Table 1: Baseline characteristics of included studies
 
Study Study design Total no of patients Hypogonadism cut off point No of patients Age (Mean ±SD) Waist circumference (cm) (Mean ±SD) BMI (Kg/m2) (Mean ±SD)
TRT Placebo TRT Placebo TRT Placebo TRT Placebo
Dhindsa (2015)[13] RCT 34 FT<225 pmmol/L 20 14 54.6± 7.9   54.6± 7.9 128 ±20   124 ± 30 39.0 ± 7.6   39.4 ± 7.9
Gianatti (2014)[8] RCT 67 TT<12 nmmol/L 37 30 62± 2.5   62± 2.5 110±4.2   115±2.75    
Hackett (2014)[14] RCT   186 TT<12 nmmol/L 91 95 61.2 ± 10.5 62.0 ± 9.3 115.1 ± 13.1 112.6 ± 13.3 33.0 ± 6.1 32.4 ± 5.5
Jones (2011)[15] RCT     137 TT<11 nmmol/L 68 69 59.9± 9.1 59.9 ± 9.4 112.7± 13.35 111.7± 15.23 32.76± 6.12 31.56 ± 5.87
Gopal (2010)[16] RCT crossover 22 FT<225 pmmol/L 22 22 44.23 ±3.29 44.23 ±3.29 93.25 ± 7.03 84.10 ± 13.86 25.44 ± 3.57 22.10 ± 4.93
Heufelder (2009)[17] RCT 32 TT<11 nmmol/L 16 16 57.3 ±1.4 55.9 ±1.5 107.9 ± 1.3 105.7± 1.4 32.1 ± 0.5 32.5 ± 0.6
Kapoor (2006)[18] RCT crossover 27 TT<12 nmmol/L 24 24 64 ±1.34 64 ±1.34 115.1± 2.4 115.1± 2.4 33 ±0.86 33 ±0.96
Boyanov (2003)[19] RCT 48 TT<15 nmmol/ 24 24 57.5 ± 4.8 57.5 ± 4.8 N/A N/A 31.08 ± 4.79 31.01 ± 4.90
Hackett (2018)[20] RCT   537 TT<12 nmmol/L 175 362 58.3± 11 65.5 ± 11.8 N/A N/A 32.6 ± 6.4 31.7± 5.9
Yassin (2019)[12] Observational study 316 TT< 12.1nmol/L 229 87 58.2 ± 9.6 66.4 ± 7.2 104.2 ± 7 101.1 ± 9.9 30.7 ± 4.1 29.8 ± 3
Khirpun (2018)[21] RCT 80 serum levels of total testosterone two times below 12.1 nmol/L or serum levels of free testosterone two times below 243 pmol/L in combination of at least two symptoms or complaints of sexual or psychological nature   40 40 53.3 ± 5.4 54.1 ± 5.6 114.3 ± 9.5 114.7 ± 9.8 34.0 ± 2.6 33.6 ± 2.9
Groti (2020)[5] RCT 55 (total testosterone [TT] below 11 nmol/L and free testosterone below 220 pmol/L) on at least two separate morning measurements after an overnight fast in addition to exhibiting at least two symptoms of sexual dysfunction (less frequent morning e   28 27 58.21 ± 7.94 62.19 ± 5.90 116.48 ± 5.07 115 ± 1.47 34.03 ± 4.37 32.63 ± 3.67
Groti (2018)[22] RCT 55 total testosterone (TT) level <11 nmol/l and/or free testosterone (FT) level <220 pmol/l   28 27 N/A N/A 116.48 ± 5.07 116.64 ± 4.96 34.03 ± 4.37 32.63 ± 3.67
Wittert (2021) [23] RCT 1007 13·0 nmol/L   504 503 59·8 ± 6·3   59·6 ± 6·4   118·4 ± 12·6   117·8 ± 11·6   34·8 (5·1)   34·6 (5·1)  
Haider (2020) [24] Prospective observational 356 total testosterone levels ≤12.1 nmol/L (350 ng/dL) and symptoms of hypogonadism   178 178 61.5 ± 5.4   63.7 ± 4.9   116.8 ± 14.3   116.9 ± 13.6   36.5 ± 4.5   33.4 ± 5.3  
