WOMEN’S HEALTH

Pre-menstrual syndrome

Complementary medicines

| Description |

• A cyclic constellation of physical, psychological and behavioural symptoms occurring monthly from the late luteal phase of the menstrual cycle to onset of menstruation1

• Aetiology may involve abnormal neurotransmitter responses to normal ovarian function, hormonal imbalances, sodium retention and nutritional defi ciencies1

• Common symptoms include irritability, anxiety, headache, depression, breast tenderness, fl uid retention, abdominal bloating, and weight gain2

• Up to 90% of women are affected by PMS to varying degrees3

- 20–32% of menstruating women report mild-to-

moderate PMS symptoms2

- 3–8% report severe symptoms (premenstrual dysphoric disorder (PMDD))2

| Management guidelines |

• Address the proposed physiologic causes of symptoms (e.g. hormonal imbalance or neurotransmitter response affecting mood)2• Manage symptoms through nonpharmacologic treatment: - dietary changes, lifestyle modifi cations, appropriate supplementation2,3

• Pharmacologic treatment (antidepressants) if non- pharmacologic approaches fail to provide adequate benefi t2,3

| Practice points|

• Chaste tree may decrease some symptoms of PMS, especially breast pain or tenderness, oedema, constipation, irritability, mood changes and headache in some women. Recommended to be taken daily as a single dose upon rising, before breakfast, and throughout the menstrual cycle10

• Vitamin B6 may improve symptoms of PMS such as breast pain or tenderness and depression in some patients. It should not be used in high doses long-term due to possible toxicity• Low magnesium is correlated with PMS and supplementation may decrease symptoms. Combination magnesium and B6 may be more effective than magnesium alone• Higher blood levels of calcium and magnesium may be associated with less severe PMS symptoms

some patients. It should not be used in high doses long-term due to possible toxicity• Low magnesium is correlated with PMS and supplementation may decrease symptoms. Combination magnesium and B6 may be more effective than magnesium alone Combination magnesium and B6 may be more effective than magnesium alone• Higher blood levels of calcium and magnesium may be associated with less severe PMS symptoms

Recommended to be taken daily as a single dose upon rising, before breakfast, and throughout

• Vitamin B6 may improve symptoms of PMS such as breast pain or tenderness and depression in some patients. It should not be used in high doses long-term due to possible toxicity

• Chaste tree may decrease some symptoms of PMS, especially breast pain or tenderness,

Recommended to be taken daily as a single dose upon rising, before breakfast, and throughout

• Chaste tree may decrease some symptoms of PMS, especially breast pain or tenderness,

Recommended to be taken daily as a single dose upon rising, before breakfast, and throughout

• Chaste tree may decrease some symptoms of PMS, especially breast pain or tenderness, oedema, constipation, irritability, mood changes and headache in some women. Recommended to be taken daily as a single dose upon rising, before breakfast, and throughout Recommended to be taken daily as a single dose upon rising, before breakfast, and throughout

• Vitamin B6 may improve symptoms of PMS such as breast pain or tenderness and depression in some patients. It should not be used in high doses long-term due to possible toxicity• Vitamin B6 may improve symptoms of PMS such as breast pain or tenderness and depression in

• Low magnesium is correlated with PMS and supplementation may decrease symptoms. Combination magnesium and B6 may be more effective than magnesium alone• Low magnesium is correlated with PMS and supplementation may decrease symptoms. Combination magnesium and B6 may be more effective than magnesium alone• Higher blood levels of calcium and magnesium may be associated with less severe PMS symptoms

• Vitamin B6 may improve symptoms of PMS such as breast pain or tenderness and depression in

• Chaste tree may decrease some symptoms of PMS, especially breast pain or tenderness, oedema, constipation, irritability, mood changes and headache in some women. Recommended to be taken daily as a single dose upon rising, before breakfast, and throughout

• Vitamin B6 may improve symptoms of PMS such as breast pain or tenderness and depression in some patients. It should not be used in high doses long-term due to possible toxicity• Low magnesium is correlated with PMS and supplementation may decrease symptoms. Combination magnesium and B6 may be more effective than magnesium alone• Higher blood levels of calcium and magnesium may be associated with less severe PMS symptoms

• Chaste tree may decrease some symptoms of PMS, especially breast pain or tenderness, • Chaste tree may decrease some symptoms of PMS, especially breast pain or tenderness,

Recommended to be taken daily as a single dose upon rising, before breakfast, and throughout Recommended to be taken daily as a single dose upon rising, before breakfast, and throughout

• Vitamin B6 may improve symptoms of PMS such as breast pain or tenderness and depression in

• Low magnesium is correlated with PMS and supplementation may decrease symptoms. Combination magnesium and B6 may be more effective than magnesium alone

• Chaste tree may decrease some symptoms of PMS, especially breast pain or tenderness, • Chaste tree may decrease some symptoms of PMS, especially breast pain or tenderness, • Chaste tree may decrease some symptoms of PMS, especially breast pain or tenderness,

