INGREDIENTS & RESEARCH

PMS and Dysmenorrhea

WHAT IS MENSTRUATION? 

Menstruation is the cyclic discharge of blood and lining from the uterus. Menstruation begins at puberty and typically occurs monthly until a woman reaches menopause (1).

There are two phases of the menstrual cycle; the follicular phase and the luteal phase. During the follicular phase, follicle stimulating hormone (FSH) and luteinizing hormone (LH), are released from the brain and transported in the blood to the ovaries. These hormones stimulate the growth of eggs in the ovaries until one matures and is released from the ovary, in a shell known as a follicle. Once the mature egg and follicle are released from the ovary, estrogen levels increase, and as a result, the FSH levels decrease. This is when ovulation begins, and the egg passes through the fallopian tube toward the uterus (2).

Following ovulation, the luteal phase begins. In this phase, what is left of the follicle becomes the corpus luteum and produces a hormone known as progesterone. This hormone is responsible for thickening the lining of the uterus and for preparing for implantation of a fertilized egg in the case of pregnancy.  However, when fertilization does not occur, the corpus luteum loses functionality and the hormones begin to decline. The endometrium then produces a chemical known as prostaglandins, that causes a series of uterine muscle contractions. These contractions cause the shedding of the endometrium. This release of the membrane tissue and blood through the vagina typically takes three to five days and completes the menstrual cycle (1,2).

Menstruation is an important and vital part of a woman’s reproductive ability. However, there are also complications that can occur during menstruation, that make it a difficult part of a woman’s reproductive functioning. Premenstrual syndrome (PMS) and dysmenorrhea are two issues that can occur during menstruation.

 

PMS AND DYSMENORRHEA

Premenstrual Syndrome (PMS):

Premenstrual syndrome is the experience of behavioral and physical symptoms in the week leading up to menstruation in a woman. The causes of PMS are not particularly well known, but it has been attributed to the surge and fluctuation of hormones that women experience during the menstrual cycle (3). Symptoms of PMS range from psychological to physiological, and progressively worsen closer to when actual menstruation begins, with most severe symptoms usually seen 1 to 2 days before menstruation (4).

Dysmenorrhea:

Dysmenorrhea is a common disorder related to menstruation and can be defined as painful menstruation.

Primary dysmenorrhea is the most common type of dysmenorrhea and onset begins shortly a girl’s first menstrual cycle. It consists of abdominal cramping pain that occurs just before menstruation begins and can last between 2 to 4 days during menstruation. Primary dysmenorrhea is typically caused by the prostaglandins, which is responsible for the muscle contractions used to shed the uterus lining (5,6).

Secondary dysmenorrhea is abdominal and pelvic pain that occurs throughout the menstrual cycle, that is caused by some type of pelvic pathology or underlying condition. The onset of secondary dysmenorrhea is typically seen as new menstrual symptoms in women aged 30 to 50 years old. The pain caused by secondary dysmenorrhea typically lasts longer than that of primary dysmenorrhea and can continue even after menstruation has ended (5,7).

 

RISK FACTORS FOR PMS AND DYSMENORRHEA

Premenstrual Syndrome (PMS):

  • Genetics (8,9)
  • Obesity (10,11)
  • Stress and anxiety (12,13)

Dysmenorrhea:

  • Increased age
  • Ethnicity
  • Uterine infections
  • Caffeine consumption
  • Alcohol consumption
  • Multiple births (5,14,15,16)

 

SYMPTOMS OF PMS AND DYSMENORRHEA

PMS:

  • Headaches
  • Bloating and water retention
  • Breast tenderness
  • Abdominal and back pain
  • Aches in joints and muscles
  • Sleep and digestion problems
  • Skin problems such as acne (3,17)

Primary Dysmenorrhea:

  • Back and thigh pain
  • Lower abdominal pain
  • Headache
  • Nausea
  • Diarrhea
  • Vomiting (18,19)

Secondary Dysmenorrhea:

  • Intensely painful menstruation
  • Painful sexual intercourse
  • Bleeding after sexual intercourse
  • Bleeding between menstrual cycles
  • Abnormally heaving blood flow during menstruation (7,18)

For more information on PMS and dysmenorrhea and diagnosis:  1. Talk to your doctor  2. Visit the Mayo Clinic website on PMS  3. Visit the Office of Women's Health website  4. Visit the American College of Obstetricians and Gynecologists website on dysmenorrhea

 

PMS AND DYSMENORRHEA FACTS AND STATISTICS

Estimates show that up to 80% of women in reproductive ages have physical challenges with menstruation (20). Between 20% to 40% of females experience more severe symptoms of PMS that affect their daily lives (3).

