Table 3.

Change over time in secondary outcomes and safety parameters in the TD + TTh and TD + placebo study arms

	TD + placebo			TD + TTh			TD + TTh vs. TD + placebo
	V1	V2	Contrast within group	V1	V2	Contrast within group	Contrast between groups at V2
Symptom score
IPSS total score	15.49 [13.74;17.25]	14.78 [12.96;16.59]	− 0.72 [− 2.88;1.44] p = 0.514	15.40 [13.43;17.37]	15.69 [13.72;17.66]	0.29 [− 2.07;2.65] p = 0.809	0.92 [− 1.78;3.61] p = 0.506
IPSS bothering score	2.88 [2.48;3.29]	2.75 [2.32;3.18]	− 0.13 [− 0.72;0.45] p = 0.659	2.94 [2.47;3.41]	2.25 [1.78;2.73]	− 0.69 [− 1.35;− 0.03] p = 0.042	− 0.50 [− 1.14;0.15] p = 0.131
NIH-CPSI	18.63 [16.92;20.33]	14.48 [12.65;16.32]	− 4.14 [− 6.63;− 1.65] p = 0.001	18.88 [16.97;20.79]	14.15 [12.17;16.14]	− 4.73 [− 7.47;− 1.99] p = 0.001	− 0.33 [− 3.05; 2.38] p = 0.810
Prostate diameters (mm)
Transverse	88.77 [66.63–110.90]	61.89 [39.05–84.74]	− 26.88 [− 58.45;4.69] p = 0.095	83.25 [59.53–106.96]	59.14 [33.61–84.67]	− 24.11 [− 58.64;10.43] p = 0.171	− 2.75 [− 37.32;31.83] p = 0.876
Longitudinal	55.37 [54.12–56.62]	56.42 [55.13–57.71]	1.05 [− .73;2.83] p = 0.249	55.55 [54.21–56.90]	56.12 [54.68–57.57]	0.57 [− 1.38;2.52] p = 0.568	− 0.29 [− 2.25;1.66] p = 0.769
Anteroposterior	39.75 [39.10–40.40]	40.00 [39.33–40.67]	0.25 [− 0.68;1.17] p = 0.600	39.87 [39.18–40.57]	41.15 [40.40–41.90]	1.28 [0.27;2.29] p = 0.013	1.15 [0.13;2.17] p = 0.027
Prostate adenoma (mm)
Transverse	46.58 [45.79–47.37]	46.23 [45.42–47.04]	− 0.35 [− 1.47;0.78] p = 0.548	46.53 [45.65–47.42]	47.21 [46.18–48.24]	0.67 [− 0.68;2.03] p = 0.329	0.97 [− 0.35;2.30] p = 0.148
Longitudinal	47.44 [46.56–48.32]	48.04 [47.14–48.95]	0.60 [− 0.65;1.86] p = 0.344	47.39 [46.45–48.33]	47.52 [46.51–48.53]	0.13 [− 1.24;1.50] p = 0.853	− 0.52 [− 1.89;0.85] p = 0.454
Anteroposterior	36.28 [35.73–36.84]	36.21 [35.64–36.77]	− 0.08 [− 0.86;0.70] p = 0.845	36.35 [35.76–36.95]	37.26 [36.59–37.92]	0.90 [0.02;1.79] p = 0.045	1.05 [0.16;1.93] p = 0.020
Prostatic arterial blood flows
Arterial peak systolic velocity (cm/s)	16.74 [15.83–17.66]	16.33 [15.37–17.29]	− 0.41 [− 1.73;0.91] p = 0.540	16.98 [16.01–17.96]	14.67 [13.62–15.75]	− 2.32 [− 3.74;− 0.89] p = 0.001	− 1.67 [− 3.10;− 0.23] p = 0.023
Acceleration (m/s2)	103.80 [96.49–111.15]	102.43 [94.79–110.08]	− 1.37 [− 11.88;9.15] p = 0.799	106.22 [98.39–114.05]	89.26 [80.38–98.14]	− 16.96 [− 28.70;− 5.22] p = 0.005	− 13.18 [− 24.96;− 1.39] p = 0.028
Hormone and binding hormone parameters
Total Testosterone (nmol/L)	10.84 [9.13;12.56]	12.81 [10.98;14.64]	1.97 [− 0.53;4.46] p = 0.123	10.57 [8.66;12.48]	16.60 [14.66;18.55]	6.03 [3.32;8.74] p < 0.0001	3.79 [1.11;6.47] p = 0.006
Calculated free testosterone (pmol/L)	169.73 [128.80;210.66]	196.74 [149.88;243.60]	27.00 [− 34.62;88.63] p = 0.390	158.03 [111.89;204.175]	308.12 [258.06;358.18]	150.09 [82.72;217.45] p < 0.0001	111.38 [42.17;180.59] p = 0.002
SHBG (nmol/L)	48.60 [44.86;52.35]	52.14 [47.84;56.43]	3.53 [− 2.13;9.20] p = 0.222	48.57 [44.35;52.78]	46.39 [41.93;50.85]	− 2.18 [− 8.26;3.90] p = 0.483	− 5.74 [− 11.99;0.50] p = 0.072
Safety parameters
Hematocrit (%)	43.26 [42.48;44.04]	41.09 [40.19;41.99]	− 2.17 [− 3.36;− 0.99] p < 0.0001	43.25 [42.33;44.16]	43.92 [42.58;45.26]	0.67 [− 0.93;2.27] p = 0.411	2.83 [1.20;4.46] p = 0.001
PSA (ng/mL)	1.99 [1.62;2.46]	1.81 [1.46;2.25]	0.91 [0.71;1.16] p = 0.438	1.94 [1.57;2.40]	2.25 [1.82;2.78]	1.16 [0.91;1.47] p = 0.228	1.24 [0.92;1.69] p = 0.164

Data are derived from multilevel mixed-effects linear regression. Results are reported as estimated marginal means (EMM) and 95% confidence interval at V1 (baseline) and V2 (after 24 weeks) in the TD study arms. Contrast in EMM and 95% confidence interval within the same group and between groups at V2 are also reported. Bold data are intended to highlight statistical significant changes

TD testosterone-deficient; TTh testosterone therapy