Hypogonadism, ED, metabolic syndrome and obesity: A pathological link supporting cardiovascular diseases

International Journal of Andrology

Volumn 32, Issue 6, 2009, Pages 587-598

  Corona, G ^a,b   Mannucci, E ^a   Forti, G ^a   Maggi, M ^a  

^a UNIVERSITY OF FLORENCE   (Italy)

^b BELLARIA HOSPITAL   (Italy)

Author keywords

Cardiovascular diseases; Erectile dysfunction; Hypogonadism; Metabolic syndrome; Obesity; Testosterone

Indexed keywords

GONADOTROPIN; LETROZOLE; PLACEBO; TESTOSTERONE; TRIACYLGLYCEROL;

ANDROGEN THERAPY; BLOOD PRESSURE; CARDIOVASCULAR DISEASE; CLINICAL TRIAL; DISEASE ASSOCIATION; ERECTILE DYSFUNCTION; GONADOTROPIN RELEASE; HUMAN; HYPERTRIGLYCERIDEMIA; HYPOGONADISM; INSULIN RESISTANCE; INSULIN SENSITIVITY; METABOLIC SYNDROME X; NONHUMAN; OBESITY; PREVALENCE; PRIORITY JOURNAL; REVIEW;

ADIPOSITY; ANDROGENS; CARDIOVASCULAR DISEASES; DIABETES MELLITUS, TYPE 2; ERECTILE DYSFUNCTION; HUMANS; HYPOGONADISM; INSULIN RESISTANCE; LIFE EXPECTANCY; LONGITUDINAL STUDIES; MALE; METABOLIC SYNDROME X; OBESITY; SYNDROME;

EID: 70049083600     PISSN: 01056263     EISSN: 13652605     Source Type: Journal    
DOI: 10.1111/j.1365-2605.2008.00951.x     Document Type: Review

References (119)

1. Alberti, K. G., Zimmet, P. Shaw, J. (2006) Metabolic syndrome a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabetic Medicine 23, 469 480.
2. Alexander, C. M., Landsman, P. B., Teutsch, S. M. Haffner, S. M., Third National Health and Nutrition Examination Survey (NHANES III); National Cholesterol Education Program (NCEP 2003) NCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older. Diabetes 52, 1210 1214.
3. Allan, C. A., Strauss, B. J., Burger, H. G., Forbes, E. A. McLachlan, R. I. (2008) Testosterone therapy prevents gain in visceral adipose tissue and loss of skeletal muscle in non-obese aging men. Journal of Clinical Endocrinology and Metabolism 93, 139 146.
4. Araujo, A. B., Kupelian, V., Page, S. T., Handelsman, D. J., Bremner, W. J. McKinlay, J. B. (2007) Sex steroids and all-cause and cause-specific mortality in men. Archives of Internal Medicine 167, 1252 1260.
5. Avogaro, P. Crepaldi, C. (1965) European association for the study of diabetes. Diabetologia 1, 137.
6. Bal, K., Oder, M., Sahin, A. S., Karataş, C. T., Demir, O., Can, E., Gümüş, B. H., Ozer, K., Sahin, O. Esen, A. A. (2007) Prevalence of metabolic syndrome and its association with erectile dysfunction among urologic patients: metabolic backgrounds of erectile dysfunction. Urology 69, 356 360.
7. Bansal, T. C., Guay, A. T., Jacobson, J., Woods, B. O. Nesto, R. W. (2005) Incidence of metabolic syndrome and insulin resistance in a population with organic erectile dysfunction. Journal of Sexual Medicine 2, 96 103.
8. Basaria, S. (2008) Androgen deprivation therapy, insulin resistance, and cardiovascular mortality: an inconvenient truth. Journal of Andrology 29, 534 539.
9. Billups, K. L., Bank, A. J., Padma-Nathan, H., Katz, S. D. Williams, R. A. (2008) Erectile dysfunction as a harbinger for increased cardiometabolic risk. International Journal of Impotence Research 20, 236 242.
10. Bivalacqua, T. J., Usta, M. F., Champion, H. C., Kadowitz, P. J. Hellstrom, W. J. (2003) Endothelial dysfunction in erectile dysfunction: role of the endothelium in erectile physiology and disease. Journal of Andrology 24 (6 Suppl S17 S37.
