This pilot study served to establish a model of acute hypogonadism in normal men, used to study the relative contributions of estrogen versus testosterone towards bone metabolism in men. The pilot study has been completed. Estrogen (E) deficiency associated with the menopause is the major cause of bone loss in aging women. However, men also lose significant amounts of bone with age, but they do not have the equivalent of menopause, and serum total testosterone (T) and E levels decline only marginally with age. In recent studies, however, we have shown that serum bioavailable T and E levels decline significantly with age in men adn correlate with bone mineral density (BMD). Moreover, in multivariate analyses, serum bioavailable E levels are better predictors of BMD in aging men than bioavailable T levels. This suggests that as in women, E may be more important than T for skeletal metabolism in men. As part of the renewal of our program project grant on osteoporosis """"""""Physiology of bone Metabolism in an Aging Population, P01 AG04875"""""""", we plan to directly test this hypothesis. In order to propose these studies, however, we need to perform a pilot study to establish an experimental model of acute hypogonadism in men using a synthetic analog of naturally occurring gonadotropin-releasing hormone (GnRH), Lupron, and to test whether under these experimental conditions these men have an increase in markers for bone resorption.
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