Effects Of Androgen Deficiency on Glucose Homeostasis

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Recently, in conjunction with collaborators at Johns Hopkins, we have been studying the effects of hypogonadism on insulin resistance and the metabolic syndrome. Patients with prostate cancer who undergo androgen deprivation therapy as part of their treatment become not only insulin resistant but more than 50% also develop the metabolic syndrome. This clearly puts them at risk for strokes and heart attacks and therefore the treatment for the prostate cancer will increase their mortality and morbidity. This is a new and evolving field of interest and data is just now appearing from other groups confirming our findings. We are currently divising a protocol to carry out a prospective study of prostate cancer patients (some of whom will have cancer-removal surgery of the prostate, some of who will receive androgen deprivation therapy and some of whom will receive both) and follow them longitudinally. We wish to determine, 1) when and why insulin resistance manifests itself and in which group, 2) introduce therapy in a subpopulation to lessen insulin resistance ( metformin, pioglitazone, exendin-4, or GLP-1) and follow outcomes, 3) quantify the degree of insulin resistance using glucose clamps, and, 4) attempt to define the mechanism of action by which androgen deprivation leads to insulin resistance. If androgen therapy continues to be a treatment for prostate cancer, proper management strategies of androgen deprived patients will be required.