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 Veldhuis, J. D. Articles by Iranmanesh, A. Search for Related Content PubMed PubMed Citation Articles by Veldhuis, J. D. Articles by Iranmanesh, A. Related Collections Male Endocrinology

Short-Term Aromatase-Enzyme Blockade Unmasks Impaired Feedback Adaptations in Luteinizing Hormone and Testosterone Secretion in Older Men

Division of Endocrinology and Metabolism, Department of Internal Medicine, Mayo Medical and Graduate Schools of Medicine, General Clinical Research Center, Mayo Clinic, Rochester, Minnesota 55905; and Endocrine Section, Medical Service, Salem Veterans Affairs Medical Center, Salem, Virginia 24153

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

The mechanisms subserving hypoandrogenemia and relative hypogonadotropism in older men are not known. The present study tests the clinical hypothesis that aging impairs hypothalamopituitary adaptations to feedback withdrawal induced by antagonism of estrogen biosynthesis. To this end, we appraised gonadal axis responses to estrogen depletion induced by anastrozole (a potent and selective aromatase inhibitor) in nine older and 11 young men vs. placebo in 17 other older and eight young men. The study design comprised a prospectively randomized, double-blind, parallel-cohort intervention. To monitor LH release, blood was sampled every 10 min for 24 h; LH concentrations were assayed by two-site monoclonal immunoradiometric assay; pulsatile LH release quantitated by a model-free discrete peak-detection technique (Cluster); feedback-dependent orderliness of LH secretion via the approximate entropy statistic; and 24-h rhythmicity of LH concentrations by cosine analysis. At baseline, older men had comparable estradiol and testosterone but lower LH concentrations than young controls. Exposure to anastrozole reduced (24-h pooled) serum estradiol concentrations by 50% (P < 0.001) and elevated mean LH concentrations by 2.1-fold (P < 0.001) in both the young and older cohorts. However, older men failed to achieve young adult augmentation of the following: 1) total testosterone concentrations (P < 0.01) or molar testosterone to SHBG ratios (P < 0.01); 2) incremental LH pulse amplitude (P < 0.001) and LH peak area (P < 0.01); 3) mean LH pulse frequency (P = 0.0044); and 4) quantifiable irregularity (approximate entropy) of LH release patterns (P < 0.001). FSH concentrations became comparable in the two age cohorts.

In summary, administration of a potent and selective aromatase antagonist reduces estradiol and elevates mean LH concentrations equivalently in young and older men. The low estrogen-feedback state in elderly men unmasks diminished incremental LH pulse amplitude and area; absence of further acceleration of LH pulse frequency; impaired regulation of the orderliness of LH release; and reduced testosterone to SHBG ratios. Thus, aging alters expected hypothalamopituitary-gonadal adaptations to short-term partial estrogen depletion in healthy men.

This article has been cited by other articles:

				G. Raven, F. H. de Jong, J.-M. Kaufman, and W. de Ronde In Men, Peripheral Estradiol Levels Directly Reflect the Action of Estrogens at the Hypothalamo-Pituitary Level to Inhibit Gonadotropin Secretion J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3324 - 3328. [Abstract] [Full Text] [PDF]

				C K Hilleson-Gayne and J A Clapper Effects of decreased estradiol-17{beta} on the serum and anterior pituitary IGF-I system in pigs J. Endocrinol., December 1, 2005; 187(3): 369 - 378. [Abstract] [Full Text] [PDF]

				P. Y. Liu, P. Y. Takahashi, P. D. Roebuck, A. Iranmanesh, and J. D. Veldhuis Aging in Healthy Men Impairs Recombinant Human Luteinizing Hormone (LH)-Stimulated Testosterone Secretion Monitored under a Two-Day Intravenous Pulsatile LH Clamp J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5544 - 5550. [Abstract] [Full Text] [PDF]

				G. G. T'Sjoen, V. A. Giagulli, H. Delva, P. Crabbe, D. De Bacquer, and J.-M. Kaufman Comparative Assessment in Young and Elderly Men of the Gonadotropin Response to Aromatase Inhibition J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5717 - 5722. [Abstract] [Full Text] [PDF]