Coronary artery disease and diabetes are major causes of morbidity and mortality in the Western countries. Unfortunately, by the time these chronic diseases present clinically, irreversible vascular damage has already occurred. Thus, it is critical to identify upstream determinants of disease and target them for preventive measures. The metabolic syndrome is characterized by dyslipidemia, hyperglycemia, hypertension and central obesity. It has been established as a precursor state in which patients are at significantly increased risk of developing cardiovascular disease. Aging is associated with a gradual decline of testosterone levels in men.1 This decrease is accompanied by changes in body composition including increases in adipose mass and decreases in lean body mass, dyslipidemia, insulin resistance and glucose metabolism dysregulation.
Epidemiological studies have established that low testosterone/low sex hormone-binding globulin can predict the development of the metabolic syndrome.2 A number of studies have found an inverse relationship between the severity of the metabolic syndrome and plasma testosterone.3 These previous studies agree with the results of Akishita et al.4 Adiposity and hyperinsulinemia may suppress sex hormone-binding globulin synthesis and therefore circulating testosterone levels.5 Furthermore, insulin and leptin have a suppressive effect on testicular steroidogenesis.6, 7 Thus, there is evidence that adiposity is a significant factor in lowering circulating levels of testosterone. Conversely, low testosterone and sex hormone-binding globulin themselves may induce metabolic syndrome.8 Thus, the question arises whether testosterone therapy could have a role in the treatment of the metabolic syndrome. There is increasing evidence that testosterone treatment has beneficial effects on visceral fat mobilization and other elements of the metabolic syndrome.9 Changes in visceral fat appeared to be a function of changes in total serum testosterone.
Serum triglycerides, total cholesterol, low-density lipoprotein cholesterol and fasting insulin levels were higher and high-density lipoprotein cholesterol levels lower in men with lower serum testosterone levels.10 In fact, men with prostate carcinoma who receive androgen ablation are prime examples of this phenomenon. In these men, there is increased total serum cholesterol, low-density lipoprotein cholesterol and triglycerides, and decreased high-density lipoprotein cholesterol. Low testosterone level in men is also associated with higher blood pressure, left ventricular mass and left ventricular hypertrophy.11 Testosterone treatment also has beneficial effects on the blood pressure of abdominally obese men.12
There is an association between serum testosterone and insulin resistance.10 In other studies, testosterone levels are frequently low in men with type 2 diabetes, and the majority of these men have symptoms of hypogonadism. Obesity is associated with low testosterone levels in diabetic men.13 As indicated above, androgen deprivation in men with prostate carcinoma leads to deterioration in insulin sensitivity and therefore increases the risk of developing type 2 diabetes mellitus.14 A single-blind randomized study of testosterone administration in men with the metabolic syndrome and recent onset of diabetes established the beneficial effects of testosterone on blood glucose control over and above the effects on diet and exercise.15 After 1 year, there were significantly more men in the testosterone-treated group who no longer met the criteria for metabolic syndrome.15 In randomized control trials, testosterone treatment improved insulin sensitivity in middle-aged abdominally obese men,16 although the findings have not been completely consistent.17
Testosterone itself may contribute to the pathogenesis of insulin resistance and diabetes by increasing skeletal muscle mass at the expense of fat mass and decreasing abdominal obesity through inhibition of lipoprotein lipase activity.16 There is a close relationship between low testosterone levels, insulin resistance and abdominal obesity. Experimental studies have shown that testosterone affects fat metabolism largely through stimulation of β-adrenergic-induced lipolysis.18 In addition, testosterone has been shown to inhibit lipoprotein lipase activity in abdominal adipose tissue, leading to decreased triglyceride uptake in central fat depots.19
Both overall and abdominal obesity may decrease testosterone levels. The effects of weight loss on testosterone and sex hormone-binding globulin have been consistent, and both overall and abdominal obesity increase glucocorticoid turnover and production. This increase results in abnormal control of the hypothalamic–pituitary–adrenal axis and possibly in mild hypoandrogenism in men.20 Obesity is also associated with abnormally increased expression and activity of the enzyme 11β-hydroxysteroid dehydrogenase type 1 in adipose tissue. This enzyme determines local glucocorticoid concentrations through interconversion of cortisol and its inactive counterpart cortisone.21 Thus, it is likely that the relationship between sex hormones and metabolic syndrome is, to some degree, bidirectional, with low sex hormone levels being predictive of the development of metabolic syndrome, which in turn is associated with a further decline in sex hormone levels.
Recent epidemiological reports have found that low testosterone levels are a predictor of mortality in elderly men.22 The results of Araujo et al.23 did not confirm this relationship between plasma testosterone and overall mortality. The study did support, however, that low testosterone levels are predictive of mortality from coronary heart disease.23
A deficiency of testosterone causes serious deterioration in men's health. The diagnosis of metabolic syndrome often leads to cardiovascular disease and diabetic complications. Thus, testosterone has even more effects on men's health than previously thought and should be regarded as an important hormone in health maintenance.
Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, Bremner WJ, McKinlay JB . 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: 589–598.
