The vulnerable man: Impact of testosterone deficiency on the uraemic phenotype

Nephrology Dialysis Transplantation

Volumn 27, Issue 11, 2012, Pages 4030-4041

  Carrero, Juan Jesús ^a,b   Stenvinkel, Peter ^a  

^a KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^b KAROLINSKA INSTITUTE   (Sweden)

Author keywords

anaemia; androgen; haemodialysis; hormone; men

Indexed keywords

ANDROGEN; ANGIOTENSIN RECEPTOR ANTAGONIST; ANTIANEMIC AGENT; CINACALCET; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; GLUCOCORTICOID; GROWTH HORMONE; HEPCIDIN; KETOCONAZOLE; NANDROLONE DECANOATE; OSTEOCLAST DIFFERENTIATION FACTOR; PLACEBO; SEX HORMONE BINDING PROTEIN; SOMATOMEDIN C; SPIRONOLACTONE; TESTOSTERONE; VITAMIN D;

ANDROGEN DEFICIENCY; ANDROGEN THERAPY; ANEMIA; ATHEROSCLEROSIS; BLEEDING; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CHRONIC KIDNEY DISEASE; COGNITIVE DEFECT; DEPRESSION; DISEASE COURSE; DRUG EFFECT; DRUG RESPONSE; DRUG SAFETY; DYSLIPIDEMIA; EDEMA; ENDOTHELIAL DYSFUNCTION; ERECTILE DYSFUNCTION; ERYTHROCYTOSIS; FLUID RETENTION; HEART DISEASE; HEART MUSCLE ISCHEMIA; HEART VENTRICLE HYPERTROPHY; HORMONE ACTION; HUMAN; HYPERTENSION; HYPOGONADISM; INJECTION PAIN; KIDNEY FAILURE; LIBIDO DISORDER; MALNUTRITION; MORTALITY; MUSCLE METABOLISM; NONHUMAN; POLYCYTHEMIA; PREVALENCE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SEXUAL FUNCTION; SIDE EFFECT; TESTOSTERONE BLOOD LEVEL; UREMIA; VITAMIN SUPPLEMENTATION;

HORMONE REPLACEMENT THERAPY; HUMANS; HYPOGONADISM; KIDNEY FAILURE, CHRONIC; MALE; MIDDLE AGED; PHENOTYPE; RENAL DIALYSIS; TESTOSTERONE; UREMIA;

EID: 84869444564     PISSN: 09310509     EISSN: 14602385     Source Type: Journal    
DOI: 10.1093/ndt/gfs383     Document Type: Review

References (142)

1. Wu FC, Tajar A, Beynon JM et al. Identification of late-onset hypo-gonadism in middle-aged and elderly men. N Engl J Med 2010; 363:123-135.
2. Allan CA, McLachlan RI. Age-related changes in testosterone and the role of replacement therapy in older men. Clin Endocrinol (Oxf) 2004; 60:653-670. (Pubitemid 38788071)
3. Zitzmann M, Faber S, Nieschlag E. Association of specific symptoms and metabolic risks with serum testosterone in older men. J Clin En-docrinol Metab 2006; 91:4335-4343. (Pubitemid 44833407)
4. Kaufman JM, Vermeulen A. The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev 2005; 26:833-876. (Pubitemid 41428540)
5. Dandona P, Rosenberg MT. A practical guide to male hypogonad-ism in the primary care setting. Int J Clin Pract 2010; 64:682-696.
6. Kupelian V, Page ST, Araujo AB 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; 91:843-850. (Pubitemid 43357748)
7. Brand JS, Van der Tweel I, Grobbee DE et al. Testosterone, sex hormone-binding globulin and the metabolic syndrome: a systematic review and meta-analysis of observational studies. Int J Epidemiol 2011; 40:189-207.
