Androgen deprivation decreases prostate specific antigen in the absence of tumor: implications for interpretation of PSA results

Clin Chem Lab Med. 2014 Mar;52(3):431-6. doi: 10.1515/cclm-2013-0535.


Background: Prostate-specific antigen (PSA) is used as an outcome measure for relapsed disease in prostate cancer. Nonetheless, there are considerable concerns about its indiscriminate use as a surrogate endpoint for cell growth or survival. We hypothesized that treatment with a luteinizing hormone releasing hormone (LHRH) analog would decrease PSA levels even in the absence of malignant disease.

Methods: We determined testosterone and PSA levels in 30 healthy volunteers after a single intramuscular injection of a LHRH depot formulation. Testosterone and PSA levels were quantified by radioimmunoassay and electrochemi-luminescence immunoassay, respectively.

Results: After an initial flare-up during the first 3 days testosterone decreased reaching castration levels in 18 of the 30 young men (60%). After the nadir on day 28, testosterone levels increased to normal again. Changes in PSA paralleled those of testosterone. Castration reduced PSA levels by 29% (95% CI 19%-39%) compared to baseline (p<0.0001).

Conclusions: LHRH superagonists decrease PSA levels by testosterone deprivation. Conferring these findings to tumor patients, decreases in PSA after treatment with LHRH analogs might not only reflect disease regression but also a direct testosterone mediated effect on PSA. Thus, PSA levels should be cautiously interpreted when patients receive hormonal therapy.

MeSH terms

  • Adolescent
  • Adult
  • Androgens / deficiency*
  • Data Interpretation, Statistical
  • False Negative Reactions
  • Gonadotropin-Releasing Hormone / administration & dosage
  • Gonadotropin-Releasing Hormone / pharmacology*
  • Humans
  • Injections
  • Male
  • Middle Aged
  • Prostate-Specific Antigen / blood*
  • Testosterone / blood
  • Time Factors
  • Young Adult


  • Androgens
  • Gonadotropin-Releasing Hormone
  • Testosterone
  • Prostate-Specific Antigen