Reviews in Endocrine and Metabolic Disorders

, Volume 16, Issue 3, pp 249–268 | Cite as

The complex and multifactorial relationship between testosterone deficiency (TD), obesity and vascular disease

  • Abdulmaged M. Traish
  • Michael Zitzmann


Testosterone deficiency (TD) is a well-established and recognized medical condition that contributes to several co-morbidities, including metabolic syndrome, visceral obesity and cardiovascular disease (CVD). More importantly, obesity is thought to contribute to TD. This complex bidirectional interplay between TD and obesity promotes a vicious cycle, which further contributes to the adverse effects of TD and obesity and may increase the risk of CVD. Testosterone (T) therapy for men with TD has been shown to be safe and effective in ameliorating the components of the metabolic syndrome (Met S) and in contributiong to increased lean body mass and reduced fat mass and therefore contributes to weight loss. We believe that appropriate T therapy in obese men with TD is a novel medical approach to manage obesity in men with TD. Indeed, other measures of lifestyle and behavioral changes can be used to augment but not fully replace this effective therapeutic approach. It should be noted that concerns regarding the safety of T therapy remain widely unsubstantiated and considerable evidence exists supporting the benefits of T therapy. Thus, it is paramount that clinicians managing obese men with TD be made aware of this novel approach to treatment of obesity. In this review, we discuss the relationship between TD and obesity and highlight the contemporary advancement in management of obesity with pharmacological and surgical approaches, as well as utilization of T therapy and how this intervention may evolve as a novel approach to treatment of obesity in men with TD .


Testosterone deficiency Hypogonadism Obesity Testosterone therapy Type 2 diabetes Metabolic syndrome Endocrine disruption 


Compliance with ethical standards

Conflict of interest

Dr. Traish declares no conflict of interest.

Prof. Dr. Michael Zitzmann has no conflict of interest to declare in regard to the content of this manuscript.


  1. 1.
    Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384(9945):766–81.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Grieve E, Fenwick E, Yang HC, Lean M. The disproportionate economic burden associated with severe and complicated obesity: a systematic review. Obes Rev. 2013;14:883–94.PubMedCrossRefGoogle Scholar
  3. 3.
  4. 4.
    Bray GA. Why do we need drugs to treat the patient with obesity? Obesity (Silver Spring). 2013;21:893–9.CrossRefGoogle Scholar
  5. 5.
    Ryan DH, Bray GA. Pharmacologic treatment options for obesity: what is old is new again. Curr Hypertens Rep. 2013;15:182–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Apovian CM, Aronne LJ, Bessesen DH, McDonnell ME, Murad MH, Pagotto U, et al. Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2015;100:342–62.PubMedCrossRefGoogle Scholar
  7. 7.
    AMA Declares Obesity as a Disease. Medscape Medical News; June 19, 2013.Google Scholar
  8. 8.
    Ochner CN, Tsai AG, Kushner RF, Wadden TA. Treating obesity seriously: when recommendations for lifestyle change confront biological adaptations. Lancet Diabetes Endocrinol. 2015;3:232–4.PubMedCrossRefGoogle Scholar
  9. 9.
    Buvat J, Montorsi F, Maggi M, Porst H, Kaipia A, Colson MH, et al. Hypogonadal men nonresponders to the PDE5 inhibitor tadalafil benefit from normalization of testosterone levels with a 1% hydroalcoholic testosterone gel in the treatment of erectile dysfunction (TADTEST study). J Sex Med. 2011;8:284–93.PubMedCrossRefGoogle Scholar
  10. 10.
    Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95:2536–59.PubMedCrossRefGoogle Scholar
  11. 11.
    Tajar A, Huhtaniemi IT, O’Neill TW, Finn JD, Pye SR, Lee DM, et al. Characteristics of androgen deficiency in late-onset hypogonadism: results from the European Male Aging Study (EMAS). J Clin Endocrinol Metab. 2012;97:1508–16.PubMedCrossRefGoogle Scholar
  12. 12.
    Haring R, Ittermann T, Völzke H, Krebs A, Zygmunt M, Felix SB, et al. Prevalence, incidence and risk factors of testosterone deficiency in a population-based cohort of men: results from the study of health in Pomerania. Aging Male. 2010;13:247–57.PubMedCrossRefGoogle Scholar
  13. 13.
    Araujo AB, Esche GR, Kupelian V, O’Donnell AB, Travison TG, Williams RE, et al. Prevalence of symptomatic androgen deficiency in men. J Clin Endocrinol Metab. 2007;92:4241–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Traish AM. Adverse health effects of testosterone deficiency (TD) in men. Steroids. 2014;88:106–16.PubMedCrossRefGoogle Scholar
  15. 15.
    Kelly DM, Jones TH. Testosterone and obesity. Obes Rev. 2015;16:581–606.PubMedCrossRefGoogle Scholar
  16. 16.
    Morgentaler A, Miner MM, Caliber M, Guay AT, Khera M, Traish AM. Testosterone therapy and cardiovascular risk: advances and controversies. Mayo Clin Proc. 2015;90:224–51.PubMedCrossRefGoogle Scholar
  17. 17.
    Zarotsky V, Huang MY, Carman W, Morgentaler A, Singhal PK, Coffin D, et al. Systematic literature review of the risk factors, comorbidities, and consequences of hypogonadism in men. Andrology. 2014;2:819–34.PubMedCrossRefGoogle Scholar
  18. 18.
    Camacho EM, Huhtaniemi IT, O’Neill TW, Finn JD, Pye SR, Lee DM, et al. Age-associated changes in hypothalamic-pituitary-testicular function in middle-aged and older men are modified by weight change and lifestyle factors: longitudinal results from the European Male Ageing Study. Eur J Endocrinol. 2013;168:445–55.PubMedCrossRefGoogle Scholar
  19. 19.
    Ahern T, Wu FC. New horizons in testosterone and the ageing male. Age Ageing. 2015;44:188–95.PubMedCrossRefGoogle Scholar
  20. 20.
    Bekaert M, Van Nieuwenhove Y, Calders P, Cuvelier CA, Batens AH, Kaufman JM, Ouwens DM, Ruige JB. Determinants of testosterone levels in human male obesity. Endocrine. 2015.Google Scholar
  21. 21.
