Metabolic changes during gonadotropin-releasing hormone agonist therapy for prostate cancer: differences from the classic metabolic syndrome

Abstract

Background: In men with prostate cancer, gonadotropin-releasing hormone (GnRH) agonists increase fat mass, decrease insulin sensitivity, and increase triglycerides, features that are shared with metabolic syndrome. To the authors' knowledge, however, less is known regarding the effects of GnRH agonists on other attributes of the metabolic syndrome.

Methods: In an open-label prospective study, 26 men with recurrent or locally advanced prostate cancer were treated with leuprolide for 12 months. Outcomes included changes in blood pressure, body composition, lipids, adipocytokines, and C-reactive protein.

Results: The mean weight, body mass index, and waist circumference increased significantly from baseline to Month 12 (P < .001 for each comparison). Fat mass increased by 11.2% +/- 1.5% (P < .001) and the percentage lean body mass decreased by 3.6% +/- 0.5% (P < .001). The total abdominal fat area increased by 16.5% +/- 2.6% (P < .001), with the accumulation of subcutaneous fat accounting for 94% of the observed increase. The waist-to-hip ratio and blood pressure did not change significantly. Serum high-density lipoprotein (HDL) cholesterol concentrations increased significantly (P = .002). Serum adiponectin levels increased by 36.4 +/- 5.9% from baseline to Month 3 and remained significantly elevated through Month 12 (P < .001). Resistin and C-reactive protein levels did not change significantly.

Conclusions: The term metabolic syndrome does not appear to adequately describe the effects of GnRH agonists in men with prostate cancer. In contrast to the metabolic syndrome, GnRH agonists increase subcutaneous fat mass, HDL cholesterol, and adiponectin, and do not alter the waist-to-hip ratio, blood pressure, or C-reactive protein level.

(c) 2008 American Cancer Society.

Figures

FIGURE 1

(A) Mean (± standard error) changes in weight, waist circumference, and waist-to-hip ratio and (B) lean body mass and fat mass during leuprolide therapy for prostate cancer. P values were for comparison of Month 12 with baseline.

FIGURE 2

(A) Mean (± standard error) changes in lipids and (B) adipocytokines during leuprolide therapy for prostate cancer. P values were derived from repeated-measures analysis of covariance. LDL indicates low-density lipoprotein; HDL, high-density lipoprotein.

FIGURE 3

Mean (± standard error) changes in C-reactive protein during leuprolide therapy for prostate cancer. The P value was derived from repeated-measures analysis of covariance.