title: Androgen-deprivation therapy and risk for biliary disease in men with prostate cancer.
abstract: BACKGROUND
  Androgen-deprivation therapy (ADT) by either a gonadotropin-releasing hormone (GnRH) agonist or bilateral orchiectomy improves disease-related outcomes of men with prostate cancer but has a variety of adverse metabolic effects including obesity, increased abdominal girth, increased triglycerides, and insulin resistance. Each is a risk factor for gallstone disease. Additionally, GnRH agonist treatment was recently shown in metabolomic analyses to increase plasma levels of some bile acids.
  
  
  OBJECTIVE
  To assess the relationship between ADT and the incidence of biliary disease in men with prostate cancer.
  
  
  METHODS
  We studied 183 842 men >65 yr of age living in Surveillance, Epidemiology, and End Results regions who were diagnosed with prostate cancer from 1992 to 2007 and followed through 2009.
  
  
  METHODS
  We calculated incidence rates for biliary disease during treatment with GnRH agonists, orchiectomy, or no therapy. We used Cox proportional hazard models to assess the association of ADT with biliary disease.
  
  
  CONCLUSIONS
  Among 183 842 men with locoregional prostate cancer, 48.4% received GnRH agonist treatment and 2.2% underwent bilateral orchiectomy during follow-up. GnRH agonist treatment was associated with a significantly higher incidence of biliary disease compared with no treatment (15.7 vs 13.4 cases per 1000 person-years; p<0.001). In adjusted analyses, GnRH agonist use was associated with the risk of biliary disease (adjusted hazard ratio: 1.10; 95% confidence interval, 1.05-1.15; p<0.001). Orchiectomy was not significantly associated with biliary disease.
  
  
  CONCLUSIONS
  GnRH agonist treatment may be associated with a greater risk of incident biliary disease.
authors: Division of Hematology and Oncology, Massachusetts General Hospital, Boston, MA, USA. Electronic address: psaylor@partners.org.
authors: Philip J
authors: PJ
authors: Saylor
authors: Division of Hematology and Oncology, Massachusetts General Hospital, Boston, MA, USA.
authors: Matthew R
authors: MR
authors: Smith
authors: Department of Health Care Policy, Harvard Medical School, Boston, MA, USA.
authors: A James
authors: AJ
authors: O'Malley
authors: Department of Health Care Policy, Harvard Medical School, Boston, MA, USA; Division of General Internal Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
authors: Nancy L
authors: NL
authors: Keating
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001649:Bile Duct Diseases / Q000453:epidemiology* / Q000209:etiology*; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D015994:Incidence; D008297:Male; D009919:Orchiectomy / Q000009:adverse effects*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D012307:Risk Factors
chemical_list: D007987:Gonadotropin-Releasing Hormone
keywords: Androgen deprivation therapy; Biliary disease; GnRH agonist; Orchiectomy; Prostate cancer