Testosterone treatment longer than 1 year shows more effects on functional hypogonadism and related metabolic, vascular, diabetic and obesity parameters (results of the 2-year clinical trial)

Figures & data

Table 1. Study population characteristics. Values reported as mean ± SD or as count (percentage).

Variable	Group P (n = 27)	Group T (n = 28)	Total (n = 55)
Age (years)	62.19 ± 5.90	58.21 ± 7.94	60.16 ± 7.23
Body weight (kg)	99.98 ± 10.97	103.14 ± 13.47	101.59 ± 12.30
BMI (kg/m^2)	32.63 ± 3.67	34.03 ± 4.37	33.34 ± 4.07
Total serum testosterone (nmol/L)	7.96 ± 1.34	7.24 ± 1.97	7.59 ± 1.71
Insulin resistance (HOMA-IR index)	10.70 ± 6.52	11.45 ± 7.34	11.08 ± 6.90
HbA1c (%)	7.89 ± 0.77	8.12 ± 1.04	8.00 ± 0.91
HbA1c (%) ≥ 7	32 (85.2%)	25 (89.3%)	48 (87.3%)
HbA1c (%) < 7	4 (14.8%)	3 (10.7%)	7 (12.7%)
Duration of T2D (years)	10.67 ± 7.25	8.86 ± 6.04	9.75 ± 6.66
0–4	4 (14.8%)	6 (21.4%)	10 (18.2%)
5–9	10 (37.0%)	14 (50.0%)	24 (43.6%)
10–14	6 (22.2%)	4 (14.3%)	10 (18.2%)
15+	7 (25.9%)	4 (14.3%)	11 (20.0%)
Arterial hypertension	26 (96.3%)	25 (89.3%)	51 (92.7%)
Dyslipidemia	27 (100.0%)	28 (100.0%)	55 (100.0%)
Current smoker	13 (48.1%)	8 (28.6%)	21 (38.2%)

Figure 1. Pooled results of 1 year of TTh on glycated hemoglobin A1c (HbA1c), n = 55.

Figure 2. Pooled results of 1 year of TTh on HOMA-IR, n = 55.

Figure 3. Pooled results of 1 year of TTh on non-HDL cholesterol, n = 55.

Table 2. Effects of testosterone treatment on parameters of metabolic syndrome after 12 months of testosterone replacement therapy—pooled results for both groups P and T (n = 55).

Parameter	Baseline	After 12 months	Change	95% CI	p Value
BMI (kg/m^2)*	31.60 (30.40 to 34.90)	31.10 (29.20 to 34.60)	−0.70 (−1.30 to 0.00)	(n/a)	<0.001
Waist circumference (cm)*	115.00 (113.40 to 119.30)	113.00 (110.00 to 118.00)	−1.50 (−2.90 to −0.70)	(n/a)	<0.001
HOMA-IR^a	10.82 ± 6.52	6.56 ± 3.78	−4.26 ± 3.65	−5.25, −3.28	<0.001
FPG (mmol/L)^b	9.77 ± 1.40	8.57 ± 1.17	−1.21 ± 1.07	−1.50, −0.92	<0.001
HbA1c (%)	7.89 ± 0.91	6.93 ± 0.72	−0.96 ± 0.73	−1.15, −0.76	<0.001
Total cholesterol (mmol/L)	5.11 ± 0.85	4.41 ± 0.65	−0.69 ± 0.57	−0.85, −0.54	<0.001
LDL cholesterol (mmol/L)	2.67 ± 0.67	2.39 ± 0.68	−0.28 ± 0.58	−0.43, −0.12	0.001
HDL cholesterol (mmol/L)	1.04 ± 0.26	1.08 ± 0.21	0.04 ± 0.23	−0.02, 0.10	0.187
Triglycerides (mmol/L)^c	2.94 ± 1.79	2.42 ± 1.53	−0.51 ± 1.17	−0.83, −0.19	0.002
Non-HDL cholesterol (mmol/L)	4.07 ± 0.83	3.33 ± 0.64	−0.74 ± 0.62	−0.90, −0.57	<0.001
Systolic blood pressure (mmHg)	135.27 ± 14.02	137.01 ± 13.35	1.75 ± 13.83	−1.99, 5.48	0.354
Diastolic blood pressure (mmHg)*	80.00 (70.00 to 80.00)	80.00 (75.00 to 85.00)	0.00 (−9.00 to 10.00)	(n/a)	0.460
TT (nmol/L)	8.51 ± 2.18	17.47 ± 2.70	8.96 ± 3.04	8.14, 9.78	<0.001
Calculated BT (nmol/L)	4.72 ± 1.36	10.10 ± 1.95	5.38 ± 2.06	4.83, 5.94	<0.001
cFT (pmol/L)	197.99 ± 60.05	428.74 ± 91.90	230.75 ± 93.12	205.58, 255.93	<0.001
SHBG (nmol/L)^d	23.00 (17.30 to 30.00)	25.00 (20.00 to 32.00)	1.00 (−3.00 to 5.00)	(n/a)	0.303
FMD (%)	4.23 ± 2.64	7.35 ± 3.92	3.12 ± 4.97	1.78, 4.46	<0.001
FMD/NMD	0.29 ± 0.20	0.46 ± 0.24	0.17 ± 0.28	0.09, 0.24	<0.001
IMT (mm)	0.83 ± 0.11	0.75 ± 0.08	−0.08 ± 0.06	−0.09, −0.06	<0.001

