The Prevalence and the Risk Factors of Testosterone Deficiency in Newly Diagnosed and Previously Known Type 2 Diabetic Men
Chen-Hsun Ho MD
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
Department of Urology, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan
Search for more papers by this authorFu-Shan Jaw PhD
Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan
Search for more papers by this authorChia-Chang Wu PhD
Department of Urology, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan
Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
Search for more papers by this authorKuan-Chou Chen PhD
Department of Urology, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan
Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
Search for more papers by this authorChih-Yuan Wang PhD
Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
Search for more papers by this authorJu-Ton Hsieh MD
Department of Urology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
Search for more papers by this authorCorresponding Author
Hong-Jeng Yu MD
Department of Urology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
Corresponding Author: Hong-Jeng Yu, MD and Shih-Ping Liu, MD, Department of Urology, National Taiwan University Hospital and College of Medicine, No.7, Chung-Shan South Road, Taipei 10001, Taiwan. Tel: +886-2-2312-3456 ext 65251; Fax: +886-2-2321-9145; E-mail: [email protected] (H.-J. Yu); [email protected] (S.-P. Liu)Search for more papers by this authorCorresponding Author
Shih-Ping Liu MD
Department of Urology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
Corresponding Author: Hong-Jeng Yu, MD and Shih-Ping Liu, MD, Department of Urology, National Taiwan University Hospital and College of Medicine, No.7, Chung-Shan South Road, Taipei 10001, Taiwan. Tel: +886-2-2312-3456 ext 65251; Fax: +886-2-2321-9145; E-mail: [email protected] (H.-J. Yu); [email protected] (S.-P. Liu)Search for more papers by this authorChen-Hsun Ho MD
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
Department of Urology, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan
Search for more papers by this authorFu-Shan Jaw PhD
Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan
Search for more papers by this authorChia-Chang Wu PhD
Department of Urology, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan
Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
Search for more papers by this authorKuan-Chou Chen PhD
Department of Urology, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan
Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
Search for more papers by this authorChih-Yuan Wang PhD
Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
Search for more papers by this authorJu-Ton Hsieh MD
Department of Urology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
Search for more papers by this authorCorresponding Author
Hong-Jeng Yu MD
Department of Urology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
Corresponding Author: Hong-Jeng Yu, MD and Shih-Ping Liu, MD, Department of Urology, National Taiwan University Hospital and College of Medicine, No.7, Chung-Shan South Road, Taipei 10001, Taiwan. Tel: +886-2-2312-3456 ext 65251; Fax: +886-2-2321-9145; E-mail: [email protected] (H.-J. Yu); [email protected] (S.-P. Liu)Search for more papers by this authorCorresponding Author
Shih-Ping Liu MD
Department of Urology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
Corresponding Author: Hong-Jeng Yu, MD and Shih-Ping Liu, MD, Department of Urology, National Taiwan University Hospital and College of Medicine, No.7, Chung-Shan South Road, Taipei 10001, Taiwan. Tel: +886-2-2312-3456 ext 65251; Fax: +886-2-2321-9145; E-mail: [email protected] (H.-J. Yu); [email protected] (S.-P. Liu)Search for more papers by this authorAbstract
Introduction
While the epidemiology of testosterone deficiency has been well described in men with previously known type 2 diabetes mellitus (T2DM), it was less reported in those with untreated, newly diagnosed T2DM.
Aim
The aim of this study was to investigate the prevalence and the risk factors of testosterone deficiency of men with newly diagnosed T2DM.
Methods
The cross-sectional study included 105 men (mean age: 61.2 ± 6.8 years) with previously known T2DM and another 81 (57.8 ± 8.8 years) with newly diagnosed T2DM. All received health checkup and sex hormone measurement at our institute in 2009.
Main Outcome Measures
We calculated the prevalence and explored the risk factors of low total (<300 ng/dL) and free (<6 ng/dL) testosterone in men with newly diagnosed and previously known T2DM.
