Statistically significant associations were not seen between the medication and breast, ovarian, bladder, kidney, gastric, or esophageal cancers, and there was a reduced risk of prostate cancer.
In contrast to prior research suggesting an increased risk of certain cancers associated with spironolactone use, data from multiple studies appear to suggest the medication is not associated with a significantly increased risk of cancer, and in certain cases may actually lower the risk.
The data, pulished in JAMA Dermatology, come from 7 studies of over 4 million patients on the use of spironolactone—approved for conditions like heart failure and hypertension and used off label for conditions like acne and androgenetic alopecia.
Across the studies, there were no statistically significant associations between the medication and breast, ovarian, bladder, kidney, gastric, or esophageal cancers, and there was a reduced risk of prostate cancer. However, the researchers of the study emphasize that the certainty of evidence was low and that future studies are warranted.
“In light of the FDA-mandated warning cautioning that ‘unnecessary use of this drug should be avoided,’ these data are reassuring that treatment with spironolactone is unlikely to be associated with a meaningful increased risk of cancer when prescribed at typical clinical doses,” explained the researchers, noting that the warning is primarily based on animal studies that have used doses as much as 150 times higher than human doses.
Three studies included in the analysis provided data on the risk of breast cancer associated with spironolactone, revealing that there was no statistically significant association between the medication and risk of disease (risk ratio [RR], 1.04). In the one study that had odds ratio (OR) data, the researchers found a decreased odds of breast cancer associated with the medication (OR, 0.75), conflicting with prior research indicating an increased risk of disease.
“For patients with acne, spironolactone represents an important alternative to oral antibiotics. While there have been concerns about use of spironolactone and the development of breast cancer, the results of this meta-analysis are reassuring,” wrote the researchers. “In addition, prior studies have suggested that use of oral antibiotics may be associated with an increased risk of breast or colon cancers. Taken together, these findings suggest that spironolactone may have lower malignant potential compared with oral antibiotics for women with acne.”
In a previous study, there were indications that spironolactone was associated with an increased risk of ovarian cancer, a hormone-sensitive cancer, particularly during the first year of treatment. However, the researchers caveat this previous finding with a note that spironolactone was more commonly used in the months prior to ovarian cancer diagnosis, potentially for the management of abdominal swelling—a common presentation of ovarian cancer—before receiving a formal diagnosis.
In the current analysis, 4 studies included data on the risk of prostate cancer with spironolactone use, revealing a reduced rate of disease associated with the medication (RR, 0.79). Delving into the different populations included among the 4 studies, the researchers found a reduced risk of disease in patients with heart failure (RR, 0.63), hypertension (RR, 0.88), and for any indication (RR, 0.76).
The researchers note that the reduced risk of prostate cancer with spironolactone is consistent with the hypothesis that spironolactone’s antiandrogenic properties could be protective against prostate cancer, an androgen-sensitive tumor.
“Because prostate cancer is one of the most common cancers in men, this factor may be a reason to consider spironolactone over other diuretics in the management of heart failure and edema in men,” wrote the group. “Spironolactone may also be a potential consideration for future study with respect to primary prevention and treatment of prostate cancer.”
Bommareddy K, Hamade H, Lopez-Olivo M, Wehner M, Tosh T, Barbieri J. Association of spironolactone use with risk of cancer: A systematic review and meta-analysis. JAMA Dermatol. Published online February 9, 2022. doi:10.1001/jamadermatol.2021.5866