8. Gordon D, Beastall GH, Thomson JA et al. Prolonged hypogonadism in male patients with rheumatoid arthritis during flares in disease activity. Br J Rheumatol 1988; 27:440-444. (Pubitemid 19028440)
9. Lapauw B, Goemaere S, Zmierczak H 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 Endo-crinol 2008; 159:459-468.
10. Yeap BB, Almeida OP, Hyde Z 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; 156:585-594. (Pubitemid 46796526)
11. Archer J. Testosterone and human aggression: an evaluation of the challenge hypothesis. Neurosci Biobehav Rev 2006; 30:319-345. (Pubitemid 43227962)
12. Van der Meij L, Buunk AP, Almela M et al. Testosterone responses to competition: the opponent's psychological state makes it challenging. Biol Psychol 2010; 84:330-335.
13. Van der Meij L, Almela M, Hidalgo V et al. Testosterone and cortisol release among Spanish soccer fans watching the 2010 World Cup Final. PLoS One 2012; 7: e34814
14. Verhave JC, Hillege HL, Burgerhof JG et al. Cardiovascular risk factors are differently associated with urinary albumin excretion in men and women. J Am Soc Nephrol 2003; 14:1330-1335. (Pubitemid 36514673)
15. Dunkel L, Raivio T, Laine J et al. Circulating luteinizing hormone receptor inhibitor(s) in boys with chronic renal failure. Kidney Int 1997; 51:777-784. (Pubitemid 27157962)
16. Schmidt A, Luger A, Horl WH. Sexual hormone abnormalities in male patients with renal failure. Nephrol Dial Transplant 2002; 17:368-371. (Pubitemid 34211129)
17. Carrero JJ, Kyriazis J, Sonmez A et al. Prolactin levels, endothelial dysfunction, and the risk of cardiovascular events and mortality in patients with CKD. Clin J Am Soc Nephrol 2012; 7:207-215.
18. Glass AR, Beach J, Vigersky RA. Hypogonadotropic hypogonadism in nephrotic rats: increased sensitivity to negative feedback effects of testosterone. Metabolism 1985; 34:574-579. (Pubitemid 15059912)
19. DeLong M, Logan JL, Yong KC et al. Renin-angiotensin blockade reduces serum free testosterone in middle-aged men on haemodialy-sis and correlates with erythropoietin resistance. Nephrol Dial Transplant 2005; 20:585-590. (Pubitemid 40378429)
20. Corona G, Boddi V, Balercia G et al. The effect of statin therapy on testosterone levels in subjects consulting for erectile dysfunction. J Sex Med 2010; 7 (4 Pt 1):1547-1556.
21. Stanworth RD, Kapoor D, Channer KS et al. Statin therapy is associated with lower total but not bioavailable or free testosterone in men with type 2 diabetes. Diabetes Care 2009; 32:541-546.
22. Strid H, Simren M, Johansson AC et al. The prevalence of gastrointestinal symptoms in patients with chronic renal failure is increased and associated with impaired psychological general well-being. Nephrol Dial Transplant 2002; 17:1434-1439.
23. Cardoso EM, Contreras LN, Tumilasci EG et al. Salivary testosterone for the diagnosis of androgen deficiency in end-stage renal disease. Nephrol Dial Transplant 2011; 26:677-683.
24. Solomon SD, Uno H, Lewis EF et al. Erythropoietic response and outcomes in kidney disease and type 2 diabetes. N Engl J Med 2010; 363:1146-1155.
25. Fernandez-Balsells MM, Murad MH, Lane M et al. Clinical review 1: adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metab 2010; 95:2560-2575.
26. Fonseca R, Rajkumar SV, White WL et al. Anemia after orchiect-omy. Am J Hematol 1998; 59:230-233.
27. Carrero JJ, Barany P, Yilmaz MI et al. Testosterone deficiency is a cause of anaemia and reduced responsiveness to erythropoiesis-sti-mulating agents in men with chronic kidney disease. Nephrol Dial Transplant 2012; 27:709-715.
