Causes and consequences of iron deficiency without anemia in the practice of gynecologist

Authors

  • T. F. Tatarchuk SI “O.M. Lukyanova Institute of Pediatrics, Obstetrics and Gynecology of the NAMS of Ukraine”; State Scientific Institution “Center for Innovative Medical Technologies of the NAS of Ukraine”, Ukraine
  • N. V. Kosei State Institution “O.M. Lukyanova IPOG of the NAMS of Ukraine”; State Scientific Institution “Center for Innovative Medical Technologies of the NAS of Ukraine", Ukraine https://orcid.org/0000-0002-5498-4143
  • N. F. Zakharenko SI “O.M. Lukyanova Institute of Pediatrics, Obstetrics and Gynecology of the NAMS of Ukraine”, Ukraine https://orcid.org/0000-0003-2934-3157
  • K. S. Pavlova SI “O.M. Lukyanova IPOG of the NAMS of Ukraine”, Ukraine https://orcid.org/0000-0003-2961-456X

DOI:

https://doi.org/10.18370/2309-4117.2020.56.13-17

Keywords:

iron deficiency, anemia, ferritin, transferrin, abnormal uterine bleeding, oral iron preparations, iron bisglycinate, tolerance

Abstract

The effect of iron deficiency (ID) without anemia on the reproductive health of women in contrast to iron deficiency anemia is still insufficiently evaluated from a clinical point of view, despite a weighty theoretical basis and a large pool of clinical observations. The purpose of this review is to systematize the ID causes without anemia in women associated and not associated with reproductive disorders, the effects of ID without anemia on reproductive health, and modern approaches to the diagnosis and treatment of this pathology. ID without anemia affects most of the physiological processes in a woman's body, including hormonal regulation, immune processes and functions of the nervous system. The negative effect of ID without anemia on a woman's reproductive function is realized through hormone-mediated and immune mechanisms. ID without anemia is currently underestimated in terms of somatic and reproductive health of women, as well as quality of life. Сlinical manifestations of ID without anemia are mostly nonspecific, which is why clinicians, focusing only on hematological parameters are often explaining them by other reasons, which leads to late diagnosis. Assessment of hematological parameters alone is accompanied by significant underdiagnosis of ID without anemia. Diagnosis of ID without anemia should be carried out in women with risk factors (abnormal uterine bleeding, heavy menstrual bleeding, etc.), as well as with dyshormonal disorders, recurrent inflammatory processes in combination with ID symptoms by assessing the ferritin and transferrin saturation.

To treat ID without anemia it is necessary to eliminate the etiological factor and carry out a sufficiently long-term supplementation with oral iron preparations with good tolerance and bioavailability. Iron bisglycinate is the form of iron intake that does not affect the mucous membrane of the gastrointestinal tract and is absorbed by the small intestine mucosa unchanged, which ensures its good tolerability and high efficiency for the correction of ID.

Author Biographies

T. F. Tatarchuk, SI “O.M. Lukyanova Institute of Pediatrics, Obstetrics and Gynecology of the NAMS of Ukraine”; State Scientific Institution “Center for Innovative Medical Technologies of the NAS of Ukraine”

MD, professor, corresponding member of the NAMS of Ukraine, deputy director for research work, head of the Endocrine Gynecology Department;

chief researcher, Department of Reproductive Health

N. V. Kosei, State Institution “O.M. Lukyanova IPOG of the NAMS of Ukraine”; State Scientific Institution “Center for Innovative Medical Technologies of the NAS of Ukraine"

MD, professor, chief researcher, Endocrine Gynecology Department;

