Update on Testosterone Replacement Therapy in Hypogonadal Men

1.

Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab. 2001;86(2):724–31. doi:10.1210/jcem.86.2.7219.PubMedCrossRef

2.

Corona G, Rastrelli G, Forti G, Maggi M. Update in testosterone therapy for men. J Sex Med. 2011;8(3):639–54. doi:10.1111/j.1743-6109.2010.02200.x. quiz 55.PubMedCrossRef

3.

Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 2002;87(2):589–98. doi:10.1210/jcem.87.2.8201.PubMedCrossRef

4.

Lakshman KM, Kaplan B, Travison TG, Basaria S, Knapp PE, Singh AB, et al. The effects of injected testosterone dose and age on the conversion of testosterone to estradiol and dihydrotestosterone in young and older men. J Clin Endocrinol Metab. 2010;95(8):3955–64. doi:10.1210/jc.2010-0102.PubMedCentralPubMedCrossRef

5.

Corona G, Mannucci E, Ricca V, Lotti F, Boddi V, Bandini E, et al. The age-related decline of testosterone is associated with different specific symptoms and signs in patients with sexual dysfunction. Int J Androl. 2009;32(6):720–8. doi:10.1111/j.1365-2605.2009.00952.x.PubMedCrossRef

6.

McGill JJ, Shoskes DA, Sabanegh ES. Androgen deficiency in older men: indications, advantages, and pitfalls of testosterone replacement therapy. Cleve Clin J Med. 2012;79(11):797–806. doi:10.3949/ccjm.79a.12010.PubMedCrossRef

7.

Wu FC, Tajar A, Beynon JM, Pye SR, Silman AJ, Finn JD, et al. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med. 2010;363(2):123–35. doi:10.1056/NEJMoa0911101.PubMedCrossRef

8.

Traish AM, Miner MM, Morgentaler A, Zitzmann M. Testosterone deficiency. Am J Med. 2011;124(7):578–87. doi:10.1016/j.amjmed.2010.12.027.PubMedCrossRef

9.

Morley JE, Patrick P, Perry 3rd HM. Evaluation of assays available to measure free testosterone. Metabolism. 2002;51(5):554–9.PubMedCrossRef

10.

Ly LP, Sartorius G, Hull L, Leung A, Swerdloff RS, Wang C, et al. Accuracy of calculated free testosterone formulae in men. Clin Endocrinol. 2010;73(3):382–8. doi:10.1111/j.1365-2265.2010.03804.x.CrossRef

11.

Wang C, Nieschlag E, Swerdloff R, Behre HM, Hellstrom WJ, Gooren LJ, et al. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. J Androl. 2009;30(1):1–9. doi:10.2164/jandrol.108.006486.PubMedCrossRef

12.

Araujo AB, O’Donnell AB, Brambilla DJ, Simpson WB, Longcope C, Matsumoto AM, et al. Prevalence and incidence of androgen deficiency in middle-aged and older men: estimates from the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 2004;89(12):5920–6. doi:10.1210/jc.2003-031719.PubMedCrossRef

13.

Bhasin S, Basaria S. Diagnosis and treatment of hypogonadism in men. Best Pract Res Clin Endocrinol Metab. 2011;25(2):251–70. doi:10.1016/j.beem.2010.12.002.PubMedCrossRef

14.

Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, et al. Testosterone therapy in men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2010;95(6):2536–59. doi:10.1210/jc.2009-2354.PubMedCrossRef

15.

Morales A, Bella AJ, Chun S, Lee J, Assimakopoulos P, Bebb R, et al. A practical guide to diagnosis, management and treatment of testosterone deficiency for Canadian physicians. Can Urol Assoc J. 2010;4(4):269–75.PubMedCentralPubMed

16.

Salonia A, Gallina A, Briganti A, Abdollah F, Suardi N, Capitanio U, et al. Preoperative hypogonadism is not an independent predictor of high-risk disease in patients undergoing radical prostatectomy. Cancer. 2011;117(17):3953–62. doi:10.1002/cncr.25985.PubMedCrossRef

17.