11. Boyanov, M. A., Boneva, Z. Christov, V. G. (2003) Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency. Aging Male 6, 1 7.
12. Brüning, J. C., Gautam, D., Burks, D. J., Gillette, J., Schubert, M., Orban, P. C., Klein, R., Krone, W., Müller-Wieland, D. Kahn, C. R. (2000) Role of brain insulin receptor in control of body weight and reproduction. Science 289, 2122 2125.
13. Burcelin, R., Thorens, B., Glauser, M., Gaillard, R. C. Pralong, F. P. (2003) Gonadotropin-releasing hormone secretion from hypothalamic neurons: stimulation by insulin and potentiation by leptEndocrinology 144, 4484 4491.
14. Corona, G., Mannucci, E., Schulman, C., Petrone, L., Mansani, R., Cilotti, A., Balercia, G., Chiarini, V., Forti, G. Maggi, M. (2006a) Psychobiologic correlates of the metabolic syndrome and associated sexual dysfunction. European Urology 50, 595 604.
15. Corona, G., Mannucci, E., Petrone, L., Balercia, G., Fisher, A. D., Chiarini, V., Forti, G. Maggi, M. (2006b) ANDROTEST: a structured interview for the screening of hypogonadism in patients with sexual dysfunction. Journal of Sexual Medicine 3, 706 715.
16. Corona, G., Mannucci, E., Petrone, L., Ricca, V., Balercia, G., Mansani, R., Chiarini, V., Giommi, R., Forti, G. Maggi, M. (2006c) Association of hypogonadism and type II diabetes in men attending an outpatient erectile dysfunction clinic. International Journal of Impotence Research 18, 190 197.
17. Corona, G., Mannucci, E., Petrone, L., Balercia, G., Paggi, F., Fisher, A. D. et al. (2007a) NCEP-ATPIII-defined metabolic syndrome, type 2 diabetes mellitus, and prevalence of hypogonadism in male patients with sexual dysfunction. Journal of Sexual Medicine 4 (4 Pt 1 1038 1045.
18. Corona, G., Mannucci, E., Petrone, L., Schulman, C., Balercia, G., Fisher, A. D., Chiarini, V., Forti, G. Maggi, M. (2007b) A comparison of NCEP-ATPIII and IDF metabolic syndrome definitions with relation to metabolic syndrome-associated sexual dysfunction. Journal of Sexual Medicine 4, 789 796.
19. Corona, G., Mannucci, E., Fisher, A. D., Lotti, F., Petrone, L., Balercia, G., Bandini, E., Forti, G. Maggi, M. (2008a) Low levels of androgens in men with erectile dysfunction and obesity. Journal of Sexual Medicine [Epub ahead of print].
20. Corona, G., Forti, G. Maggi, M. (2008b) Why can patients with erectile dysfunction be considered lucky? The association with testosterone deficiency and metabolic syndrome. The Aging Male 11, 193 199.
21. Corona, G., Fagioli, G., Mannucci, E., Romeo, A., Rossi, M., Lotti, F. et al. (2008c) Penile Doppler ultrasound in patients with ED: role of peak systolic velocity measured in the flaccid state in predicting arteriogenic ED and silent coronary artery disease. Journal of Sexual Medicine [Epub ahead of print].
22. Corona, G., Mannucci, E., Lotti, F., Fisher, A. D., Bandini, E., Balercia, G., Forti, G. Maggi, M. (2008d) Pulse pressure, an index of arterial stiffness, is associated with androgen deficiency and impaired penile blood flow in men with ED. Journal of Sexual Medicine 6, 284 292.
23. Courtenay, W. H. Keeling, R. P. (2000) Men, gender, and health: toward an interdisciplinary approach. Journal of American College Health 48, 243.
24. Demir, T., Demir, O., Kefi, A., Comlekci, A., Yesil, S. Esen, A. (2006) Prevalence of erectile dysfunction in patients with metabolic syndrome. International Journal of Urology 13, 385 388.
25. Derby, C. A., Zilber, S., Brambilla, D., Morales, K. H. McKinlay, J. B. (2006) Body mass index, waist circumference and waist to hip ratio and change in sex steroid hormones: the Massachusetts Male Ageing Study. Clinical Endocrinolology (Oxf), 65, 125 131.
26. Despres, J. P. Lemieux, I. (2006) Abdominal obesity and metabolic syndrome. Nature 444, 881 887.
27. Dhindsa, S., Prabhakar, S., Sethi, M., Bandyopadhyay, A., Chaudhuri, A. Dandona, P. (2004) Frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes. Journal of Clinical Endocrinology and Metabolism 89, 5462 5468.
28. Ding, E. L., Song, Y., Malik, V. S. Liu, S. (2006) Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. Journal of the American Medical Association 295, 1288 1299.
29. Einhorn, D., Reaven, G. M., Cobin, R. H., Ford, E., Ganda, O. P., Handelsman, Y. et al. (2003) American College of Endocrinology position statement on the insulin resistance syndrome. Endocrine Practice 9, 237 252.
30. Erkelens, D. W., de Bruin, T. W. Castro Cabezas, M. (1993) Tulp syndrome. Lancet 342, 1536 1537.
31. Esposito, K., Giugliano, F., Martedì, E., Feola, G., Marfella, R., D'Armiento, M. Giugliano, D. (2005) High proportions of erectile dysfunction in men with the metabolic syndrome. Diabetes Care 28, 1201 1203.
32. Esposito, K., Giugliano, F., Ciotola, M., De Sio, M., D'Armiento, M. Giugliano, D. (2008) Obesity and sexual dysfunction, male and female. International Journal of Impotence Research 20, 358 365.
33. Expert Panel on Detection Evaluation, Treatment of High Blood Cholesterol in Adults. (2001) Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). Journal of the American Medical Association 285, 2486 2497.
34. Ferrannini, E., Natali, A., Bell, P., Cavallo-Perin, P., Lalic, N. Mingrone, G. (1997) Insulin resistance and hypersecretion in obesity. European Group for the Study of Insulin Resistance (EGIR). Journal of Clinical Investigation 100, 1166 1173.
35. Francavilla, S., Bocchio, M., Pelliccione, F., Necozione, S. Francavilla, F. (2005) Vascular aetiology of erectile dysfunction. International Journal of Andrology 28 Suppl 2 35 39.
36. Gazzaruso, C., Giordanetti, S., De Amici, E., Bertone, G., Falcone, C., Geroldi, D., Fratino, P., Solerte, S. B. Garzaniti, A. (2004) Relationship between erectile dysfunction and silent myocardial ischemia in apparently uncomplicated type 2 diabetic patients. Circulation 110, 22 26.
37. Giagulli, V. A., Kaufman, J. M. Vermeulen, A. (1994) Pathogenesis of the decreased androgen levels in obese men. Journal of Clinical Endocrinology and Metabolism 79, 997 1000.
38. Grundy, S. M. (2007) Metabolic syndrome: a multiplex cardiovascular risk factor. Journal of Clinical Endocrinology and Metabolism 92, 399 404.
39. Guay, A. Jacobson, J. (2007) The relationship between testosterone levels, the metabolic syndrome (by two criteria), and insulin resistance in a population of men with organic erectile dysfunction. Journal of Sexual Medicine 4 (4 Pt 1 1046 1055.
40. Gündüz, M. I., Gümüs, B. H. Sekuri, C. (2004) Relationship between metabolic syndrome and erectile dysfunction. Asian Journal of Andrology 6, 355 358.
41. Haffner, S. M., Shaten, J., Stern, M. P., Smith, G. D. Kuller, L. (1996) Low levels of sex hormone-binding globulin and testosterone predict the development of non-insulin-dependent diabetes mellitus in men. MRFIT Research Group. Multiple Risk Factor Intervention Trial. American Journal of Epidemiology 143, 889 897.
42. Hughes, G. S., Mathur, R. S. Margolius, H. S. (1989) Sex steroid hormones are altered in essential hypertension. Journal of Hypertension 7, 181 187.
43. Isidori, A. M., Caprio, M., Strollo, F., Moretti, C., Frajese, G., Isidori, A. Fabbri, A. (1999) Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels. Journal of Clinical Endocrinology and Metabolism 84, 3673 3680.
44. Isidori, A. M., Strollo, F., Morè, M., Caprio, M., Aversa, A., Moretti, C., Frajese, G., Riondino, G. Fabbri, A. (2000) Leptin and aging: correlation with endocrine changes in male and female healthy adult populations of different body weights. Journal of Clinical Endocrinology and Metabolism 85, 1954 1962.
45. Isidori, A. M., Giannetta, E., Greco, E. A., Gianfrilli, D., Bonifacio, V., Isidori, A., Lenzi, A. Fabbri, A. (2005a) Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clinical Endocrinology (Oxf) 63, 280 293.
46. Isidori, A. M., Giannetta, E., Gianfrilli, D., Greco, E. A., Bonifacio, V., Aversa, A., Isidori, A., Fabbri, A. Lenzi, A. (2005b) Effects of testosterone on sexual function in men: results of a meta-analysis. Clinical Endocrinology (Oxf) 63, 381 394.
47. Jones, R. D., Nettleship, J. E., Kapoor, D., Jones, H. T. Channer, K. S. (2005) Testosterone and atherosclerosis in aging men: purported association and clinical implications. American Journal of Cardiovascular Drugs 5, 141 154.
48. Kahn, R., Buse, J., Ferrannini, E., Stern, M. American Diabetes Association; European Association for the Study of Diabetes. (2005) The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 28, 2289 2304. (Pubitemid 41242486)
49. Kapoor, D., Goodwin, E., Channer, K. S. Jones, T. H. (2006) Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. European Journal Endocrinology 154, 899 906.
50. Kapoor, D., Clarke, S., Stanworth, R., Channer, K. S. Jones, T. H. (2007) The effect of testosterone replacement therapy on adipocytokines and C-reactive protein in hypogonadal men with type 2 diabetes. European Journal of Endocrinology 156, 595 602.
51. Kaukua, J., Pekkarinen, T., Sane, T. Mustajoki, P. (2003) Sex hormones and sexual function in obese men losing weight. Obesity Research 11, 689 694.
52. Khaw, K. T., Dowsett, M., Folkerd, E., Bingham, S., Wareham, N., Luben, R., Welch, A. Day, N. (2007) 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 116, 2694 2701.
53. Kupelian, V., Page, S. T., Araujo, A. B., Travison, T. G., Bremner, W. J. McKinlay, J. B. (2006a) Low sex hormone-binding globulin, total testosterone, and symptomatic androgen deficiency are associated with development of the metabolic syndrome in non-obese men. Journal of Clinical Endocrinology and Metabolism 91, 843 850.
54. Kupelian, V., Shabsigh, R., Araujo, A. B., O'Donnell, A. B. McKinlay, J. B. (2006b) Erectile dysfunction as a predictor of the metabolic syndrome in aging men: results from the Massachusetts Male Aging Study. Journal of Urology 176, 222 226. (Pubitemid 43815376)
55. Kylin, E. (1923) Studien ueber das hypertonie-hyperglykamie- hyperurikamiesyndrom. Zentralblatt Fuer Innere 44, 105 127.
56. Laaksonen, D. E., Niskanen, L., Punnonen, K., Nyyssonen, K., Tuomainen, T. P., Salonen, R., Rauramaa, R. Salonen, J. T. (2003) Sex hormones, inflammation and the metabolic syndrome: a population-based study. European Journal of Endocrinology 149, 601 608.
57. Laaksonen, D. E., Niskanen, L., Punnonen, K., Nyyssönen, K., Tuomainen, T. P., Valkonen, V. P., Salonen, R. Salonen, J. T. (2004) Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care 27, 1036 1041.
58. Laaksonen, D. E., Niskanen, L., Punnonen, K., Nyyssonen, K., Tuomainen, T. P., Valkonen, V. P. Salonen, J. T. (2005) The metabolic syndrome and smoking in relation to hypogonadism in middle-aged men: a prospective cohort study. Journal of Clinical Endocrinology and Metabolism 90, 712 719.
59. Labropoulos, B., Velonakis, E., Oekonomakos, P., Laskaris, J. Katsimades, D. (1982) Serum sex hormones in patients with coronary disease and their relationship to known factors causing atherosclerosis. Cardiology 69, 98 103.
