Medications That Can Increase PSA Levels
Testosterone replacement therapy is the primary medication that increases PSA levels, with elevations occurring regardless of administration route, though intramuscular formulations produce the most significant increases. 1, 2
Testosterone Replacement Therapy
Testosterone therapy consistently raises PSA levels in hypogonadal men, with the magnitude of increase varying by delivery method:
- Intramuscular testosterone (enanthate 200-300 mg every 2-3 weeks) produces the most significant PSA elevation (mean difference 0.271 ng/mL vs controls) 1
- Endogenous testosterone elevation via clomiphene citrate (50 mg three times weekly) raises PSA levels the highest among all methods 2
- Transdermal testosterone patches (5 mg daily) yield the least PSA response but still produce measurable increases 2, 3
Clinical Mechanism and Implications
- PSA production is under direct control of circulating androgens acting through androgen receptors, with the PSA gene being up-regulated by androgens at both protein and mRNA levels 4
- PSA levels are inappropriately low in hypogonadal men and may mask underlying prostate cancer 2
- After testosterone normalization, PSA typically increases from baseline by 0.15-0.27 ng/mL depending on formulation 1
- Long-term transdermal testosterone treatment shows PSA velocity remains negligible (0.00-0.03 ng/mL/year) after initial stabilization 3
Medications That Do NOT Increase PSA
Alpha-Blockers (Tamsulosin)
- Tamsulosin does not affect PSA levels and requires no PSA adjustment during monitoring 5
- This distinguishes it from 5-alpha-reductase inhibitors, which decrease PSA by approximately 50% 5
5-Alpha-Reductase Inhibitors
- Finasteride and dutasteride decrease (not increase) PSA levels by approximately 50% after 6-12 months, though this effect is highly variable 6, 5
- Only 35% of men demonstrate the expected 40-60% PSA decrease, while 30% show greater than 60% reduction 6
Herbal Supplements
- Saw palmetto and other herbal supplements may affect PSA levels through phytoestrogenic compounds, though the exact composition and specific effects remain poorly understood 6, 7
- Over 20% of men visiting prostate cancer screening clinics take herbal supplements that could potentially influence PSA 6, 7
Other Conditions That Elevate PSA (Not Medications)
While not medications, these factors must be excluded when evaluating PSA elevations:
- Prostatitis causes dramatic PSA increases and is more likely than cancer in men with very high PSA velocity 6
- Prostate massage, ultrasonography, cystoscopic examination, and prostate biopsy all cause clinically significant elevations 4
- Acute urinary retention and renal failure can elevate PSA 4
- Benign prostatic hyperplasia (BPH) and urethral/prostatic trauma 8
Critical Clinical Pitfalls
- Always measure baseline PSA before initiating testosterone therapy to avoid missing underlying prostate cancer that may be masked by low testosterone 2, 9
- Recheck PSA 2-3 months after starting testosterone replacement to establish a new baseline 2
- Sharp PSA increases during testosterone therapy warrant evaluation for prostatitis (6 of 7 cases with PSA >4 ng/mL had prostatitis, not cancer) 3
- Use the same laboratory assay for serial PSA measurements, as different assays are not interchangeable due to different calibration standards 6, 8
- Laboratory variability in PSA testing ranges from 20-25%, so confirm mildly elevated PSA in 3-6 months before proceeding to biopsy 8