SYSTEMATIC ANALYSIS OF FUNDAMENTAL AND CLINICAL RESEARCH, AS JUSTIFICATION FOR THE USE OF ESTROGEN-CONTAINING DRUGS WITH THE PREPARATIONS OF MAGNESIUM AND PYRIDOXINE
Abstract
Estrogen-containing preparations are widely used in gynecology today for hormone replacement therapy (HRT), as oral contraceptives (OC) and otherwise. Data obtained in large-scale clinical-epidemiological studies showed that intake of estrogen preparations, even of the so-called low-dose ones is associated with certain side effects and with heightened risk of thromboembolism-associated conditions (ischemic stroke, myocardial infarction), of breast cancer and of mortality from cardiovascular events. Available data indicate that estrogens exert negative influence upon metabolism of vitamin В6 and magnesium. Both micronutrients produce proven positive impact upon human health,
reducing, in particular, the risk of ischemic stroke, myocardial infarction and cardiovascular mortality. Therefore then, part of side effects of estrogen preparations could be eliminated or significantly reduced if HRT and OC are carried out with background intake of magnesium preparations and pyridoxine. This paper presents results of systematic analysis of data from fundamental and clinical-epidemiological studies of the influence of estrogens on metabolism of vitamin В6 and magnesium. Results of the analysis indicate that maintaining adequate levels of magnesium and pyridoxine in the body is indispensable for implementation of physiological effects and prevention of pathological effects of estrogens. Detailed description of molecular mechanisms of the discussed interactions is presented. Promising results of use of
magnesium preparations and pyridoxine in treatment of estrogen-dependent conditions are shown.
reducing, in particular, the risk of ischemic stroke, myocardial infarction and cardiovascular mortality. Therefore then, part of side effects of estrogen preparations could be eliminated or significantly reduced if HRT and OC are carried out with background intake of magnesium preparations and pyridoxine. This paper presents results of systematic analysis of data from fundamental and clinical-epidemiological studies of the influence of estrogens on metabolism of vitamin В6 and magnesium. Results of the analysis indicate that maintaining adequate levels of magnesium and pyridoxine in the body is indispensable for implementation of physiological effects and prevention of pathological effects of estrogens. Detailed description of molecular mechanisms of the discussed interactions is presented. Promising results of use of
magnesium preparations and pyridoxine in treatment of estrogen-dependent conditions are shown.
About the Authors
O. A. Gromova
Russian Satellite Center, Trace Element Institute for UNESCO, Moscow, Ivanovo State Medical Academy, Ministry of Public Health of the Russian Federation
Russian Federation
Russian Federation
O. A. Limanova
Ivanovo State Medical Academy, Ministry of Public Health of the Russian Federation
Russian Federation
Russian Federation
I. Yu. Torshin
Russian Satellite Center, Trace Element Institute for UNESCO, Moscow
Russian Federation
Russian Federation
References
1. Громова О.А. Магний и пиридоксин. Основы знаний. М. 2006; с. 43.
2. Громова О.А. Бухарина Е.В. Галицкая С.А. Гришина T.P., Волков А.Ю., Мокроусов А.А. Коррекция дефицита магния у женщин с предменструальным синдромом. Акушерство и гинекология. 2003; 5: 48-52.
3. Инструкция по медицинскому применению Магне В6 форте.
4. Лебедев В.А. с соавт. Вопросы гинекологии, акушерства и перинатологии. 2008; 7 (1): 20-25.
5. Назарова Н.М., Прилепская В.Н., Межевитинова Е.А. Профилактика побочных реакций при гормональной контрацепции препаратом Магне-В6. Акушерство и гинекология. 2003; 4: 52-54.
6. Руководство по контрацепции. Под ред. B.H. Прилепской. 2-е изд. M. 2010.
7. Торшин И.Ю., Громова О.А. 25 мгновений молекулярной фармакологии. Иваново;2012.
8. Торшин И.Ю., Громова О.А., Серов В.Н., Керимкулова Н.В., Лиманова О.А., Никифорова Н.В. Мировой опыт использования пиридоксина: экспериментальная и клиническая база применения в акушерско-гинекологической практике. Гинекология. 2013; 1: 63-67.
9. Alexander R.T., Hoenderop J.G., Bindels R.J. Molecular determinants of magnesium homeostasis: insights from human disease. J. Am. Soc. Nephrol. 2008; 19 (8): 1451-8 doi.
10. Bercovici J.P., Mabin D. Vitamin B 6 deficiency following the taking of estrogens. Nouv Presse Med. 1977; 6 (27): 2439.
11. Blum M., Kitai E., Ariel Y., Schnierer M., Bograd H. Oral contraceptive lowers serum magnesium. Harefuah. 1991; 121 (10): 363-364.
12. Bureau I., Anderson R.A., Arnaud J., Raysiguier Y., Favier A.E., Roussel A.M. Trace mineral status in post menopausal women: impact of hormonal replacement therapy. J. Trace Elem. Med. Biol. 2002; 16 (1): 9-13.