SD: Standard deviation, Ft: free testosterone, TT: total testosterone
 
 
 
 
 
 
Table 2: Baseline glucometabolic, lipid and blood pressure parameters
Study Fasting plasma glucose (mmol/L) (Mean ±SD) Fasting serum insulin (Mean ±SD) HbA1c % Free testosterone (Mean ±SD) Total testosterone (Mean ±SD) HOMA-IR (Mean ±SD) Mean total cholesterol (Mean ±SD) Systolic blood pressure (Mean ±SD) Diastolic blood pressure (Mean ±SD)
  TRT Placebo TRT Placebo TRT Placebo TRT Placebo TRT Placebo TRT Placebo TRT Placebo TRT Placebo TRT Placebo
Dhindsa (2015)[13] 6.99 ± 0.44   6.60 ± 0.55 13.6 ± 3   11.8 ± 2.2 6.8 ± 0.9    7 ±1.4 156.5 ± 45.11 145.74 ± 41.6   9 ± 2.9   8.3 ± 2.8 9 ± 2.9   8.3 ± 2.8 4.06 ± 0.98 4.03 ±0.95   N/A N/A N/A N/A
Gianatti (2014)[8] 9.57 ± 3.78 9.11 ± 3.65 N/A N/A 7.7 ± 1.3 7.5 ± 1.2 187.7 ± 57.0 181.2 ± 63.6 9.2 ± 3.1 8.9 ± 3.8 4.1 ± 2.0 3.7 ± 2.6 4.15± 0.90 4.08± 0.9 140.2 ± 15.9 137.1 ± 13.0 79.4 ± 9.4 77.5 ± 8.9
Hackett (2014)[14] 9.05 ± 3.18 8.49 ± 2.84 20.88 ± 22.83 18.17 ± 15.7 N/A N/A 198 ± 49.3 202.4 ± 62.1 9.2± 2.6 9.5± 3.3 5.9± 3.8 4.9± 3.3 4.51± 1.17 4.55± 1.01 138.6± 17.30 136.7± 17.12 82.5± 10.23 81.6± 9.50
Jones (2011)[15] 7.9 ± 4.3 9.2 ± 3.4 12.80 ± 8.95 17.86 ± 24.72 6.43 ± 2.20 7.69 ± 2.77 177.57 ± 60.19 177.57 ± 60.19 10.1 ± 3.7 10.1 ± 3.7 5.50 ± 6.82 6.45 ± 8.75 4.7 ± 0.9 4.0 ± 1.0 115.83 ± 5.15 118.40 ± 9.97 82.00 ± 6.93 79.00 ± 3.16
Gopal (2010)[16] 7.9 ± 0.2 8.3 ± 0.2 19.03 ± 0.63 16.8 ± 0.87 7.5 ± 0.1 7.5 ± 0.1 200 ± 0.00 200 ± 0.00 10.5 ± 0.2 10.4 ±0.2 5.6 ± 0.3 6.1 ± 0.4 N/A N/A 104.5± 2.6 143.5± 2.1 85.6± 0.9 85.0± 1.0
Heufelder (2009)[17] 7.83 ± 0.49 7.6 ± 0.43 13.68 ± 1.95 12.37 ± 1.87 7.28 ±0.19 7.28 ±0.19 N/A N/A 8.63 ±0.51 8.63 ±0.51 N/A N/A 5.11 ±0.17 4.95± 0.15 127.6± 2.8 131± 3.1 74± 1.4 74± 1.4
Kapoor (2006)[18] 8.0 ± 2.6 8.4 ± 2.8 N/A N/A 10.4 ± 1.6 10.3 ± 1.6 N/A N/A 9.56 ± 2.33 10.76 ± 3.0 N/A N/A 5.50 ± 1.41 5.59 ± 1.49 122 ± 8 120 ± 8 80 ± 4 76 ± 6
Boyanov (2003)[19] N/A N/A N/A N/A 7.6 ± 1.3 7.5 ± 1.5 210 ± 124.5 175 ± 67.9 9.7 ± 4.4 8.9 ± 3.2 N/A N/A 4.5 ± 1.1 4.1 ± 1.0 141.8± 16.1 139.4± 16.8 81.4 ± 10.4 78.2 ± 10.4
Hackett (2018)[20] 5.3 ± 0.8 4.9 ± 1.3 N/A N/A 5.9 ± 0.2 5.9 ± 0.2 N/A N/A 8.2 ± 2.1 9.6 ± 2.4 N/A N/A 6.9 ± 1.2 6.4 ± 1.4 136.9 ± 13.5 129.8 ± 12.7 81.2 ± 8.9 84.7 ± 6.7
Yassin (2019)[12] 8.1 ± 3.7 8.7 ± 5.0 N/A N/A 7.8 ± 2.4 7.9 ± 2.4 208 ± 142 223 ± 140 9.6 ± 2.7 9.9 ± 2.6 N/A N/A 6.1 ± 1.2 5.9 ± 1.5 N/A N/A N/A N/A
