Amplified nocturnal luteinizing hormone (LH) secretory burst frequency with selective attenuation of pulsatile (but not basal) testosterone secretion in healthy aged men: Possible Leydig cell desensitization to endogenous LH signaling—A clinical research center study

The specific mechanisms underlying the relative hypogonadism of aging remain to be elucidated fully. We used frequent venous sampling (every 2.5 min), sensitive and specific LH and testosterone assays, and deconvolution analysis of the endocrine time series to delineate the differences between healthy young (n = 10, age 21-34 yr) and aged (n = 8, age 62-74 yr) men in the nocturnal secretion of LH and testosterone and their half-lives. We found that elderly men vs. young men had more frequent bursts of LH secretion (1.4 vs. 0.9/h, P = 0.003), less testosterone secreted per testosterone secretory burst (9.2 vs. 17.0 nmol/L, P = 0.021), and less testosterone secreted per hour (10.7 vs. 25.0 nmol/L.h, P = 0.05). As the frequency of nocturnal LH secretory bursts increased, the frequency of testosterone bursts decreased (r = -0.746, P = 0.034). We conclude that healthy aging is associated with diminished nocturnal testosterone production attributable to 1) a decrement in the mass of testosterone released per burst and 2) an inadequate response by the pituitary gland to enhance testosterone production via an accelerated LH secretory pulse frequency. We speculate that this may reflect a partial desensitization of Leydig cells to LH.