This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, P. Y. Articles by Veldhuis, J. D. Search for Related Content PubMed PubMed Citation Articles by Liu, P. Y. Articles by Veldhuis, J. D. Related Collections Neuroendocrinology and Pituitary Male Endocrinology

Aging in Healthy Men Impairs Recombinant Human Luteinizing Hormone (LH)-Stimulated Testosterone Secretion Monitored under a Two-Day Intravenous Pulsatile LH Clamp

Endocrine Research Unit (P.Y.L., P.D.R., J.D.V.), Department of Internal Medicine, Mayo School of Graduate Medical Education, General Clinical Research Center, and Department of Internal Medicine (P.Y.T.), Division of Primary Care Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905; and Salem Veterans Affairs Hospital (A.I.), Salem, Virginia 24153

Address all correspondence and requests for reprints to: Johannes D. Veldhuis, Endocrine Research Unit, Department of Internal Medicine, Mayo School of Graduate Medical Education, General Clinical Research Center, Mayo Clinic, Rochester, Minnesota 55905. E-mail: veldhuis.johannes{at}mayo.edu.

Context: Testosterone (Te) depletion in aging men in principle could reflect deficits in the hypothalamus, pituitary gland, or testis. Available pharmacological studies of possible failure of Leydig cell steroidogenesis remain inconclusive.

Objective: The objective of the study was to assess Te secretion in older and young men in response to near physiological LH stimulation.

Intervention: Pulsatile iv infusion of recombinant human LH was administered for 2 d to stimulate Te secretion during suppression of endogenous LH concentrations with a potent selective GnRH receptor antagonist (ganirelix).

Subjects/Context: Healthy older (aged 60–73 yr, n = 8) and young (19–30 yr, n = 13) men were studied in an academic setting.

Measures: Pulsatile LH and Te concentrations on the second day of exogenous LH stimulation were measured.

Results: Serum ganirelix concentrations and infused LH pulse increments were similar by age. In contrast, older subjects manifested: 1) reduced mean Te concentrations (P = 0.016), Te peak heights (P = 0.014), increments (P = 0.010), summed areas (P < 0.013), and interpeak Te concentrations (P = 0.023); 2) decreased Te to LH concentration ratios (P = 0.002); 3) diminished LH-Te feed-forward synchrony (P = 0.020); and 4) a blunted amplitude (P = 0.036) and advanced phase (P = 0.013) of diurnal Te rhythms.

Conclusion: A novel regimen of pulsatile LH stimulation for 48 h during GnRH receptor blockade unmasks deficits in pulsatile, basal, synchronous, and nyctohemeral Te secretion in healthy older men. These findings do not exclude concomitant defects in GnRH outflow and/or Te-negative feedback in the aging male.

This article has been cited by other articles:

				S. Schlatt, C. R Pohl, J. Ehmcke, and S. Ramaswamy Age-Related Changes in Diurnal Rhythms and Levels of Gonadotropins, Testosterone, and Inhibin B in Male Rhesus Monkeys (Macaca mulatta) Biol Reprod, July 1, 2008; 79(1): 93 - 99. [Abstract] [Full Text] [PDF]

				P. Y. Takahashi, P. Votruba, M. Abu-Rub, K. Mielke, and J. D. Veldhuis Age Attenuates Testosterone Secretion Driven by Amplitude-Varying Pulses of Recombinant Human Luteinizing Hormone during Acute Gonadotrope Inhibition in Healthy Men J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3626 - 3632. [Abstract] [Full Text] [PDF]

				B. B Yeap, O. P Almeida, Z. Hyde, P. E Norman, S A P. Chubb, K. Jamrozik, and L. Flicker In men older than 70 years, total testosterone remains stable while free testosterone declines with age. The Health in Men Study Eur. J. Endocrinol., May 1, 2007; 156(5): 585 - 594. [Abstract] [Full Text] [PDF]