A randomized, double-blind, placebo-controlled trial of testosterone gel on body composition and health-related quality-of-life in men with hypogonadal to low-normal levels of serum testosterone and symptoms of androgen deficiency over 6 months with 12 months open-label follow-up

Figures & data

Table I.  Baseline demographic and clinical characteristics in the ITT population, according to the study group.

Variable	Testosterone (N = 183)	Placebo (N = 179)	p Value
Age (y)	61.9 ± 6.6	62.1 ± 6.3	0.67
Age range (y)	50–80	48–80
Caucasian no. (%)	182 (99.5%)	174 (97.2%)	0.09
Height (cm)	175.3 ± 6.8	175.9 ± 7.3	0.38
Weight (kg)	87.5 ± 12.1	88.9 ± 11.2	0.28
Body mass index* (kg/m^2)
Mean	28.5 ± 3.3	28.7 ± 3.0	0.45
Obesity (BMI ≥ 30) no. (%)	62 (33.9%)	59 (33.0%)	0.85
Testosterone (nmol/L^†)
Total level	10.4 ± 2.6	10.6 ± 2.6	0.56
Range	0.6–15.0	1.4–14.8
Bioavailable level	4.8 ± 1.1	4.8 ± 1.1	0.99
Previous androgen therapy n (%)	6 (3.3%)	5 (2.8%)	0.82
Aging Males’ Symptom (AMS) scale^‡
Total score	47.5 ± 8.9	47.1 ± 8.6	0.65
Psychological subscale	11.9 ± 4.0	11.9 ± 3.9	0.98
Somatic subscale	19.6 ± 4.4	19.5 ± 4.0	0.75
Sexual subscale	16.0 ± 3.1	15.7 ± 3.0	0.38
Radiological measurements
Bone mineral density (g/cm^2)	1.20 ± 0.10	1.22 ± 0.11	0.13
Bone mass (kg)	2.95 ± 0.50	3.06 ± 0.54	0.053
Lean body mass (kg)	58.2 ± 7.1	59.2 ± 6.5	0.14
Fat mass (kg)	25.9 ± 7.4	26.1 ± 7.3	0.85

Plus–minus values are means ±SD. AMS, aging males’ symptoms; BMI, body mass index; ITT, intention-to-treat.

*The body-mass index is the weight in kilograms divided by the square of the height in meters.

†To convert the values for total or bioavailable testosterone to ng/dL divide by 0.03467.

‡Reference values for the AMS:

Total score: ≤ 26 (no impairment), ≥ 50 (severe impairment).

Psychological subscale: ≤ 5 (no impairment), ≥ 12 (severe impairment);

Somatic subscale: ≤ 8 (no impairment), ≥ 19 (severe impairment);

Sexual subscale: ≤ 5 (no impairment), ≥11 (severe impairment [46,47]).

Table II.  Outcomes at 6 months during the randomized phase, according to treatment group.

Variable	Testosterone (N = 183)			Placebo (N = 179)			p Value
	Baseline	6 months	Mean change	Baseline	6 months	Mean change
Radiological measurements
Bone mineral density (g/cm^2)	1.20 (0.01)	1.20 (0.01)	0.004 (0.002)	1.22 (0.01)	1.22 (0.01)	0.001 (0.002)	0.41
Bone mass (kg)	2.95 (0.04)	2.96 (0.04)	0.002 (0.006)	3.06 (0.04)	3.06 (0.04)	0.002 (0.006)	0.96
Lean body mass (kg)	58.2 (0.5)	59.4 (0.5)	1.28 (0.15)	59.2 (0.5)	59.2 (0.5)	0.02 (0.10)	<0.001
Fat mass (kg)	25.9 (0.5)	24.8 (0.5)	−1.16 (0.16)	26.1 (0.5)	25.9 (0.6)	−0.14 (0.12)	<0.001
Body mass (kg)	87.1 (0.9)	87.2 (0.9)	0.12 (0.17)	88.4 (0.8)	88.2 (0.8)	−0.13 (0.17)	0.29
Aging Males’ Symptom (AMS) scale*
Total score	47.5 (0.7)	37.0 (0.8)	−10.54 (0.75)	47.1 (0.6)	39.9 (0.7)	−7.19 (0.78)	0.002
Psychological subscale	11.9 (0.3)	9.0 (0.3)	−2.89 (0.26)	11.9 (0.3)	9.7 (0.3)	−2.12 (0.29)	0.049
Somatic subscale	19.6 (0.3)	15.3 (0.4)	−4.30 (0.33)	19.5 (0.3)	16.1 (0.3)	−3.35 (0.36)	0.053
Sexual subscale	16.0 (0.2)	12.7 (0.3)	−3.37 (0.31)	15.7 (0.2)	14.1 (0.3)	−1.69 (0.27)	<0.001

