A gonadotropin-releasing hormone antagonist reduces serum adrenal androgen levels in prostate cancer patients

BMC Urol. 2017 Aug 29;17(1):70. doi: 10.1186/s12894-017-0261-z.

Abstract

Background: Adrenal androgens play an important role in the development of castration-resistant prostate cancer therapeutics. The effect of gonadotropin-releasing hormone (GnRH) antagonists on adrenal androgens has not been studied sufficiently. We measured testicular and adrenal androgen levels in patients treated with a GnRH antagonist.

Methods: This study included 47 patients with histologically proven prostate cancer. All of the patients were treated with the GnRH antagonist degarelix. The mean patient age was 73.6 years. Pre-treatment blood samples were collected from all of the patients, and post-treatment samples were taken at 1, 3, 6, and 12 months after starting treatment. Testosterone (T), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), 17β-estradiol (E2), and androstenedione (A-dione) were measured by liquid chromatography-mass spectrometry. Dehydroepiandrosterone-sulfate (DHEA-S), luteinizing hormone, and follicle-stimulating hormone levels were measured by electro-chemiluminescence immunoassays.

Results: A significant reduction in T level (97.3% reduction) was observed in the patients 1 month after initiating treatment. In addition, levels of DHT, E2, DHEA-S, and A-dione decreased 1 month after initiating treatment (93.3, 84.9, 16.8, and 35.9% reduction, respectively). T, DHT, E2, DHEA-S, and A-dione levels remained significantly suppressed (97.1, 94.6, 85.3, 23.9, and 40.5% reduction, respectively) 12 months after initiating treatment. A significant decrease in DHEA level (15.4% reduction) was observed 12 months after initiating treatment.

Conclusions: Serum adrenal androgen levels decreased significantly in patients treated with a GnRH antagonist. Thus, long-term GnRH antagonist treatment may reduce serum adrenal androgen levels.

Keywords: Adrenal androgen; GnRH antagonist; Prostate cancer.

MeSH terms

  • Adrenal Glands / metabolism
  • Aged
  • Androgens / biosynthesis
  • Androgens / blood*
  • Gonadotropin-Releasing Hormone / antagonists & inhibitors*
  • Humans
  • Male
  • Oligopeptides / therapeutic use*
  • Prostatic Neoplasms / blood*
  • Prostatic Neoplasms / drug therapy*
  • Testis / metabolism

Substances

  • Androgens
  • Oligopeptides
  • acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide
  • Gonadotropin-Releasing Hormone