13. Cabodi S., Moro L., Baj G., Smeriglio M., Di Stefano P., Gippone S. et al. p130Cas interacts with estrogen receptor alpha and modulates non-genomic estrogen signaling in breast cancer cells. J. Cell. Sci. 2004; 117: 1603-11.
14. Cho M.S., Lee K.S., Lee Y.K. Relationship between the serum parathyroid hormone and magnesium levels in continuous ambulatory peritoneal dialysis (CAPD) patients using lowmagnesium peritoneal dialysate. Korean. J. Intern. Med. 2002; 17 (2): 114-121.
15. Christiansen C., Riss B.J. Five years with continuous combined estrogen progesterone therapy: Effect on calcium metabolism, lipoproteins and bleeding pattern. Br. J. Obstet. Gynaecol. 1990; 97: 1087-92.
16. Czaja J.A. Ovarian influences on primate food intake. Physics. Behav. 1978; 21: 923.
17. Davis B.A., Cowing B.E. Pyridoxal supplementation reduces cell proliferation and DNA synthesis in estrogen-dependent and -independent mammary carcinoma cell lines. Nutr. Cancer. 2000; 38 (2): 281-286.
18. Doll H., Brown S., Thurston A., Vessey M. Pyridoxine (vitamin B6) and the premenstrual syndrome: a randomized crossover trial. J. R. Coll. Gen. Pract. 1989; 39 (326): 364-368.
19. Dullo P., Vedi N. Changes in serum calcium, magnesium and inorganic phosphorus levels during different phases of the menstrual cycle. J. Hum. Reprod. Sci. 2008; 1 (2): 77-80.
20. European Food Safety Authority, EFSA, 2006. Tolerable upper intake levels for vitamins and minerals. www.efsa.europa.eu/en/ndatopics/docs/ndatolerableuil.pdf.
21. Friso S., Jacques P.F., Wilson P.W., Rosenberg I.H., Selhub J. Low circulating vitamin B(6) is associated with elevation of the inflammation marker C-reactive protein independently of plasma homocysteine levels. Circulation. 2001; 103: 2788-91.
22. Fu X.D., Cui Y.H., Lin G.P., Wang T.H. Nongenomic effects of 17beta-estradiol in activation of the ERK1/ERK2 pathway induces cell proliferation through upregulation of cyclin D1 expression in bovine artery endothelial cells. Gynecol. Endocrinol. 2007; 23: 131-7.
23. Fukai F., Murayama A. Association and dissociation of estrogen receptor with estrogen receptor-binding factors is regulated by Mg2+. J. Biochem. 1984 Apr; 95 (4): 1227-30.
24. Gibson R.S. «Assessment of vitamin B6 status.» Principles of Nutritional Assessment (2nd ed.). New York: Oxford University Press. 2005; 575-594.
25. Goksel B.K., Torun D., Karaca S., Karatas M., Tan M., Sezgin N., Benli S., Sezer S., Ozdemir N. Is low blood magnesium level associated with hemodialysis headache? Headache. 2006; 46 (1): 40-45.
26. Groenestege W.M., Hoenderop J.G., van den Heuvel L., Knoers N., Bindels R.J. The epithelial Mg2+ channel transient receptor potential melastatin 6 is regulated by dietary Mg2+ content and estrogens. J. Am. Soc. Nephrol. 2006; 17 (4): 1035-43.
27. Hameed A., Majeed T., Rauf S. Effect of oral and injectable contraceptives on serum calcium, magnesium and phosphorus in women. J. Ayub. Med. Coll. Abbottabad. 2001; 13 (3): 24-25.
28. Handa R.J., Mani S.K., Uht R.M. Estrogen receptors and the regulation of neural stress responses. Neuroendocrinology. 2012; 96 (2): 111-8 doi.
29. Heiss G., Wallace R., Anderson G.L., Aragaki A., Beresford S.A., Brzyski R., Chlebowski R.T., Gass M., LaCroix A., Manson J.E., Prentice R.L., Rossouw J., Stefanick M.L. Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin. JAMA. 2008; 299 (9): 1036-1045.
30. Higdon J. En Evidence-Based Approach to Vitamins and minerals. New York-Stuttgart. 2005.
31. Hoorn E.J., Zietse R. Disorders of calcium and magnesium balance: a physiology-based approach. Pediatr. Nephrol. 2012.
32. Hsch A.J., Peck E.J., Clark J.H. Progesterone antagonism of estrogen receptor and estrogen induced growth. Nature. 1975; 254: 337-9.
33. Kielczykowska M., Musik I., Hordyjewska A., Boguszewska A., Lewandowska A., Pasternak K. Oral administration of lithium increases tissue magnesium contents but not plasma magnesium level in rats. Pharmacol. Rep. 2007; 59 (3): 291-295.
34. Koh E.T., Owen W.L., Om A.S. Exogenous oestrogen affects calcium metabolism differently from exogenous testosterone in ovariectomized or orchiectomized rats fed a high fructose diet severely deficient in magnesium. Magnes. Res. 1996; 9 (1): 23-31.
