Menstrual Blood Loss Determines Iron Status in Premenopausal Blood Donors

Volumes of menstrual blood loss are consistently and significantly negatively associated with ferritin and hemoglobin levels in premenopausal female blood donors, according to new research.¹

Many blood services base donation interval- and iron supplementation policies on age, sex, and ferritin screening — as a result of menstrual blood loss and the potential for pregnancy, premenopausal women are at increased risk for both anemia and iron deficiency.

“Although blood services recognize premenopausal women to be at higher risk of iron deficiency and anemia, and previous studies suggest menstruation is associated with lower iron status in blood donors, to our knowledge, none of them utilize information on volume of blood loss or any other factors related to female reproductive health in donor selection or interval guidelines,” wrote the investigative team, led by Sofie Ekroos, faculty of medicine, University of Helsinki.

In recent decades, notable concern has been made over the global decrease in blood donation, with recent health events, including the COVID-19 pandemic, leading to an acute shortage of blood products and worsening the product.²

Despite processes to ensure donor safety, frequent whole blood donors are in danger of developing iron deficiency, which can progress to iron deficiency anemia. The World Health Organization (WHO) guidelines define anemia as hemoglobin levels <120 g/L and iron deficiency as serum ferritin levels <15 µg/L.³

On average, women lose ~40 mL of blood during one menstrual cycle — heavy menstrual bleeding (HMB) is defined as a loss of ≥80 mL yet remains underdiagnosed.⁴ However, women are often highly motivated to donate blood, making it important to understand how these factors underline the risk of iron deficiency and anemia in a donor population.⁵

In the current study, Ekroos and colleagues investigated how menstrual blood loss is associated with changes in ferritin and hemoglobin levels in female blood donors, and whether other female reproductive variables are linked to iron deficiency or anemia risk.¹

Donor InSight is a prospective, longitudinal nationwide cohort study of blood donors in the Netherlands, with three questionnaires on menstruation, with the final including blood sampling. Complete information was collected from 1005 (74%) participants, of which 964 were included in the final sample: 473 premenopausal and 491 postmenopausal women whole blood donors.

The alkaline hematin method is considered reliable for quantifying menstrual blood loss but is impractical for clinical use. A pictorial blood assessment chart (PBAC) is a semiquantitative method allowing menstruating individuals to measure the number of used menstrual products, the degree of staining, and the number and size of present blood clots.

Women who reported menstruation were assigned as premenopausal. Women who reported not menstruating due to menopause, hysterectomy, or bilateral oophorectomy and those ≥55 years old were assigned as postmenopausal.

Both ferritin and hemoglobin levels were lower in premenopausal women and 61 (13%) of this population had HMB (PBAC ≥150). Upon analysis, Ekroos and colleagues identified a significant and consistent negative association between PBAC score and hemoglobin and ferritin levels.

After variable importance analysis, the PBAC score accounted for most explained variance for hemoglobin (8%), second only to the number of days since the last whole blood donation (8%).

Further analysis revealed HMB was associated with anemia (odds ratio [OR], 3.56; 95% CI, 1.45 - 8.85) and the use of levonorgestrel-releasing intrauterine device (LNG-IUD) was negatively associated with iron deficiency (OR, 0.06; 95% CI, 0.01 - 0.44). After controlling for menstrual blood loss, age showed no association with iron status.

Incorporating PBAC into donor collection could be difficult, according to Ekroos and colleagues, as female donors may not be aware their menstrual blood loss is categorized as HMB. However, they indicated that adding questions on clinical features of HMB could help identify high-risk women.

“As our results suggest that blood donors could benefit from donation intervals based at least partially on information of menstruation and hormonal contraception use, accounting for these may be an important piece to this puzzle,” Ekroos and colleagues wrote.

References

1. _{Ekroos S, Karregat J, Toffol E, Castrén J, Arvas M, van den Hurk K. Menstrual blood loss is an independent determinant of hemoglobin and ferritin levels in premenopausal blood donors. Acta Obstet Gynecol Scand. Published online June 10, 2024. doi:10.1111/aogs.14890}
2. _{Nieto-Calvache AJ, Quintero-Santacruz M, Macia-Mejía C, López-Girón MC, Vergara-Galliadi LM, Ariza F. Dangerous shortage of blood banks as an indirect effect of SARS-CoV-2: An obstetrics perspective. Int J Gynaecol Obstet. 2020;151(3):424-430. doi:10.1002/ijgo.13409}
3. _{Peuranpää P, Heliövaara-Peippo S, Fraser I, Paavonen J, Hurskainen R. Effects of anemia and iron deficiency on quality of life in women with heavy menstrual bleeding. Acta Obstet Gynecol Scand. 2014;93(7):654-660. doi:10.1111/aogs.12394}
4. _{Mullen J, Baekken L, Bergström H, Björkhem Bergman L, Ericsson M, Ekström L. Fluctuations in hematological athlete biological passport biomarkers in relation to the menstrual cycle. Drug Test Anal. 2020;12(9):1229-1240. doi:10.1002/dta.2873}
5. _{Carver A, Chell K, Davison TE, Masser BM. What motivates men to donate blood? A systematic review of the evidence. Vox Sang. 2018;113(3):205-219. doi:10.1111/vox.12625}