Kerri Beckmann1,2, Hans Garmo3, Bertil Lindahl4, Lars Holmberg5, Pär Stattin5, Jan Adolfsson6, J Kennedy Cruickshank7, Mieke Van Hemelrijck8,9. 1. Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Studies, King's College London, London, UK. Kerri.beckmann@kcl.ac.uk. 2. University of South Australia Cancer Research Institute, University of South Australia, Adelaide, SA, Australia. Kerri.beckmann@kcl.ac.uk. 3. Regional Cancer Centre Uppsala, Uppsala University Hospital, Uppsala, Sweden. 4. Uppsala Clinical Research Center, Uppsala University Hospital, Uppsala, Sweden. 5. Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden. 6. CLINTEC-Department, Karolinska Institutet, Stockholm, Sweden. 7. Department of Nutritional Studies, School of Life Course Sciences, King's College London, London, UK. 8. Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Studies, King's College London, London, UK. 9. Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
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.
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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