Fernandez-Balsells MM, Murad MH, Lane M, Lampropulos JF, Albuquerque F, Mullan RJ, 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(6):2560–75. doi:10.1210/jc.2009-2575.PubMedCrossRef

18.

Niskanen L, Laaksonen DE, Punnonen K, Mustajoki P, Kaukua J, Rissanen A. Changes in sex hormone-binding globulin and testosterone during weight loss and weight maintenance in abdominally obese men with the metabolic syndrome. Diabetes Obes Metab. 2004;6(3):208–15. doi:10.1111/j.1462-8902.2004.00335.x.PubMedCrossRef

19.•

Feneley MR, Carruthers M. Is testosterone treatment good for the prostate? Study of safety during long-term treatment. J Sex Med. 2012;9(8):2138–49. doi:10.1111/j.1743-6109.2012.02808.x. Long-term (up to 20 years) TRT with appropriate monitoring shows no increase in the incidence of PCa compared to the general population.PubMedCrossRef

20.

Haider A, Gooren LJ, Padungtod P, Saad F. Concurrent improvement of the metabolic syndrome and lower urinary tract symptoms upon normalisation of plasma testosterone levels in hypogonadal elderly men. Andrologia. 2009;41(1):7–13. doi:10.1111/j.1439-0272.2008.00880.x.PubMedCrossRef

21.

Zacharin MR, Pua J, Kanumakala S. Bone mineral density outcomes following long-term treatment with subcutaneous testosterone pellet implants in male hypogonadism. Clin Endocrinol. 2003;58(6):691–5.CrossRef

22.

Hellstrom WJ, Paduch D, Donatucci CF. Importance of hypogonadism and testosterone replacement therapy in current urologic practice: a review. Int Urol Nephrol. 2012;44(1):61–70. doi:10.1007/s11255-010-9879-4.PubMedCrossRef

23.

Behre HM, Bohmeyer J, Nieschlag E. Prostate volume in testosterone-treated and untreated hypogonadal men in comparison to age-matched normal controls. Clin Endocrinol. 1994;40(3):341–9.CrossRef

24.

Douglas TH, Connelly RR, McLeod DG, Erickson SJ, Barren 3rd R, Murphy GP. Effect of exogenous testosterone replacement on prostate-specific antigen and prostate-specific membrane antigen levels in hypogonadal men. J Surg Oncol. 1995;59(4):246–50.PubMedCrossRef

25.

Pearl JA, Berhanu D, Francois N, Masson P, Zargaroff S, Cashy J, et al. Testosterone supplementation does not worsen lower urinary tract symptoms. J Urol. 2013;190(5):1828–33. doi:10.1016/j.juro.2013.05.111.PubMedCrossRef

26.

Hsueh PR, Graybill JR, Playford EG, Watcharananan SP, Oh MD, Ja’alam K, et al. Consensus statement on the management of invasive candidiasis in intensive care units in the Asia-Pacific region. Int J Antimicrob Ag. 2009;34(3):205–9. doi:10.1016/J.Ijantimicag.2009.03.014.CrossRef

27.

Araujo 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(10):3007–19. doi:10.1210/jc.2011-1137.PubMedCentralPubMedCrossRef

28.

Haring R, Volzke H, Steveling A, Krebs A, Felix SB, Schofl C, 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(12):1494–501. doi:10.1093/eurheartj/ehq009.PubMedCrossRef

29.

Lin JW, Lee JK, Wu CK, Caffrey JL, Chang MH, Hwang JJ, et al. Metabolic syndrome, testosterone, and cardiovascular mortality in men. J Sex Med. 2011;8(8):2350–60. doi:10.1111/j.1743-6109.2011.02343.x.PubMedCrossRef

30.

Wehr E, Pilz S, Boehm BO, Grammer TB, Marz W, Obermayer-Pietsch B. Low free testosterone levels are associated with all-cause and cardiovascular mortality in postmenopausal diabetic women. Diabetes Care. 2011;34(8):1771–7. doi:10.2337/dc11-0596.PubMedCentralPubMedCrossRef

31.