Recommended to be taken daily as a single dose upon rising, before breakfast, and throughout Recommended to be taken daily as a single dose upon rising, before breakfast, and throughout Recommended to be taken daily as a single dose upon rising, before breakfast, and throughout Recommended to be taken daily as a single dose upon rising, before breakfast, and throughout

• Vitamin B6 may improve symptoms of PMS such as breast pain or tenderness and depression in some patients. It should not be used in high doses long-term due to possible toxicity• Low magnesium is correlated with PMS and supplementation may decrease symptoms. Combination magnesium and B6 may be more effective than magnesium alone• Higher blood levels of calcium and magnesium may be associated with less severe PMS symptoms

some patients. It should not be used in high doses long-term due to possible toxicity• Low magnesium is correlated with PMS and supplementation may decrease symptoms. Combination magnesium and B6 may be more effective than magnesium alone• Higher blood levels of calcium and magnesium may be associated with less severe PMS symptoms

• Vitamin B6 may improve symptoms of PMS such as breast pain or tenderness and depression in some patients. It should not be used in high doses long-term due to possible toxicity

Recommended to be taken daily as a single dose upon rising, before breakfast, and throughout

• Vitamin B6 may improve symptoms of PMS such as breast pain or tenderness and depression in some patients. It should not be used in high doses long-term due to possible toxicity

Recommended to be taken daily as a single dose upon rising, before breakfast, and throughout

• Chaste tree may decrease some symptoms of PMS, especially breast pain or tenderness,

Recommended to be taken daily as a single dose upon rising, before breakfast, and throughout

• Chaste tree may decrease some symptoms of PMS, especially breast pain or tenderness,

some patients. It should not be used in high doses long-term due to possible toxicity• Vitamin B6 may improve symptoms of PMS such as breast pain or tenderness and depression in

Recommended to be taken daily as a single dose upon rising, before breakfast, and throughout

• Chaste tree may decrease some symptoms of PMS, especially breast pain or tenderness,

| Primary recommendation |

CHASTE TREE (Vitex agnus-castus)

Mechanism of action• May decrease oestrogen levels and increase progesterone levels by inhibiting the release of follicle-stimulating hormone and stimulating of luteinising hormone4

• More recent research suggests vitex may act via neurotransmitters (dopaminergic) and/or opioid receptors to reduce prolactin secretion.5,6 Prolactin

may be elevated premenstrually and is associated with premenstrual mastalgia6

Research

• Several clinical trials have found that vitex may decrease some symptoms of PMS, especially breast pain or tenderness (mastalgia), oedema, constipation, irritability, depressed mood/mood alterations, anger, and headache in some women7

• Results range from being up to twice as effective as placebo to similar to placebo or vitamin B6

| Primary recommendation |

| WOMEN’S HEALTH | 2

• In PMDD, vitex extract 20-40 mg/d for 8 weeks may be comparable to fl uoxetine 20-40 mg/d. Vitex may be more effective for physical symptoms (breast tenderness, swelling, cramps, food cravings), while fl uoxetine may be more effective for psychological symptoms (depression, irritability, insomnia, nervous tension)• Three systematic reviews support vitex in reducing physical PMS and PMDD symptoms and poor mood relative to placebo1,8,9

Adverse effects• May cause nausea, acne, allergic reactions, headaches, and dyspepsia5

Interactions• None clinically signifi cant noted in the literature10

• Interactions have NOT been noted with the low-dose oral contraceptive pill6

Dosage• Typically found in table/capsule form or as a liquid extract• Dosage range: equivalent to dried fruit 1.5-3 g/d10

• Dosage of the fruit extract is 20 to 40 mg/d although higher doses (up to 1,800 mg/d) have been used4

• Manufacturers have recommended that vitex preparations be taken daily as a single dose upon rising, before breakfast, throughout the menstrual cycle10

| Secondary recommendations |

VITAMIN B6

Mechanism of action • Role in neurotransmitter biosynthesis (serotonin, dopamine)11

• Role in synthesis of prostaglandins and fatty acids11

ResearchThere is some evidence that B6 can improve symptoms of PMS such as breast pain or tenderness (mastalgia) and PMS-related depression in some patients.12

• A 1999 meta-analysis (9 trials; n=940) found vitamin B6 100 mg/d was signifi cantly better than placebo in relieving overall PMS symptoms and in relieving mood and depression.13 Continuous vitamin B6 treatment of 50–150 mg/day may be benefi cial for some PMS symptoms14

• A 2007 RCT (n=160) found vitamin B6 80 mg/d signifi cantly decreased a number of psychological and physical symptoms including moodiness, irritability, anxiety, depression, forgetfulness, teariness, fatigue, sugar cravings, increased appetite and oedema15

• Another 2007 controlled trial compared B6 with bromocriptine and found vitamin B6 100 mg/d and bromocriptine were more effective than placebo for reducing the mean premenstrual symptom score after 3 months. B6 had a higher response rate and fewer side effects16

