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World Journal of Urology

, Volume 32, Issue 3, pp 669–676 | Cite as

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

  • Luis A. Kluth
  • Shahrokh F. Shariat
  • Christian Kratzik
  • Scott Tagawa
  • Guru Sonpavde
  • Malte Rieken
  • Douglas S. Scherr
  • Karl Pummer
Invited Review

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.

Keywords

Androgen deprivation therapy Hypothalamic–pituitary–gonadal axis Prostate cancer GnRH analogues GnRH antagonist LHRH agonist 

Abbreviations

ADT

Androgen deprivation therapy

DHT

Dihydrotestosterone

FSH

Follicle-stimulating hormone

GnRH

Gonadotropin-releasing hormone

GnRHR

Gonadotropin-releasing hormone receptor

HPG

Hypothalamic–pituitary–gonadal

LH

Luteinizing hormone

LHRH

Luteinizing-hormone-releasing hormone

PCa

Prostate cancer

SHBG

Sex hormone-binding globulin

VEGF

Vascular endothelial growth factor

PSA

Prostate-specific antigen

Notes

Acknowledgments

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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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Luis A. Kluth
    • 1
  • Shahrokh F. Shariat
    • 1
    • 2
    • 3
  • Christian Kratzik
    • 3
  • Scott Tagawa
    • 1
    • 2
  • Guru Sonpavde
    • 4
  • Malte Rieken
    • 1
  • Douglas S. Scherr
    • 1
  • Karl Pummer
    • 5
    • 6
    • 7
  1. 1.Department of UrologyWeill Cornell Medical CollegeNew YorkUSA
  2. 2.Division of Hematology and Medical OncologyWeill Cornell Medical CollegeNew YorkUSA
  3. 3.Department of UrologyMedical University of ViennaViennaAustria
  4. 4.Section of Medical Oncology, Department of MedicineUniversity of Alabama at Birmingham (UAB)BirminghamUSA
  5. 5.Division of Oncology, Department of Internal MedicineMedical University of Graz (MUG)GrazAustria
  6. 6.Department of UrologyMedical University of Graz (MUG)GrazAustria
  7. 7.Research Facility for BiostatisticsMedical University of Graz (MUG)GrazAustria

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