Ruige JB, Ouwens DM, Kaufman JM. Beneficial and adverse effects of testosterone on the cardiovascular system in men. J Clin Endocrinol Metab. 2013;98(11):4300–10. doi:10.1210/jc.2013-1970.PubMedCrossRef

32.

Ruige JB, Mahmoud AM, De Bacquer D, Kaufman JM. Endogenous testosterone and cardiovascular disease in healthy men: a meta-analysis. Heart. 2011;97(11):870–5. doi:10.1136/hrt.2010.210757.PubMedCrossRef

33.

Laughlin GA, Barrett-Connor E, Bergstrom J. Low serum testosterone and mortality in older men. J Clin Endocrinol Metab. 2008;93(1):68–75. doi:10.1210/jc.2007-1792.PubMedCentralPubMedCrossRef

34.

Corona G, Rastrelli G, Monami M, Guay A, Buvat J, Sforza A, et al. Hypogonadism as a risk factor for cardiovascular mortality in men: a meta-analytic study. Eur J Endocrinol / Eur Fed Endocr Soc. 2011;165(5):687–701. doi:10.1530/EJE-11-0447.CrossRef

35.

Svartberg J, von Muhlen D, Mathiesen E, Joakimsen O, Bonaa KH, Stensland-Bugge E. Low testosterone levels are associated with carotid atherosclerosis in men. J Intern Med. 2006;259(6):576–82. doi:10.1111/j.1365-2796.2006.01637.x.PubMedCrossRef

36.

Tirabassi G, Gioia A, Giovannini L, Boscaro M, Corona G, Carpi A, et al. Testosterone and cardiovascular risk. Intern Emerg Med. 2013;8 Suppl 1:S65–9. doi:10.1007/s11739-013-0914-1.PubMedCrossRef

37.

Yeap BB, Hyde Z, Almeida OP, Norman PE, Chubb SA, Jamrozik K, et al. Lower testosterone levels predict incident stroke and transient ischemic attack in older men. J Clin Endocrinol Metab. 2009;94(7):2353–9. doi:10.1210/jc.2008-2416.PubMedCrossRef

38.

English KM, Mandour O, Steeds RP, Diver MJ, Jones TH, Channer KS. Men with coronary artery disease have lower levels of androgens than men with normal coronary angiograms. Eur Heart J. 2000;21(11):890–4. doi:10.1053/euhj.1999.1873.PubMedCrossRef

39.

Rosano GM, Sheiban I, Massaro R, Pagnotta P, Marazzi G, Vitale C, et al. Low testosterone levels are associated with coronary artery disease in male patients with angina. Int J Impot Res. 2007;19(2):176–82. doi:10.1038/sj.ijir.3901504.PubMedCrossRef

40.

Phillips GB, Castelli WP, Abbott RD, McNamara PM. Association of hyperestrogenemia and coronary heart disease in men in the Framingham cohort. Am J Med. 1983;74(5):863–9.PubMedCrossRef

41.

Wu FC, Tajar A, Pye SR, Silman AJ, Finn JD, O’Neill TW, et al. 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(7):2737–45. doi:10.1210/jc.2007-1972.PubMedCrossRef

42.

Somani B, Khan S, Donat R. Screening for metabolic syndrome and testosterone deficiency in patients with erectile dysfunction: results from the first UK prospective study. BJU Int. 2010;106(5):688–90. doi:10.1111/j.1464-410X.2009.09145.x.PubMedCrossRef

43.

Vikan T, Schirmer H, Njolstad I, Svartberg J. Low testosterone and sex hormone-binding globulin levels and high estradiol levels are independent predictors of type 2 diabetes in men. Eur J Endocrinol / Eur Fed Endocr Soc. 2010;162(4):747–54. doi:10.1530/EJE-09-0943.CrossRef

44.

Mulligan T, Frick MF, Zuraw QC, Stemhagen A, McWhirter C. Prevalence of hypogonadism in males aged at least 45 years: the HIM study. Int J Clin Pract. 2006;60(7):762–9. doi:10.1111/j.1742-1241.2006.00992.x.PubMedCentralPubMedCrossRef

45.

Dhindsa S, Miller MG, McWhirter CL, Mager DE, Ghanim H, Chaudhuri A, et al. Testosterone concentrations in diabetic and nondiabetic obese men. Diabetes Care. 2010;33(6):1186–92. doi:10.2337/dc09-1649.PubMedCentralPubMedCrossRef

46.

Krasnoff JB, Basaria S, Pencina MJ, Jasuja GK, Vasan RS, Ulloor J, 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(6):2790–9. doi:10.1210/jc.2009-2680.PubMedCentralPubMedCrossRef

47.

Carrero JJ, Qureshi AR, Nakashima A, Arver S, Parini P, Lindholm B, et al. Prevalence and clinical implications of testosterone deficiency in men with end-stage renal disease. Nephrol, Dial, Transplant: Off Publ Eur Dial Transplant Assoc-Eur Renal Assoc. 2011;26(1):184–90. doi:10.1093/ndt/gfq397.CrossRef

48.

Torkler S, Wallaschofski H, Baumeister SE, Volzke H, Dorr M, Felix S, et al. Inverse association between total testosterone concentrations, incident hypertension and blood pressure. Aging Male: Off J Int Soc Study Aging Male. 2011;14(3):176–82. doi:10.3109/13685538.2010.529194.CrossRef

49.

Corona G, Monami M, Rastrelli G, Aversa A, Tishova Y, Saad F, et al. Testosterone and metabolic syndrome: a meta-analysis study. J Sex Med. 2011;8(1):272–83. doi:10.1111/j.1743-6109.2010.01991.x.PubMedCrossRef

50.

Kapoor D, Clarke S, Stanworth R, Channer KS, Jones TH. The effect of testosterone replacement therapy on adipocytokines and C-reactive protein in hypogonadal men with type 2 diabetes. Eur J Endocrinol / Eur Fed Endocr Soc. 2007;156(5):595–602. doi:10.1530/EJE-06-0737.CrossRef

51.

Kaplan SA, Johnson-Levonas AO, Lin J, Shah AK, Meehan AG. Elevated high sensitivity C-reactive protein levels in aging men with low testosterone. Aging Male: Off J Int Soc Study Aging Male. 2010;13(2):108–12. doi:10.3109/13685530903440424.CrossRef

52.

Corona G, Rastrelli G, Vignozzi L, Mannucci E, Maggi M. Testosterone, cardiovascular disease and the metabolic syndrome. Best Pract Res Clin Endocrinol Metab. 2011;25(2):337–53. doi:10.1016/j.beem.2010.07.002.PubMedCrossRef

53.

Haring R, Teumer A, Volker U, Dorr M, Nauck M, Biffar R, et al. Mendelian randomization suggests non-causal associations of testosterone with cardiometabolic risk factors and mortality. Andrology. 2013;1(1):17–23. doi:10.1111/j.2047-2927.2012.00002.x.PubMedCrossRef

54.

Saad F. Androgen therapy in men with testosterone deficiency: can testosterone reduce the risk of cardiovascular disease? Diabetes Metab Res Rev. 2012;28 Suppl 2:52–9. doi:10.1002/dmrr.2354.PubMedCrossRef

55.

Raynaud JP. Prostate cancer risk in testosterone-treated men. J Steroid Biochem Mol Biol. 2006;102(1–5):261–6. doi:10.1016/j.jsbmb.2006.09.032.PubMedCrossRef

56.

Buvat J, Montorsi F, Maggi M, Porst H, Kaipia A, Colson MH, 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(1):284–93. doi:10.1111/j.1743-6109.2010.01956.x.PubMedCrossRef

57.

