types of ADT, indicating that other mechanisms than the mere lack of testosterone is involved. In observational studies and a post hoc analysis of randomized controlled trials, a higher rate of CVD events was found in patients treated with GnRH receptor agonists compared with bilateral orchiectomy or GnRH antagonists 4, 5, 9. These studies are hypothesis‐generating and the findings await confirmation in randomized trials with CVD as a prespecified end point, but the idea of a divergent effect of orchiectomy, GnRH agonists and antagonists on atherosclerosis‐related disease is supported by experimental studies.…”

“…ADT is the first‐line treatment for metastatic PCa and an adjuvant therapy to radiotherapy for locally advanced PCa. Unfortunately, apart from improving survival and quality of life, ADT treatment has been associated with an excess risk of cardiovascular disease (CVD), including myocardial infarction 2, 3, 4, 5, 6, 7…”

Managing cardiovascular risk in high‐risk prostate cancer

“…CV risks might be increased by ADT, 5 suggesting that careful consideration of ADT modality is required before initiating treatment. However, ADT should not be withheld from men when indicated, as the priority should be optimal PC treatment.…”