Alleged concerns regarding risk of cardiovascular disease with testosterone replacement therapy (TRT) have been promulgated recently. However, a large and growing number of intervention studies show to the contrary that TRT reduces cardiovascular risk factors and confers multiple beneficial health effects. Thus, fears promoted by some recent flawed studies need to be critically re-evaluated.
This article gives an overview of studies that have investigated health effects and safety of TRT. As outlined here, the position that testosterone deficiency (TD) should be regarded as a risk factor for cardiovascular disease is supported by a rapidly expanding body of evidence.[2-4]
Key effects of testosterone replacement therapy (TRT)
* TRT has beneficial effects on body composition:
Increased muscle mass (size) / fat-free mass / lean body mass [5-20]
Reduced waist circumference and visceral fat mass [6, 7, 16, 21-42]
Reduced total body fat mass / percent body fat [5, 6, 8-12, 14, 17, 19, 20, 29, 43, 44]
Weight loss [23, 30, 33-39, 41, 45]
Improved muscle function and exercise capacity [9, 44, 46, 47]
* TRT has beneficial effects on lipid profile:
Reduced Total cholesterol (TC) [8, 31-34, 36, 41-43, 45, 48-50]
Reduced TC / HDL ratio 
Reduced LDL cholesterol [8, 33, 34, 36, 41-43, 49-51]
Reduced triglycerides (TGs) [24-26, 33, 34, 36, 41, 42, 45]
Reduced Lp(a) 
Increased HDL levels [24, 33, 34, 36, 41, 45, 51]
* TRT has beneficial effects on cardiovascular function:
Reduced arterial stiffness [13, 52]
Reduced CIMT (carotid intima media thickness) 
Reduced blood pressure [22, 33, 34, 36, 37, 40, 41]
Increased circulating endothelial progenitor cell (EPC) number 
Decreased levels of osteoprotegerin (a novel independent marker of cardiovascular risk) 
* TRT has beneficial effects on glucose metabolism, which reduce risk of diabetes:
Increased insulin sensitivity [7, 13, 14, 17, 19, 24, 25, 28, 31, 37, 39, 46, 49]
Reduced glucose levels [22, 24, 26, 30, 31, 33, 34, 36, 39, 41]
Reduced HbA1c levels [24, 30-34, 36, 37, 49]
* TRT has beneficial effects on inflammatory parameters:
Decreased levels of liver enzymes [34, 36]
Decreased CRP levels [21, 24, 28, 33, 34, 36, 55, 56]
Reduction in inflammatory cytokines (TNF-alpha and IL-1beta) [21, 48]
Increase in anti-inflammatory cytokines (IL-10) 
* TRT has beneficial effects on the skeleton:
Increased bone mineral density (BMD) [10, 12, 55, 57]
* TRT increases longevity:
Reduced risk of mortality and improved survival [58, 59]
* TRT boosts sexual function:
Increased libido, improved erectile function and ejaculatory function [6, 11, 12, 29, 30, 38, 41-43, 49, 60-64]
* TRT has beneficial effects on quality of life:
Less fatigue and improvement in energy, mood, vitality [11, 12, 20, 38, 41, 42, 62, 65, 66]
* Multiple long-term registry studies confirm beneficial key effects: [23, 33, 35-37, 41, 67]
- TRT effectively restores physiological T levels within the first 12 months and these restored T levels are maintained with T therapy throughout the entire study period, which at this point is up to 6-7 years.
- Long-term TRT results in a marked and sustained reduction in body weight, waist circumference, BMI, CRP (C-reactive protein; an inflammatory biomarker), HbA1c and improves the lipid profile by reducing total cholesterol, LDL and triglycerides while increasing HDL.
- It is especially notable that the long-term reductions in body weight, waist circumference and HbA1c keep progressing throughout 5 years, and further improve after each year of TRT.
