Study of Women with SCD Suggests C-Reactive Protein Level Link to Menstrual Cycle

A study has found that in women with sickle cell disease (SCD), levels of the inflammation biomarker C-reactive protein (CRP) are higher during the follicular phase of the menstrual cycle than during the luteal phase. The findings, published online in Blood Vessels, Thrombosis & Hemostasis, have implications for the cause and severity of vaso-occlusive episodes (VOEs) in SCD.

The study was conducted by Andrea Roe MD, MPH, and Jessica Wu, MD, of the Perelman School of Medicine at the University of Pennsylvania, with Kandace Gollomp, MD, and Veronica Bochenek, BA, of the Children’s Hospital of Philadelphia.

Overall CRP levels are already elevated in patients who have SCD and are further increased during VOEs. The investigators sought to determine whether a relationship exists between menstrual cycle phase and CRP levels.

“Women with SCD often report increased frequency and/or severity of vaso-occlusive episodes around their menses, and there is some evidence that hormonal contraceptives can impact vaso-occlusive pain, suggesting a potential connection between hormonal changes and SCD symptoms,” Dr. Wu explained in remarks forwarded to Heme Today.

The investigators analyzed frozen plasma samples from both men and women of reproductive age with SCD. All patients’ CRP levels were examined, and in the samples from female patients, the menstrual cycle phase at time of sample collection was estimated using measurements of estradiol, progesterone, and luteinizing hormone levels.

Analysis revealed that in women with SCD, CRP levels were markedly higher during the follicular phase of the menstrual cycle as compared with the luteal phase, at 8.80 mg/L versus 0.82 mg/L (P=0.03). Conversely, analysis across patients of both sexes found CRP levels did not significantly differ by SCD genotype, use of hydroxyurea, or patient’s sex.

“As this [the follicular phase] represents the portion of the menstrual cycle when patients are menstruating and often experiencing more frequent VOEs, our data suggest that this link between inflammatory changes and the hormonal fluctuations of the menstrual cycle could be an underlying factor to this clinical pattern,” Dr. Wu elaborated.

The investigators noted that further prospective studies are needed to confirm these findings and ascertain any associations between biomarker patterns and the symptoms experienced by patients.

Reference

Wu J, et al. Blood Vessels, Thrombosis & Hemostasis. Published online April 9, 2025. https://doi.org/10.1016/j.bvth.2025.100067