Journal Article

Association of testosterone-induced increase in neutrophil and monocyte counts with thromboembolic events: The TRAVERSE trial

Nissen, Steven E., Bhasin, Shalender, Shang, Yili V., Li, Xue, Miller, Michael G., Patel, Rinal, Lincoff, A. Michael, Chan, Anna, Travison, Thomas G., Gagliano-Jucá, Thiago, Artz, Andrew S., Pencina, Karol M.

2025

Overview

•In the TRAVERSE trial, testosterone replacement therapy in hypogonadal men increased circulating neutrophil and monocyte counts and decreased lymphocyte and platelet counts.•As reported previously, testosterone replacement therapy in the TRAVERSE Trial was associated with a higher incidence of pulmonary embolism than placebo treatment. Here we show that changes from baseline in neutrophil and monocyte counts in testosterone-treated men were positively associated with occurrence of VTE.•Men with higher baseline and on-treatment neutrophil and monocyte counts were at higher risk of MACE.•Neutrophil and monocyte counts should be considered in the evaluation of VTE risk prior to starting TRT in men with hypogonadism. In epidemiological studies, higher leukocyte and platelet counts are associated with increased risk of cardiovascular events. Effects of testosterone replacement therapy (TRT) on leukocyte subsets and platelets in men with hypogonadism and association of circulating leukocyte subtypes and platelets during TRT with cardiovascular events remain unknown. In the TRAVERSE Trial, 5,204 men, 45-80 years with hypogonadism and preexisting or increased risk of cardiovascular disease (CVD) were randomized to transdermal testosterone or placebo gel daily for up to 5 years. We determined the effect of TRT on neutrophils, monocytes, lymphocytes and platelets and association of changes in leukocyte subtypes and platelets with risk of major adverse cardiovascular (MACE) and venous thromboembolism (VTE) events. TRT was associated with significantly greater increase in neutrophils and monocytes, and greater decrease in lymphocytes and platelets than placebo. Changes in neutrophil (odds ratio for 1 SD increase in cell count (OR) 1.32 [1.01, 1.73]) and monocyte (OR 1.39 [1.08, 1.79]) counts were associated with increased risk of VTE, accounting for TRT. Neutrophil and monocyte counts at baseline and on-treatment were also associated with increased risk of MACE, adjusting for treatment (baseline: neutrophils OR 1.18 [1.06,1.31], monocytes OR 1.16 [1.05,1.29]; on-treatment neutrophils: OR 1.25 [1.12, 1.40]; monocytes: OR 1.18 [1.06,1.31]). TRT increased circulating neutrophils and monocytes and decreased lymphocytes and platelets in men with hypogonadism. Changes in monocyte and neutrophil counts were associated with increased risk of VTE. Neutrophil and monocyte counts should be considered when evaluating VTE risk in hypogonadal men treated with TRT. URL:https://clinicaltrials.gov/study/NCT03518034. Unique identifier: NCT03518034. The study was initially registered on March 5, 2018, and the first participant was enrolled on May 23, 2018.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Aged / Aged, 80 and over / Blood / Blood platelets / Cardiovascular disease / Cardiovascular diseases / Clinical trials / Epidemiology / Health risks / Health services / Heart attacks / Heart diseases / Hormone replacement therapy / Hormone Replacement Therapy - methods / Humans / Hypogonadism / Hypogonadism - blood / Hypogonadism - complications / Hypogonadism - drug therapy / Leukocyte Count / Leukocytes / Leukocytes (neutrophilic) / Lymphocytes / Male / Middle Aged / Monocytes / Monocytes - drug effects / Neutrophils / Neutrophils - drug effects / Pathophysiology / Placebos / Platelets / Prostate cancer / Pulmonary embolisms / Risk / Testosterone / Testosterone - administration & dosage / Testosterone - adverse effects / Testosterone - therapeutic use / Thromboembolism / Thrombosis / Venous Thromboembolism - blood / Venous Thromboembolism - epidemiology