leading researcher, Department of Reproductive Health 

N. F. Zakharenko, SI “O.M. Lukyanova Institute of Pediatrics, Obstetrics and Gynecology of the NAMS of Ukraine”

MD, chief researcher, Endocrine Gynecology Department

K. S. Pavlova, SI “O.M. Lukyanova IPOG of the NAMS of Ukraine”

Obstetrician gynecologist, graduate student, Endocrine Gynecology Department,

References

  1. Allen, L.H. “Anemia and iron deficiency: effect on pregnancy outcome.” Am J Clin Nutr 71 (2000): 1280–4.
  2. Bothwell, T.H. “Iron requirements in pregnancy and strategies to meet them.” Am J Clin Nutr 72 (2000): 257–64.
  3. Cao, C., O’Brien, K.O. “Pregnancy and iron homeostasis: an update.” Nutr Rev 71 (2013): 35–51.
  4. Soppi, E. “Iron Deficiency without Anemia – Common, Important, Neglected.” Clin Case Rep Rev 5 (2019): 1–7.
  5. Cappellini, M.D., Comin-Colet, J., De Francisco, A., et al. “Iron deficiency across chronic inflammatory conditions: international expert opinion on definition, diagnosis, and management.” Am J Hematol 92 (2017): 1068–78.
  6. World Health Organization. Available from: [www.who.int/vmnis/indicators/haemoglobin].
  7. Beard, J.L., et al. “Iron metabolism: a com prehensive review.” Nutr Rev 54 (1996): 295–317.
  8. Milto, I.V., et al. “Molecular and cellular bases of iron metabolism in humans.” Biochemistry (Moscow) 81.6 (2016): 549–64.
  9. Monsen, E.R. “Iron nutrition and absorption: dietary factors which impact iron bioavailability.” J Am Diet Assoc 88 (1988): 786–90.
  10. Roy, C.N., Enns, C.A. “Iron homeostasis: new tales from the crypt.” Blood, The Journal of the American Society of Hematology 96.13 (2000): 4020–7.
  11. Fairweather-Tait, S.J., de Sesmaisons, A. “Approaches used to estimate bioavailability when deriving dietary reference values for iron and zinc in adults.” Proceedings of the Nutrition Society 78.1 (2019): 27–33.
  12. Frazer, D.M., Anderson, G.J. “The regulation of iron transport.” Biofactors 40 (2014): 206–14.
  13. Sharp, P., Srai, S.K. “Molecular mechanism involved in intestinal iron absorption.” Work J Gastroenterol 13 (2007): 47161.
  14. Dev, S., Babitt, J.L. “Overview of iron metabolism in health and disease.” Hemodialysis International 21 (2017): S6–S20.
  15. Yiannikourides, A., Latunde-Dada, G.O. “A short review of iron metabolism and pathophysiology of iron disorders.” Medicines 6.3 (2019): 85.
  16. Fuqua, B.K., et al. “Intestinal iron absorption.” J Trace Elem Med Biol 26 (2012): 115–9.
  17. Camaschella, C. “New insights into iron deficiency and iron deficiency anemia.” Blood reviews 31.4 (2017): 225–33.
  18. Kim, J., Wessling-Resnick, M. “Iron and mechanisms of emotional behavior.” The Journal of nutritional biochemistry 25.11 (2014): 1101–7.
  19. Pino, J., et al. “Iron-restricted diet affects brain ferritin levels, dopamine metabolism and cellular prion protein in a region-specific manner.” Frontiers in Molecular Neuroscience 10 (2017): 145.
  20. Musallam, K.M., Taher, A.T. “Iron deficiency beyond erythropoiesis: should we be concerned?” Current Medical Research and Opinion 34.1 (2018): 81–93.
  21. Aisen, P., et al. “Chemistry and biology of eukaryotic iron metabolism.” Int J Biochem Cell Biol 33 (2001): 940–59.
  22. Allen, R.P. “Restless leg syndrome/Willis-Ekbom disease pathophysiology.” Sleep Med Clin 10 (2015): 207–14.
  23. Kennedy, B.C., et al. Long-term brain and behavioral consequences of early-life iron deficiency. Fetal development. Springer. Cham (2016): 295–316.
  24. Doom, J.R., Georgieff, M.K. “Striking while the iron is hot: understanding the biological and neurodevelopmental effects of iron deficiency to optimize intervention in early childhood.” Current pediatrics reports 2.4 (2014): 291–8.
  25. Mehmood, T., et al. “Response to intravenous iron in patients with iron deficiency anemia (IDA) and restless leg syndrome (Willis–Ekbom disease).” Sleep medicine 15.12 (2014): 1473–6.