Values reported as mean ± SD or as median (interquartile range). Paired t-test or Wilcoxon signed ranks test p Values reported. HOMA-IR, homeostatic model assessment of insulin resistance; SHBG, sex-hormone binding globulin; FMD, flow-mediated dilatation; FMD/NMD, flow-mediated dilatation (%) divided by nitrogen-mediated dilatation (%); IMT, intima-media thickness.

^aData distribution deviates from normal according to Shapiro–Wilk test (p = 0.004); HOMA-IR mean difference after 12 months, two outliers removed to ensure normal distribution (n = 53): −3.87 ± 3.08; 95% CI: −4.72, −3.02; p < 0.001.

^bData distribution deviates from normal according to Shapiro–Wilk test (p = 0.004); FPG mean difference after 12 months, one outlier removed to ensure normal distribution (n = 54): −1.28 ± 0.89 mmol/L; 95% CI: −1.53, −1.04; p < 0.001.

^cData distribution deviates from normal according to Shapiro–Wilk test (p < 0.001); triglycerides mean difference after 12 months, three outliers removed to ensure normal distribution (n = 52): −0.31 ± 0.82 mmol/L; 95% CI: −0.54, −0.08; p = 0.009.

^dData distribution deviates from normal according to Shapiro–Wilk test (p < 0.05); values reported as median (interquartile range); 95% CI values unavailable; Wilcoxon signed ranks test p value (exact two-sided) reported.

Figure 4. Pooled results of 1 year of TTh on FMD of brachial artery, n = 55.

Figure 5. Pooled results of 1 year of TTh on IMT of carotid arteries, n = 55.

Table 3. Effects of testosterone treatment on parameters of metabolic syndrome after 24 months of therapy—results for group T (n = 28).

