Risk of iron deficiency in naturally menstruating women : a thesis presented in partial fulfilment of the requirements for the degree of Master of Science in Nutrition and Dietetics, Massey University, Auckland, New Zealand

Abstract

Background: Iron deficiency is a common nutrient deficiency that disproportionately affects women and is often attributed to menstrual blood loss in reproductive-aged women. Although iron biomarker fluctuations across the menstrual cycle have been reported in eumenorrheic women, the relationship between iron status and subclinical ovulatory disturbances (SOD) remains unclear. Studies are yet to explore iron biomarkers in women across multiple menstrual cycles, while characterising hormonal profiles for comparisons both between and within ovulatory status groups. Objectives: To investigate variations in iron status between and within the menstrual cycle, considering ovulatory status and the influence of SOD in naturally menstruating women. Methods: Ninety-seven healthy, naturally menstruating women participated in a prospective longitudinal cohort study across three to five menstrual cycles. Participants attended six laboratory sessions across the early-follicular, late-follicular and mid-luteal phases of the menstrual cycle. Serum ferritin (SF), haemoglobin (Hb), serum iron (SI), total iron-binding capacity (TIBC), transferrin saturation (TSAT) and C-reactive protein (CRP), were analysed alongside female sex steroid hormones (oestradiol and progesterone). Ovulatory status was determined using mid-luteal progesterone, with ≥10nmol/L classified as ovulatory and <10nmol/L or a luteal phase <10 days classified as SOD. A multiple linear regression analysis was conducted to identify predictors of SF change from baseline to study end. Results: At baseline, 27.8% of participants were iron-insufficient (SF <30 µg/L), while 70.1% and 18.6% of participants were classified as ovulatory or SOD, respectively. Iron biomarker concentrations were comparable between groups in all phases, except for higher TSAT in the late-follicular phase among ovulatory participants (p=0.049). All iron biomarkers, except Hb (p=0.942), significantly differed across menstrual cycle phases among ovulatory participants, whereas no such variation was observed among SOD participants. Change in CRP was the only significant predictor of SF change across the study (β=1.58 (95% CI 0.84, 2.32), p<0.001). Conclusion: Menstrual cycle phase fluctuations in iron biomarkers were evident only in ovulatory women, suggesting altered iron regulation in those with SOD. Although the mechanisms underlying cyclical variations in iron biomarker concentrations among ovulatory women remain unclear, our study provides novel insights into iron status in women who present with SOD.