Muller M, Grobbee DE, den Tonkelaar I, Lamberts SW, van der Schouw YT . Endogenous sex hormones and metabolic syndrome in aging men. J Clin Endocrinol Metab 2005; 90: 2618–2623.
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: 443–452.
Akishita M, Fukai S, Hashimoto M, Kameyama Y, Nomura K, Nakamura T, Ogawa S, Iijima K, Eto M, Ouchi Y . Association of low testosterone level with metabolic syndrome and its components in middle-aged Japanese men. Hypertension Res (e-pub ahead of print 26 March 2010; doi:1038/hr.2010.43).
Kaufman JM, Vermeullen A . The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev 2005; 26: 833–876.
Pitteloud N, Hardin M, Dwyer AA, Valassi E, Yialamas M, Elahi D, Hayes FJ . Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men. J Clin Endocrinol Metab 2005; 90: 2636–2641.
Isodori AM, Caprio M, Strollo F, Moretti C, Frajese G, Isidori A, Fabbri A . Leptin and androgens in male obesity: evidence for leptin contribution to reduce androgen levels. J Clin Endocrinol Metab 1999; 84: 3673–3680.
Laaksonen DE, Niskanen L, Punnonen K, Nyyssönen K, Tuomainen TP, Valkonen VP, Salonen R, Salonen JT . Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care 2004; 27: 1036–1041.
Allen CA, Strauss BJ, Burger HG, Forbes EA, McLachlan RI . Testosterone therapy prevents gain in visceral adipose tissue and loss of skeletal muscle in non-obese aging men. J Clin Endocrinol Metab 2008; 93: 139–146.
Simon D, Charles MA, Nahoul K, Orssaud G, Kremski J, Hully V, Joubert E, Papoz L, Eschwege E . Association between plasma total testosterone and cardiovascular risk factors in healthy adult men: the Telecom Study. J Clin Endocrinol Metab 1997; 82: 682–685.
Svartberg J, von Muhlen D, Schirmer H, Barrett-Connor E, Sundfjord J, Jorde R . Association of endogenous testosterone with blood pressure and left ventricular mass in men. The Tromso Study. Eur J Endocrinol 2004; 150: 65–71.
Marin P, Holmang S, Gustafsson C, Jönsson L, Kvist H, Elander A, Eldh J, Sjöström L, Holm G, Björntorp P . Androgen treatment of abdominally obese men. Obes Res 1993; 1: 245–251.
Kapoor D, Aldred H, Clark S, Channer KS, Jones TH . Clinical and biochemical assessment of hypogonadism in men with type 2 diabetes: correlations with bioavailable testosterone and visceral adiposity. Diabetes Care 2007; 30: 911–917.
Smith RM, Lee H, Nathan DM . Insulin sensitivity during combined androgen blockade for prostate cancer. J Clin Endocrinol Metab 2006; 91: 1305–1308.
Heufelder A, Gooren L, Bunck M, Saad F . Treatment with diet and exercise plus transdermal testosterone reverses the metabolic syndrome and improves glycemic control in hypogonadal men with newly diagnosed type 2 diabetes. Endocrine Society Meeting Abstract Book 2008, 461–462.
Marin P, Holmang S, Jönsson L, Sjöström L, Kvist H, Holm G, Lindstedt G, Björntorp P . 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.
Liu PY, Wishart SM, Celermajer DS, Jimenez M, Pierro ID, Conway AJ, Handelsman DJ . Do reproductive hormones modify insulin sensitivity and metabolism in older men? A randomized, placebo controlled clinical trial of recombinant human chronic gonadotropin. Eur J Endocrinol 2003; 148: 55–66.
Xu X, De Pergola G, Bjorntorp P . The effects of androgens on the regulation of lipolysis in adipose precursor cells. Endocrinology 1990; 126: 1229–1234.
Marin P, Oden B, Bjorntorp P . Assimilation and mobilization of triglycerides in subcutaneous abdominal and femoral adipose tissue in vivo in men: effects of androgens. J Clin Endocrinol Metab 1995; 80: 239–243.
Rask E, Olsson T, Söderberg S, Andrew R, Livingstone DE, Johnson O, Walker BR . Tissue-specific dysregulation of cortisol metabolism in human obesity. J Clin Endocrinol Metab 2001; 86: 1418–1421.
Masuzaki H, Paterson J, Shinyama H, Morton NM, Mullins JJ, Seckl JR, Flier JS . A transgenic model of visceral obesity and metabolic syndrome. Science 2001; 294: 2166–2170.
Sores MM, Matsumoto AM, Sloan KL, Kivlahan DR . Low testosterone and mortality in male veterans. Arch Intern Med 2006; 166: 1660–1665.
Araujo A, Kupelian V, Page ST, Handelsman DJ, Bremner WJ, McKinlay JB . Sex steroids and all-cause mortality and cause-specific mortality in men. Arch Intern Med 2007; 167: 1252–1260.
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Kawano, H. The relationship between testosterone and metabolic syndrome. Hypertens Res 33, 537–538 (2010). https://doi.org/10.1038/hr.2010.52