Effect of 12-months testosterone replacement therapy on bone mineral density and markers of bone turnover in testicular cancer survivors – results from a randomized double-blind trial

Figures & data

Table 1. Baseline characteristics of 69 included testicular cancer survivors.

	Testosterone (N = 35)	Placebo (N = 34)
Age at study inclusion (median, IQR)	42 (35–47)	44 (37–49)
Time since orchiectomy, years (median, IQR)	5 (3–10)	5 (3–13)
Treatment, No. (%)
Orchiectomy only	10 (29)	21 (62)
Cisplatin-based chemotherapy	13 (37)	8 (24)
Abdominal radiotherapy	6 (17)	2 (6)
Chemotherapy and radiotherapy	4 (11)	2 (6)
Orchiectomy and radiotherapy to the contralateral testicle due to germ cell neoplasia in situ	2 (6)	1 (3)
Luteinizing hormone, IU/L (median, IQR)	8.0 (5.0–9.0)	7.7 (6.0–9.9)
Free testosterone, pmol/L (median, IQR)	329.7 (291.6–409.3)	315.7 (263.7–382.8)
Total testosterone, nmol/L (median, IQR)	17.6 (15.1–20.6)	15.0 (13.3–18.2)
Body mass index, kg/m^2 (median, IQR)	24.8 (23.3–27.6)	27.0 (24.0–28.6)
Smoking, No. (%)
Never	13 (37)	13 (38)
Current	13 (37)	12 (35)
Former	8 (23)	9 (27)
Alcohol, units per week, No. (%)
None	6 (17)	6 (18)
< 7	13 (37)	16 (47)
7–14	10 (29)	9 (27)
14-21	3 (9)	3 (9)
> 21	2 (6)	0 (0)
Level of physical activity, No. (%)
Reading, watching tv, etc	3 (9)	3 (9)
Walking, riding a bicycle, etc	14 (40)	16 (47)
Practising sport at least four times per week	16 (46)	13 (38)
Intense exercise several times per week	1 (3)	2 (6)
PTH, pg/mL (median, IQR)	4.8 (4.2–5.9)	4.8 (3.8–5.0)
TSH uIU/mL (median, IQR)	1.7 (1.2–2.5)	2.4 (1.7–3.1)
Free, ionized calcium, mmol/L (median, IQR)	1.22 (1.19–1.23)	1.20 (1.19–1.22)
Alkaline Phosphatase, U/L (median, IQR)	60.0 (55.0–69.0)	67.5 (54.0–80.0)
25-hydroxy vitamin D, nmol/L (median, IQR)	38.5 (30.0–48.0)	39.5 (28.0–74.0)
Vitamin D supplement at baseline, No. (%)	4 (11)	5 (15)

Figure 1. Mean scores with 95% confidence intervals of whole-body bone mass density (BMD), lumbar spine BMD and left femoral neck BMD at baseline, 6 months, 12 months, and 3 months post-treatment (15 months). Purple lines represent mean values for patients treated with placebo and orange lines represent patients treated with testosterone. BMD is presented as total BMD (g/cm²) and T-score.

Table 2. Mean difference in outcomes between patients treated with testosterone and patients treated with placebo during treatment (6 and 12 months) and 3 months post-treatment (15 months). The difference in changes between groups is reported with 95% confidence intervals and was estimated with a linear mixed effects model. CTX-1: C-terminal telopeptides of Type I collagen. PINP: Procollagen Type I N-Terminal Peptide.

	6 months	12 months	15 months
L2-L4 BMD
Total (g/cm^2)	0.01 (−0.01, 0.02)	0.01 (−0.01, 0.03)	0.00 (−0.02, 0.02)
T-score	0.08 (−0.06, 0.23)	0.07 (−0.10, 0.25)	−0.01 (−0.18, 0.16)
BMD of left femoral neck
Total (g/cm^2)	−0.02 (−0.07, 0.03)	0.00 (−0.01, 0.02)	0.00 (−0.02, 0.01)
T-score	0.04 (−0.04, 0.12)	0.05 (−0.05, 0.14)	0.12 (−0.01, 0.25)
Total body BMD
Total (g/cm^2)	0.01 (0.00, 0.03)	0.01 (−0.01, 0.02)	0.00 (−0.01, 0.02)
T-score	0.17 (−0.01, 0.34)	0.08 (−0.08, 0.23)	0.06 (−0.11, 0.22)
CTX-1 (ng/L)	27.94 (−25.09, 80.98)	−0.102 (−57.15, 56.95)	−28.46 (−85.41, 28.48)
P1NP (µg/L)	6.758 (−0.43, 13.95)	11.65 (3.96, 19.35)	7.242 (−0.43, 14.92)

Figure 2. Mean scores with 95% confidence intervals of C-terminal telopeptides of Type 1 collagen (CTX-1) and Procollagen Type 1 N-Terminal Peptide (P1NP) at baseline, 6 months, 12 months, and 3 months post-treatment (15 months). Purple lines represent mean values for patients treated with placebo and orange lines represent patients treated with testosterone.

Data availability statement

According to Danish law individual patient data that underlie the results reported in this paper cannot be shared. Anonymized access to data might be possible, please contact the corresponding author regarding this. Study protocol can be shared upon request.