Current topics in testosterone replacement of hypogonadal men

Best Practice and Research: Clinical Endocrinology and Metabolism

Volumn 29, Issue 1, 2015, Pages 77-90

  Nieschlag, Eberhard ^a,b  

^a UNIVERSITY HOSPITAL MÜNSTER   (Germany)

^b KING ABDULAZIZ UNIVERSITY   (Saudi Arabia)

Author keywords

Cardiovascular disease; Diabetes mellitus; Late onset hypogonadiam; Metabolic syndrome; Osteoporosis; Primary hypogonadism; Secondary hypogonadism; Sexual function; Testosterone preparations; Testosterone substitution

Indexed keywords

HEMOGLOBIN; TESTOSTERONE; ANDROGEN; TESTOSTERONE UNDECANOATE;

ANDROGEN THERAPY; BONE DENSITY; CARDIOVASCULAR DISEASE; COMORBIDITY; HUMAN; HYPOGONADISM; METABOLIC SYNDROME X; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; OSTEOPOROSIS; PROSTATE CANCER; REVIEW; SEXUAL BEHAVIOR; SEXUAL FUNCTION; TESTOSTERONE BLOOD LEVEL; TIME TO TREATMENT; ANALOGS AND DERIVATIVES; HORMONE SUBSTITUTION; MALE; TOPICAL DRUG ADMINISTRATION; TREATMENT OUTCOME;

ADMINISTRATION, TOPICAL; ANDROGENS; HORMONE REPLACEMENT THERAPY; HUMANS; HYPOGONADISM; MALE; TESTOSTERONE; TREATMENT OUTCOME;

EID: 84927928119     PISSN: 1521690X     EISSN: 15321908     Source Type: Journal    
DOI: 10.1016/j.beem.2014.09.008     Document Type: Review

References (106)

