Androgen Deprivation Therapy for Prostate Cancer Is Associated with Cardiovascular Morbidity and Mortality: A Meta-Analysis of Population-Based Observational Studies

Abstract

BackgroundThere is no consensus regarding whether androgen deprivation therapy (ADT) is associated with cardiovascular disease (CVD) and cardiovascular mortality (CVM). The objective of this study was to determine the role of ADT for prostate cancer (PCa) in development of cardiovascular events (CVD and CVM).Methods and FindingsWe performed a meta-analysis from population-based observational studies comparing ADT vs control aimed at treating PCa in patients with PCa, reporting either CVD or CVM as outcome. Publications were searched using Medline, Embase, Cochrane Library Central Register of observational studies database up to May 31th 2014, and supplementary searches in publications from potentially relevant journals. 6 studies were identified with a total of 129,802 ADT users and 165,605 controls investigating the relationship between ADT and CVD. The incidence of CVD was 10% higher in ADT groups, although no significant association was observed (HR = 1.10, 95%CIs: 1.00–1.21; P = 0.06). For different types of ADT, CVD was related with gonadotropin-releasing hormone (GnRH) (HR = 1.19, 95%CIs: 1.04–1.36; P<0.001) and GnRH plus oral antiandrogen (AA) (HR = 1.46, 95%CIs: 1.03–2.08; P = 0.04), but not with AA alone or orchiectomy. For CVM, 119,625 ADT users and 150,974 controls from 6 eligible studies were included, pooled results suggested that ADT was associated with CVM (HR = 1.17, 95%CIs: 1.04–1.32; P = 0.01). Significantly increased CVM was also detected in GnRH and GnRH plus AA groups. When patients received other treatments (e.g. prostatectomy and radiotherapy) were ruled out of consideration, more increased CVD (HR = 1.19, 95%CIs: 1.08–1.30; P<0.001) and CVM (HR = 1.30, 95%CIs: 1.13–1.50; P<0.001) were found in men treated with ADT monotherapy.ConclusionsADT is associated with both CVD and CVM. Particularly, GnRH alone and GnRH plus AA can significantly increase the incidence of cardiovascular events in patients with PCa.

Inflammation, cardiometabolic markers and functional changes in a randomized controlled trial of a 12-month exercise program for prostate cancer men

“…[9][10][11] In our study, we observed that supervised regular exercise training decreased inflammation, reduced car diovascular risk, and improved functional status in men with high grade PCa during ADT with RT. The exercise program prescribed (duration, fre quency, and intensity) was designed in accordance with the American Cancer Society recommen dations for cancer patients.…”

“…recurrence. 10,11 It has been well documented that the incidence of cardiovascular events is signif icantly higher for individuals who smoke, have diabetes, hypertension, chronic pulmonary ob struction, high body mass index (BMI), high lev els of triglycerides (TGs) and creatinine, and low levels of high density lipoprotein (HDL) choles terol. However, even among study participants without these traditional risk factors, elevated lev els of inflammatory markers (interleukin [IL]1β, IL 6, tumor necrosis factor α [TNF α]) prove to be the best predictors for coronary heart disease and congestive heart failure.…”

Effects of androgen-deprivation therapy on hypercoagulability in prostate cancer patients: A prospective, longitudinal study

“…[9][10][11][12][13] Although the literature investigating this association is still controversial secondary to differences in study design, outcomes, and at-risk populations studied, several meta-analyses of observational studies have suggested a link between ADT and CV disease and mortality. 14,15 This increased risk of CV events has been observed largely during the first year after initiation of testosterone therapy. [11][12][13] There have been several proposed mechanisms explaining these more acute physiological changes as compared to the development of metabolic syndrome with prolonged ADT use.…”

Long-term Impact of Androgen Deprivation Therapy on Cardiovascular Morbidity after Radiotherapy for Clinically Localized Prostate Cancer

“…6 Additional analyses using the SEER database, 19 Danish Cancer Registry, 20 and Swedish PcBaSE 21 have corroborated this data, yet others have found no clear association between use of gonadotropin-releasing hormone agonists and CE risk. 22 Meta-analyses have been conducted to reconcile this data, 23,24 but fundamental weaknesses of observational studies limit interpretation. For instance, while observational studies provide large patient cohorts for study, they are particularly susceptible to bias from inconsistent ICD-9 coding and inconsistent or limited patient follow-up.…”