28. Mirand EA, Gordon AS, Wenig J. Mechanism of testosterone action in erythropoiesis. Nature 1965; 206:270-272.
29. Coviello AD, Kaplan B, Lakshman KM et al. Effects of graded doses of testosterone on erythropoiesis in healthy young and older men. J Clin Endocrinol Metab 2008; 93:914-919. (Pubitemid 351398573)
30. Bachman E, Feng R, Travison T et al. Testosterone suppresses hepci-din in men: a potential mechanism for testosterone-induced erythro-cytosis. J Clin Endocrinol Metab 2010; 95:4743-4747.
31. Nicolas G, Chauvet C, Viatte L et al. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest 2002; 110:1037-1044.
32. Nicolas G, Bennoun M, Porteu A et al. Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proc Natl Acad Sci USA 2002; 99:4596-4601. (Pubitemid 34286030)
33. Kalinchenko SY, Tishova YA, Mskhalaya GJ 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; 73:602-612.
34. Richardson JR, Jr, Weinstein MB. Erythropoietic response of dia-lyzed patients to testosterone administration. Ann Intern Med 1970; 73:403-407.
35. Neff MS, Goldberg J, Slifkin RF et al. A comparison of androgens for anemia in patients on hemodialysis. N Engl J Med 1981; 304:871-875. (Pubitemid 11101070)
36. Gaughan WJ, Liss KA, Dunn SR et al. A 6-month study of low-dose recombinant human erythropoietin alone and in combination with androgens for the treatment of anemia in chronic hemodialysis patients. Am J Kidney Dis 1997; 30:495-500. (Pubitemid 27422295)
37. Lee MS, Ahn SH, Song JH. Effects of adjuvant androgen on anemia and nutritional parameters in chronic hemodialysis patients using low-dose recombinant human erythropoietin. Korean J Intern Med 2002; 17:167-173.
38. Ballal SH, Domoto DT, Polack DC et al. Androgens potentiate the effects of erythropoietin in the treatment of anemia of end-stage renal disease. Am J Kidney Dis 1991; 17:29-33.
39. Sheashaa H, Abdel-Razek W, El-Husseini A et al. Use of nandro-lone decanoate as an adjuvant for erythropoietin dose reduction in treating anemia in patients on hemodialysis. Nephron Clin Pract 2005; 99: c102-c106 (Pubitemid 40522792)
40. Barton Pai A, Chretien C, Lau AH. The effects of nandrolone de-canoate on nutritional parameters in hemodialysis patients. Clin Nephrol 2002; 58:38-46. (Pubitemid 34752992)
41. Carrero JJ, Chmielewski M, Axelsson J et al. Muscle atrophy, inflammation and clinical outcome in incident and prevalent dialysis patients. Clin Nutr 2008; 27:557-564.
42. Herbst KL, Bhasin S. Testosterone action on skeletal muscle. Curr Opin Clin Nutr Metab Care 2004; 7:271-277. (Pubitemid 40340664)
43. Baumgartner RN, Waters DL, Gallagher D et al. Predictors of skeletal muscle mass in elderly men and women. Mech Ageing Dev 1999; 107:123-136. (Pubitemid 29138849)
44. Roy TA, Blackman MR, Harman SM et al. Interrelationships of serum testosterone and free testosterone index with FFM and strength in aging men. Am J Physiol Endocrinol Metab 2002; 283: E284-E294 (Pubitemid 34827443)
45. Van den Beld AW, de Jong FH, Grobbee DE et al. Measures of bioa-vailable serum testosterone and estradiol and their relationships with muscle strength, bone density, and body composition in elderly men. J Clin Endocrinol Metab 2000; 85:3276-3282.
46. Schaap LA, Pluijm SM, Smit JH et al. The association of sex hormone levels with poor mobility, low muscle strength and incidence of falls among older men and women. Clin Endocrinol (Oxf) 2005; 63:152-160. (Pubitemid 41097983)
47. Araujo AB, Travison TG, Bhasin S et al. Association between testosterone and estradiol and age-related decline in physical function in a diverse sample of men. J Am Geriatr Soc 2008; 56:2000-2008.