In 2013 worldwide reports, up to 90% of adolescent girls and 50% of women suffer from dysmenorrhea. Of that amount, 10% to 20% of girls and women indicate that their experience is severe and debilitating (21).

 

MEDICAL TREATMENT OF PMS AND DYSMENORRHEA

The first line pharmacological treatment for PMS is serotonin reuptake inhibitors (SSRIs), which are antidepressants and have been shown to alleviate both psychological and physiological symptoms (22,23). Serotonin reuptake inhibitors include:

  • Fluoxetine: marketed as Luoxetine HCl, Rapiflux, Sarafem, Selfemra (24)
  • Paroxetine: marketed as Brisdelle, Paxil, Paxil CR, Pexeva (25)
  • Sertraline: marketed as Zoloft (26)
  • Escitalopram: marketed as Lexapro (27)
  • Citalopram: marketed as CeleXA (28)
  • Side-effects of these SSRIs include edema, anxiety, restlessness, blurred vision, rapid heart rate, gastrointestinal problems, unusual mood and behaviors, decreased libido, drowsiness, skin rashes, seizures, and trouble breathing (24,25,26,27,28).

Another line of pharmacological treatment for PMS is hormonal contraceptives (17). These include:

  • Progestin: marketed as, Next Choice, Option 2, Ovrette, Plan B, Prochieve, Prometrium (29)
  • Low dose estrogen: marketed as Enjuvia, Alora, Divigel (30)
  • Side-effects of these include changes in vaginal bleeding, blood clots, numbness in extremities and chest, headaches, dry mouth, excessive thirst, frequent urination, loss of appetite, and depression (29).

In treating dysmenorrhea, the first line of pharmacological treatments is nonsteroidal anti-inflammatory drugs (NSAIDs) (31). These include:

  • Celecoxib: marketed as Celebrex, NuDroxiPAK, SmartRx, CapXib Kit (32)
  • Ibuprofen: marketed as Midol, Advil, Motrin (33)
  • Side-effects of these include liver problems, bleeding of stomach and intestines, risk of heart failure, edema in face and extremities, blood in urine and stool, headache, dizziness, blurred vision, fatigue, vomiting blood, and muscle pain.

 

NATURAL WAYS TO HELP SUPPORT HEALTHY MENSTRUATION

Practices to Help Support Healthy Menstruation:

  • Exercise
  • Reduce salty food intake
  • Eat a diet high in fish, eggs, fruit and vegetables
  • Have positive social relationships
  • Social support
  • Reduce social stress (34,35)

Natural Supplements That Help Support Healthy Menstruation:

 