    Ng Tang Fui M, Dupuis P, Grossmann M. Lowered testosterone in male obesity: mechanisms, morbidity and management. Asian J Androl. 2014;16:223–31.CrossRefGoogle Scholar
  22. 22.
    Antonio L, Wu FC, O’Neill TW, Pye SR, Carter EL, Finn JD, et al. Associations between sex steroids and the development of metabolic syndrome: a longitudinal study in European men. J Clin Endocrinol Metab. 2015;100:1396–404.PubMedCrossRefGoogle Scholar
  23. 23.
    Bann D, Wu FC, Keevil B, Lashen H, Adams J, Hardy R, et al. Changes in testosterone related to body composition in late midlife: Findings from the 1946 British birth cohort study. Obesity (Silver Spring). 2015;23:1486–92.CrossRefGoogle Scholar
  24. 24.
    Wu FC. Caveat emptor: does testosterone treatment reduce mortality in men? J Clin Endocrinol Metab. 2012;97:1884–6.PubMedCrossRefGoogle Scholar
  25. 25.
    Yeap BB. Testosterone and ill-health in aging men. Nat Clin Pract Endocrinol Metab. 2009;5:113–21.PubMedCrossRefGoogle Scholar
  26. 26.
    Yeap BB. Are declining testosterone levels a major risk factor for ill-health in aging men? Int J Impot Res. 2009;21:24–36.PubMedCrossRefGoogle Scholar
  27. 27.
    Yeap BB, Almeida OP, Hyde Z, Norman PE, Chubb SA, Jamrozik K, et al. Healthier lifestyle predicts higher circulating testosterone in older men: the Health In Men Study. Clin Endocrinol (Oxf). 2009;70:455–63.CrossRefGoogle Scholar
  28. 28.
    Traish AM. Outcomes of testosterone therapy in men with testosterone deficiency (TD): part II. Steroids. 2014;88:117–26.PubMedCrossRefGoogle Scholar
  29. 29.
    Traish AM. Testosterone and weight loss: the evidence. Curr Opin Endocrinol Diabetes Obes. 2014;21:313–22.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Saboor Aftab SA, Kumar S, Barber TM. The role of obesity and type 2 diabetes mellitus in the development of male obesity-associated secondary hypogonadism. Clin Endocrinol (Oxf). 2013;78:330–7.CrossRefGoogle Scholar
  31. 31.
    Dandona P, Aljada A, Bandyopadhyay A. Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol. 2004;25:4–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Rastrelli G, Carter EL, Ahern T, Finn JD, Antonio L, O’Neill TW, et al. Development of and Recovery from Secondary Hypogonadism in Ageing Men: Prospective Results from the EMAS. J Clin Endocrinol Metab. 2015;22:jc20151571.Google Scholar
  33. 33.
    Mulligan T, Frick MF, Zuraw QC, Stemhagen A, McWhirter C. Prevalence of hypogonadism in males aged at least 45 years: the HIM study. Int J Clin Pract. 2006;60:762–9.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Allen NE, Appleby PN, Davey GK, Key TJ. Lifestyle and nutritional determinants of bioavailable androgens and related hormones in British men. Cancer Causes Control. 2002;13:353–63.PubMedCrossRefGoogle Scholar
  35. 35.
    Gapstur SM, Gann PH, Kopp P, Colangelo L, Longcope C, Liu K. Serum androgen concentrations in young men: a longitudi- nal analysis of associations with age, obesity, and race. The CARDIA male hormone study. Cancer Epidemiol Biomark. 2002;11(10 Pt 1):1041–7.Google Scholar
  36. 36.
    Jensen TK, Andersson AM, Jørgensen N, et al. Body mass index in relation to semen quality and reproductive hormones among 1,558 Danish men. Fertil Steril. 2004;82:863–70.PubMedCrossRefGoogle Scholar
  37. 37.
    Svartberg J, von Mühlen D, Schirmer H, Barrett-Connor E, Sundfjord J, Jorde R. Association of endogenous testosterone with blood pressure and left ventricular mass in men. The Tromsø Study. Eur J Endocrinol. 2004;150:65–71.PubMedCrossRefGoogle Scholar
  38. 38.
    Svartberg J, von Mühlen D, Sundsfjord J, Jorde R. Waist circumference and testosterone levels in community dwelling men. The Tromsø Study. Eur J Epidemiol. 2004;19:657–63.PubMedCrossRefGoogle Scholar
  39. 39.
    Corona G, Mannucci E, Ricca V, et al. The age-related decline of testosterone is associated with different specific symptoms and signs in patients with sexual dysfunction. Int J Androl. 2009;32:720–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Glass AR, Swerdloff RS, Bray GA, Dahms WT, Atkinson RL. Low serum testosterone and sex-hormone-binding-globulin in mas- sively obese men. J Clin Endocrinol Metab. 1977;45:1211–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Zumoff B, Strain GW, Miller LK, et al. Plasma free and non- sex-hormone-binding-globulin-bound testosterone are decreased in obese men in proportion to their degree of obesity. J Clin Endocrinol Metab. 1990;71:929–31.PubMedCrossRefGoogle Scholar
  42. 42.
    Pasquali R, Casimirri F, Cantobelli S, et al. Effect of obesity and body fat distribution on sex hormones and insulin in men. Metabolism. 1991;40:101–4.PubMedCrossRefGoogle Scholar
  43. 43.
    Laaksonen DE, Niskanen L, Punnonen K, et al. Sex hormones, inflammation and the metabolic syndrome: a population-based study. Eur J Endocrinol. 2003;149:601–8.PubMedCrossRefGoogle Scholar
  44. 44.
    Kapoor D, Goodwin E, Channer KS, Jones TH. Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol. 2006;154:899–906.PubMedCrossRefGoogle Scholar
  45. 45.
    Hackett G, Cole N, Bhartia M, Kennedy D, Raju J, Wilkinson P. Testosterone replacement therapy with long-acting testosterone undecanoate improves sexual function and quality-of-life param- eters vs. placebo in a population of men with type 2 diabetes. J Sex Med. 2013;10:1612–27.PubMedCrossRefGoogle Scholar
  46. 46.
