Female magnesium deficiency and its management: review of current knowledge

   Magnesium is an important cofactor for metabolic reactions involving more than 300 enzymes, regulating a series of fundamental processes, such as myocardial contraction and blood pressure control, glucose regulation, participation in neuromuscular transmission. The prevalence of magnesium deficiency in various cohorts of fertile age women comprises up to 73.8 %. In clinical studies it was demonstrated that magnesium deficiency is associated with diseases and states such as dysmenorrhea, premenstrual syndrome (PMS), polycystic ovary syndrome (POS), climacteric syndrome, osteoporosis, use of combined oral contraceptives (COCs) and menopausal hormone therapy (MHT). Magnesium supplementation in combination with basic therapy can positively affect course and outcome of such pathologies. Magnesium organic salts could be used for countering magnesium deficiency. Among such agents, magnesium citrate has some advantage used in combination with pyridoxine (vitamin B₆) providing additional effects. Health care professionals should be guided by the criteria for Mg-containing preparation selection, defined by the Russian Society of Obstetricians and Gynecologists (RSOG).

1. Grober U., Schmidt J., Kisters K. Magnesium in prevention and therapy. Nutrients. 2015;7(9):8199–226. doi: 10.3390/nu7095388.

2. Bertinato J., Wu Xiao C., Ratnayake W.M. et al. Lower serum magnesium concentration is associated with diabetes, insulin resistance, and obesity in South Asian and white Canadian women but not men. Food Nutr Res. 2015;59(1):25974. doi: 10.3402/fnr.v59.25974.

3. Al Alawi M.A., Majoni S.W., Falhammar H. Magnesium and human health: perspectives and research directions. Int J Endocrinol. 2018;2018:9041694. doi: 10.1155/2018/9041694.

4. Gromova O.A., Torshin I.Yu., Rudakov K.V. et al. Magnesium deficiency – a significant risk factor for comorbidity: results of large-scale screening of magnesium status in Russian regions. [Nedostatochnost' magniya – dostovernyj faktor riska komorbidnyh sostoyanij: rezul'taty krupnomasshtabnogo skrininga magnievogo statusa v regionah Rossii]. Farmateka. 2013;(6):115–29. (In Russ.).

5. Blinov D.V., Ushakova T.I., Makatsaria N.A. et al. Hormonal contraception and magnesium deficiency: a subanalysis of the MAGYN study. [Gormonal'naya kontracepciya i deficit magniya: rezul'taty subanaliza issledovaniya MAGYN]. Obstetrics, Gynecology and Reproduction. 2017;11(1):36–48. (In Russ.). doi: 10.17749/2313-7347.2017.11.1.036-048.

6. Blinov D.V., Zimovina U.V., Dzhobava E.M. Management of magnesium deficiency in pregnant women: pharmacoepidemiological study. [Vedenie beremennyh s deficitom magniya: farmakoepidemiologicheskoe issledovanie]. FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2014;7(2):23–32. (In Russ.).

7. Makatsariya A.D., Bitsadze V.O, Blinov D.V. et al. Pregnant women with symptoms of magnesium deficiency in Russian Federation: MAGIC 2 study results. Magnes Res. 2016;29(3):81. URL: https://www.researchgate.net/publication/316007448_Pregnant_women_with_symptoms_of_magnesium_deficiency_in_Russian_Federation_MAGIC_2_study_results..

8. Blinov D.V., Zimovina J.V., Sandakova E.A., Ushakova T.I. Magnesium deficiency of patients with hormone dependent diseases: pharmacoepidemiological profile and life quality assessment. [Deficit magniya u pacientok s gormonal'no-zavisimymi zabolevaniyami: farmakoepidemiologicheskij profil' i ocenka kachestva zhizni]. FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2015;8(2):16–24. (In Russ.). URL: https://cyberleninka.ru/article/n/defitsit-magniya-u-patsientok-s-gormonalno-zavisimymi-zabolevaniyami-farmakoepidemiologicheskiy-profil-i-otsenka-kachestva-zhizni.