1. Nieschlag E, Behre HM, Nieschlag S, editors. Andrology: Male reproductive health and dysfunction. 3rd ed. Heidelberg: Springer; 2010.
2. Nieschlag E. Male hypogonadism and infertility. In: Wass AH, Stewart PM, Amiel SA, et al., editors. Oxford textbook of endocrinology and diabetes. 2nd ed. Oxford: Oxford, University Press; 2011. p. 1331-480.
3. Wang C, Nieschlag E, Swerdloff R, et al. Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA and ASA recommendations. Eur J Endocrinol 2008; 159: 507-14.
4. Bhasin S, Cunningham GR, Hayes FJ, et al., Task Force, Endocrine Society. Testosterone therapy in men with androgen deficiency syndromes: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metabolism 2010; 6. 2536-259.
5. Dohle GR, Arvers S, Bettocchi C, et al. Guidelines on male hypogonadism. Eur Assoc Urol 2012. www.uroweb.org.
6. Swerdloff RS, Wang CL. Review of guidelines on diagnosis and treatment of testosterone deficiency. In: Nieschlag E, Behre HM, Nieschlag S, editors. Testosterone: Action, deficiency, substitution. 4th ed. Cambridge: Cambridge University Press; 2012. p. 408-20.
7. Layton JB, Li D, Meier CR, et al. Testosterone lab testing and initiation in the United Kingdom and the United States, 2000-2011. J Clin Endocrinol Metabolism 2014; 99: 835-42.
8. Gan EH, Pattman S, Pearce S HS, et al. A UK epidemic of testosterone prescribing, 2001-2010. Clin Endocrinol 2013; 79: 564-70.
9. Diver MJ, Imtiaz KE, Ahmad AM, et al. Diurnal rhythms of serum total, free and bioavailable testosterone and of SHBG in middle-aged men compared with those in young men. Clin Endocrinol 2003; 58: 710-7.
10. Kelleher S, Conway AJ, Handelsman DJ. Blood testosterone threshold for androgen deficiency symptoms. J Clin Endocrinol Metabolism 2004; 89: 3813-7.
11. Zitzmann M, Faber S, Nieschlag E. Association of specific symptoms and metabolic risks with serum testosterone in older men. J Clin Endocrinol Metabolism 2006; 91: 4335-43.
12. Nieschlag E, Behre HM, Bouchard P, et al. Testosterone replacement therapy: Current trends and future directions. Hum Reprod Update 2004; 10: 409-19.
13. Wu FC, Tajar A, Beynon JM, et al., EMAS Group. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med 2010; 363: 123-35.
14. Gooren LJ, Behre HM. Diagnosing and treating testosterone deficiency in different parts of the world: Changes between 2006 and 2010. Aging Male 2012; 15: 22-7.
15. Bhasin S, Pencina M, Jasuja GK, et al. Reference ranges for testosterone in men generated using liquid chromatography tandem mass spectrometry in a community-based sample of healthy nonobese young men in the Framingham heart study and applied to three geographically distinct cohorts. J Clin Endocrinol Metabolism 2011; 96: 2430-9.
16. Sartorius G, Spasevska S, Idan A, et al. Serum testosterone, dihydrotestosterone and estradiol concentrations in older men self-reporting very good health: The healthy man study. Clin Endocrinol 2012; 77: 755-63.
17. Huhtaniemi IT, Tajar A, Lee DM, et al., EMAS Group. Comparison of serum testosterone and estradiol measurements in 3174 European men using platform immunoassay and mass spectrometry; relevance for the diagnostics in aging men. Eur J Endocrinol 2012; 166: 983-91.
18. Frost M, Wraae K, Nielsen TL, et al. Similar reference intervals for total testosterone in healthy young and elderly men: Results from the Odense androgen study. Clin Endocrinol 2013; 78: 743-51.
19. Morris PD, Malkin CJ, Channer KS, et al. A mathematical comparison of techniques to predict biologically available testosterone in a cohort of 1072 men. Eur J Endocrinol 2004; 151: 241-9.
20. Rosner W, Auchus RJ, Azziz R, et al. Position statement: Utility, limitations, and pitfalls in measuring testosterone: An endocrine society position statement. J Clin Endocrinol Metabolism 2007; 92: 405-13.
21. Simoni M, Fanelli F, Roli L, et al. Methodology for measuring testosterone, dihydrotestosterone and sex hormonebinding globulin in a clinical setting. In: Nieschlag E, Behre HM, Nieschlag S, editors. Testosterone: Action, deficiency, substitution. 4th ed. Cambridge: Cambridge University Press; 2012. p. 60-86.
22. Haring R, Baumeister SE, Nauck M, et al. Testosterone and cardiometabolic risk in the general population-The impact of measurement method on risk associations: A comparative study between immunoassay and mass spectrometry. Eur J Endocrinol 2013; 169: 463-70.
23. Handelsman DJ, Wartofsky L. Requirement for mass spectrometry sex steroid assays in the Journal of Clinical Endocrinology and Metabolism. J Clin Endocrinol Metabolism 2013; 98: 3971-3.
24. Nieschlag E, Nieschlag S. Testosterone deficiency: A historical perspective [Invited review] Asian J Androl 2014; 16: 161-8.
25. Nieschlag E, Wang CH, Handelsman DJ, et al., editors. Guidelines for the use of androgens. Geneva: WHO Special Programme of Research, Development and Research Training in Human Reproduction; 1992.
