The human hypothalamic-pituitary-testicular axis maintains testosterone production and spermatogenesis through an intricate feedforward and feedback system involving the intermittent exchange of neurohormonal signals. The chief components of this ensemble are hypothalamic gonadotropin-releasing hormone, pituitary luteinizing hormone, and testicular sex steroids (testosterone and estradiol). Epidemiological data and clinical experiments jointly indicate that healthy older men have lower bioavailable and free testosterone concentrations, higher sex hormone-binding globulin concentrations, and decreased daily testosterone secretion rates, compared with young individuals. Aging also disrupts quantifiable synchrony among sleep stage, the secretion of luteinizing hormone, testosterone, prolactin, and follicle-stimulating hormone, and the oscillations in nocturnal penile tumescence, denoting erosion of coordinate central neurohormonal outflow. How age affects spermatogenesis in healthy populations is not known. This article summarizes how aging in men is marked by multisite regulatory failure within the gonadal axis.
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