    Corona G, Rastrelli G, Maggi M. Diagnosis and treatment of late-onset hypogonadism: systematic review and meta-analysis of TRT outcomes. Best Pract Res Clin Endocrinol Metab. 2013;27:557–79.PubMedCrossRefGoogle Scholar
  47. 47.
    Nguyen PL, Alibhai SM, Basaria S, D’Amico AV, Kantoff PW, Keating NL, et al. 2006; Adverse effects of androgen deprivation therapy and strategies to mitigate them. Eur Urol. 2015;67:825–36.PubMedCrossRefGoogle Scholar
  48. 48.
    Braunstein LZ, Chen MH, Loffredo M, Kantoff PW, D’Amico AV. Obesity and the Odds of Weight Gain following Androgen Deprivation Therapy for Prostate Cancer. Prostate Cancer. 2014;2014:230812.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Seible DM, Gu X, Hyatt AS, Beard CJ, Choueiri TK, Efstathiou JA, et al. Weight gain on androgen deprivation therapy: which patients are at highest risk? Urology. 2014;83:1316–21.PubMedCrossRefGoogle Scholar
  50. 50.
    Hamilton EJ, Gianatti E, Strauss BJ, Wentworth J, Lim-Joon D, Bolton D, et al. Increase in visceral and subcutaneous abdominal fat in men with prostate cancer treated with androgen deprivation therapy. Clin Endocrinol (Oxf). 2011;74:377–83.CrossRefGoogle Scholar
  51. 51.
    Kim HS, Moreira DM, Smith MR, Presti Jr JC, Aronson WJ, Terris MK, et al. A natural history of weight change in men with prostate cancer on androgen-deprivation therapy (ADT): results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. BJU Int. 2011;107:924–8.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Saad F, Haider A, Doros G, Traish A. Long-term treatment of hypogonadal men with testosterone produces substantial and sustained weight loss. Obesity (Silver Spring). 2013;21:1975–81.CrossRefGoogle Scholar
  53. 53.
    Francomano D, Bruzziches R, Barbaro G, Lenzi A, Aversa A. Effects of testosterone undecanoate replacement and withdrawal on cardio-metabolic, hormonal and body composition outcomes in severely obese hypogonadal men: a pilot study. J Endocrinol Invest. 2014;37:401–11.PubMedCrossRefGoogle Scholar
  54. 54.
    Haider A, Yassin A, Doros G, Saad F. Effects of long-term testosterone therapy on patients with “diabesity”: results of observational studies of pooled analyses in obese hypogonadal men with type 2 diabetes. Int J Endocrinol 2014; Article ID: 683515.Google Scholar
  55. 55.
    Yassin A, Doros G. Testosterone therapy in hypogonadal men results in sustained and clinically meaningful weight loss. Clin Obes. 2013;3:73–83.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Saad F, Yassin A, Doros G, Haider A. Effects of long-term treatment with testosterone on weight and waist size in 411 hypogonadal men with obesity classes I-III: observational data from two registry studies. Int J Obes (Lond). 2015. doi: 10.1038/ijo.2015.139.Google Scholar
  57. 57.
    Corona G, Rastrelli G, Monami M, Saad F, Luconi M, Lucchese M, et al. Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis. Eur J Endocrinol. 2013;168:829–43.PubMedCrossRefGoogle Scholar
  58. 58.
    Pye SR, Huhtaniemi IT, Finn JD, Lee DM, O’Neill TW, Tajar A, et al. Late-onset hypogonadism and mortality in aging men. EMAS Study Group. J Clin Endocrinol Metab. 2014;99:1357–66.PubMedCrossRefGoogle Scholar
  59. 59.
    Allan CA, McLachlan RI. Androgens and obesity. Curr Opin Endocrinol Diabetes Obes. 2010;17:224–32.PubMedCrossRefGoogle Scholar
  60. 60.
    Allan CA, Strauss BJ, Burger HG, Forbes EA, McLachlan RI. Testosterone therapy prevents gain in visceral adipose tissue and loss of skeletal muscle in nonobese aging men. J Clin Endocrinol Metab. 2008;93:139–46.PubMedCrossRefGoogle Scholar
  61. 61.
    Wu FC, Tajar A, Pye SR, Silman AJ, Finn JD, O’Neill TW, et al. Hypothalamic -pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. J Clin Endocrinol Metab. 2008;93:2737–45.PubMedCrossRefGoogle Scholar
  62. 62.
    Dhindsa S, Miller MG, McWhirter CL, Mager DE, Ghanim H, Chaudhuri A, et al. Testosterone concentrations in diabetic and nondiabetic obese men. Diabetes Care. 2010;33:1186–92.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Travison TG, Araujo AB, Kupelian V, O’Donnell AB, McKinlay JB. The relative contributions of aging, health, and lifestyle factors to serum testosterone decline in men. J Clin Endocrinol Metab. 2007;92:549–55.PubMedCrossRefGoogle Scholar
  64. 64.
    Basaria S. Testosterone levels for evaluation of androgen deficiency. JAMA. 2015;313:1749–50.PubMedCrossRefGoogle Scholar
  65. 65.
    Yeap BB, Almeida OP, Hyde Z, Norman PE, Chubb SA, Jamrozik K, et al. In men older than 70 years, total testosterone remains stable while free testosterone declines with age. The Health in Men Study. Eur J Endocrinol. 2007;156:585–94.PubMedCrossRefGoogle Scholar
  66. 66.
    Elfhag K, Rössner S. Who succeeds in maintaining weight loss? A conceptual review of factors associated with weight loss maintenance and weight regain. Obes Rev. 2005;6:67–85.PubMedCrossRefGoogle Scholar
  67. 67.
    Kaufman JM, Vermeulen A. The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev. 2005;26:833–76.PubMedCrossRefGoogle Scholar
  68. 68.
    Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. J Clin Endocrinol Metab. 2001;86:724–31.PubMedCrossRefGoogle Scholar
  69. 69.
    Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 2002;87:589–98.PubMedCrossRefGoogle Scholar
  70. 70.