48. Krasnoff JB, Basaria S, Pencina MJ et al. Free testosterone levels are associated with mobility limitation and physical performance in community-dwelling men: the Framingham Offspring Study. J Clin Endocrinol Metab 2010; 95:2790-2799.
49. Orwoll E, Lambert LC, Marshall LM et al. Endogenous testosterone levels, physical performance, and fall risk in older men. Arch Intern Med 2006; 166:2124-2131. (Pubitemid 44631401)
50. Stenvinkel P, Barany P, Chung SH et al. A comparative analysis of nutritional parameters as predictors of outcome in male and female ESRD patients. Nephrol Dial Transplant 2002; 17:1266-1274. (Pubitemid 34812073)
51. Carrero JJ. Gender differences in chronic kidney disease: underpinnings and therapeutic implications. Kidney Blood Press Res 2010; 33:383-392.
52. Carrero JJ, Qureshi AR, Parini P et al. Low serum testosterone increases mortality risk among male dialysis patients. J Am Soc Nephrol 2009; 20:613-620.
53. Mendler L, Baka Z, Kovacs-Simon A et al. Androgens negatively regulate myostatin expression in an androgen-dependent skeletal muscle. Biochem Biophys Res Commun 2007; 361:237-242. (Pubitemid 47102291)
54. Kovacheva EL, Hikim AP, Shen R et al. Testosterone supplementation reverses sarcopenia in aging through regulation of myostatin, c-Jun NH2-terminal kinase, Notch, and Akt signaling pathways. Endocrinology 2010; 151:628-638.
55. Gentile MA, Nantermet PV, Vogel RL et al. Androgen-mediated improvement of body composition and muscle function involves a novel early transcriptional program including IGF1, mechano growth factor, and induction of {beta}-catenin. J Mol Endocrinol 2010; 44:55-73.
56. Johansen KL, Mulligan K, Schambelan M. Anabolic effects of nan-drolone decanoate in patients receiving dialysis: a randomized controlled trial. JAMA 1999; 281:1275-1281. (Pubitemid 29174478)
57. Johansen KL, Painter PL, Sakkas GK et al. Effects of resistance exercise training and nandrolone decanoate on body composition and muscle function among patients who receive hemodialysis: a randomized, controlled trial. J Am Soc Nephrol 2006; 17:2307-2314. (Pubitemid 44141922)
58. Srinivas-Shankar U, Roberts SA, Connolly MJ 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; 95:639-650.
59. Travison TG, Basaria S, Storer TWet al. Clinical meaningfulness of the changes in muscle performance and physical function associated with testosterone administration in older men with mobility limitation. J Gerontol A Biol Sci Med Sci 2011; 66:1090-1099.
60. Brockenbrough AT, Dittrich MO, Page ST et al. Transdermal androgen therapy to augment EPO in the treatment of anemia of chronic renal disease. Am J Kidney Dis 2006; 47:251-262. (Pubitemid 43121328)
61. Giannoulis MG, Martin FC, Nair KS et al. Hormone replacement therapy and physical function in healthy older men. Time to talk hormones? Endocr Rev 2012; 33:314-377.
62. Sattler FR, Castaneda-Sceppa C, Binder EF et al. Testosterone and growth hormone improve body composition and muscle performance in older men. J Clin Endocrinol Metab 2009; 94:1991-2001.
63. Giannoulis MG, Jackson N, Shojaee-Moradie F et al. The effects of growth hormone and/or testosterone on whole body protein kinetics and skeletal muscle gene expression in healthy elderly men: a randomized controlled trial. J Clin Endocrinol Metab 2008; 93:3066-3074.