* Safety of TRT
- The most common side effects of TRT are increases in hematocrit and PSA.[42, 68] However, these elevations occur within the first 12 months, and thereafter remain stable with continued TRT for up to 5 years. This corroborates findings from a previous 3 year-long study which demonstrated that elevations (within the reference range) of hemacocrit and PSA plateau at 12 months and 6 months respectively, after initiation of TRT.
- 5 years of TRT also does not change the International Prostate Symptom Score (IPSS), maximum urinary flow (Qmax) rate, post-void residual (PVR) volume, or prostate size. Thus, long-term TRT does not impact negatively on lower urinary tract symptoms (LUTS) and prostate volume.
What is known
Testosterone deficiency (TD), a.k.a hypogonadism, is a common clinical condition, affecting almost 40% of men aged 45 years and older. Observational studies report associations of lower testosterone levels with poorer health outcomes in ageing men, including frailty, reduced sexual activity, insulin resistance, cognitive decline, cardiovascular events and mortality [71, 72]. Decreased testosterone levels also are associated with increased risks of osteoporosis, metabolic syndrome, type 2 diabetes. 
Men with the metabolic syndrome have lower testosterone levels than age-matched men without the metabolic syndrome [22, 74-78], and risk of developing the metabolic syndrome is lower in men with higher testosterone levels.[79-83] Similarly, men with type 2 diabetes have lower testosterone levels than men without a history of diabetes [84-90], and risk of type 2 diabetes is lower in men with high testosterone levels.[91-94] Likewise, men with coronary artery disease have lower testosterone levels than age-matched men without coronary artery disease [95, 96], and risk of cardiovascular events  and cardiovascular death  is lower in men with high testosterone levels.
What new studies show
A comprehensive review of TRT interventions confirms that TRT is safe if treatment and monitoring are appropriately executed. The evidence available to date does not support recently raised concerns about potential detrimental cardiovascular effects of testosterone therapy. Instead, a growing number of interventions studies show that TRT has multiple beneficial effects, as outlined above.
It is notable that TRT also has beneficial effects on novel risk factors like osteoprotegerin  and circulating (in the blood stream) endothelial progenitor cells (EPCs). There is now emerging evidence that osteoprotegerin contributes to the development of atherosclerosis and cardiovascular diseases by amplifying the adverse effects of inflammation and several traditional risk factors, such as dyslipidemia, endothelial dysfunction, diabetes and hypertension. This is supported by studies showing that severity of atherosclerosis is significantly associated with higher osteoprotegerin levels, and findings that osteoprotegerin is an independent predictor of cardiovascular events [99, 100] and heart disease. [99, 101]
This being that case, it is interesting that TRT reduces osteoprotegerin levels. Endothelial progenitor cells number is another relatively unknown health indicator.
The level of circulating endothelial progenitor cells, which play a critical role in repair of blood vessel injuries, has been shown to predict the occurrence of future cardiovascular events and death from cardiovascular causes. In line with this, a reduced number of circulating endothelial progenitor cells is an independent predictor of atherosclerosis progression.  Low levels of testosterone are associated with a low number of circulating endothelial progenitor cells  and testosterone replacement therapy has been demonstrated to induce an increase in circulating endothelial progenitor cell number, possibly via a direct effect on the bone marrow.[53, 104] Emerging research shows that testosterone an important role in the development and maturation of endothelial progenitor cells, and regulates vascular (endothelial) function. Because of the critical role of the inner lining of blood vessels (aka endothelium) in regulating erectile function, a better understanding of the function of endothelial progenitor cells may pave the way to development of new therapeutic approaches for the treatment of erectile dysfunction.
