Is it time to offer routine screening for iron deficiency in healthy adolescent females?

Iron deficiency (ID), with or without anaemia, is a widespread global health issue. Recent research shows that the prevalence of ID and its associated burden, measured in disability‐adjusted life years (DALYs), continues to rise over time, with sex being a key influencing factor. 1 Women aged 10–60 years consistently experience higher rates of ID and a more significant burden of disease than men. In 2017, ID was the fifth leading cause of DALYs among women of reproductive age and the leading cause of DALYs in children aged 5–14 years across both sexes. 2 While it is more common in low‐income countries, it also persists in wealthier nations. Despite its profound impact, ID remains underdiagnosed and undertreated worldwide. Studies indicate that ID affects approximately 10%–30% of adolescents worldwide, with higher rates among females and in low socioeconomic status. 3 , 4 , 5 , 6 , 7 , 8 , 9 Adolescents are at an increased risk of ID owing to the demands of rapid physical, mental and social development. Their expanding muscle mass, increased blood volume, rising haemoglobin levels and increased enzyme production all require more iron. 10 Menstruating individuals face additional iron loss with the onset of menarche. 9 , 11 , 12 , 13 , 14 , 15 Inadequate dietary supply is common among adolescents who consume vegetarian diets, are food‐selective and restrict food intake owing to weight concerns. 16 , 17 , 18 , 19 , 20 Increased hepcidin levels, particularly in obesity, and intense sports activities further reduce iron availability. 6 , 21 A systematic review and meta‐analysis of 122 studies conducted over 41 years, involving 17 519 athletes from 23 countries and 62 sports, found that approximately 54% of student athletes had ferritin levels <50 μg/L, and 23% were classified as having ID (ferritin <20 μg/L). 22 Iron deficiency can have significant health consequences, particularly in adolescents. Physically, individuals may experience fatigue and diminished endurance owing to the role of iron in oxygen transport and energy metabolism. 5 In athletes, ID was independently associated with reduced VO 2 peak and a lower likelihood of reaching optimal aerobic capacity. 23 Cognitive and developmental impairments are notable because iron is essential for oxygen transportation, DNA synthesis, myelin formation and neurotransmitter metabolism. Iron deficiency, with or without anaemia, can impair memory, cause attention deficits and reduce academic performance. 7 It is also associated with an increased risk of depressive and anxiety symptoms, as well as behavioural issues, such as social difficulties and heightened emotional distress. 24 Iron supplementation effectively reduces anaemia and improves serum ferritin levels, whereas frequent and prolonged supplementation has a more significant effect on ferritin levels. 25 Iron supplementation enhances cognitive functions, such as verbal learning and memory, in non‐anaemic, iron‐deficient adolescent girls. 26 However, evidence of effects of iron supplementation on broader cognitive and academic performance is mixed, and further research is needed to understand the impact of iron interventions on adolescents' learning and school success. 27 Studies have demonstrated that providing iron to women with normal haemoglobin but ferritin levels below 50 μg/L significantly alleviates fatigue symptoms. 12 , 28 Similarly, iron effectively relieved the symptoms of restless legs syndrome caused by low serum ferritin levels. 29 In athletes, iron treatment was shown to improve the aerobic capacity. 30

All authors wrote the paper.

