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. DESIGN, SETTING, AND PARTICIPANTS: 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. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: 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. RESULTS AND LIMITATIONS: 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.