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

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.

Effectiveness of GnRH Antagonists and Agonists in Patients with Hormone-Sensitive Prostate Cancer: A Retrospective Study

“…Moreover, degarelix overcomes the problems of first- and second-generation antagonists, such as short lasting efficacy and the induction of allergic reactions [ 16 , 18 , 19 ], becoming a popular option for medical castration. It has been reported that antagonists can not only achieve the suppression of testosterone secretion through the inhibition of the GnRH receptor, luteinizing hormone secretion and follicle-stimulating hormone secretion, but also significantly reduce the adrenal-derived androgen level in serum [ 20 ]. Intermittent treatment with degarelix can maintain the inhibition of PSA and improve sexual function as well as the quality of life [ 20 ].…”

Progress in Clinical Research on Gonadotropin-Releasing Hormone Receptor Antagonists for the Treatment of Prostate Cancer

“…This phenomenon may be attributed to degarelix’s ability to also reduce serum adrenal androgen levels in patients with prostate cancer. 22 Furthermore, in the first 1–2 weeks of treatment, the median LH and FSH levels of patients in the leuprolide group increased due to the mechanism of action; however, median LH and FSH levels in the degarelix group declined more rapidly after the start of the treatment and remained suppressed until the end of the study. 8 At the end of the 12-month study, median FSH levels in the 240/80 mg degarelix, 240/160 mg degarelix and leuprolide groups decreased by 88.5%, 89.0% and 54.8%, respectively.…”

Sex steroids in the tumor microenvironment and prostate cancer progression

“…In addition, serum adrenal androgens may decrease to a lesser extent following LHRH antagonists (Miyazawa et al 2017). Studies with orchiectomy or LHRH agonists suggest that DHEA does not change substantially following ADT (Xu et al 2002, Oka et al 2003.…”