title: Serum sex steroids depict a nonlinear u-shaped association with high-risk prostate cancer at radical prostatectomy.
abstract: OBJECTIVE
  To assess the association between preoperative serum total testosterone (tT), 17β-estradiol (E(2)), sex hormone-binding globulin (SHBG), and tT-E(2) ratio values with high-risk prostate cancer (as defined by the National Comprehensive Cancer Network practice guidelines) at radical prostatectomy.
  
  
  METHODS
  Serum E(2), tT, and SHBG were dosed the day before surgery (7:00-11:00 am) in a cohort of 724 candidates to radical prostatectomy. Restricted cubic spline functions tested the association between predictors (i.e., model 1: age, body mass index, and serum tT, E(2), and SHBG levels; model 2: tT-E(2) values instead of tT and E(2) levels) and high-risk prostate cancer.
  
  
  RESULTS
  Low-, intermediate-, or high-risk prostate cancer was found in 251 (34.7%), 318 (43.9%), and 155 (21.4%) patients, respectively. Patients in the high-risk class showed the lowest tT, E(2), and tT-E(2) ratio values (all P ≤ 0.02). At univariate analysis, only age, tT, E(2), and tT-E(2) ratio values were significantly associated with high-risk prostate cancer (all P ≤ 0.006). At multivariate analyses considering model 1 variables, age (P = 0.03), serum tT (all P < 0.001), and E(2) (all P ≤ 0.01) were associated with high-risk prostate cancer; only tT-E(2) ratios achieved independent predictor status for high-risk prostate cancer (all P < 0.001) when considering model 2. Both the lowest and the highest tT, E(2), and tT-E(2) values depicted a nonlinear U-shaped significant association with high-risk prostate cancer.
  
  
  CONCLUSIONS
  These data showed that preoperative serum sex steroids are independent predictors of high-risk prostate cancer, depicting a nonlinear U-shaped association.
authors.affiliation: Department of Urology, University Vita-Salute San Raffaele, Milan, Italy. salonia.andrea@hsr.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Salonia
authors.forename: Firas
authors.initials: F
authors.lastname: Abdollah
authors.forename: Umberto
authors.initials: U
authors.lastname: Capitanio
authors.forename: Nazareno
authors.initials: N
authors.lastname: Suardi
authors.forename: Alberto
authors.initials: A
authors.lastname: Briganti
authors.forename: Andrea
authors.initials: A
authors.lastname: Gallina
authors.forename: Renzo
authors.initials: R
authors.lastname: Colombo
authors.forename: Matteo
authors.initials: M
authors.lastname: Ferrari
authors.forename: Giulia
authors.initials: G
authors.lastname: Castagna
authors.forename: Patrizio
authors.initials: P
authors.lastname: Rigatti
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004958:Estradiol / Q000097:blood*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D057234:Preoperative Period; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology / Q000601:surgery; D012306:Risk; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D013739:Testosterone / Q000097:blood*
chemical_list: D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol