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Background: Crohn's disease is an inflammatory chronic bowel disease characterized by an imbalanced production of pro-inflammatory mediators (tumor necrosis factor-α) and an increased recruitment of leukocytes to the site of inflammation. Low serum testosterone is associated with an increase in inflammatory factors, while testosterone administration reduces them. There is evidence for an immunomodulatory effect of testosterone on differentiation of regulatory T cells., Materials and Methods: The research was carried out in clinics in Germany and Syria. The study was a cumulative, prospective, registry study with an increasing number of men over time receiving testosterone. While men diagnosed with Crohn's disease received appropriate treatment for Crohn's disease, they were tested for testosterone deficiency (cut-off point ≤12.1 nmol/L). In total, 92 men received parenteral testosterone undecanoate 1000 mg/12 weeks for up to 7 years. Fourteen men opted not to receive testosterone and served as a comparison group., Results: In men receiving testosterone, the Crohn's Disease Activity Index declined from 239.36±36.96 to 71.67±3.26 at 84 months (p<0.0001 vs. baseline). C-reactive protein levels decreased from 12.89±8.64 to 1.78±1.37 mg/L at 84 months (p<0.0001 vs. baseline). Leukocyte count decreased from 11.93±2.85 to 6.21±1.01×109/L (p<0.0001 at 84 months vs. baseline). No changes were observed in the comparison group. There were no significant side effects of testosterone., Conclusions: Normalizing serum testosterone in hypogonadal men with Crohn's disease had a positive effect on the clinical course, also evidenced by biochemical parameters. Testosterone administration appeared safe.