35. Leklem J.E. Vitamin B-6: a status report. J. Nutr. 1990; 120: 1503-1507.
36. Levin E.R. Cellular functions of plasma membrane estrogen receptors. Steroids. 2002; 67: 471-5.
37. Lidegaard O. Oral contraception and risk of a cerebral thromboembolic attack: results of a case-control study. BMJ. 1993; 306 (6883): 956-963.
38. Lui A., Lumeng L., Aronoff G.R., Li T.K. Relationship between body store of vitamin B6 and plasma pyridoxal-P clearance: metabolic balance studies in humans. J. Lab. Clin. Med. 1985; 106 (5): 491-497.
39. Lussana F., Zighetti M.L., Bucciarelli P., Cugno M., Cattaneo M. Blood levels of homocysteine, folate, vitamin B6 and B12 in women using oral contraceptives compared to non-users. Thromb Res. 2003; 112 (1-2): 37-41.
40. Matsuzaki H., Fuchigami M., Miwa M. Dietary magnesium supplementation suppresses bone resorption via inhibition of parathyroid hormone secretion in rats fed a highphosphorus diet. Magnes Res. 2010; 23 (3): 126-30 doi.
41. McNair P., Christiansen C., Transbol I. Effect of menopause and estrogen substitutional therapy on magnesium metabolism. Miner. Electrolyte Metab. 1984; 10: 84-7.
42. Moriarty K., Kim K.H., Bender J.R. Minireview: estrogen receptor-mediated rapid signaling. Endocrinology. 2006; 147: 5557-63.
43. Morris M.S., Picciano M.F., Jacques P.F., Selhub J. Plasma pyridoxal 5'-phosphate in the US population: the National Health and Nutrition Examination Survey, 2003-2004. Am. J. Clin. Nutr. 2008; 87 (5): 1446-1454.
44. Muneyyirci-Delale O., Nacharaju V.L., Dalloul M., Altura B.M., Altura B.T. Serum ionized magnesium and calcium in women after menopause: inverse relation of estrogen with ionized magnesium. Fertil. Steril. 1999; 71 (5): 869-872.
45. Olatunbosun D.A., Adeniyi F.A., Adadevoh B.K. Effect of oral contraceptives on Serum magnesium levels. Int. J. Fertil. 1974; 19 (4): 224-226.
46. Pandya A.K., Chandwani S., Das T.K., Pandya T.K. Serum calcium, magnesium and inorganic phosphorus levels during various phases of menstrual cycle. Indian. J. Physiol. Pharmacol. 1995; 39: 411-4.
47. Pasternak K., Sztanke M., Borzecki A. Magnesium concentration in rat tissues receiving sex hormones and vitamin E. Ann. Univ. Mariae Curie Sklodowska Med. 2004; 59 (2): 114-118.
48. Pitkin R.M., Renolds W.A., William G.A., Nargis G.K. Calcium regulating hormones during the menstrual cycle. J. Clin. Endocrinol. Metabol. 1978; 47: 626-32.
49. Poromaa I.S., Segebladh B. Adverse mood symptoms with oral contraceptives. Acta Obstet. Gynecol. Scand. 2012; 91 (4): 420-7 doi.
50. Prentice R.L., Thomas D.B. On the epidemiology of oral contraceptives and disease. Adv. Cancer. Res. 1987; 49: 285-401.
51. Revankar C.M., Cimino D.F., Sklar L.A., Arterburn J.B., Prossnitz E.R. A transmembrane intracellular estrogen receptor mediates rapid cell signaling. Science. 2005; 307: 1625-30.
52. Rose D.P., Adams P.W. Oral contraceptives and tryptophan metabolism: effects of oestrogen in low dose combined with a progestagen and of a low-dose progestagen (megestrol acetate) given alone. J. Clin. Pathol. 1972; 25: 252-8.
53. Rosenberg M.J., Waugh M.S., Meehan T.E. Use and misuse of oral contraceptives: risk indicators for poor pill taking and discontinuation. Contraception. 1995; 51 (5): 283-288.
54. Schwingl P.J., Ory H.W., Visness C.M. Estimates of the risk of cardiovascular death attributable to low-dose oral contraceptives in the United States. Am. J. Obstet. Gynecol. 1999; 180 (1): 241-249.
55. Seelig M.S. Increased need for magnesium with the use of combined oestrogen and calcium for osteoporosis treatment. Magnes. Res. 1990; 3 (3): 197-215.
56. Solomon S.F., Kurere M.S., Callway D.M. Menstrual cycle and basal metabolic rate in women. Am. J. Clin. Nutr. 1982; 36: 611-6.
57. Torshin I.Y., Gromova O.A. Magnesium & Pyridoxine: Fundamental Studies & Clinical Practice. Nova Science. NY. 2009.
58. Torshin I.Yu. Bioinformatics in the postgenomic era: physiology and medicine. Nova Biomedical Books. NY. 2007.
For citation:
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. Obstetrics, Gynecology and Reproduction. 2013;7(3):35-50. (In Russ.)
Views: 318
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Email this article 
