The role of magnesium deficiency correction in the rehabilitation of women with climacteric syndrome and surgical menopause: results of the MAGYN study

Introduction. It is believed to be relevant to assess a profile in patients not using menopausal hormone therapy (non-MHT) with climacteric syndrome (CS) and surgical menopause, because this cohort includes patients with malignant neoplasms of the reproductive system at the stage of rehabilitation after radical surgery, for whom few study data in real-world data are available.

Aim: to describe a profile of non-MHT women with CS and surgical menopause included in the MAGYN study.

Materials and Methods. A non-interventional epidemiological study screened for magnesium deficiency in 1528 non-MHT women with CS and surgical menopause; 29 patients were at recovery period after radical surgical treatment of reproductive system cancer (vulvar, cervical, endometrial, ovarian, and breast cancer). The number and proportion of women with magnesium deficiency was assessed using the Magnesium Deficiency Questionnaire (MDQ), and a biochemical blood test was performed to measure serum magnesium concentration. Quality of life (QoL) was assessed using the World Health Organization Quality of Life Brief Version (WHOQOL-BREF). There were analyzed general somatic pathology, complaints, symptoms of magnesium deficiency by using visual analog scale, as well as the data of drug therapy, including a combination of magnesium citrate + vitamin B6 (pyridoxine) applied for 4 weeks.

Results. According to the MDQ, the prevalence of magnesium deficiency was 72.3 % (55.1 % with moderate and 15.2 % with severe deficiency). Of 469 women, serum magnesium concentration ≤ 0.80 mmol/L was found in 377 (80.38 %), ≤ 0.70 mmol/L – in 278 (59.28 %). Surgical menopause was significantly more common in patients with magnesium deficiency (13.0 %). Among the symptoms of CS in patients with magnesium deficiency, neuropsychiatric symptoms were significantly more common: 47.3 % vs. 43.2 % (p = 0.035). After 4 weeks of therapy, the MDQ score decreased from 46.0 ± 12.7 to 29.2 ± 15.1 points (p < 0.001), serum magnesium level increased to 0.79 ± 0.23 mmol/L. The WHOQOL-BREF demonstrated a significantly improved QoL compared to pre-therapy, including physical and psychological well-being (21.1 ± 4.5 vs. 26.2 ± 3.5 score; p < 0.001), selfperception (18,2 ± 3.7 vs. 22.2 ± 3.6 score; p < 0.001), social well-being (24.8 ± 4.9 vs. 28.1 ± 4.4 score; p < 0.001) and satisfaction with microsocial support (9.3 ± 2.7 vs. 11.0 ± 2.8 score; p < 0.001).

Conclusion. The high prevalence of magnesium deficiency and its close relationship with symptoms decreasing QoL (neuropsychic symptoms, hot flashes, irritability, sleep disturbances, fatigue, chronic stress, frequent headaches, etc.) have been confirmed. Further research is needed to assess an effect of magnesium deficiency correction as part of complex medical rehabilitation on the QoL of women with malignant neoplasms of the reproductive system after radical surgery.

1. Begovich E., Solopova A.G., Khlopkova S.V. et al. Assessing sexual dysfunction in patients with external genital endometriosis. [Ocenka seksual'noj disfunkcii u bol'nyh naruzhnym genital'nym endometriozom]. Obstetrics, Gynecology and Reproduction. 2022;16(4):354–64. (In Russ.). https://doi.org/10.17749/2313-7347/ob.gyn.rep.2022.345.

2. Begovich E., Solopova A.G., Khlopkova S.V. et al. Quality of life and psychoemotional status in patients with external genital endometriosis. [Kachestvo zhizni i osobennosti psihoemocional'nogo statusa bol'nyh naruzhnym genital'nym endometriozom]. Obstetrics, Gynecology and Reproduction. 2022;16(2):122–33. (In Russ.). https://doi.org/10.17749/2313-7347/ob.gyn.rep.2022.283.

3. Sandzhieva L.N., Solopova A.G., Blinov D.V. et al. Comparatively analyzed quality of life in patients with atypical endometrial hyperplasia and endometrial cancer during various rehabilitation activities. [Sravnitel'nyj analiz kachestva zhizni u pacientok s atipicheskoj giperplaziej i rakom endometriya pri razlichnyh reabilitacionnyh meropriyatiyah]. Obstetrics, Gynecology and Reproduction. 2022;16(4):410–25. (In Russ.). https://doi.org/10.17749/2313-7347/ob.gyn.rep.2022.344.