In a study involving 493 adolescents and young adults, ID (ferritin <15 μg/L or transferrin saturation < 15%) and iron deficiency anaemia (IDA) (ID with haemoglobin ≤11 g/dL) were evaluated. 43 Among females ( n  = 350), 34.6% had ID and 6.3% had IDA, with nearly one‐third of those with ID lacking identifiable risk factors. Among males, 12.6% had ID, although none were diagnosed with IDA (most likely due to the restrictive definition), and over one‐third of those with ID had no identifiable risk factors. This suggests that the current screening methods would have missed over 50% of ID cases in females and over 95% in males. In another study, the use of ID risk assessment questionnaires in 96 female individuals 12–21 years old failed to predict objective measures of iron status, 44 highlighting the need for improved screening strategies. In a study of 1756 adolescent females, the sensitivity and specificity of haemoglobin testing for predicting ID were 15.6% (95% CI: 9.4%–21.8%) and 99.2% (95% CI: 98.7%–99.8%), respectively. 45 In a community‐based screening of reproductive‐aged women using fingertip haemoglobin testing, those with ID had similar haemoglobin concentrations to those without (11.89 ± 1.11 g/dL vs. 12.15 ± 0.71 g/dL, p  = 0.364) and were no more likely to be anaemic (40% vs. 35%, p  = 1.000), highlighting the limitation of haemoglobin alone in identifying ID. 46 In 1998, the Centers for Disease Control and Prevention (CDC) issued recommendations for preventing and treating ID in the United States. These guidelines recommend screening non‐pregnant women for IDA with haemoglobin levels every 5–10 years throughout their reproductive years. 47 More recently, in 2023, the International Federation of Gynecology and Obstetrics (FIGO) recommended routine blood tests to evaluate ID in women of reproductive age, starting at menarche. FIGO emphasized the use of serum ferritin as the primary marker of iron status, with transferrin saturation measured in cases where chronic inflammation was suspected. 48 When ID is identified in adolescent girls or non‐pregnant women, heavy menstrual bleeding (HMB) should be considered as a potential underlying cause, necessitating further evaluation and appropriate management (Table  2 ). 13 , 49 , 50 , 51 , 52 , 53 Clinical indicators of HMB include the need to change sanitary products every 1–2 h, episodes of flooding, menstrual duration longer than 7 days, passage of clots larger than 2.5 cm in diameter or blood loss that impacts physical, social or emotional well‐being and/or leads to ID. 53 The Pictorial Bleeding Assessment Chart (PBAC), a validated visual tool, identifies HMB with scores >100 and has been updated for modern menstrual products. 54 Conditions associated with heavy menstrual bleeding (HMB). Abbreviations: HMB, heavy menstrual bleeding; SSRI, selective serotonin reuptake inhibitors; TSH, thyroid‐secreting hormone; VWD, von Willibrand disease. In 2023, MacLean et al. proposed a universal screening for ID in non‐pregnant women and adolescent girls of reproductive age. 55 They recommended assessing serum ferritin levels and a complete blood count, beginning within 3 years of menarche for all women or earlier for those with risk factors (Table  3 ). Their analysis highlighted that screening adolescent girls for ID met the WHO criteria for screening tests. 56 Iron deficiency is a prevalent health issue in this population, presenting early detectable signs and symptoms, an accurate diagnostic test and an effective, accessible and affordable treatment. The cost of screening and treatment versus the cost of undiagnosed ID may also support its implementation. 55 Risk factors for iron deficiency in female adolescents. In 2024, multiple Polish medical societies, including the Pediatric Society, Pediatric Hematology/Oncology Society, Neonatology Society and Family Medicine Society, issued updated guidelines for preventing and managing ID in children and adolescents. These guidelines recommend routine laboratory testing for ID in girls following menarche, with screening at least every 5 years thereafter. 21 More frequent screening is advised for at‐risk adolescents, particularly those with a history of ID, those following low‐iron diets and those experiencing HMB.

Serum ferritin is widely recognized as the most specific and cost‐effective biomarker for evaluating iron stores in the body. Establishing standardized ferritin thresholds that align with physiological norms is essential for accurately diagnosing low iron stores. However, current guidelines differ, which may lead to the potential underdiagnosis or overdiagnosis of ID. The World Health Organization (WHO) defines ferritin thresholds as <12 μg/L for children and <15 μg/L for women, but these values were based on expert opinion rather than physiological data, and the method used to determine cut‐offs was not detailed. 31 A study analysing data from The National Health and Nutrition Examination Survey (NHANES) identified a serum ferritin threshold of 25 μg/L for non‐pregnant women aged 15–49 years. 32 This threshold was derived using restricted cubic spline models that assessed the physiological relationship between serum ferritin and both haemoglobin and soluble transferrin receptor concentrations in healthy individuals. Data from 62 anaemic individuals with either bone marrow‐confirmed ID ( n  = 54) or a documented response to iron therapy ( n  = 8) showed that ferritin <12 μg/L yielded a sensitivity of only 25% for the diagnosis of ID. 33 In contrast, increasing the threshold to <30 μg/L significantly improved sensitivity to 92%. The soluble transferrin receptor showed a sensitivity of 92%, outperforming ferritin at the <12 μg/L threshold and matching the performance of ferritin at the <30 μg/L threshold. Increasingly, experts recommend a ferritin cut‐off of 30 μg/L for healthy males and females over 15 years. 34 , 35 , 36 , 37 Although ferritin is the most reliable marker of iron stores, it can be elevated during inflammation, potentially masking ID. Therefore, measuring C‐reactive protein (CRP) or α1‐acid glycoprotein alongside ferritin helps distinguish true ID from inflammation‐related conditions in relevant cases. 38 , 39 Additionally, transferrin saturation and soluble transferrin receptor levels can provide further insights, particularly in cases where ferritin levels may be unreliable due to inflammatory conditions 40 , 41 (Table  1 ). Pros and cons of the different tests used for the diagnosis of iron deficiency (ID). Abbreviations: ID, iron deficiency; TIBC, total iron‐binding capacity.

