| Men Assessed
as Having Low Serum Testosterone
|
|
Brill et al, 2002[92] |
10 men 60–78 years old with morning serum T 200–450 ng/dL (6.9–15.6 nM), serum prolactin below 25 μg/L, LH and FSH below 20 IU/L, IGF-I below 200 μg/L. |
T patch 5 mg/day or placebo x 1 month with each subject serving as his own control; subjects also received growth hormone with or without T (not discussed here); randomization method not given. |
No change in eccentric/concentric knee extension/flexion strength, hamstring flexibility, or eyes-closed non-dominant-leg balance test. ↑Fat-free mass by 1 of 2 measurement techniques. No change in % body fat or BMI. |
3 |
|
Casaburi et al, 2004[84] |
53 men 55–80 years old with COPD (FEV1 ≤60% of predicted, FEV1: VC ratio ≤60%) and serum T ≤400 ng/dL (13.9 nM); 6 dropouts were excluded from analysis. |
T enanthate 100 mg (n = 23) or placebo (n = 24) IM weekly with or without resistance training x10 weeks; randomization method not given. |
T + no training group: Compared to placebo + training: ↑trunk lean mass, ↓% fat. Compared to placebo groups: ↑arm and total lean mass; ↓leg and total fat. Compared to placebo + no training: ↑leg lean mass and leg press strength; ↓leg press fatigue and peak work rate. No change: arm and trunk fat, maximal inspiratory pressure, peak O2 uptake, lactic acidosis threshold, constant work rate duration. |
5 |
| T + strength training group: Compared to placebo groups: ↑arm, trunk, leg, and total lean mass; ↓leg, total, and % fat. |
| Compared to non-training groups: ↑leg press strength and peak oxygen uptake; ↓leg press fatigue. Compared to T + no training: ↑peak work rate. Compared to placebo + no training: ↑lactic acidosis threshold. No change: arm and trunk fat, maximum inspiratory pressure, constant work rate duration. |
|
Clague et al, 1999[165] |
14 men mean age 68.1 with total T <400 ng/dL (13.9 nM). |
T enanthate 200 mg (n = 7) or placebo (n = 7) IM every 2 weeks x 12 weeks, with muscle testing every 4 weeks; randomization method not given. |
No change in handgrip, knee extensor, and knee flexor strength, leg extensor power, step height. |
4 |
|
Emmelot-Vonk et al, 2008[91] |
237 men 60–80 years old with total T <395 ng/dL (13.7 nM); 30 dropouts were excluded from analysis. |
T undecanoate 80 mg (n = 120) or placebo (n = 117) capsules twice daily x 6 months; a randomization list without stratification using blocks of 6 was computer-generated using the ADLS. |
↓Total body fat mass and body fat percentage; ↑total body lean mass. No change in grip strength, leg extensor strength, timed get up and go test.; No change in BMI, intra-abdominal fat mass. |
5 |
|
Ferrando et al, 2001[93] |
12 healthy men, mean age 67–68 with serum total T ≤480 ng/dL (16.7 nM). |
T enanthate (n = 7) or placebo (n = 5) IM (dosage adjusted to maintain nadir serum T concentrations 17–28 nM) weekly x 1 month, then every 2 weeks x 6 months; randomization method not given. |
No change at 1 month in strength. At 6 months: ↑strength for bicep curl, tricep extension, leg extension. No change in leg-curl strength and knee extension endurance in the dominant leg. ↑Total lean body mass, leg lean mass, leg muscle volume; ↓fasting protein breakdown % body fat. No change in arm lean mass |
0 |
|
Hildreth et al, 2013[94] |
167 men over 60 years old (mean age 66) with total T 200–350 ng/dL (6.9–12.1 nM); 24 dropouts were excluded from analysis. |
T gel 1% 2.5, 5.0 g (n = 111), or placebo (n = 56) daily x 12 months, with or without progressive resistance exercise training; randomization was performed using permuted block randomization with random block sizes. |
