@article{7aed71f56f4b460b8746e8065b2cb895,
title = "Low Free Testosterone and Prostate Cancer Risk: A Collaborative Analysis of 20 Prospective Studies",
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.",
keywords = "Androgens, Epidemiology, Pooled analysis, Prospective studies, Prostate cancer, Sex hormones, Testosterone",
author = "Watts, {Eleanor L.} and Appleby, {Paul N.} and Aurora Perez-Cornago and Bueno-de-Mesquita, {H. Bas} and Chan, {June M.} and Chu Chen and Cohn, {Barbara A.} and Cook, {Michael B.} and Leon Flicker and Freedman, {Neal D.} and Giles, {Graham G.} and Edward Giovannucci and Gislefoss, {Randi E.} and Hankey, {Graeme J.} and Rudolf Kaaks and Paul Knekt and Kolonel, {Laurence N.} and Tatsuhiko Kubo and {Le Marchand}, Lo{\"i}c and Luben, {Robert N.} and Tapio Luostarinen and Satu M{\"a}nnist{\"o} and Metter, {E. Jeffrey} and Kazuya Mikami and Milne, {Roger L.} and Kotaro Ozasa and Platz, {Elizabeth A.} and Quir{\'o}s, {J. Ram{\'o}n} and Harri Rissanen and Norie Sawada and Meir Stampfer and Stanczyk, {Frank Z.} and P{\"a}r Stattin and Akiko Tamakoshi and Tangen, {Catherine M.} and Thompson, {Ian M.} and Tsilidis, {Konstantinos K.} and Shoichiro Tsugane and Giske Ursin and Lars Vatten and Weiss, {Noel S.} and Yeap, {Bu B.} and Allen, {Naomi E.} and Key, {Timothy J.} and Travis, {Ruth C.}",
note = "Funding Information: Funding/Support and role of the sponsor : Centralised pooling, checking, and data analysis were supported by Cancer Research UK grants C8221/A19170 and C8221/A20986. Funding Information: V) with the Department of Health Services, Cancer Research Program (grant number: UM1 CA182883); National Institutes of Health/National Cancer Institute (grant numbers: CA167552, CA055075, CA133891, CA141298, CA09001, CA131945, CA34944, CA37429, CA40360, CA097193); National Institutes of Health/National Heart, Lung and Blood Institute (grant numbers: HL26490, HL34595); Dana-Farber Cancer Institute Mazzone Awards Program; National Cancer Institute (grant number U01 CA164973); National Health and Medical Research Council of Australia. EPIC Spain wishes to acknowledge the Regional Governments of Asturias, Andalucia, Navarra, Murcia, and Basque Country for funding. The authors wish to thank the Massachusetts Male Aging Study for contributing data for their analysis. Acknowledgements: The authors thank the men who participated in the collaborating studies, the research staff, collaborating laboratories, and funding agencies in each of the studies. Details of funding for the original studies are found in the relevant publications. These include the following: the Intramural Research Program of the National Institute on Aging, National Institute of Health; Eunice Kennedy Shriver National Institute of Child Health and Development; National Institutes of Health and Department of Health and Human Services (grant number: HHSN275201100020C); California Department of Public Health as part of the state-wide cancer reporting program mandated by California Health and Safety Code Section 103885; National Cancer Institute's Surveillance, Epidemiology and End Results Program awarded to the Cancer Prevention Institute of California (grant number: HHSN261201000140C); National Cancer Institute's Surveillance, Epidemiology and End Results Program awarded to the University of Southern California (grant number: HHSN261201000035C); National Cancer Institute's Surveillance, Epidemiology and End Results Program awarded to the Public Health Institute; Centers for Disease Control and Prevention's National Program of Cancer Registries (grant number: HHSN261201000034C); California Department of Public Health (grant number: U58DP003862-01); Cancer Research Fund, under Interagency Agreement #97-12013 (University of California contract #98-00924 ",
year = "2018",
month = nov,
doi = "10.1016/j.eururo.2018.07.024",
language = "English (US)",
volume = "74",
pages = "585--594",
journal = "European Urology",
issn = "0302-2838",
publisher = "Elsevier",
number = "5",
}