Intravenous iron for the treatment of fatigue in nonanemic, premenopausal women with low serum ferritin concentration

Abstract

This is the first study to investigate the efficacy of intravenous iron in treating fatigue in nonanemic patients with low serum ferritin concentration. In a randomized, double-blinded, placebo-controlled study, 90 premenopausal women presenting with fatigue, serum ferritin < 50 ng/mL, and hemoglobin > 120 g/L were randomized to receive either 800 mg of intravenous iron (III)-hydroxide sucrose or intravenous placebo. Fatigue and serum iron status were assessed at baseline and after 6 and 12 weeks. Median fatigue at baseline was 4.5 (on a 0-10 scale). Fatigue decreased during the initial 6 weeks by 1.1 in the iron group compared with 0.7 in the placebo group (P ‫؍‬ .07). Efficacy of iron was bound to depleted iron stores: In patients with baseline serum ferritin < 15 ng/mL, fatigue decreased by 1.8 in the iron group compared with 0.4 in the placebo group (P ‫؍‬ .005), and 82% of iron-treated compared with 47% of placebo-treated patients reported improved fatigue (P ‫؍‬ .03). Drug-associated adverse events were observed in 21% of iron-treated patients and in 7% of placebo-treated patients (P ‫؍‬ .05); none of these events was serious. Intravenous administration of iron improved fatigue in iron-deficient, nonanemic women with a good safety and tolerability profile. The efficacy of intravenous iron was bound to a serum ferritin concentration < 15 ng/mL. Continuing Medical Education onlineThis activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Medscape, LLC and the American Society of Hematology. Medscape, LLC is accredited by the ACCME to provide continuing medical education for physicians. Medscape, LLC designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 70% minimum passing score and complete the evaluation at http://www.medscape.org/journal/blood; and (4) view/print certificate. For CME questions, see page 3450. Disclosures This study was funded by Vifor Pharma (Villars-sur-Glâne, Switzerland). The sponsor of the study was involved in the trial design and was responsible for data collection and storage. The authors had full access to all data and were responsible for the analysis and interpretation of the data presented in this publication. Christian Breymann is a consulting expert for Vifor Pharma in the field of obstetrics and gynecology. The remaining authors, the Associate Editor Martin S. Tallman, and the CME questions author Laurie Barclay, freelance writer and reviewer, Medscape, LLC, declare no competing financial interests. Learning objectives Upon completion of th...

Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial

“…3 Their study was shorter in duration (one month) and did not limit inclusion to severe fatigue; nevertheless, the effect size was similar to that in our study, except for hemoglobin, which was not measured after treatment. In addition, Krayenbuehl and coauthors 13 found significant effects on fatigue following intravenous iron therapy and reported a similar effect, although not significant, on hemoglobin. The effects of iron on hemoglobin concentration seem to be similar to those observed in postpartum nonanemic women, 14 military women with iron deficiency 15 and nonanemic women following blood donation.…”

“…16 These changes apparently occur within six weeks of starting treatment. 13 Patterson and colleagues' observational findings suggested that iron could improve quality of life. 17 However, the effect size for quality of life appears to be smaller than for fatigue alone; thus, our study was underpowered to reveal a significant effect.…”

Is Iron Deficiency in the Absence of Anemia Associated With Fatigue in Inflammatory Bowel Disease?

“…While the authors made the case that iron deficiency anemia was clearly detrimental, it was not established whether iron deficiency in the absence of anemia was detrimental. More recent findings from controlled studies in healthy women have suggested a link between iron deficiency and fatigue (43)(44)(45)(46) or learning and memory (47).…”

Iron sucrose – characteristics, efficacy and regulatory aspects of an established treatment of iron deficiency and iron-deficiency anemia in a broad range of therapeutic areas

“…Finally, a placebo-controlled study in fatigued, nonanemic premenopausal women with low ferritin levels (Hb ‡ 12 g/dl, serum ferritin £ 50 ng/ml) showed a trend for greater improvement in fatigue (Brief Fatigue Inventory questionnaire) in patients treated with IS (4 times 200 mg iron over 2 weeks) that reached significance in those with serum ferritin £ 15 ng/ml [60].…”

“…iron products). Among the 36 published clinical studies [45][46][47][48][49][50][55][56][57][58][59][60]64,65,70,74,[76][77][78][79][80][81][82][83][84][85][86][87][88][89][90][91] that are included in the clinical dossier of Venofer, 26 reported at least some details about adverse drug events; 3 of those reported at least possibly related serious adverse events (all nonfatal, Table 2) [51,76,77]. Three reports included only general statements on safety without further details (e.g., no serious adverse reactions were noted) [47,48,64].…”