Intermittent signal exchange serves to encode repeated incremental adjustments among central-neural centers and the ensemble of glands comprising any given axis. Interglandular communication proceeds dynamically via pulsatile and basal modes of hormone release, deterministic (dose-responsive) interfaces, and apparently stochastic (randomly varying) processes. Physiological investigations of the time-dependent control of neurohormone secretion and action depend upon valid reconstruction of such interactive signaling. Recent technical and experimental advances afford new and fundamental insights into such composite mechanisms that maintain precise homeostasis in health, and show susceptibility to disruption in disease. Underlying concepts are becoming more readily understandable intuitively without full rehearsal of detailed analytical and statistical facets that undergird computer-assisted methods. Accordingly, the present overview highlights core precepts that guide the implementation of sensitive, specific and utilitarian technologies to quantitate neuroendocrine adaptations in pathophysiology. The aging male gonadal axis provides a well studied paradigmatic platform to illustrate the formulation and implementation of analytical strategies in diverse systems.