REFERENCES

  1. Menstruation - National Library of Medicine - PubMed Health. https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0023146/. Accessed April 21, 2018.
  2. Reed B, Carr B. The Normal Menstrual Cycle and the Control of Ovulation. https://www.ncbi.nlm.nih.gov/books/NBK279054/.  Accessed April 21, 2018.
  3. Premenstrual syndrome: Overview. https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0072449/.  Accessed April 21, 2018.
  4. Pearlstein T, Yonkers K, Fayyad R, Gillespie J. Pretreatment pattern of symptom expression in premenstrual dysphoric disorder. J Affect Disord. 2005;85(3):275-282. doi:10.1016/j.jad.2004.10.004.
  5. Dysmenorrhea: Painful Periods FAQs.https://www.acog.org/-/media/For-Patients/faq046.pdf?dmc=1&ts=20180421T1146196467.  Accessed April 21, 2018.
  6. Dysmenorrhea. Am Fam Physician2005;71(2):285-291. Accessed April 21, 2018.
  7. Lumsden M, Iliodromiti S. Evaluation of dysmenorrhea - Differential diagnosis of symptoms. http://bestpractice.bmj.com/topics/en-us/420.  Accessed April 21, 2018.
  8. TRELOAR S, HEATH A, MARTIN N. Genetic and environmental influences on premenstrual symptoms in an Australian twin sample. Psychol Med. 2002;32(01). doi:10.1017/s0033291701004901.
  9. Jahanfar S, Lye M, Krishnarajah I. The Heritability of Premenstrual Syndrome. Twin Research and Human Genetics. 2011;14(05):433-436. doi:10.1375/twin.14.5.433.
  10. Masho S, Adera T, South-Paul J. Obesity as a risk factor for premenstrual syndrome. Journal of Psychosomatic Obstetrics & Gynecology. 2005;26(1):33-39. doi:10.1080/01443610400023049.
  11. Bertone-Johnson E, Hankinson S, Willett W, Johnson S, Manson J. Adiposity and the Development of Premenstrual Syndrome. J Womens Health. 2010;19(11):1955-1962. doi:10.1089/jwh.2010.2128.
  12. Perkonigg A, Yonkers K, Pfister H, Lieb R, Wittchen H. Risk Factors for Premenstrual Dysphoric Disorder in a Community Sample of Young Women. J Clin Psychiatry. 2004;65(10):1314-1322. doi:10.4088/jcp.v65n1004.
  13. Jahromi B, Pakmehr S, Hagh-Shenas H. Work Stress, Premenstrual Syndrome and Dysphoric Disorder: Are There Any Associations?. Iran Red Crescent Med J2011;13(3):199-202.
  14. Harada T. Dysmenorrhea and Endometriosis in Young Women. Yonago Acta Med2013;56(4):81-84.
  15. Taran F, Stewart E, Brucker S. Adenomyosis: Epidemiology, Risk Factors, Clinical Phenotype and Surgical and Interventional Alternatives to Hysterectomy. Geburtshilfe Frauenheilkd. 2013;73(09):924-931. doi:10.1055/s-0033-1350840.
  16. Khan A, Shehmar M, Gupta J. Uterine fibroids: current perspectives. Int J Womens Health. 2014:95. doi:10.2147/ijwh.s51083.
  17. Yonkers K, O'Brien P, Eriksson E. Premenstrual syndrome. The Lancet. 2008;371(9619):1200-1210. doi:10.1016/s0140-6736(08)60527-9.
  18. Proctor M, Farquhar C. Diagnosis and management of dysmenorrhoea. BMJ. 2006;332(7550):1134-1138. doi:10.1136/bmj.332.7550.1134.
  19. Period pain: Overview. https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0072508/.  Accessed April 21, 2018.
  20. Bhatia S, Bhatia S. Diagnosis and Treatment of Premenstrual Dysphoric Disorder. Am Fam Physician2002;66(7):1239-1249.
  21. Berkley K. Primary Dysmenorrhea: An Urgent Mandate. Pain: Clinical Updates2018;21(3).
  22. Marjoribanks J, Brown J, O'Brien P, Wyatt K. Selective serotonin reuptake inhibitors for premenstrual syndrome. Cochrane Database of Systematic Reviews. 2013. doi:10.1002/14651858.cd001396.pub3.
  23. Steiner M, Pearlstein T, Cohen L et al. Expert Guidelines for the Treatment of Severe PMS, PMDD, and Comorbidities: The Role of SSRIs. J Womens Health. 2006;15(1):57-69. doi:10.1089/jwh.2006.15.57.
  24. Fluoxetine (By mouth) - National Library of Medicine - PubMed Health. https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0010346/?report=details. Accessed April 21, 2018.
