Menstruation-induced vaso-occlusive crisis in women with sickle cell disease

Abstract Introduction: Sickle cell disease (SCD) affects approximately 100,000 people in the United States. Pain is a well-known complication of the disease, with vaso-occlusive crisis (VOC) being a common reason for patients to seek acute care. Pain in SCD leads to approximately $3 billion dollars in health care costs. Many studies have described sex-based differences in pain amongst patients with SCD, with women experiencing more pain than men. One such potential etiology of these differences includes the relationship between menstruation and SCD pain. The pathophysiology underlying the association between menstruation and SCD pain remains unknown. Furthermore, little is known about the role that hormonal contraceptives (HC) play in mitigating SCD pain. In this single center retrospective chart review of patients seeking care at the Ohio State University Wexner Medical Center (OSUWMC), we examined the frequency of menstruation-induced VOC and any correlation with the use of HC. Methods: This study is a retrospective, single-center chart review utilizing ICD-10 codes to capture patients who sought care at OSUWMC from 01/01/2016 to 12/31/2024 with SCD; patients with female sex assigned at birth were identified via chart review using the electronic medical record. Data were then captured on the frequency of acute care visits (defined as emergency department (ED) and/or day hospital visits) and hospital admissions related to SCD pain based on documented chief complaint or admission diagnosis. Univariate and multivariate logistic regression models were applied to assess the association between patient-reported menstruation-induced VOC, acute care visits, and patient characteristics including SCD genotype and comorbidities, pharmacologic and non-pharmacologic SCD management, and HC use (defined as any combination or progestin only pill, hormonal intrauterine device, or hormonal arm implant) which were obtained via chart review. Results: A total of 240 females with SCD were identified during the study period, 51.3% (n=123) of whom had severe sickle cell genotypes, SS or SB0. The median age was 35 (19 – 80) and 236 (98.3%) identified as Black or African-American, 3 (1.3%) identified as Latina, and 1 (0.4%) identified as being of mixed race. Of all women with SCD identified, 43.9% (n=105) used hormonal contraception, 40.4% (n=97) had a history of dysmenorrhea, and 42.5% (n=102) had documented patient-reported menstruation-induced pain. Of the women who experienced menstruation-induced pain, only 22.9% (n=55) took HC. The median number of acute care visits and hospital admissions for pain were 3 (range 0-100) and 1 (range 0-22), respectively. In the univariate analysis, having menstruation-induced VOC was significantly associated with several factors: acute care visits for pain (OR, 95% CI:1.05, 1.02-1.09, p<0.01), hospital admissions for pain (OR, 95% CI: 1.13, 1.04-1.22, p<0.01), history of acute chest syndrome (OR, 95% CI: 1.99, 1.04-1.22, p=0.01), history of dysmenorrhea (OR, 95% CI: 6.33, 3.58-11.19, p<0.0001), use of disease-modifying therapy (OR, 95% CI: 1.82, 1.09-3.06, p=0.02), and hormonal contraception use (OR, 95% CI: 2.04, 1.21-3.43, p=0.01). In the multivariate analysis, only acute care visits (OR, 95% CI: 1.04, 1.01-1.07, p=0.01) and history of dysmenorrhea (OR, 95% CI: 5.95, 3.32-10.66, p <0.0001) remained significantly associated with menstruation-induced VOC. Conclusion: Previous studies have shown women with SCD have higher rates of acute care visits for pain. There is an association between menstruation-induced pain and HC use in one of the statistical models. The significant relationship between menstruation-induced pain and rate of acute care visits for pain highlights an important potential target for addressing acute pain rates in women with SCD. Additionally, the findings suggest that there may be certain women who are at risk of higher odds of acute health care utilization given a correlation between the presence of dysmenorrhea and menstruation-induced SCD pain. Due to limitations in the retrospective nature of the study, prospective studies are needed to determine how dysmenorrhea management may affect the incidence of menstruation-induced VOC in the SCD population. Future directions include evaluating the effect of type of hormonal contraception on the presence of dysmenorrhea and menstruation-induced VOC as well as determining the underlying pathophysiology between menstruation and menstruation-induced VOC.