    Derby CA, Zilber S, Brambilla D, Morales KH, McKinlay JB. Body mass index, waist circumference and waist to hip ratio and change in sex steroid hormones: the Massachusetts Male Ageing Study. Clin Endocrinol. 2006;65:125–31.CrossRefGoogle Scholar
  71. 71.
    Mohr BA, Bhasin S, Link CL, O’Donnell AB, McKinlay JB. The effect of changes in adiposity on testosterone levels in older men: longitudinal results from the Massachusetts Male Aging Study. Eur J Endocrinol. 2006;155:443–9.PubMedCrossRefGoogle Scholar
  72. 72.
    Travison TG, Araujo AB, O’Donnell AB, Kupelian V, McKinlay JB. A population-level decline in serum testosterone levels in American men. J Clin Endocrinol Metab. 2007;92:196–202.PubMedCrossRefGoogle Scholar
  73. 73.
    Lapauw B, Goemaere S, Zmierczak H, Van Pottelbergh I, Mahmoud A, Taes Y, et al. The decline of serum testosterone levels in community-dwelling men over 70 years of age: descriptive data and predictors of longitudinal changes. Eur J Endocrinol. 2008;159:459–68.PubMedCrossRefGoogle Scholar
  74. 74.
    Vermeulen A, Kaufman JM, Giagulli VA. Influence of some biological indexes on sex hormone-binding globulin and androgen levels in aging or obese males. J Clin Endocrinol Metab. 1996;81:1821–6.PubMedGoogle Scholar
  75. 75.
    Coviello AD, Haring R, Wellons M, Vaidya D, Lehtimak IT, Keildson S, et al. A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple loci implicated in sex steroid hormone regulation. PLoS Genet. 2012;8, e1002805.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Cohen P. The hypogonadal-obesity-cycle. Med Hypothesis. 1999;52:49–51.CrossRefGoogle Scholar
  77. 77.
    Jones TH. Testosterone associations with erectile dysfunction, diabetes, and the metabolic syndrome. Eur Urol. 2007;6:847–57.CrossRefGoogle Scholar
  78. 78.
    Guay A, Seftel AD, Traish A. Hypogonadism in men with erectile dysfunction may be related to a host of chronic illnesses. Int J Impot Res. 2010;22:9–19.PubMedCrossRefGoogle Scholar
  79. 79.
    Kyrou I, Tsigos C. Chronic stress, visceral obesity and gonadal dysfunction. Hormones (Athens). 2008;7:287–93.CrossRefGoogle Scholar
  80. 80.
    Corona G, Vignozzi L, Sforza A, Mannucci E, Maggi M. Obesity and late-onset hypogonadism.Mol Cell Endocrinol. 2015.Google Scholar
  81. 81.
    Tajar A, Forti G, O’Neill TW, Lee DM, Silman AJ, Finn JD, et al. Characteristics of secondary, primary, and compensated hypogonadism in aging men: evidence from the European Male Ageing Study. J Clin Endocrinol Metab. 2010;95:1810–8.PubMedCrossRefGoogle Scholar
  82. 82.
    Corona G, Rastrelli G, Morelli A, Vignozzi L, Mannucci E, Maggi M. Hypogonadism and Metabolic Syndrome. J Endocrinol Invest. 2011;34:557–67.PubMedCrossRefGoogle Scholar
  83. 83.
    Hofstra J, Loves S, van Wageningen B, et al. High prevalence of hypogonadotropic hypogonadism in men referred for obesity treatment. Neth J Med. 2008;66:103–9.PubMedGoogle Scholar
  84. 84.
    Pasquali R. Obesity and androgens: Facts and perspectives. Fertil Steril. 2006;85:1319–40.PubMedCrossRefGoogle Scholar
  85. 85.
    Isidori AM, Giannetta E, Greco EA, et al. Effects of testos- terone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clin Endocrinol (Oxf). 2005;63:280–93.CrossRefGoogle Scholar
  86. 86.
    Mammi C, Calanchini M, Antelmi A, et al. Androgens and adipose tissue in males: a complex and reciprocal interplay. Int J Endocrinol. 2012;2012:789653.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Traish AM, Abdou R, Kypreos KE. Androgen deficiency and atherosclerosis: The lipid link. Vascul Pharmacol. 2009;51:303–13.PubMedCrossRefGoogle Scholar
  88. 88.
    Traish AM, Abdallah B, Yu G. Androgen deficiency and mitochondrial dysfunction: implications for fatigue, muscle dysfunction, insulin resistance, diabetes, and cardiovascular disease. Horm Mol Biol Clin Investig. 2011;8:431–44.PubMedGoogle Scholar
  89. 89.
    Yu G, Traish AM. Induced testosterone deficiency: from clinical presentation of fatigue, erectile dysfunction and muscle atrophy to insulin resistance and diabetes. Horm Mol Biol Clin Investig. 2011;8:425–30.PubMedGoogle Scholar
  90. 90.
    Pugeat M, Nader N, Hogeveen K, Raverot G, Déchaud H, Grenot C. Sex hormone-binding globulin gene expression in the liver: drugs and the metabolic syndrome. Mol Cell Endocrinol. 2010;316:53–9.PubMedCrossRefGoogle Scholar
  91. 91.
    Michalakis K, Mintziori G, Kaprara A, Tarlatzis BC, Goulis DG. The complex interaction between obesity, metabolic syndrome and reproductive axis: a narrative review. Metabolism. 2013;62:457–78.PubMedCrossRefGoogle Scholar
  92. 92.
    Chazenbalk G, Singh P, Irge D, Shah A, Abbott DH, Dumesic DA. Androgens inhibit adipogenesis during human adipose stem cell commitment to preadipocyte formation. Steroids. 2013;78:920–6.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Gupta V, Bhasin S, Guo W, Singh R, Miki R, Chauhan P, et al. Effects of dihydrotestosterone on differentiation and proliferation of human mesenchymal stem cells and preadipocytes. Mol Cell Endocrinol. 2008;296:32–40.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Singh R, Artaza JN, Taylor WE, Braga M, Yuan X, Gonzalez-Cadavid NF, et al. Testosterone inhibits adipogenic differentiation in 3T3-L1 cells: nuclear translocation of androgen receptor complex with beta-catenin and T-cell factor 4 may bypass canonical Wnt signaling to down-regulate adipogenic transcription factors. Endocrinology. 2006;147:141–54.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Singh R, Artaza JN, Taylor WE, Gonzalez-Cadavid NF, Bhasin S. Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/2 pluripotent cells through an androgen receptor-mediated pathway. Endocrinology. 2003;144:5081–8.PubMedCrossRefGoogle Scholar
  96. 96.
