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

Journal of Sexual Medicine

Volumn 10, Issue 6, 2013, Pages 1612-1627

  Hackett, Geoffrey ^a   Cole, Nigel ^b   Bhartia, Mithun ^a   Kennedy, David ^a   Raju, Jessie ^a   Wilkinson, Peter ^c  

^a UNIVERSITY HOSPITALS BIRMINGHAM NHS FOUNDATION TRUST   (United Kingdom)

^b Cloisters Practice   (United Kingdom)

^c Wilkinson Associates   (United Kingdom)

Author keywords

AMS Ageing Male Symptom Score; HADS Hospital Anxiety and Depression Scale; IIEF International Index of Erectile Function; LOH late onset hypogonadism; NICE National Institute for Health and Clinical Excellence; QoF quality outcome framework; T2D type 2 diabetes; TDS testosterone deficiency syndrome; TRT testosterone replacement therapy; TU Testosterone Undecanoate

Indexed keywords

ANGIOTENSIN RECEPTOR ANTAGONIST; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CALCIUM CHANNEL BLOCKING AGENT; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; EXENDIN 4; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INSULIN; NITRATE; ORAL ANTIDIABETIC AGENT; PHOSPHODIESTERASE V INHIBITOR; PLACEBO; PROSTATE SPECIFIC ANTIGEN; TESTOSTERONE; TESTOSTERONE UNDECANOATE;

ADULT; AGED; ARTICLE; COHORT ANALYSIS; CONTROLLED STUDY; DEPRESSION; DIABETIC PATIENT; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG WITHDRAWAL; ERECTILE DYSFUNCTION; GENERAL PRACTICE; HEMATOCRIT; HORMONE SUBSTITUTION; HOSPITAL ANXIETY AND DEPRESSION SCALE; HUMAN; HYPOGONADISM; INJECTION SITE PAIN; INTERNATIONAL INDEX OF ERECTILE FUNCTION; MAJOR CLINICAL STUDY; MALE; MALE SEXUAL DYSFUNCTION; MOOD; MULTICENTER STUDY; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; ORGASM; PENIS ERECTION; PRIMARY MEDICAL CARE; PRIORITY JOURNAL; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; SELF REPORT; SEXUAL INTERCOURSE; SEXUAL SATISFACTION; TESTOSTERONE BLOOD LEVEL; UNSPECIFIED SIDE EFFECT;

EID: 84878704250     PISSN: 17436095     EISSN: 17436109     Source Type: Journal    
DOI: 10.1111/jsm.12146     Document Type: Article

References (53)

