Obesity, Leptins, Hypogonadism and Waist–Hip Ratio in men: An Interplay

  • J. Elizabeth
  • C. Rakshita
  • S. Ramkumar


Adipose tissue and androgens have a reciprocal link in obese men. Hypogonadism is a nonspecific term for decreased testicular function. It is diagnosed by the low serum testosterone levels and low serum gonadotropin levels due to various etiologies. A deficiency of Testosterone is associated with decreased libido, male erectile dysfunction, excessive sweating and symptoms associated with aging like lack of energy, fatigue, central adiposity, reduced strength, cognitive decline and depression (Davidson et al. 1983; Yesavage et al. 1985). Many of the symptoms are seen in men with increasing age and are not specific in all cases of hypogonadism. Obesity predicts increased mortality due to the link with co morbidities such as diabetes mellitus, cardiovascular disease, the Metabolic Syndrome and Obstructive sleep apnoea (Poirier et al. 2006). Anthropometric measurements like Body Mass Index (BMI), Waist Hip Ratio (WHR) and Waist Circumference (WC) and Waist to Height Ratio (WHtR) have been used as tools to assess obesity and hence the cardiovascular risk status in individuals with hypogonadism. The Waist Hip Ratio (WHR) measurement is considered a good indicator of abdominal obesity which predisposes to serious health risks. The WHO recommends these measurements as a universal criterion for the detection of obesity. WHR which is a better measure of abdominal fat accumulation has been implicated as a more sensitive predictor of cardiovascular risk than BMI (Cambien et al. 1980; Yusuf et al. 2005). There is a fundamental relationship between energy balance and reproductive function in the mammalian species wherein population growth is controlled during times of scarcity. Recent epidemiological studies have shown that Androgens play an important role in the pathogenesis of Metabolic Syndrome in men. Conversely hypogonadism can develop in established metabolic syndrome (Laaksonen et al. 2005). Studies have shown that Androgen therapy has been found to reduce visceral abdominal obesity which is the main target in the treatment of obesity in hypogonadal men (Schroeder et al. 2004). The WHR is not recommended to be used as a lone indicator of cardiovascular disease in an obese individual as it was thought earlier. Recent studies have shown Waist Circumference to be a better tool to assess the cardiovascular risk than WHR.


Metabolic Syndrome Waist Circumference Testosterone Level Testosterone Replacement Hypogonadotropic Hypogonadism 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Body mass index


