Spironolactone use is associated with lower prostate cancer risk: a population-wide case-control study

Abstract

Background

Spironolactone, a cheap effective diuretic used to manage hypertension and heart failure, also has anti-androgenic effects through its non-selective binding to steroid receptors, and hence may affect prostate cancer (PCa) risk. This study investigated the association between spironolactone use and PCa risk. For comparison, we also examined associations with thiazide diuretics which do not have anti-androgenic properties.

Methods

A matched case-control study was undertaken using population-wide data from the Prostate Cancer Data Base Sweden (PCBaSe). All PCa cases diagnosed from 2014 to 2016 were matched by birth year and county with PCa-free controls selected from the general population (1:5). Multivariable conditional logistic regression was used to examine associations between spironolactone use (dose and duration) and PCa risk, and similarly for thiazides.

Results

Three percent of the 31,591 cases and 4% of the 156,802 controls had been prescribed spironolactone. Multivariable analyses indicated reduced risk of PCa among those ever exposed to spironolactone (odds ratio [OR] 0.83; 95% confidence interval [CI]: 0.76–0.89), with a stronger association for current users (OR: 0.77, 95% CI: 0.69–0.86) than past users (OR: 0.88; 95% CI: 0.79–0.97) and decreasing risk with increasing dose (p-trend < 0.001). No association was observed for thiazide exposure and PCa risk. Biases due to differences in prescribing patterns or frequency of PSA testing may have influenced these findings.

Conclusion

PCa risk was reduced among men exposed to the diuretic spironolactone. Further investigation of spironolactone’s potential chemopreventive effects is warranted.

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Fig. 1: Odds ratios for prostate cancer according to dose intensity and length of exposure to spironolactone and thiazide diuretics.

Data availability

Data can be accessed from data custodians of NPCR/PCBaSe [www.npcr.se] via an application to the reference group which should be submitted to par.stattin@surgsci.uu.se.

Code availability

Standard commands in the statistical package Stata (v14) were used in analyses.

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Acknowledgements

This project was made possible by the continuous work of the National Prostate Cancer Register of Sweden steering group: PS (Chair), Ingela Franck Lissbrant (Co-chair), Camilla Thellenberg Karlsson, Ove Andrén, Magnus Törnblom, Stefan Carlsson, Marie Hjälm-Eriksson, David Robinson, Mats Andén, Jonas Hugosson, Ola Bratt, Johan Stranne, Maria Nyberg, Göran Ahlgren, Olof Ståhl, Fredrik Sandin, and Karin Hellström.

Funding

PCBaSe is supported by The Swedish Research Council (2017-00847) and The Swedish Cancer Society (16 0700). KB is funded through a NHMRC Early Career Research Fellowship (GNT1124210). These funding bodies played no role in the design, analysis and interpretation of this study, nor writing or approving this manuscript.

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Correspondence to Kerri Beckmann.

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Beckmann, K., Garmo, H., Lindahl, B. et al. Spironolactone use is associated with lower prostate cancer risk: a population-wide case-control study. Prostate Cancer Prostatic Dis (2020). https://doi.org/10.1038/s41391-020-0220-8

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