Results
Men with previously known T2DM were older and had higher diastolic pressure and greater fasting glucose. There was no significant difference in total (358.0 [155.0] ng/dL vs. 363.0 [154.0] ng/dL, P = 0.68) and free (7.2 [2.5] ng/dL vs. 7.4 [2.4] ng/dL, P = 0.84) testosterone and sex-hormone binding globulin (SHBG) (27.3 [22.3] nmol/L vs. 28.7 [14.9] nmol/L, P = 0.46). The prevalence of low total and free testosterone was 28.4% and 21.0%, respectively, in men with newly diagnosed T2DM, and was 26.7% and 19.0% in those with previously known T2DM. In men with previously known T2DM, better glycemic control (HbA1c <7%) was associated with a higher level of total testosterone and a lower risk of low total testosterone. Men with newly diagnosed and previously known T2DM shared similar risk factors of low total testosterone, including high HbA1c (≥7%), low SHBG (<20 nmol/L), obesity, hyperuricemia, hypertriglycemia, and metabolic syndrome. Elevated prostate-specific antigen was a protective factor of low total testosterone. However, none of these factors was associated with low free testosterone.
Conclusions
The prevalence and the risk factors of testosterone deficiency are similar between newly diagnosed and previously known type 2 diabetic men. Ho C-H, Jaw F-S, Wu C-C, Chen K-C, Wang C-Y, Hsieh J-T, Yu H-J, and Liu S-P. The prevalence and the risk factors of testosterone deficiency in newly diagnosed and previously known type 2 diabetic men. J Sex Med 2015;12:389–397.
References
- 1Dhindsa S, Prabhakar S, Sethi M, Bandyopadhyay A, Chaudhuri A, Dandona P. Frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes. J Clin Endocrinol Metab 2004; 89: 5462–5468.
- 2Grossmann M, Thomas MC, Panagiotopoulos S, Sharpe K, Macisaac RJ, Clarke S, Zajac JD, Jerums G. Low testosterone levels are common and associated with insulin resistance in men with diabetes. J Clin Endocrinol Metab 2008; 93: 1834–1840.
- 3Kapoor 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.
- 4Ho CH, Yu HJ, Wang CY, Jaw FS, Hsieh JT, Liao WC, Pu YS, Liu SP. Prediabetes is associated with an increased risk of testosterone deficiency, independent of obesity and metabolic syndrome. PLoS ONE 2013; 8: e74173.
- 5Yassin DJ, El Douaihy Y, Yassin AA, Kashanian J, Shabsigh R, Hammerer PG. Lower urinary tract symptoms improve with testosterone replacement therapy in men with late-onset hypogonadism: 5-year prospective, observational and longitudinal registry study. World J Urol 2014; 32: 1049–1054.
- 6Garcia-Cruz E, Leibar-Tamayo A, Romero-Otero J, Asiain I, Carrion A, Castaneda R, Mateu L, Luque P, Cardenosa O, Alcaraz A. Marked testosterone deficiency-related symptoms may be associated to higher metabolic risk in men with low testosterone levels. J Sex Med 2014; 11: 2292–2301.
- 7Martinez-Jabaloyas JM, group D-Ss. Testosterone deficiency in patients with erectile dysfunction: When should a higher cardiovascular risk be considered? J Sex Med 2014; 11: 2083–2091.
- 8Corona G, Rastrelli G, Monami M, Guay A, Buvat J, Sforza A, Forti G, Mannucci E, Maggi M. Hypogonadism as a risk factor for cardiovascular mortality in men: A meta-analytic study. Eur J Endocrinol 2011; 165: 687–701.
- 9Araujo AB, Dixon JM, Suarez EA, Murad MH, Guey LT, Wittert GA. Clinical review: Endogenous testosterone and mortality in men: A systematic review and meta-analysis. J Clin Endocrinol Metab 2011; 96: 3007–3019.
- 10Ruige JB, Mahmoud AM, De Bacquer D, Kaufman JM. Endogenous testosterone and cardiovascular disease in healthy men: A meta-analysis. Heart 2011; 97: 870–875.
- 11 Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2014.
- 12Corona G, Rastrelli G, Balercia G, Lotti F, Sforza A, Monami M, Forti G, Mannucci E, Maggi M. Hormonal association and sexual dysfunction in patients with impaired fasting glucose: A cross-sectional and longitudinal study. J Sex Med 2012; 9: 1669–1680.
