Spironolactone ‘unlikely’ to elevate cancer risks

While the level of evidence was generally low, spironolactone was not associated with statistically significant increased risk for a number of cancers, according to findings from a retrospective meta-analysis.

“While originally approved for the management of heart failure, hypertension and edema, spironolactone is commonly used off label in the management of acne, hidradenitis, androgenetic alopecia and hirsutism,” Kanthi Bommareddy, MD, of the University of Miami Miller School of Medicine and Holy Cross Health in Fort Lauderdale, Florida, and colleagues wrote. “However, spironolactone carries an official warning from the U.S. Food and Drug Administration regarding potential for tumorigenicity.”

In the review of PubMed, Cochrane Library, Embase and Web of Science databases, the researchers assessed the pooled occurrence of cancers among adults aged 18 years or older who had ever been treated with spironolactone. Studies conducted through June 11, 2021, were included.

Particular focus was paid to breast and prostate cancers for the primary endpoint analysis.

The final analysis included 4,528,332 individuals (mean age, 62.6 to 72 years; 17.2% to 54.4% women) from seven studies. Sample sizes for the data sets ranged from 18,035 to 2.3 million participants.

Results showed no statistically significant association for spironolactone use and breast cancer risk (RR = 1.04; 95% CI, 0.86-1.22). However, the researchers noted that the certainty of this finding was “very low.”

While the certainty of evidence for spironolactone use and prostate cancer risk was also very low, the researchers did observe a decreased risk for malignancy in this group (RR = 0.79; 95% CI, 0.68-0.9).

Looking at other cancers, the results failed to demonstrate an association between use of the study drug and risk for a number of malignancies, including ovarian cancer (RR = 1.52; 95% CI, 0.84-2.2) and bladder cancer (RR = 0.89; 95% CI, 0.71-1.07). The certainty of evidence for these two cancers was very low.

For kidney cancer (RR = 0.96; 95% CI, 0.85-1.07), gastric cancer (RR = 1.02; 95% CI, 0.8-1.24) and esophageal cancer (RR = 1.09; 95% CI, 0.91-1.27), there was also no statistically significant risk, and the certainty of evidence was low.

“This systematic review and meta-analysis provides reassuring data that use of spironolactone, an important treatment for patients with acne, hidradenitis, androgenetic alopecia and hirsutism, is unlikely to be associated with a substantial increased risk of cancer,” the researchers concluded.

“However, the certainty of the evidence was low. Future studies are needed, particularly among diverse populations such as younger individuals and those with acne or hirsutism.”