60. Laughlin, G. A., Barrett-Connor, E. May, S. (2006) Sex-specific association of the androgen to oestrogen ratio with adipocytokine levels in older adults: the Rancho Bernardo Study. Clinical Endocrinology (Oxf) 65, 506 513.
61. Laughlin, G. A., Barrett-Connor, E. Bergstrom, J. (2008) Low serum testosterone and mortality in older men. Journal of Clinical Endocrinology and Metabolism 93, 68 75.
62. Lin, H. Y., Xu, Q., Yeh, S., Wang, R. S., Sparks, J. D. Chang, C. (2005) Insulin and leptin resistance with hyperleptinemia in mice lacking androgen receptor. Diabetes 2005, 54, 1717 1725.
63. Lin, H. Y., Yu, I. C., Wang, R. S., Chen, Y. T., Liu, N. C., Altuwaijri, S. et al. (2008) Increased hepatic steatosis and insulin resistance in mice lacking hepatic androgen receptor. Hepatology 47, 1924 1935.
64. Loves, S., Ruinemans-Koerts, J. de Boer, H. (2008) Letrozole once a week normalizes serum testosterone in obesity-related male hypogonadism. European Journal of Endocrinology 158, 741 747.
65. Ma, R. C., So, W. Y., Yang, X., Yu, L. W., Kong, A. P., Ko, G. T., Chow, C. C., Cockram, C. S., Chan, J. C. Tong, P. C. (2008) Erectile dysfunction predicts coronary heart disease in type 2 diabetes. Journal of the American College of Cardiology 51, 2045 2050.
66. Maggi, M. (2008) Gender differences mirrored: andro-pause, a palindromic meno-pause or just a lean pause? Journal of Sexual Medicine 5, 2454 2463.
67. Maggi, M., Schulman, C., Quinton, R., Langham, S. Uhl-Hochgraeber, K. (2007) The burden of testosterone deficiency syndrome in adult men: economic and quality-of-life impact. Journal of Sexual Medicine 4 (4 Pt 1 1056 1069.
68. Mannucci, E., Lambertucci, L., Monami, M., Fedeli, A., Chiasserini, V., Marchionni, N., Masotti, G. Ungar, A. (2006) Pulse pressure and mortality in hypertensive type 2 diabetic patients. A cohort study. Diabetes/Metabolism Research and Reviews 22, 172 175.
69. Mannucci, E., Monami, M., Bardini, G., Sposato, I., Ungar, A., Pepe, G., Masotti, G., Marchionni, N. Rotella, C. M. (2007) Metabolic syndrome and pulse pressure. Diabetes, Obesity and Metabolism 9, 600 602.
70. Mannucci, E., Monami, M., Cresci, B., Pala, L., Bardini, G., Petracca, M. G., Dicembrini, I., Pasqua, A., Buiatti, E. Rotella, C. M. (2008) National Cholesterol Education Program and International Diabetes Federation definitions of metabolic syndrome in the prediction of diabetes. Results from the FIrenze-Bagno A Ripoli study. Diabetes, Obesity and Metabolism 10, 430 435.
71. Marin, P., Oden, B. Bjorntorp, P. (1996) Assimilation and mobilization of triglycerides in subcutaneous abdominal and femoral adipose tissue in vivo in men: effects of androgens. Journal of Clinical Endocrinology and Metabolism 80, 239 243.
72. Meigs, J. B., Rutter, M. K., Sullivan, L. M., Fox, C. S., D'Agostino, R. B. Sr. Wilson, P. W. (2007) Impact of insulin resistance on risk of type 2 diabetes and cardiovascular disease in people with metabolic syndrome. Diabetes Care 30, 1219 1225.
73. Monami, M., Lambertucci, L., Ungar, A., Pieri, M., Masotti, G., Marchionni, N. Mannucci, E. (2006) Is the third component of metabolic syndrome really predictive of outcomes in type 2 diabetic patients? Diabetes Care 29, 2515 2517.
74. Monami, M., Marchionni, N., Masotti, G. Mannucci, E. (2007a) Prognostic value of International Diabetes Federation and Adult Treatment Panel III definitions of metabolic syndrome in Type 2 diabetic patients: what makes the difference? Journal of Endocrinological Investigation 30, 626 630.
