Advertisement

Clinical Drug Investigation

, Volume 27, Issue 1, pp 51–58 | Cite as

Pilot Study of the Efficacy and Safety of a Modified-Release Magnesium 250mg Tablet (Sincromag®) for the Treatment of Premenstrual Syndrome

  • S. Quaranta
  • M. A. Buscaglia
  • M. G. Meroni
  • E. Colombo
  • S. CellaEmail author
Original Research Article

Abstract

Background: Magnesium deficiency has been implicated as a possible contributing factor to some symptoms of premenstrual syndrome (PMS) and several studies have reported a lower intracellular magnesium concentration in women with PMS. Thus, it has been suggested that magnesium supplementation may improve certain symptoms in women with PMS.

Objective: This open-label study assessed the efficacy and safety of a patented modified-release magnesium 250mg tablet for improving symptoms in women affected by PMS.

Methods: After a 3-month observational period, women aged 18–5 years with a regular menstrual cycle (from 25–35 days) who were affected by PMS (determined by a score of >-25 points on a PMS questionnaire) [n = 41] were given the modified-release magnesium tablet over three menstrual cycles, beginning 20 days after the start of their last menstrual period and continuing until the start of their next menstrual period.

Results: PMS symptoms improved during magnesium treatment. After 3 months, the mean total PMS score (primary endpoint), as assessed by the investigator using Moos’ Modified Menstrual Distress Questionnaire, was significantly lower than before therapy (p < 0.0001). During the same period, the mean PMS scores, as recorded in patients’ diaries (secondary efficacy variables), also showed significant improvements (p < 0.0001 for all subscales). The relative decreases in total PMS scores, as assessed by investigator and patient, were 35.1% and 33.5%, respectively. The magnesium tablet was well tolerated, with vertigo the only treatment-related adverse event reported (one patient).

Conclusions: We concluded that modified-release magnesium was effective in reducing premenstrual symptoms in women with PMS in this preliminary study.

Keywords

Melatonin Luteinising Hormone Menstrual Cycle Screen Visit Magnesium Deficiency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

The publication of this manuscript was supported by an educational grant from Zambon Group S.p.A. The editorial assistance of Marit Moen, Wolters Kluwer Health Medical Communications, is gratefully acknowledged.

The authors have no potential conflicts of interest that are directly relevant to the contents of this study.

