title: Bench-to-bedside development of agonists and antagonists of luteinizing hormone-releasing hormone for treatment of advanced prostate cancer.
abstract: BACKGROUND
  Androgen deprivation therapy (ADT) has been the standard of care for treating patients with hormone-sensitive advanced prostate cancer (PCa) for 3 decades. The agonists of luteinizing hormone-releasing hormone (LHRH), also called gonadotropin-releasing hormone, are still the most frequently used form of medical ADT.
  The application of agonists of LHRH has improved and modernized the treatment of advanced PCa; millions of patients have benefited from therapy with LHRH agonists as a preferred alternative to surgical castration, as the psychological effects and perpetuity of orchiectomy are undesirable for most men. Despite their efficacy, agonists of LHRH have several shortcomings, including initial surge in testosterone, producing exacerbation of clinical symptoms, and microsurges in testosterone that might occur after each administration. A new, alternate approach to ADT is emerging with the improvements in antagonists of LHRH. This class of LHRH analogues produces a direct and immediate blockade of pituitary LHRH receptors and leads to a more rapid suppression of testosterone without an initial surge or subsequent microsurges. Degarelix, a third-generation LHRH antagonist, is the only antagonist with a low histamine-releasing activity that is currently on the market for clinical use in advanced PCa with improved testosterone suppression, better control of follicle-stimulating hormone and prostate-specific antigen, and which offers a prolonged delay to progression and more favorable effects on serum alkaline phosphatase.
  
  
  CONCLUSIONS
  Although LHRH agonists are still the mainstay for treatment of advanced PCa, antagonists of LHRH offer an alternative as a pharmacological approach.
authors.affiliation: Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education, Miami, FL; Department of Urology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL. Electronic address: ferencrick@gmail.com.
authors.forename: Ferenc G
authors.initials: FG
authors.lastname: Rick
authors.affiliation: Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education, Miami, FL; Department of Pathology, Miller School of Medicine, University of Miami, Miami, FL; Division of Hematology/Oncology, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL; Division of Endocrinology, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL; Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL.
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Schally
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D011966:Receptors, LHRH / Q000819:agonists / Q000627:therapeutic use*
chemical_list: D000726:Androgen Antagonists; D011966:Receptors, LHRH
keywords: Advanced prostate cancer; GnRH; Hormonal therapy; LHRH