Testosterone Replacement Therapy Does Not Cause Prostate Cancer or Blood Clots
Based on the highest quality evidence available, testosterone replacement therapy (TRT) does not cause prostate cancer or venous thromboembolism in men, though proper monitoring remains essential to detect pre-existing occult malignancies. 1, 2, 3
Prostate Cancer Risk
No Causative Relationship Established
There is no compelling evidence that testosterone has a causative role in prostate cancer. 1
Studies using stored plasma samples failed to show any difference in testosterone levels between men who developed prostate cancer 7-25 years later and those who did not. 1
A 2004 New England Journal of Medicine review of 12 prospective studies found no significant relationship between serum androgen levels and prostate cancer development. 1
Prostate cancer becomes more prevalent precisely when testosterone levels decline with age, contradicting a causative relationship. 1
A 2014 meta-analysis of 22 randomized controlled trials involving 2,351 patients found no statistically significant increased risk of prostate cancer with TRT, regardless of administration route (injection, transdermal, or oral). 4
The Real Risk: Unmasking Pre-Existing Cancer
Among hypogonadal men with normal PSA and digital rectal exam who underwent prostate biopsy before starting TRT, 14% had occult prostate cancer (median age 64 years). 5
TRT may unmask pre-existing occult prostate cancer rather than cause new malignancies. 1, 6
The FDA label notes that geriatric patients may be at increased risk of prostatic carcinoma, though conclusive evidence is lacking. 7
Required Monitoring Protocol for Your 67-Year-Old Patient
Before Starting TRT
Obtain baseline PSA and perform digital rectal examination. 1, 5
If PSA >4.0 ng/mL or abnormal digital rectal exam findings (nodule, asymmetry, increased firmness), perform prostate biopsy before initiating TRT. 1
During TRT
Monitor PSA every 3-6 months during the first year, then every 6-12 months if stable. 5
Perform prostate biopsy if PSA increases by ≥1.0 ng/mL per year (the typical increase with TRT is only 0.30-0.43 ng/mL). 5
Maintain a low threshold for biopsy with any concerning changes on digital rectal examination. 1
Monitor hemoglobin and hematocrit periodically to detect polycythemia. 7
Venous Thromboembolism Risk
No Increased Risk Demonstrated
A 2015 case-control study of 30,572 men found no association between testosterone therapy and VTE risk (adjusted OR 0.90,95% CI 0.73-1.12). 2
This finding was consistent across all routes of administration: topical (aOR 0.80), transdermal (aOR 0.91), and intramuscular (aOR 1.15). 2
A 2021 systematic review and meta-analysis of 13 randomized controlled trials (5,050 men) confirmed no increased VTE risk with TRT compared to placebo (RR 1.03,95% CI 0.49-2.14). 3
Similar null findings were observed for both deep vein thrombosis and pulmonary embolism specifically. 3
Important Caveat
While the pooled evidence shows no increased risk, the 95% confidence intervals are wide, meaning a clinically important increased risk cannot be completely ruled out. 3
The quality of evidence is considered low due to study heterogeneity and risk of bias. 3
Clinical Bottom Line for Your 67-Year-Old Patient
You can proceed with TRT without specific concern for causing prostate cancer or blood clots, provided you:
Exclude pre-existing prostate cancer through baseline PSA and digital rectal exam (with biopsy if abnormal). 1, 5
Implement rigorous PSA monitoring every 3-6 months initially. 5
Perform biopsy promptly if PSA rises ≥1.0 ng/mL per year. 5
Monitor for polycythemia with periodic hemoglobin/hematocrit checks. 7