64. Surampudi PN, Wang C, Swerdloff R. Hypogonadism in the aging male diagnosis, potential benefits, and risks of testosterone replacement therapy. Int J Endocrinol 2012; 2012:625434
65. Lawrence IG, Price DE, Howlett TA et al. Correcting impotence in the male dialysis patient: experience with testosterone replacement and vacuum tumescence therapy. Am J Kidney Dis 1998; 31:313-319. (Pubitemid 28106424)
66. Zarrouf FA, Artz S, Griffith J et al. Testosterone and depression: systematic review and meta-analysis. J Psychiatr Pract 2009; 15:289-305.
67. Murray AM. Cognitive impairment in the aging dialysis and chronic kidney disease populations: an occult burden. Adv Chronic Kidney Dis 2008; 15:123-132. (Pubitemid 351343871)
68. Halen NV, Cukor D, Constantiner M et al. Depression and mortality in end-stage renal disease. Curr Psychiatry Rep 2012; 14:36-44.
69. Fink HA, Ewing SK, Ensrud KE et al. Association of testosterone and estradiol deficiency with osteoporosis and rapid bone loss in older men. J Clin Endocrinol Metab 2006; 91:3908-3915. (Pubitemid 44536863)
70. Oury F, Sumara G, Sumara O et al. Endocrine regulation of male fertility by the skeleton. Cell 2011; 144:796-809.
71. Isidori AM, Giannetta E, Greco EA et al. Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clin Endocrinol (Oxf) 2005; 63:280-293. (Pubitemid 41233445)
72. Doumouchtsis KK, Kostakis AI, Doumouchtsis SK et al. The effect of sexual hormone abnormalities on proximal femur bone mineral density in hemodialysis patients and the possible role of RANKL. Hemodial Int 2008; 12:100-107. (Pubitemid 351247386)
73. Meng J, Ohlsson C, Laughlin GA et al. Associations of estradiol and testosterone with serum phosphorus in older men: the Osteoporotic Fractures in Men study. Kidney Int 2010; 78:415-422.
74. Yilmaz MI, Sonmez A, Qureshi AR et al. Endogenous testosterone, endothelial dysfunction, and cardiovascular events in men with non-dialysis chronic kidney disease. Clin J Am Soc Nephrol 2011; 6:1617-1625.
75. Wehr E, Pilz S, Boehm BO et al. Association of vitamin D status with serum androgen levels in men. Clin Endocrinol (Oxf) 2010; 73:243-248.
76. Nimptsch K, Platz EA, Willett WC et al. Association between plasma 25-OH vitamin D and testosterone levels in men. Clin Endo-crinol (Oxf) 2012; 77:106-112.
77. Lee DM, Tajar A, Pye SR et al. Association of hypogonadism with vitamin D status: the European Male Ageing Study. Eur J Endocri-nol 2012; 166:77-85.
78. Pilz S, Frisch S, Koertke H et al. Effect of vitamin D supplementation on testosterone levels in men. Horm Metab Res 2011; 43:223-225.
79. Carrero JJ, de Jager DJ, Verduijn M et al. Cardiovascular and non-cardiovascular mortality among men and women starting dialysis. Clin J Am Soc Nephrol 2011; 6:1722-1730.
80. Blagosklonny MV. Why men age faster but reproduce longer than women: mTOR and evolutionary perspectives. Aging (Albany NY) 2010; 2:265-273.
81. Malkin CJ, Channer KS, Jones TH. Testosterone and heart failure. Curr Opin Endocrinol Diabetes Obes 2010; 17:262-268.
82. Corona G, Rastrelli G, Monami M et al. Hypogonadism as a risk factor for cardiovascular mortality in men: a meta-analytic study. Eur J Endocrinol 2011; 165:687-701.
83. Carrero JJ, Qureshi AR, Nakashima A et al. Prevalence and clinical implications of testosterone deficiency in men with end-stage renal disease. Nephrol Dial Transplant 2011; 26:184-190.
84. Kyriazis J, Tzanakis I, Stylianou K et al. Low serum testosterone, arterial stiffness and mortality in male haemodialysis patients. Nephrol Dial Transplant 2011; 26:2971-2977.