    Mauras N, Hayes V, Welch S, et al. Testosterone deficiency in young men: marked alterations in whole body protein kinetics, strength, and adiposity. J Clin Endocrinol Metab. 1998;83:1886–92.PubMedGoogle Scholar
  97. 97.
    Rana K, Fam BC, Clarke MV, Pang TP, Zajac JD, MacLean HE. Increased adiposity in DNA binding-dependent androgen receptor knockout male mice associated with decreased voluntary activity and not insulin resistance. Am J Physiol Endocrinol Metab. 2010;301:E767–78.CrossRefGoogle Scholar
  98. 98.
    McInnes KJ, Smith LB, Hunger NI, Saunders PT, Andrew R, Walker BR. Deletion of the androgen receptor in adipose tissue in male mice elevates retinol binding protein 4 and reveals independent effects on visceral fat mass and on glucose homeostasis. Diabetes. 2012;61:1072–81.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Semirale AA, Zhang XW, Wiren KM. Body composition changes and inhibition of fat development in vivo implicates androgen in regulation of stem cell lineage allocation. J Cell Biochem. 2011;112:1773–86.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Saad F, Aversa A, Isidori AM, Gooren LJ. Testosterone as potential effective therapy in treatment of obesity in men with testosterone deficiency: a review. Curr Diabetes Rev. 2012;8:131–43.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    DeFronzo RA, Jacot E, Jequier E, Maeder E, Wahren J, Felber JP. The effect of insulin on the disposal of intravenous glucose. Results from indirect calorimetry and hepatic and femoral venous catheterization. Diabetes. 1981;30:1000–7.PubMedCrossRefGoogle Scholar
  102. 102.
    Baron AD, Brechtel G, Wallace P, Edelman SV. Rates and tissue sites of non-insulin- and insulin-mediated glucose uptake in humans. Am J Physiol. 1988;255:E769–74.PubMedGoogle Scholar
  103. 103.
    Hammoud A, Gibson M, Hunt SC, Adams TD, Carrell DT, Kolotkin RL, et al. Effect of Roux-en-Y gastric bypass surgery on the sex steroids and quality of life in obese men. J Clin Endocrinol Metab. 2009;94:1329–32.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    De Maddalena C, Vodo S, Petroni A, Aloisi AM. Impact of testosterone on body fat composition. J Cell Physiol. 2012;227:3744–8.PubMedCrossRefGoogle Scholar
  105. 105.
    Kelly DM, Nettleship JE, Akhtar S, Muraleedharan V, Sellers DJ, Brooke JC, et al. Testosterone suppresses the expression of regulatory enzymes of fatty acid synthesis and protects against hepatic steatosis in cholesterol-fed androgen deficient mice. Life Sci. 2014;109:95–103.PubMedCrossRefGoogle Scholar
  106. 106.
    Calvo N, Beltrán-Debón R, Rodríguez-Gallego E, Hernández-Aguilera A, Guirro M, Mariné-Casadó R, et al. Liver fat deposition and mitochondrial dysfunction in morbid obesity: An approach combining metabolomics with liver imaging and histology. World J Gastroenterol. 2015;21:7529–44.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Pratchayasakul W, Sa-Nguanmoo P, Sivasinprasasn S, Pintana H, Tawinvisan R, Sripetchwandee J, et al. Obesity accelerates cognitive decline by aggravating mitochondrial dysfunction, insulin resistance and synaptic dysfunction under estrogen-deprived conditions. Horm Behav. 2015;72:68–77.PubMedCrossRefGoogle Scholar
  108. 108.
    Heinonen S, Buzkova J, Muniandy M, Kaksonen R, Ollikainen M, Ismail K, Hakkarainen A, Lundbom J, Lundbom N, Vuolteenaho K, Moilanen E, Kaprio J, Rissanen A, Suomalainen A, Pietiläinen KH. Impaired mitochondrial biogenesis in adipose tissue in acquired obesity. Diabetes. 2015.Google Scholar
  109. 109.
    Alam MA, Rahman MM. Mitochondrial dysfunction in obesity: potential benefit and mechanism of Co-enzyme Q10 supplementation in metabolic syndrome. J Diabetes Metab Disord. 2014;13:60.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Bullon P, Newman HN, Battino M. Obesity, diabetes mellitus, atherosclerosis and chronic periodontitis: a shared pathology via oxidative stress and mitochondrial dysfunction? Periodontol 2000. 2014;64:139–53.PubMedCrossRefGoogle Scholar
  111. 111.
    García-Ruiz C, Baulies A, Mari M, García-Rovés PM, Fernandez-Checa JC. Mitochondrial dysfunction in non-alcoholic fatty liver disease and insulin resistance: cause or consequence? Free Radic Res. 2013;47:854–68.PubMedCrossRefGoogle Scholar
  112. 112.
    Bournat JC, Brown CW, Bournat JC, Brown CW. Mitochondrial dysfunction in obesity. Curr Opin Endocrinol Diabetes Obes. 2010;17:446–52.PubMedCrossRefGoogle Scholar
  113. 113.
    Garcia-Roves PM. Mitochondrial pathophysiology and type 2 diabetes mellitus. Arch Physiol Biochem. 2011;117:177–87.PubMedCrossRefGoogle Scholar
  114. 114.
    Niemann B, Chen Y, Teschner M, Li L, Silber RE, Rohrbach S, et al. Obesity induces signs of premature cardiac aging in younger patients: the role of mitochondria. J Am Coll Cardiol. 2011;57:577–85.PubMedCrossRefGoogle Scholar
  115. 115.
