Cyclical fluctuations of iron biomarkers in women: Diagnostic implications for iron deficiency
Iron deficiency (ID) and iron deficiency anemia (IDA) are common in women of reproductive age, but the influence of menstrual cycle phase on iron biomarkers is not well defined and is often overlooked in clinical and public health assessments. To assess phase-specific variation in iron biomarkers an...
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| Vydané v: | Practical laboratory medicine Ročník 47; s. e00512 |
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Elsevier B.V
01.12.2025
Elsevier |
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| Abstract | Iron deficiency (ID) and iron deficiency anemia (IDA) are common in women of reproductive age, but the influence of menstrual cycle phase on iron biomarkers is not well defined and is often overlooked in clinical and public health assessments.
To assess phase-specific variation in iron biomarkers and the prevalence of ID and IDA in non-pregnant women aged 18–44 years using 2003–2006 NHANES data.
We analyzed 1484 women with complete reproductive and iron status data. Menstrual cycle phase was categorized as menstruation (day 1–5), follicular phase (6−15), early/mid luteal phase (16–23), and late luteal phase (24–35). Eight biomarkers were analyzed: serum iron (SI), transferrin saturation (%TS), soluble transferrin receptor (sTfR), ferritin, erythrocyte protoporphyrin (EPP), hemoglobin (Hb), mean corpuscular volume (MCV) and body iron index (BII). ID and IDA were defined using ferritin-, MCV- and BII-based diagnostic models. All statistical models accounted for the complex design of the NHANES survey.
SI and %TS were lowest during menstruation and increased across the cycle, peaking in the early/mid-luteal phase (SI: p = 0.001; %TS: p = 0.003). sTfR was highest during menstruation (p < 0.05) compared to other phases, consistent with increased iron requirements. Ferritin, EPP, Hb and MCV remained stable across phases. The prevalence of ID varied by model (10.5 %–22.0 %) but showed no consistent phase differences. In contrast, the prevalence of IDA decreased after menstruation, with composite IDA estimates dropping from 7.5 % during menstruation to 3.7 % in the late luteal phase (p = 0.033).
Iron biomarkers and IDA prevalence vary systematically across the menstrual cycle, with iron status being lowest during menstruation and recovering in the luteal phase. Consideration of menstrual phase may improve diagnostic accuracy and interpretation of iron biomarkers in women of reproductive age.
•Iron biomarkers (serum iron, transferrin saturation, sTfR) fluctuate significantly across menstrual phases.•Iron deficiency is most frequently detected in the early follicular phase.•Considering menstrual phase may improve diagnostic accuracy for iron deficiency and anemia in reproductive-age women. |
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| AbstractList | Iron deficiency (ID) and iron deficiency anemia (IDA) are common in women of reproductive age, but the influence of menstrual cycle phase on iron biomarkers is not well defined and is often overlooked in clinical and public health assessments.
To assess phase-specific variation in iron biomarkers and the prevalence of ID and IDA in non-pregnant women aged 18–44 years using 2003–2006 NHANES data.
We analyzed 1484 women with complete reproductive and iron status data. Menstrual cycle phase was categorized as menstruation (day 1–5), follicular phase (6−15), early/mid luteal phase (16–23), and late luteal phase (24–35). Eight biomarkers were analyzed: serum iron (SI), transferrin saturation (%TS), soluble transferrin receptor (sTfR), ferritin, erythrocyte protoporphyrin (EPP), hemoglobin (Hb), mean corpuscular volume (MCV) and body iron index (BII). ID and IDA were defined using ferritin-, MCV- and BII-based diagnostic models. All statistical models accounted for the complex design of the NHANES survey.
SI and %TS were lowest during menstruation and increased across the cycle, peaking in the early/mid-luteal phase (SI: p = 0.001; %TS: p = 0.003). sTfR was highest during menstruation (p < 0.05) compared to other phases, consistent with increased iron requirements. Ferritin, EPP, Hb and MCV remained stable across phases. The prevalence of ID varied by model (10.5 %–22.0 %) but showed no consistent phase differences. In contrast, the prevalence of IDA decreased after menstruation, with composite IDA estimates dropping from 7.5 % during menstruation to 3.7 % in the late luteal phase (p = 0.033).