T treated groups analyzed in aggregate. In subjects with resistance training, no change in physical functional performance tests: upper body strength and flexibility, lower body strength, balance, and endurance, stair climb speed and 6-min walk, strength (bench press, incline press, overhead pull-down, seated row, average upper body, grip strength, knee extension, knee flexion, seated leg press, average lower body), power (leg extensor). ↓Fat mass; ↑overall and arm fat free mass. No change in weight, BMI, trunk fat mass, appendicular and leg fat-free mass, waist and hip circumferenceIn subjects without PRT: ↑Lower body strength, strength for bench and incline press, average upper body and grip strength. No change in physical functional performance test total score, upper body strength and flexibility, lower body balance and endurance, stair climb speed and 6-min walk, strength for overhead pull-down, seated row, knee extension/flexion, seated leg press, and average lower body, power (leg extensor). ↑Appendicular and arm fat free mass. ↓Overall and trunk fat mass, waist circumference. No change in weight, BMI, overall and leg fat-free mass, hip circumference |
5 |
|
Kenny et al, 2001[166] |
67 men >65 years old (mean age 76) with bioavailable T <128 ng/dL (4.44 nM); 23 dropouts were excluded from analysis. |
T patch 5 mg (n = 34) or placebo (n = 33) daily x 1 year; all received 500 mg calcium and 400 IU vitamin D supplements; randomization method not given. |
No change in BMI, % body fat or lean mass. No change in PASE (Physical Activity Scale for the Elderly) score. PASE includes 8-ft walk speed, chair rise, single-leg stance, supine-to-stand, and get up and go time. |
4 |
|
Kenny et al, 2010[80] |
131 men ≥60 years old (mean age 77.1) with T <350 ng/dL (12.1 nM), physical frailty, and BMD T-score at the hip ≤ —2.0 or a nontraumatic fracture within last 5 years; delays in recruitment and lack of funds resulted in ≥16 months of follow-up with analysis performed at 12 months; 69 dropouts excluded from analysis. |
T gel 5 mg (n = 69) or placebo (n = 62) daily x 16 months; all subjects maintained calcium intake of 1500 mg/day and were given 1000 IU cholecalciferol/day; randomization with block sizes (2 or 4) stratified by frailty status |
↑Total body lean mass, appendicular skeletal muscle mass; No change in total body fat %. No change in hand grip/ leg press strength or PASE |
5 |
|
Ly et al, 2001[11] |
37 healthy men >60 years old (mean age 68.2) with plasma T ≤429 ng/dL (14.9 nM); 4 dropouts were excluded from analysis or for some measures, missing data imputed using last observation carried forward |
0.7% DHT gel 70 mg (n = 17) or placebo (n = 16) daily x 3 months, followed by 1 month of observation; method of randomization inadequately explained |
↑Dominant knee flexion peak torque from 2–4 months. No change in waist:hip ratio, lean mass, peak torque for knee extension, nondominant knee flexion, shoulder flexion/extension, maximal horizontal forward reach of the outstretched right arm without losing balance; standing balance time with feet tandem, eyes closed, 18 meter fast walk, time to stand up and sit 5x. ↓Body weight (month 4), fat mass (months 2–4), skinfold thickness (months 2–4). |
5 |
|
Nair et al, 2006[95] |
62 men >60 years old with bioavailable T <3.6 nM (104 ng/dL); incomplete follow-up for some subjects, 4 subjects did not complete study. |
Transdermal T patch 5 mg (n = 30) or placebo (n = 32) x 24 months; randomization method not given. Additional arms included women and included other tx (not discussed here) |
No change in peak VO2, peak torque of isometric dominant knee extension, strength for seated chest press and double leg press. ↑Fat-free mass. No change in body weight, BMI, body fat %, visceral:total fat ratio, visceral fat, thigh-muscle area |
4 |
|
Okun et al, 2006[85] |
30 men mean age 68 with Parkinson disease and free T <100 pg/mL (347 pM). |
200 mg T enanthate (n = 15) or placebo (n = 15) IM every 2 weeks x 8 weeks; dose could be adjusted upwards based on free T measured every 2 weeks; randomization method not given. |