26. Finkelstein JS, Lee H, Burnett-Bowie SA, et al. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med 2013; 369: 1011-22.
27. Sartorius GA, Ly LP, Handelsman DJ. Male sexual function can be maintained without aromatization: Randomized placebo-controlled trial of dihydrotestosterone (DHT) in healthy, older men for 24 months. J Sex Med 2014; 11: 2562-70.
28. Jasuja R, Zacharov MN, Bhasin S. The state-of-The-art in the development of selective androgen receptor modulators. In: Nieschlag E, Behre HM, Nieschlag S, editors. Testosterone: Action, deficiency, substitution. 4th ed. Cambridge: Cambridge University Press; 2012. p. 459-69.
29. Dalton JT, Taylor RP, Mohler ML, et al. Selective androgen receptor modulators for the prevention and treatment of muscle wasting associated with cancer. Curr Opin Support Palliat Care 2013; 7: 345-51.
30. Behre HM, Nieschlag E. Testosterone preparations for clinical use in males. In: Nieschlag E, Behre HM, Nieschlag S, editors. Testosterone: Action, deficiency, substitution. 4th ed. Cambridge: Cambridge University Press; 2012. p. 309-35.
31. Nieschlag E, Büchter D, von Eckardstein S, et al. Repeated intramuscular injections of testosterone undecanoate for substitution therapy in hypogonadal men. Clin Endocrinol 1999; 51: 757-63.
32. Zitzmann M, Nieschlag E. 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 Metabolism 2007; 92: 3844-53.
33. Brabrand S, Fosså SD, Cvancarova M, et al. Androgen substitution with testosterone undecanoate in survivors of bilateral testicular cancer requires individually-adjusted injection intervals. Br J Urol Int 2011; 107: 1080-7.
34. Mackey MA, Conway AJ, Handelsman DJ. Tolerability of intramuscular injections of testosterone ester in oil vehicle. Hum Reprod 1995; 108. 62-865.
35. Endo Pharmaceuticals Solutions. In: Aveed™ (testosterone undecanoate) for testosterone replacement for treatment of hypogonadism: Briefing documentation joint meeting of Reproductive Health Drugs Advisory Committee & Drug Safety Risk Management Advisory Committee meeting; April 18, 2013. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ReproductiveHealthDrugsAdvisoryCommittee/UCM348092.pdf.
36. Wang C, Harnett M, Dobs AS, et al. Pharmacokinetics and safety of long-acting testosterone undecanoate injections in hypogonadal men: An 84-week phase III clinical trial. J Androl 2010; 31: 457-65.
37. Pastuszak AW, Mittakanti H, Liu JS, et al. Pharmacokinetic evaluation and dosing of subcutaneous testosterone pellets. J Androl 2012; 33: 927-37.
38. Kelleher S, Turner L, Howe C, et al. Extrusion of testosterone pellets: A randomized controlled clinical study. Clin Endocrinol 1999; 51: 469-71.
39. Fennell C, Sartorius G, Ly LP, et al. Randomized cross-over clinical trial of injectable vs. implantable depot testosterone for maintenance of testosterone replacement therapy in androgen deficient men. Clin Endocrinol 2010; 73: 102-9.
40. Nieschlag E, Mauss J, Coert A, et al. Plasma androgen levels in men after oral administration of testosterone or testosterone undecanoate. Acta Endocrinol (Copenh) 1975; 79: 366-74.
41. Bagchus WM, Hust R, Maris F, et al. Important effect of food on the bioavailability of oral testosterone undecanoate. Pharmacotherapy 2003; 23: 319-25.
42. Gooren LJG, Polderman KH. Safety aspects of androgen therapy. In: Nieschlag E, Behre HM, editors. Testosterone: Action, deficiency, substitution. 1st ed. Heidelberg: Springer; 1990. p. 182-203.
43. Yin A, Alfadhli E, Htun M, et al. Dietary fat modulates the testosterone pharmacokinetics of a new self-emulsifying formulation of oral testosterone undecanoate in hypogonadal men. J Androl 2012; 33: 1282-90.
44. Korbonits M, Kipnes M, Grossman AB. Striant SR: A novel, effective and convenient testosterone therapy for male hypogonadism. Int J Clin Pract 2004; 58: 1073-80.
45. Dinsmore WW, Wyllie MG. The long-term efficacy and safety of a testosterone mucoadhesive buccal tablet in testosterone-deficient men. Br J Urol Int 2012; 110: 162-9.
46. Behre HM, von Eckardstein S, Kliesch S, et al. Long-term substitution therapy of hypogonadal men with transscrotal testosterone over 7-10 years. Clin Endocrinol 1999; 50: 629-35.
47. Raynaud JP, Augés M, Liorzou L, et al. Adhesiveness of a new testosterone-in-adhesive matrix patch after extreme conditions. Int J Pharm 2009; 375: 28-32.
48. Wang C, Cunningham G, Dobs A, 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 Metabolism 2004; 89: 2085-98.
49. McNicholas T, Ong T. Review of Testim gel. Expert Opin Pharmacother 2006; 7: 477-84.
50. Behre HM, Tammela TL, Arver S, 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.
