The hypothalamic–pituitary–gonadal axis and prostate cancer: implications for androgen deprivation therapy

Abstract

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.

Prognostic value of alkaline phosphatase in hormone-sensitive prostate cancer: a systematic review and meta-analysis

“…However, systemic therapy based on androgen deprivation remains the standard primary treatment strategy in patients with metastatic HSPC. Despite adequate therapy, the disease eventually progresses to a castration-resistant prostate cancer (CRPC) [4]. To improve PC outcomes, prognostic tools have been developed to help in the daily clinical decision making and patient counselling [5][6][7][8].…”

Surgical management of pituitary metastases

“…Degarelix, bind immediately and competitively to LHRH receptors in the pituitary gland which results in a rapid decrease in luteinising hormone, follicle-stimulating hormone, and testosterone levels [24].…”

Pentoxifylline mitigates detrimental impact of chronic nonbacterial prostatitis on sperm characteristics, reproductive hormones and histopathology in rats

“…In turn, LH also stimulates testosterone secretion and synthesis from testicular Leydig cell. On the other hand, the spermatogonial cell survival improves via the LH and FSH secretion (Adedara et al., ; Kluth et al., ) . Few studies have shown that there is a relationship between the levels of reproductive hormones and CNP (Byun et al., ; Dimitrakov et al., ; Pontari et al., 2004).…”