Exp Clin Endocrinol Diabetes 2011; 119(1): 30-35
DOI: 10.1055/s-0030-1261918
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Is Hypoandrogenemia a Component of Metabolic Syndrome in Males?

S. K. Singh1 , R. Goyal1 , 2 , D. D. Pratyush1 , 2
  • 1Department of Endocrinology & Metabolism, Banaras Hindu University, Varanasi
  • 2Both authors contributed equally
Further Information

Publication History

received 21.01.2010 first decision 10.04.2010

accepted 16.06.2010

Publication Date:
05 August 2010 (online)

Abstract

Objectives: This study was done to assess testosterone deficiency in males with metabolic syndrome (MetS) and the effect of testosterone replacement on insulin resistance and biochemical parameters of this syndrome with hypogonadism. Sixty three males fulfilling the International Diabetes Federation 2005 MetS guidelines as cases and 32 healthy males as controls with the mean age of 35.29±8.16 and 34±6.76 years respectively were enrolled in the study. Fasting blood samples were collected for gonadal profile and insulin assay. Homeostasis model assessment for insulin resistance (HOMA-IR) and free testosterone index were calculated. Hypogonadism was defined when the calculated free testosterone value was <0.225 nmol/L.

Findings: Total and calculated free testosterone, sex hormone binding globulin (SHBG) were lower in cases than controls (P<0.001). Hypogonadism was seen in 19 (30%) cases with MetS while 1 (3.1%) in controls. MetS cases with hypogonadism had significantly higher HOMA-IR than eugonadal cases. Hypogonadotropic hypogonadism was observed in 16 (84%) cases. Treatment with oral Testosterone 40 mg twice a day for 3 months led to significant improvement of HOMA-IR (P≤0.001) in the MetS males with hypogonadism.

Conclusions: This study revealed that males with MetS with or without diabetes had lower serum testosterone than their age matched healthy subjects. Hypogonadism was also common in subjects with MetS. Testosterone therapy to correct hypoandrogenimia improved insulin sensitivity and other biochemical parameters except High density lipoprotein cholesterol in MetS. This emphasizes that hypogonadism in all men with MetS or MetS in all men with hypogonadism needs clinical evaluation and subsequent management.

