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

Milena Braga-Basaria,  From the Department of Medicine, Division of Endocrinology and Metabolism, Johns Hopkins University School

Journal of Clinical Oncology, Vol 24, No 24 (August 20), 2006: pp. 3979-3983
Prostate cancer (PCa) is one of the most common cancers in men with an increasing incidence. Local surgery and/or radiation therapy are the preferred treatment modalities in men with locally confined PCa. However, in men with recurrent or metastatic PCa, androgen-deprivation therapy (ADT) is used. This is achieved either with bilateral orchiectomy or with gonadotropin-releasing hormone agonists. The resulting profound hypogonadism is responsible for adverse consequences such as an increase in body mass index (BMI), increased fat mass, reduced lean body mass (LBM) and muscle strength, osteoporosis, sexual dysfunction, and poor quality of life.  These adverse effects are a direct consequence of hypogonadism because they have significantly higher prevalence in men on ADT compared with men with PCa who underwent local surgery and/or radiation therapy and age-matched controls.2

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.

Epidemiologic evidence suggests that low testosterone levels in men predict the development of metabolic syndrome.  Because men with PCa undergoing ADT have castrate levels of testosterone, they provide an excellent model to study the association between hypogonadism and metabolic syndrome. We found that more than half of the men receiving long-term ADT had metabolic syndrome compared with one fifth of the men in the other two groups. Hyperglycemia and abdominal obesity were the major determinants of the higher prevalence of metabolic syndrome in this group. Because men in the three groups were of similar age and race, these observations suggest that hypogonadism in men on ADT may directly influence the development of metabolic syndrome.

In conclusion, more than half of the men with PCa undergoing long-term ADT met the criteria for metabolic syndrome. The metabolic syndrome in this population was independent of age and race and implicates hypogonadism as the likely cause. These complications of ADT

The metabolic syndrome is characterized by a group of metabolic risk factors in one person. They include:
  • Abdominal obesity (excessive fat tissue in and around the abdomen)
  • Atherogenic dyslipidemia (blood fat disorders — high triglycerides, low HDL cholesterol and high LDL cholesterol — that foster plaque buildups in artery walls)
  • Elevated blood pressure
  • Insulin resistance or glucose intolerance (the body can’t properly use insulin or blood sugar)
  • Prothrombotic state (e.g., high fibrinogen or plasminogen activator inhibitor–1 in the blood)
  • Proinflammatory state (e.g., elevated C-reactive protein in the blood)

People with the metabolic syndrome are at increased risk of coronary heart disease and other diseases related to plaque buildups in artery walls (e.g., stroke and peripheral vascular disease) and type 2 diabetes. The metabolic syndrome has become increasingly common in the United States. It’s estimated that over 50 million Americans have it.

The dominant underlying risk factors for this syndrome appear to be abdominal obesity and insulin resistance. Insulin resistance is a generalized metabolic disorder, in which the body can’t use insulin efficiently. This is why the metabolic syndrome is also called the insulin resistance syndrome.