  25. Paroxetine (By mouth) - National Library of Medicine - PubMed Health. https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0011606/?report=details.  Accessed April 21, 2018.
  26. Sertraline (By mouth) - National Library of Medicine - PubMed Health.  https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0012108/.  Accessed April 21, 2018.
  27. Escitalopram (By mouth) - National Library of Medicine - PubMed Health.  https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0010165/.  Accessed April 21, 2018.
  28. Citalopram (By mouth) - National Library of Medicine - PubMed Health. https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0009639/?report=details.  Accessed April 21, 2018.
  29. Progestin (Oral route, Parenteral route, Vaginal route) - National Library of Medicine - PubMed Health. https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0011857/.  Accessed April 21, 2018.
  30. Menopause--Medicines to Help You. https://www.fda.gov/ForConsumers/ByAudience/ForWomen/ucm118627.htm#estonly.  Accessed April 21, 2018.
  31. OSAYANDE A, MEHULIC S. Diagnosis and Initial Management of Dysmenorrhea. Am Fam Physician2014;89(5):341-346.
  32. Celecoxib (By mouth) - National Library of Medicine - PubMed Health. https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0009526/?report=details.  Accessed April 21, 2018.
  33. Ibuprofen (By mouth) - National Library of Medicine - PubMed Health. https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0010648/?report=details.  Accessed April 21, 2018.
  34. Reid R. Premenstrual Dysphoric Disorder (Formerly Premenstrual Syndrome). https://www.ncbi.nlm.nih.gov/books/NBK279045/.  Accessed April 21, 2018.
  35. Abadi Bavil D, Dolatian M, Mahmoodi Z, Akbarzadeh Baghban A. Comparison of lifestyles of young women with and without primary dysmenorrhea. Electron Physician. 2016;8(3):2107-2114. doi:10.19082/2107.
  36. Zamani M, Neghab N, Torabian S. Therapeutic effect of Vitex agnus castus in patients with premenstrual syndrome. Acta Med Iran2012;50(2):101-106.
  37. Rafieian-Kopaei M, Movahedi M. Systematic Review of Premenstrual, Postmenstrual and Infertility Disorders of Vitex Agnus Castus. Electron Physician. 2017;9(1):3685-3689. doi:10.19082/3685.
  38. Schellenberg R. Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo-controlled study. BMJ. 2001;322(7279):134-137. doi:10.1136/bmj.322.7279.134.
  39. Lauritzen C, Reuter H, Repges R, Böhnert K, Schmidt U. Treatment of premenstrual tension syndrome with Vitex agnus castus controlled, double-blind study versus pyridoxine. Phytomedicine. 1997;4(3):183-189. doi:10.1016/s0944-7113(97)80066-9.
  40. Berger D, Schaffner W, Schrader E, Meier B, Brattström A. Efficacy of Vitex agnus castus L. extract Ze 440 in patients with pre-menstrual syndrome (PMS). Arch Gynecol Obstet. 2000;264(3):150-153. doi:10.1007/s004040000123.
  41. Loch E, Selle H, Boblitz N. Treatment of Premenstrual Syndrome with a Phytopharmaceutical Formulation Containing Vitex agnus castus. Journal of Women's Health & Gender-Based Medicine. 2000;9(3):315-320. doi:10.1089/152460900318515.
  42. Prilepskaya V, Ledina A, Tagiyeva A, Revazova F. Vitex agnus castus: Successful treatment of moderate to severe premenstrual syndrome. Maturitas. 2006;55:S55-S63. doi:10.1016/j.maturitas.2006.06.017.
  43. Momoeda M, Sasaki H, Tagashira E, Ogishima M, Takano Y, Ochiai K. Efficacy and Safety of Vitex agnus-castus Extract for Treatment of Premenstrual Syndrome in Japanese Patients: A Prospective, Open-label Study. Adv Ther. 2014;31(3):362-373. doi:10.1007/s12325-014-0106-z.
  44. He Z, Chen R, Zhou Y et al. Treatment for premenstrual syndrome with Vitex agnus castus: A prospective, randomized, multi-center placebo-controlled study in China. Maturitas. 2009;63(1):99-103. doi:10.1016/j.maturitas.2009.01.006.
