title: Low levels of serum testosterone in middle-aged men impact pathological features of prostate cancer.
abstract: BACKGROUND
  Serum testosterone deficiency increases with aging. Age is also a major risk factor for prostate cancer (PrCa) and PCa tumors are more frequently diagnosed among men >65 years old. We evaluated the relationship between preoperative serum testosterone and clinical/ pathological features of PrCa in middle-aged and elderly patients.
  
  
  METHODS
  A total of 605 PrCa patients who underwent robotic-assisted radical prostatectomy between September 2010 and January 2013 at the University of Pennsylvania, and who had serum testosterone levels measured using Elecsys Testosterone II Immunoassay were included in this IRB-approved protocol. Androgen deficiency was determined as serum free testosterone (FT) <47 pg/ml and total testosterone (TT) <193 ng/dl. Demographic, clinical and tumor characteristics of men with low vs. normal TT or FT were compared using t-test or chi-square tests. Logistic regression was used to determine associations of clinical and pathological variables with FT or TT levels.
  
  
  RESULTS
  Among middle-aged men (45-64 years;n= 367), those with low FT and low TT had, on average, a higher BMI (29.7 vs. 27.4,P< 0.01; and 32.2 vs. 27.6;P< 0.01, respectively) and higher proportion of Gleason 8-10 PrCa (13.3% vs. 4.8%,P= 0.011; and 19.2% vs. 5.1%,P= 0.012) compared to men with normal FT and normal TT values. Patients with low FT had also higher number of positive cores on biopsy (3.9 vs. 3.1P= 0.019) and greater tumor volume (7.9 ml vs. 6.1 ml,P= 0.045) compared to those with normal FT. Among men ≥65 years (n= 135) there was no difference in prostatectomy specimens of PrCa between patients with low or normal FT or TT.
  
  
  CONCLUSIONS
  Among men aged 45-64 years low serum pretreatment FT and TT predicted more aggressive features of PrCa in prostatectomy specimens. In middle-aged patients low testosterone levels measured pre-operatively may indicate more aggressive disease parameters.
authors.affiliation: Division of Urology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Department of Urology, New York University School of Medicine, New York, NY, USA.
authors.forename: Elton
authors.initials: E
authors.lastname: Llukani
authors.affiliation: Division of Urology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Katz
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY, USA; Department of Urology, Albert Einstein College of Medicine, New York, NY, USA.
authors.forename: Ilir
authors.initials: I
authors.lastname: Agalliu
authors.affiliation: Division of Urology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Lightfoot
authors.affiliation: Division of Urology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Sue-Jean S
authors.initials: SS
authors.lastname: Yu
authors.affiliation: Division of Urology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Kathrins
authors.affiliation: Department of Urology, Temple University Health System, Philadelphia, PA, USA.
authors.forename: Ziho
authors.initials: Z
authors.lastname: Lee
authors.affiliation: Division of Urology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Yu-Kai
authors.initials: YK
authors.lastname: Su
authors.affiliation: Division of Urology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Monahan Agnew
authors.affiliation: Division of Urology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: McGill
authors.affiliation: Department of Urology, Temple University Health System, Philadelphia, PA, USA.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Eun
authors.affiliation: Division of Urology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: David I
authors.initials: DI
authors.lastname: Lee
keywords: Gleason score; Localized prostate cancer; Middle age; Robotic-assisted laparoscopic prostatectomy; Testosterone