Novel modalities for appraising individual and coordinate pulsatile hormone secretion: The paradigm of luteinizing hormone and testosterone release in the aging male

To quantify aging- and disease-associated alterations in the integrative and interactive components of a pulsatile neuroendocrine axis, novel biomathematical strategies are required. Here, I illustrate as an investigative paradigm otherwise subtle aging-dependent disturbances of the gonadotropin-releasing-hormone (GnRH)-luteinizing hormone (LH)-testosterone feedback axis in men, in whom strong age-related contrasts become evident via any of four strategies applied alone or in combination: (1) intensified blood sampling schedules to capture the temporal structure of episodic hormone (LH and testosterone) secretion; (2) deconvolution analysis as a technique to quantify underlying pituitary and gonadal hormone secretory rates from the observed plasma hormone concentration profiles; (3) approximate entropy as a scale- and model-independent measure of the serial regularity or orderliness of the hormone release process over time; and (4) cross-approximate entropy (cross-ApEn) to quantify joint asynchrony between two concurrent pulse trains without confounding by variable lag. These new methodologies are introduced and reviewed briefly, a stochastic differential equation feedback construct alluded to, and the resultant insights into distinct alterations of the aging male gonadotropic axis highlighted. In summary, the new experimental strategies of intensified venous sampling, multiparameter deconvolution analysis, approximate entropy, and cross-approximate entropy unveil new mechanisms underlying dynamic neuroendocrine-axis activity, as exemplified by aging-associated disruption of the human male reproductive axis.