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Updated: Jul 6, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Metabolic changes during gonadotropin-releasing hormone agonist therapy for prostate cancer: differences from the
Matthew R Smith1, Hang Lee, Francis McGovern
1Department of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. smith.matthew@mgh.harvard.edu
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.
Insights
Gonadotropin-releasing hormone (GnRH) agonists used in prostate cancer treatment significantly increase fat mass and alter lipid profiles. These changes differ from metabolic syndrome criteria, suggesting a distinct impact on male patients.
Area of Science:
- Endocrinology
- Oncology
- Metabolic Health
Background:
- Gonadotropin-releasing hormone (GnRH) agonists are used to treat prostate cancer.
- These agonists can induce metabolic changes similar to metabolic syndrome, including increased fat mass and decreased insulin sensitivity.
- The full spectrum of metabolic effects of GnRH agonists in prostate cancer patients is not well understood.
Purpose of the Study:
- To investigate the comprehensive effects of GnRH agonists on metabolic parameters in men with prostate cancer.
- To compare the observed metabolic changes with the established criteria for metabolic syndrome.
Main Methods:
- An open-label prospective study involving 26 men with prostate cancer treated with leuprolide for 12 months.
- Evaluated changes in blood pressure, body composition (fat mass, lean body mass), lipid profiles, adipocytokines, and C-reactive protein.
Main Results:
- Significant increases in weight, body mass index, waist circumference, and total abdominal fat mass (primarily subcutaneous) were observed.
- Lean body mass decreased, while high-density lipoprotein (HDL) cholesterol and adiponectin levels significantly increased.
- No significant changes were noted in waist-to-hip ratio, blood pressure, resistin, or C-reactive protein levels.
Conclusions:
- The metabolic effects of GnRH agonists in prostate cancer patients do not fully align with the definition of metabolic syndrome.
- GnRH agonists uniquely increase subcutaneous fat, HDL cholesterol, and adiponectin while not significantly altering waist-to-hip ratio or blood pressure.
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