Menstrual cycle phase linked to inflammation in women with sickle cell disease

Menstrual cycle phase linked to inflammation in women with sickle cell disease | Image Credit: © 9nong - © 9nong - stock.adobe.com.

The follicular phase of the menstrual cycle may be linked to significant increases in C-reactive protein (CRP), which is an indicator of inflammation, in patients with sickle cell disease, according to a recent study published in Blood Vessels, Thrombosis & Hemostasis.¹

SCD, presenting as abnormally shaped blood cells, is the most common inherited red blood cells disorder among US patients, often leading to debilitating painful vasoocclusive events (VOEs) that require hospitalization. However, this new data allows for insight into VOE patterns in women with the condition.¹

Investigating VOE patterns in relation to menstrual cycles

“We know both from the literature and anecdotally from our patients that women with SCD have VOEs that cluster around their menstrual periods. We wanted to examine the potential reason behind that,” said Jessica Wu, MD, lead study author and a resident physician at the Perelman School of Medicine.¹

Stored plasma samples with diagnostic codes for SCD were obtained from the Penn Medicine BioBank repository, with SCD diagnosis, genotype, and reproductive age data obtained from electronic medical records.² Exclusion criteria included pregnancy, VOE hospitalization, and treatment at an emergency department during sample collection.

Female sex hormones and determining menstrual phases

Female sex hormones were also measured, including progesterone, estradiol, and luteinizing hormone. A Roche Cobas e411 Analyzer was used to complete lab work.²

Ovulation was determined through a cutoff progesterone level of 1.75 ng/mL. This allowed for differentiation between follicular and luteal phases of the menstrual cycle. Samples were compared between these 2 cycles, along with patient sex, SCD genotype, and hydroxyurea use.²

Key findings on CRP and hormonal levels

There were 31 plasma samples included in the final analysis, with a mean CRP concentration of 4.45 mg/L. No significant differences in CRP concentration were reported based on genotype, nor based on treatment status with hydroxyurea.²

A median estradiol of 64.4 pg/mL was measured in patients categorized in the follicular phase, alongside a median progesterone of 0.42 ng/mL and median luteinizing hormone of 11.4 IU/L. Among those categorized in the luteal phase, these measures were 106.9 pg/mL, 7.34 ng/mL, and 4.48 IU/L, respectively.²

Inflammation markers higher in the follicular phase

Higher CRP was also reported in women in the follicular phase, at 8.80 mg/L vs 0.82 mg/L among those in the luteal phase. Additional elevations among women in the follicular phase included neutrophil and platelet counts, aspartate aminotransferase, cortisol, and thrombin-antithrombin complexes.²

Significant increases in median platelet counts were reported among female patients in the follicular phase vs male patients, at 383 k/µl vs 219 k/µl, respectively. Overall, the data highlighted female patients with SCD in the follicular presenting with significantly higher CRP vs those in the luteal phase.²

Implications and potential interventions

Wu noted these results are supported by trends observed in menstrual cycles among the general population.¹ However, female patients with SCD experienced significantly higher CRP vs those without SCD, at 8.80 mg/L vs 0.74 mg/L.

According to investigators, this may provide a target for intervention. Future studies will be needed to evaluate menstrual patterns of other biomarkers linked to SCD and correlate the findings with clinical symptoms.

“Many hormonal contraceptives can suppress menstruation or suppress the hormone fluctuations that occur from cycle to cycle, so contraceptives could help these patients manage their pain crises,” said Wu.¹

References

1. Menstrual cycle may contribute to sickle cell disease pain crises. American Society of Hematology. April 9, 2025. Accessed April 14, 2025. https://www.eurekalert.org/news-releases/1079526
2. Wu J, Bochenek V, Gollomp K, Roe AH. C-reactive protein and the menstrual cycle in females with sickle cell disease. Blood Vessels, Thrombosis & Hemostasis. 2025. doi:10.1016/j.bvth.2025.100067