Supplemental Table 1. Effect of Testosterone Treatment on Organ Weight in Mice (% of body weight, mean ± SD).

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1 Supplemental Table 1. Effect of Testosterone Treatment on Organ Weight in Mice ( of body weight, mean ± SD). a. Steady-state, high dose T (0 mg/kg, weekly for 7 mo, n = per group) Sample F M T Kidney weight 1.19± ± ±0.13 a 1.8±0.19 b Spleen weight 0.41± ± ± ±0.03 a p < 0.001, smaller than all other groups. b p < 0.001, greater than all other groups, One-way ANOVA followed with Tukey s test. b. Short-term, high dose T (0 mg/kg, 2 injection in 2 weeks, n = 8 per group) Sample F FT T Kidney weight 1.01± ±0.23 a 0.92± ±0.2 b Spleen weight 0.39± ± ± ±0.0 a p < 0.001, FT > F; b p < 0.001, T >. One-way ANOVA followed with Tukey s test. c. Short-term low dose T ( mg/kg, 3 injections in 2 weeks, n = 7 per group) Sample F FT P, t test Kidney weight 1.0 ± ± 0.2 <0.0 Spleen weight 0.30 ± ± F: vehicle-treated female, M: vehicle-treated male, : vehicle-treated castrated male, FT: testosterone-treated female, T: testosteronetreated castrated male.

2 Supplemental Table 2. Selected hematological parameters a. Comparison between intact males and females (results are shown as mean ± SD, n = 8 for males, and n = 12 for females, t test). Female mean SD Male mean SD p value b. Comparison between castrated males with and without short-term high dose testosterone treatment (n = 8, t test). mean SD T mean SD p value c. Comparison between females with and without short-term low dose testosterone treatment (n = 7, t test). F mean SD FT mean SD p value

3 d. Comparison between females with and without long-term high dose testosterone treatment (n = 8, t test). F mean SD FT mean SD p value e. Comparison between castrated males with and without long-term high dose testosterone treatment (n = 8, t test). mean SD T mean SD p value : red blood cells, : hematocrits, : hemoglobin, : distribution width, : mean corpuscular volume, : mean corpuscular hemoglobin concentration, : hemoglobin distribution width, retic: reticulocyte count, : reticulocyte hemoglobin content. F: female, : castrated male.

4 Serum testosterone (ng/ml) * ** 0.0 control d1 d3 d Supplemental Figure 1. Serum testosterone at various time points post injection. Adult female mice were injected with testosterone propionate (0 mg/kg) on day 0. Blood was collected on day 1, 3, and (n = 3 1). Serum testosterone was analyzed by LC-MS/MS. *p < 0.001, lower than all other groups, **p<0.001, greater than all other groups, One-way ANOVA, followed with Tukey s test.

5 Erythrocyte packing difference () Whole blood viscosity (cp) B Hematocrits () A ** C # T # T. T Day 0 Day 14 T Shear rate (s -1 ) P i = Plasma viscosity (cp, 172 s -1 ) Elongation rate () D E P m = 0.96 T T Shear force (Pa) Supplemental Figure 2. Effect of short-term testosterone treatment on blood viscosity in adult castrated male mice. Adult castrated male mice were injected weekly with vehicle or testosterone propionate (0 mg/kg) for two weeks. (A) Hematocrits, (B) erythrocyte packing difference, (C) whole blood viscosity, (D) plasma viscosity, measured at shear rate of 172s -1, (E) erythrocyte elongation rate. Results are shown as mean ± SD, n = 6-8. : castrated male, T: castrated male treated with testosterone. ** p < 0.01, paired t test; # p < 0.0, p < 0.01, unpaired t test.

6 Whole blood viscosity (cp) A F FT Shear Rate (1/s) Elongation rate () B F FT Shear force (Pa) Supplemental Figure 3. Effect of short-term low dose testosterone treatment on blood viscosity in adult female mice. Adult female mice were treated with testosterone propionate ( mg/kg) on day 0, 7, and 11. Blood was collected on day 14 for the measurements. (A) whole blood viscosity, and (B) erythrocyte deformability. Results are shown are mean ± SD, n = 7 per group. F: vehicle-treated, FT: testosterone-treated.

7 Hematocrits () Whole blood viscosity (cp) A C T T P m = Shear rate (s -1 ) Plasma viscosity (cp, 172 s -1 ) Elongation () B D T T P m = Shear force (Pa) # Supplemental Figure 4. Effect of long-term testosterone treatment on blood viscosity in adult castrated male mice. Adult castrated male mice were treated weekly with testosterone propionate (0 mg/kg) for 7 months. (A) hematocrits (B) plasma viscosity,(c) whole blood viscosity, and (D) erythrocyte deformability. Results are shown are mean ± SD, n = per group. # p < 0.0, p < 0.01, unpaired t test. : castrated males, T: castrated males treated with testosterone.

8 WBV M shear rate 1/s Elongation rate () M shear rate (Pa) Supplemental Figure. Effect of long-term castration on blood viscosity and erythrocyte elongation rate in adult male mice. Results are repotted from data presented in Figure 1 (intact male) and Supplemental Figure 4, long-term castrated male). Hematopoietic indices are shown in Table 1a and Table 1e. Results are shown are mean ± SD, n = per group. M: normal males, : castrated males.