Association of Spironolactone Use With Risk of Cancer: A Systematic Review and Meta-analysis.

Area of Science:

• Oncology
• Pharmacology
• Epidemiology

Background:

• Spironolactone, initially for heart failure and hypertension, is now widely used off-label for dermatologic conditions like acne and hirsutism.
• A US Food and Drug Administration warning highlights spironolactone's potential for tumorigenicity, necessitating further investigation into its cancer risks.

Purpose of the Study:

• To conduct a meta-analysis determining the pooled cancer occurrence, specifically breast and prostate cancers, in individuals treated with spironolactone.
• To assess the association between spironolactone exposure and the risk of various cancers.

Main Methods:

• A comprehensive literature search was performed across PubMed, Cochrane Library, Embase, and Web of Science up to June 2021.
• Seven eligible studies involving over 4.5 million individuals were synthesized using random effects meta-analysis.
• Risk of bias was assessed using the Newcastle-Ottawa Scale, with all included studies deemed low risk.

Main Results:

• Spironolactone use showed no statistically significant association with an increased risk of breast cancer (RR, 1.04; 95% CI, 0.86-1.22).
• A statistically significant association was found between spironolactone use and a decreased risk of prostate cancer (RR, 0.79; 95% CI, 0.68-0.90).
• No significant associations were observed for ovarian, bladder, kidney, gastric, or esophageal cancers, though certainty of evidence was generally low to very low.

Conclusions:

• Spironolactone use is not associated with a substantial increased risk of cancer and may be linked to a reduced risk of prostate cancer.
• The overall certainty of the evidence is low, underscoring the need for future research in diverse populations.
• Further studies are recommended, particularly in younger individuals and those with dermatologic conditions for whom spironolactone is prescribed off-label.