Exploratory study: Iron trends in aging women with sickle cell disease

Abstract A subset of individuals with sickle cell disease (SCD) develop progressive iron overload with age due to increased lifetime blood transfusions. However, longitudinal studies examining iron status in women with SCD are limited, especially those with a focus on the menopausal transition, a period that may contribute to increasing ferritin levels due to the cessation of menstrual blood loss. This single-institution exploratory study evaluated iron trends with aging in adult women with SCD seen at the University of Illinois Sickle Cell Center between January 2021 and November 2024. Exclusion criteria included a history of stem cell transplant. 112 patients (≥18 years) were identified via retrospective chart review. Data collected included age, last menstrual period, longitudinal ferritin and transferrin saturation (TSAT) measurements, and SCD genotype, categorized as HbSS (n=66), HbSC (n=29), HbSB+ (n=11), or HbSB0 (n=6). Patients were grouped by age: post-menopausal 50+ (n=46), perimenopausal 31-49 (n=41), and pre-menopausal 18-30 (n=25). The pre-menopausal group had a smaller sample size due to limited availability of iron studies. As expected, median ferritin increased with age: 592.8 in the post-menopausal group, 218 in the perimenopausal group, and 176 in the pre-menopausal group. TSAT had a non-significant downward trend: 29.2, 32, and 34.3, respectively. Median values were used to account for outliers. Moderate positive Spearman correlations were also found between genotype severity and ferritin (ρ=0.50) and TSAT (ρ=0.59). As the raw distributions of ferritin and TSAT were highly skewed, log transformation was applied to approximate a normal distribution. Residual analysis revealed that age was a statistically significant positive predictor of log-transformed ferritin when SCD genotypes were accounted for (β = 0.025, p=0.015), suggesting that older age is independently associated with higher ferritin levels. In contrast, no significant association was observed between age and log-transformed TSAT (β = 0.0011, p=0.77). This study highlights age-related increases in ferritin among women with SCD, particularly post-menopause. SS patients had the highest ferritin and TSAT levels, likely due to a cumulative effect of lifetime blood transfusions and cessation of menstruation. These findings emphasize the importance of iron status monitoring in aging women with SCD to mitigate risks of iron overload and improve outcomes. Future studies will compare iron trends with an age-matched control group and explore hormonal influences, particularly estrogen, on iron metabolism.