Given the high prevalence of ID in adolescents, the question arises as to whether targeted or universal screening initiatives are warranted. Most guidelines recommend screening for ID among adolescents with risk factors or signs and symptoms of anaemia. 42

Emerging evidence highlights ID as a prevalent yet frequently overlooked health concern among adolescents, particularly females. In addition to its immediate health benefits to adolescent girls, screening during adolescence may also reduce the risk of ID during pregnancy, which is associated with adverse outcomes for both mother and child. Current screening strategies primarily target symptomatic individuals or those with established risk factors; however, this approach fails to identify a substantial proportion of affected individuals. Given the high prevalence of ID, its significant impact on both physical and cognitive health and the well‐documented benefits of early intervention, routine screening should be considered an essential component of adolescent preventive care. Universal haemoglobin and ferritin testing in menstruating adolescents, ideally commencing at ages 14–15, approximately 3 years post‐menarche, could facilitate earlier detection and timely treatment, ultimately mitigating the long‐term burden of ID and IDA. While ‘3 years post‐menarche’ may be a more clinical marker, the age‐based screening is more practical for policy and implementation, particularly as the average age of menarche still remains 12–13 years despite a gradual decline over recent decades. 57 , 58 , 59 While our recommendations are directed at adolescent girls, implementing a 5‐year screening interval is likely to facilitate the continued identification and management of ID into young adulthood. We are aware that accessing preventive primary care services can be a significant barrier to routine screening. Although adolescents often value having a trusted healthcare provider, they frequently do not attend preventive care appointments due to practical barriers and prior experiences of feeling dismissed or disrespected during healthcare encounters. 60 , 61 Strategies to address these challenges include improving care coordination, educating families and providers about the role of primary care and adapting services to be more adolescent‐friendly and accessible. 61 Educating adolescents and their families on the importance of preventing ID, including its impact on physical health, cognition, school performance and quality of life, may also increase motivation to participate in screening and follow‐up care. Leveraging community‐based settings such as schools, youth centres and extracurricular programmes can offer a way to reach adolescents who may otherwise disengage from traditional healthcare systems. 62 , 63 Incorporating adolescent‐friendly features such as online scheduling, text‐based reminders and walk‐in or after‐hours screening events could enhance participation. Importantly, any screening initiative must be accompanied by clear, respectful communication and accessible follow‐up care to ensure both engagement and effective treatment. Concerns about labelling healthy adolescents with a ‘disease’ can be mitigated by presenting screening for ID as a proactive step to support overall health and development, rather than as a diagnostic label. Diagnosing ID in female adolescents provides an opportunity to engage them in broader discussions on nutrition, physical activity, sleep and overall well‐being, including substance use and reproductive health. Haematologists have knowledge of iron metabolism that helps us understand the reasons for ID, for instance, in athletes and women with HMB who may need evaluation for bleeding disorders. We could partner with primary care doctors to ensure that screening extends beyond the commonly used serum iron (Table  1 ), in favour of more informative and clinically meaningful parameters. Haematologists could also contribute to managing ID, particularly in cases where there is no response to oral iron therapy. While ferrous sulphate remains a commonly used and affordable option, its unpleasant taste, odour and gastrointestinal side effects often limit adherence. More palatable and better‐tolerated formulations are available, though they are more expensive. 64 Additionally, it is suggested that alternate‐day dosing may enhance absorption and reduce side effects, offering a more effective and tolerable treatment strategy. 65 Future research should focus on optimizing screening protocols, assessing the cost‐effectiveness of routine screening and evaluating the impact of early intervention on academic performance, athletic capacity and overall adolescent health.

No relevant conflicts of interest declared by all authors.