Sex-stratified analysis of complete blood count parameters in Helicobacter pylori infection: A retrospective cohort study revealing distinct hematological mechanisms

Background Helicobacter pylori infection affects approximately 50% of the global population and is associated with hematological manifestations. Despite established associations with anemia, sex-specific effects remain unexplored, limiting our understanding of differential mechanisms and personalized treatment strategies. Methods We conducted a retrospective cohort study using electronic medical records from 2015–2024 at King Khalid University Hospital, Saudi Arabia. Among 1,895 patients with enteric infections, we identified 165 H. pylori -positive patients and 163 H. pylori -negative participants frequency-matched by age and sex from family medicine clinics. Nine complete blood count parameters were analyzed from tests performed within 10 days before or 2 days after H. pylori diagnosis. Sex-stratified analyses were performed via a two-way ANOVA to test for sex × H. pylori interactions, with Cohen's d effect sizes reported. Results Significant sex × H. pylori interactions were observed for hematocrit ( p  = 0.0146) and red blood cell count ( p  = 0.0122). Males demonstrated anemia with large effect sizes for hematocrit (d=-0.619, p  < 0.001), hemoglobin (d=-0.512, p  = 0.005), and RBC count (d=-0.407, p  = 0.026). Females exhibited changes in red cell indices: reduced mean corpuscular volume (d=-0.392, p  = 0.006), mean corpuscular hemoglobin (d=-0.295, p  = 0.036), and elevated red cell distribution width (d = 0.337, p  = 0.017). H. pylori infection significantly increased anemia rates in males (32.3% vs 11.5%, p  = 0.010) but not in females (31.1% vs 24.5%, p  = 0.372), with an overall rate of 27.3% vs 19.0%. Conclusions H. pylori infection affects males and females through distinct hematological mechanisms. Males experience anemia affecting hemoglobin and hematocrit, whereas females develop changes in red cell indices. These findings from our retrospective cohort study support the use of sex-specific diagnostic and treatment strategies.