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 Isidori, A. M. Articles by Fabbri, A. Search for Related Content PubMed PubMed Citation Articles by Isidori, A. M. Articles by Fabbri, A.

Leptin and Androgens in Male Obesity: Evidence for Leptin Contribution to Reduced Androgen Levels¹

Cattedra di Andrologia, Dipartimento di Fisiopatologia Medica, Università La Sapienza (A.M.I., M.C., A.I., A.F.), Italian National Research Centers on Aging (F.S.), Cattedra di Endocrinologia, Universita’ Tor Vergata (C.M., G.F.), 00100 Rome, Italy; and the Department of Endocrinology (A.F.), St. Bartholomew’s Hospital, ECIA 7BE London, United Kingdom

Address correspondence and requests for reprints to: Andrea Fabbri, M.D., Ph.D., Cattedra di Andrologia, Dipartimento di Fisiopatologia Medica, Università di Roma La Sapienza, 00161-Rome, Italy. E-mail: a.fabbri{at}caspur.it

Leptin circulates in plasma at concentrations that parallel the amount of fat reserves. In obese males, androgen levels decline in proportion to the degree of obesity. Recently, we have shown that in rodent Leydig cells leptin inhibits hCG-stimulated testosterone (T) production via a functional leptin receptor isoform; others have found that leptin inhibits basal and hCG-induced T secretion by testis from adult rats. In this study, we further investigated the relationship linking leptin and androgens in men. Basal and hCG-stimulated leptin and sex hormone levels were studied in a large group of men ranging from normal weight to very obese (body mass index, 21.8–55.7). Initial cross-sectional studies showed that circulating leptin and fat mass (FM) were inversely related with total and free T (r = -0.51 and r = -0.38, P < 0.01 and P < 0.05, respectively). Multiple regression analysis indicated that the correlation between leptin or FM and T was not lost after controlling for SHBG and/or LH and/or estradiol (E₂) levels and that leptin was the best hormonal predictor of the lower androgen levels in obesity. Dynamic studies showed that in obese men the area under the curve of T and free T to LH/hCG stimulation (5000 IU im) was 30–40% lower than in controls and inversely correlated with leptin levels (r = -0.45 and r = -0.40, P < 0.01 and P < 0.05, respectively). Also, LH/hCG-stimulation caused higher increases in 17-OH-progesterone to T ratio in obese men than in controls, whereas no differences were observed between groups either in stimulated E₂ levels or in the E₂/T ratio. In all subjects, the percentage increases from baseline in the 17-OH-progesterone to T ratio were directly correlated with leptin levels or FM (r = 0.40 and r = 0.45, P < 0.01), but not with E₂ or other hormonal variables. In conclusion, our studies, together with previous in vitro findings, indicate that excess of circulating leptin may be an important contributor to the development of reduced androgens in male obesity.

This article has been cited by other articles:

				G. I Hackett Review: Androgens, erectile dysfunction and cardiovascular risk in type 2 diabetes The British Journal of Diabetes & Vascular Disease, September 1, 2009; 9(5): 214 - 217. [Abstract] [PDF]

				V. J Kay and C. L R Barratt Male obesity: impact on fertility The British Journal of Diabetes & Vascular Disease, September 1, 2009; 9(5): 237 - 241. [Abstract] [PDF]

				B. Kornmann, E. Nieschlag, M. Zitzmann, J. Gromoll, M. Simoni, and S. Von Eckardstein Body Fat Content and Testosterone Pharmacokinetics Determine Gonadotropin Suppression After Intramuscular Injections of Testosterone Preparations in Normal Men J Androl, September 1, 2009; 30(5): 602 - 613. [Abstract] [Full Text] [PDF]

				A. T. Guay The Emerging Link Between Hypogonadism and Metabolic Syndrome J Androl, July 1, 2009; 30(4): 370 - 376. [Abstract] [Full Text] [PDF]

				A. M. Traish, A. Guay, R. Feeley, and F. Saad The Dark Side of Testosterone Deficiency: I. Metabolic Syndrome and Erectile Dysfunction J Androl, January 1, 2009; 30(1): 10 - 22. [Abstract] [Full Text] [PDF]

