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



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.


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.


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.


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.


  1. 1.

    Mills KT, Bundy JD, Kelly TN, Reed JE, Kearney PM, Reynolds K, et al. Global disparities of hypertension prevalence and control: a systematic analysis of population-based studies from 90 countries. Circulation. 2016;134:441–50.

    Article  Google Scholar 

  2. 2.

    Lloyd T, Hounsome L, Mehay A, Mee S, Verne J, Cooper A. Lifetime risk of being diagnosed with, or dying from, prostate cancer by major ethnic group in England 2008-2010. BMC Med. 2015;13:171.

    Article  Google Scholar 

  3. 3.

    Negoita S, Feuer EJ, Mariotto A, Cronin KA, Petkov VI, Hussey SK, et al. Annual report to the nation on the status of cancer, part II: recent changes in prostate cancer trends and disease characteristics. Cancer. 2018;124:2801–14.

    Article  Google Scholar 

  4. 4.

    Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018;39:3021–104.

    Article  Google Scholar 

  5. 5.

    Brown MJ, Williams B, Morant SV, Webb DJ, Caulfield MJ, Cruickshank JK, et al. Effect of amiloride, or amiloride plus hydrochlorothiazide, versus hydrochlorothiazide on glucose tolerance and blood pressure (PATHWAY-3): a parallel-group, double-blind randomised phase 4 trial. Lancet Diabetes Endocrinol. 2016;4:136–47.

    CAS  Article  Google Scholar 

  6. 6.

    Williams B, MacDonald TM, Morant S, Webb DJ, Sever P, McInnes G, et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet. 2015;386:2059–68.

    CAS  Article  Google Scholar 

  7. 7.

    Sica DA. Pharmacokinetics and pharmacodynamics of mineralocorticoid blocking agents and their effects on potassium homeostasis. Heart Fail Rev. 2005;10:23–29.

    CAS  Article  Google Scholar 

  8. 8.

    Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N. Engl J Med. 1999;341:709–17.

    CAS  Article  Google Scholar 

  9. 9.

    Corvol P, Michaud A, Menard J, Freifeld M, Mahoudeau J. Antiandrogenic effect of spirolactones: mechanism of action. Endocrinology. 1975;97:52–58.

    CAS  Article  Google Scholar 

  10. 10.

    Cao L, Zhang S, Jia CM, He W, Wu LT, Li YQ, et al. Antihypertensive drugs use and the risk of prostate cancer: a meta-analysis of 21 observational studies. BMC Urol. 2018;18:17.

    Article  Google Scholar 

  11. 11.

    Rodriguez C, Jacobs EJ, Deka A, Patel AV, Bain EB, Thun MJ, et al. Use of blood-pressure-lowering medication and risk of prostate cancer in the Cancer Prevention Study II Nutrition Cohort. Cancer Causes Control. 2009;20:671–9.

    Article  Google Scholar 

  12. 12.

    Siltari A, Murtola TJ, Talala K, Taari K, Tammela TLJ, Auvinen A. Antihypertensive drugs and prostate cancer risk in a Finnish population-based cohort. Scand J Urol. 2018;52:321–7.

    CAS  Article  Google Scholar 

  13. 13.

    Kemppainen KJ, Tammela TL, Auvinen A, Murtola TJ. The association between antihypertensive drug use and incidence of prostate cancer in Finland: a population-based case-control study. Cancer Causes Control. 2011;22:1445–52.

    Article  Google Scholar 

  14. 14.

    Chuang YW, Yu MC, Huang ST, Yang CK, Chen CH, Lo YC, et al. Spironolactone and the risk of urinary tract cancer in patients with hypertension: a nationwide population-based retrospective case-control study. J Hypertens. 2017;35:170–7.

    CAS  Article  Google Scholar 

  15. 15.

    Mackenzie IS, Morant SV, Wei L, Thompson AM, MacDonald TM. Spironolactone use and risk of incident cancers: a retrospective, matched cohort study. Br J Clin Pharm. 2017;83:653–63.

    CAS  Article  Google Scholar 

  16. 16.

    Roush GC, Sica DA. Diuretics for hypertension: a review and update. Am J Hypertens. 2016;29:1130–7.

    CAS  Article  Google Scholar 

  17. 17.

    Van Hemelrijck M, Wigertz A, Sandin F, Garmo H, Hellstrom K, Fransson P, et al. Cohort Profile: the National Prostate Cancer Register of Sweden and Prostate Cancer data Base Sweden 2.0. Int J Epidemiol. 2013;42:956–67.

    Article  Google Scholar 

  18. 18.

    Tomic K, Berglund A, Robinson D, Hjalm-Eriksson M, Carlsson S, Lambe M, et al. Capture rate and representativity of The National Prostate Cancer Register of Sweden. Acta Oncol. 2015;54:158–63.

    Article  Google Scholar 

  19. 19.

    Nationellt vårdprogram för prostatacancer Cis. 2019. http://www.cancercentrum.se/samverkan/cancerdiagnoser/prostata/vardprogram/gallande-vardprogram-prostatacancer/. Viewed Dec 2019.

  20. 20.

    Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373–83.

    CAS  Article  Google Scholar 

  21. 21.

    Liang Z, Xie B, Li J, Wang X, Wang S, Meng S, et al. Hypertension and risk of prostate cancer: a systematic review and meta-analysis. Sci Rep. 2016;6:31358.

    CAS  Article  Google Scholar 

  22. 22.

    Rathnayake D, Sinclair R. Use of spironolactone in dermatology. Skinmed. 2010;8:328–32.

    PubMed  Google Scholar 

  23. 23.

    Sirmans SM, Pate KA. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol. 2013;6:1–13.

    Article  Google Scholar 

  24. 24.

    Liss MA, Thompson IM. Prostate cancer prevention with 5-alpha reductase inhibitors: concepts and controversies. Curr Opin Urol. 2018;28:42–45.

    Article  Google Scholar 

  25. 25.

    Heinlein CA, Chang C. Androgen receptor in prostate cancer. Endocr Rev. 2004;25:276–308.

    CAS  Article  Google Scholar 

  26. 26.

    Chapman N, Dobson J, Wilson S, Dahlof B, Sever PS, Wedel H, et al. Effect of spironolactone on blood pressure in subjects with resistant hypertension. Hypertension. 2007;49:839–45.

    CAS  Article  Google Scholar 

  27. 27.

    Jeunemaitre X, Chatellier G, Kreft-Jais C, Charru A, DeVries C, Plouin PF, et al. Efficacy and tolerance of spironolactone in essential hypertension. Am J Cardiol. 1987;60:820–5.

    CAS  Article  Google Scholar 

  28. 28.

    Dhondt B, Buelens S, Van Besien J, Beysens M, De Bleser E, Ost P et al. Abiraterone and spironolactone in prostate cancer: a combination to avoid. Acta Clin Belg. 2019;74:439–44.

    Article  Google Scholar 

  29. 29.

    Flynn T, Guancial EA, Kilari M, Kilari D. Case report: spironolactone withdrawal associated with a dramatic response in a patient with metastatic castrate-resistant prostate cancer. Clin Genitourin Cancer. 2017;15:e95–e97.

    Article  Google Scholar 

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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.


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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