Abstract

Metabolic disorders such as diabetes, obesity and the metabolic syndrome have been shown to modulate prostate cancer risk and aggressiveness in population-based and experimental studies. While associations between these conditions are modest and complex, two consistent findings have emerged. Firstly, there is observational evidence that obesity and associated insulin excess are linked to increased prostate cancer aggressiveness and worse outcomes. Secondly and somewhat paradoxically, long-standing diabetes may be protective against prostate cancer development. This apparent paradox may be due to the fact that long-standing diabetes is associated with insulin depletion and decreased insulin like growth factor 1 signalling. Men with obesity or diabetes have moderate reductions in their androgen levels. The interconnectedness of metabolic and androgen status complicates the dissection of the individual roles of these factors in prostate cancer development and progression. Metabolic factors and androgens may promote prostate carcinogenesis via multiple mechanisms including inflammation, adipokine action, fatty acid metabolism and insulin growth factor signalling. Moreover androgen deprivation, given to men with prostate cancer, has adverse metabolic consequences that need to be taken into account when estimating the risk benefit ratio of this therapy. In this review, we will discuss the current epidemiological and mechanistic evidence regarding the interactions between metabolic conditions, sex steroids and prostate cancer risk and management.