				A. M. Traish, F. Saad, and A. Guay The Dark Side of Testosterone Deficiency: II. Type 2 Diabetes and Insulin Resistance J Androl, January 1, 2009; 30(1): 23 - 32. [Abstract] [Full Text] [PDF]

				S. Loves, J. Ruinemans-Koerts, and H. de Boer Letrozole once a week normalizes serum testosterone in obesity-related male hypogonadism Eur. J. Endocrinol., May 1, 2008; 158(5): 741 - 747. [Abstract] [Full Text] [PDF]

				T. L. Nielsen, C. Hagen, K. Wraae, K. Brixen, P. H. Petersen, E. Haug, R. Larsen, and M. Andersen Visceral and Subcutaneous Adipose Tissue Assessed by Magnetic Resonance Imaging in Relation to Circulating Androgens, Sex Hormone-Binding Globulin, and Luteinizing Hormone in Young Men J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2696 - 2705. [Abstract] [Full Text] [PDF]

				D Kapoor, S Clarke, R Stanworth, K S Channer, and T H Jones The effect of testosterone replacement therapy on adipocytokines and C-reactive protein in hypogonadal men with type 2 diabetes Eur. J. Endocrinol., May 1, 2007; 156(5): 595 - 602. [Abstract] [Full Text] [PDF]

				D. Kapoor, H. Aldred, S. Clark, K. S. Channer, and T. H. Jones Clinical and Biochemical Assessment of Hypogonadism in Men With Type 2 Diabetes: Correlations with bioavailable testosterone and visceral adiposity Diabetes Care, April 1, 2007; 30(4): 911 - 917. [Abstract] [Full Text] [PDF]

				D Kapoor, E Goodwin, K S Channer, and T H Jones Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur. J. Endocrinol., June 1, 2006; 154(6): 899 - 906. [Abstract] [Full Text] [PDF]

				N. Pitteloud, M. Hardin, A. A. Dwyer, E. Valassi, M. Yialamas, D. Elahi, and F. J. Hayes Increasing Insulin Resistance Is Associated with a Decrease in Leydig Cell Testosterone Secretion in Men J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2636 - 2641. [Abstract] [Full Text] [PDF]

				E. Giovannucci, E. B. Rimm, Y. Liu, M. Leitzmann, K. Wu, M. J. Stampfer, and W. C. Willett Body Mass Index and Risk of Prostate Cancer in U.S. Health Professionals J Natl Cancer Inst, August 20, 2003; 95(16): 1240 - 1244. [Abstract] [Full Text] [PDF]

				M. Caprio, E. Fabbrini, G. Ricci, S. Basciani, L. Gnessi, M. Arizzi, A. R. Carta, M. U. De Martino, A. M. Isidori, G. V. Frajese, et al. Ontogenesis of Leptin Receptor in Rat Leydig Cells Biol Reprod, April 1, 2003; 68(4): 1199 - 1207. [Abstract] [Full Text] [PDF]

				O. Ukkola, T. Rankinen, J. Gagnon, A. S. Leon, J. S. Skinner, J. H. Wilmore, D. C. Rao, and C. Bouchard A Genome-Wide Linkage Scan for Steroids and SHBG Levels in Black and White Families: The HERITAGE Family Study J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3708 - 3720. [Abstract] [Full Text] [PDF]

				A. Polito, A. Fabbri, A. Ferro-Luzzi, M. Cuzzolaro, L. Censi, D. Ciarapica, E. Fabbrini, and D. Giannini Basal metabolic rate in anorexia nervosa: relation to body composition and leptin concentrations Am. J. Clinical Nutrition, June 1, 2000; 71(6): 1495 - 1502. [Abstract] [Full Text] [PDF]

				A. M. Isidori, F. Strollo, M. Morè, M. Caprio, A. Aversa, C. Moretti, G. Frajese, G. Riondino, and A. Fabbri Leptin and Aging: Correlation with Endocrine Changes in Male and Female Healthy Adult Populations of Different Body Weights J. Clin. Endocrinol. Metab., May 1, 2000; 85(5): 1954 - 1962. [Abstract] [Full Text]