References

  1. 1.
    International Statistical Classification of Diseases and Health Related Problems — ICD-1 Edition. WHO 1987Google Scholar
  2. 2.
    American College of Obstetricians and Gynecologists (ACOG). Premenstrual syndrome (ACOG practice bulletin no. 15). Washington (DC): ACOG; 2000Google Scholar
  3. 3.
    Diagnostic and Statistical manual of Mental Disorders, Fourth Edition. American Psychiatric Association, 1994Google Scholar
  4. 4.
    Halbreich U. The diagnosis of premenstrual syndromes and premenstrual dysphoric disorder: clinical procedures and research perspectives. Gynecol Endocrinol 2004 Dec; 19(6): 320–34PubMedCrossRefGoogle Scholar
  5. 5.
    Dalton K. What is PMS? J Roy Coll Gen Pract 1982; 32:717–23Google Scholar
  6. 6.
    Johnson SR. The epidemiology and social impact of premenstrual symptoms. Clin Obstet Gynecol 1987; 30; 367–6PubMedCrossRefGoogle Scholar
  7. 7.
    Winer SA, Rapkin AJ. Premenstrual disorders: prevalence, etiology and impact. J Reprod Med 2006; 51; 339–47PubMedGoogle Scholar
  8. 8.
    Freeman EW, Sondheimer SJ. Premenstrual dysphoric disorder: recognition and treatment. Prim Care Companion J Clin Psychiatry 2003 Feb; 5(1): 30–9PubMedCrossRefGoogle Scholar
  9. 9.
    Abraham GE. Nutritional factors in the etiology of the premenstrual tension syndromes. J Reprod Med 1983 Jul; 28(7): 446–64PubMedGoogle Scholar
  10. 10.
    Halbreich U. Gonadal hormones and antihormones serotonin and mood. Psychopharmacol Bull 1990; 26: 291–5PubMedGoogle Scholar
  11. 11.
    Halbreich U, Tworek H. Altered serotonergic activity in women with dysphoric premenstrual syndromes. Int J Psychiatry Med 1993; 23: 1–27Google Scholar
  12. 12.
    Genazzani AR, Lucchesi A, Stomati M, et al. Effects of sex steroid hormones on the neuroendocrine system. Eur J Contracept Reprod Health Care 1997; 2: 63–9PubMedCrossRefGoogle Scholar
  13. 13.
    Seippel L, Backstrom T. Luteal-phase estradiol relates to symptom severity in patient with premenstrual syndrome. J Clin Endocrinol Metab 1998; 83: 1988–92PubMedCrossRefGoogle Scholar
  14. 14.
    Magos AL, Brewster E, Singh R, et al. The effect of norethister-one in postmenopausal women on estrogen therapy: a model for the premenstrual syndrome. Br J Obstect Gynecol 1986; 93: 1290–6CrossRefGoogle Scholar
  15. 15.
    Bjorn I, Bixo M, Nojd KS, et al. Negative mood changes during hormone replacement therapy: a comparison between two progestogens. Am J Obstet Gynecol 2000; 183: 1419–26PubMedCrossRefGoogle Scholar
  16. 16.
    Parry BL, Berga SL, Kripke DF, et al. Altered waveform of plasma nocturnal melatonin secretion in premenstrual depression. Arch Gen Psychiatry 1990; 47: 1139–46PubMedCrossRefGoogle Scholar
  17. 17.
    Parry BL, Newton RP. Chronobiological basis of female-specific mood disorders. Neuropsychopharmacology 2001; 25(Suppl. 5): S102–8PubMedCrossRefGoogle Scholar
  18. 18.
    Pacchierotti C, Iapichino S, Bossini L, et al. Melatonin in psychiatric disorders: a review on the melatonin involvement in psychiatry. Front Neuroendocrinol 2001; 22: 18–32PubMedCrossRefGoogle Scholar
  19. 19.
    Deuster PA, Dolev E, Bernier LL. Magnesium and zinc status during the menstrual cycle. Am J Obstet Gynecol 1987; 157: 964–68PubMedGoogle Scholar
  20. 20.
    Facchinetti F, Borella P, Valentini M, et al. Premenstrual increase of intracellular magnesium levels in women with ovulatory, asymptomatic menstrual cycles. Gynecol Endocrinol 1988; 2: 249–56PubMedCrossRefGoogle Scholar
  21. 21.
    Muneyyirci-Delale O, Dalloul M, Nacharaju V L, et al. Serum ionized magnesium and calcium and sex hormones in healthy young men: importance of serum progesterone level. Fertility Sterility 1999; 72: 817–22CrossRefGoogle Scholar
  22. 22.
    Muneyyirci-Delale O, Nacharaju VL, Dalloul M, et al. Serum ionized magnesium and calcium in women after menopause: inverse relation of estrogen with ionized magnesium. Fertility Sterility 1999; 71: 869–72CrossRefGoogle Scholar
  23. 23.
    Schlemmer A, Podenphant J, Riis BJ, et al. Urinary magnesium in early postmenopausal women: influence of hormone therapy on calcium. Magnesium Trace Elements 1991-1992; 10: 34–9Google Scholar
  24. 24.
    Rosenstein DL, Elin RJ, Hosseini JM, et al. Magnesium measures across the menstrual cycle in premenstrual syndrome. Biological Psychiatry 1994; 35: 557–61PubMedCrossRefGoogle Scholar
  25. 25.
    Parry BL, Berga SL, Kripke DF, et al. Altered waveform of plasma nocturnal melatonin secretion in premenstrual depression. Arch Gen Psychiatry 1990; 47: 1139–46PubMedCrossRefGoogle Scholar