Parameter	Baseline (group T)	After 24 months	Change	95% CI	p Value
BMI (kg/m^2)	34.03 ± 4.37	32.45 ± 4.74	−1.59 ± 1.44	−2.14, −1.03	<0.001
Waist circumference (cm)	116.48 ± 5.07	112.96 ± 5.21	−3.51 ± 2.73	−4.57, −2.46	<0.001
HOMA-IR	11.45 ± 7.34	5.51 ± 4.21	−5.94 ± 4.31	−7.61, −4.26	<0.001
FPG (mmol/L)	10.06 ± 1.44	8.23 ± 1.09	−1.83 ± 0.20	−2.23, −1.43	<0.001
HbA1c (%)	8.12 ± 1.04	6.60 ± 0.77	−1.51 ± 0.90	−1.87, −1.16	<0.001
Total cholesterol (mmol/L)	5.31 ± 0.91	4.34 ± 0.61	−0.97 ± 0.59	−1.20, −0.74	<0.001
LDL cholesterol (mmol/L)^a	2.79 ± 0.77	2.39 ± 0.56	−0.40 ± 0.65	−0.65, −0.15	0.003
HDL cholesterol (mmol/L)	1.01 ± 0.22	1.15 ± 0.22	0.15 ± 0.21	0.07, 0.23	0.001
Triglycerides (mmol/L)^b	2.86 ± 1.49	1.86 ± 0.78	−0.99 ± 1.23	−1.47, −0.52	<0.001
Non-HDL cholesterol (mmol/L)	4.31 ± 0.90	3.19 ± 0.62	−1.12 ± 0.67	−1.38, −0.86	<0.001
Systolic blood pressure (mmHg)	134.64 ± 10.71	133.75 ± 10.77	−0.89 ± 12.59	−5.78, 3.99	0.710
Diastolic blood pressure (mmHg)	77.50 ± 5.85	77.32 ± 6.24	−0.18 ± 8.01	−3.28, 2.93	0.907
TT (nmol/L)	7.24 ± 1.97	23.50 ± 4.81	16.26 ± 4.89	14.36, 18.15	<0.001
Calculated BT (nmol/L)^c	3.74 ± 0.97	13.93 ± 3.39	10.19 ± 3.42	8.86, 11.51	<0.001
cFT (pmol/L)^d	155.54 ± 41.11	594.04 ± 147.09	438.50 ± 146.87	381.55, 495.45	<0.001
SHBG (nmol/L)^e	26.50 (17.25 to 35.00)	23.50 (19.00 to 31.50)	−2.00 (−3.75 to 5.75)	(n/a)	0.976
FMD (%)	4.68 ± 2.82	7.14 ± 3.19	2.46 ± 3.97	0.75, 0.92	0.003
FMD/NMD	0.31 ± 0.21	0.44 ± 0.21	0.13 ± 0.29	0.02, 0.24	0.023
IMT (mm)	0.86 (0.82 to 0.93)	0.73 (0.69 to 0.76)	−0.14 (−0.17 to −0.10)	(n/a)	<0.001
AMS sexual sub-score (q. 15 + 16 + 17)	9.00 (8.00 to 11.75)	8.00 (6.00 to 9.00)	−7.00 (−10.00 to −1.25)	(n/a)	0.005
AMS total score	40.00 (35.50 to 47.75)	39.00 (31.00 to 46.00)	−35.50 (−42.50 to −7.75)	(n/a)	0.060

Values reported as mean ± SD or as median (interquartile range). Paired t-test or Wilcoxon signed ranks test p values reported. HOMA-IR, homeostatic model assessment of insulin resistance; SHBG, sex-hormone binding globulin; FMD, flow-mediated dilatation; FMD/NMD, flow-mediated dilatation (%) divided by nitrogen-mediated dilatation (%); IMT, intima-media thickness; AMS, Aging Males’ Symptoms questionnaire.

^aData distribution deviates from normal according to Shapiro–Wilk test (p = 0.009); LDL mean difference after 24 months, one outlier removed to ensure normal distribution (n = 27): −0.32 ± 0.49 mmol/L; 95% CI: −0.51, −0.12; p = 0.002.

^bData distribution deviates from normal according to Shapiro–Wilk test (p < 0.001); triglycerides mean difference after 24 months, two outliers removed to ensure normal distribution (n = 26): −0.72 ± 0.75 mmol/L; 95% CI: −1.02, −0.42; p < 0.001.

^cData distribution deviates from normal according to Shapiro–Wilk test (p = 0.017); calculated BT mean difference after 24 months, one outlier removed to ensure normal distribution (n = 27): 9.77 ± 2.68 nmol/L; 95% CI: 8.71, 10.83; p < 0.001.

^dData distribution deviates from normal according to Shapiro–Wilk test (p = 0.021); cFT mean difference after 24 months, one outlier removed to ensure normal distribution (n = 27): 421.11 ± 116.65 pmol/L; 95% CI: 374.96, 467.26; p < 0.001.

^eData distribution deviates from normal according to Shapiro–Wilk test (p < 0.05); values reported as median (interquartile range); 95% CI values unavailable; Wilcoxon signed ranks test p value (exact two-sided) reported.

Figure 6. Group T results of 2 years of TTh on glycated hemoglobin A1c (HbA1c), n = 28.

Figure 7. Group T results of 2 years of TTh on HOMA-IR, n = 28.

Figure 8. Group T results of 2 years of TTh on non-HDL cholesterol, n = 28.

Figure 9. Group T results of 2 years of TTh on FMD of brachial artery, n = 28.

Figure 10. Group T results of 2 years of TTh on IMT of carotid arteries, n = 28.