    Zitzmann M. Testosterone deficiency, insulin resistance and the metabolic syndrome. Nat Rev Endocrinol. 2009;5:673–81.PubMedCrossRefGoogle Scholar
  116. 116.
    Morote J, Gómez-Caamaño A, Alvarez-Ossorio JL, Pesqueira D, Tabernero A, Gómez Veiga F, et al. The metabolic syndrome and its components in patients with prostate cancer on androgen deprivation therapy. J Urol. 2015;193:1963–9.PubMedCrossRefGoogle Scholar
  117. 117.
    Urushima H, Inomata-Kurashiki Y, Nishimura K, Sumi R, Shimomura I, Nonomura N, et al. The effects of androgen deprivation therapy with weight management on serum aP2 and adiponectin levels in prostate cancer patients. Aging Male. 2015;18:72–6.PubMedCrossRefGoogle Scholar
  118. 118.
    Trost LW, Serefoglu E, Gokce A, Linder BJ, Sartor AO, Hellstrom WJ. Androgen deprivation therapy impact on quality of life and cardiovascular health, monitoring therapeutic replacement. J Sex Med. 2013;10 Suppl 1:84–101.PubMedCrossRefGoogle Scholar
  119. 119.
    Andrès E, Eschwege P, Lang H, Moreau JL, Peiffert D, Thiery-Vuillemin A, et al. Metabolic impact of androgen deprivation therapy for prostate cancer. Prog Urol. 2012;22 Suppl 2:S39–47.PubMedCrossRefGoogle Scholar
  120. 120.
    Timilshina N, Breunis H, Alibhai SM. Impact of androgen deprivation therapy on weight gain differs by age in men with nonmetastatic prostate cancer. J Urol. 2012;188:2183–8.PubMedCrossRefGoogle Scholar
  121. 121.
    García-Cruz E, Leibar-Tamayo A, Romero-Otero J, Asiaín I, Carrión A, Castañeda R, et al. Marked testosterone deficiency-related symptoms may be associated to higher metabolic risk in men with low testosterone levels. J Sex Med. 2014;11:2292–301.PubMedCrossRefGoogle Scholar
  122. 122.
    Charakida M, Khan T, Johnson W, Finer N, Woodside J, Whincup PH, et al. Lifelong patterns of BMI and cardiovascular phenotype in individuals aged 60–64 years in the 1946 British birth cohort study: an epidemiological study. Lancet Diab Endocrinol. 2014;2:648–54.CrossRefGoogle Scholar
  123. 123.
    Finkelstein EA, Trogdon JG, Brown DS, Allaire BT, Dellea PS, Kamal-Bahl SJ. The lifetime medical cost burden of overweight and obesity: implications for obesity prevention. Obesity (Silver Spring). 2008;16:1843–8.CrossRefGoogle Scholar
  124. 124.
    Adabag S, Huxley RR, Lopez FL, Chen LY, Sotoodehnia N, Siscovick D, et al. Obesity related risk of sudden cardiac death in the atherosclerosis risk in communities study. Heart. 2015;101:215–21.PubMedCrossRefGoogle Scholar
  125. 125.
    Sjöström L, Narbro K, Sjöström CD, Karason K, Larsson B, Wedel H, et al. Swedish obese subjects study. Effect of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357:741–72.PubMedCrossRefGoogle Scholar
  126. 126.
    Sjöström L, Peltonen M, Jacobson P, Sjöström CD, Karason K, Wedel H, et al. Bariatric surgery and long-term cardiovascular events. JAMA. 2012;307:56–65.PubMedCrossRefGoogle Scholar
  127. 127.
    Wadden TA, Victoria LW, Moran CH, Bailer BA. Lifestyle modification for obesity: new developments in diet, physical activity, and behavior therapy. Circulation. 2012;125(1):157–1170.Google Scholar
  128. 128.
    Moyer VA. Screening for and management of obesity in adults: U.S. Preventive Services Task Force Recommendation. Ann Intern Med. 2012;157:373–8.PubMedGoogle Scholar
  129. 129.
    Dyson PA. The therapeutics of lifestyle management on obesity. Diabetes Obes Metab. 2010;12:941–6.PubMedCrossRefGoogle Scholar
  130. 130.
    Look AHEAD Research Group, Wing RR. Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: four-year results of the Look AHEAD trial. Arch Intern Med. 2010;170:1566–75.Google Scholar
  131. 131.
    Johansson K, Neovius M, Hemmingsson E. Effects of anti-obesity drugs, diet, and exercise on weight-loss maintenance after a very-low-calorie diet or low-calorie diet: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr. 2014;99:14–23.PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Astrup A, Carraro R, Finer N, Harper A, Kunesova M, Lean ME, et al. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int J Obes (Lond). 2012;36:843–54.CrossRefGoogle Scholar
  133. 133.
    Giagulli VA, Carbone MD, Ramunni MI, Licchelli B, De Pergola G, Sabbà C, Guastamacchia E, Triggiani V. Adding liraglutide to lifestyle changes, metformin and testosterone therapy boosts erectile function in diabetic obese men with overt hypogonadism. Andrology. 2015. doi:  10.1111/andr.12099.
  134. 134.
    Nauck M, Frid A, Hermansen K, Thomsen AB, During M, Shah N, et al. Long-term efficacy and safety comparison of liraglutide, glimepiride and placebo, all in combination with metformin in type 2 diabetes: 2-year results from the LEAD-2 study. Diabetes Obes Metab. 2013;15:204–12.PubMedCrossRefGoogle Scholar
  135. 135.
    Li CJ, Yu Q, Yu P, Yu TL, Zhang QM, Lu S, et al. Changes in liraglutide-induced body composition are related to modifications in plasma cardiac natriuretic peptides levels in obese type 2 diabetic patients. Cardiovasc Diabetol. 2014;13:36.PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Carlsson LM, Peltonen M, Ahlin S, Anveden Å, Bouchard C, Carlsson B, et al. Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects. N Engl J Med. 2012;367:695–704.PubMedCrossRefGoogle Scholar
  137. 137.
    Diabetes Prevention Program Research Group. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009;374:1677–86.PubMedCentralCrossRefGoogle Scholar
  138. 138.
