Differential effects of testosterone on circulating neutrophils, monocytes, and platelets in men: Findings from two trials

Background Testosterone treatment increases erythrocytes in men, but its effects on leukocyte and platelet counts are unknown and could affect its safety. Objective To determine whether testosterone affects circulating leukocytes and platelets in men. Methods Secondary analyses of two randomized testosterone trials were performed: the 5α‐reductase (5aR) and OPTIMEN trials. In 5aR trial, 102 healthy men, 21‐50 years (mean age 38), received a long‐acting GnRH agonist, and 50, 125, 300, or 600 mg/week testosterone enanthate (TE) plus placebo or 2.5 mg / day dutasteride for 20 weeks. In OPTIMEN, 78 functionally limited men, ≥65 years (mean age 72) with protein intake ≤ 0.83 g kg −1  day −1 , were randomized to controlled diets with 0.8 g kg −1  day −1 protein or 1.3 g kg −1  day −1 protein plus placebo or TE (100 mg/week) for 6 months. Changes from baseline in total and differential leukocyte count, and platelet count were evaluated. Results In 5aR, testosterone administration was associated with increases in total leukocyte (estimated change from baseline 40, 490, 1230, and 1280 cells/µL, P  < .001), neutrophil (65.1, 436.1, 1177.2, and 1192.2 cells/µL, P  < .001), monocyte (−20.2, 24.5, 90.6, and 143.9 cells/µL, P  < .001), platelet (−7.3, 8.4, 8.7, and 8.9 × 10 3 cells/µL, P  = .033), and erythrocyte counts. Testosterone did not affect absolute lymphocyte count. Similar increase in total leukocyte count was observed with testosterone treatment in OPTIMEN (change 0.77 × 10 3 cells/µL, P vs placebo = 0.004). Conclusions Testosterone administration in men differentially increases neutrophil and monocyte counts. These findings, together with its erythropoietic effects, suggest that testosterone promotes the differentiation of hematopoietic progenitors into the myeloid lineage. These findings have potential mechanistic, therapeutic, and safety implications.