75. Monami, M., Marchionni, N., Masotti, G. Mannucci, E. (2007b) IDF and ATP-III definitions of metabolic syndrome in the prediction of all-cause mortality in type 2 diabetic patients. Diabetes, Obesity and Metabolism 9, 350 353.
76. Montorsi, F., Briganti, A., Salonia, A., Rigatti, P., Margonato, A., Macchi, A., Galli, S., Ravagnani, P. M. Montorsi, P. (2003) Erectile dysfunction prevalence, time of onset and association with risk factors in 300 consecutive patients with acute chest pain and angiographically documented coronary artery disease. European Urology 44, 360 364.
77. Montorsi, P., Ravagnani, P. M., Galli, S., Salonia, A., Briganti, A., Werba, J. P. Montorsi, F. (2006) Association between erectile dysfunction and coronary artery disease: Matching the right target with the right test in the right patient. European Urology 50, 721 731. (Pubitemid 44332685)
78. Morales, V., Santana, P., Díaz, R., Tabraue, C., Gallardo, G., López Blanco, F., Hernández, I., Fanjul, L. F. Ruiz de Galarreta, C. M. (2003) Intratesticular delivery of tumor necrosis factor-alpha and ceramide directly abrogates steroidogenic acute regulatory protein expression and Leydig cell steroidogenesis in adult rats. Endocrinology 144, 4763 4772.
79. Morelli, A., Corona, G., Filippi, S., Ambrosini, S., Forti, G., Vignozzi, L. Maggi, M. (2007) Which patients with sexual dysfunction are suitable for testosterone replacement therapy? Journal of Endocrinological Investigation 30, 880 888.
80. Morgagni, G. B. (1975) The Seats and Causes of Diseases Investigated by Anatomy [De sidibus er acsusis morborum per anatomen indagata], Vol. 1. Remondini, Padova.
81. Muller, M., Grobbee, D. E., den Tonkelaar, I., Lamberts, S. W. van der Schouw, Y. T. (2005) Endogenous sex hormones and metabolic syndrome in aging men. Journal of Clinical Endocrinology and Metabolism 90, 2618 2623. (Pubitemid 40686299)
82. Niskanen, L., Laaksonen, D. E., Punnonen, K., Mustajoki, P., Kaukua, J. Rissanen, A. (2004) Changes in sex hormone-binding globulin and testosterone during weight loss and weight maintenance in abdominally obese men with the metabolic syndrome. Diabetes Obesity and Metabolism 6, 208 215.
83. Oh, J. Y., Barrett-Connor, E., Wedick, N. M., Wingard, D. L. Rancho Bernardo Study. (2002) Endogenous sex hormones and the development of type 2 diabetes in older men and women: the Rancho Bernardo study. Diabetes Care 25, 55 60.
84. Page, S. T., Kupelian, V., Bremner, W. J. McKinlay, J. B. (2006) The androgen receptor gene CAG repeat polymorphism does not predict increased risk of heart disease: longitudinal results from the Massachusetts Male Ageing Study. Clinical Endocrinology (Oxf) 65, 333 339.
85. Paick, J. S., Yang, J. H., Kim, S. W. Ku, J. H. (2007) Severity of erectile dysfunction in married impotent patients: interrelationship with anthropometry, hormones, metabolic profiles and lifestyle. International Journal of Urology 14, 48 53.
86. Pasquali, R., Casimirri, F., De Iasio, R., Mesini, P., Boschi, S., Chierici, R., Flamia, R., Biscotti, M. Vicennati, V. (1995) Insulin regulates testosterone and sex hormone-binding globulin concentrations in adult normal weight and obese men. Journal of Clinical Endocrinology and Metabolis 80, 654 658.
87. Pitteloud, N., Mootha, V. K., Dwyer, A. A., Hardin, M., Lee, H., Eriksson, K. F. et al. (2005a) Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men. Diabetes Care 28, 1636 1642.
88. Pitteloud, N., Hardin, M., Dwyer, A. A., Valassi, E., Yialamas, M., Elahi, D. Hayes, F. J. (2005b) Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men. Journal of Clinical Endocrinology and Metabolism 90, 2636 2641.
