Testosterone – Intramuscular injection

Amory et al, 2004 26 Amory J.K.

Watts N.B.

Easley K.A.

et al. Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone. 36 mo TE 200 mg every 2 wk Testosterone 24 71 (4) 9.9 (1.6) NIH funded

Placebo 24 71 (5) 10.5 (1.7)

Aversa et al, 2010 27 Aversa A.

Bruzziches R.

Francomano D.

et al. Effects of testosterone undecanoate on cardiovascular risk factors and atherosclerosis in middle-aged men with late-onset hypogonadism and metabolic syndrome: results from a 24-month, randomized, double-blind, placebo-controlled study. 24 mo TU 1000 mg Testosterone 40 58 (10) 8.33 (2.4) Not mentioned

Placebo 10 57 (8) 9 (1.7)

Borst et al, 2014 28 Borst S.E.

Yarrow J.F.

Conover C.F.

et al. Musculoskeletal and prostate effects of combined testosterone and finasteride administration in older hypogonadal men: a randomized, controlled trial. 12 mo TE 125 mg every week Testosterone 14 69.2 (8) 245 (73) ng/dL External grant and pharmaceutical company

Testosterone + F 17 64.2 (4.8) 242 (147) ng/dL

Placebo 16 70.8 (9.7) 264 (92) ng/dL

Placebo + F 13 69.5 (9.2) 240 (110) ng/dL

Crawford et al, 2003 23 Crawford B.A.

Liu P.Y.

Kean M.T.

Bleasel J.F.

Handelsman D.J. Randomized placebo-controlled trial of androgen effects on muscle and bone in men requiring long-term systemic glucocorticoid treatment. 12 mo ME 200 mg every 2 wk Testosterone 18 58.7 (4.9) 13.8 (0.4) Partly by pharmaceutical company

Placebo 16 59.9 (4) 15.7 (0.5)

Gianatti et al, 2014 29 Gianatti E.J.

Dupuis P.

Hoermann R.

et al. Effect of testosterone treatment on glucose metabolism in men with type 2 diabetes: a randomized controlled trial. 40 wk TU 1000 mg every 12 wk Median (IQR) Median (IQR) Pharmaceutical company

Testosterone 45 62 (58-68) 8.7 (7.1-11.1)

Placebo 43 62 (57-67) 8.5 (7.2-11)

Hackett et al, 2014 30 Hackett G.

Cole N.

Bhartia M.

et al. The response to testosterone undecanoate in men with type 2 diabetes is dependent on achieving threshold serum levels (the BLAST study). 30 wk TU 1000 mg every 12 wk Testosterone 97 61.2 (10.5) 9.2 (3.1) Self funded + pharmaceutical company (drugs)

Placebo 102 62 (9.3) 8.9 (3.8)

Hall et al, 1996 31 Hall G.M.

Larbre J.P.

Spector T.D.

Perry L.A.

Da Silva J.A. A randomized trial of testosterone therapy in males with rheumatoid arthritis. 9 mo TE 250 mg for 1 month, then 250 mg every 2 wk Testosterone 17 60.8 (9.7) † † Overall, including both testosterone and control arms. 15.9 (6.5) † † Overall, including both testosterone and control arms. Partly funded by pharmaceutical company

Placebo 18

Hoyos et al, 2012 32 Hoyos C.M.

Yee B.J.

Phillips C.L.

Machan E.A.

Grunstein R.R.

Liu P.Y. Body compositional and cardiometabolic effects of testosterone therapy in obese men with severe obstructive sleep apnoea: a randomised placebo-controlled trial. 18 wk TU 1000 mg /12 wk Testosterone 33 48 (1.6) 13.2 (5.3) External grant and pharmaceutical company

Placebo 34 49 (1.6) 13.4 (5.1)

Kalinchenko et al, 2010 33 Kalinchenko S.Y.

Tishova Y.A.

Mskhalaya G.J.

Gooren L.J.

Giltay E.J.