1. Wu FW, Tajar A, Beynon JM, Pye SR, Silman AJ, Finn JD, O'Neill TW; for the EMAS Group. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med 2010;363:123-135.
2. Isidori AM, Giannetta E, Gianfrilli D, Greco EA, Bonifacio V, Aversa A. Effects of testosterone on sexual function in men: Results of a meta-analysis. Clin Endocrinol (Oxf) 2005;63:381-394.
3. Bassin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM. Testosterone therapy in adult men with androgen deficiency syndrome: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2006;91:1995-2010.
4. Hackett G, Cole N, Deshpande A, Popple M, Kennedy D, Wilkinson P. Biochemical hypodonadism and type 2 diabetes in primary care. Br J Diabetes Vasc Dis 2009;9:226-231.
5. Bacon CG, Hu FG, Giavannucci E, Glasser D, Mittelmann M. Type and duration of diabetes with erectile dysfunction in a large cohort of men. Diabetes Care 2002;25:1458-1463.
6. Dhindsa S, Prabhakar S, Sethi M, Bandyopadhyay A, Chaudhuri A, Dandona P. Frequent occurrence of hypogonadotrophic hypogonadism in type 2 diabetes. J Clin Endocrinol Metab 2004;89:5462-5468.
7. de Groot M, Anderson R, Freedland K, Clourse RE, Lustman PJ. Association of depression and diabetes complications: a meta-analysis. Psychosom Med 2001;63:619-630.
8. Hintikka J, Niskanen L, Koivumaa-Honkanen H, Tolmunen T, Honkalampi K, Lehto SM, Viinamäki H. Hypogonadism, decreased sexual desire, and long-term depression in middle-aged men. J Sex Med 2009;6:2049-2057.
9. Rizvi SJ, Kennedy SH, Ravindran LN, Giacobbe P, Eisfeld BS, Mancini D, McIntyre RS. The relationship between testosterone and sexual function in depressed and healthy men. J Sex Med 2010;7:816-825.
10. Shores MM, Sloan KL, Matsumoto AM, Moceri VM, Felker B, Kivlahan DR. Increased incidence of diagnosed depressive illness in hypogonadal older men. Arch Gen Psychiatry 2004;61:162-167.
11. Kapoor 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.
12. Giltay EJ, Tishova YA, Mskhalaya GJ, Gooren LJ, Saad F, Kalinchenko SY. Effects of testosterone supplementation on depressive symptoms and sexual dysfunction in hypogonadal men with the metabolic syndrome. J Sex Med 2010;7:2572-2582.
13. Pope HG, Amiaz R, Brennan BP, Orr G, Weiser M, Kelly JF, Kanayama G, Siegel A, Hudson JI, Seidman SN. Parallel group placebo controlled trial of testosterone gel in major men with depressive order displaying incomplete response to standard anti-depressant treatment. J Clin Psychopharmacol 2010;30:126-134.
14. Emmelot-Vonk MH, Verhaar HJ, Nakhai-Pour HR, Grobbee DE, van der Schow YT. Effects of testosterone supplementation on sexual function in ageing men: A 6-month randomized controlled trial. Int J Impot Res 2009;21:129-138.
15. Marburger M, Wilson TH, Ritmaster RS. Low serum testosterone levels are poor predictors of sexual function. BJU Int 2011;108:256-262.
16. Saad F, Aversa A, Isidori A, Zafalon L, Zitzmann M, Gooren L. Onset of effects of testosterone replacement and time span until maximal effect is achieved. Eur J Endocrinol 2011;165:675-685.
17. Khaw KT, Dowsett M, Folkerd E, Bingham S, Wareham N, Luben R, Welch A, Day N. 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.
18. Oh JY, Barrett-Connor E, Wedick NM, Wingard DL, Rancho Bernardo Study. 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.
19. Shores MM, Matsumoto AM, Sloan KL, Kivlahan DR. Low serum testosterone and mortality in male veterans. Arch Intern Med 2006;166:1660-1665.
20. Anderson RJ, Freedman KE, Clouse RE, Lustman PJ. The prevalence of co-morbid depression in adults with diabetes: A meta-analysis. Diabetes Care 2001;724:1069-1078.
21. Diabetes in the UK 2010. Available at: http://www.diabetes.org.uk/Documents/Reports/Diabetes_in_the_UK_2010.pdf (accessed March 18, 2013).
22. National Health Service. Quality outcome framework in diabetes 2012/13. Available at: http://www.nhsemployers.org/Aboutus/Publications/Documents/ (accessed June 17, 2012).
23. Home P, Mant J, Diaz J, Turner C; on behalf of the Guideline Development Group. Management of type 2 diabetes: Summary of updated NICE guidance. BMJ 2008;336:1306-1308.
24. Hackett G, Kell P, Ralph D, etal. British Society for Sexual Medicine guidelines on the management of erectile dysfunction. J Sex Med 2008;5:1841-1846.
25. Vickers MA, Satyanarayana R. Phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction in patients with diabetes mellitus. Int J Impot Res 2002;14:466-471. Low response in T2D.
26. Jones TH, Arver S, Behre H, Buvat J, Meuleman E, Moncada I, Morales AM, Volterrani M, Yellowlees A, Howell JD, Channer KS. A placebo controlled study on the effects of transdermal testosterone gel in hypogonadal men with type II diabetes or metabolic syndrome in diabetic control and insulin sensitivity: The TIMES 2 study. Diabetes Care 2011;34:828-837.
27. Shabsigh R, Kaufman JM, Steidle C, Padma-Nathan H. Randomized study of testosterone gel as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone. J Urol 2004;172:658-663.
28. Wang C, Nieschlag E, Swerdloff RS, Behre H, Hellstrom WJ, Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morales A, Morley JE, Schulman C, Thompson IM, Weidner W, Wu FC. Investigation, treatment, and monitoring of late-onset hypogonadism in males; ISA, ISSAM, EAU, EAA, ASA Recommendation. Eur Urol 2009;55:21-130.