89. Pitteloud, N., Dwyer, A. A., Decruz, S., Lee, H., Boepple, P. A., Crowley, W. F. Jr. Hayes, F. J. (2008) Inhibition of LH secretion by testosterone in men requires aromatization for its pituitary but not its hypothalamic effects: evidence from the tandem study of normal and gonadotrophin-releasing hormone-deficient men. Journal of Clinical Endocrinology and Metabolism 93, 784 791.
90. Reaven, G. M. (1988) Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37, 1595 1607.
91. Rodriguez, A., Muller, D. C., Metter, E. J., Maggio, M., Harman, S. M., Blackman, M. R. Andres, R. (2007) Aging, androgens, and the metabolic syndrome in a longitudinal study of aging. Journal of Clinical Endocrinology and Metabolism 92, 3568 3572. (Pubitemid 47435336)
92. Rosano, G. M., Sheiban, I., Massaro, R., Pagnotta, P., Marazzi, G., Vitale, C., Mercuro, G., Volterrani, M., Aversa, A. Fini, M. (2007) Low testosterone levels are associated with coronary artery disease in male patients with angina. International Journal of Impotence Reserch 19, 176 182.
93. Saad, F., Gooren, L. J., Haider, A. Yassin, A. (2008) A dose-response study of testosterone on sexual dysfunction and features of the metabolic syndrome using testosterone gel and parenteral testosterone undecanoate. Journal of Andrology 29, 102 105.
94. Shabsigh, R., Arver, S., Channer, K. S., Eardley, I., Fabbri, A., Gooren, L., Heufelder, A., Jones, H., Meryn, S. Zitzmann, M. (2008) The triad of erectile dysfunction, hypogonadism and the metabolic syndrome. International Journal of Clinical Practice 62, 791 798.
95. Sinal, C. J., Tohkin, M., Miyata, M., Ward, J. M., Lambert, G. Gonzalez, F. J. (2000) Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell 102, 731 744.
96. Smith, G. D., Ben-Shlomo, Y., Beswick, A., Yarnell, J., Lightman, S. Elwood, P. (2005) Cortisol, testosterone, and coronary heart disease: prospective evidence from the Caerphilly study. Circulation 112, 332 340.
97. Stehouwer, C. D., Henry, R. M. Ferreira, I. (2008) Arterial stiffness in diabetes and the metabolic syndrome: a pathway to cardiovascular disease. Diabetologia 51, 527 539.
98. Stellato, R. K., Feldman, H. A., Hamdy, O., Horton, E. S. McKinlay, J. B. (2000) Testosterone, sex hormone-binding globulin, and the development of type 2diabetes in middle-aged men: prospective results from the Massachusetts male aging study. Diabetes Care 23, 490 494.
99. Svartberg, J. (2007) Epidemiology: testosterone and the metabolic syndrome. International Journal of Impotence Research 19, 124 128.
100. Svartberg, J., von Mühlen, D., Schirmer, H., Barrett-Connor, E., Sundfjord, J. Jorde, R. (2004) Association of endogenous testosterone with blood pressure and left ventricular mass in men. The Tromsø Study. European Journal of Endocrinology 150, 65 71.
101. Thompson, I. M., Tangen, C. M., Goodman, P. J., Probstfield, J. L., Moinpour, C. M. Coltman, C. A. (2005) Erectile dysfunction and subsequent cardiovascular disease. Journal of the American Medical Association 294, 2996 3002.
102. Tibblin, G., Adlerberth, A., Lindstedt, G. Björntorp, P. (1996) The pituitary-gonadal axis and health in elderly men: a study of men born in 1913. Diabetes 45, 1605 1609.
103. Traish, A. M., Guay, A. T., Feeley, R. Saad, F. (2008a) The dark side of testosterone deficiency: I. Metabolic syndrome & erectile dysfunction. Journal of Andrology [Epub ahead of print].
104. Traish, A. M., Saad, F. Guay, A. T. (2008b) The dark side of testosterone deficiency: II. Type 2 diabetes & insulin resistance. Journal of Andrology [Epub ahead of print].
