Older males secrete luteinizing hormone and testosterone more irregularly, and jointly more asynchronously, than younger males

Steven M. Pincus, Thomas Mulligan, Ali Iranmanesh, Sylvia Gheorghiu, Michael Godschalk, Johannes D. Veldhuis

Research output: Contribution to journalArticlepeer-review

315 Scopus citations


New statistical perspectives on the secretory patterns of both luteinizing hormone (LH) and testosterone (T) may prove useful in further understanding the aging process, and possibly ultimately in improving the diagnosis and treatment of spermatogenetic failure and loss of sexual interest. We examined serum concentration time-series for LH and T in 14 young (21-34 years of age) and 11 aged (62-74 years of age) healthy men. Fur each subject, blood samples were obtained at 2.5-min intervals during a sleep period, with an average sampling duration of 7 hr. For each of LH and T, we used the model-independent statistic approximate entropy (ApEn) to quantify the irregularity of the serum concentration time-series; to quantify, joint LH-T secretory asynchrony, we employed the recently introduced cross-ApEn. Although mean (and SD) LH and T concentrations were indistinguishable in the two age groups (P > 0.25), for LH, aged subjects had greater ApEn values (1.525 ± 0.221) than younger individuals (1.207 ± 0.252), P < 0.003, indicating more irregular secretion in the older cohort. Fur T, aged subjects also had greater ApEn values (1.622 ± 0.120) than younger counterparts (1.384 ± 0.228), P < 0.004. In young, but not older men, ApEn(T) significantly exceeded ApEn (LH), P < 0.02. Aged subjects had greater cross-ApEn values (1.961 ± 0.121) than younger subjects (1.574 ± 0.249), P < 10-4, with nearly 100% sensitivity and specificity, indicating greater LH-T asynchrony in the older group. In conjunction with previous findings of greater irregularity of growth hormone release with increasing age, we propose that increased secretory irregularity with advancing age may be a widespread hormonal phenomenon. Finally, theoretically, we clarify the need for quantifications such as ApEn and cross-ApEn via a study of a 'variable lag' pulsatile process, and empirically note the potential wide applicability of cross-ApEn to quantify asynchrony in interconnected (hormonal) networks.

Original languageEnglish (US)
Pages (from-to)14100-14105
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number24
StatePublished - Nov 26 1996


  • aging
  • approximate entropy
  • pulsatility
  • reproduction
  • variable lag process

ASJC Scopus subject areas

  • General


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