Table 1.
Characteristics of placebo-controlled randomized clinical trials of testosterone replacement therapy (TRT) reporting CV events
| Author/Year | Mode | Dose | Study duration | Age | Subjects in TRT group | Subjects in placebo group | Serum T at entry | Health status |
|---|---|---|---|---|---|---|---|---|
| Amory 2004 [32] | i.m. | 100 mg TE/week | 36 months | 71 ± 4 (SD) | 24 | 24 | 302 ± 48 (SD) ng/dL | hypogonadal |
| Aversa 2010 [33] | i.m. | 1,000 mg TU/12 week | 24 months | 58 ± 10 (SD) | 40 | 10 | 259 ± 48 (SD) ng/dL | hypogonadal |
| Borst 2014 [34] | i.m. | 125 mg TE/week | 12 months | 69.2 ± 8.0 (SD) | 31 | 29 | 264 ± 92 (SD) ng/dL | hypogonadal |
| Caminiti 2009 [35] | i.m. | 1,000 mg TU/8 week | 4.5 months | 66 to 76 | 35 | 35 | 230 ± 180 (SD) ng/dL | hypogonadal, heart failure |
| Ferrando 2002 [36] | i.m. | 100 mg TE/week | 6 months | 67 ± 3 (SD) | 7 | 5 | <480 ng/dL | eugonadal |
| Hackett 2014 [37] | i.m. | 1000 mg TU/6 to 12 weeks | 7.5 months | 18 to 80 | 97 | 102 | 301 ± 11 (SD) ng/dL | hypogonadal, type 2 diabetes |
| Hall 1996 [38] | i.m. | 250 mg TE/4 weeks | 9 months | 60.8 ± 9.7 (SD) | 17 | 18 | 458 ± 187 (SD) ng/dL | eugonadal, rheumatoid arthritis |
| Ho 2011 [39] | i.m. | 1,000 mg TU/10 to 14 weeks | 24 months | ≥40 | 60 | 60 | <345 ng/dL | low normal T |
| Hoyos 2012 [40] | i.m. | 1,000 mg TU/6 weeks | 4.5 months | 49 ± 12 (SD) | 33 | 34 | 388 ± 152 (SD) ng/dL | eugonadal, obese, sleep apnea |
| Kalichenko 2010 [41] | i.m. | 1,000 mg TU/6 to 12 weeks | 7.5 months | 49 to 53 | 113 | 71 | <345 ng/dL | low normal T, metabolic syndrome |
| Kenny 2004 [42] | i.m. | 200 mg TE/3 weeks | 3 months | 81 ± 5 (SD) | 6 | 5 | 410 ± 112 (SD) ng/dL | mild cognitive impairment |
| Sih 1997 [43] | i.m. | 200 mg TC/2 weeks | 12 months | 65 ± 7 (SD) | 17 | 15 | 233 ± 20 (SD) ng/dL | hypogonadal |
| Svartberg 2004 [44] | i.m. | 250 mg TE/4 weeks | 6 months | 64 ± 6.5 (SD) | 15 | 14 | 590 ± 164 (SD) ng/dL | eugonadal, COPD |
| Svartberg 2008 [45] | i.m. | 1,000 mg TU/6 to 12 weeks | 12 months | 69 ± 5 (SD) | 19 | 19 | 239 ± 54 (SD) ng/dL | hypogonadal |
| Sheffield-Moore 2011 [46] | i.m. | 100 mg TE/week | 5 months | 73 ± 8 (SD) | 8 | 8 | <500 ng/dL | eugonadal |
| Tan 2013 [47] | i.m. | 1,000 mg TU/8 weeks | 12 months | 53.8 ± 8.3 (SD) | 56 | 58 | <345 ng/dL | low normal T |
| *Basaria 2010 [7] | gel | 100 to 150 mg T/day | 6 months* | 74 ± 5 (SD) | 106 | 103 | 250 ± 57 (SD) ng/dL | hypogonadal, mobility limited |