Iron biomarkers and IDA prevalence vary systematically across the menstrual cycle, with iron status being lowest during menstruation and recovering in the luteal phase. Consideration of menstrual phase may improve diagnostic accuracy and interpretation of iron biomarkers in women of reproductive age.
•Iron biomarkers (serum iron, transferrin saturation, sTfR) fluctuate significantly across menstrual phases.•Iron deficiency is most frequently detected in the early follicular phase.•Considering menstrual phase may improve diagnostic accuracy for iron deficiency and anemia in reproductive-age women. Background: Iron deficiency (ID) and iron deficiency anemia (IDA) are common in women of reproductive age, but the influence of menstrual cycle phase on iron biomarkers is not well defined and is often overlooked in clinical and public health assessments. Aim: To assess phase-specific variation in iron biomarkers and the prevalence of ID and IDA in non-pregnant women aged 18–44 years using 2003–2006 NHANES data. Methods: We analyzed 1484 women with complete reproductive and iron status data. Menstrual cycle phase was categorized as menstruation (day 1–5), follicular phase (6−15), early/mid luteal phase (16–23), and late luteal phase (24–35). Eight biomarkers were analyzed: serum iron (SI), transferrin saturation (%TS), soluble transferrin receptor (sTfR), ferritin, erythrocyte protoporphyrin (EPP), hemoglobin (Hb), mean corpuscular volume (MCV) and body iron index (BII). ID and IDA were defined using ferritin-, MCV- and BII-based diagnostic models. All statistical models accounted for the complex design of the NHANES survey. Results: SI and %TS were lowest during menstruation and increased across the cycle, peaking in the early/mid-luteal phase (SI: p = 0.001; %TS: p = 0.003). sTfR was highest during menstruation (p < 0.05) compared to other phases, consistent with increased iron requirements. Ferritin, EPP, Hb and MCV remained stable across phases. The prevalence of ID varied by model (10.5 %–22.0 %) but showed no consistent phase differences. In contrast, the prevalence of IDA decreased after menstruation, with composite IDA estimates dropping from 7.5 % during menstruation to 3.7 % in the late luteal phase (p = 0.033). Conclusions: Iron biomarkers and IDA prevalence vary systematically across the menstrual cycle, with iron status being lowest during menstruation and recovering in the luteal phase. Consideration of menstrual phase may improve diagnostic accuracy and interpretation of iron biomarkers in women of reproductive age. |
| ArticleNumber | e00512 |
| Author | Silveyra, Patricia Aguree, Sixtus Owora, Arthur |
| Author_xml | – sequence: 1 givenname: Sixtus orcidid: 0000-0002-2374-4462 surname: Aguree fullname: Aguree, Sixtus email: saguree@iu.edu organization: Department of Applied Health Science, Indiana University School of Public Health-Bloomington, Bloomington, IN, USA – sequence: 2 givenname: Arthur surname: Owora fullname: Owora, Arthur organization: Department of Pediatrics, School of Medicine, Indiana University, Indianapolis, IN, USA – sequence: 3 givenname: Patricia surname: Silveyra fullname: Silveyra, Patricia organization: Department of Environmental and Occupational Health, Indiana University Bloomington, Bloomington, IN, USA |
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| Cites_doi | 10.1007/s00421-022-05048-5 10.1080/17461391.2021.2018503 10.1093/ajcn/58.5.705 10.1111/bjh.13906 10.1037/pha0000057 10.1093/eurheartj/ehad586 10.1093/ajcn/32.10.2115 10.1210/en.2011-2045 10.1182/blood-2002-10-3071 10.1208/s12248-016-9875-4 10.3390/nu8090540 10.3945/ajcn.117.155978 10.1111/j.1753-4887.1995.tb05481.x 10.1002/ajh.20782 10.1016/j.cca.2007.04.008 10.1111/aogs.14890 10.1007/s00277-013-1901-3 10.3390/ijms15034077 10.3945/ajcn.2008.27151 10.1001/jama.1997.03540360041028 10.1002/hem3.108 10.1016/S0140-6736(07)61235-5 10.1079/BJN20051493 10.1515/CCLM.2002.091 |
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| Keywords | Transferrin saturation Menstrual cycle Iron deficiency Serum ferritin Iron deficiency anemia Iron biomarkers |
| Language | English |
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| Title | Cyclical fluctuations of iron biomarkers in women: Diagnostic implications for iron deficiency |
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