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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.

SUBMITTER: Watts EL 

PROVIDER: S-EPMC6195673 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

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

Watts Eleanor L EL   Appleby Paul N PN   Perez-Cornago Aurora A   Bueno-de-Mesquita H Bas HB   Chan June M JM   Chen Chu C   Cohn Barbara A BA   Cook Michael B MB   Flicker Leon L   Freedman Neal D ND   Giles Graham G GG   Giovannucci Edward E   Gislefoss Randi E RE   Hankey Graeme J GJ   Kaaks Rudolf R   Knekt Paul P   Kolonel Laurence N LN   Kubo Tatsuhiko T   Le Marchand Loïc L   Luben Robert N RN   Luostarinen Tapio T   Männistö Satu S   Metter E Jeffrey EJ   Mikami Kazuya K   Milne Roger L RL   Ozasa Kotaro K   Platz Elizabeth A EA   Quirós J Ramón JR   Rissanen Harri H   Sawada Norie N   Stampfer Meir M   Stanczyk Frank Z FZ   Stattin Pär P   Tamakoshi Akiko A   Tangen Catherine M CM   Thompson Ian M IM   Tsilidis Konstantinos K KK   Tsugane Shoichiro S   Ursin Giske G   Vatten Lars L   Weiss Noel S NS   Yeap Bu B BB   Allen Naomi E NE   Key Timothy J TJ   Travis Ruth C RC  

European urology 20180801 5


<h4>Background</h4>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.<h4>Objective</h4>To examine whether men with low concentrations of circulating free testosterone have a  ...[more]

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