Testosterone Therapy and PSA Levels in Males
Yes, testosterone therapy can cause an increase in PSA levels in males, with studies showing a mean increase of approximately 0.47 ng/mL over 12 months of treatment. 1
PSA Changes During Testosterone Therapy
Expected PSA Changes
- Testosterone replacement therapy (TRT) typically causes a small but statistically significant increase in PSA levels compared to placebo 2, 1
- In men receiving TRT for 12 months, PSA increased by an average of 0.47 ng/mL compared to only 0.06 ng/mL in the placebo group 1
- Approximately 5% of men on TRT experience PSA increases ≥1.7 ng/mL, and 2.5% experience increases ≥3.4 ng/mL 1
- The increase is most pronounced with intramuscular (IM) testosterone administration compared to other routes 2
Timing of PSA Changes
- Initial PSA rises during the first year of therapy are common and generally not indicative of prostate cancer 3
- PSA levels typically stabilize after normalization of testosterone for most men on long-term therapy 4
Monitoring Recommendations
Baseline Assessment
- Measure serum PSA levels prior to initiating testosterone therapy in all men over 40 years of age 5
- If baseline PSA is elevated, a second PSA test should be performed to rule out spurious elevation 5
- Men with persistently elevated PSA should undergo further evaluation, potentially including reflex testing and prostate biopsy, before starting TRT 5
Follow-up Monitoring
- Monitor PSA levels every 3-6 months for the first year of treatment and annually thereafter 5
- Perform digital rectal examination at the same intervals 5
- Consider more frequent PSA testing in men with risk factors for prostate cancer 5
When to Consider Prostate Biopsy
- PSA increase of more than 1.0 ng/mL during the first six months of treatment 5
- PSA increase of more than 0.4 ng/mL per year after the first year of treatment 5
- Any abnormality detected on digital rectal examination 5
- Total PSA rising above 4.0 ng/mL 5
Clinical Implications
Prostate Cancer Risk
- Current evidence does not demonstrate that testosterone therapy increases the risk of developing prostate cancer 5
- The AUA guidelines provide a strong recommendation (Grade B evidence) that clinicians should inform patients of the absence of evidence linking testosterone therapy to prostate cancer development 5
- PSA increases during TRT appear to "unmask" rather than cause prostate cancer 6
Special Populations
- Men with a history of treated prostate cancer require special consideration:
- Post-radical prostatectomy: TRT may be considered in men with favorable pathology and undetectable PSA 5
- Post-radiation therapy: Studies suggest no significant PSA changes or cancer progression with TRT 5
- Active surveillance: Limited data, but patients with and without high-grade prostatic intraepithelial neoplasia on TRT did not show significant PSA increases or increased cancer diagnosis 5
Common Pitfalls and Caveats
- Misinterpreting initial PSA rise: An initial rise in PSA during the first year of TRT is common and not necessarily indicative of prostate cancer 3
- Ignoring route of administration: Intramuscular testosterone administration causes greater PSA increases than other routes 2
- Inadequate baseline evaluation: Failing to obtain proper baseline PSA levels before starting therapy may mask underlying prostate pathology 6
- Inconsistent monitoring: Irregular PSA monitoring may miss clinically significant changes that warrant further evaluation 5
- Overreaction to minor fluctuations: Small PSA fluctuations (less than 0.4 ng/mL per year after the first year) are generally not concerning 5
By following these evidence-based monitoring protocols, clinicians can safely administer testosterone therapy while appropriately monitoring for prostate health.