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. 30 wk TU 1000 mg/12 wk Testosterone 113 51.6 6.7 Pharmaceutical company

Placebo 71 52.8 7.5

Konaka et al, 2015 62 Konaka H.

Sugimoto K.

Orikasa H.

et al. Effects of long term androgen replacement therapy on the physical and mental statuses of aging males with late-onset hypogonadism: a multicenter randomized controlled trial in Japan (EARTH Study). 52 wk TE 250 mg/4 wk Testosterone 169 65.6 (9) N/A External grant

Placebo 165 67.6 (9.4)

Seidman et al, 2001 34 Seidman S.N.

Spatz E.

Rizzo C.

Roose S.P. Testosterone replacement therapy for hypogonadal men with major depressive disorder: a randomized, placebo-controlled clinical trial. 6 wk TE 200 mg/wk Testosterone 15 53.6 269.5 ng/dL External grant (partly) + author consultant for pharmaceutical company

Placebo 17 49.7 263.5 ng/dL

Sih et al, 1997 35 Sih R.

Morley J.E.

Kaiser F.E.

Perry H.M.

Patrick P.

Ross C. Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. 52 wk TC 200 mg/2 wk Testosterone 17 65 (7) 10.2 (0.9) Not mentioned

Placebo 15 68 (6) 8.1 (0.7)

Stout et al, 2012 36 Stout M.

Tew G.A.

Doll H.

et al. Testosterone therapy during exercise rehabilitation in male patients with chronic heart failure who have low testosterone status: a double-blind randomized controlled feasibility study. 12 wk ME 100 mg/2 wk Testosterone 20 68.3 (5.3) 10.4 (2.7) External grant

Placebo 20 65.9 (8.8) 11.2 (2.6)

Sullivan et al, 2005 37 Sullivan D.H.

Roberson P.K.

Johnson L.E.

et al. Effects of muscle strength training and testosterone in frail elderly males. 12 wk TE 50 mg week 1, weeks 2-12 100 mg Testosterone 37 78.1 (6.3) 293.5 (141.2) ng/dL External grant

Placebo 34 78.3 (6.6) 331.9 (173.2) ng/dL

Svartberg et al, 2004 38 Svartberg J.

Aasebo U.

Hjalmarsen A.

Sundsfjord J.

Jorde R. Testosterone treatment improves body composition and sexual function in men with COPD, in a 6-month randomized controlled trial. 26 wk TE 250 mg/month Testosterone 15 64.5 (6.5) 21.6 (5.7) External grant

Placebo 14 67.5 (5.8) 20.5 (5.7)

Svartberg et al, 2008 39 Svartberg J.

Agledahl I.

Figenschau Y.

Sildnes T.

Waterloo K.

Jorde R. Testosterone treatment in elderly men with subnormal testosterone levels improves body composition and BMD in the hip. 52 wk TU 1000 mg/12 wk Testosterone 19 69 (5) 8.4 (1.7) External grant + pharmaceutical company (drugs)

Placebo 19 69 (5) 8.2 (2.1)

Tong et al, 2012 40 Tong S.F.

Ng C.J.

Lee B.C.

et al. Effect of long-acting testosterone undecanoate treatment on quality of life in men with testosterone deficiency syndrome: a double blind randomized controlled trial. 48 wk TU 1000 mg/12 wk Testosterone 60 53.4 (7.5) 8.9 (2.0) Pharmaceutical company

Placebo 60 53.0 (8.2) 9.1 (1.8)

Testosterone – transdermal patch or topical gel

English et al, 2000 42 English K.M.

Steeds R.P.

Jones T.H.

Diver M.J.

Channer K.S. Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: a randomized, double-blind, placebo-controlled study. 12 wk T patch 5 mg Testosterone 25 62 (2) 13.55 (0.78) Not mentioned but drug supplied by pharmaceutical company (drugs)

Placebo 25 62 (2) 12.38 (0.72)

Malkin et al, 2006 46 Malkin C.J.