85. Muller M, Van den Beld AW, Bots ML et al. Endogenous sex hormones and progression of carotid atherosclerosis in elderly men. Circulation 2004; 109:2074-2079. (Pubitemid 38620214)
86. Hak AE, Witteman JC, de Jong FH et al. Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam study. J Clin Endocrinol Metab 2002; 87:3632-3639. (Pubitemid 34879505)
87. Karakitsos D, Patrianakos AP, De Groot E et al. Androgen deficiency and endothelial dysfunction in men with end-stage kidney disease receiving maintenance hemodialysis. Am J Nephrol 2006; 26:536-543. (Pubitemid 46143875)
88. Zhang Y, Ouyang P, Post WS et al. Sex-steroid hormones and elec-trocardiographic QT-interval duration: findings from the third National Health and Nutrition Examination Survey and the MultiEthnic Study of Atherosclerosis. Am J Epidemiol 2011; 174:403-411.
89. Bai CX, Kurokawa J, Tamagawa M et al. Nontranscriptional regulation of cardiac repolarization currents by testosterone. Circulation 2005; 112:1701-1710. (Pubitemid 41368145)
90. Drici MD, Burklow TR, Haridasse V et al. Sex hormones prolong the QT interval and downregulate potassium channel expression in the rabbit heart. Circulation 1996; 94:1471-1474. (Pubitemid 26307281)
91. Laughlin GA, Barrett-Connor E, Bergstrom J. Low serum testosterone and mortality in older men. J Clin Endocrinol Metab 2008; 93:68-75.
92. Khaw KT, Dowsett M, Folkerd E et al. Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) Prospective Population Study. Circulation 2007; 116:2694-2701. (Pubitemid 350291241)
93. Haring R, Volzke H, Steveling A et al. Low serum testosterone levels are associated with increased risk of mortality in a population-based cohort of men aged 20-79. Eur Heart J 2010; 31:1494-1501.
94. Smith GD, Ben-Shlomo Y, Beswick A et al. Cortisol, testosterone, and coronary heart disease: prospective evidence from the Caer-philly study. Circulation 2005; 112:332-340. (Pubitemid 41022073)
95. Yeap BB, Hyde Z, Almeida OP et al. Lower testosterone levels predict incident stroke and transient ischemic attack in older men. J Clin Endocrinol Metab 2009; 94:2353-2359.
96. Wehr E, Pilz S, Boehm BO et al. Low free testosterone is associated with heart failure mortality in older men referred for coronary angio-graphy. Eur J Heart Fail 2011; 13:482-488.
97. Wang C, Jackson G, Jones TH et al. Low testosterone associated with obesity and the metabolic syndrome contributes to sexual dysfunction and cardiovascular disease risk in men with type 2 diabetes. Diabetes Care 2011; 34:1669-1675.
98. Ruige JB, Mahmoud AM, De Bacquer D et al. Endogenous testosterone and cardiovascular disease in healthy men: a meta-analysis. Heart 2011; 97:870-875.
99. Ohlsson C, Barrett-Connor E, Bhasin S 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; 58:1674-1681.
100. Nettleship JE, Jones TH, Channer KS et al. Physiological testosterone replacement therapy attenuates fatty streak formation and improves high-density lipoprotein cholesterol in the Tfm mouse: an effect that is independent of the classic androgen receptor. Circulation 2007; 116:2427-2434. (Pubitemid 350145077)
101. English KM, Steeds RP, Jones TH et al. Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: a randomized, double-blind, placebo-controlled study. Circulation 2000; 102:1906-1911.
102. Smith JC, Bennett S, Evans LM et al. The effects of induced hypo-gonadism on arterial stiffness, body composition, and metabolic parameters in males with prostate cancer. J Clin Endocrinol Metab 2001; 86:4261-4267. (Pubitemid 32848544)
103. Hanke H, Lenz C, Hess B et al. Effect of testosterone on plaque development and androgen receptor expression in the arterial vessel wall. Circulation 2001; 103:1382-1385. (Pubitemid 32220628)
104. Foresta C, Zuccarello D, De Toni L et al. Androgens stimulate endothelial progenitor cells through an androgen receptor-mediated pathway. Clin Endocrinol (Oxf) 2008; 68:284-289.