No change in motor function as measured by a videotaped Unified Parkinson’s Disease Rating Scale (UPDRS) evaluation. |
4 |
|
Page et al, 2005[81] |
48 men age 65–83 (mean 71) with morning serum total T <350 ng/dL (12.1 nM), classified as sedentary (≤60 min/week of moderate-intensity recreational physical activity); 13 dropouts excluded from analysis |
T enanthate 200 mg (n = 24) or placebo (n = 24) IM every 2 weeks x 36 months; subjects also received T with finasteride (not discussed here); randomization method not given |
↑Improvement in timed physical performance, right handgrip strength. No change in body weight, left handgrip strength, peak torques of knee/ankle flexion/extension. ↓Total fat mass, % body fat, right leg fat, trunk fat. ↑Lean body mass, waist:hip circumference ratio |
4 |
|
Sih et al, 1997[104] |
32 men (mean age 68 for placebo and 65 for T) with bioavailable blood T ≤60 ng/dL (2.1 nM); 3 T subjects dropped due to an abnormal increase in hematocrit of ≥52% |
T cypionate 200 mg (n = 17) or placebo (n = 15) IM every 14–17 days x 12 months; randomization by random number |
↑Grip strength. No change in body weight, BMI |
4 |
|
Srinivas-Shankar et al, 2010[53] |
297 men ≥65 years old (mean age 73) with physical frailty and total T ≤345 ng/dL (12 nM); 31 dropouts excluded from analysis |
T 50 mg (n = 136) or placebo (n = 138) gel daily x 6 months; dosage adjusted if T concentrations remained outside the target range (18–30 nM); subjects randomized in blocks of 10 by computer-generated sequence |
↑Isometric knee extension peak torque↑LBM, ↓fat mass. No change in isokinetic knee extension peak torque, isometric/ isokinetic knee flexion peak torque, grip strength, aggregate locomotor function (ALF) test, physical performance test (PPT), 6 minute walk, PASE, Tinetti gait/balance test. |
5 |
|
Snyder et al, 1999[96] |
108 men >65 years old with serum T <495 ng/dL (17.2 nM); 12 dropouts were excluded from analysis. |
T patch 6 mg (n = 54) or placebo (n = 54) daily x 36 months; every 3 months T concentration was checked and dosage was decreased to 4 mg/day if serum T was >1000 ng/dL; randomization method not given. |
No change in weight, BMI, tissue mass, trunk fat mass, arm/leg lean mass, strength for knee extension/ flexion and handgrip, time to walk and number of steps in 25 feet, time to walk 12 stairs. ↓Fat mass, arm/leg fat mass. ↑Lean mass, trunk lean mass |
4 |
|
Sullivan et al, 2005[82] |
71 men ≥65 years old (mean age 78.2) with serum total T <480 ng/dL (16.7 nM) and a recent functional decline; 10 dropouts were excluded from analysis. |
T enanthate 100 mg (n = 37) or placebo (n = 34) IM weekly with low- or high-intensity resistance strength training x 12 weeks; randomization stratified by arbitrary score of physical ability; within each stratum, subjects randomized with blocks sizes in multiples of 4 and randomly varied |
No change in strength for chest and leg press, performance testing score (sit-to-stand maneuver, habitual and maximal safe gait speed tests, stair climb). ↑Mid-thigh cross-sectional muscle area |
5 |
|
Travison et al, 2011[83] |
209 men ≥65 years old with total serum T 100–350 ng/dL (3.5–12.1 nM) or free serum T <50 pg/mL (174 pM) with mobility limitations; analysis restricted to 165 men with a baseline assessment and at least one outcome assessment. |
T 100 mg (n = 106) or placebo (n = 103) gel daily x 6 months; after 2 weeks, dose level was increased or decreased by 50% based on serum T; randomization by computer-generated table in blocks of 6 stratified by age |
↑Strength for leg and chest press, loaded stair-climbing power, loaded walk speed. No change in grip strength, unloaded walking speed, unloaded stair-climbing power. ↑Total lean mass, appendicular skeletal muscle mass. ↓Total fat mass, appendicular fat mass. ↑Cardiovascular-related AEs with T (23 vs 5) |