    Sjöström L, Peltonen M, Jacobson P, Ahlin S, Andersson-Assarsson J, Anveden Å, et al. Association of bariatric surgery with long-term remission of type 2 diabetes and with microvascular and macrovascular complications. JAMA. 2014;311:2297–304.PubMedCrossRefGoogle Scholar
  139. 139.
    Arterburn DE, Olsen MK, Smith VA, Livingston EH, Van Scoyoc L, Yancy Jr WS, et al. Association between bariatric surgery and long-term survival. JAMA. 2015;313:62–70.PubMedCrossRefGoogle Scholar
  140. 140.
    Chang SH, Stoll CR, Song J, Varela JE, Eagon CJ, Colditz GA. The effectiveness and risks of bariatric surgery: an updated systematic review and meta-analysis, 2003–2012. JAMA Surg. 2014;149:275–87.PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Brethauer SA, Aminian A, Romero-Talamás H, Batayyah E, Mackey J, Kennedy L, et al. Can diabetes be surgically cured? Long-term metabolic effects of bariatric surgery in obese patients with type 2 diabetes mellitus. Ann Surg. 2013;258:628–37.PubMedPubMedCentralGoogle Scholar
  142. 142.
    Chen SY, Stem M, Schweitzer MA, Magnuson TH, Lidor AO. Assessment of post-discharge complications after bariatric surgery: A National Surgical Quality Improvement Program analysis. Surgery. 2015;158:777–86.PubMedCrossRefGoogle Scholar
  143. 143.
    Gadde KM. Current pharmacotherapy for obesity: extrapolation of clinical trials data to practice. Expert Opin Pharmacother. 2014;15:809–22.PubMedCrossRefGoogle Scholar
  144. 144.
    Calderón B, Galdón A, Calañas A, Peromingo R, Galindo J, García-Moreno F, et al. Effects of bariatric surgery on male obesity-associated secondary hypogonadism: comparison of laparoscopic gastric bypass with restrictive procedures. Obes Surg. 2014;24:1686–92.PubMedCrossRefGoogle Scholar
  145. 145.
    Maciejewski ML, Livingston EH, Smith VA, et al. Survival among high-risk patients after bariatric surgery. JAMA. 2011;305:2419–26.PubMedCrossRefGoogle Scholar
  146. 146.
    Himpens J, Cadière GB, Bazi M, Vouche M, Cadière B, Dapri G. Long-term outcomes of laparoscopic adjustable gastric banding. Arch Surg. 2011;146:802–7.PubMedCrossRefGoogle Scholar
  147. 147.
    Pellitero S, Olaizola I, Alastrue A, Martínez E, Granada ML, Balibrea JM, et al. Hypogonadotropic hypogonadism in morbidly obese males is reversed after bariatric surgery. Obes Surg. 2012;22:1835–42.PubMedCrossRefGoogle Scholar
  148. 148.
    Aversa A, Bruzziches R, Francomano D, Rosano G, Isidori AM, Lenzi A, et al. Effects of testosterone undecanoate on cardiovascular risk factors and atherosclerosis in middle-aged men with late-onset hypogonadism and metabolic syndrome: results from a 24-month, randomized, double-blind, placebo-controlled study. J Sex Med. 2010;7:3495–503.PubMedCrossRefGoogle Scholar
  149. 149.
    Aversa A, Bruzziches R, Francomano D, Greco EA, Fornari R, Di Luigi L, et al. Effects of long-acting testosterone undecanoate on bone mineral density in middle-aged men with late-onset hypogonadism and metabolic syndrome: results from a 36 months controlled study. Aging Male. 2012;15:96–102.PubMedCrossRefGoogle Scholar
  150. 150.
    Behre HM, Tammela TL, Arver S, Tolrá JR, Bonifacio V, Lamche M, et al. A randomized, double-blind, placebo-controlled trial of testosterone gel on body composition and health-related quality-of-life in men with hypogonadal to low-normal levels of serum testosterone and symptoms of androgen deficiency over 6 months with 12 months open-label follow-up. Aging Male. 2012;15:198–207.PubMedCrossRefGoogle Scholar
  151. 151.
    Finkelstein JS, Lee H, Burnett-Bowie S-A, Pallais JC, Yu EW, Borges LF, et al. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. 2013;369:1011–22.PubMedPubMedCentralCrossRefGoogle Scholar
  152. 152.
    Francomano D, Lenzi A, Aversa A. Effects of five-year treatment with testosterone undecanoate on metabolic and hormonal parameters in ageing men with metabolic syndrome. Int J Endocrinol 2014; Article ID: 527470.Google Scholar
  153. 153.
    Borst SE, Yarrow JF, Conover CF, Nseyo U, Meuleman JR, Lipinska JA, et al. Musculoskeletal and prostate effects of combined testosterone and finasteride administration in older hypogonadal men: a randomized, controlled trial. Am J Physiol Endocrinol Metab. 2014;306:E433–42.PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    Kapoor D, Aldred H, Clark S, Channer KS, Jones TH. Clinical and biochemical assessment of hypogonadism in men with type 2 diabetes. Diabetes Care. 2007;30:911–7.PubMedCrossRefGoogle Scholar
  155. 155.
    Svartberg J, Agledahl I, Figenschau Y, Sildnes T, Waterloo K, Jorde R. Testosterone treatment in elderly men with subnormal testosterone levels improves body composition and BMD in the hip. Int J Impot Res. 2008;20:378–87.PubMedCrossRefGoogle Scholar
  156. 156.
    Pexman-Fieth C, Behre HM, Morales A, Kan-Dobrosky N, Miller MG. A 6-month observational study of energy, sexual desire, and body proportions in hypogonadal men treated with a testosterone 1 % gel. Aging Male. 2014;17:1–11.PubMedPubMedCentralCrossRefGoogle Scholar
  157. 157.
    Heufelder AE, Saad F, Bunck MC, Gooren L. Fifty-two-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;30:726–33.PubMedCrossRefGoogle Scholar
  158. 158.
