Increases in Sex Hormones during Anti-Tumor Necrosis Factor a Therapy in Adolescents with Crohn's Disease

Objective To evaluate children with Crohn's disease for inverse relationships between systemic inflammatory cytokines and sex hormone regulation in the context of anti-tumor necrosis factor alpha (TNF-alpha) therapy. Study design An observational study design was used to assess sex hormone and gonadotropin levels at the time of initiation of anti-TNF-alpha therapy and 10 weeks and 12 months later in 72 adolescents (Tanner stage 2-5) with Crohn's disease. Mixed-model linear regression was used to evaluate relationships between hormone levels, systemic inflammation, and dual-energy x-ray absorptiometry whole-body fat mass Z scores over the study interval. Results Sex hormone Z scores increased significantly during the 10-week induction interval: testosterone Z scores in male patients increased from a median of -0.36 to 0.40 (P < .05) and estradiol Z scores in females increased from -0.35 to -0.02 (P < .01). In mixed model regression, the pediatric Crohn's disease activity index score, cytokine levels, and measures of inflammation were significantly and negatively associated with sex hormone Z scores and with luteinizing hormone and follicle-stimulating hormone levels, adjusted for sex and Tanner stage. Sex hormone and gonadotropin levels were not associated with body mass index or fat mass Z-scores. Conclusions Crohn's disease is associated with delayed maturation, and initiation of anti-TNF-alpha therapy was associated with significant and rapid increases in sex hormone and gonadotropin levels, in association with improvements in disease activity and measures of inflammation. These data are consistent with preclinical studies of the effects of inflammation on sex hormone regulation.