Abstract
BackgroundAdrenal 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.MethodsThis 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.ResultsA 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.ConclusionsSerum adrenal androgen levels decreased significantly in patients treated with a GnRH antagonist. Thus, long-term GnRH antagonist treatment may reduce serum adrenal androgen levels.
Highlights
Adrenal androgens play an important role in the development of castration-resistant prostate cancer therapeutics
We previously reported that long-term luteinizing hormone-releasing hormone (LH-RH) agonist treatment reduced adrenal androgen levels via LH
T levels decreased significantly (97.3% reduction) in gonadotropin-releasing hormone (GnRH) antagonist-treated patients 1 month after initiating treatment compared to those at baseline
Summary
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. The disease is dependent on androgens; patients are often treated with androgen deprivation therapy [2]. Gonadotropin-releasing hormone (GnRH) antagonists block receptors directly, thereby rapidly suppressing testosterone (T) without the T surge and flare. No clinical studies on the GnRH antagonist degarelix have reported evidence of a T surge or flare [3,4,5,6]. Various drugs that interact with androgen receptors (ARs) have been developed and used clinically.
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