MP-16.06 Changes in Body Composition, Development of Metabolic Syndrome (X) and Pathological Fractures in Men on Long-Term Androgen Deprivation Therapy

Abstract Context: Prostate cancer (PCa) is the most common cancer in men. Androgen-deprivation therapy (ADT) is generally employed in the treatment of locally advanced and metastatic PCa. Although its use as an adjuvant therapy has resulted in improved survival in some patients, ADT has negative consequences. Complications like osteoporosis, sexual dysfunction, gynecomastia, and adverse body composition are well known. Recently, metabolic complications like insulin resistance, diabetes, dyslipidemia, and metabolic syndrome have emerged, which may be responsible for the increased cardiovascular mortality in this population. Evidence Acquisition: A MEDLINE search was conducted for articles published over the last 20 yr based on the key words androgen deprivation therapy AND insulin resistance, hyperglycemia, diabetes, dyslipidemia, metabolic syndrome, and cardiovascular disease. Relevant studies in non-PCa populations evaluating the association between testosterone and metabolism were also reviewed and briefly mentioned where relevant. Evidence Synthesis: Prospective studies evaluating early (3–6 months) metabolic changes of ADT show development of hyperinsulinemia; however, glucose levels remain normal. Cross-sectional studies of men undergoing long-term (≥12 months) ADT reveal higher prevalence of diabetes and metabolic syndrome compared with controls. Furthermore, men undergoing ADT also experience higher cardiovascular mortality. Conclusion: Long-term prospective studies of ADT are needed to determine the timing of onset of these metabolic complications and to investigate the mechanism behind them. In the meantime, we recommend baseline and serial screening for fasting glucose, lipids, and other cardiovascular risk factors in men receiving ADT. Glucose tolerance tests and cardiac evaluation may be required in selected cases.

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Obesity and Hypertriglyceridemia Produce Cognitive Impairment

Endocrinology ◽

10.1210/en.2007-1722 ◽

2008 ◽

Vol 149 (5) ◽

pp. 2628-2636 ◽

Cited By ~ 233

Author(s):

Susan A. Farr ◽

Kelvin A. Yamada ◽

D. Allan Butterfield ◽

H. Mohammad Abdul ◽

Lin Xu ◽

...

Keyword(s):

Oxidative Stress ◽

Metabolic Syndrome ◽

Cognitive Impairment ◽

Long Term Potentiation ◽

Metabolic Syndrome X ◽

Leptin Resistance ◽

Syndrome X ◽

Obese Mice ◽

The Brain

Obesity is associated with cognitive impairments. Long-term mechanisms for this association include consequences of hyperglycemia, dyslipidemia, or other factors comprising metabolic syndrome X. We found that hypertriglyceridemia, the main dyslipidemia of metabolic syndrome X, is in part responsible for the leptin resistance seen in obesity. Here we determined whether triglycerides have an immediate and direct effect on cognition. Obese mice showed impaired acquisition in three different cognitive paradigms: the active avoidance T-maze, the Morris water maze, and a food reward lever press. These impairments were not attributable to differences in foot shock sensitivity, swim speed, swimming distance, or voluntary milk consumption. Impaired cognition in obese mice was improved by selectively lowering triglycerides with gemfibrozil. Injection into the brain of the triglyceride triolein, but not of the free fatty acid palmitate, impaired acquisition in normal body weight mice. Triolein or milk (97% of fats are triglycerides), but not skim milk (no triglycerides), impaired maintenance of the N-methyl-d-aspartate component of the hippocampal long-term synaptic potential. Measures of oxidative stress in whole brain were reduced by gemfibrozil. We conclude that triglycerides mediate cognitive impairment as seen in obesity, possibly by impairing maintenance of the N-methyl-d-aspartate component of hippocampal long-term potentiation, and that lowering triglycerides can reverse the cognitive impairment and improve oxidative stress in the brain.

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Metabolic Syndrome in Men With Prostate Cancer Undergoing Long-Term Androgen-Deprivation Therapy

Journal of Clinical Oncology ◽

10.1200/jco.2006.05.9741 ◽

2006 ◽

Vol 24 (24) ◽

pp. 3979-3983 ◽

Cited By ~ 373

Author(s):

Milena Braga-Basaria ◽

Adrian S. Dobs ◽

Denis C. Muller ◽

Michael A. Carducci ◽

Majnu John ◽

...

Keyword(s):

Prostate Cancer ◽

Metabolic Syndrome ◽

Androgen Deprivation Therapy ◽

Abdominal Obesity ◽

Local Treatment ◽

Androgen Deprivation ◽

Control Group ◽

Male Hypogonadism ◽

And Control

Purpose Prostate cancer (PCa) is one of the most common cancers in men. Men with recurrent or metastatic PCa are treated with androgen-deprivation therapy (ADT), resulting in profound hypogonadism. Because male hypogonadism is a risk factor for metabolic syndrome and men with PCa have high cardiovascular mortality, we evaluated the prevalence of metabolic syndrome in men undergoing long-term ADT. Patients and Methods This was a cross-sectional study. We evaluated 58 men, including 20 with PCa undergoing ADT for at least 12 months (ADT group), 18 age-matched men with nonmetastatic PCa who had received local treatment and were recently found to have an increasing prostate-specific antigen (non-ADT group), and 20 age-matched controls (control group). Men in the non-ADT and control groups were eugonadal. Metabolic syndrome was defined according to the Adult Treatment Panel III criteria. Results Mean age was similar among the groups. Men on ADT had significantly higher body mass index and lower total and free testosterone levels. The prevalence of metabolic syndrome was higher in the ADT group compared with the non-ADT (P < .01) and control (P = .03) groups. Among the components of metabolic syndrome, men on ADT had a higher prevalence of abdominal obesity and hyperglycemia. Androgen-deprived men also had elevated triglycerides compared with controls (P = .02). The prevalence of hypertension and low high-density lipoprotein levels were similar. Conclusion These data suggest that metabolic syndrome was present in more than 50% of the men undergoing long-term ADT, predisposing them to higher cardiovascular risk. Abdominal obesity and hyperglycemia were responsible for this higher prevalence. We recommend prospective studies to further delineate this association.

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