  45. MA L, Lin S, Chen R, Wang X. Treatment of moderate to severe premenstrual syndrome with Vitex agnus castus (BNO 1095) in Chinese women. Gynecological Endocrinology. 2010;26(8):612-616. doi:10.3109/09513591003632126.
  46. Turner S, Mills S. A double-blind clinical trial on a herbal remedy for premenstrual syndrome: a case study. Complement Ther Med 1993;1:73-77.
  47. Dietz B, Hajirahimkhan A, Dunlap T, Bolton J. Botanicals and Their Bioactive Phytochemicals for Womens Health. Pharmacol Rev. 2016;68(4):1026-1073. doi:10.1124/pr.115.010843.
  48. Khayat S, Kheirkhah M, Behboodi Moghadam Z, Fanaei H, Kasaeian A, Javadimehr M. Effect of Treatment with Ginger on the Severity of Premenstrual Syndrome Symptoms. ISRN Obstetrics and Gynecology. 2014;2014:1-5. doi:10.1155/2014/792708.
  49. Chen C, Barrett B, Kwekkeboom K. Efficacy of Oral Ginger (Zingiber officinale) for Dysmenorrhea: A Systematic Review and Meta-Analysis. Evidence-Based Complementary and Alternative Medicine. 2016;2016:1-10. doi:10.1155/2016/6295737.
  50. Daily J, Zhang X, Kim D, Park S. Efficacy of Ginger for Alleviating the Symptoms of Primary Dysmenorrhea: A Systematic Review and Meta-analysis of Randomized Clinical Trials. Pain Medicine. 2015;16(12):2243-2255. doi:10.1111/pme.12853.
  51. Jenabi E. The effect of ginger for relieving of primary dysmenorrhoea. The Journal of Pakistan Medical Association2013;63(1):8-10.
  52. Rahnama P, Montazeri A, Huseini H, Kianbakht S, Naseri M. Effect of Zingiber officinale R. rhizomes (ginger) on pain relief in primary dysmenorrhea: a placebo randomized trial. BMC Complement Altern Med. 2012;12(1). doi:10.1186/1472-6882-12-92.
  53. Pattanittum P, Kunyanone N, Brown J et al. Dietary supplements for dysmenorrhoea. Cochrane Database of Systematic Reviews. 2016. doi:10.1002/14651858.cd002124.pub2.
  54. Kashefi F, Khajehei M, Tabatabaeichehr M, Alavinia M, Asili J. Comparison of the Effect of Ginger and Zinc Sulfate on Primary Dysmenorrhea: A Placebo-Controlled Randomized Trial. Pain Management Nursing. 2014;15(4):826-833. doi:10.1016/j.pmn.2013.09.001.
  55. Fathizadeh N, Ebrahimi E, Valiani M, Tavakoli N, Hojat Yar M. Evaluating the effect of magnesium and magnesium plus vitamin B6 supplement on the severity of premenstrual syndrome. Iran J Nurs Midwifery Res2010;15(1):401-405.
  56. Wyatt K, Dimmock P, Jones P, Shaughn O'Brien P. Efficacy of vitamin B-6 in the treatment of premenstrual syndrome: systematic review. BMJ. 1999;318(7195):1375-1381. doi:10.1136/bmj.318.7195.1375
  57. dysmenorrhea. Cochrane Database of Systematic Reviews. 2001. doi:10.1002/14651858.cd002124.
  58. Whelan A, Jurgens T, Naylor H. Herbs, vitamins and minerals in the treatment of premenstrual syndrome: a systematic review. The Canadian Journal of Clinical Pharmacology2009;16(3):407-429.
  59. De Souza M, Walker A, Robinson P, Bolland K. A Synergistic Effect of a Daily Supplement for 1 Month of 200 mg Magnesium plus 50 mg Vitamin B6for the Relief of Anxiety-Related Premenstrual Symptoms: A Randomized, Double-Blind, Crossover Study. Journal of Women's Health & Gender-Based Medicine. 2000;9(2):131-139. doi:10.1089/152460900318623.
  60. Wyatt KM, Dimmock PW, Jones PW. Poor-quality studies suggest that vitamin B6 use is beneficial in premenstrual syndrome. Western Journal of Medicine2000;172(4):245.
  61. Nikkhah S, Dolatian M, Naghii M, Zaeri F, Taheri S. Effects of boron supplementation on the severity and duration of pain in primary dysmenorrhea. Complement Ther Clin Pract. 2015;21(2):79-83. doi:10.1016/j.ctcp.2015.03.005.
  62. Younesy S, Amiraliakbari S, Esmaeili S, Alavimajd H, Nouraei S. Effects of fenugreek seed on the severity and systemic symptoms of dysmenorrhea. Journal of Reproduction and Infertility2014;15(1):41-48.