Low testosterone levels together with standard risk factors can be used to improved health risk prediction, and may actually represent a valuable biomarker for indication of cardiovascular disease risk. Due to the strong associations of low testosterone levels with detrimental health outcomes, it is likely that TD contributes, at least partly, to aging related health deterioration. It has therefore been suggested that testosterone deficiency should be regarded as a risk factor for cardiovascular disease.[2-4]
As outlined above, there is now ample evidence to argue that tetosterone deficiency should be an element in the definition of the metabolic syndrome. In the long run, the beneficial effects of TRT on the metabolic parameters outlined above would protect against development of the main killers; cardiovascular disease and type-2 diabetes. There is a high prevalence of tetosterone deficiency in type-2 diabetics [84-90], and because multiple studies demonstrate metabolic benefits of TRT in type-2 diabetic patients [24, 30, 31, 45, 49, 107] it has been suggested that testosterone supplementation be regarded as a new therapy for diabetes. There is also mounting data to support use of TRT in treatment of obesity. [23, 33, 35-37, 41, 67, 109, 110]
1. Traish, A.M., Outcomes of testosterone therapy in men with testosterone deficiency (TD): Part II. Steroids, 2014.
2. Ullah, M.I., et al., Testosterone deficiency as a risk factor for cardiovascular disease. Horm Metab Res, 2011. 43(3): p. 153-64.
3. Jones, T.H., Testosterone deficiency: a risk factor for cardiovascular disease? Trends Endocrinol Metab, 2010. 21(8): p. 496-503.
4. Maggio, M. and S. Basaria, Welcoming low testosterone as a cardiovascular risk factor. Int J Impot Res, 2009. 21(4): p. 261-4.
5. Bhasin, S., et al., Effect of testosterone supplementation with and without a dual 5alpha-reductase inhibitor on fat-free mass in men with suppressed testosterone production: a randomized controlled trial. JAMA, 2012. 307(9): p. 931-9.
6. Finkelstein, J.S., et al., Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med, 2013. 369(11): p. 1011-22.
7. Marin, P., M. Krotkiewski, and P. Bjorntorp, Androgen treatment of middle-aged, obese men: effects on metabolism, muscle and adipose tissues. Eur J Med, 1992. 1(6): p. 329-36.
8. Page, S.T., et al., Exogenous testosterone (T) alone or with finasteride increases physical performance, grip strength, and lean body mass in older men with low serum T. J Clin Endocrinol Metab, 2005. 90(3): p. 1502-10.
9. Srinivas-Shankar, U., et al., Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab, 2010. 95(2): p. 639-50.
10. Svartberg, J., et al., Testosterone treatment in elderly men with subnormal testosterone levels improves body composition and BMD in the hip. Int J Impot Res, 2008. 20(4): p. 378-87.
11. Wang, C., et al., Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. J Clin Endocrinol Metab, 2000. 85(8): p. 2839-53.
12. Wang, C., et al., Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. J Clin Endocrinol Metab, 2004. 89(5): p. 2085-98.
13. Hoyos, C.M., et al., Body compositional and cardiometabolic effects of testosterone therapy in obese men with severe obstructive sleep apnoea: a randomised placebo-controlled trial. Eur J Endocrinol, 2012. 167(4): p. 531-41.
14. Naharci, M.I., et al., Effect of testosterone on insulin sensitivity in men with idiopathic hypogonadotropic hypogonadism. Endocr Pract, 2007. 13(6): p. 629-35.
15. Brodsky, I.G., P. Balagopal, and K.S. Nair, Effects of testosterone replacement on muscle mass and muscle protein synthesis in hypogonadal men--a clinical research center study. J Clin Endocrinol Metab, 1996. 81(10): p. 3469-75.
16. Allan, C.A., et al., Testosterone therapy prevents gain in visceral adipose tissue and loss of skeletal muscle in nonobese aging men. J Clin Endocrinol Metab, 2008. 93(1): p. 139-46.
17. Malkin, C.J., T.H. Jones, and K.S. Channer, The effect of testosterone on insulin sensitivity in men with heart failure. Eur J Heart Fail, 2007. 9(1): p. 44-50.
18. Frederiksen, L., et al., Testosterone therapy increased muscle mass and lipid oxidation in aging men. Age (Dordr), 2012. 34(1): p. 145-56.
19. Juang, P.S., et al., Testosterone with dutasteride, but not anastrazole, improves insulin sensitivity in young obese men: a randomized controlled trial. J Sex Med, 2014. 11(2): p. 563-73.
