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

Testosterone replacement therapy was associated with significantly greater increases in neutrophil and monocyte counts compared to placebo.

• Study population: 5,204 men aged 45-80 years with hypogonadism and preexisting or increased risk of cardiovascular disease
• Participants were randomized to transdermal testosterone or placebo gel daily for up to 5 years in the TRAVERSE Trial (NCT03518034)
• The increases in neutrophils and monocytes were statistically significant compared to placebo
• TRT also produced greater decreases in lymphocytes and platelets than placebo

Changes in neutrophil counts were associated with increased risk of venous thromboembolism (VTE), independent of treatment assignment.

• Odds ratio for 1 SD increase in neutrophil count: OR 1.32 [95% CI: 1.01, 1.73]
• This association was assessed accounting for TRT assignment
• The association was based on changes in neutrophil counts during the trial period

Changes in monocyte counts were associated with increased risk of VTE, independent of treatment assignment.

• Odds ratio for 1 SD increase in monocyte count: OR 1.39 [95% CI: 1.08, 1.79]
• This association was assessed accounting for TRT assignment
• Monocyte changes showed a stronger association with VTE risk than neutrophil changes

Baseline neutrophil and monocyte counts were associated with increased risk of major adverse cardiovascular events (MACE), adjusting for treatment.

• Baseline neutrophil count: OR 1.18 [95% CI: 1.06, 1.31] per 1 SD increase
• Baseline monocyte count: OR 1.16 [95% CI: 1.05, 1.29] per 1 SD increase
• Associations were adjusted for treatment assignment

On-treatment neutrophil and monocyte counts were associated with increased risk of MACE, adjusting for treatment.

• On-treatment neutrophil count: OR 1.25 [95% CI: 1.12, 1.40] per 1 SD increase
• On-treatment monocyte count: OR 1.18 [95% CI: 1.06, 1.31] per 1 SD increase
• On-treatment neutrophil counts showed a stronger association with MACE than baseline neutrophil counts

In epidemiological studies, higher leukocyte and platelet counts are associated with increased risk of cardiovascular events.

• Prior to this study, the effects of TRT on leukocyte subsets and platelets in men with hypogonadism were unknown
• The association of circulating leukocyte subtypes and platelets during TRT with cardiovascular events was also previously unknown
• This background motivated the investigation of leukocyte changes in the context of TRT