Spitzer M, Basaria S, Travison TG, Davda MN, Paley A, Cohen B, et al. Effect of testosterone replacement on response to sildenafil citrate in men with erectile dysfunction: a parallel, randomized trial. Ann Intern Med. 2012;157(10):681–91. doi:10.7326/0003-4819-157-10-201211200-00004.PubMedCrossRef

58.••

Raynaud JP, Gardette J, Rollet J, Legros JJ. Prostate-specific antigen (PSA) concentrations in hypogonadal men during 6 years of transdermal testosterone treatment. BJU Int. 2013;111(6):880–90. doi:10.1111/j.1464-410X.2012.11514.x. PSA did not change nor did the incidence of PCa increase significantly while on TRT. It has never been shown that TRT leads to enhanced prostate growth.PubMedCrossRef

59.

Khera M, Bhattacharya RK, Blick G, Kushner H, Nguyen D, Miner MM. Changes in prostate specific antigen in hypogonadal men after 12 months of testosterone replacement therapy: support for the prostate saturation theory. J Urol. 2011;186(3):1005–11. doi:10.1016/j.juro.2011.04.065.PubMedCrossRef

60.

Ho CC, Tong SF, Low WY, Ng CJ, Khoo EM, Lee VK, 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):260–5. doi:10.1111/j.1464-410X.2011.10755.x.PubMedCrossRef

61.

Kaufman JM, Miller MG, Garwin JL, Fitzpatrick S, McWhirter C, Brennan JJ. Efficacy and safety study of 1.62% testosterone gel for the treatment of hypogonadal men. J Sex Med. 2011;8(7):2079–89. doi:10.1111/j.1743-6109.2011.02265.x.PubMedCrossRef

62.

Morgentaler A, Traish AM. Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth. Eur Urol. 2009;55(2):310–20. doi:10.1016/j.eururo.2008.09.024.PubMedCrossRef

63.

Marks LS, Mazer NA, Mostaghel E, Hess DL, Dorey FJ, Epstein JI, et al. Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. JAMA. 2006;296(19):2351–61. doi:10.1001/jama.296.19.2351.PubMedCrossRef

64.

Isbarn H, Pinthus JH, Marks LS, Montorsi F, Morales A, Morgentaler A, et al. Testosterone and prostate cancer: revisiting old paradigms. Eur Urol. 2009;56(1):48–56. doi:10.1016/j.eururo.2009.03.088.PubMedCrossRef

65.

Atan A, Tuncel A, Yesil S, Balbay D. Serum testosterone level, testosterone replacement treatment, and prostate cancer. Adv Urol. 2013;2013:275945. doi:10.1155/2013/275945.PubMedCentralPubMedCrossRef

66.

Guay AT, Perez JB, Fitaihi WA, Vereb M. Testosterone treatment in hypogonadal men: prostate-specific antigen level and risk of prostate cancer. Endocr Pract: Off J Am Coll Endocrinol Am Assoc Clin Endocrinol. 2000;6(2):132–8. doi:10.4158/EP.6.2.132.CrossRef

67.

Cooper CS, MacIndoe JH, Perry PJ, Yates WR, Williams RD. The effect of exogenous testosterone on total and free prostate specific antigen levels in healthy young men. J Urol. 1996;156(2 Pt 1):438–41. discussion 41–2.PubMedCrossRef

68.

Gooren LJ. A ten-year safety study of the oral androgen testosterone undecanoate. J Androl. 1994;15(3):212–5.PubMed

69.

Endogenous H, Prostate Cancer Collaborative G, Roddam AW, Allen NE, Appleby P, Key TJ. Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J Natl Cancer Inst. 2008;100(3):170–83. doi:10.1093/jnci/djm323.CrossRef

70.

Shabsigh R, Crawford ED, Nehra A, Slawin KM. Testosterone therapy in hypogonadal men and potential prostate cancer risk: a systematic review. Int J Impot Res. 2009;21(1):9–23. doi:10.1038/ijir.2008.31.PubMedCrossRef

71.

Calof OM, Singh AB, Lee ML, Kenny AM, Urban RJ, Tenover JL, 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 Med Sci. 2005;60(11):1451–7.CrossRef

72.

Morgentaler A, Lipshultz LI, Bennett R, Sweeney M, Avila Jr D, Khera M. Testosterone therapy in men with untreated prostate cancer. J Urol. 2011;185(4):1256–60. doi:10.1016/j.juro.2010.11.084.PubMedCrossRef

73.

