This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart 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 Pagotto, U. Articles by Pasquali, R. Search for Related Content PubMed PubMed Citation Articles by Pagotto, U. Articles by Pasquali, R.

Testosterone Replacement Therapy Restores Normal Ghrelin in Hypogonadal Men

Endocrine Unit, Department of Internal Medicine and Gastroenterology, and Center for Applied Biomedical Research (U.P., A.G., C.P., S.G., M.C., R.P.), Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy 40138; Department of Gastroenterology (B.O.), Innenstadt University Hospital, Munich, 80336 Germany; and German Institute of Human Nutrition (T.C., M.T.), 14558 Bergholz-Rehbrücke, Berlin, Germany

Address all correspondence and requests for reprints to: Renato Pasquali, M.D., Endocrinology Unit, Department of Internal Medicine and Gastroenterology, Sant’Orsola-Malpighi Hospital, Via Massarenti 9, 40138 Bologna, Italy. E-mail: rpasqual{at}almadns.unibo.it.

We recently described a connection between androgens and ghrelin in women affected by the polycystic ovary syndrome. To further investigate the interaction between sex steroids and ghrelin, we investigated circulating ghrelin levels in a group of hypogonadal men before and after therapeutic intervention aiming at normalization low testosterone (T) concentrations. Seven hypogonadal men were compared with nine overweight/moderately obese men matched for body mass index and body fat distribution parameters, as well as with 10 normal weight controls. Total and free T and plasma ghrelin levels were significantly lower in the hypogonadal men than in the control groups. Hypogonadal men also had a significantly higher insulin resistance state. Ghrelin levels were positively correlated with both total and free T concentrations. A significant correlation was also found between ghrelin and the anthropometric parameters and the insulin resistance indexes. However, in a multiple regression analysis in which a correction for all covariants was performed, only the relationship with total and free T persisted. After the 6-month replacement T therapy, ghrelin levels of hypogonadal patients increased and did not differ significantly in comparison with both control groups. The positive correlation between ghrelin and androgens still persisted after T replacement therapy, after adjusting for confounding variables. These data further indicate that sex hormones modulate circulating ghrelin concentrations in humans. This may be consistent with the concept that ghrelin may exert a relevant role in the endocrine network connecting the control of the reproductive system with the regulation of energy balance.

This work was supported by a grant awarded by the Fondazione Cassa di Risparmio (Bologna, Italy) and a grant of the Italian Ministry of University (Rome, COFIN, 2002, to U.P.).

Abbreviations: BMI, Body mass index; FFA, free fatty acids; HOMA, homeostasis model assessment; PCOS, polycystic ovary syndrome; QUICKI, quantitative insulin-sensitivity check index; T, testosterone; WHR, waist-to-hip ratio.

This article has been cited by other articles:

				M. Wald, M. Miner, and A. D. Seftel State of the Art Reviews: Male Menopause: Fact or Fiction? American Journal of Lifestyle Medicine, April 1, 2008; 2(2): 132 - 141. [Abstract] [PDF]

				M. Kluge, P. Schussler, M. Uhr, A. Yassouridis, and A. Steiger Ghrelin Suppresses Secretion of Luteinizing Hormone in Humans J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3202 - 3205. [Abstract] [Full Text] [PDF]

				M. C Garcia, M. Lopez, C. V Alvarez, F. Casanueva, M. Tena-Sempere, and C. Dieguez Role of ghrelin in reproduction Reproduction, March 1, 2007; 133(3): 531 - 540. [Abstract] [Full Text] [PDF]

				K. J. Mackelvie, G. S. Meneilly, D. Elahi, A. C. K. Wong, S. I. Barr, and J.-P. Chanoine Regulation of Appetite in Lean and Obese Adolescents after Exercise: Role of Acylated and Desacyl Ghrelin J. Clin. Endocrinol. Metab., February 1, 2007; 92(2): 648 - 654. [Abstract] [Full Text] [PDF]

				E. L. Ding, Y. Song, V. S. Malik, and S. Liu Sex Differences of Endogenous Sex Hormones and Risk of Type 2 Diabetes: A Systematic Review and Meta-analysis JAMA, March 15, 2006; 295(11): 1288 - 1299. [Abstract] [Full Text] [PDF]

				Y. Lebenthal, G. Gat-Yablonski, B. Shtaif, A. Padoa, M. Phillip, and L. Lazar Effect of Sex Hormone Administration on Circulating Ghrelin Levels in Peripubertal Children J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 328 - 331. [Abstract] [Full Text] [PDF]

				R. Giordano, A. Picu, U. Pagotto, R. De Iasio, L. Bonelli, F. Prodam, F. Broglio, L. Marafetti, R. Pasquali, M. Maccario, et al. The negative association between total ghrelin levels, body mass and insulin secretion is lost in hypercortisolemic patients with Cushing's disease Eur. J. Endocrinol., October 1, 2005; 153(4): 535 - 543. [Abstract] [Full Text] [PDF]

				J. M. Garcia, M. Garcia-Touza, R. A. Hijazi, G. Taffet, D. Epner, D. Mann, R. G. Smith, G. R. Cunningham, and M. Marcelli Active Ghrelin Levels and Active to Total Ghrelin Ratio in Cancer-Induced Cachexia J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2920 - 2926. [Abstract] [Full Text] [PDF]

				E. Kellokoski, S. M. Poykko, A. H. Karjalainen, O. Ukkola, J. Heikkinen, Y. A. Kesaniemi, and S. Horkko Estrogen Replacement Therapy Increases Plasma Ghrelin Levels J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2954 - 2963. [Abstract] [Full Text] [PDF]

				S. Grinspoon, K. K. Miller, D. B. Herzog, K. A. Grieco, and A. Klibanski Effects of Estrogen and Recombinant Human Insulin-Like Growth Factor-I on Ghrelin Secretion in Severe Undernutrition J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3988 - 3993. [Abstract] [Full Text] [PDF]

				M. S. Racine, K. V. Symons, C. M. Foster, and A. L. Barkan Augmentation of Growth Hormone Secretion after Testosterone Treatment in Boys with Constitutional Delay of Growth and Adolescence: Evidence against an Increase in Hypothalamic Secretion of Growth Hormone-Releasing Hormone J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3326 - 3331. [Abstract] [Full Text] [PDF]

				G. Marchesini, U. Pagotto, E. Bugianesi, R. De Iasio, R. Manini, E. Vanni, R. Pasquali, N. Melchionda, and M. Rizzetto Low Ghrelin Concentrations in Nonalcoholic Fatty Liver Disease Are Related to Insulin Resistance J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 5674 - 5679. [Abstract] [Full Text] [PDF]