World J Mens Health.  2021 Jul;39(3):429-443. 10.5534/wjmh.200109.

Cardiovascular Risks of Androgen Deprivation Therapy for Prostate Cancer

Affiliations
  • 1Endocrinology Unit, Medical Department, Azienda-Usl, Maggiore-Bellaria Hospital, Bologna, Italy
  • 2Andrology, Female Endocrinology and Gender Incongruence Unit, Department of Experimental, Clinical and Biomedical Sciences, University of Florence, Florence, Italy
  • 3Urology Unit, Surgical Department, Azienda Usl, Maggiore-Bellaria Hospital, Bologna, Italy
  • 4Department of Urology, Sahlgrenska University Hospital, Goteborg, Sweden
  • 5Endocrinology Unit, Department of Experimental, Clinical and Biomedical Sciences, University of Florence, Florence, Italy

Abstract

Androgen deprivation therapy (ADT) is the gold standard treatment in patients with locally advanced or metastatic prostate cancer (PC). Emerging evidence has documented a tight association between ADT and body composition, along with metabolic profile impairment. These alterations might underpin the observed ADT-related increase in cardiovascular (CV) and thromboembolic (venous thromboembolism, VTE) mortality and morbidity. However, the specific mechanisms underlying these associations have not yet been completely elucidated. In the present review we summarize and discussed the available evidence linking ADT to increased cardio-metabolic risk, using both preclinical and clinical data. When possible, metaanalytic studies were preferred. Preclinical evidence, using a rabbit model of gonadotrophin-releasing hormone analogueinduced hypogonadism, indicates that the induced condition is associated with a dramatic increase in visceral adiposity and with an impairment of acetylcholine induced vascular relaxation, along with an increased propensity towards fatty liver. This suggests a direct role of ADT in inducing a worsened metabolic profile. In contrast, available clinical data are not sufficient to clarify a direct pathogeniclink between reduced testosterone (T) and altered metabolism. In fact, although T deprivation is associated with an altered metabolism, it is possible that the association between ADT and CV or VTE risk could simply be the result of a selection bias, related to the poor health status of patients with advanced PC. Despite the aforementioned considerations, all patients who are candidatesfor ADT should be screened for CV risk factors at baseline and monitored during the therapy. Life-style modifications and physical exercise are strongly encouraged.

Keyword

Androgen deprivation therapy; Cardiovascular risk; Diabetes; Hypogonadism; Prostate cancer; Testosterone
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