9. Schimatschek H.F., Rempis R. Prevalence of hypomagnesemia in an unselected German population of 16,000 individuals. Magnes Res. 2001;14(4):283–90.

10. De Baaij J.H.F., Hoenderop J.G.J., Bindels R.J.M. Magnesium in man: implications for health and disease. Physiol Rev. 2015;95(1):1–46. doi: 10.1152/physrev.00012.2014.

11. Olza J., Aranceta-Bartrina J., González-Gross M. et al. Reported dietary intake, disparity between the reported consumption and the level needed for adequacy and food sources of calcium, phosphorus, magnesium and vitamin D in the Spanish population: findings from the ANIBES study. Nutrients. 2017;9(2):168. doi: 10.3390/nu9020168.

12. Olza J., Aranceta-Bartrina J., González-Gross M. et al. Reported dietary intake and food sources of zinc, selenium, and vitamins A, E and C in the Spanish population: findings from the ANIBES study. Nutrients. 2017;9(7):697. doi: 10.3390/nu9070697.

13. Jahnen-Dechent W., Ketteler M. Magnesium basics. Clin Kidney J. 2012;5(Suppl 1):i3–i14. doi: 10.1093/ndtplus/sfr163.

14. Danziger J., William J.H., Scott D.J. et al. Proton-pump inhibitor use is associated with low serum magnesium concentrations. Kidney Int. 2013;83(4):692–9. doi: 10.1038/ki.2012.452.

15. Naumov D.E. Thermosensitive ion channels TRPM8 (review). [Termochuvstvitel'nye ionnye kanaly TRPM8 (obzor literatury)]. Byulleten' fiziologii i patologii dyhaniya. 2011;(42):89–96. (In Russ.).

16. Gromova O.A., Gogoleva I.V. Application of magnesium in the mirror of evidence-based medicine and fundamental research in therapy. Magnesium deficiency and stress concept. [Primenenie magniya v zerkale dokazatel'noj mediciny i fundamental'nyh issledovanij v terapii. Deficit magniya i koncepciya stressa]. Trudnyj pacient. 2007;5(11):29–38. (In Russ.).

17. Voets T., Nilius B., Hoefs S. et al. TRPM6 Forms the Mg²⁺ influx channel involved in intestinal and renal Mg²⁺ absorption. J Biol Chem. 2004;279(1):19–25. doi: 10.1074/jbc.M311201200.

18. Schlingmann K.P., Gudermann T. A critical role of TRPM channel-kinase for human magnesium transport. J Physiol. 2005;566(Pt 2):301–8. doi: 10.1113/jphysiol.2004.080200.

19. Pilchova I., Klacanova K., Tatarkova Z. et al. The involvement of Mg²⁺ in regulation of cellular and mitochondrial functions. Oxid Med Cell Longev. 2017;2017:6797460. doi: 10.1155/2017/6797460.

20. Sontia B., Touyz R.M. Magnesium transport in hypertension. Pathophysiology. 2007;14(3–4):205–11. doi: 10.1016/j.pathophys.2007.09.005.

21. Mutnuri S., Fernandez I., Kochar T. Suppression of parathyroid hormone in a patient with severe magnesium depletion. Case Rep Nephrol. 2016;2016:2608538. doi: 10.1155/2016/2608538.

22. Viering D.H.H.M., de Baaij J.H.F., Walsh S.B. et al. Genetic causes of hypomagnesemia, a clinical overview. Pediatr Nephrol. 2017;32(7):1123–35. doi: 10.1007/s00467-016-3416-3.

23. Seo J.W., Park T.J. Magnesium metabolism. Electrolyte Blood Press. 2008;6(2):86–95. doi: 10.5049/EBP.2008.6.2.86.

24. Pham P.C.T., Pham P.-A.T., Pham S.V. et al. Hypomagnesemia: a clinical perspective. Int J Nephrol Renovasc Dis. 2014;7:219–30. doi: 10.2147/IJNRD.S42054.