    Kalinchenko SY, Tishova YA, Mskhalaya GJ, Gooren LJG, Giltay EJ, Saad F. Effects of testosterone supplementation on markers of the metabolic syndrome and inflammation in hypogonadal men with the metabolic syndrome: the double-blinded placebo-controlled Moscow study. Clin Endocrinol (Oxf). 2010;73:602–12.CrossRefGoogle Scholar
  159. 159.
    Zitzmann M, Mattern A, Hanisch J, Gooren L, Jones H, Maggi M. IPASS: a study on the tolerability and effectiveness of injectable testosterone undecanoate for the treatment of male hypogonadism in a worldwide sample of 1,438 men. J Sex Med. 2013;10:579–88.PubMedCrossRefGoogle Scholar
  160. 160.
    Nedogoda SV, Barykina IN, Salasyuk AS, Smirnova VO and Khripaeva VJ. Effects of testosterone replacement therapy on cardio-metabolic, hormonal and anthropometric parameters in obese hypogonadal men with metabolic syndrome. Obesity: Open Access 2015.Google Scholar
  161. 161.
    Haider A, Meergans U, Traish A, Saad F, Doros G, Lips P, et al. Progressive improvement of T-scores in men with osteoporosis and subnormal serum testosterone levels upon treatment with testosterone over six years. Int J Endocrinol 2014; Article ID: 496948.Google Scholar
  162. 162.
    Saad F, Yassin A, Almehmadi Y, Doros G, Gooren L. Effects of long-term testosterone replacement therapy, with a temporary intermission, on glycemic control of nine hypogonadal men with type 1 diabetes mellitus - a series of case reports. Aging Male. 2015;18:164–8.PubMedCrossRefGoogle Scholar
  163. 163.
    Hackett G, Cole N, Bhartia M, Kennedy D, Raju J, Wilkinson P, et al. Testosterone replacement therapy improves metabolic parameters in hypogonadal men with type 2 diabetes but not in men with coexisting depression: The BLAST Study. J Sex Med. 2014;11:840–56.PubMedCrossRefGoogle Scholar
  164. 164.
    Hackett G, Cole N, Bhartia M, Kennedy D, Raju J, Wilkinson P, et al. The response to testosterone undecanoate in men with type 2 diabetes is dependent on achieving threshold serum levels (the BLAST study). Int J Clin Pract. 2014;68:203–15.PubMedCrossRefGoogle Scholar
  165. 165.
    Bhattacharya RK, Khera M, Blick G, Kushner H, Nguyen D, Miner MM. Effect of 12 months of testosterone replacement therapy on metabolic syndrome components in hypogonadal men: data from the Testim Registry in the US (TRiUS). BMC Endocr Disord. 2011;11:18.PubMedPubMedCentralCrossRefGoogle Scholar
  166. 166.
    Bhattacharya RK, Khera M, Blick G, Kushner H, Miner MM. Testosterone replacement therapy among elderly males: the Testim Registry in the US (TRiUS). Clin Interv Aging. 2012;7:321–30.PubMedPubMedCentralCrossRefGoogle Scholar
  167. 167.
    Garcia JA, Sanchez PE, Fraile C, Escovar P. Testosterone undecanoate improves erectile dysfunction in hypogonadal men with the metabolic syndrome refractory to treatment with phosphodiesterase type 5 inhibitors alone. Andrologia. 2011;43:293–6.PubMedCrossRefGoogle Scholar
  168. 168.
    Haider A, Zitzmann M, Doros G, Isbarn H, Hammerer P, Yassin A. Incidence of prostate cancer in hypogonadal men receiving testosterone therapy: observations from 5-year median followup of 3 registries. J Urol. 2015;193:80–6.PubMedCrossRefGoogle Scholar
  169. 169.
    Baillargeon J, Kuo YF, Fang X, Shahinian VB. Long-term exposure to testosterone therapy and the risk of high grade prostate cancer. J Urol. 2015.Google Scholar
  170. 170.
    Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, et al. Adverse events associated with testosterone administration. N Engl J Med. 2010;363:109–22.PubMedPubMedCentralCrossRefGoogle Scholar
  171. 171.
    Xu L, Freeman G, Cowling BJ, Schooling CM. Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials. BMC Med. 2013;11:108.PubMedPubMedCentralCrossRefGoogle Scholar
  172. 172.
    Vigen R, O’Donnell CI, Barón AE, Grunwald GK, Maddox TM, Bradley SM, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310:1829–3186. Erratum in: JAMA. 2014 Mar 5;311(9):967.PubMedCrossRefGoogle Scholar
  173. 173.
    Finkle WD, Greenland S, Ridgeway GK, Adams JL, Frasco MA, Cook MB, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One. 2014;9(1), e85805.PubMedPubMedCentralCrossRefGoogle Scholar
  174. 174.
    Baillargeon J, Urban RJ, Kuo YF, Ottenbacher KJ, Raji MA, Du F, et al. Risk of Myocardial Infarction in Older Men Receiving Testosterone Therapy. Ann Pharmacother. 2014;48:1138–44.PubMedPubMedCentralCrossRefGoogle Scholar
  175. 175.
    Baillargeon J, Urban RJ, Morgentaler A, Glueck CJ, Baillargeon G, Sharma G, et al. Risk of Venous Thromboembolism in Men Receiving Testosterone Therapy. Mayo Clin Proc. 2015;90:1038–45.PubMedCrossRefGoogle Scholar
  176. 176.
    Sharma R, Oni OA, Gupta K, Chen G, Sharma M, Dawn B, Sharma R, Parashara D, Savin VJ, Ambrose JA, Barua RS. Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men. Eur Heart J. 2015.Google Scholar
  177. 177.
    Tan RS, Cook KR, Reilly WG. Myocardial Infarction and Stroke Risk in Young Healthy Men Treated with Injectable Testosterone. Int J Endocrinol. 2015;2015:970750.PubMedPubMedCentralGoogle Scholar
  178. 178.
    Etminan M, Skeldon SC, Goldenberg SL, Carleton B, Brophy JM. Testosterone therapy and risk of myocardial infarction: a pharmacoepidemiologic study. Pharmacotherapy. 2015;35:72–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of UrologyBoston University School of MedicineBostonUSA
  2. 2.Clinical AndrologyCentre for Reproductive Medicine and AndrologyMuensterGermany

Personalised recommendations