Basal metabolic rate


Coronary artery disease


Corticotropin releasing factor


Fat free mass


Fat mass


Follicle stimulating hormone


Glucagon like peptide-1


Gonadotropin releasing hormone


Human chorionic gonadotropin


Idiopathic hypogonadotropic hypogonadism


Kilo Dalton


Leptin gene


Leptin receptor


Luteinising hormone


Magnetic resonance imaging


Melanocyte stimulating hormone


Neuropeptide Y


Protein convertase subilisin/kexin type 1


Serum hormone binding globulin


Waist circumference


Waist hip ratio


Waist to height ratio


  1. Cambien F, Richard JL, Ducimetiere P. Etude des antecedents familiaux de cardiopathies ischemiques et d’hypertension arterielle en liaison avec la prevalence des facteurs de risque et l’incidence des cardiopathies ischemiques. L’Etude Prospective Parisienne. Rev Epidemiol Sante Publique. 1980;28:21.PubMedGoogle Scholar
  2. Caprio M, Isidori AM, Carta AR, Moretti C, Dufau ML, Fabbri A. Expression of Functional Leptin Receptors in Rodent Leydig Cells. Endocrinology. 1999;140:4939–47.PubMedCrossRefGoogle Scholar
  3. Caro JF, Kolaczynski JW, Nyce MR, Ohannesian JP, Opentanova I, Goldman WH, Lynn RB, Zhang PL, Sinha MK, Considine RV. Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet. 1996;348:159–61.PubMedCrossRefGoogle Scholar
  4. Carr DB, Utzschneider KM, Hull RL, Kodama K, Retzlaff BM, Brunzell JD, Shofer JB, Fish BE, Knopp RH, Kahn SE. Intra-abdominal fat is a major determinant of the National Cholesterol Education Program Adult Treatment Panel III criteria for the metabolic syndrome. Diabetes. 2004;53:2087–94.PubMedCrossRefGoogle Scholar
  5. Chen H, Charlat O, Tartaglia LA, Woolf EA, Weng X, Ellis SJ, Lakey ND, Culpepper J, More KJ, Breitbart RE, Duyk GM, Tepper RI, Morgenstern JP. Evidence That the Diabetes Gene Encodes the Leptin Receptor: Identification of a Mutation in the Leptin Receptor Gene in db/db Mice. Cell. 1996;9(84):491–5.CrossRefGoogle Scholar
  6. Cohen PG. Aromatase, adiposity, aging and disease. The hypogonadal- metabolicatherogenic-disease and aging connection. Med Hypotheses. 2001;56:702–8.PubMedCrossRefGoogle Scholar
  7. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL, Caro JF. Serum Immunoreactive-Leptin Concentrations in Normal-Weight and Obese Humans. N Eng J Med. 1996;334:292–5.CrossRefGoogle Scholar
  8. Davidson JM, Chen JJ, Crapo L, Gray GD, Greenleaf WJ, Catania JA. Hormonal Changes and Sexual Function in Aging Men. J Clin Endocrinol Metab. 1983;57:71–7.PubMedCrossRefGoogle Scholar
  9. Friedman J. Role of leptin and its receptors in the control of body weight. In: WF Blum, W Kiess, W Rascher, editors. Leptin – the voice of the adipose tissue. Heidelberg: J&J Edition, JA Barth Verlag; 1997;3–22.Google Scholar
  10. Griffin JE, Wilson JD. In Chapter-16, Disorders of the testes and male reproductive tract, in Wilson Foster, Kronenberg et al. Williams text book of endocrinology, 9th edn. p. 819–75.Google Scholar
  11. Katznelson L, Finkelstein JS, Schoenfeld DA, Rosenthal DI, Anderson EJ, Klibanski A. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. J Clin Endocrinol Metab. 1996;81:4358–65.PubMedCrossRefGoogle Scholar
  12. Kilciler G, Ozata M, Oktenli C, Sanisoglu SY, Bolu E, Bingol N, Kilciler M, Ozdemir IC, Kutlu M. Diurnal Leptin Secretion Is Intact in Male Hypogonadotropic Hypogonadism and Is Not Influenced by exogenous Gonadotropins. J Clin Endocrinol Metab. 2002;87:5023–9.PubMedCrossRefGoogle Scholar
  13. Laaksonen DE, Niskanen L, Punnonen K, K Nyyssönen, Tuomainen TP, Valkonen VP, Salonen JT. The Metabolic Syndrome and Smoking in Relation to Hypogonadism in Middle-Aged Men: A Prospective Cohort Study. J Clin Endocrinol Metab. 2005;90(2):712–9.PubMedCrossRefGoogle Scholar
  14. Markku S, Sandler DP, Hoppin JA, Blair A, Baird DD. Reduced Fertility Among Overweight and Obese Men. Epidemiology. 2006;17(5):520–3.CrossRefGoogle Scholar
  15. Montague CT, Prins JB, Sanders L, Digby JE, O’Rahilly S. Depot- and sex-specific differences in human leptin mRNA expression: implications for the control of regional fat distribution. Diabetes. 1997;46(3):342–7.PubMedCrossRefGoogle Scholar
  16. Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser. 2000;894: i–xii, 1–253.Google Scholar
  17. Oksanen L, Kaprio J, Mustajoki P, Kontula K. A common pentanucleotide polymorphism of the 3’-untranslated part of the leptin receptor gene generates a putative stem-loop motif in the mRNA and is associated with serum insulin levels in obese individuals. Int J Obes. 1998;22:634–40.CrossRefGoogle Scholar
  18. Piji H, Toornnvliet AC, Meinders AE. Serum leptin in normal weight and obese humans. N Engl J Med. 1996;334:1544.CrossRefGoogle Scholar
  19. Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, Eckel RH. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the council on Nutrition, Physical Activity, and Metabolism. Circulation. 2006;113(6):898–918.PubMedCrossRefGoogle Scholar
  20. Pugeat M, Crave JC, Elmidani M. J Ster Biochem Mol Biol. 1991;40: 841–9.CrossRefGoogle Scholar
  21. Rita RK, Dobs, Adrian S. Androgen deficiency, diabetes and the metabolic syndrome in men. Curr Opin Endocrinol Diabetes Obes. 2007;14: 226–34.CrossRefGoogle Scholar
  22. Rodriguez A, Muller DC, Metter EJ, Maggio M, Harman SM, Blackman MR, Andres R. Aging, androgens, and the metabolic syndrome in a longitudinal study of aging. J Clin Endocrinol Metab. 2007;92:3568–72.PubMedCrossRefGoogle Scholar
  23. Rolf C, Eckardstein SV, Koken U, Nieschlag E. Testosterone substitution of hypogonadal men prevents the age-dependent increases in body mass index, body fat and leptin seen in healthy ageing men: results of a cross-sectional study. Eur J Endocrinol. 2002;146:505–11.PubMedCrossRefGoogle Scholar
  24. Schroeder ET, Zheng L, Ong MD, Martinez C, Flores C, Stewart Y, Azen C, Sattler FR. J Clin Endocrinol Metab. 2004;89:4863–72.PubMedCrossRefGoogle Scholar
  25. Seidell JC, BjÖrntorp P, SjÖstrÖm L, Kvist H, Sannerstedt R. Visceral fat accumulation in men is positively associated with insulin, glucose, and C-peptide levels, but negatively with testosterone levels. Metabolism. 1990;39:897–901.PubMedCrossRefGoogle Scholar
  26. Snyder PJ, Peachey H, Berlin JA, Hannoush P, Haddad G, Dlewati A, Santana J, Loh L, Lenrow DA, Holmes JH, Kapoor SC, Atkinson LE, Strom BL. Effects of Testosterone Replacement in Hypogonadal Men. J Clin Endocrinol Metab. 2000;85(8).Google Scholar
  27. Vaan Gaal LF, Wauters MA, Mertens IL, Considine RV, De Leeuw IH. Clinical endocrinology of human leptin. Intern J Obes. 1999;23:29–36.CrossRefGoogle Scholar
  28. Widjaja A, Lill C, Radam C. LEIPZIG. 1997;263–8.Google Scholar
  29. Wilding J, Widdowson P, Williams G. Br Med Bull. 1997;53:286–306.PubMedCrossRefGoogle Scholar
  30. Yesavage JA, Davidson J, Widrow L, Berger PA. Plasma testosterone levels, depression, sexuality, and age. Biol Psych. 1985;20(2):222–5.Google Scholar
  31. Yusuf S, Hawken S, Ounpuu S, Bautista L, Franzosi MG, Commerford P, Lang CC, Rumboldt Z, Onen CL, Lisheng L, Tanomsup S, Wangai Jr P, Razak F, Sharma AM, Anand SS, INTERHEART Study Investigators.Obesity and the risk of myocardial infarction in 27,000 participants from 52 countries: a case-control study. Lancet. 2005;366: 1640–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Clinical Associate Professor of PhysiologyAmrita Institute of Medical SciencesKochiIndia

Personalised recommendations