25. Lajer H., Daugaard G. Cisplatin and hypomagnesemia. Cancer Treat Rev. 1999;25(1):47–58. doi: 10.1053/ctrv.1999.0097.

26. Bagnis C.I., Deray G. Amphotericin B nephrotoxicity. Saudi J Kidney Dis Transpl. 2002;13(4):481–91.

27. Lee C.H., Kim G.-H. Electrolyte and acid-base disturbances induced by clacineurin inhibitors. Electrolyte Blood Press. 2007;5(2):126–30. doi: 10.5049/EBP.2007.5.2.126.

28. Sivakumar J. Proton pump inhibitor-induced hypomagnesaemia and hypocalcaemia : case review. Int J Physiol Pathophysiol Pharmacol. 2016;8(4):169–74.

29. Atsmon J., Dolev E. Drug-induced hypomagnesaemia: scope and management. Drug Saf. 2005;28(9):763–88. doi: 10.2165/00002018-200528090-00003.

30. Makatsariya A.D., Dzhobava E.M., Bitsadze V.O. et al. Observational study of outpatient women in hormone dependent conditions with magnesium deficiency and receiving Magne B6® Forte in Russia (MAGYN Study). Magnes Res. 2016;29(3):82. URL: https://www.researchgate.net/publication/316007423_Observational_study_of_outpatient_women_in_hormone_dependent_conditions_with_magnesium_deficiency_and_receiving_Magne_B6_Forte_in_Russia_MAGYN_Study..

31. Ryu A., Kim T.H. Premenstrual syndrome : a mini review. Maturitas. 2015;82(4):436–40. doi: 10.1016/j.maturitas.2015.08.010.

32. Rosenstein D.L., Elin R.J., Hosseini J.M. et al. Magnesium measures across the menstrual cycle in premenstrual syndrome. Biol Psychiatry. 1994;35(8):557–61. doi: 10.1016/0006-3223(94)90103-1.

33. Sherwood R.A., Rocks B.F., Stewart A., Saxton R.S. Magnesium and the premenstrual syndrome. Ann Clin Biochem. 1986;23(Pt 6):667–70. doi: 10.1177/000456328602300607.

34. Muneyyirci-Delale O., Nacharaju V.L., Altura B.M., Altura B.T. Sex steroid hormones modulate serum ionized magnesium and calcium levels throughout the menstrual cycle in women. Fertil Steril. 1998;69(5):958–2. doi: 10.1016/S0015-0282(98)00053-3.

35. Tonick S., Muneyyirci-Delale O. Magnesium in women’s health and gynecology. Open J Obstet Gynecol. 2016;6(5):325–33. doi: 10.4236/ojog.2016.65041.

36. Facchinetti F., Sances G., Borella P. et al. Magnesium prophylaxis of menstrual migraine: effects on intracellular magnesium. Headache. 1991;31(5):298–301. doi: 10.1111/j.1526-4610.1991.hed3105298.x.

37. Walker A.F., De Souza M.C., Vickers M.F. et al. Magnesium supplementation alleviates premenstrual symptoms of fluid retention. J Womens Health. 1998;7(9):1157–65. doi: 10.1089/jwh.1998.7.1157.

38. Quaranta S., Buscaglia M.A., Meroni M.G. et al. Pilot study of the efficacy and safety of a modified-release magnesium 250 mg tablet (Sincromag) for the treatment of premenstrual syndrome. Clin Drug Investig. 2007;27(1):51–8. doi: 10.2165/00044011-200727010-00004.

39. De Souza M.C., Walker A.F., Robinson P.A., Bolland K. A synergistic effect of a daily supplement for 1 month of 200 mg magnesium plus 50 mg vitamin B6 for the relief of anxiety-related premenstrual symptoms: a randomized, double-blind, crossover study. J Womens Health Gend Based Med. 2000;9(2):131–9. doi: 10.1089/152460900318623.

40. Fathizadeh N., Ebrahimi E., Valiani M. et al. Evaluating the effect of magnesium and magnesium plus vitamin B6 supplement on the severity of premenstrual syndrome. Iran J Nurs Midwifery Res. 2010;15(Suppl 1):401–5.