5 |
|
Wittert et al, 2003[97] |
76 healthy men age ≥60 (mean 68.5) with ≥2 symptoms on the ADAM questionnaire, a ratio of T/sex-hormone binding globulin of 0.3–0.5, serum total T >230 ng/dL (8 nM); 18 dropouts were excluded from analysis. |
T undecanoate 80 mg (n = 39) or placebo (n = 37) twice daily x 12 months; randomization with blocks of 4 as part of a proprietary system |
No change in grip, quadriceps, and calf strength;No change in body weight. ↑Lean body mass; ↓% body fat |
5 |
|
Borst et al, 2014[167] |
60 men ≥60 years old with serum testosterone concentration ≤300 ng/dL (10.4 nM) or bioavailable testosterone ≤70 ng/dl (2.4 nM). 40 completed. Randomized by computer program |
4 groups: T enanthate 125 mg/ week IM X 52 weeks and finasteride 5 mg/day; T enanthate and oral placebo; vehicle i.m and finasteride, or vehicle IM and placebo. |
Testosterone, compared to finasteride or placebo, increased strength (leg press, knee flexion and extension, chest press, triceps extension, and grip strength), body fat-free mass. Total fat mass reduced 3.87 kg. Lumbar spine and hip BMD increased |
5 |
| HIV-Negative Menwith Normal Serum Testosterone |
|
Amory et al, 2002[86] |
25 men 58–86 years old undergoing knee replacement surgery; 3 dropouts were excluded from analysis. |
T enanthate 600 mg (n = 10) or placebo (n = 12) IM 21, 14, 7, and 1 day before surgery; randomized using a random number sequence. |
↑Standing function at post-operative day 3. No change in standing function at post-operative day 35, walking and stair climbing tests, length of hospital stay |
5 |
|
Bakhshi et al, 2000[90] |
15 men ≥65 years old who had been admitted to the Geriatric Evaluation and Management unit for rehabilitation; 1 subject in the T group died unexpectedly 2 weeks after admission on the day of his planned discharge probably as the result of a cardiovascular event. |
T enanthate 100 mg (n = 9) or placebo (n = 6) IM weekly until discharge or for a maximum of 8 weeks; subjects received rehabilitation therapy as appropriate to their needs; randomization method not given. |
↑Functional Independence Measure and grip strength compared to baseline; difference compared to placebo not reported, but no difference in either endpoint compared to placebo by t-test performed by us. |
4 |
|
Caminiti et al, 2009[18]; Schwartz et al, 2011[87] |
70 men 66–76 years old (mean age 70) with stable CHF (NYHA II or III) and LV EF <40%; 6 dropouts (4 on T and 2 on placebo) were excluded from analysis. |
T undecanoate 1000 mg (n = 35) or saline (n = 35) IM at 6 and 12 weeks. Subjects said to be randomized, randomization method not given |
↑Peak VO2, peak workload, distance walked in 6 minutes, leg muscle strength, knee extension/flexion peak torque. ↓Ventilation/CO2 output. ↑Body weight, BMI |
4, 5 |
|
Dohn et al, 1968[13] |
44 men with leg claudication or ulcers attributed to arteriosclerosis in 43 men and to Buerger’s disease in 1 man; age not given. Two men did not complete study. Numbers in tables add to 86 subjects. Not possible to tell for sure how many men were analyzed. |
Aqueous T isobutyrate 300 mg or meprobamate as placebo every 14 days for 3 months; route of administration not given; double-blinded, randomization not discussed |
No effect on subject improvement, walking test |
3 |
|
Crawford et al, 2003[88] |
43 men >20 years old (mean age 60.3) on long-term glucocorticoid therapy; 14 dropouts were excluded from analysis. |
T mixed esters 200 mg (n = 18) or placebo (n = 16) IM every 2 weeks x 12 months; all received calcium carbonate 600 mg daily; randomization method not given. Nandrolone not discussed. |
↑Peak knee extension/flexion torque. ↑Lean mass. ↓Fat mass. No change in body weight, BMI, waist circumference, waist:hip ratio, skinfold thickness. |
3 |
|
Griggs et al, 1989[89] |
