Low Free Testosterone and Prostate Cancer Risk: A Collaborative Analysis of 20 Prospective Studies

Eleanor L. Watts, Paul N. Appleby, Aurora Perez-Cornago, H. Bas Bueno-de-Mesquita, June M. Chan, Chu Chen, Barbara A. Cohn, Michael B. Cook, Leon Flicker, Neal D. Freedman, Graham G. Giles, Edward Giovannucci, Randi E. Gislefoss, Graeme J. Hankey, Rudolf Kaaks, Paul Knekt, Laurence N. Kolonel, Tatsuhiko Kubo, Loïc Le Marchand, Robert N. LubenTapio Luostarinen, Satu Männistö, E. Jeffrey Metter, Kazuya Mikami, Roger L. Milne, Kotaro Ozasa, Elizabeth A. Platz, J. Ramón Quirós, Harri Rissanen, Norie Sawada, Meir Stampfer, Frank Z. Stanczyk, Pär Stattin, Akiko Tamakoshi, Catherine M. Tangen, Ian M. Thompson, Konstantinos K. Tsilidis, Shoichiro Tsugane, Giske Ursin, Lars Vatten, Noel S. Weiss, Bu B. Yeap, Naomi E. Allen, Timothy J. Key, Ruth C. Travis

Research output: Contribution to journalArticle

Abstract

Background: Experimental and clinical evidence implicates testosterone in the aetiology of prostate cancer. Variation across the normal range of circulating free testosterone concentrations may not lead to changes in prostate biology, unless circulating concentrations are low. This may also apply to prostate cancer risk, but this has not been investigated in an epidemiological setting. Objective: To examine whether men with low concentrations of circulating free testosterone have a reduced risk of prostate cancer. Design, setting, and participants: Analysis of individual participant data from 20 prospective studies including 6933 prostate cancer cases, diagnosed on average 6.8 yr after blood collection, and 12 088 controls in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group. Outcome measurements and statistical analysis: Odds ratios (ORs) of incident overall prostate cancer and subtypes by stage and grade, using conditional logistic regression, based on study-specific tenths of calculated free testosterone concentration. Results and limitations: Men in the lowest tenth of free testosterone concentration had a lower risk of overall prostate cancer (OR = 0.77, 95% confidence interval [CI] 0.69–0.86; p < 0.001) compared with men with higher concentrations (2nd–10th tenths of the distribution). Heterogeneity was present by tumour grade (phet = 0.01), with a lower risk of low-grade disease (OR = 0.76, 95% CI 0.67–0.88) and a nonsignificantly higher risk of high-grade disease (OR = 1.56, 95% CI 0.95–2.57). There was no evidence of heterogeneity by tumour stage. The observational design is a limitation. Conclusions: Men with low circulating free testosterone may have a lower risk of overall prostate cancer; this may be due to a direct biological effect, or detection bias. Further research is needed to explore the apparent differential association by tumour grade. Patient summary: In this study, we looked at circulating testosterone levels and risk of developing prostate cancer, finding that men with low testosterone had a lower risk of prostate cancer. We found that men with low circulating free testosterone had a 23% reduced risk of overall prostate cancer, but there was some evidence that these men had an increased risk of developing high-grade disease.

Original languageEnglish (US)
Pages (from-to)585-594
Number of pages10
JournalEuropean Urology
Volume74
Issue number5
DOIs
StatePublished - Nov 2018

Keywords

  • Androgens
  • Epidemiology
  • Pooled analysis
  • Prospective studies
  • Prostate cancer
  • Sex hormones
  • Testosterone

ASJC Scopus subject areas

  • Urology

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    Watts, E. L., Appleby, P. N., Perez-Cornago, A., Bueno-de-Mesquita, H. B., Chan, J. M., Chen, C., Cohn, B. A., Cook, M. B., Flicker, L., Freedman, N. D., Giles, G. G., Giovannucci, E., Gislefoss, R. E., Hankey, G. J., Kaaks, R., Knekt, P., Kolonel, L. N., Kubo, T., Le Marchand, L., ... Travis, R. C. (2018). Low Free Testosterone and Prostate Cancer Risk: A Collaborative Analysis of 20 Prospective Studies. European Urology, 74(5), 585-594. https://doi.org/10.1016/j.eururo.2018.07.024