4. Sandzhieva L.N., Solopova A.G., Blinov D.V. et al. Personalized comprehensive rehabilitation program after surgical treatment of endometrial cancer: results of a prospective randomized comparative study. [Personificirovannaya programma kompleksnoj reabilitacii posle hirurgicheskogo lecheniya raka endometriya: rezul'taty prospektivnogo randomizirovannogo sravnitel'nogo issledovaniya]. Obstetrics, Gynecology and Reproduction. 2022;16(2):143–57. (In Russ.). https://doi.org/10.17749/2313-7347/ob.gyn.rep.2022.318.

5. 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.). https://doi.org/10.17749/2077-8333/epi.par.con.2022.115.

6. Korennaya V.V. The use of herbal medicine and low-dose hormone replacement therapy in menopause. [Primenenie fitoterapii i nizkodozirovannoj zamestitel'noj gormonal'noj terapii v klimaktericheskij period]. Zhurnal ROAG. 2009;(4):44–8. (In Russ.).

7. Solopova A.G., Blinov D.V., Demyanov S.V. et al. Epigenetic aspects inrehabilitation of female cancer patients. [Epigeneticheskie aspekty reabilitacii onkoginekologicheskih bol'nyh]. FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2022;15(2):294–303. (In Russ.). https://doi.org/10.17749/2070-4909/farmakoekonomika.2022.141.

8. Gromova O.A., Torshin I.Yu. Magnesium and "diseases of civilization": a practical guide. [Magnij i "bolezni civilizacii": prakticheskoe rukovodstvo]. Moscow: GEOTAR-Media, 2018. 799 p. (In Russ.).

9. Aydin H., Deyneli O., Yavuz D. et al. Short-term oral magnesium supplementation suppresses bone turnover in postmenopausal osteoporotic women. Biol Trace Elem Res. 2010;133(2):136–43. https://doi.org/10.1007/s12011-009-8416-8.

10. Babak G.A. Magnesium and human health. [Magnij i zdorov'e cheloveka]. Medicinskaya panorama. 2003;(2):26–9. (In Russ.).

11. Smith T.J. Magnesium supplement for menopausal hot flashes. J Clin Oncol. 2009;27(7):1151–2. https://doi.org/10.1200/JCO.2009.21.3629.

12. Park H., Parker G.L., Boardman C.H. et al. A pilot phase II trial of magnesium supplements to reduce menopausal hot flashes in breast cancer patients. Support Care Cancer. 2011;19(6):859–63. https://doi.org/10.1007/s00520-011-1099-7.

13. Framework for FDA’S Real-World Evidence Program. FDA, 2018. 40 р. Available at: https://www.fda.gov/media/120060/download. [Accessed: 27.07.2022].

14. Omelyanovskiy V.V., Maksimkina E.A., Ivakhnenko O.I. et al. Improvements to the formation of lists of drugs for medical use: analysis of changes in the Government Decree no. 871. [Sovershenstvovanie sistemy formirovaniya perechnej lekarstvennyh preparatov dlya medicinskogo primeneniya: analiz izmenenij Postanovleniya Pravitel'stva RF №871]. FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2020;13(2):113–23. (In Russ.). https://doi.org/10.17749/2070-4909/farmakoekonomika.2020.032.

15. Kolbin A.S., Gomon Yu.M., Kasimova A.R. et al. The real practice of clinical and economic research of drugs included in the Federal Program of High-Cost Nosologies. [Real'naya praktika provedeniya klinikoekonomicheskih issledovanij lekarstvennyh sredstv, vhodyashchih v federal'nuyu programmu vysokozatratnyh nozologij]. FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2022;15(1):87–105. (In Russ.). https://doi.org/10.17749/2070-4909/farmakoekonomika.2022.107.

16. 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.). https://doi.org/10.17749/2070-4909/farmakoekonomika.2022.132.

17. Blinov D.V., Solopova A.G., Sandzhieva L.N. et al. Strengthening medical rehabilitation services in health system: a situation analysis. FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. [Sovershenstvovanie organizacii medicinskoj reabilitacii v sisteme zdravoohraneniya: analiz situacii]. 2022;15(2):237–49. (In Russ.). https://doi.org/10.17749/2070-4909/farmakoekonomika.2022.140.

18. 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.). https://doi.org/10.17749/2070-4909.2015.8.2.016-024.