  63. Harel Z, Biro F, Kottenhahn R, Rosenthal S. Supplementation with omega-3 polyunsaturated fatty acids in the management of dysmenorrhea in adolescents. Am J Obstet Gynecol. 1996;174(4):1335-1338. doi:10.1016/s0002-9378(96)70681-6.
  64. Deutch B, Jørgensen E, Hansen J. Menstrual discomfort in Danish women reduced by dietary supplements of omega-3 PUFA and B12 (fish oil or seal oil capsules). Nutrition Research. 2000;20(5):621-631. doi:10.1016/s0271-5317(00)00152-4.
  65. Goldberg R, Katz J. A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain. Pain. 2007;129(1):210-223. doi:10.1016/j.pain.2007.01.020.
  66. Hosseinlou A, Alinejad V, Alinejad M, Aghakhani N. The Effects of Fish Oil Capsules and Vitamin B1 Tablets on Duration and Severity of Dysmenorrhea in Students of High School in Urmia-Iran. Glob J Health Sci. 2014;6(7). doi:10.5539/gjhs.v6n7p124.
  67. The Efficacy of Viburnum Opulus 3X in the Treatment of Primary Dysmenorrhea https://clinicaltrials.gov/ct2/show/NCT02467543.  Accessed April 24, 2018.
  68. Penland J, Johnson P. Dietary calcium and manganese effects on menstrual cycle symptoms. Am J Obstet Gynecol. 1993;168(5):1417-1423. doi:10.1016/s0002-9378(11)90775-3.
  69. Bendich A. The Potential for Dietary Supplements to Reduce Premenstrual Syndrome (PMS) Symptoms. J Am Coll Nutr. 2000;19(1):3-12. doi:10.1080/07315724.2000.10718907.
  70. Thys-Jacobs S, Starkey P, Bernstein D, Tian J. Calcium carbonate and the premenstrual syndrome: Effects on premenstrual and menstrual symptoms. Am J Obstet Gynecol. 1998;179(2):444-452. doi:10.1016/s0002-9378(98)70377-1.
  71. Alvir J, Thys-Jacobs S. Premenstrual and menstrual symptom clusters and response to calcium treatment. Psychopharmacol Bull1991;27(2):145-148.
  72. Thys-Jacobs S, Ceccarelli S, Bierman A, Weisman H, Cohen M, Alvir J. Calcium supplementation in premenstrual syndrome. J Gen Intern Med. 1989;4(3):183-189. doi:10.1007/bf02599520.
  73. Bertone-Johnson E, Hankinson S, Bendich A, Johnson S, Willett W, Manson J. Calcium and Vitamin D Intake and Risk of Incident Premenstrual Syndrome. Arch Intern Med. 2005;165(11):1246. doi:10.1001/archinte.165.11.1246.
  74. Tamborini A, Taurelle R. Value of standardized Ginkgo biloba extract (EGb 761) in the management of congestive symptoms of premenstrual syndrome. Rev Fr Gynecol Obstet1993;88(7-9):447-457.
  75. Ozgoli G, Selselei E, Mojab F, Majd H. A Randomized, Placebo-Controlled Trial of Ginkgo biloba L.in Treatment of Premenstrual Syndrome. The Journal of Alternative and Complementary Medicine. 2009;15(8):845-851. doi:10.1089/acm.2008.0493.
  76. Facchinetti F, Borella P, Sances G, Fioroni L, Nappi R, Genazzani A. Oral magnesium successfully relieves premenstrual mood changes. Obstet Gynecol1991;78(2):177-181.
  77. WALKER A, DE SOUZA M, VICKERS M, ABEYASEKERA S, COLLINS M, TRINCA L. Magnesium Supplementation Alleviates Premenstrual Symptoms of Fluid Retention. J Womens Health. 1998;7(9):1157-1165. doi:10.1089/jwh.1998.7.1157.
  78. Facchinetti F, Sances G, Borella P, Genazzani A, Nappi G. Magnesium Prophylaxis of Menstrual Migraine: Effects on Intracellular Magnesium. Headache: The Journal of Head and Face Pain. 1991;31(5):298-301. doi:10.1111/j.1526-4610.1991.hed3105298.x.
  79. Agha-Hosseini M, Kashani L, Aleyaseen A et al. Crocus sativus L. (saffron) in the treatment of premenstrual syndrome: a double-blind, randomised and placebo-controlled trial. BJOG: An International Journal of Obstetrics and Gynaecology. 2008;115(4):515-519. doi:10.1111/j.1471-0528.2007.01652.x.
  80. London R, Murphy L, Kitlowski K, Reynolds M. Efficacy of alpha-tocopherol in the treatment of the premenstrual syndrome. J Reprod Med1987;32(6):400-404.
  81. London R, Sundaram G, Murphy L, Goldstein P. The effect of alpha-tocopherol on premenstrual symptomatology: a double-blind study. J Am Coll Nutr. 1983;2(2):115-122. doi:10.1080/07315724.1983.10719916.