105. Turner, N. Heilbronn, L. K. (2008) Is mitochondrial dysfunction a cause of insulin resistance? Trends in Endocrinology and Metabolism. [Epub ahead of print].
106. Vague, J. (1947) La differentiation sexuelle. Facteur determinant des formes de l'obesitè. Press Medicine 30, 339 340.
107. Vermeulen, A., Kaufman, J. M., Deslypere, J. P. Thomas, G. (1993) Attenuated luteinizing hormone (LH) pulse amplitude but normal LH pulse frequency, and its relation to plasma androgens in hypogonadism of obese men. Journal of Clinical Endocrinology and Metabolism 76, 1140 1146.
108. Wang, S., Lai, K., Moy, F. J., Bhat, A., Hartman, H. B. Evans, M. J. (2006) The nuclear hormone receptor farnesoid X receptor (FXR) is activated by androsterone. Endocrinology 147, 4025 4033.
109. Wang, C., Nieschlag, E., Swerdloff, R., Behre, H. M., Hellstrom, W. J., Gooren, L. J. et al. (2008) Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. European Urology [Epub ahead of print].
110. Wisniewski, A. B., Migeon, C. J., Meyer-Bahlburg, H. F., Gearhart, J. P., Berkovitz, G. D., Brown, T. R. Money, J. (2000) Complete androgen insensitivity syndrome: long-term medical, surgical, and psychosexual outcome. Journal of Clinical Endocrinology and Metabolism 85, 2664 2669.
111. World Health Organization 1999) Definition and Classification of Diabetes Mellitus and its Complications Report of a WHO Consultation. Part 1: Diagnosis and Classification of Diabetes Mellitus. World Health organization, Geneva publ.noWHO/NCD/NCS/99.2. http://whqlibdoc.who.int/inq/1999/who-ncd-ncs-99.2.pdf
112. Wu, F. C., Tajar, A., Pye, S. R., Silman, A. J., Finn, J. D., O'Neill, T. W., Bartfai, G., Casanueva, F., Forti, G., Giwercman, A., Huhtaniemi, I. T., Kula, K., Punab, M., Boonen, S., Vanderschueren, D. European Male Aging Study Group 2008) Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. Journal of Clinical Endocrinology and Metabolism 93, 2737 2745.
113. Wu, F. C. W. von Eckardstein, A. (2003) Androgens and coronary artery disease. Endocrine Review 24, 183 217.
114. Xu, A., Chan, K. W., Hoo, R. L., Wang, Y., Tan, K. C., Zhang, J. et al. (2005) Testosterone selectively reduces the high molecular weight form of adiponectin by inhibiting its secretion from adipocytes. Journal of Biological Chemistry 280, 18073 18080.
115. Yanase, T., Fan, W., Kyoya, K., Min, L., Takayanagi, R., Kato, S. Nawata, H. (2008) Androgens and metabolic syndrome: lessons from androgen receptor knock out (ARKO) mice. Journal of Steroid Biochemistry and Molecular Biology 109, 254 257.
116. Yialamas, M. A., Dwyer, A. A., Hanley, E., Lee, H., Pitteloud, N. Hayes, F. J. (2007) Acute sex steroid withdrawal reduces insulin sensitivity in healthy men with idiopathic hypogonadotropic hypogonadism. Journal of Clinical Endocrinology and Metabolism 92, 4254 4259.
117. Yu, I. C., Lin, H. Y., Liu, N. C., Wang, R. S., Sparks, J. D., Yeh, S. Chang, C. (2008) Hyperleptinemia without obesity in male mice lacking androgen receptor in adipose tissue. Endocrinology 149, 2361 2368.
118. Zitzmann, M., Gromoll, J., von Eckardstein, A. Nieschlag, E. (2003) The CAG repeat polymorphism in the androgen receptor gene modulates body fat mass and serum concentrations of leptin and insulin in men. Diabetologia 2003, 46, 31 39.
119. Zumoff, B., Strain, G. W., Miller, L. K., Rosner, W., Senie, R., Seres, D. S. Rosenfeld, R. S. (1990) Plasma free and non-sex-hormone-binding-globulin- bound testosterone are decreased in obese men in proportion to their degree of obesity. Journal of Clinical Endocrinology and Metabolis 71, 929 931.