41. Dadak K., Makatsaria A.D., Blinov D.V., Zimovina U.V. Clinical and biochemical aspects of the use of magnesium in obstetrics, gynecology and perinatology. [Klinicheskie i biohimicheskie aspekty primeneniya preparatov magniya v akusherstve, ginekologii i perinatologii]. Obstetrics, Gynecology and Reproduction. 2014;8(2):69–78. (In Russ.).

42. Cherkasova N.Yu., Fomina A.V., Filippova O.V. The analysis of the market of pharmaceuticals for dysmenorrhea treatment. [Analiz rynka lekarstvennyh sredstv dlya lecheniya dismenorei]. FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2013;6(3):36–9. (In Russ.).

43. Unanyan A.L., Alimov V.A., Arakelov S.E. et al. Pharmacoepidemiology of original drotaverine use in dysmenorrhea: results of an international multicenter study. [Farmakoepidemiologiya ispol'zovaniya original'nogo drotaverina pri dismenoree: rezul'taty mezhdunarodnogo mnogocentrovogo issledovaniya]. FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2014;7(3):44–50. (In Russ.).

44. Orazov M.R., Chayka A.V., Nosenko E.N. Elimination of chronic pelvic pain caused by adenomyosis with progestogens new generation. [Kupirovanie hronicheskoj tazovoj boli, obuslovlennoj adenomiozom, progestagenami novogo pokoleniya]. Obstetrics, Gynecology and Reproduction. 2014;8(3):6–10. (In Russ.).

45. Dzhobava E.M. Safety aspects of using drotaverine in obstetric patients. [Voprosy bezopasnosti primeneniya drotaverina v akusherskoj praktike]. Obstetrics, Gynecology and Reproduction. 2018;12(1):54–60. (In Russ.). doi: 10.17749/2313-7347.2018.12.1.054-060.

46. Proctor M.L., Farquhar C.M. Dysmenorrhoea. BMJ Clin Evid. 2007;2007:0813.

47. Proctor M., Murphy P. A. Herbal and dietary therapies for primary and secondary dysmenorrhoea. Cochrane Database Syst Rev. 2001;(3):CD002124. doi: 10.1002/14651858.CD002124.

48. Seifert B., Wagler P., Dartsch S. et al. Magnesium – a new therapeutic alternative in primary dysmenorrhea. Zentralbl Gynakol. 1989;111(11):755–60. (In German).

49. Parazzini F., Di Martino M., Pellegrino P. Magnesium in the gynecological practice : a literature review. Magnes Res. 2017;30(1):1–7. doi: 10.1684/mrh.2017.0419.

50. Fontana-Klaiber H., Hogg B. Therapeutic effects of magnesium in dysmenorrhea. Schweiz Rundsch Med Prax. 1990;79(16):491–4. (In German).

51. Benassi L., Barletta F.P., Baroncini L. et al. Effectiveness of magnesium pidolate in the prophylactic treatment of primary dysmenorrhea. Clin Exp Obstet Gynecol. 1992;19(3):176–9.

52. Higdon J. An evidence-based approach to vitamins and minerals: health benefits and intake recommendations. Stuttgart, New York: Thieme, 2012. 282 p.

53. Olatunji L.A., Oyeyipo I.P., Micheal O.S., Soladoye A.O. Effect of dietary magnesium on glucose tolerance and plasma lipid during oral contraceptive administration in female rats. Afr J Med Med Sci. 2008;37(2):135–9.

54. Akinloye O., Adebayo T.O., Oguntibeju O.O. et al. Effects of contraceptives on serum trace elements, calcium and phosphorus levels. West Indian Med J. 2011;60(3):308–15.

55. Muneyyirci-Delale O., Nacharaju V.L., Dalloul M. et al. Divalent cations in women with PCOS: implications for cardiovascular disease. Gynecol Endocrinol. 2001;15(3):198–201. doi: 10.1080/gye.15.3.198.201.