51. Kühnert B, Byrne M, Simoni M, et al., for the Wolff Multi-Centre Study Group. Testosterone substitution with a new transdermal, hydroalcoholic gel applied to scrotal or non-scrotal skin: A multicentre trial. Eur J Endocrinol 2005; 153: 317-26.
52. de Ronde W. Hyperandrogenism after transfer of topical testosterone gel: Case report and review of published and unpublished studies. Hum Reprod 2009; 24: 425-8.
53. Nelson D, Ho J, Pacaud D, et al. Virilization in two pre-pubertal children exposed to topical androgen. J Pediatr Endocrinol Metabolism 2013; 24: 1-5.
54. Isidori AM, Giannetta E, Gianfrilli D, et al. Effects of testosterone on sexual function in men: Results of a meta-analysis. Clin Endocrinol 2005; 63: 381-94.
55. Saad F, Aversa A, Isidori AM, et al. Onset of effects of testosterone treatment and time span until maximum effects are achieved. Eur J Endocrinol 2011; 165: 675-85.
56. Lee KK, Berman N, Alexander GM, et al. A simple self-report diary for assessing psychosexual function in hypogonadal men. J Androl 2003; 24: 688-98.
57. Rosen RC, Araujo AB, Connor, et al. The NERI Hypogonadism Screener: Psychometric validation in male patients and controls. Clin Endocrinol 2011; 74: 248-56.
58. Buvat J, Montorsi F, Maggi M, 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.
59. Maggi M, Behre HG. Testosterone and erection. In: Nieschlag E, Behre HM, Nieschlag S, editors. Testosterone: Action, deficiency, substitution. 4th ed. Cambridge: Cambridge University Press; 2012. p. 251-67.
60. Yassin DJ, Yassin AA, Hammerer PG. Combined testosterone and vardenafil treatment for restoring erectile function in hypogonadal patients who failed to respond to testosterone therapy alone. J Sex Med 2014; 11: 543-52.
61. Nehra A, Jackson G, Miner M, et al. Diagnosis and treatment of erectile dysfunction for reduction of cardiovascular risk. J Urol 2013; 189: 2031-8.
62. Snyder PJ, Peachey H, Hannoush P, et al. Effect of testosterone treatment on bone mineral density in men over 65 years of age. J Clin Endocrinol Metabolism 1999; 84: 1966-72.
63. Rodriguez-Tolrá J, Torremadé J, di Gregorio S, et al. Effects of testosterone treatment on bone mineral density in men with testosterone deficiency syndrome. Andrology 2013; 1: 570-5.
64. LeBlanc ES, Nielson CM, Marshall LM, et al., Osteoporotic Fractures in Men Study Group. The effects of serum testosterone, estradiol, and sex hormone binding globulin levels on fracture risk in older men. J Clin Endocrinol Metabolism 2009; 94: 3337-46.
65. Ohlsson C, Vandenput L. The role of estrogens for male bone health. Eur J Endocrinol 2009; 160: 883-9.
66. Zitzmann M, Brune M, Kornmann B, et al. The CAG repeat polymorphism in the androgen receptor gene affects bone density and bone metabolism in healthy males. Clin Endocrinol 2001; 55: 649-57.
67. Tirabassi G, Delli Muti N, Gioia A, et al. Effects of testosterone replacement therapy on bone metabolism in male postsurgical hypogonadotropic hypogonadism: Focus on the role of androgen receptor CAG polymorphism. J Endocrinol Investig 2014 Jan 24 [Epub ahead of print].
68. Haider A, Meergans U, Traish A, 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. http://dx.doi.org/10. 1155/2014/496948. ID 496948.
69. Bojesen A, Birkebæk N, Kristensen K, et al. Bone mineral density in Klinefelter syndrome is reduced and primarily determined by muscle strength and resorptive markers, but not directly by testosterone. Osteoporos Int 2011; 22: 1441-50.
70. Tüttelmann F, Gromoll J. Novel genetic aspects of Klinefelter's syndrome. Mol Hum Reprod 2010; 16: 386-95.
71. Watts NB, Adler RA, Bilezikian JP, et al. Osteoporosis in men: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metabolism 2012; 97: 1802-22.
72. Sonmez A, Haymana C, Bolu E, et al. Metabolic syndrome and the effect of testosterone treatment in young men with congenital hypogonadotropic hypogonadism. Eur J Endocrinol 2011; 164: 759-64.
73. Nieschlag E. Klinefelter Syndrome: The commonest form of hypogonadism, but often overlooked or untreated. Dtsch Arzteblatt Int 2013; 110: 347-53.
74. Saad F, Haider A, Doros G, et al. Long-term treatment of hypogonadal men with testosterone produces substantial and sustained weight loss. Obes (Silver Springs) 2013; 20. http://dx.doi.org/10.1002/oby.20407 [Epub ahead of print].
75. Traish AM, Haider A, Doros G, 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: 314-29.
76. Haring R, Völzke H, Felix SB, et al. Prediction of metabolic syndrome by low serum testosterone levels in men: Results from the study of health in Pomerania. Diabetes 2009; 58: 2027-31.
77. Heufelder AE, Saad F, Bunck MC, 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: 726-33.
78. Muraleedharan V, Marsh H, Kapoor D, 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: 725-33.
79. Hackett G, Cole N, Bhartia M, 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: 1612-27.
