title: Endogenous and exogenous testosterone and the risk of prostate cancer and increased prostate-specific antigen (PSA) level: a meta-analysis.
abstract: OBJECTIVE
  To review and quantify the association between endogenous and exogenous testosterone and prostate-specific antigen (PSA) and prostate cancer.
  
  
  METHODS
  Literature searches were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Prospective cohort studies that reported data on the associations between endogenous testosterone and prostate cancer, and placebo-controlled randomized trials of testosterone replacement therapy (TRT) that reported data on PSA and/or prostate cancer cases were retained. Meta-analyses were performed using random-effects models, with tests for publication bias and heterogeneity.
  
  
  RESULTS
  Twenty estimates were included in a meta-analysis, which produced a summary relative risk (SRR) of prostate cancer for an increase of 5 nmol/L of testosterone of 0.99 (95% confidence interval [CI] 0.96, 1.02) without heterogeneity (I² = 0%). Based on 26 trials, the overall difference in PSA levels after onset of use of TRT was 0.10 ng/mL (-0.28, 0.48). Results were similar when conducting heterogeneity analyses by mode of administration, region, age at baseline, baseline testosterone, trial duration, type of patients and type of TRT. The SRR of prostate cancer as an adverse effect from 11 TRT trials was 0.87 (95% CI 0.30; 2.50). Results were consistent across studies.
  
  
  CONCLUSIONS
  Prostate cancer appears to be unrelated to endogenous testosterone levels. TRT for symptomatic hypogonadism does not appear to increase PSA levels nor the risk of prostate cancer development. The current data are reassuring, although some caution is essential until multiple studies with longer follow-up are available.
authors.affiliation: Strathclyde Institute of Global Public Health at iPRI, Ecully Lyon Ouest, France. peter.boyle@i-pri.org.|International Prevention Research Institute, Lyon, France. peter.boyle@i-pri.org.
authors.forename: Peter
authors.initials: P
authors.lastname: Boyle
authors.affiliation: Strathclyde Institute of Global Public Health at iPRI, Ecully Lyon Ouest, France.|International Prevention Research Institute, Lyon, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Koechlin
authors.affiliation: Strathclyde Institute of Global Public Health at iPRI, Ecully Lyon Ouest, France.|International Prevention Research Institute, Lyon, France.
authors.forename: Maria
authors.initials: M
authors.lastname: Bota
authors.affiliation: International Prevention Research Institute, Lyon, France.
authors.forename: Alberto
authors.initials: A
authors.lastname: d'Onofrio
authors.affiliation: Institute of Carcinogenesis, Moscow, Russia.
authors.forename: David G
authors.initials: DG
authors.lastname: Zaridze
authors.affiliation: Urologie, Centre Hospitalier Lyon Sud, Pierre-Bénite, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Perrin
authors.affiliation: Irish Cancer Society, Dublin, Ireland.
authors.forename: John
authors.initials: J
authors.lastname: Fitzpatrick
authors.affiliation: Department of Urology, Cellular and Molecular Medicine, Johns Hopkins Medicine, Marburg, Baltimore, MD, USA.
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Burnett
authors.affiliation: Strathclyde Institute of Global Public Health at iPRI, Ecully Lyon Ouest, France.|International Prevention Research Institute, Lyon, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Boniol
mesh_terms: D006801:Humans; D008297:Male; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000139:chemically induced* / Q000453:epidemiology; D018570:Risk Assessment; D013739:Testosterone / Q000009:adverse effects* / Q000097:blood*
chemical_list: D013739:Testosterone; D017430:Prostate-Specific Antigen
keywords: meta-analysis; prostate cancer; prostate-specific antigen; testosterone