Pugh P.J.

West J.N.

van Beek V.J.

Jones T.H.

Channer K.S. Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial. 12 mo T patch 5 mg Testosterone 37 63.1 (10.7) 13.9 (5.3) External grant with pharmaceutical company (drugs)

Placebo 39 64.9 (9.3) 12.1 (5.4)

Nair et al, 2006 47 Nair K.S.

Rizza R.A.

O'Brien P.

et al. DHEA in elderly women and DHEA or testosterone in elderly men. 104 wk T patch 5 mg Testosterone 30 66.2 357.3 ng/dL External grant

Placebo 32 67.1 398.4 ng/dL

Raynaud et al, 200848 ∗ ∗ Study did not have a placebo control arm. 52 wk T patch 4.8 mg Testosterone 1 188 42 (12.7) 132 (92) ng/dL Pharmaceutical company

TE 250 mg Testosterone 2 36 40.7 (10.5) 148 (95) ng/dL

Snyder et al, 2001 49 Snyder P.J.

Peachey H.

Berlin J.A.

et al. Effect of transdermal testosterone treatment on serum lipid and apolipoprotein levels in men more than 65 years of age. 156 wk T patch 4-6 mg Testosterone 54 73 (5.9) 367 (79) ng/dL External grant with pharmaceutical company (drug)

Placebo 54 73.1 (5.8) –

Basaria et al, 2010 7 Basaria S.

Coviello A.D.

Travison T.G.

et al. Adverse events associated with testosterone administration. 26 wk T gel 100 mg Testosterone 106 74 (6) 250 (57) ng/dL External grant

Placebo 103 74 (5) 236 (66) ng/dL

Basaria et al, 2015 (JAMA) 57 Basaria S.

Harman M.

Travison T.G.

et al. Effects of testosterone administration for 3 years on subclinical atherosclerosis progression in older men with low or low-normal testosterone levels: a randomized clinical trial. 36 mo T gel 75 gm Testosterone 156 66.9 (5) 307.2 (64.3) ng/dL External grant with pharmaceutical company (drugs)

Placebo 152 68.3 (5.3) 307.4 (67.4) ng/dL

Basaria et al, 2015 (Pain) 58 Basaria S.

Travison T.G.

Alford D.

et al. Effects of testosterone replacement in men with opioid induced androgen deficiency. 14 wk T gel 50 mg Median [IQR] External grant

Testosterone 43 48 (9) 243 (183-286)

Placebo 41 50 (6) 251 (195-313)

Behre et al, 2012 26 wk T gel 50 mg Testosterone 183 61.9 (6.6) 10.4 (2.6) Pharmaceutical company

Placebo 179 62.1 (6.3) 10.6 (2.6)

Frederiksen et al, 2012 59 Frederiksen L.

Hojlund K.

Hougaard D.M.

et al. Testosterone therapy decreases subcutaneous fat and adiponectin in aging men. 6 mo T gel 50 mg Median [IQR] Median [IQR] Drugs sponsored by pharmaceutical company

Testosterone 23 68 (62-72) 12.2 (9.5-15.7)

Placebo 23 67 (65-69) 18.7 (14.9-25.4)

Hildreth et al, 2013 43 Hildreth K.L.

Barry D.W.

Moreau K.L.

et al. Effects of testosterone and progressive resistance exercise in healthy, highly functioning older men with low-normal testosterone levels. 52 wk T gel 2.5 g Testosterone 111 66.5 (5.8) 297.7 (43.4) † † Overall, including both testosterone and control arms. External grant

Placebo 56 66.5 (5.2)

Jones et al, 2011 44 Jones T.H.

Arver S.

Behre H.M.

et al. Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 study). 52 wk T gel 2% Testosterone 108 59.9 (9.1) 9.2 (2.6) Pharmaceutical company

Placebo 112 59.9 (9.4) 9.5 (3.3)

Kaufman et al, 2011 61 Kaufman J.M.

