The hypothalamic–pituitary–gonadal axis and prostate cancer: implications for androgen deprivation therapy
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Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) may play important roles in prostate cancer (PCa) progression. Specifically, LH expression in PCa tissues has been associated with metastatic disease with a poor prognosis, while FSH has been shown to stimulate prostate cell growth in hormone-refractory PCa cell lines. Gonadotropin-realizing hormone (GnRH) analogues are common agents used for achieving androgen deprivation in the treatment for PCa. GnRH analogues include LH-releasing hormone (LHRH) agonists and GnRH antagonists, both of which exhibit distinct mechanisms of action that may be crucial in terms of their overall clinical efficacy. LHRH agonists are typically used as the primary therapy for most patients and function via a negative-feedback mechanism. This mechanism involves an initial surge in testosterone levels, which may worsen clinical symptoms of PCa. GnRH antagonists provide rapid and consistent hormonal suppression without the initial surge in testosterone levels associated with LHRH agonists, thus representing an important therapeutic alternative for patients with PCa. The concentrations of testosterone and dihydrotestosterone are significantly reduced after treatment with both LHRH agonists and GnRH antagonists. This reduction in testosterone concentrations to castrate levels results in significant, rapid, and consistent reductions in prostatic-specific antigen, a key biomarker for PCa. Evidence suggests that careful maintenance of testosterone levels during androgen deprivation therapy provides a clinical benefit to patients with PCa, emphasizing the need for constant monitoring of testosterone concentrations throughout the course of therapy.
KeywordsAndrogen deprivation therapy Hypothalamic–pituitary–gonadal axis Prostate cancer GnRH analogues GnRH antagonist LHRH agonist
Androgen deprivation therapy
Gonadotropin-releasing hormone receptor
Sex hormone-binding globulin
Vascular endothelial growth factor
The authors thank Corey Mandel, PhD, in association with ApotheCom for providing editorial assistance supported by Ferring Pharmaceuticals.
Conflict of interest
LAK: no financial disclosure/conflict of interest; SFS: advisory board for Ferring Pharmaceuticals; CK: no financial disclosure/conflict of interest; ST: consultant and member of speakers’ bureau for Sanofi-Aventis, Janssen, Medivation/Astellas; GS: research support from Novartis, Pfizer, BMS, Celgene, Bellicum Pharmaceuticals, and Sanofi-Aventis; speaker/advisory board for Novartis, Pfizer, GSK Astellas, Dendreon, Janssen, Sanofi-Aventis, and Amgen; MR: no financial disclosure/conflict of interest; DSS: advisory board for Imolux Inc.; and KP: no financial disclosure/conflict of interest.
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