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Submitted on November 17, 2005
Accepted on January 18, 2006
Division of Hematology-Oncology (MRS), Mallinckrodt General Clinical Research Center (HL), and Diabetes Center (DMN) at the Massachusetts General Hospital, Boston, MA
* To whom correspondence should be addressed. E-mail: smith.matthew{at}mgh.harvard.edu.
Context: Gonadotropin-releasing hormone agonists markedly increase fat mass in men with prostate cancer but little is known about the effects of treatment on insulin sensitivity.
Objective: To assess the effects of short-term gonadotropin-releasing hormone agonist treatment on insulin sensitivity.
Design: Prospective 12-week study.
Setting: General clinical research center.
Patients or Other Participants: We studied 25 men with locally advanced or recurrent prostate cancer, no radiographic evidence of metastases, and no history of diabetes mellitus, and no evidence of diabetes mellitus at baseline visit.
Intervention: Leuprolide depot and bicalutamide
Main Outcome Measures: Oral glucose tolerance tests and body composition assessment by dual energy x-ray absorptiometry were performed at baseline and week 12. The primary study outcome was change in insulin sensitivity index.
Results: Mean (± SE) percentage fat body mass increased by 4.3 ± 1.3% from baseline to week 12 (P = 0.002). Insulin sensitivity index decreased by 12.9 ± 7.6% (P = 0.02). Insulin sensitivity by homeostatic model assessment decreased by 12.8 ± 5.9% (P = 0.02). Fasting plasma insulin levels increased by 25.9 ± 9.3% (P = 0.04). Mean glycosylated hemoglobin also increased significantly (P < 0.001).
Conclusions: Short-term treatment with leuprolide and bicalutamide significantly increased fat mass and decreased insulin sensitivity in men with prostate cancer. These observations suggest that gonadotropin-releasing hormone agonists may increase the risk of diabetes mellitus and cardiovascular disease in older men.
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