| Brockenbrough 2006 [48] | gel | 100 mg T/day | 6 months | 58.9 ± 14.9 (SD) | 19 | 21 | 218 ± 64 (SD) ng/dL | hypogonadal, renal disease |
| Glintborg 2013 [49] | gel | 50 to 100 mg T/day | 6 months | 62 to 72 | 20 | 18 | <210 ng/dL | hypogonadal, obese |
| Hildreth 2013 [50] | gel | 25 to 50 mg T/day | 12 months | 66.6 ± 5.8 (SD) | 96 | 47 | 294 ± 38 (SD) ng/dL | hypogonadal |
| Jones 2011 [51] | gel | 60 mg T/day | 12 months | 37 to 77 | 108 | 112 | 265 ± 75 (SD) ng/dL | hypogonadal, metabolic syndrome |
| Kaufman 2011 [52] | gel | 20 to 80 mg T/day | 6 months | 53.6 ± 9.5 (SD) | 234 | 40 | mean =294 ng/dL | hypogonadal |
| Kenny 2010 [53] | gel | 50 mg T/day | 12 to 24 months | 79.9 ± 7.3 (SD) | 69 | 62 | 380 ± (SD) ng/dL | eugonadal, osteoporosis |
| Marin 1993 [54] | gel | 125 mg T/day | 9 months | 56.7 ± 2.2 (SD) | 11 | 10 | 434 ± 23 (SD) ng/dL | eugonadal, obese |
| Spitzer 2012 [55] | gel | 100 to 300 mg T/day | 3.5 months | 55.1 ± 8.3 (SD) | 70 | 70 | 248 ± 62 (SD) ng/dL | hypogonadal, erectile dysfunction |
| Srinivas-Shankar 2010 [56] | gel | 50 mg T/day | 6 months | 73.7 ± 5.7 (SD) | 138 | 136 | 313 ± 89 (SD) ng/dL | low normal T, frail |
| English 2000 [17] | patch | 5 mg T/day | 3 months | 69 ± 2 (SD) | 25 | 25 | 390 ± 22 (SD) ng/dL | eugonadal, stable angina |
| Malkin 2006 [57] | patch | 5 mg T/day | 12 months | 63.1 ± 10.7 (SD) | 37 | 39 | 400 ± 152 (SD) ng/dL | eugonadal, heart failure |
| Merza 2005 [58] | patch | 5 mg T/day | 6 months | 63 ± 9 (SD) | 20 | 19 | 242 ± 95 (SD) ng/dL | hypogonadal |
| Nair 2006 [59] | patch | 5 mg T/day | 24 months | 61 to 72 | 27 | 31 | bioavailable T <103 ng/dL | hypogonadal |
| Snyder 2001 [60] | patch | 6 mg T/day | 36 months | 71.3 ± 5.8 (SD) | 54 | 54 | <475 ng/dL | eugonadal |
| Chapman 2009 [61] | oral | 160 mg TU/day | 12 months | 78 ± 4 (SD) | 11 | 12 | 541 ± 35 (SD) ng/dL | eugonadal, undernourished |
| Copenhagen study 1986 [62]a | oral | 600 mg micronized T/day | 8 to 62 months | 24 to 79 | 134 | 87 | not measured | alcoholic cirrhosis |
| Emmelot-Vonk 2008 [63] | oral | 80 mg TU/day | 6 months | 67.1 ± 5.0 (SD) | 120 | 117 | 316 ± 54 (SD) ng/dL | low normal T |
| Legros 2009 [64] | oral | 80 to 240 mg TU/day | 12 months | 58.6 ± 5.7 (SD) | 237 | 79 | free T <7.5 ng/dL | hypogonadal |
aStudy was stopped early. COPD. chronic obstructive pulmonary disease; i.m., intramuscular; SD, standard deviation; T, testosterone; TC, testosterone cypionate; TE, testosterone enanthate; TU, testosterone undecanoate.