20. Behre, H.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(4): p. 198-207.
21. Kalinchenko, S.Y., et al., 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(5): p. 602-12.
22. Bhattacharya, R.K., et al., 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: p. 18.
23. Saad, F., et al., Long-term treatment of hypogonadal men with testosterone produces substantial and sustained weight loss. Obesity (Silver Spring), 2013. 21(10): p. 1975-81.
24. Heufelder, A.E., et al., 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(6): p. 726-33.
25. Marin, P., Testosterone and regional fat distribution. Obes Res, 1995. 3 Suppl 4: p. 609S-612S.
26. Marin, P., et al., Androgen treatment of abdominally obese men. Obes Res, 1993. 1(4): p. 245-51.
27. Marin, P., et al., Assimilation of triglycerides in subcutaneous and intraabdominal adipose tissues in vivo in men: effects of testosterone. J Clin Endocrinol Metab, 1996. 81(3): p. 1018-22.
28. Aversa, 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(10): p. 3495-503.
29. Aversa, A., et al., Efficacy and safety of two different testosterone undecanoate formulations in hypogonadal men with metabolic syndrome. J Endocrinol Invest, 2010. 33(11): p. 776-83.
30. Boyanov, M.A., Z. Boneva, and V.G. Christov, Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency. Aging Male, 2003. 6(1): p. 1-7.
31. Kapoor, D., 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): p. 899-906.
32. Hackett, G., 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(3): p. 840-56.
33. Haider, A., et al., Hypogonadal obese men with and without diabetes mellitus type 2 lose weight and show improvement in cardiovascular risk factors when treated with testosterone: an observational study. . Obes Res Clin Pract 2013.
34. Haider, A., et al., 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. International Journal of Endocrinology, 2014: p. Article ID 683515.
35. Yassin, A. and G. Doros, Testosterone therapy in hypogonadal men results in sustained and clinically meaningful weight loss. Clin Obes, 2013. 3(3-4): p. 73-83.
36. Traish, A.M., et al., Long-term testosterone therapy in hypogonadal men ameliorates elements of the metabolic syndrome: an observational, long-term registry study. Int J Clin Pract, 2014. 68(3): p. 314-29.
37. Francomano, D., A. Lenzi, and A. Aversa, Effects of five-year treatment with testosterone undecanoate on metabolic and hormonal parameters in ageing men with metabolic syndrome. Int J Endocrinol, 2014. 2014: p. 527470.
38. Pexman-Fieth, C., et al., 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): p. 1-11.
39. Strollo, F., et al., Low-intermediate dose testosterone replacement therapy by different pharmaceutical preparations improves frailty score in elderly hypogonadal hyperglycaemic patients. Aging Male, 2013. 16(2): p. 33-7.
40. Li, J.Y., et al., Effects of androgen supplementation therapy on partial androgen deficiency in the aging male: a preliminary study. Aging Male, 2002. 5(1): p. 47-51.
41. Yassin, D.J., et al., Long-term testosterone treatment in elderly men with hypogonadism and erectile dysfunction reduces obesity parameters and improves metabolic syndrome and health-related quality of life. J Sex Med, 2014. 11(6): p. 1567-76.
42. Zitzmann, M., et al., 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(2): p. 579-88.
43. Permpongkosol, S., N. Tantirangsee, and K. Ratana-olarn, Treatment of 161 men with symptomatic late onset hypogonadism with long-acting parenteral testosterone undecanoate: effects on body composition, lipids, and psychosexual complaints. J Sex Med, 2010. 7(11): p. 3765-74.
44. Stout, M., et al., Testosterone therapy during exercise rehabilitation in male patients with chronic heart failure who have low testosterone status: a double-blind randomized controlled feasibility study. Am Heart J, 2012. 164(6): p. 893-901.
45. Mitkov, M.D., I.Y. Aleksandrova, and M.M. Orbetzova, Effect of transdermal testosterone or alpha-lipoic acid on erectile dysfunction and quality of life in patients with type 2 diabetes mellitus. Folia Med (Plovdiv), 2013. 55(1): p. 55-63.