80. Banks E, Joshy G, Abhayaratna WP, et al. Erectile dysfunction severity as a risk marker for cardiovascular disease hospitalisation and all-cause mortality: A prospective cohort study. PLOS Med 2013. http://dx.doi.org/10.1371/journal. pmed.1001372 [Epub ahead of print].
81. Channer KS, Jones TH. Testosterone and cardiovascular disease. In: Nieschlag E, Behre HM, Nieschlag S, editors. Testosterone: Action, deficiency, substitution. 4th ed. Cambridge: Cambridge University Press; 2012. p. 207-34.
82. Vorona E, Nieschlag E. Sequelae of doping with anabolic steroids. In: Nieschlag E, Behre HM, Nieschlag S, editors. Testosterone: Action, deficiency, substitution. 4th ed. Cambridge: Cambridge University Press; 2012. p. 535-46.
83. Liao CH, Wu YN, Lin FY, et al. Testosterone replacement therapy can increase circulating endothelial progenitor cell number in men with late onset hypogonadism. Andrology 2013; 1: 563-9.
84. Toma M, McAlister FA, Coglianese EE, et al. Testosterone supplementation in heart failure: A meta-analysis. Circ Heart Fail 2012; 5: 315-21.
85. Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone administration. N Engl J Med 2010; 363: 109-22.
86. Xu L, Freeman G, Cowling BJ, et al. Testosterone therapy and cardiovascular events among men: A systematic review and meta-analysis of placebo-controlled randomized trials. BMC Med 2013; 11: 108.
87. Vigen R, O'Donnell CI, Barón AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. J Am Med Assoc 2013; 310: 1829-36.
88. Finkle WD, Greenland S, Ridgeway GK, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One 2014 Jan; 9: E85805.
89. Shores MM, Smith NL, Forsberg CW, et al. Testosterone treatment and mortality in men with low testosterone levels. J Clin Endocrinol Metabolism 2012; 97: 2050-8.
90. Page ST, Lin DW, Mostaghel EA, et al. Persistent intraprostatic androgen concentrations after medical castration in healthy men. J Clin Endocrinol Metabolism 2006; 91: 3850-6.
91. Mostaghel EA, Lin DW, Amory JK, et al. Impact of male hormonal contraception on prostate androgens and androgen action in healthy men: A randomized, controlled trial. J Clin Endocrinol Metabolism 2012; 97: 2809-17.
92. Cheung AS, Pattison D, Bretherton I, et al. Cardiovascular risk and bone loss in men undergoing androgen deprivation therapy for non-metastatic prostate cancer: Implementation of standardized management guidelines. Andrology 2013; 1: 583-9.
93. Pastuszak AW, Pearlman AM, Lai WS, et al. Testosterone replacement therapy in patients with prostate cancer after radical prostatectomy. J Urol 2013; 190: 639-44.
94. Nielsen J, Pelsen B, Sørensen K. Follow-up of 30 Klinefelter males treated with testosterone. Clin Genet 1988; 33: 262-9.
95. Rogol AD, Swerdloff RS, Reiter EO, et al. A multicenter, open-label, observational study of testosterone gel (1%) in the treatment of adolescent boys with Klinefelter syndrome or anorchia. J Adolesc Health 2014; 54: 20-5.
96. Samango-Sprouse CA, Sadeghin T, Mitchell FL, et al. Positive effects of short course androgen therapy on the neurodevelopmental outcome in boys with 47,XXY syndrome at 36 and 72 months of age. Am J Med Genet A 2013; 161A: 501-8.
97. Nieschlag E,Werler S, Wistuba J, et al. New approaches to the Klinefelter syndrome. Ann d' Endocrinol (Paris) 2014; 75: 88-97.
98. Mehta A, Bolyakov A, Roosma J, et al. Successful testicular sperm retrieval in adolescents with Klinefelter syndrome treated with at least 1 year of topical testosterone and aromatase inhibitor. Fertil Steril 2013; 100: 970-4.
99. Van Saen D, Gies I, De Schepper J, et al. Can pubertal boys with Klinefelter syndrome benefit from spermatogonial stem cell banking? Hum Reprod 2012; 27: 323-30.
100. Büchter D, Behre HM, Kliesch S, et al. Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: A review of 42 cases. Eur J Endocrinol 1998; 139: 298-303.
101. 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 studies. J Gerontol Ser A Biol Sci Med Sci 2005; 60: 1451-7.
102. Sartorius GA, Handelsman DJ. Testicular dysfunction in systemic diseases. In: Nieschlag E, Behre HM, Nieschlag S, editors. Andrology: Male reproductive health and dysfunction. 3rd ed. Heidelberg: Springer; 2010. p. 339-64.
103. Grossmann M. Low testosterone in men with type 2 diabetes: Significance and treatment. J Clin Endocrinol Metabolism 2011; 96: 2341-53.
104. Camacho EM, Huhtaniemi IT, O'Neill, et al., EMAS Group. 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.
105. Yeap BB, Almeida OP, Hyde Z, et al. Healthier lifestyle predicts higher circulating testosterone in older men: The health in men study. Clin Endocrinol 2009; 70: 455-63.
106. Shi Z, Araujo AB, Martin S, et al. Longitudinal changes in testosterone over five years in community-dwelling men. J Clin Endocrinol Metabolism 2013; 98: 3289-97.