Erosion of endogenous testosterone-driven negative feedback on pulsatile luteinizing hormone secretion in healthy aging men

Abstract

The present study tests the intuition that successful aging in men is marked by: 1) impaired feedforward by endogenous LH concentrations (con) of testosterone (Te) secretion (sec); and/or 2) attenuated feedback by unmanipulated Te con of LH sec. The goal was to assess both implicit linkages analytically without disrupting normal pathway coupling. This strategy required: 1) assay of paired LH and Te con sampled every 10 min for 24 h in 13 older (O) (ages 60-78 yr) and 13 young (Y) (ages 18-30 yr) men; 2) deconvolution-based estimation of LH and Te sec rates; 3) lag-specific cross-correlation analyses of the relationships between LH and Te con and sec; and 4) statistical contrasts by age stratum. Salient outcomes were: 1) O and Y men maintain comparable LH con drive of Te sec, viz maximal r = +0.51 and r = +0.52, respectively, at an optimal time lag of 50 min (both P < 0.001 against random LH and Te associations); 2) elderly subjects exhibit reduced Te con inhibition of LH sec [minimal r = -0.008 (O) vs. r = -0.10 (Y), P < 0.01 at a time lag of 40 min]; 3) mean (24-h) LH con do not differ by age; and 4) molar Te/sex hormone-binding globulin con are lower in the elderly than in Y individuals (P < 0.01). In conclusion, noninvasive analyses predict that attenuation of endogenous Te feedback restraint on the hypothalamo-pituitary unit may be an early biological marker of adaptive changes in the GnRH-LH-Te ensemble axis in the healthy O male.