  26. Earley, C.J., et al. “Altered brain iron homeostasis and dopaminergic function in restless legs syndrome (Willis–Ekbom disease).” Sleep medicine 15.11 (2014): 1288–1301.
  27. Verbon, E.H., et al. “Iron and immunity.” Annual Review of Phytopathology 55 (2017).
  28. Attia, M.A., et al. “Effect of iron deficiency anemia and its treatment on cell mediated immunity.” Indian Journal of Hematology and Blood Transfusion 25.2 (2009): 70–7.
  29. Das, I., et al. “Impact of iron deficiency anemia on cell-mediated and humoral immunity in children: A case control study.” Journal of natural science, biology, and medicine 5.1 (2014): 158.
  30. Hassan, T.H., et al. “Impact of iron deficiency anemia on the function of the immune system in children.” Medicine 95.47 (2016).
  31. Pitt-Rivers, R., Tata, J.R. The thyroid hormones. Elsevier (2013).
  32. Khatiwada, S., et al. “Association between iron status and thyroid function in Nepalese children.” Thyroid research 9.1 (2016): 2.
  33. Ashraf, T.S., et al. “Chronic anemia and thyroid function.” Acta Bio Medica: Atenei Parmensis 88.1 (2017): 119.
  34. Szczepanek-Parulska, E., Hernik, A., Ruchała, M. “Anemia in thyroid diseases.” Pol Arch Intern Med 127.5 (2017): 352–60.
  35. Saad, M.J.A., Morais, S.L., Saad, S.T.O. “Reduced cortisol secretion in patients with iron deficiency.” Annals of nutrition and metabolism 35.2 (1991): 111–5.
  36. Soliman, A.T., et al. “Iron deficiency anemia and glucose metabolism.” Acta Bio Medica: Atenei Parmensis 88.1 (2017): 112.
  37. Jones, G., Prosser, D.E., Kaufmann, M. “Cytochrome P450-mediated metabolism of vitamin D.” Journal of lipid research 55.1 (2014): 13–31.
  38. Li, G.F., et al. “Iron homeostasis in osteoporosis and its clinical implications.” Osteoporosis International 23.10 (2012): 2403–8.
  39. World Health Organization. The Global Prevalence of Anemia in 2011. Geneva. WHO (2015).
  40. Percy, L., et al. “Iron deficiency and iron deficiency anemia in women.” Best Pract Clin Obstet Gynaecol 40 (2017): 55–67.
  41. Lopez, A., et al. “Iron deficiency anaemia.” The Lancet 387.10021 (2016): 907–16.
  42. Clénin, G.E., et. al.“The treatment of iron deficiency without anaemia (in otherwise healthy persons).” Swiss Med Wkly 147 (2017): w14434.
  43. Johnson, S., et al. “Iron deficiency without anemia: a common yet under-recognized diagnosis in young women with heavy menstrual bleeding.” Journal of pediatric and adolescent gynecology 29.6 (2016): 628–31.
  44. Peyrin-Biroulet, L., et al. “Guidelines on the diagnosis and treatment of iron deficiency across indications: a systematic review.” Am J Clin Nutr 102 (2015): 1585–94.
  45. Picciano, M.F. “Pregnancy and lactation: physiological adjustments, nutritional requirements and the role of dietary supplements.” J Nutr 133 (2003): 1997S–2002S.
  46. Ratledge, C., et al. “Iron metabolism in pathogenic bacteria.” Ann Rev Microbiol 54 (2000): 881–941.
  47. Winn, N.C., Volk, K.M., Hasty, A.H. “Regulation of tissue iron homeostasis: the macrophage ‘ferrostat’.” JCI insight 5.2 (2020).
  48. Skaar, E.P.“The battle for iron between bacterial pathogens and their vertebrate hosts.” PLoS Pathog 6 (2010): e1000949.
  49. Benotti, P., et al. “Iron nutrition and metabolic surgery: the next quality improvement challenge.” Bariatric Times 16.3 (2019): 8–11.
  50. Blanco-Rojo, R., Vaquero, M.P. “Iron bioavailability from food fortification to precision nutrition. A review.” Innovative Food Science & Emerging Technologies 51 (2019): 126–38.
  51. Yu, D., Huo, J., Xie, L., et al. “Meta-analysis of studies on cut-off value of serum ferritin for identifying iron deficiency”. Wei Sheng Yan Jiu 42 (2013): 228–35.
  52. Goodnough, L.T. “Iron deficiency syndromes and iron–restricted erythropoiesis (CME).” Transfusion 52.7 (2012): 1584–92.