40 men 18–65 years old (mean age 33.3 years for T and 41.5 years for placebo) with myotonic dystrophy and a typical distribution of weakness (but ambulatory); 3 dropouts were excluded from analysis. |
T enanthate or placebo 3 mg/kg IM weekly x 12 months; number of subjects/group not given; evaluations every 3 months; randomization performed using computer-generated random numbers, stratified by grip strength and previous T tx |
↑Time to climb stairs. No change in arm volume, weight, manual muscle testing, myometry, grip dynamometry, forced vital capacity (VC), maximum voluntary ventilation, maximum expiratory pressure, time to walk 30 feet, time to cut standard square. ↑Creatinine excretion (↑muscle mass) |
4 |
|
Hentzer & Madsen, 1967[40] |
39 males with arterial insufficiency; 3 drop outs. |
200 mg T (n = 19) or placebo (n = 17) IM weekly for 3 weeks, then once every second week for 6 months; consecutive patients assigned to tx or placebo by record numbers. |
No change in grip strength, walking distance. |
3 |
|
Svartberg et al, 2004[43] |
29 men 54–75 years old (mean age 66 years) with moderate to severe COPD; 2 dropouts were excluded from analysis. |
T enanthate 250 mg (n = 15) or placebo (n = 14) IM every 4 weeks x 26 weeks; method of randomization not discussed |
No change in BMI, forced VC, forced expiratory volume, 6-minute walk. ↑Fat-free mass. ↓Total body fat mass (at 12 weeks). |
4 |
|
Mirdamadi et al, 2014[22] |
50 males age 50–70 with CHF |
T enanthate 250 mg IM or saline placebo IM every 4 weeks for 12 weeks |
No difference between groups in muscle strength or body weight. Both groups improved in 6-minute walking distance; no post-intervention effect was seen. |
3 |
|
Giannoulis et al, 2006[168] |
Healthy men 65–80 years old with circulating IGF-I <50th percentile for the local age-specific range; of those meeting criteria, the 80 subjects with the lowest T concentration but without T deficiency, mean 397.6 ng/dL (13.8 nM); 5 subjects were excluded because PSA concentrations met revised exclusion criteria and 6 dropouts were excluded from analysis. |
T 5 mg or placebo transdermal patch daily x 6 months; randomization was performed using computer-generated pre-allocated study numbers; growth hormone arm not discussed here |
No change in knee flexion/extension peak torque/force, hand-grip peak force, VO2 max. No change in BMI, hip/waist ratio, lean body mass, subcutaneous/cross-sectional abdominal visceral/total body fat, mid-thigh muscle cross sectional area. |
5 |
| HIV-Positive Men |
|
Bhasin et al, 2007[98] |
88 HIV-positive men 18–70 years old with abdominal obesity and serum total T 125–400 ng/dL (4.3–13.9 nM); 8 dropouts were excluded from analysis. |
Transdermal T gel 100 mg (n = 44) or placebo (n = 44) daily x 24 weeks; randomization stratified by RNA copy number with approximate balance within each site |
↓Total abdominal, subcutaneous abdominal, trunk, extremity, and whole body fat mass; waist circumference; waist:hip ratio. ↑Trunk, extremity, and total lean mass. No change in visceral fat area, body weight, BMI |
5 |
|
Bhasin et al, 1998[103] |
41 HIV-positive men 18–60 years old with serum T <400 ng/dL (13.9 nM); 9 dropouts were excluded from analysis. |
T patch 5 mg (n = 20) or placebo (n = 21) daily x 12 weeks; randomization method not given |
No change in strength (squat and bench press); ↓Fat mass. No change in lean body mass (LBM), fat-free mass, total body weight |
3 |
|
Bhasin et al, 2000[99] |
61 HIV-positive men 18–50 years old with involuntary weight loss, serum total T <349 ng/dL (12.1 nM); 12 dropouts were excluded from analysis. |
T enanthate 100 mg (n = 32) or placebo (n = 29) IV x 16 weeks with or without resistance exercise; randomization by random number table stratified by age in blocks of 16. |