46. Caminiti, G., et al., Effect of long-acting testosterone treatment on functional exercise capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure a double-blind, placebo-controlled, randomized study. J Am Coll Cardiol, 2009. 54(10): p. 919-27.
47. Ferrando, A.A., et al., Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. Am J Physiol Endocrinol Metab, 2002. 282(3): p. E601-7.
48. Malkin, C.J., et al., The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab, 2004. 89(7): p. 3313-8.
49. Jones, T.H., et al., Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 study). Diabetes Care, 2011. 34(4): p. 828-37.
50. Zgliczynski, S., et al., Effect of testosterone replacement therapy on lipids and lipoproteins in hypogonadal and elderly men. Atherosclerosis, 1996. 121(1): p. 35-43.
51. Zitzmann, M. and E. Nieschlag, Androgen receptor gene CAG repeat length and body mass index modulate the safety of long-term intramuscular testosterone undecanoate therapy in hypogonadal men. J Clin Endocrinol Metab, 2007. 92(10): p. 3844-53.
52. Yaron, M., et al., Effect of testosterone replacement therapy on arterial stiffness in older hypogonadal men. Eur J Endocrinol, 2009. 160(5): p. 839-46.
53. Liao, C.H., et al., Testosterone replacement therapy can increase circulating endothelial progenitor cell number in men with late onset hypogonadism. Andrology, 2013. 1(4): p. 563-9.
54. Frederiksen, L., et al., Osteoprotegerin levels decrease during testosterone therapy in aging men and are associated with changed distribution of regional fat. Horm Metab Res, 2013. 45(4): p. 308-13.
55. Aversa, A., 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(2): p. 96-102.
56. Kapoor, D., et al., The effect of testosterone replacement therapy on adipocytokines and C-reactive protein in hypogonadal men with type 2 diabetes. Eur J Endocrinol, 2007. 156(5): p. 595-602.
57. Wang, C., et al., Effects of transdermal testosterone gel on bone turnover markers and bone mineral density in hypogonadal men. Clin Endocrinol (Oxf), 2001. 54(6): p. 739-50.
58. Shores, M.M., et al., Testosterone treatment and mortality in men with low testosterone levels. J Clin Endocrinol Metab, 2012. 97(6): p. 2050-8.
59. Muraleedharan, V., et al., Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes. Eur J Endocrinol, 2013. 169(6): p. 725-33.
60. Bolona, E.R., et al., Testosterone use in men with sexual dysfunction: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clin Proc, 2007. 82(1): p. 20-8.
61. Allan, C.A., et al., Testosterone therapy increases sexual desire in ageing men with low-normal testosterone levels and symptoms of androgen deficiency. Int J Impot Res, 2008. 20(4): p. 396-401.
62. Hackett, G., et al., Testosterone replacement therapy with long-acting testosterone undecanoate improves sexual function and quality-of-life parameters vs. placebo in a population of men with type 2 diabetes. J Sex Med, 2013. 10(6): p. 1612-27.
63. Amiaz, R., et al., Testosterone gel replacement improves sexual function in depressed men taking serotonergic antidepressants: a randomized, placebo-controlled clinical trial. J Sex Marital Ther, 2011. 37(4): p. 243-54.
64. Corona, G., et al., Testosterone supplementation and sexual function: a meta-analysis study. J Sex Med, 2014. 11(6): p. 1577-92.
65. Tong, S.F., et al., Effect of long-acting testosterone undecanoate treatment on quality of life in men with testosterone deficiency syndrome: a double blind randomized controlled trial. Asian J Androl, 2012. 14(4): p. 604-11.
66. Ho, C.C., et al., A randomized, double-blind, placebo-controlled trial on the effect of long-acting testosterone treatment as assessed by the Aging Male Symptoms scale. BJU Int, 2012. 110(2): p. 260-5.
