title: Circulating sex steroids and prostate cancer: introducing the time-dependency theory.
abstract: OBJECTIVE
  We sought whether serum total testosterone (tT), estradiol (E2), tT/E2 ratio, and sex hormone-binding globulin (SHBG) significantly fluctuate throughout time in men with prostate cancer (PCa).
  
  
  METHODS
  Circulating hormones were measured in a cohort of 631 candidates for radical prostatectomy. Hormone levels were analyzed according to either patient age, stratified into quartiles, or body mass index (BMI). Linear regression analyses tested the association between sex steroids and continuously coded patient age and BMI values.
  
  
  RESULTS
  No significant differences were found among age quartiles regarding serum tT levels and tT/E2 ratio. Conversely, E2 and SHBG levels significantly increased throughout time (all, p ≤ 0.001). Total T did not linearly change according to continuously coded patient age; in contrast, E2 and SHBG linearly increased (all, p ≤ 0.001), whereas tT/E2 decreased (p = 0.016) with aging. Rate of hypogonadism significantly increased with aging (p = 0.04). Total T, T/E2 ratio, and SHBG linearly decreased along with BMI increases (all p ≤ 0.02), whereas serum E2 did not significantly change. Rate of hypogonadism significantly increased with BMI increases (p < 0.001).
  
  
  CONCLUSIONS
  In contrast with longitudinal studies in the general male population, these data indirectly suggest that serum tT levels could be stable over time in PCa patients. This finding led to formulation of a "time-dependency theory", which postulates that the endocrine biology of prostate tissue is dependent on the exposure time at a given concentration of sex steroid, which, in turn, fluctuates throughout the lifespan of the individual.
authors.affiliation: Department of Urology, University Vita-Salute San Raffaele, Via Olgettina 60, 20132, Milan, Italy. saloniaandrea@yahoo.com
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: Andrea
authors.initials: A
authors.lastname: Gallina
authors.forename: Giulia
authors.initials: G
authors.lastname: Castagna
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Clementi
authors.forename: Alberto
authors.initials: A
authors.lastname: Briganti
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; D015331:Cohort Studies; D018450:Disease Progression; D004958:Estradiol / Q000097:blood*; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood* / Q000378:metabolism; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D013739:Testosterone / Q000097:blood*; D013997:Time Factors
chemical_list: D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol