Neuroendocrine aspects of testosterone insufficiency with aging

As men age, there is a progressive decline in serum total testosterone: lev els and a more marked reduction in free, or bioavailable, testosterone leve ls. Aging is associated with a progressive increase in serum gonadotropin l evels, which may, in part, reflect gradual testicular dysfunction, However, multiple lines of evidence indicate that neuroendocrine control of reprodu ction is altered with advancing age. Aging is associated with loss of the l uteinizing hormone (LH) circadian rhythm with blunted early morning LH puls es. Studies utilizing pulse analysis and responsiveness to exogenous gonado tropin-releasing hormone (GnRH) suggest that aging is associated with decre ases in GnRH pulse amplitude leading to falls in LH pulse amplitude. There are age-associated alterations in LH pulse characteristics that may be due to primary changes in hypothalamic control of gonadotropin secretion or to alterations in hypothalamic-pituitary responsiveness to hypothalamic and go nadal factors, These alterations in LH pulse dynamics may lead further to d iminished testicular stimulation, Age-related changes in gonadotropin secre tion/regulation and testicular function may lead to a new homeostasis of te stosterone metabolism that includes reductions in-serum total testosterone and free testosterone levels.