56. Sharifi F., Mazloomi S., Hajihosseini R. et al. Serum magnesium concentrations in polycystic ovary syndrome and its association with insulin resistance. Gynecol Endocrinol. 2012;28(1):7–11. doi: 10.3109/09513590.2011.579663.

57. O’Shaughnessy A., Muneyyirci-Delale O., Nacharaju V.L. et al. Circulating divalent cations in asymptomatic ovarian hyperstimulation and in vitro fertilization patients. Gynecol Obstet Invest. 2001;52(4):237–42. doi: 10.1159/000052982.

58. Bird S.T., Hartzema A.G., Brophy J.M. et al. Risk of venous thromboembolism in women with polycystic ovary syndrome: a population-based matched cohort analysis. CMAJ. 2013;185(2):E115–20. doi: 10.1503/cmaj.120677.

59. Gromova O.A., Limanova O.A., Torshin I.Yu. Systematic analysis of fundamental and clinical research, as justification for the use of estrogen-containing drugs with the preparations of magnesium and pyridoxine. [Sistematicheskij analiz fundamental'nyh i klinicheskih issledovanij ukazyvaet na neobhodimost' sovmestnogo ispol'zovaniya estrogen-soderzhashchih preparatov s preparatami piridoksina i magniya]. Obstetrics, Gynecology and Reproduction. 2013;7(3):35–50. (In Russ.).

60. Farsinejad-Marj M., Saneei P., Esmaillzadeh A. Dietary magnesium intake, bone mineral density and risk of fracture : a systematic review and meta-analysis. Osteoporos Int. 2016;27(4):1389–99. doi: 10.1007/s00198-015-3400-y.

61. Gur A., Colpan L., Nas K. et al. The role of trace minerals in the pathogenesis of postmenopausal osteoporosis and a new effect of calcitonin. J Bone Miner Metab. 2002;20(1):39–43. doi: 10.1007/s774-002-8445-y.

62. Brodowski J. Levels of ionized magnesium in women with various stages of postmenopausal osteoporosis progression evaluated on the basis of densitometric examinations. Przegl Lek. 2000;57(12):714–6. (In Polish).

63. Magnesium deficiency in obstetrics and gynecology: results of a national meeting. [Deficit magniya v akusherstve i ginekologii: rezul'taty nacional'nogo soveshchaniya]. Obstetrics, Gynecology and Reproduction. 2014;8(2):6–10. (In Russ.).

64. Solopova A.G., Blinov D.V., Begovich E. et al. Neurological disorders after hysterectomy: from pathogenesis to clinical manifestations. [Nevrologicheskie rasstrojstva posle gisterektomii: ot patogeneza k klinike]. Epilepsy and paroxysmal conditions. 2022;14(1):54–64. (In Russ.). doi: 10.17749/2077-8333/epi.par.con.2022.115.

65. Blinov D.V., Solopova A.G., Plutnitskiy A.N. et al. Strengthening health care to provide rehabilitation services for women with cancer diseases of the reproductive system. [Organizaciya zdravoohraneniya v sfere reabilitacii pacientok s onkologicheskimi zabolevaniyami reproduktivnoj sistemy]. FARMAKOEKONOMIKA. Modern pharmacoeconomics and pharmacoepidemiology. 2022;15(1):119–30. (In Russ.). URL: https://cyberleninka.ru/article/n/organizatsiya-zdravoohraneniya-v-sfere-reabilitatsii-patsientok-s-onkologicheskimi-zabolevaniyami-reproduktivnoy-sistemy..

66. Blinov D.V., Solopova А.G., Achkasov Е.Е. et al. Medical rehabilitation of patients with menopausal syndrome and surgical menopause: contribution of magnesium deficiency correction. [Medicinskaya reabilitaciya pacientok s klimaktericheskim sindromom i hirurgicheskoj menopauzoj: vklad korrekcii deficita magniya]. FARMAKOEKONOMIKA. Modern pharmacoeconomics and pharmacoepidemiology. 2022;15(4):478–90. (In Russ.). doi: 10.17749/2070-4909/farmakoekonomika.2022.159.