105. Liu D, Dillon JS. Dehydroepiandrosterone stimulates nitric oxide release in vascular endothelial cells: evidence for a cell surface receptor. Steroids 2004; 69:279-289. (Pubitemid 38748724)
106. Webb CM, Elkington AG, Kraidly MM et al. Effects of oral testosterone treatment on myocardial perfusion and vascular function in men with low plasma testosterone and coronary heart disease. Am J Cardiol 2008; 101:618-624. (Pubitemid 351625084)
107. Malkin CJ, Jones RD, Jones TH et al. Effect of testosterone on ex vivo vascular reactivity in man. Clin Sci (Lond) 2006; 111:265-274. (Pubitemid 44599873)
108. Carrero JJ, Stenvinkel P. Inflammation in end-stage renal disease- what have we learned in 10 years? Semin Dial 2010; 23:498-509.
109. Carrero JJ, Park SH, Axelsson J et al. Cytokines, atherogenesis, and hypercatabolism in chronic kidney disease: a dreadful triad. Semin Dial 2009; 22:381-386.
110. Fukata J, Imura H, Nakao K. Cytokines as mediators in the regulation of the hypothalamic-pituitary-adrenocortical function. J En-docrinol Invest 1994; 17:141-155. (Pubitemid 24280436)
111. Jones TH, Kennedy RL. Cytokines and hypothalamic-pituitary function. Cytokine 1993; 5:531-538. (Pubitemid 24072054)
112. Malkin CJ, Pugh PJ, Jones RD et al. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab 2004; 89:3313-3318. (Pubitemid 38951897)
113. Corrales JJ, Almeida M, Burgo R et al. Androgen-replacement therapy depresses the ex vivo production of inflammatory cyto-kines by circulating antigen-presenting cells in aging type-2 diabetic men with partial androgen deficiency. J Endocrinol 2006; 189:595-604. (Pubitemid 43922123)
114. Gungor O, Kircelli F, Carrero JJ et al. Endogenous testosterone and mortality in male hemodialysis patients: is it the result of aging? Clin J Am Soc Nephrol 2010; 5:2018-2023.
115. Haring R, Nauck M, Volzke H et al. Low serum testosterone is associated with increased mortality in men with stage 3 or greater nephropathy. Am J Nephrol 2011; 33:209-217.
116. Araujo AB, Dixon JM, Suarez EA et al. Clinical review: endogenous testosterone and mortality in men: a systematic review and meta-analysis. J Clin Endocrinol Metab 2011; 96:3007-3019.
117. Silbiger S, Neugarten J. Gender and human chronic renal disease. Gend Med 2008; 5 (Suppl A): S3-S10 (Pubitemid 351455227)
118. Neugarten J, Acharya A, Silbiger SR. Effect of gender on the progression of nondiabetic renal disease: a meta-analysis. J Am Soc Nephrol 2000; 11:319-329. (Pubitemid 30064855)
119. Ji H, Menini S, Mok K et al. Gonadal steroid regulation of renal injury in renal wrap hypertension. Am J Physiol Renal Physiol 2005; 288: F513-F520 (Pubitemid 40279457)
120. Cho MH, Jung KJ, Jang HS et al. Orchiectomy attenuates kidney fibrosis after ureteral obstruction by reduction of oxidative stress in mice. Am J Nephrol 2012; 35:7-16.
