LHRH Antagonists Restore Serum Testosterone Faster Than LHRH Agonists in Prostate Cancer Patients After Radiotherapy

Prostate. 2025 Jul;85(10):919-931. doi: 10.1002/pros.24899. Epub 2025 Apr 2.

Abstract

Introduction: Maintaining a castration level of testosterone (TST) during radiation therapy combined with androgen deprivation therapy (ADT) is an essential strategy in the treatment of prostate cancer; however, hypogonadism can cause various complications. The aim was to compare serum TST recovery between LHRH agonists and LHRH antagonists.

Methods: A total of 131 patients who underwent radiation therapy with ADT for prostate cancer were retrospectively analyzed. Serum TST levels after termination of ADT including LHRH agonists and antagonists were compared. Cox proportional hazards model and the Kaplan-Meier method were used for statistical analysis.

Results: Median age, baseline TST, nadir TST, and duration of ADT were 71 years, 535 ng/dL, 10.92 ng/dL, and 12 months, respectively. Multivariate analysis identified significant associations of initial PSA ≥ 10.92 ng/mL (p = 0.0366), ADT ≥ 360 days (p = 0.0408), nadir TST ≤ 19 ng/dL (p = 0.0003), and LHRH agonist (p = 0.0027) with delayed TST recovery to castration level (50 ng/dL). We created a risk model based on these four independent risk factors (Low: 0-1 factor/Intermediate: 2 factors/High Risk: 3-4 factors). Each risk group significantly differentiated the TST recovery to castration level. Even after propensity score matching, recovery of TST to castration level and therapeutic level (200 ng/dL) was significantly delayed in the LHRH agonist group compared with the LHRH antagonist group (p = 0.0016, p = 0.0389, respectively).

Conclusion: LHRH antagonists restored serum TST to castration and therapeutic levels faster than LHRH agonists in prostate cancer patients undergoing radiation therapy with ADT.

Keywords: ADT; LHRH antagonist; prostate cancer; testosterone recovery.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androgen Antagonists / therapeutic use
  • Gonadotropin-Releasing Hormone* / agonists
  • Gonadotropin-Releasing Hormone* / antagonists & inhibitors
  • Humans
  • Male
  • Middle Aged
  • Prostatic Neoplasms* / blood
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / radiotherapy
  • Retrospective Studies
  • Testosterone* / blood

Substances

  • Testosterone
  • Gonadotropin-Releasing Hormone
  • Androgen Antagonists