Adverse effects• High doses of vitamin B6 taken over a long period of time may cause peripheral neuropathy. This is unlikely to occur at doses <200 mg/d17

Interactions10

• Amiodarone: B6 may increase risk of photosensitivity• A number of medications may decrease B6 levels and/or increase B6 requirements: antibiotics, hydralazine, isoniazid, L-dopa, oral contraceptives, penacillamine, phenobarbitone, phenytoin and theophylline

Dosage• Typically found in tablet form

• Dosage range: 100–500 mg/d10 Doses of 50-100 mg/d seem to work as effectively as higher doses12

MAGNESIUM (Mg)

• Women (20–25y) with PMS may have lower Mg levels and the risk of PMS may correlate with the level of defi ciency18

• A 2010 randomised controlled trial found that the combination of Mg and vitamin B6 was more effective than Mg or placebo alone in decreasing PMS symptoms19

MAGNESIUM (Mg)

VITAMIN B6

REFERENCES 1. Jang SH, Kim D, Choi MS. Effects and treatment methods of acupuncture and herbal medicine for premenstrual syndrome/premenstrual dysphoric disorder: systematic review. BMC Complement Altern Med 2014; 14:11. 2. Biggs WS, Demuth RH. Premenstrual syndrome and premenstrual dysphoric disorder. Am Fam Phys 2011; 84(8):818-924. 3. Jarvis CI, Lynch AM, Morin AK. Management strategies for premenstrual syndrome/premenstrual dysphoric disorder. Ann Pharmacother 2008; 42(7):967-78. 4. Roemheld-Hamm B. Chasteberry. Am Fam Physician 2005;72:821-4 5. Daniele C, Thompson Coon J, Pittler MH, et al. Vitex agnus castus: a systematic review of adverse events. Drug Saf 2005; 28(4):319-32. 6. Bone K, Mills S. Principles and Practice of Phytotherapy. Elsevier 2013 7. Natural Medicines Database 2016. Vitex agnus-castus professional monograph. 8. Whelan AM, Jurgens TM, Naylor H. Herbs, vitamins and minerals in the treatment of premenstrual syndrome: a systematic review. Can J Clin Pharmacol 2009; 16(3):e407-29. 9. Dante G, Facchinetti F. Herbal treatments for alleviating premenstrual symptoms: a systematic review. J Psychosom Obstet Gynaecol 2011; 32(1):42-51. 10. Braun L, Cohen M. Herbs and Natural Supplements 4th ed. Elsevier 2015 11. Ebrahimi E, Khayati Motlagh S, Nemati S, et al. Effects of magnesium and vitamin B6 on the severity of premenstrual syndrome symptoms. J Caring Sci. 2012; 1(4):183-9. 12. Natural Medicines database 2016. Pyridoxine professional monograph 13. Wyatt KM, Dimmock PW, Jones PW, et al. Effi cacy of vitamin B6 in the treatment of premenstrual syndrome: a systematic review. BMJ 1999; 318(7195):1375-81. 14. Canning S, Waterman M, Louise Dye L. Dietary supplements and herbal remedies for premenstrual syndrome (PMS): a systematic research review of the evidence for their effi cacy. J Reprod Infant Psychol 2006; 24(4):363-78. 15. Kashanian M, Mazinani R, Jalalmanesh S. Pyridoxine (vitamin B6) therapy for premenstrual syndrome. Int J Gynaecol Obstet 2007; 96(1):43-4. 16. Sharma P, Kulshrestha S, Singh GM, Bhagoliwal A. Role of bromocriptine and pyridoxine in premenstrual syndrome. Indian J Physiol Pharmacol 2007;51(4):368-74 17. Higdon J. An evidence-based approach to vitamins and minerals. Thieme 2003 18. Saeedian KA, Amani R, Cheraghian B. The Association between the risk of premenstrual syndrome and vitamin D, calcium, and magnesium Status among university Students: a case control study. Health Promot Perspect 2015; 5(3):225-30. 19. 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(Suppl1):401-5. 20. Natural Medicines database 2016. Evening primrose oil professional monograph

Contact education@blackmoresinstitute.org Healthcare Professional Advisory Service 1800 151 493 Website blackmoresinstitute.org

| Diet and lifestyle recommendations |

• Premenstrual decreases in caffeine, salt, and refi ned sugars may help reduce fl uid retention, bloating, and weight gain3

• A healthy diet rich in complex carbohydrates may improve dysphoric mood state3

• Increasing dietary calcium and vitamin D intake may help relieve PMS symptoms2

• Cognitive behavioural therapy (including relaxation) may help PMS/PMDD symptoms3

• Acupuncture1,3 and massage3 may improve PMS symptoms

Note on:

EVENING PRIMROSE OIL (Oenothera biennis)

• Most clinical studies show that taking evening primrose oil orally does not relieve symptoms

associated with PMS. However, it has been suggested that studies should last at least six months for the benefi t of evening primrose oil to become apparent. Most studies published have lasted no more than four months20

EVENING PRIMROSE OIL (Oenothera biennis)