Androgens, diabetes and prostate cancer

    1. Gary Wittert1
    1. Department of Medicine Austin Health, University of Melbourne, Studley Road, Heidelberg, Victoria 3084, Australia
      1Discipline of Medicine, Royal Adelaide Hospital, University of Adelaide, Level 6, Eleanor Harrald Building, Adelaide, South Australia 5000, Australia
    1. (Correspondence should be addressed to G Wittert; Email: gary.wittert{at}


    Metabolic disorders such as diabetes, obesity and the metabolic syndrome have been shown to modulate prostate cancer (PCa) risk and aggressiveness in population-based and experimental studies. While associations between these conditions are modest and complex, two consistent findings have emerged. First, there is observational evidence that obesity and associated insulin excess are linked to increased PCa aggressiveness and worse outcomes. Secondly and somewhat paradoxically, long-standing diabetes may be protective against PCa development. This apparent paradox may be due to the fact that long-standing diabetes is associated with insulin depletion and decreased IGF1 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 PCa development and progression. Metabolic factors and androgens may promote prostate carcinogenesis via multiple mechanisms including inflammation, adipokine action, fatty acid metabolism and IGF signalling. Moreover, androgen deprivation, given to men with PCa, 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 PCa risk and management.

    • Revision received 11 April 2012
    • Accepted 17 April 2012
    • Made available online as an Accepted Preprint 18 April 2012
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