Khirpun (2018)[21] 10.06 ± 1.44 9.77 ± 1.40 N/A N/A 8.12 ± 1.04 7.89 ± 0.77 208 ± 142 223 ± 140 7.24 ± 1.97 7.96 ± 1.34 11.45 ± 7.34 10.82 ± 6.52 5.31 ± 0.91 5.11 ± 0.85 134.64 ± 10.71 138.15 ± 13.24 77.50 ± 5.85 78.89 ± 5.25
Groti (2020)[5] 10.06 ± 1.44 9.60 ± 1.44 26.03 ± 15.86 24.89 ± 13.90 8.12 ± 1.04 7.89 ± 0.77 N/A N/A 7.24 ± 1.97 7.96 ± 1.34 11.45 ± 7.34 10.70 ± 6.52 5.31 ± 0.91 5.31 ± 0.97 134.64 ± 10.71 138.15 ± 13.24 77.50 ± 5.85 78.89 ± 5.25
Groti (2018)[22] 10.06 ± 1.44 9.60 ± 1.44 26.03 ± 15.86 24.89 ± 13.90 8.12 ± 1.04 7.89 ± 0.77 N/A N/A 7.24 ± 1.97 7.96 ± 1.34 11.45 ± 7.34 10.70 ± 6.52 5.31 ± 0.91 5.31 ± 0.97 134.64 ± 10.71 138.15 ± 13.24 77.50 ± 5.85 78.89 ± 5.25
Wittert (2021) [23]   6·1 ± 0·9   6·1 ± 0·9   N/A N/A 5·7 ± 0·5   5·7 ± 0·5   N/A N/A 13·4 ± 4·1   13·9 ± 4·6 N/A N/A N/A N/A 138.52± 14.2   139.88± 14   85.45± 8.5   85.13± 8.3  
Haider (2020) [24]   7.8 ± 1.2   6.3 ± 0.7   28.6 ± 4.0   24.9 ± 2.9   Forest plot Forest plot N/A N/A 9.3 ± 1.7   9.8 ± 1.1   9.8 ± 2.0   7.1 ± 1.3   8.3 ± 1.1   7.1 ± 1.2   163.0 ± 13.3   145.6 ± 14.6   97.6 ± 10.8   84.8 ± 10.3  
SD: Standard deviation, HOMA-IR: Homeostasis model of insulin resistance, HbA1c: glycated hemoglobin
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table 3:  Secondary outcomes
Outcome Testosterone placebo Effect size [CI] Overall P value heterogeneity
Total cholesterol -0.71 [-1.22, -0.21]   0.10 [-016, 0.35]   -0.32 [-0.64, 0.00] 0.05 87.2
Triglyceride -0.47 [-0.75, - 0.20]   0.03 [-021, 0.27]   -0.23 [-0.47, 0.00]   0.05 86.6
LDL cholesterol -0.20 [-1.12, 0.73]   0.17 [-0.13, 0.46]   -0.02 [-0.52, 0.48]   0.94 0
HDL cholesterol 0.10 [0.01, 0.20]   0.03 [-0.07, 0.13]   0.07 [0.00, 0.13]   0.04 8.7
Body fat -0.98 [-1.59, -0.38]   -0.54 [-1.12, 0.03]   -0.75 [-1.17, -0.34]   0.0004 6.4
Waist circumference -3.98 [-6.48, -1.48]   0.73 [-1.44, 2.89]   -1.68 [3.43, 0.07]   0.06 87.1
BMI -1.12 [-2.98, 0.74]   0.05 [-0.51, 0.61]   -0.56 [-1.48, 0.36]   0.23 27.5
SBP -0.90 [-12.07, 10.26]   -0.19 [-3.19, 2.81]   -0.51 [-6.24, 5.11]   0.85 0
DBP -3.09 [-5.52, -0.65]   -0.23 [-1.98, 1.52]   -1.68 [-3.16, -0.21]   0.03 71.3
IIEF 6.98 [3.62, 10.33]   -3.94 [-10.97, 3.10]   1.66 [-6.75, 10.06]   0.70 86.7
AMS -16.80 [-26.96, -6.64]   4.90 [-9.05, 18.85]   -5.94 [-21.87, 9.98]   0.46 83.5
Mortality -       0.24 [0.15, 0.37]   <0.00001 0
CI: Confidence interval, LDL: low density lipoprotein, HDL: High density lipoprotein, BMI: Body mass index; SBP: Systolic blood pressure, DBP: Diastolic blood pressure, IIEF: international index of erectile function, AMS: Aging male score.