Spironolactone potentially chemopreventive in men

Exposure to the diuretic spironolactone may reduce the risk of developing prostate cancer by about 17 percent, a study has found.

The study included 31,591 men with prostate cancer and 156,802 matched healthy controls. In total, 846 patients (3 percent) and 5,571 controls (4 percent) had been prescribed spironolactone, while 935 (3 percent) and 4,530 (3 percent), respectively, were exposed to thiazides. Use of diabetes medications was slightly lower among patients than controls.

Multivariable conditional logistic regression analyses revealed a lower risk of prostate cancer among individuals exposed to spironolactone (odds ratio [OR], 0.83, 95 percent confidence interval [CI], 0.76–0.89). The chemopreventive effect was more pronounced for current users (OR, 0.77, 95 percent CI, 0.69–0.86) than past users (OR, 0.88, 95 percent CI, 0.79–0.97) and with increasing dose intensity (p<0.001).

There was no association observed between thiazide exposure and prostate cancer risk.

Pointing out the biological plausibility of the results, the researchers said that spironolactone is structurally similar to progesterone, exerts antiandrogenic effects, and is sometimes used off-label to treat hyper-androgenic conditions such as hirsutism (excess female hair growth), adult acne, and polycystic ovary syndrome. Therefore, it is possible that spironolactone reduces prostate cancer risk via a similar mechanism involving androgen receptor blockade. [Heart Fail Rev 2005;10:23-29; Skinmed 2010;8:328-332; Clin Epidemiol 2013;6:1-13]

Alternatively, the results may be explained by a masking effect, whereby spironolactone lowers prostate-specific antigen (PSA) levels without affecting prostate cancer risk, the researchers added. Lower PSA levels could lead to fewer referrals for biopsy, and consequently, less opportunity for PCa detection. But in the current study, no evidence of increased risk of high grade or more advanced prostate cancer was seen among men exposed to spironolactone.

More studies are needed to investigate spironolactone’s potential chemopreventive effects.