67. Haider, A., et al., 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. 2014: p. 683515.
68. Bhasin, S., et al., Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab, 2010. 95(6): p. 2536-59.
69. Francomano, D., et al., Effects of 5-year treatment with testosterone undecanoate on lower urinary tract symptoms in obese men with hypogonadism and metabolic syndrome. Urology, 2014. 83(1): p. 167-73.
70. Mulligan, T., et al., Prevalence of hypogonadism in males aged at least 45 years: the HIM study. Int J Clin Pract, 2006. 60(7): p. 762-9.
71. Yeap, B.B., A.B. Araujo, and G.A. Wittert, Do low testosterone levels contribute to ill-health during male ageing? Crit Rev Clin Lab Sci, 2012. 49(5-6): p. 168-82.
72. Yeap, B.B., Are declining testosterone levels a major risk factor for ill-health in aging men? Int J Impot Res, 2009. 21(1): p. 24-36.
73. Yeap, B.B., Testosterone and ill-health in aging men. Nat Clin Pract Endocrinol Metab, 2009. 5(2): p. 113-21.
74. Singh, S.K., R. Goyal, and D.D. Pratyush, Is hypoandrogenemia a component of metabolic syndrome in males? Exp Clin Endocrinol Diabetes, 2011. 119(1): p. 30-5.
75. Maggio, M., et al., Association between hormones and metabolic syndrome in older Italian men. J Am Geriatr Soc, 2006. 54(12): p. 1832-8.
76. Garcia-Cruz, E., et al., Metabolic syndrome in men with low testosterone levels: relationship with cardiovascular risk factors and comorbidities and with erectile dysfunction. J Sex Med, 2013. 10(10): p. 2529-38.
77. Grosman, H., et al., Association between testosterone levels and the metabolic syndrome in adult men. Aging Male, 2014: p. 1-5.
78. Yeap, B.B., et al., Differential associations of testosterone, dihydrotestosterone and oestradiol with physical, metabolic and health-related factors in community-dwelling men aged 17-97 years from the Busselton Health Survey. Clin Endocrinol (Oxf), 2014. 81(1): p. 100-8.
79. Kupelian, V., et al., Low sex hormone-binding globulin, total testosterone, and symptomatic androgen deficiency are associated with development of the metabolic syndrome in nonobese men. J Clin Endocrinol Metab, 2006. 91(3): p. 843-50.
80. Rodriguez, A., et al., Aging, androgens, and the metabolic syndrome in a longitudinal study of aging. J Clin Endocrinol Metab, 2007. 92(9): p. 3568-72.
81. Tsujimura, A., et al., Is low testosterone concentration a risk factor for metabolic syndrome in healthy middle-aged men? Urology, 2013. 82(4): p. 814-9.
82. Tong, P.C., et al., Association of testosterone, insulin-like growth factor-I, and C-reactive protein with metabolic syndrome in Chinese middle-aged men with a family history of type 2 diabetes. J Clin Endocrinol Metab, 2005. 90(12): p. 6418-23.
83. Haring, R., et al., Prediction of metabolic syndrome by low serum testosterone levels in men: results from the study of health in Pomerania. Diabetes, 2009. 58(9): p. 2027-31.
84. Grossmann, M., et al., Low testosterone levels are common and associated with insulin resistance in men with diabetes. J Clin Endocrinol Metab, 2008. 93(5): p. 1834-40.
85. Chandel, A., et al., Testosterone concentration in young patients with diabetes. Diabetes Care, 2008. 31(10): p. 2013-7.
86. Hernandez-Mijares, A., et al., Testosterone levels in males with type 2 diabetes and their relationship with cardiovascular risk factors and cardiovascular disease. J Sex Med, 2010. 7(5): p. 1954-64.
87. Dhindsa, S., et al., Testosterone concentrations in diabetic and nondiabetic obese men. Diabetes Care, 2010. 33(6): p. 1186-92.
88. Anderson, S.G., et al., Screening for hypogonadism in diabetes 2008/9: results from the Cheshire Primary Care cohort. Prim Care Diabetes, 2012. 6(2): p. 143-8.