- 13Corona G, Giorda CB, Cucinotta D, Guida P, Nada E, group S-Ds. The SUBITO-DE study: Sexual dysfunction in newly diagnosed type 2 diabetes male patients. J Endocrinol Invest 2013; 36: 864–868.
- 14Corona G, Giorda CB, Cucinotta D, Guida P, Nada E, Gruppo di studio S-D. Sexual dysfunction at the onset of type 2 diabetes: The interplay of depression, hormonal and cardiovascular factors. J Sex Med 2014; 11: 2065–2073.
- 15 American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2012; 35(3 suppl): S64–71.
- 16Meier JJ, Baller B, Menge BA, Gallwitz B, Schmidt WE, Nauck MA. Excess glycaemic excursions after an oral glucose tolerance test compared with a mixed meal challenge and self-measured home glucose profiles: Is the OGTT a valid predictor of postprandial hyperglycaemia and vice versa? Diabetes Obes Metab 2009; 11: 213–222.
- 17Onat A, Can G, Cicek G, Ayhan E, Dogan Y, Kaya H. Fasting, non-fasting glucose and HDL dysfunction in risk of pre-diabetes, diabetes, and coronary disease in non-diabetic adults. Acta Diabetol 2013; 50: 519–528.
- 18Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Costa F; American Heart Association; National Heart, Lung, and Blood Institute. Diagnosis and management of the metabolic syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005; 112: 2735–2752.
- 19Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 1999; 84: 3666–3672.
- 20Tsai EC, Matsumoto AM, Fujimoto WY, Boyko EJ. Association of bioavailable, free, and total testosterone with insulin resistance: Influence of sex hormone-binding globulin and body fat. Diabetes Care 2004; 27: 861–868.
- 21Allan CA. Sex steroids and glucose metabolism. Asian J Androl 2014; 16: 232–238.
- 22Traish AM, Saad F, Guay A. The dark side of testosterone deficiency: II. Type 2 diabetes and insulin resistance. J Androl 2009; 30: 23–32.
- 23Stellato RK, Feldman HA, Hamdy O, Horton ES, McKinlay JB. 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: 490–494.
- 24Lakshman KM, Bhasin S, Araujo AB. Sex hormone-binding globulin as an independent predictor of incident type 2 diabetes mellitus in men. J Gerontol A Biol Sci Med Sci 2010; 65: 503–509.
- 25Oh JY, Barrett-Connor E, Wedick NM, Wingard DL. Endogenous sex hormones and the development of type 2 diabetes in older men and women: The Rancho Bernardo study. Diabetes Care 2002; 25: 55–60.
- 26Keating NL, O'Malley AJ, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol 2006; 24: 4448–4456.
- 27Corona 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: 557–579.
- 28Grossmann M. Low testosterone in men with type 2 diabetes: Significance and treatment. J Clin Endocrinol Metab 2011; 96: 2341–2353.
- 29Travison 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: 549–555.
- 30Wu FC, Tajar A, Pye SR, Silman AJ, Finn JD, O'Neill TW, Bartfai G, Casanueva F, Forti G, Giwercman A, Huhtaniemi IT, Kula K, Punab M, Boonen S, Vanderschueren D, European Male Aging Study Group. 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: 2737–2745.
- 31Oskui PM, French WJ, Herring MJ, Mayeda GS, Burstein S, Kloner RA. Testosterone and the cardiovascular system: A comprehensive review of the clinical literature. J Am Heart Assoc 2013; 2: e000272.
- 32Corona G, Rastrelli G, Monami M, Saad F, Luconi M, Lucchese M, Facchiano E, Sforza A, Forti G, Mannucci E, Maggi M. Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: A systematic review and meta-analysis. Eur J Endocrinol 2013; 168: 829–843.
- 33Kapoor D, Channer KS, Jones TH. Rosiglitazone increases bioactive testosterone and reduces waist circumference in hypogonadal men with type 2 diabetes. Diabetes Vasc Dis Res 2008; 5: 135–137.
