Management of Elevated PSA on Testosterone Therapy
For men on testosterone replacement therapy with elevated PSA, refer to urology immediately if PSA rises above 4.0 ng/mL, increases by ≥1.0 ng/mL in the first 6 months of treatment, or increases by >0.4 ng/mL per year thereafter. 1, 2
Immediate Referral Criteria While on Testosterone
Absolute PSA Thresholds
- Refer to urology if PSA exceeds 4.0 ng/mL regardless of baseline value 1, 2
- This threshold carries a 17-32% cancer detection rate and warrants urologic evaluation 3
PSA Velocity Thresholds (More Important Than Absolute Values)
Refer immediately if PSA increases ≥1.0 ng/mL during the first 6 months of testosterone therapy 1, 2, 4
Refer if PSA increases >0.4 ng/mL per year after the first 6 months of therapy 1, 2, 3
For PSA increases of 0.7-0.9 ng/mL, repeat PSA in 3-6 months and refer if any further increase 1, 2
Digital Rectal Examination Findings
- Any abnormal DRE finding mandates immediate referral regardless of PSA level 1, 3
- Specifically refer for any nodule, asymmetry, or areas of increased firmness 1, 2
- DRE is particularly sensitive for detecting cancers in men on testosterone and may be more reliable than PSA alone 5
Monitoring Protocol While on Testosterone
Baseline Requirements Before Starting Testosterone
- Obtain baseline PSA and perform DRE before initiating therapy 1
- If baseline PSA >4.0 ng/mL or abnormal DRE, perform prostate biopsy before starting testosterone 1
- Confirm hypogonadism with morning testosterone measurements on at least two separate days 6
Follow-Up Monitoring Schedule
- Check PSA, DRE, and testosterone levels every 3-6 months for the first year 1
- After the first year, monitor annually if stable 1
- Assess for urinary symptoms at each visit 1
Clinical Context and Nuances
Understanding PSA Changes on Testosterone
The typical PSA increase with testosterone therapy is modest (0.30-0.43 ng/mL), making larger increases highly concerning 1, 4. Importantly, testosterone does not cause prostate cancer but may unmask existing occult disease 1, 7. Multiple studies show no compelling evidence that higher testosterone levels increase prostate cancer risk 1, 7.
When Prostate Cancer is Detected
- Prostate cancer may become clinically apparent within months to a few years after initiating testosterone 5
- Cancers detected during testosterone therapy tend to be moderate to high grade (Gleason 6-10) 5
- Median PSA at diagnosis tends to be relatively low (5.1 ng/mL), emphasizing the importance of velocity changes over absolute values 5
Special Considerations
- Men with prostatic intraepithelial neoplasia (PIN) can receive testosterone with appropriate monitoring, as they do not show greater PSA increases than men without PIN 8
- PSA levels may be inappropriately low in hypogonadal men and can mask underlying cancer 9
- After testosterone normalization, PSA levels remain stable for ≥5 years in men without cancer 10
Common Pitfalls to Avoid
Do not delay referral waiting for PSA to exceed 4.0 ng/mL if velocity criteria are met 2, 4
Do not rely solely on PSA—integrate DRE findings into decision-making 1, 5
- DRE proved more sensitive than PSA in detecting cancers in testosterone-treated men 5
Do not continue testosterone without proper monitoring 1
- Patients followed by non-urologists were monitored less frequently and had delayed cancer detection 5
Do not order additional workup (free PSA, imaging) before referral 3
- These are urologist's tools for biopsy decision-making, not primary care tests 3
What to Tell the Patient
- Testosterone therapy requires vigilant prostate monitoring but does not cause prostate cancer 1, 7
- Regular PSA and DRE monitoring allows early detection and potential cure of any unmasked cancers 1
- Most men on testosterone do not develop prostate cancer—the incidence is approximately 1-5%, similar to screening programs 7, 10
- Any significant PSA rise requires urologic evaluation, which may include prostate biopsy 1