67. Blinov D.V., Solopova A.G., Achkasov E.E et al. The role of magnesium deficiency correction in the rehabilitation of women with climacteric syndrome and surgical menopause: results of the MAGYN study. [Rol' korrekcii deficita magniya v reabilitacii zhenshchin s klimaktericheskim sindromom i hirurgicheskoj menopauzoj: rezul'taty issledovaniya MAGYN]. Obstetrics, Gynecology and Reproduction. 2022;16(6):676–91. (In Russ.). doi: 10.17749/2313-7347/ob.gyn.rep.2022.371.

68. Blinov D.V., Solopova A.G., Achkasov E.E. et al. Strengthening rehabilitation for patients with ovarian tumors: current approaches and future directions. [Organizaciya reabilitacii pacientok s opuholyami yaichnikov: sovremennye podhody i budushchie napravleniya. FARMAKOEKONOMIKA. Modern pharmacoeconomics and pharmacoepidemiology. 2023;16(2):303–16. (In Russ.). URL: https://www.elibrary.ru/ip_restricted.asp?rpage=https%3A%2F%2Fwww%2Eelibrary%2Eru%2Fitem%2Easp%3Fedn%3Ddcaony..

69. Blinov D.V., Solopova A.G., Achkasov E.E. et al. Algorithm for the provision of comprehensive psychotherapeutic support to women experiencing neuropsychiatric symptoms during rehabilitation following the treatment of malignant neoplasms of the reproductive system. [Algoritm kompleksnoj psihoterapevticheskoj podderzhki dlya zhenshchin s psihonevrologicheskimi simptomami v period reabilitacii posle lecheniya zlokachestvennyh novoobrazovanij reproduktivnoj sistemy]. Epilepsy and paroxysmal conditions. 2023;15(3):232–45. (In Russ.). doi: 10.17749/2077-8333/epi.par.con.2023.168.

70. Magne B6. Instructions for medical use. ЛСР-007053/09. [Magne B6. Instrukciya po medicinskomu primeneniyu. ЛСР-007053/09]. (In Russ.). Available at: http://www.grls.rosminzdrav.ru. [Accessed: 13. 01. 2024].

71. Magne B6 Forte. Instructions for medical use. ЛСР-007053/09. [Magne B6 Forte. Instrukciya po medicinskomu primeneniyu. ЛСР-007053/09]. (In Russ.). Available at: http://www.grls.rosminzdrav.ru. [Accessed: 13. 01. 2024].

72. Dizhevskaya E.V. Multidisciplinary approach to the correction of magnesium-deficient conditions. [Mul'tidisciplinarnyj podhod k korrekcii magnij-deficitnyh sostoyanij]. Obstetrics, Gynecology and Reproduction. 2015;9(3):68–85. (In Russ.).

73. Dizhevskaya E.V. Exchange of scientific data and expert opinions on pharmacotherapy and during pregnancy: traditional and modern approaches III International Expert Council on the problems of magnesium deficiency in obstetrics and gynecology. [Obmen nauchnymi dannymi i ekspertnymi mneniyami po farmakoterapi i v techenie beremennosti: tradicionnye i sovremennye podhody III Mezhdunarodnyj ekspertnyj sovet po problemam deficita magniya v akusherstve i ginekologii]. Obstetrics, Gynecology and Reproduction. 2015;9(4):93–101. (In Russ.).

74. Plenum of the Presidium of the Russian Society of Obstetricians and Gynecologists. [O Plenume Prezidiuma Rossijskogo obshchestva akusherov-ginekologov]. Akusherstvo i ginekologiya. 2015;(5):113–5. (In Russ.).

75. Gromova O.A. Magnesium deficit as modern nutritional issue in children and adolescents. [Deficit magniya kak problema sovremennogo pitaniya u detej i podrostkov]. Pediatricheskaya farmakologiya. 2014;(1):20–30. (In Russ.).

76. Ranade V.V., Somberg J.C. Bioavailability and pharmacokinetics of magnesium after administration of magnesium salts to humans. Am J Ther. 2001;8(5):345–57. doi: 10.1097/00045391-200109000-00008.