- 34Corona G, Monami M, Rastrelli G, Aversa A, Sforza A, Lenzi A, Forti G, Mannucci E, Maggi M. Type 2 diabetes mellitus and testosterone: A meta-analysis study. Int J Androl 2011; 34: 528–540.
- 35Jones TH, Arver S, Behre HM, Buvat J, Meuleman E, Moncada I, Morales AM, Volterrani M, Yellowlees A, Howell JD, Channer KS. Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 study). Diabetes Care 2011; 34: 828–837.
- 36Yassin DJ, Doros G, Hammerer PG, Yassin AA. 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: 1567–1576.
- 37Dhindsa S, Miller MG, McWhirter CL, Mager DE, Ghanim H, Chaudhuri A, Dandona P. Testosterone concentrations in diabetic and nondiabetic obese men. Diabetes Care 2010; 33: 1186–1192.
- 38Corona G, Rastrelli G, Morelli A, Vignozzi L, Mannucci E, Maggi M. Hypogonadism and metabolic syndrome. J Endocrinol Invest 2011; 34: 557–567.
- 39Mogri M, Dhindsa S, Quattrin T, Ghanim H, Dandona P. Testosterone concentrations in young pubertal and post-pubertal obese males. Clin Endocrinol (Oxf) 2013; 78: 593–599.
- 40Xu H, Jiang HW, Ding GX, Zhang H, Zhang LM, Mao SH, Ding Q. Diabetes mellitus and prostate cancer risk of different grade or stage: A systematic review and meta-analysis. Diabetes Res Clin Pract 2013; 99: 241–249.
- 41Gacci M, Vignozzi L, Sebastianelli A, Salvi M, Giannessi C, De Nunzio C, Tubaro A, Corona G, Rastrelli G, Santi R, Nesi G, Serni S, Carini M, Maggi M. Metabolic syndrome and lower urinary tract symptoms: The role of inflammation. Prostate Cancer Prostatic Dis 2013; 16: 101–106.
- 42Gacci M, Corona G, Vignozzi L, Salvi M, Serni S, De Nunzio C, Tubaro A, Oelke M, Carini M, Maggi M. Metabolic syndrome and benign prostatic enlargement: A systematic review and meta-analysis. BJU Int 2014; doi: 10.1111/bju.12728.
- 43Corona G, Boddi V, Lotti F, Gacci M, Carini M, De Vita G, Sforza A, Forti G, Mannucci E, Maggi M. The relationship of testosterone to prostate-specific antigen in men with sexual dysfunction. J Sex Med 2010; 7: 284–292.
- 44Morgentaler A. Testosterone replacement therapy and prostate cancer. Urol Clin North Am 2007; 34: 555–563, vii.
- 45Rastrelli G, Corona G, Vignozzi L, Maseroli E, Silverii A, Monami M, Mannucci E, Forti G, Maggi M. Serum PSA as a predictor of testosterone deficiency. J Sex Med 2013; 10: 2518–2528.
- 46Cooper CS, Perry PJ, Sparks AE, MacIndoe JH, Yates WR, Williams RD. Effect of exogenous testosterone on prostate volume, serum and semen prostate specific antigen levels in healthy young men. J Urol 1998; 159: 441–443.
- 47Monath JR, McCullough DL, Hart LJ, Jarow JP. Physiologic variations of serum testosterone within the normal range do not affect serum prostate-specific antigen. Urology 1995; 46: 58–61.
- 48Dhindsa S, Upadhyay M, Viswanathan P, Howard S, Chaudhuri A, Dandona P. Relationship of prostate-specific antigen to age and testosterone in men with type 2 diabetes mellitus. Endocr Pract 2008; 14: 1000–1005.
- 49Bhatia V, Chaudhuri A, Tomar R, Dhindsa S, Ghanim H, Dandona P. Low testosterone and high C-reactive protein concentrations predict low hematocrit in type 2 diabetes. Diabetes Care 2006; 29: 2289–2294.
- 50Maggio M, Basaria S, Ble A, Lauretani F, Bandinelli S, Ceda GP, Valenti G, Ling SM, Ferrucci L. Correlation between testosterone and the inflammatory marker soluble interleukin-6 receptor in older men. J Clin Endocrinol Metab 2006; 91: 345–347.