From the Guidelines
Testosterone replacement therapy (TRT) may cause a mild increase in Prostate-Specific Antigen (PSA) levels, but this increase is usually modest and not clinically concerning in most men. When men start TRT, PSA levels commonly rise by about 0.3-0.5 ng/mL during the first 3-6 months of treatment, after which they generally stabilize 1. This initial increase reflects the restoration of normal androgenic stimulation of prostate tissue rather than pathological growth.
Monitoring Protocols
Monitoring protocols typically include measuring PSA before starting TRT, again after 3-6 months of treatment, and then annually thereafter 1. A concerning pattern would be a PSA increase of more than 1.0 ng/mL within any 12-month period or a PSA velocity greater than 0.35 ng/mL per year after stabilization.
Key Considerations
These patterns would warrant further evaluation, possibly including referral to a urologist. The relationship between testosterone and prostate health is complex; contrary to older beliefs, current evidence suggests that TRT does not increase prostate cancer risk in men without pre-existing prostate cancer, and normal testosterone levels are actually important for prostate health 1. Men with a history of prostate cancer should discuss TRT with both their endocrinologist and urologist, as special considerations apply in these cases.
Recommendations for Monitoring
Recommendations for monitoring include determining baseline voiding history, performing digital rectal examination, and performing blood tests for baseline testosterone levels, PSA, and hematocrit or hemoglobin 1. Follow-up monitoring should include efficacy evaluation with dosage adjustment for sub-optimal response at 1 to 2 months, and monitoring evaluation with repeated testing every 3 to 6 months for the first year and annually thereafter.
From the Research
Testosterone Replacement Therapy and PSA Levels
- The relationship between testosterone replacement therapy (TRT) and prostate-specific antigen (PSA) levels is complex and has been studied extensively.
- A systematic review and meta-analysis published in 2015 2 found that TRT does not increase PSA levels in men being treated for hypogonadism, except when it is given intramuscularly (IM), and even the increase with IM administration is minimal.
- Another study published in 2014 3 found that short-term TRT was more likely to increase PSA levels than treatment with placebo, but long-term data are warranted with justifiable end points.
- A study published in 1995 4 found that exogenous testosterone administration did not significantly correlate with serum PSA or prostate-specific membrane antigen (PSMA) levels in hypogonadal men.
- A study published in 1990 5 found that finasteride, a 5 alpha-reductase inhibitor, decreased whole tissue dihydrotestosterone (DHT) and increased tissue testosterone (T) concentrations, and that epithelial cell PSA and DHT values significantly decreased in finasteride-treated patients.
Effects of Testosterone on PSA Levels
- The effect of testosterone on PSA levels is not entirely clear, with some studies suggesting that PSA levels are under androgenic influence, especially in patients with adenocarcinoma of the prostate.
- However, other studies have found that testosterone administration does not significantly correlate with serum PSA or PSMA levels in hypogonadal men 4.
- The use of finasteride, a 5 alpha-reductase inhibitor, has been shown to decrease PSA levels, but this may be due to its effect on DHT rather than testosterone 6, 5.
Clinical Implications
- The clinical implications of the relationship between TRT and PSA levels are important, as PSA is a primary screening tool for prostate cancer.
- The findings of these studies suggest that TRT may not significantly increase the risk of prostate cancer, but long-term data are needed to confirm this 2, 3.
- Clinicians should carefully monitor PSA levels in patients undergoing TRT, especially if they are given IM, and consider the potential effects of finasteride on PSA levels 6, 2, 5.