T with no-exercise group: no change in strength for leg press, leg curls, bench press, latissimus pulls, overhead press; ↑Body weight, muscle volume; no change in fat-free and fat mass, total body water (TBW), TBW:fat-free mass ratio, LBM of arms/legs/trunk. T with exercise group: no changes in any measure |
4 |
|
Coodley et al, 1997[105] |
39 HIV-positive men 18–60 years old with AIDS and weight loss; 4 dropouts were excluded from analysis. |
T cypionate 200 mg (n = 17) or placebo (n = 18) IM every 2 weeks x 3 months followed by tx switch x 3 months; randomization method not given |
No change in weight, triceps and scapula skinfold |
3 |
|
Dobs et al, 1999[113] |
133 men with AIDS age 18–65+ who had lost 5–20% of baseline weight with a morning serum total T concentration ≤400 ng/dL (13.9 nM) or free T concentration ≤16 pg/mL (56 pM); 15 T and 20 placebo subjects did not complete. |
T 15-mg (n = 67) or placebo (n = 66) patch applied 20–24 hours/day to shaved scrotal skin for 12 weeks; assessments at weeks 4, 8, and 12; randomization method not given |
No effect on body cell mass or weight. |
3 |
|
Fairfield et al, 2001[107] |
54 HIV-positive men (mean age 38 years) with normal serum free T >12 pg/dL (0.4 pM) and wasting; 11 dropouts were excluded from analysis. |
T 200 mg (n = 24) or placebo (n = 26) IM weekly with or without progressive resistance training x 12 weeks; patients were stratified by body weight, but randomization method not given |
↑Thigh muscle attenuation on computerized tomography (CT) only in subjects who received training. Strength testing was evaluated only with respect to attenuation by CT, not tx group. |
4 |
|
Grinspoon et al, 1998[100] |
51 HIV-positive men mean age 42 with free T <11.9 pg/dL (0.4 pM) and wasting; 11 dropouts were excluded from analysis. |
T enanthate 300 mg (n = 21) or placebo (n = 19) IM every 3 weeks x 6 months; subjects stratified by body weight and megestrol acetate use; randomization using a permuted block algorithm |
No change in fat mass, TBW, exercise performance (6-minute walk test, timed sit-to-stand test, timed get-up-and-go test). ↑Fat-free mass, LBM, muscle mass, total body potassium content |
5 |
|
Grinspoon et al, 2000[101] |
54 HIV-positive men with wasting and serum free T >42 pM (1.2 ng/dL); 11 dropouts were excluded from analysis. |
T enanthate 200 mg (n = 24) or placebo (n = 26) IM weekly x 12 weeks with progressive strength training + aerobic conditioning or no training; randomization with permuted-block algorithm (blocks of 8). |
↑Peak isometric force for shoulder extension and elbow flexion. No change in peak isometric force for knee flexion/extension and dorsiflexion. Grip strength results were not reported. ↑Weight, LBM, arm muscle area, leg muscle area |
5 |
|
Knapp et al, 2008[41] |
61 HIV-positive men 18–60 years old (mean age 43) with unintentional weight loss or BMI <20 and serum T <400 ng/dL (13.9 nM); 4 placebo-assigned and 9 T-assigned subjects dropped out and were analyzed using the last observation carried forward. |
T enanthate 300 mg (n = 30) or placebo (n = 31) IM weekly x 16 weeks; computer-generated randomization list with a block size of 6 |
No change in physical function measures (stair-climbing power, walking speed, load-carrying ability), muscle performance (leg press strength, leg press power, leg press fatigability). ↑Fat-free mass. No change in fat mass, total weight, % body fat. |
5 |
|
Sardar et al, 2010[106] |
104 HIV-positive men >18 years old with involuntary weight loss or BMI <20; randomized subjects evaluated using ITT analysis. |
Sustanon 250 = T propionate 30 mg, phenylproprionate 60 mg, isocaproate 60 mg, and decanoate 100 mg (n = 42) or placebo (n = 20) IM every 2 weeks x 12 weeks; computer-generated randomization tables in a 2:1 ratio |
↑Weight. No change in BMI, waist and hip circumference, waist:hip ratio, triceps and scapula skinfold thickness, mid-arm circumference, % body fat |
5 |