Values are means (and SE between brackets), based on the ITT population with the last observation carried forward (LOCF).

*Reference values for the AMS:

 Total score: ≤ 26 (no impairment), ≥ 50 (severe impairment).

 Psychological subscale: ≤ 5 (no impairment), ≥ 12 (severe impairment);

 Somatic subscale: ≤ 8 (no impairment), ≥ 19 (severe impairment);

 Sexual subscale: ≤ 5 (no impairment), ≥11 (severe impairment [46,47])).

Figure 1.  Changes in outcomes during the trial according to treatment status. Error bars represent standard error (SE). *: p < 0.05 for difference between the two groups. **: p < 0.001 for difference between the two groups. Figure 1 is based on data from individual patients without applying imputation methods.

Figure 2.  Mean (SD) changes in lean body mass at 6 months with testosterone versus placebo in all patients (a), and in patients grouped by age (b) and by baseline serum total testosterone levels (c).

Table III.  Effect of Testosterone on the main outcomes at 6 months during the randomized phase, in subgroups.

Subgroup	No. testosterone/no. placebo	Mean difference in fat mass	p Value	Mean difference in AMS total score	p Value
All patients	183/178	−1.01 (0.20)	<0.001	−3.35 (1.08)	0.002
Age
<60 y	70/59	−0.92 (0.34)	0.008	−2.91 (1.96)	0.14
60 to <80 y	90/95	−1.19 (0.28)	<0.001	−4.31 (1.52)	0.005
≥80 y	23/24	−0.85 (0.50)	0.09	−0.83 (2.12)	0.70
Total testosterone
<10 nmol/L	73/65	−1.13 (0.31)	<0.001	−4.81 (1.74)	0.006
10 to <12 nmol/L	56/39	−0.34 (0.38)	0.38	−1.41 (1.88)	0.45
12 to <15 nmol/L	54/74	−1.43 (0.37)	<0.001	−3.47 (2.00)	0.08
Body−mass index
<30 kg/m2	121/119	−0.88 (0.24)	<0.001	−4.49 (1.30)	0.001
≥30 kg/m2	62/59	−1.27 (0.38)	0.001	−4.75 (1.41)	0.005

AMS indicates Aging Males’ Symptom scale.

Values are mean differences in the change over 6 months between the testosterone and placebo groups (and SE between brackets), based on the ITT population with the last observation carried forward (LOCF).

Table IV.  Discontinuations due to increases of serum PSA >1 ng/mL and/or >50% above value at screening.

	All patients	< 65 years	≥ 65 years
Placebo 1–6 months	4 (2.2%)	3 (2.5%)	1 (1.8%)
Testosterone 1–6 months	2 (1.1%)	2 (1.7%)	0
Open label 6–12 months	20 (6.6%)	13 (6.4%)	7 (6.7%)
Open label 12–18 months	9 (7.0%)	5 (6.4%)	4 (8.0%)

Heinemann LA, Zimmermann T, Vermeulen A, Thiel C, Hummel W. A new ‘aging males’ symptoms’ rating scale. Aging Male 1999;2:105–114.

 Google Scholar

Heinemann LA, Saad F, Zimmermann T, Novak A, Myon E, Badia X, Potthoff P, et al. The Aging Males’ Symptoms (AMS) scale: update and compilation of international versions. Health Qual Life Outcomes 2003;1:15.

 PubMedGoogle Scholar