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Insulin Sensitivity during Combined Androgen Blockade for Prostate Cancer

Division of Hematology-Oncology (M.R.S.), Mallinckrodt General Clinical Research Center (H.L.), and Diabetes Center (D.M.N.), Massachusetts General Hospital, Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: Matthew R. Smith, M.D., Ph.D., Massachusetts General Hospital, Cox 640, 100 Blossom Street, Boston, Massachusetts 02114. E-mail: smith.matthew{at}mgh.harvard.edu.

Context: GnRH agonists markedly increase fat mass in men with prostate cancer, but little is known about the effects of treatment on insulin sensitivity.

Objective: The objective of the study was to assess the effects of short-term GnRH agonist treatment on insulin sensitivity.

Design: This was a prospective 12-wk study.

Setting: The study was conducted at a general clinical research center.

Patients or Other Participants: We studied 25 men with locally advanced or recurrent prostate cancer, no radiographic evidence of metastases, no history of diabetes mellitus, and no evidence of diabetes mellitus at baseline visit.

Intervention: Leuprolide depot and bicalutamide were used in the study.

Main Outcome Measures: Oral glucose tolerance tests and body composition assessment by dual-energy x-ray absorptiometry were performed at baseline and wk 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 wk 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 GnRH agonists may increase the risk of diabetes mellitus and cardiovascular disease in older men.

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