Can spironolactone cause cancer?

Spironolactone and Cancer Risk

Spironolactone does not increase the risk of most human cancers and may actually decrease prostate cancer risk, despite animal studies showing tumorigenicity in rats at high doses. 1, 2, 3

Evidence on Cancer Risk

Animal Studies vs. Human Data

• The FDA label notes that spironolactone has been shown to be tumorigenic in rat studies, with effects on endocrine organs and liver when administered at high doses (50-500 mg/kg/day) 2
• However, human epidemiological data contradicts these animal findings:
  • A systematic review of 4.5 million individuals showed no increased risk of breast, ovarian, bladder, kidney, gastric, or esophageal cancer with spironolactone use 1, 3
  • Spironolactone use is actually associated with decreased prostate cancer risk (RR 0.79; 95% CI 0.68-0.90) 1, 3, 4

Specific Cancer Types

1. Prostate Cancer: Significantly reduced risk (HR 0.69; 95% CI 0.60-0.80) 4
2. Breast Cancer: No significant association (RR 1.04; 95% CI 0.86-1.22) 3
3. Gynecologic Cancers:
   • Ovarian: No significant association (RR 1.52; 95% CI 0.84-2.20) 3, 5
   • Endometrial/Uterine: No significant increased risk with long-term use 5
4. Other Cancers: No significant association with bladder, kidney, gastric, or esophageal cancers 3

Important Clinical Considerations

Apparent Cancer Associations

• Some studies show increased cancer diagnoses in the first year of spironolactone use, but this is likely due to reverse causality:
  • Symptoms from undiagnosed cancers may lead to spironolactone prescription 5
  • Similar patterns seen with other diuretics like furosemide, suggesting this is not specific to spironolactone 5

Special Considerations in Prostate Cancer

• While spironolactone generally reduces prostate cancer risk, it should be avoided in patients already on abiraterone for prostate cancer treatment 6
• In androgen-depleted environments (like during abiraterone treatment), spironolactone may paradoxically act as an androgen receptor agonist 6

Potential Anti-Cancer Effects

• Some research suggests spironolactone may have anti-cancer properties by:
  • Suppressing DNA damage repair
  • Reducing survivin expression (an anti-apoptotic protein)
  • Chemosensitizing cancer cells to certain non-DNA-damaging anticancer drugs 7

Clinical Algorithm for Spironolactone Use

1. For general patients: No cancer-related contraindications to spironolactone use
2. For patients with history of cancer: No evidence suggests avoiding spironolactone
3. Exception: Avoid in prostate cancer patients on abiraterone due to potential antagonistic effects
4. Monitoring: Standard monitoring for spironolactone side effects (electrolytes, renal function) is sufficient; no special cancer monitoring needed

Common Pitfalls to Avoid

• Don't withhold spironolactone due to cancer concerns in patients who would benefit from it for approved indications
• Don't confuse animal data with human outcomes - the tumorigenicity seen in rats at high doses has not translated to human cancer risk
• Don't misinterpret early cancer diagnoses after spironolactone initiation as causation - this is likely reverse causality
• Don't use spironolactone with abiraterone in prostate cancer patients