Androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone (GnRH) agonist, but not bilateral orchiectomy, may increase the risk of biliary disease in patients with prostate cancer (PCa), researchers reported.

Philip J. Saylor, MD, of Massachusetts General Hospital in Boston, and colleagues analyzed data from 183,842 men older than 65 years and who were diagnosed with PCa from 1992 to 2007. Of these,48.4% received GnRH agonist 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 1,000 person-years). In adjusted analyses, GnRH agonist treatment was associated with a significant 10% increased risk of biliary disease, dr. Saylor’s group reported online ahead of print in European Urology.

Based on an additional 2.3 events per 1,000 person-years, the investigators said they would expect one new case of biliary disease for each 435 men treated with a GnRH agonist for one year.

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In addition, the risk of biliary disease rose with increasing duration of GnRH agonist treatment. Compared with men not received ADT, those who received GnRH agonist treatment for 7-12 months, 13-24 months, and 25 or more months had a significant 7%, 15%, and 20% increased risk of biliary disease, respectively.

“These findings may result from ADT-associated central adiposity, increases in serum triglycerides and fasting insulin, alterations in plasma bile acids, or other factors,” the authors concluded.

The investigators identified biliary disease using diagnosis codes for acute cholecystectomy or common bile duct stones, open or laparoscopic cholecystectomy, biliary drainage, biliary tract surgery, and other procedures.

In a discussion of study strengths, the authors that the study included a large number of older men representing more than one fourth of the U.S. population and their analyses were hypothesis driven. They pointed out that some known adverse effects of ADT are described risk factors for gallstone disease, including obesity, increased abdominal girth, hypertriglyceridemia, and insulin resistance.

“Given these factors and the recent observation that plasma bile acids rise during GnRH agonist therapy, we hypothesized that the incidence of biliary disease would be higher in men receiving this therapy.”

The researchers also pointed to some study limitations. For example, they identified disease outcomes based on administrated data that may be subject to error. In addition, they studied older men living in a number of specific regions in the U.S. “We therefore cannot be certain that out findings can be generalized,” they stated.

Dr. Saylor’s group also pointed out that differences in healthcare utilization may lead to differences in ascertainment of disease. “Men who receive GnRH agonist treatment are typically seen in a clinic and may be more likely to have symptoms noted and diagnoses reported,” the authors wrote. “Nevertheless, our results were robust to definitions of biliary disease that required patients to undergo a surgical procedure.”