Miller M.G.

Fitzpatrick S.

McWhirter C.

Brennan J.J. One-year efficacy and safety study of a 1.62% testosterone gel in hypogonadal men: results of a 182-day open-label extension of a 6-month double-blind study. 26 wk T gel 25 mg Testosterone 234 53.6 (9.5) 9.8 Pharmaceutical company

Placebo 40 55.5 (10.3) 10.2

Kenny et al, 2010 45 Kenny A.M.

Kleppinger A.

Annis K.

et al. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels, low bone mass, and physical frailty. 24 mo T gel 50 mg Testosterone 69 77.9 (7.3) 380.4 (179.5) ng/dL External grant with pharmaceutical company (drugs)

Placebo 62 76.3 (8) 417.8 (192.5) ng/dL

Srinivas Shankar et al, 2010 50 Srinivas-Shankar U.

Roberts S.A.

Connolly M.J.

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. 6 mo T gel 50 mg Testosterone 138 73.7 (5.7) 11 (3.2) Pharmaceutical company

Placebo 136 73.9 (6.4) 10.9 (3.1)

Steidle et al, 2003 51 Steidle C.

Schwartz S.

Jacoby K.

et al. AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function. 13 wk T gel 50 mg Testosterone 1 99 58.1 (9.7) 8.1 (2.0) Pharmaceutical company

T gel 100 mg Testosterone 2 106 56.8 (10.6) 8.1 (2.2)

T patch 5 mg Testosterone 3 102 60.5 (9.7) 8.3 (2.4)

Placebo 99 56.8 (10.8) 7.9 (2.8)

Paduch et al, 2015 60 Paduch D.A.

Polzer P.K.

Ni X.

Basaria S. Testosterone replacement in androgen-deficient men with ejaculatory dysfunction: a randomized controlled trial. 16 wk T solution 2% Testosterone 36 48.4 (9.8) 214 (56) ng/dL Pharmaceutical company

Placebo 40 52.7 (9.3) 223 (53) ng/dL

Testosterone – Oral

Aversa et al, 2010 52 Aversa A.

Bruzziches R.

Francomano D.

Spera G.

Lenzi A. Efficacy and safety of two different testosterone undecanoate formulations in hypogonadal men with metabolic syndrome. 26 wk T tablet 160 mg Testosterone 1 10 57 (8) – Not mentioned

TU 1000 mg Testosterone 2 32 58 (10)

Placebo Placebo 10 55 (5)

Copenhagen group, 1986 53 Testosterone treatment of men with alcoholic cirrhosis: a double blind study. Copenhagen Study Group for Liver Diseases. 8 to 62 mo T tablet 600 mg Testosterone 134 53 – External grant

Placebo 87 53 –

Cornoldi et al, 2010 54 Cornoldi A.

Caminiti G.

Marazzi G.

et al. Effects of chronic testosterone administration on myocardial ischemia, lipid metabolism and insulin resistance in elderly male diabetic patients with coronary artery disease. 12 wk T tablet 120 mg Testosterone 43 74.5 (8) – Not mentioned

Placebo 44 75.6 (11) –

Emmelot-Vonk et al, 2008 26 wk T tablet 160 mg Testosterone 120 67.1 (5) 11 (1.9) External grant with pharmaceutical company (drugs)

Placebo 117 67.4 (4.9) 10.4 (1.9)

Legros et al, 2009 56 Legros J.J.

Meuleman E.J.

Elbers J.M.

et al. Oral testosterone replacement in symptomatic late-onset hypogonadism: effects on rating scales and general safety in a randomized, placebo-controlled study. 52 wk T tablet 80 mg Testosterone 1 78 59.5 (6.5) 12.8 (4.2) † † Overall, including both testosterone and control arms. Pharmaceutical company

T tablet 160 mg Testosterone 2 82 58.4 (5.7)

T tablet 240 mg Testosterone 3 77 58.6 (5.7)