title: Quantifying observational evidence for risk of fatal and nonfatal cardiovascular disease following androgen deprivation therapy for prostate cancer: a meta-analysis.
abstract: BACKGROUND
  Whether androgen deprivation therapy (ADT) for men with prostate cancer (PCa) increases the risk of cardiovascular disease (CVD) remains controversial. Pooled analyses using data from randomised controlled trials suggest no increased risk of fatal CVD following ADT, but no pooled analyses exist for observational studies.
  
  
  OBJECTIVE
  To perform a meta-analysis using observational data on ADT and risk of CVD events in men with PCa.
  
  
  METHODS
  PubMed and Embase were searched using predefined inclusion criteria to perform meta-analyses on associations between types of ADT and nonfatal and fatal CVD outcomes using information from observational studies. Random effects meta-analyses were conducted to estimate relative risks (RRs) and 95% confidence intervals (CIs).
  
  
  RESULTS
  A total of eight observational studies were identified studying at least one type of ADT and a nonfatal or fatal CVD outcome. The RR for risk of any type of nonfatal CVD was 1.38 (95% CI, 1.29-1.48) for men with PCa on gonadotropin-releasing hormone (GnRH) agonists, compared with men not treated with ADT. When analysing nonfatal ischemic heart disease only, the RR was 1.39 (95% CI, 1.26-1.54). The associations between GnRH agonists and nonfatal or fatal myocardial infarction or stroke were even stronger: RR: 1.57 (95% CI, 1.26-1.94) and RR: 1.51 (95% CI, 1.24-1.84), respectively. The results for other types of ADT in relation to the risk of any nonfatal CVD were RR: 1.44 (95% CI, 1.28-1.62) for orchiectomy and RR: 1.21 (95% CI, 1.07-1.367) for antiandrogens.
  
  
  CONCLUSIONS
  Observational data show a consistent positive association between ADT and the risk of CVD. This finding supports the need for future randomised trials of PCa patients that include older patients and men with multiple comorbidities to better reflect the general population.
  
  
  RESULTS
  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.
authors.affiliation: King's College London, Division of Cancer Studies, Cancer Epidemiology Group, London, UK. Electronic address: Cecilia.bosco@kcl.ac.uk.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Bosco
authors.affiliation: Ferring Pharmaceuticals, Clinical R&D, Copenhagen, Denmark.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Bosnyak
authors.affiliation: Ferring Pharmaceuticals, Clinical R&D, Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Malmberg
authors.affiliation: Karolinska Institute, Stockholm, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Adolfsson
authors.affiliation: Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Keating
authors.affiliation: King's College London, Division of Cancer Studies, Cancer Epidemiology Group, London, UK.
authors.forename: Mieke
authors.initials: M
authors.lastname: Van Hemelrijck
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000401:mortality; D004967:Estrogens / Q000627:therapeutic use*; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists / Q000037:antagonists & inhibitors; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000453:epidemiology* / Q000401:mortality; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000628:therapy*; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology* / Q000401:mortality
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D004967:Estrogens; D007987:Gonadotropin-Releasing Hormone
keywords: Androgen deprivation therapy; Cardiovascular disease; Morbidity; Mortality; Prostate cancer