Kaufman JM, Graydon RJ. Androgen replacement after curative radical prostatectomy for prostate cancer in hypogonadal men. J Urol. 2004;172(3):920–2. doi:10.1097/01.ju.0000136269.10161.32.PubMedCrossRef

74.

Khera M, Grober ED, Najari B, Colen JS, Mohamed O, Lamb DJ, et al. Testosterone replacement therapy following radical prostatectomy. J Sex Med. 2009;6(4):1165–70. doi:10.1111/j.1743-6109.2009.01161.x.PubMedCrossRef

75.

Pastuszak AW, Pearlman AM, Lai WS, Godoy G, Sathyamoorthy K, Liu JS, et al. Testosterone replacement therapy in patients with prostate cancer after radical prostatectomy. J Urol. 2013;190(2):639–44. doi:10.1016/j.juro.2013.02.002.PubMedCrossRef

76.

Sarosdy MF. Testosterone replacement for hypogonadism after treatment of early prostate cancer with brachytherapy. Cancer. 2007;109(3):536–41. doi:10.1002/cncr.22438.PubMedCrossRef

77.

Khera M. Androgens and erectile function: a case for early androgen use in postprostatectomy hypogonadal men. J Sex Med. 2009;6 Suppl 3:234–8. doi:10.1111/j.1743-6109.2008.01159.x.PubMedCrossRef

78.

Dohle GR, Arver S, Bettocchi C, Kliesch S, Punab M, de Ronde W. Guidelines on male hypogonadism. European Association of Urology 2014. http://www.uroweb.org/guidelines/online-guidelines/.

79.•

Food and Drug Administration. Joint meeting of the Bone, Reproductive and Urologic Drug Advisory Committee and the Drug Safety and Risk Management Advisory Committee. 2014. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ReproductiveHealthDrugsAdvisoryCommittee/UCM418144.pdf. TRT’s effect on CVD safety is not well understood and warrants further investigation.

80.

Corona G, Monami M, Rastrelli G, Aversa A, Sforza A, Lenzi A, et al. Type 2 diabetes mellitus and testosterone: a meta-analysis study. Int J Androl. 2011;34(6 Pt 1):528–40. doi:10.1111/j.1365-2605.2010.01117.x.PubMedCrossRef

81.

Haffner SM, Karhapaa P, Mykkanen L, Laakso M. Insulin resistance, body fat distribution, and sex hormones in men. Diabetes. 1994;43(2):212–9.PubMedCrossRef

82.

Haffner SM, Mykkanen L, Valdez RA, Katz MS. Relationship of sex hormones to lipids and lipoproteins in nondiabetic men. J Clin Endocrinol Metab. 1993;77(6):1610–5. doi:10.1210/jcem.77.6.8263149.PubMed

83.

Maggio M, Basaria S, Ble A, Lauretani F, Bandinelli S, Ceda GP, et al. Correlation between testosterone and the inflammatory marker soluble interleukin-6 receptor in older men. J Clin Endocrinol Metab. 2006;91(1):345–7. doi:10.1210/jc.2005-1097.PubMedCrossRef

84.

Malkin CJ, Pugh PJ, Morris PD, Kerry KE, Jones RD, Jones TH, et al. Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life. Heart. 2004;90(8):871–6. doi:10.1136/hrt.2003.021121.PubMedCentralPubMedCrossRef

85.

Malkin CJ, Pugh PJ, Jones RD, Kapoor D, Channer KS, Jones TH. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab. 2004;89(7):3313–8. doi:10.1210/jc.2003-031069.PubMedCrossRef

86.

Hall J, Jones RD, Jones TH, Channer KS, Peers C. Selective inhibition of L-type Ca2+ channels in A7r5 cells by physiological levels of testosterone. Endocrinology. 2006;147(6):2675–80. doi:10.1210/en.2005-1243.PubMedCrossRef

87.

Corona G, Rastrelli G, Morelli A, Vignozzi L, Mannucci E, Maggi M. Hypogonadism and metabolic syndrome. J Endocrinol Investig. 2011;34(7):557–67. doi:10.3275/7806.