121. Metcalfe PD, Leslie JA, Campbell MT et al. Testosterone exacerbates obstructive renal injury by stimulating TNF-alpha production and increasing proapoptotic and profibrotic signaling. Am J Physiol Endocrinol Metab 2008; 294: E435-E443 (Pubitemid 351231472)
122. Elliot SJ, Berho M, Korach K et al. Gender-specific effects of endogenous testosterone: female alpha-estrogen receptor-deficient C57Bl/6J mice develop glomerulosclerosis. Kidney Int 2007; 72:464-472. (Pubitemid 47237609)
123. Reckelhoff JF, Zhang H, Srivastava K. Gender differences in development of hypertension in spontaneously hypertensive rats: role of the renin-angiotensin system. Hypertension 2000; 35 (1 Pt 2):480-483. (Pubitemid 30054220)
124. Reckelhoff JF, Yanes LL, Iliescu R et al. Testosterone supplementation in aging men and women: possible impact on cardiovascular-renal disease. Am J Physiol Renal Physiol 2005; 289: F941-F948 (Pubitemid 41447048)
125. Doublier S, Lupia E, Catanuto P et al. Testosterone and 17beta-es-tradiol have opposite effects on podocyte apoptosis that precedes glomerulosclerosis in female estrogen receptor knockout mice. Kidney Int 2011; 79:404-413.
126. Xu Q, Wells CC, Garman JH et al. Imbalance in sex hormone levels exacerbates diabetic renal disease. Hypertension 2008; 51:1218-1224. (Pubitemid 351398951)
127. Eiam-Ong S, Buranaosot S, Eiam-Ong S et al. Nutritional effect of nandrolone decanoate in predialysis patients with chronic kidney disease. J Ren Nutr 2007; 17:173-178. (Pubitemid 46617296)
128. Iglesias P, Carrero JJ, Diez JJ. Gonadal dysfunction in men with chronic kidney disease: clinical features, prognostic implications and therapeutic options. J Nephrol 2012; 25:31-42.
129. Haddad RM, Kennedy CC, Caples SM et al. Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clin Proc 2007; 82:29-39. (Pubitemid 46036319)
130. Gooren LJ, Behre HM. Diagnosing and treating testosterone deficiency in different parts of the world: changes between 2006 and 2010. Aging Male 2012; 15:22-27.
131. Brand TC, Canby-Hagino E, Thompson IM. Testosterone replacement therapy and prostate cancer: a word of caution. Curr Urol Rep 2007; 8:185-189. (Pubitemid 46806646)
132. Morgentaler A, Traish AM. Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of andro-gen-dependent growth. Eur Urol 2009; 55:310-320.
133. Roddam AW, Allen NE, Appleby P et al. Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J Natl Cancer Inst 2008; 100:170-183. (Pubitemid 351480553)
134. Carpenter WR, Robinson WR, Godley PA. Getting over testosterone: postulating a fresh start for etiologic studies of prostate cancer. J Natl Cancer Inst 2008; 100:158-159. (Pubitemid 351480558)
135. Calof OM, Singh AB, Lee ML et al. Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. J Gerontol A Biol Sci Med Sci 2005; 60:1451-1457. (Pubitemid 41798454)
136. Bhasin S, Cunningham GR, Hayes FJ et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2010; 95:2536-2559.
137. Sullivan ML, Martinez CM, Gennis P et al. The cardiac toxicity of anabolic steroids. Prog Cardiovasc Dis 1998; 41:1-15. (Pubitemid 28385246)
138. Pugh PJ, Jones RD, West JN et al. Testosterone treatment for men with chronic heart failure. Heart 2004; 90:446-447. (Pubitemid 38406925)
139. Liu PY, Yee B, Wishart SM et al. The short-term effects of highdose testosterone on sleep, breathing, and function in older men. J Clin Endocrinol Metab 2003; 88:3605-3613. (Pubitemid 37034502)
140. Basaria S, Coviello AD, Travison TG et al. Adverse events associated with testosterone administration. N Engl J Med 2010; 363:109-122.
141. Laughlin GA, Goodell V, Barrett-Connor E. Extremes of endogenous testosterone are associated with increased risk of incident coronary events in older women. J Clin Endocrinol Metab 2010; 95:740-747.
142. Albaaj F, Sivalingham M, Haynes P et al. Prevalence of hypogo-nadism in male patients with renal failure. Postgrad Med J 2006; 82:693-696. (Pubitemid 44786879)