  26. 26.
    Parry BL, Udell C, Elliott JA, et al. Blunted phase-shift responses to morning bright light in premenstrual dysphoric disorder. J Biol Rhythms 1997; 12: 443–56PubMedGoogle Scholar
  27. 27.
    Parry BL, Berga SL, Mostofi N, et al. Plasma melatonin circadian rhythms during the menstrual cycle and after light therapy in premenstrual dysphoric disorder and normal control subjects. J Biol Rhythms 1997; 12: 47–64PubMedCrossRefGoogle Scholar
  28. 28.
    Durlach J, Pages N, Bac P, et al. Chronopathological forms of magnesium depletion with hypofunction or with hyperfunction of the biological clock. Magnes Res 2000; 15: 263–8Google Scholar
  29. 29.
    Durlach J, Pages N, Bac P, et al. Biorhythms and possible central regulation of magnesium status, phototherapy, darkness therapy and chronopathological forms of magnesium depletion. Agnes Res 2002; 15: 49–66Google Scholar
  30. 30.
    Seippel L, Backstrom T. Luteal-phase estradiol relates to symptom severity in patients with premenstrual syndrome. J Clin Endocrinol Metab 1998 Jun; 83(6): 1988–92PubMedCrossRefGoogle Scholar
  31. 31.
    Licinio J, Negrao AB, Mantzoros C, et al. Synchronicity of frequently sampled, 24-h concentrations of circulating leptin, luteinizing hormone, and estradiol in healthy women. Proc Natl Acad Sci U S A 1998 Mar 3; 95(5): 2541–6PubMedCrossRefGoogle Scholar
  32. 32.
    Norjavaara E, Ankarberg C, Albertsson-Wikland K. Diurnal rhythm of 17 beta-estradiol secretion throughout pubertal development in healthy girls: evaluation by a sensitive radioimmunoassay. J Clin Endocrinol Metab 1996 Nov; 81(11): 4095–102PubMedCrossRefGoogle Scholar
  33. 33.
    Moos RH. The development of a menstrual distress questionnaire. Psychosom Med 1968 Nov-Dec; 30(6): 853–67PubMedGoogle Scholar
  34. 34.
    Ross C, Coleman G, Stojanovska C. Factor structure of the modified Moos Menstrual Distress Questionnaire: assessment of prospectively reported follicular, menstrual and premenstrual symptomatology. J Psychosom Obstet Gynaecol 2003 Sep; 24(3): 163–74PubMedCrossRefGoogle Scholar
  35. 35.
    Freeman EW, Rickeis K. Characteristics of placebo responses in medical treatment of premenstrual syndrome. Am J Psychiatry 1999 Sep; 156(9): 1403–8PubMedGoogle Scholar
  36. 36.
    Walker AF, De Souza MC, Vickers MF, et al. Magnesium supplementation alleviates premenstrual symptoms of fluid retention. J Womens Health 1998 Nov; 7(9): 1157–65PubMedCrossRefGoogle Scholar
  37. 37.
    De Souza MC, Walker AF, Robinson PA, et al. A synergistic effect of a daily supplement for 1 month of 200mg magnesium plus 50mg vitamin B6 for the relief of anxiety-related premenstrual symptoms: a randomized, double-blind, crossover study. J Womens Health Gend Based Med 2000 Mar; 9(2): 131–9CrossRefGoogle Scholar
  38. 38.
    Webley GE, Lenton EA. The temporal relationship between melatonin and prolactin in women. Fertil Steril 1987 Aug; 48(2): 218–22PubMedGoogle Scholar
  39. 39.
    Mitamura R, Yano K, Suzuki N, et al. Diurnal rhythms of luteinizing hormone, follicle-stimulating hormone, testosterone, and estradiol secretion before the onset of female puberty in short children. J Clin Endocrinol Metab 2000 Mar; 85(3): 1074–80PubMedCrossRefGoogle Scholar
  40. 40.
    Barbeau A, Rojo-Ortea JM, Brecht HM, et al. Deficience en magnesium et dopamine cerebrale. In: Durlack J. editor. First International Symposium on Magnesium Deficit in Human Pathology. Paris: F Vittel, 1973; 149–52Google Scholar
  41. 41.
    Ben-Jonathan N, Hnasko R. Dopamine as a prolactin inhibitor. Endocrine Reviews 2001; 22(6): 724–63PubMedCrossRefGoogle Scholar
  42. 42.
    Khine K, Rosenstein DL, Elin RJ, et al. Magnesium (Mg) retention and mood effects after intravenous Mg infusion in premenstrual dysphoric disorder. Biol Psychiatry. Epub 2005 Sep 28, 2006 Feb 15; 59(4): 327–33CrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  • S. Quaranta
    • 1
  • M. A. Buscaglia
    • 1
  • M. G. Meroni
    • 2
  • E. Colombo
    • 2
  • S. Cella
    • 3
    Email author
  1. 1.Unità Operativa Ostetricia e GinecologiaAzienda Ospedaliera Ospedale San Carlo BorromeoMilanItaly
  2. 2.Unità Operativa Ostetricia e GinecologiaAzienda Ospedaliera di Busto ArsizioVareseItaly
  3. 3.Presso Dipartimento di Farmacologia, Chemioterapia e Tossicologia MedicaFacoltà di Medicina e Chirurgia Università di MilanoItaly

Personalised recommendations