Circulating sex steroids and prostate cancer: introducing the time-dependency theory
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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).
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.
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).
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.
KeywordsTestosterone 17β estradiol Sex hormone-binding globulin Prostate cancer Radical prostatectomy
The authors thank Dragonfly Editorial for reviewing the language in this manuscript.
Conflict of interest
The authors declare that they have no conflict of interest.
- 1.Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, Bremner WJ, McKinlay JB (2002) Age trends in the level of serum testosterone and other hormones in middleaged men: longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metab 87:589–598. doi: 10.1210/jc.87.2.589 PubMedCrossRefGoogle Scholar
- 2.Wu FC, Tajar A, Beynon JM, Pye SR, Silman AJ, Finn JD, O’Neill TW, Bartfai G, Casanueva FF, Forti G, Giwercman A, Han TS, Kula K, Lean ME, Pendleton N, Punab M, Boonen S, Vanderschueren D, Labrie F, Huhtaniemi IT, EMAS Group (2010) Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med 363:123–135. doi: 10.1056/NEJMoa0911101 PubMedCrossRefGoogle Scholar
- 3.Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, Eder R, Tennstedt S, Ulloor J, Zhang A, Choong K, Lakshman KM, Mazer NA, Miciek R, Krasnoff J, Elmi A, Knapp PE, Brooks B, Appleman E, Aggarwal S, Bhasin G, Hede-Brierley L, Bhatia A, Collins L, LeBrasseur N, Fiore LD, Bhasin S (2010) Adverse events associated with testosterone administration. N Engl J Med 363:109–122. doi: 10.1056/NEJMoa1000485 PubMedCrossRefGoogle Scholar
- 9.Imamoto T, Suzuki H, Fukasawa S, Shimbo M, Inahara M, Komiya A, Ueda T, Shiraishi T, Ichikawa T (2005) Pretreatment serum testosterone level as a predictive factor of pathological stage in localized prostate cancer patients treated with radical prostatectomy. Eur Urol 47:308–312. doi: 10.1016/j.eururo.2004.11.003 PubMedCrossRefGoogle Scholar
- 11.Salonia A, Abdollah F, Capitanio U, Gallina A, Suardi N, Briganti A, Zanni G, Ferrari M, Castiglione F, Clementi MC, Rigatti P, Montorsi F (2012) Preoperative sex steroids are significant predictors of early biochemical recurrence after radical prostatectomy. World J Urol [Epub ahead of print]. doi: 10.1007/s00345-012-0856-7
- 12.Salonia A, Abdollah F, Capitanio U, Suardi N, Briganti A, Gallina A, Colombo R, Ferrari M, Castagna G, Rigatti P, Montorsi F (2012) Serum sex steroids depict a nonlinear U-shaped association with high-risk prostate cancer at radical prostatectomy. Clin Cancer Res 18:3648–3657. doi: 10.1158/1078-0432.CCR-11-2799 PubMedCrossRefGoogle Scholar
- 15.Green F, Page D, Fleming I (2002) American joint committee on cancer staging manual, 6th edn. Sprinter, New YorkGoogle Scholar
- 16.Wang C, Nieschlag E, Swerdloff R, Behre HM, Hellstrom WJ, Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morales A, Morley JE, Schulman C, Thompson IM, Weidner W, Wu FC, International Society of Andrology, International Society for the Study of Aging Male, European Association of Urology, European Academy of Andrology, American Society of Andrology (2009) Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. Eur Urol 55:121–130. doi: 10.1016/j.eururo.2008.08.033 PubMedCrossRefGoogle Scholar
- 17.National Institutes of Health, National Heart, Lung, and Blood Institute (1998) Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults—the evidence report. Obes Res 6(suppl):51S–210SGoogle Scholar
- 24.Sinnecker GH, Hiort O, Nitsche EM, Holterhus PM, Kruse K (1997) Functional assessment and clinical classification of androgen sensitivity in patients with mutations of the androgen receptor gene. German Collaborative Intersex Study Group. Eur J Pediatr 156:7–14. doi: 10.1007/s004310050542 PubMedCrossRefGoogle Scholar
- 27.van der Sluis TM, Meuleman EJ, van Moorselaar RJ, Bui HN, Blankenstein MA, Heijboer AC, Vis AN (2012) Intraprostatic testosterone and dihydrotestosterone. Part II: concentrations after androgen hormonal manipulation in men with benign prostatic hyperplasia and prostate cancer. BJU Int 109:183–188. doi: 10.1111/j.1464-410X.2011.10652.x PubMedCrossRefGoogle Scholar
- 29.Mostaghel EA, Page ST, Lin DW, Fazli L, Coleman IM, True LD, Knudsen B, Hess DL, Nelson CC, Matsumoto AM, Bremner WJ, Gleave ME, Nelson PS (2007) Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. Cancer Res 67:5033–5041. doi: 10.1158/0008-5472.CAN-06-3332 PubMedCrossRefGoogle Scholar
- 30.van der Sluis TM, Vis AN, van Moorselaar RJ, Bui HN, Blankenstein MA, Meuleman EJ, Heijboer AC (2012) Intraprostatic testosterone and dihydrotestosterone. Part I: concentrations and methods of determination in men with benign prostatic hyperplasia and prostate cancer. BJU Int 109:176–182. doi: 10.1111/j.1464-410X.2011.10651.x PubMedCrossRefGoogle Scholar