29. Schubert M, Minnemann T, Hübler D, Rouskova D, Christoph A, Oettel M, Ernst M, Mellinger U, Krone W, Jockenhövel F. Intramuscular testosterone undecanoate: Pharmacokinetic aspects of a novel testosterone formulation during long term treatment for men with hypogonadism. J Clin Endocrinol Metab 2004;89:5429-5434.
30. Vermeulen 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.
31. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983;67:361-370.
32. Heinemann LAJ, Zimmermann T, Vermeulen A, Thiele C, Hummel W. A new 'Aging male's symptoms' (AMS) rating scale. Aging Male 1999;2:105-114.
33. Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A. The International Index of Erectile Function (IIEF): A multidimensional scale for assessment of erectile dysfunction. Urology 1997;49:822-830.
34. Khera M, Bhattacharya RK, Blick G, Kushner H, Nguyen D, Miner MM. Improved sexual function with testosterone replacement therapy in hypogonadal men: Real-world data from the Testim Registry in the United States (TRiUS). J Sex Med 2011;8:3204-3213.
35. Corona G, Rastrelli G, Forti G, Maggi M. Update in testosterone therapy for men. J Sex Med 2011;8:639-654.
36. Price DW, Yong M, Rubin R, Perreault L, Bray G, Marrero D, Knowler WC, Barrett-Connor E, Lacoursiere DY; Diabetes Prevention Program Research Group. Depression as a predictor of weight regain amongst weight losers in the Diabetes Prevention Programme. Diabetes Care 2013;36:216-221.
37. Zitzmann M, Mattern A, Hanisch J, Looren L, Jones H, Maggi M. IPASS, a study on the tolerability and effectiveness of injectable testosterone undecanoate for the treatment of male hypogonadism in a worldwide sample of 1, 438 men. J Sex Med 2012;10:579-588.
38. Yassin AA, Saad F, Traish A. Testosterone undecanoate restores erectile function in a subset of patients with venous leakage: A series of case reports. J Sex Med 2006;3:727-735.
39. Eardley I. Optimising response to PDE5 inhibitors: Converting non-responders to responders. Eur Urol 2006;50:31-33.
40. Spitzer M, Basaria S, Travison TG, Davda MN, Paley A, Cohen B, Mazer NA, Knapp PE, Hanka S, Lakshman KM, Ulloor J, Zhang A, Orwoll K, Eder R, Collins L, Mohammed N, Rosen RC, DeRogatis L, Bhasin S. Effect of testosterone replacement on response to sildenafil citrate in men with erectile dysfunction. Ann Intern Med 2012;157:681-691.
41. Dinan TG. Inflammatory markers in depression. Curr Opin Psychiatry 2009;22:32-36.
42. Papelbaum M, Moreira R, Coutinho W, Kupfer R, Zagury L, Freitas S, Appolinário JC. Depression, glycemic control and type 2 diabetes. Diabetol Metab Syndr 2011;3:26-30.
43. Cienchauski P, Katon W, Rossi M. Depression and diabetes, impact of depressive symptoms on treatment adherence, function and costs. Arch Intern Med 2000;160:3278-3285.
44. Shabsigh R, Crawford ED, Nehra A, Slawin KM. Testosterone therapy in hypogonadal men and prostate cancer risk: A systemic review. Int J Impot Res 2009;21:9-23.
45. Calof OM, Singh AB, Lee ML, Kenny AM, Urban RJ, Tenover JL, Bhasin S. Adverse events associated with testosterone replacement in middle aged and older men; A meta-analysis of randomised placebo controlled trials. J Gerontol 2005;60:1451-1457.
46. Leibowitz RL, Dorff TB, Tucker S, Symanowski J, Vogelzang NJ. Testosterone replacement in prostate cancer survivors with hypogonadal symptoms. BJU Int 2010;105:1397-1401.
47. Marks LS, Mazer NA, Mostaghel E, Hess DL, Dorey FJ, Epstein JL. Effect of testosterone replacement therapy on prostate tissue in men with late onset hypogonadism; a randomised controlled trial. JAMA 2009;296:2351-2361.
48. Shegehara K, Sugimoto K, Konaka H, Ijimana M, Fukushima M, Maeda Y, Mizokami A, Koh E, Origasa H, Iwamoto T, Namiki M. Androgen replacement therapy contributes to improving lower urinary tract symptoms in patients with hypogonadism and benign prostatic hypertrophy; a randomised controlled study. Aging Male 2011;14:53-58.
49. Pechersky AV, Mazurov V, Semiglazov F, Karpischenco AL, etal. Androgen administration in middle aged and ageing men; effects of oral testosterone undecanoate on dihydrotestosterone, oestradiol and prostate volume. Int J Androl 2002;25:119-125.
50. Parsons JK. Benign prostatic hypertrophy and lower urinary tract symptoms, epidemiology and risk factors. Curr Bladder Dysfunct Rep 2010;5:212-218.
51. Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM. Adverse events associated with testosterone administration. N Engl J Med 2012;363:109-122.
52. Huhtaniemi IT, Tajar A, Lee DM, O'Neill TW, Finn JD, Bartfai G, Boonen S, Casanueva FF, Giwercman A, Han TS, Kula K, Labrie F, Lean ME, Pendleton N, Punab M, Silman AJ, Vanderschueren D, Forti G, Wu FC; EMAS Group. Comparison of serum testosterone and oestradiol measurements in 3, 174 European men using platform immunoassay and mass spectrometry; relevance for the diagnostics in aging men. Eur J Endocrinol 2012;166:983-991.
53. Kalinchenko S, Tishova Y, Mskhalaya G, Gooren L, Giltay E, Saad F. 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.