19. Serov V.N., Baranov I.I., Blinov D.V. et al. Results of investigation of magnesium deficiency in patients with hormone-dependent diseases. [Rezul'taty issledovaniya deficita magniya u pacientok s gormonal'nozavisimymi zabolevaniyami]. Akusherstvo i ginekologiya. 2015;(6):91–7. (In Russ.).

20. 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). Magnesium Research. 2016;29(3):82. (In Russ.). https://doi.org/10.1684/mrh.2016.0399.

21. Blinov D.V., Ushakova T.I., Makatsariya 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.). https://doi.org/10.17749/2313-7347.2017.11.1.036-048.

22. Slagle P. Magnificent Magnesium. The Way Up Newsletter. Vol. 30, 08-15-01. Available at: https://www.thewayup.com/newsletters/081501.htm. [Accessed: 27.07.2022].

23. WHOQOL: Measuring Quality of Life. World Health Organization, 2004. Available at: https://www.who.int/tools/whoqol/whoqol-bref. [Accessed: 27.07.2022].

24. Gromova O.A., Kalacheva A.G., Torshin I.Yu. et al. Magnesium deficiency is a significant risk factor for comorbidities: 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.).

25. Makatsariya A.D., Bitsadze V.O., Khizroeva D.Kh., Jobava E.M. Prevalence of magnesium deficiency in pregnant. [Rasprostranennost' deficita magniya u beremennyh zhenshchin]. Voprosy ginekologii, akusherstva i perinatologii. 2012;11(5):25–35. (In Russ.).

26. Serov V.N., Blinov D.V., Zimovina U.V., Jobava E.M. Results of an investigation of the prevalence of magnesium deficiency in pregnant women. [Rezul'taty issledovaniya rasprostranennosti deficita magniya u beremennyh]. Akusherstvo i ginekologiya. 2014;(6):33–40. (In Russ.).

27. 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.).

28. 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. Magnesium Research. 2016;29(3):81. https://doi.org/10.1684/mrh.2016.0399.

29. Mendes P.M.V., Bezerra D.L.C., Dos Santos L.R. et al. Magnesium in breast cancer: what is its influence on the progression of this disease? Biol Trace Elem Res. 2018;184(2):334–9. https://doi.org/10.1007/s12011-017-1207-8.

30. Blaszczyk U., Duda-Chodak A. Magnesium: its role in nutrition and carcinogenesis. Rocz Panstw Zakl Hig. 2013;64(3):165–71.

31. Bezerra D.L.C., Mendes P.M.V., de Sousa Melo S.R. et al. Hypomagnesemia and its relationship with oxidative stress markers in women with breast cancer. Biol Trace Elem Res. 2021;199(12):4466–74. https://doi.org/10.1007/s12011-021-02579-4.

32. Huang W.-Q., Long W.-Q., Mo X.-F. et al. Direct and indirect associations between dietary magnesium intake and breast cancer risk. Sci Rep. 2019;9(1):5764. https://doi.org/10.1038/s41598-019-42282-y.

33. Tarasov E.A., Blinov D.V., Zimovina U.V., Sandakova E.A. Magnesium deficiency and stress: Issues of their relationship, diagnostic tests, and approaches to therapy. [Deficit magniya i stress: voprosy vzaimosvyazi, testy dlya diagnostiki i podhody k terapii]. Terapevticheskii Arkhiv. 2015;87(9):114-122. (In Russ.). https://doi.org/10.17116/terarkh2015879114-122.

34. Akarachkova E.S., Baidauletova A.I., Belyaev A.A. et al. Stress: causes and consequences, treatment and prevention. Clinical guidelines. [Stress: prichiny i posledstviya, lechenie i profilaktika. Klinicheskie rekomendacii]. Saint Petersburg: Skifiya-print; Moscow: Profmedpress, 2020. 138 p. (In Russ.).

35. Gromova O.A., Kalacheva A.G., Torshin I.Yu. et al. About the diagnosis of magnesium deficiency. Part 1. [O diagnostike deficita magniya. Chast' 1]. Arhiv" vnutrennej mediciny. 2014;(2):5–10. (In Russ.). https://doi.org/10.20514/2226-6704-2014-0-2-5-10.

36. Gromova O.A., Kalacheva A.G., Torshin I.Yu. et al. About the diagnosis of magnesium deficiency. Part 2. [O diagnostike deficita magniya. Chast' 2]. Arhiv" vnutrennej mediciny. 2014;(3):6–10. (In Russ.). https://doi.org/10.20514/2226-6704-2014-0-3-6-10.