Impact of testosterone therapy on bone turnover markers in obese males with type 2 diabetes and functional hypogonadism

Figures & data

Table 1. Study population baseline characteristics: key anthropometrical, biochemical and clinical values.

	Study population	Group P	Group T
Subjects recruited (n)	55	27	28
Age (years)	60.16 ± 7.234	62.19 ± 5.903	58.21 ± 7.941
Type 2 diabetes duration (years)	9.75 ± 6.662	10.67 ± 7.248	8.86 ± 6.041
Smoking status
Current smoker	13 (23.6%)	7 (25.9%)	6 (21.4%)
Never smoked	21 (38.2%)	13 (48.2%)	8 (28.6%)
Quit smoking	21 (38.2%)	7 (25.9%)	14 (50.0%)
Arterial hypertension	49 (89.1%)	24 (88.9%)	25 (89.3%)
Hyperlipidemia	55 (100.0%)	27 (100.0%)	28 (100.0%)
Anti-hypertensive therapy	49 (89.1%)	24 (88.9%)	25 (89.3%)
Statin therapy	29 (52.7%)	15 (55.6%)	14 (50%)
Thiazide therapy	8 (14.5%)	2 (7.4%)	6 (21.4%)
Anti-resorptive therapy	1 (1.8%)	0 (0.0%)	1 (3.6%)
Body mass index (kg/m^2)	31.9 (31–36.3)	31.4 (30.8–32.9)	33.6 (31–37.05)
Waist circumference (cm)	116.56 ± 4.969	116.64 ± 4.962	116.48 ± 5.066
Systolic blood pressure (mmHg)	136.36 ± 12.036	138.15 ± 13.240	134.64 ± 10.709
Diastolic blood pressure (mmHg)	78.18 ± 5.558	78.89 ± 5.250	77.5 ± 5.853
Fasting plasma glucose (mmol/L)	9.84 ± 1.446	9.60 ± 1.442	10.06 ± 1.439
Glycated hemoglobin A1c (%)	8.00 ± 0.914	7.89 ± 0.769	8.12 ± 1.037
Serum insulin (mIU/L)	25.47 ± 14.805	24.89 ± 13.899	26.03 ± 15.864
Homeostatic Model Assessment of Insulin Resistance index	11.08 ± 6.896	10.70 ± 6.522	11.45 ± 7.339
Total testosterone (nmol/L)	7.595 ± 1.7120	7.959 ± 1.3391	7.243 ± 1.9682
Calculated bioavailable testosterone (nmol/L)	4.167 ± 1.0505	4.611 ± 0.9542	3.739 ± 0.9711
Calculated free testosterone (pmol/L)	173.5 ± 46.07	192.1 ± 44.13	155.5 ± 41.11
Estradiol (nmol/L)	0.0904 ± 0.05192	0.0904 ± 0.0467	0.0904 ± 0.05738
25(OH)D (nmol/L)	69.78 ± 24.931	68.63 ± 23.931	70.88 ± 26.249
Total cholesterol (mmol/L)	5.311 ± 0.9327	5.307 ± 0.9719	5.314 ± 0.9111
LDL-cholesterol (mmol/L)	2.795 ± 0.8577	2.796 ± 0.9545	2.793 ± 0.7707
HDL-cholesterol (mmol/L)	1.027 ± 0.2718	1.048 ± 0.3167	1.007 ± 0.2243
Triglycerides (mmol/L)	3.180 ± 2.4503	3.515 ± 3.1508	2.857 ± 1.4926
Aging Male Symptoms Score	39 (35–43)	37 (35–41)	40 (35.5–47.75)
Serum creatinine (μmol/L)	80.71 ± 13.162	80.07 ± 12.661	81.32 ± 13.832
Lumbar bone mineral density (g/cm^2)	0.9179 ± 0.15180	0.9267 ± 0.17693	0.9093 ± 0.12564
Femoral neck bone mineral density (g/cm^2)	1.0334 ± 0.18740	0.9955 ± 0.16072	1.0699 ± 0.20626

Values are reported as mean ± SD when normally distributed, as median (interquartile range) when distribution was skewed, and as count (percentage within population/group) for clinical parameters.

Table 2. Changes in bone turnover markers in obese males with functional hypogonadism and type 2 diabetes on testosterone therapy (TTh) over the 2-year course of the study.

	Group P (n = 27)	p value	Group T (n = 27)	p value
CTX (pmol/L)
Baseline	1055 (676–1344)		897 (679–1506)
After 1 year	911 (556–1152)	0.053	523 (364–835)	<0.001*
After 2 years	453 (365–665)	0.001*	388 (265–619)	<0.001*
PINP (μg/L)
Baseline	32.7 ± 8.6		28.7 ± 7.9
After 1 year	32.1 ± 9.4	1.000	25.3 ± 6.8	0.023*
After 2 years	28.4 ± 7.0	0.030*	20.8 ± 6.1	<0.001*

Group P participants were receiving placebo during first year of the study and were then switched to testosterone undecanoate. Group T participants were receiving testosterone undecanoate throughout the entire 2-year course of the study. CTX levels are reported as median (inter-quartile range) and PINP levels as mean ± SD. p Values (with Bonferroni correction applied) marked with an asterisk (*) represent statistically significant change from the baseline.

Table 3. Changes in bone mineral density in obese males with functional hypogonadism and type 2 diabetes on testosterone therapy (TTh) over the 2-year course of the study.

	Group P (n = 16)	p value	Group T (n = 16)	p value
DXA femoral hip (g/cm^2)
Baseline	0.9765 ± 0.18417		0.9270 ± 0.12338
After 2 years	1.0023 ± 0.12486	0.619	0.9940 ± 0.21152	0.194
DXA lumbar spine (g/cm^2)
Baseline	1.0328 ± 0.14955		1.1231 ± 0.22574
After 2 years	1.0697 ± 0.19205	0.390	1.1982 ± 0.23891	0.019*

Group P participants were receiving placebo during first year of the study and were then switched to testosterone undecanoate. Group T participants were receiving testosterone undecanoate throughout the entire 2-year course of the study. Values are reported as mean ± SD. p Values marked with an asterisk (*) represent statistically significant change from the baseline.

Table 4. Changes in testosterone levels in obese males with functional hypogonadism and type 2 diabetes on testosterone therapy (TTh) over the 2-year course of the study.

	Group P (n = 27)	p value	Group T (n = 28)	p value
Total testosterone (nmol/L)
Baseline	7.96 ± 1.34		7.24 ± 1.97
12 months	9.83 ± 1.51	<0.001*	17.04 ± 3.07	<0.001*
24 months	17.92 ± 2.21	<0.001*	23.50 ± 4.91	<0.001*
Calculated bioavailable testosterone (nmol/L)
Baseline	4.61 ± 0.95		3.74 ± 0.97
12 months	5.73 ± 0.89	<0.001*	9.50 ± 1.89	<0.001*
24 months	10.72 ± 1.84	<0.001*	13.93 ± 3.39	<0.001*
Calculated free testosterone (pmol/L)
Baseline	192.07 ± 44.13		155.54 ± 41.11
12 months	242.00 ± 42.23	<0.001*	403.84 ± 90.34	<0.001*
24 months	454.56 ± 87.78	<0.001*	594.04 ± 147.09	<0.001*

Group P participants were receiving placebo during first year of the study and were then switched to testosterone undecanoate. Group T participants were receiving testosterone undecanoate throughout the entire 2-year course of the study. Values are reported as mean ± SD. p Values marked with an asterisk (*) represent statistically significant change from the baseline.