88.•

Jones TH, Arver S, Behre HM, Buvat J, Meuleman E, Moncada I, et al. Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 study). Diabetes Care. 2011;34(4):828–37. doi:10.2337/dc10-1233. TRT improved the risk factors for cardiovascular health including lipid profiles, insulin resistance, lipoprotein A levels, as well as improving sexual health.PubMedCentralPubMedCrossRef

89.

He J, Bhasin S, Binder EF, Yarasheski KE, Castaneda-Sceppa C, Schroeder ET, et al. Cardiometabolic risks during anabolic hormone supplementation in older men. Obesity. 2013;21(5):968–75. doi:10.1002/oby.20081.PubMedCentralPubMedCrossRef

90.

Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, et al. Adverse events associated with testosterone administration. N Engl J Med. 2010;363(2):109–22. doi:10.1056/NEJMoa1000485.PubMedCentralPubMedCrossRef

91.

Vigen R, O’Donnell CI, Baron AE, Grunwald GK, Maddox TM, Bradley SM, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310(17):1829–36. doi:10.1001/jama.2013.280386.PubMedCrossRef

92.

Finkle WD, Greenland S, Ridgeway GK, Adams JL, Frasco MA, Cook MB, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One. 2014;9(1):e85805. doi:10.1371/journal.pone.0085805.PubMedCentralPubMedCrossRef

93.

NCT01377103 trial. https://clinicaltrials.gov/ct2/show/NCT01377103?term=NCT01377103&rank=1.

94.

Isidori AM, Giannetta E, Greco EA, Gianfrilli D, Bonifacio V, Isidori A, et al. Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clin Endocrinol. 2005;63(3):280–93. doi:10.1111/j.1365-2265.2005.02339.x.CrossRef

95.

Aversa A, Bruzziches R, Francomano D, Greco EA, Fornari R, Di Luigi L, 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: Off J Int Soc Study Aging Male. 2012;15(2):96–102. doi:10.3109/13685538.2011.631230.CrossRef

96.

Spitzer M, Huang G, Basaria S, Travison TG, Bhasin S. Risks and benefits of testosterone therapy in older men. Nat Rev Endocrinol. 2013;9(7):414–24. doi:10.1038/nrendo.2013.73.PubMedCrossRef

97.

Sinha-Hikim I, Artaza J, Woodhouse L, Gonzalez-Cadavid N, Singh AB, Lee MI, et al. Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy. Am J Physiol Endocrinol Metab. 2002;283(1):E154–64. doi:10.1152/ajpendo.00502.2001.PubMedCrossRef

98.

Sinha-Hikim I, Cornford M, Gaytan H, Lee ML, Bhasin S. Effects of testosterone supplementation on skeletal muscle fiber hypertrophy and satellite cells in community-dwelling older men. J Clin Endocrinol Metab. 2006;91(8):3024–33. doi:10.1210/jc.2006-0357.PubMedCrossRef

99.

Sinha-Hikim I, Roth SM, Lee MI, Bhasin S. Testosterone-induced muscle hypertrophy is associated with an increase in satellite cell number in healthy, young men. Am J Physiol Endocrinol Metab. 2003;285(1):E197–205. doi:10.1152/ajpendo.00370.2002.PubMedCrossRef

100.

Zarrouf FA, Artz S, Griffith J, Sirbu C, Kommor M. Testosterone and depression: systematic review and meta-analysis. J Psychiatr Pract. 2009;15(4):289–305. doi:10.1097/01.pra.0000358315.88931.fc.PubMedCrossRef

101.

Shores MM, Kivlahan DR, Sadak TI, Li EJ, Matsumoto AM. A randomized, double-blind, placebo-controlled study of testosterone treatment in hypogonadal older men with subthreshold depression (dysthymia or minor depression). J Clin Psychiatry. 2009;70(7):1009–16.PubMedCrossRef

At a glance: The STEP trials

Springer Medicine

Update on Testosterone Replacement Therapy in Hypogonadal Men

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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