References

  • 1 Alberti KGMM, Zimmet P, Shaw J. The IDF epidemiology task force consensus group: metabolic syndrome: a new worldwide definition.  Lancet. 2005;  366 1059-1062
  • 2 Anderson PJ, Critchley JA, Chan JC. et al . Factor analysis of the metabolic syndrome: obesity vs. insulin resistance as the central abnormality.  Int J Obesity. 2001;  25 1782-1788
  • 3 Barrett TG, Bundey SE. Wolfram (DIDMOAD) syndrome.  J Med Genet. 1997;  34 838-841
  • 4 Bhasin S. Effects of testosterone administration on fat distribution, insulin sensitivity and atherosclerosis progression.  Clin Infect Dis. 2003;  37 (S 02) S142-S149
  • 5 Bojesen A, Kristensen K, Birkebaek NH. et al . The metabolic syndrome is frequent in Klinefelter's syndrome and is associated with abdominal obesity and hypogonadism.  Diabetes Care. 2006;  29 1591-1598
  • 6 Boyanov MA, Boneva A, Christov VG. Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency.  Aging Male. 2003;  6 17
  • 7 Corona G, Mannucci E, Petrone L. et al . NCEP-ATPIII-defined metabolic syndrome, type 2 diabetes mellitus and prevalence of hypogonadism in male patients with sexual dysfunction.  J Sex Med. 2007;  4 1038-1045
  • 8 Corona G, Mannucci E, Petrone L. et al . A comparison of NCEP-ATPIII and IDF metabolic syndrome definitions with relation to metabolic syndrome-associated sexual dysfunction.  J Sex Med. 2007;  4 789-796
  • 9 Dhindsa S, Prabhakar S, Sethi M. et al . Frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes.  J Clin Endocrinol Metab. 2004;  89 5462-5468
  • 10 Ford ES. Prevalence of the metabolic syndrome defined by the International Diabetes Federation among adults in the US.  Diabetes Care. 2005;  28 2745-2749
  • 11 Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.  Clin Chem. 1972;  18 499-502
  • 12 Ganesh HK, Vijaya Sarathi HA, George J. et al . Prevalence of hypogonadism in patients with Type 2 Diabetes mellitus in an Asian Indian study group.  Endocr Pract. 2009;  15 513-520
  • 13 Guay AT. The emerging link between hypogonadism and metabolic syndrome.  J Androl. 2009;  30 370-376
  • 14 Haffner SM, Karhapaa P, Mykkanen L. et al . Insulin resistance, body fat distribution, and sex hormones in men.  Diabetes. 1994;  43 212-219
  • 15 Haffner SM, Valdez RA, Stern MP. et al . Obesity, body fat distribution and sex hormones in men.  Int J Obes Relat Metab Disord. 1993;  17 643-649
  • 16 Haring R, Henry Völzke, Stephan BF. et al . Prediction of metabolic syndrome by low serum testosterone levels in men results from the Study of Health in Pomerania.  Diabetes. 2009;  58 2027-2031
  • 17 Harman SM, Metter EJ, Tobin JD. et al . Longitudinal effects of aging on serum total and free testosterone levels in healthy men: Baltimore Longitudinal Study of Aging.  J Clin Endocrinol Metab. 2001;  86 724-731
  • 18 Heufelder AE, Saad F, Bunck MC. et al . 52–Week treatment with diet and exercise plus transdermal testosterone reverses the metabolic syndrome and improves glycemic control in men with newly diagnosed type 2 diabetes and subnormal plasma testosterone.  J Androl. 2009;  30 726-733
  • 19 Isidori AM, Caprio M, Strollo F. et al . Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels.  J Clin Endocrinol Metab. 1999;  84 3673-3680
  • 20 Kapoor D, Goodwin E, Channer KS. et al . Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes.  Eur J Endocrinol. 2006;  154 (6) 899-906
  • 21 Kaufman JM, Vermeulen A. The decline of androgen levels in elderly men and its clinical and therapeutic implications.  Endocr Rev. 2005;  26 833-876
  • 22 Khaw KT, Dowsett M, Folkerd E. et al . Endogenous testosterone and mortality due to all causes, cardiovascular disease and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) Prospective Population Study.  Circulation. 2007;  116 2694-2701
  • 23 Laaksonen DE, Niskanen L, Punnonen K. et al . Sex hormones, inflammation and the metabolic syndrome.  Eur J Endo. 2003;  149 601-607
  • 24 Laaksonen DE, Niskanen L, Punnonen K. et al . Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men.  Diabetes Care. 2004;  27 (5) 1036-1041
  • 25 Malkin CJ, Pugh PJ, Jones TH. et al . Testosterone for secondary prevention in men with ischaemic heart disease.  Q J Med. 2003;  96 521-529
  • 26 Marin P, Holmang S, Jonsson L. et al . The effects of testosterone treatment on body composition and metabolism in middle-aged obese men.  Int J Obes Relat Metab Disord. 1992;  16 991-997
  • 27 Matthews DR, Hosker JP, Rudenski AS. et al . Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.  Diabetologia. 1985;  28 412-419
  • 28 Medlej R, Wasson J, Baz P. et al . Diabetes Mellitus and Optic atrophy: A study of Wolfram Syndrome in the Lebanese population.  J Clin Endocrinol Metab. 2004;  89 1656-1661
  • 29 Oh JY, Barrett-Conner E, Wedick NM. et al . Endogenous sex hormones and the development of type 2 diabetes in older men and women: The Rancho Bernardo Study.  Diabetes Care. 2002;  25 55-60
  • 30 Pitteloud N, Hardin M, Dwyer AA. et al . Increasing insulin resistance is associated with a decrease in leydig cell testosterone secretion in men.  J Clin Endocrinol Metab. 2005;  90 2636-2641
  • 31 Phillips GB, Jing T, Heymsfield SB. Relationships in men of sex hormones, insulin, adiposity and risk factors for myocardial infarction.  Metabolism. 2003;  52 784-790
  • 32 Reaven GM. Role of insulin resistance in human disease.  Diabetes. 1988;  37 1595-1607
  • 33 Stefan N, Schick F, Häring H-U. Sex hormone–binding globulin and risk of type 2 diabetes.  N Engl J Med. 2009;  361; 27 2675-2676
  • 34 Stellato RK, Feldman HA, Hamdy O. et al . Testosterone, sex hormonebinding globulin and the development of type 2 diabetes in middle-aged Men.  Diabetes Care. 2000;  23 490-494
  • 35 Svartberg J, Muhlen DV, Sundsfjord J. Waist circumference and testosterone levels in community dwelling men. The Tromso study.  Eur J Epidemiol. 2004;  19 657-663
  • 36 Swerdlow AJ, Higgins CD, Schoemaker MJ. et al . The UK Clinical Cytogenetics Group: Mortality in patients with Klinefelter Syndrome in Britain: a cohort study.  J Clin Endocrinol Metab. 2005;  90 6516-6522
  • 37 Tsai EC, Atsumoto AM, Fujimoto WY. et al . Association of Bioavailable, Free and Total testosterone with insulin resistance influence of sex hormone–binding globulin and body fat.  Diabetes Care. 2004;  27 861-868
  • 38 Vermeulen A, Kaufman JM. Diagnosis of hypogonadism in the aging male.  Aging Male. 2002;  5 170-176
  • 39 Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum.  J Clin Endocrinol Metab. 1999;  84 3666-3672
  • 40 World Health Organization .Definition, diagnosis and classification of Diabetes Mellitus and its complications. Report of a WHO consultation. Part 1: Diagnosis and classification of Diabetes Mellitus Geneva: WHO Department of Noncommunicable Disease Surveillance; 1999. http://www.who.int 1-59 http://www.who.int

Correspondence

Dr. S. K. SinghDM 

Department of Endocrinology

and Metabolism

Institute of Medical Sciences

Banaras Hindu University

Varanasi-221005

Uttar Pradeshm

India

Phone: +91/542/230 9374

Fax: +91/542/233 69222

Email: sksendocrine@yahoo.com