89. Ogbera, O.A., et al., Hypogonadism and subnormal total testosterone levels in men with type 2 diabetes mellitus. J Coll Physicians Surg Pak, 2011. 21(9): p. 517-21.
90. Dhindsa, S., et al., Frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes. J Clin Endocrinol Metab, 2004. 89(11): p. 5462-8.
91. Ding, E.L., et al., Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA, 2006. 295(11): p. 1288-99.
92. Vikan, T., et al., Low testosterone and sex hormone-binding globulin levels and high estradiol levels are independent predictors of type 2 diabetes in men. Eur J Endocrinol, 2010. 162(4): p. 747-54.
93. Oh, J.Y., 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(1): p. 55-60.
94. Stellato, R.K., et al., Testosterone, sex hormone-binding globulin, and the development of type 2 diabetes in middle-aged men: prospective results from the Massachusetts male aging study. Diabetes Care, 2000. 23(4): p. 490-4.
95. English, K.M., et al., Men with coronary artery disease have lower levels of androgens than men with normal coronary angiograms. Eur Heart J, 2000. 21(11): p. 890-4.
96. Malkin, C.J., et al., Low serum testosterone and increased mortality in men with coronary heart disease. Heart, 2010. 96(22): p. 1821-5.
97. Ohlsson, C., et al., High serum testosterone is associated with reduced risk of cardiovascular events in elderly men. The MrOS (Osteoporotic Fractures in Men) study in Sweden. J Am Coll Cardiol, 2011. 58(16): p. 1674-81.
98. Montagnana, M., et al., The role of osteoprotegerin in cardiovascular disease. Ann Med, 2013. 45(3): p. 254-64.
99. Davenport, C., et al., Identifying coronary artery disease in men with type 2 diabetes: osteoprotegerin, pulse wave velocity, and other biomarkers of cardiovascular risk. J Hypertens, 2011. 29(12): p. 2469-75.
100. Livaudais, J.C., et al., Educating Hispanic women about breast cancer prevention: evaluation of a home-based promotora-led intervention. J Womens Health (Larchmt), 2010. 19(11): p. 2049-56.
101. Vik, A., et al., Serum osteoprotegerin is a predictor for incident cardiovascular disease and mortality in a general population: the Tromso Study. J Thromb Haemost, 2011. 9(4): p. 638-44.
102. Werner, N., et al., Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med, 2005. 353(10): p. 999-1007.
103. Schmidt-Lucke, C., et al., Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation, 2005. 111(22): p. 2981-7.
104. Foresta, C., et al., Reduced number of circulating endothelial progenitor cells in hypogonadal men. J Clin Endocrinol Metab, 2006. 91(11): p. 4599-602.
105. Traish, A.M. and A. Galoosian, Androgens modulate endothelial function and endothelial progenitor cells in erectile physiology. Korean J Urol, 2013. 54(11): p. 721-31.
106. Saad, F. and L. Gooren, The role of testosterone in the metabolic syndrome: a review. J Steroid Biochem Mol Biol, 2009. 114(1-2): p. 40-3.
107. Cai, X., et al., Metabolic effects of testosterone replacement therapy on hypogonadal men with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. Asian J Androl, 2014. 16(1): p. 146-52.
108. Corona, G., et al., Following the common association between testosterone deficiency and diabetes mellitus, can testosterone be regarded as a new therapy for diabetes? Int J Androl, 2009. 32(5): p. 431-41.
109. Saad, F., et al., Testosterone as potential effective therapy in treatment of obesity in men with testosterone deficiency: a review. Curr Diabetes Rev, 2012. 8(2): p. 131-43.
110. Saad, F. and L.J. Gooren, The role of testosterone in the etiology and treatment of obesity, the metabolic syndrome, and diabetes mellitus type 2. J Obes, 2011. 2011.
111. Vlachopoulos, C., et al., Plasma total testosterone and incident cardiovascular events in hypertensive patients. Am J Hypertens, 2013. 26(3): p. 373-81.