  53. Comín–Colet, J., et al. “Iron deficiency is a key determinant of health–related quality of life in patients with chronic heart failure regardless of anaemia status.” European journal of heart failure 15.10 (2013): 1164–72.
  54. Patterson, A.J., et al. “Iron deficiency, general health and fatigue: results from the Australian Longitudinal Study on Women's Health.” Qual Life Res 9 (2000): 491–7.
  55. Bruner, A., Joffe, A., Duggan, A., et al. “Randomised study of cognitive effects of iron supplementation in non-anemic iron-deficient adolescent girls.” Lancet 348 (1996): 992.
  56. Chavarro, J.E., et al.“Iron intake and risk of ovulatory infertility.” Obstet Gynecol 108 (2006): 1145–52.
  57. Li, Y.Q., et al. “Severe iron deficiency is associated with a reduced conception rate in female rats.” Gynecol Obstet Invest 77 (2013): 19–23.
  58. Aleshire, S.L., et al. “Localization of transferrin and its receptor in ovarian follicular cells: morphologic studies in relation to follicular development.” Fertil Steril 51 (1989): 444–9.
  59. Briggs, D.A., et al. “Transferrin in the developing ovarian follicle: evidence for denovo expression by granulosa cells.” Mol Hum Reprod 5 (1999): 1107–14.
  60. Miller, E.M. “The reproductive ecology of iron in women.” American Journal of Physical Anthropology 159 (2016): 172–95.
  61. Kolesarova, A., et al. “In vitro assessment of iron effect on porcine ovarian granulosa cells: secretory activity, markers of proliferation and apoptosis.” Physiol Res 60 (2011): 503–10.
  62. Georgsen, M., et al. “Serum ferritin level is inversely related to number of previous pregnancy losses in women with recurrent pregnancy loss.” Fertility and Sterility (2020).
  63. Verstraelen, H., Delanghe, J., Roelens, K., et al. “Subclinical iron deficiency is a strong predictor of bacterial vaginosis in early pregnancy.” BMC Infect Dis 5.55 (2005).
  64. Naderi, N., Etaati, Z., Rezvani Joibari, M., et al. “Immune deviation in recurrent vulvovaginal candidiasis: correlation with iron deficiency anemia.” Iran J Immunol 10.2 (2013): 118–26.
  65. Mirza, F.G., et al. “Impact and management of iron deficiency and iron deficiency anemia in women’s health.” Expert review of hematology 11.9 (2018): 727–36.
  66. Munro, M.G. “Abnormal uterine bleeding: A well–travelled path to iron deficiency and anemia.” International Journal of Gynecology & Obstetrics (2020).
  67. DeWayne Ashmead, H. “The absorption and metabolism 01 iron amino acid chelate.” Archivos latinoamericanos de nutricion 51.1 (2001): 13–21.
  68. Milman, N., et al. “Ferrous bisglycinate 25 mg iron is as effective as ferrous sulfate 50 mg iron in the prophylaxis of iron deficiency and anemia during pregnancy in a randomized trial.” Journal of perinatal medicine 42.2 (2014): 197–206.
  69. Ferrari, P., et al. “Treatment of mild non-chemotherapy-induced iron deficiency anemia in cancer patients: comparison between oral ferrous bisglycinate chelate and ferrous sulfate.” Biomedicine & Pharmacotherapy 66.6 (2012): 414–8.
  70. Perveen, A., et al. “Comparison of Conventional and Newer Iron Preparations for the Treatment of Iron Deficiency Anaemia in Children.” Journal of Rawalpindi Medical College 24.2 (2020): 112–6.

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Published

2020-12-29

How to Cite

Tatarchuk, T. F., Kosei, N. V., Zakharenko, N. F., & Pavlova, K. S. (2020). Causes and consequences of iron deficiency without anemia in the practice of gynecologist. REPRODUCTIVE ENDOCRINOLOGY, (56), 13–17. https://doi.org/10.18370/2309-4117.2020.56.13-17

Issue

No. 56 (2020)

Section

Gynecology

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Copyright (c) 2020 T. F. Tatarchuk, N. V. Kosei, N. F. Zakharenko, K. S. Pavlova

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