Association of Spironolactone Use With Risk of Cancer
Bibliographic record
Abstract
IMPORTANCE: 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. However, spironolactone carries an official warning from the US Food and Drug Administration regarding potential for tumorigenicity. OBJECTIVE: To determine the pooled occurrence of cancers, in particular breast and prostate cancers, among those who were ever treated with spironolactone. DATA SOURCES: PubMed, Cochrane Library, Embase, and Web of Science were searched from inception through June 11, 2021. The search was restricted to studies in the English language. STUDY SELECTION: Included studies reported the occurrence of cancers in men and women 18 years and older who were exposed to spironolactone. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers (K.B. and H.H.) selected studies, extracted data, and appraised the risk of bias using the Newcastle-Ottawa Scale. Studies were synthesized using random effects meta-analysis. MAIN OUTCOMES AND MEASURES: Cancer occurrence, with a focus on breast and prostate cancers. RESULTS: Seven studies met eligibility criteria, with sample sizes ranging from 18 035 to 2.3 million and a total population of 4 528 332 individuals (mean age, 62.6-72.0 years; in the studies without stratification by sex, women accounted for 17.2%-54.4%). All studies were considered to be of low risk of bias. No statistically significant association was observed between spironolactone use and risk of breast cancer (risk ratio [RR], 1.04; 95% CI, 0.86-1.22; certainty of evidence very low). There was an association between spironolactone use and decreased risk of prostate cancer (RR, 0.79; 95% CI, 0.68-0.90; certainty of evidence very low). There was no statistically significant association between spironolactone use and risk of ovarian cancer (RR, 1.52; 95% CI, 0.84-2.20; certainty of evidence very low), bladder cancer (RR, 0.89; 95% CI, 0.71-1.07; certainty of evidence very low), kidney cancer (RR, 0.96; 95% CI, 0.85-1.07; certainty of evidence low), gastric cancer (RR, 1.02; 95% CI, 0.80-1.24; certainty of evidence low), or esophageal cancer (RR, 1.09; 95% CI, 0.91-1.27; certainty of evidence low). CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis, spironolactone use was not associated with a substantial increased risk of cancer and was associated with a decreased risk of prostate cancer. However, the certainty of the evidence was low and future studies are needed, including among diverse populations such as younger individuals and those with acne or hirsutism.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.007 | 0.038 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.008 |
| Bibliometrics | 0.004 | 0.006 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".