Testosterone Replacement Therapy and Peptide Therapy in Patients with Family History of Colon Cancer and Personal History of Colon Polyps
Testosterone replacement therapy (TRT) and peptide therapy should be approached with caution in patients with a family history of colon cancer and personal history of colon polyps, but they are not absolutely contraindicated when appropriate monitoring is in place.
Risk Assessment for Colorectal Cancer
- Approximately 20% of colon cancer cases are associated with familial clustering, and first-degree relatives of patients with newly diagnosed colorectal adenomas or invasive colorectal cancer are at increased risk for colorectal cancer 1
- Individuals with a family history of colorectal cancer have a 3-4 times higher risk than the general population, particularly if there are two or more first-degree relatives with CRC 2
- Patients with a personal history of colon polyps require regular surveillance colonoscopies regardless of hormone therapy status 1
Testosterone and Colorectal Cancer Risk
- Recent studies suggest that testosterone may play a role in colorectal carcinogenesis through various pathways 3
- Testosterone has been associated with increased risk of developing colorectal cancer in some animal studies, where orchidectomized male rats exhibited lower risk of developing CRC 3
- The presence of membrane androgen receptors (mARs) versus intracellular androgen receptors (iARs) may have different effects on CRC development, with mARs potentially having anti-neoplastic effects 3
Recommendations for Patients with Family History and Polyps
- For patients with a family history of colon cancer and personal history of polyps, enhanced surveillance is recommended regardless of hormone therapy status 1, 2
- Colonoscopy screening should begin at age 40 or 10 years before the age of diagnosis of the youngest affected relative, whichever comes first 2
- Surveillance intervals should be determined based on the findings from previous colonoscopies, with more frequent intervals (3-5 years) for those with advanced adenomas or multiple polyps 2
Monitoring Recommendations if Starting TRT
- Before initiating TRT in patients with family history of colon cancer and personal history of polyps, ensure the patient is up-to-date with appropriate colonoscopy surveillance 1, 2
- Consider more frequent colonoscopy surveillance during TRT treatment (every 3-5 years) depending on the number, size, and histology of previous polyps 1, 2
- Monitor for gastrointestinal symptoms that could indicate colorectal neoplasia during TRT treatment 3
- Consider measuring serum unbound testosterone as a potential biomarker along with carcinoembryonic antigen (CEA) in patients on TRT with high risk for CRC 3
Special Considerations
- Patients with hereditary syndromes such as Lynch syndrome (HNPCC) or familial adenomatous polyposis (FAP) have significantly higher risk of developing CRC and may require more careful consideration before initiating TRT 1
- The risk-benefit ratio should be carefully evaluated in patients with advanced adenomas (villous features, high-grade dysplasia, or ≥1 cm in size) as these represent higher risk lesions 1, 2
- Consider genetic counseling and testing for patients with strong family history of colorectal cancer before initiating hormone therapy 1, 2
Conclusion
While there are theoretical concerns about testosterone potentially promoting colorectal neoplasia, there are no absolute contraindications to TRT or peptide therapy in patients with a family history of colon cancer and personal history of non-cancerous polyps. The key is appropriate risk stratification and enhanced surveillance with regular colonoscopies. The decision to initiate therapy should be made after discussing potential risks and benefits, with emphasis on adherence to recommended colorectal cancer screening protocols.