C-reactive protein and the menstrual cycle in females with sickle cell disease

Females with sickle cell disease (SCD) experience more frequent and severe vaso-occlusive episodes (VOEs) than males. Many also report perimenstrual timing of VOEs, suggesting cyclic variation in pain risk. C-reactive protein (CRP) is a robust inflammatory marker that is elevated at baseline in patients with SCD and rises during VOEs. Cyclic patterns of inflammatory markers in female patients with SCD have not been previously examined. This study examined the relationship between CRP and menstrual cycle phase in female patients with SCD. Frozen plasma samples from reproductive-aged adult patients with SCD were analyzed. Estradiol, progesterone, and luteinizing hormone levels were measured in female patient samples to estimate menstrual cycle phase at time of collection. CRP levels were compared by SCD genotype, hydroxyurea treatment, female vs male sex, and menstrual cycle phase in the female subgroup. CRP levels did not differ significantly by SCD genotype (SS vs SC), hydroxyurea use, or sex. However, in females with SCD, median CRP levels were significantly higher during the follicular phase than the luteal phase (8.80 mg/L [2.7-10.5] vs 0.82 mg/L [0.6-2.1]; P = .03). Although there were no differences in CRP levels in patients with SCD by sex, genotype, or hydroxyurea use, our results suggest that female patients have cyclicity in inflammation across the menstrual cycle that may predispose them to VOEs during the follicular phase. Further study is needed to validate these findings prospectively and to correlate biomarker patterns with clinical symptoms.