Older men manifest multifold synchrony disruption of reproductive neurohormone outflow

Under a working clinical hypothesis that aging putatively disrupts neuroend ocrine control mechanisms, here we test a specific corollary notion that tr ansitions in sleep stage, oscillations in nocturnal penile tumescence (NPT; a neurogenically organized signal), and the rates of instantaneous secreti on of LH and/or testosterone are jointly synchronous in healthy young, but not older, men. To this end, we evaluated 10 young (aged 21-31 yr) and 8 ol der (aged 65-74 yr) men by intensive overnight multisite monitoring, viz. s imultaneous electro-encephalogram and NPT recordings (every 30 s) and remot e blood sampling (every 2.5 min) to quantitate LH and testosterone release. Waveform-independent deconvolution and cross-correlation analyses of these neurohormone outflow measures revealed that healthy young men sustain four salient physiological linkages overnight: 1) a strong inverse (confirmator y) relationship between sleep stage and NPT activity, such that deeper slee p is accompanied by suppression of NPT; 2) consistent coupling between NPT and testosterone secretion, wherein heightened NPT activity respectively pr ecedes and follows increased testosterone secretion by 12.5-32.5 and 50-60 min; 3) evident synchrony between sleep stage and testosterone secretion, i n which testosterone secretion increases over a 30-min window (-2.5 to 25 m in) while sleep deepens; and 4) a close temporal linkage between instantane ous LH release and NPT oscillations, whereby LH secretion increases 55-62.5 min before and again 5-30 min after NPT declines. In contrast, older men m anifested global loss of expected young adult synchrony; namely 1) abolitio n of the inverse relationship between sleep stage and NPT, 2) decorrelation of NPT oscillations and testosterone secretion, 3) decoupling of testoster one release and deep sleep, and 4) abrogation of the Linkage between LH sec retion and penile detumescence. In summary, high intensity overnight monitoring of multiple reproductive ne uroendocrine outflow measures simultaneously in young men delineates promin ent neurophysiological coupling among sleep transitions and NPT activity, L H and testosterone secretion or NPT oscillations, and testosterone secretio n and deepening sleep stage. In contrast, healthy older men exhibit near-un iversal disruption of physiological young adult synchronicity. Thus, we con clude that male reproductive aging is marked by erosion of coordinate regul ation among sleep transitions, central nervous system-directed NPT activity , and hypothalamically driven episodic GnRH/LH (and thereby Leydig cell tes tosterone) secretion. Whether analogous multifold uncoupling of neurohormon e signals emerges in the course of reproductive aging in women or in nonhum an species is not yet known.