Pre Menstrual Syndrome

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• A cyclic constellation of physical, psychological and behavioural symptoms occurring monthly from the late luteal phase of the menstrual cycle to onset of menstruation 1 • Aetiology may involve abnormal neurotransmitter responses to normal ovarian function, hormonal imbalances, sodium retention and nutritional defi ciencies 1 • Common symptoms include irritability, anxiety, headache, depression, breast tenderness, fl uid retention, abdominal bloating, and weight gain 2 • Up to 90% of women are affected by PMS to varying degrees 3 -20-32% of menstruating women report mild-to-moderate PMS symptoms 2 -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 supplementation 2,3 • Pharmacologic treatment (antidepressants) if nonpharmacologic approaches fail to provide adequate benefi t 2,3

| 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 cycle

Research
There is some evidence that B6 can improve symptoms of PMS such as breast pain or tenderness (mastalgia) and PMS-related depression in some patients. 12A 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. 13Continuous vitamin B6 treatment of 50-150 mg/day may be benefi cial for some PMS symptoms 14 • 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 oedema 15 • 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 effects 16

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/d 17 • A healthy diet rich in complex carbohydrates may improve dysphoric mood state 3 • Increasing dietary calcium and vitamin D intake may help relieve PMS symptoms 2 • Cognitive behavioural therapy (including relaxation) may help PMS/PMDD symptoms 3 • Acupuncture 1,3 and massage 3 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 months 20 EVENING PRIMROSE OIL (Oenothera biennis)

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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, oestrogen levels and increase progesterone levels by inhibiting the release of follicle-stimulating hormone and stimulating of luteinising hormone 4 • More recent research suggests vitex may act via neurotransmitters (dopaminergic) and/or opioid receptors to reduce prolactin secretion. 5,6Prolactin may be elevated premenstrually and is associated with premenstrual mastalgia 6 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 women 7 • Results range from being up to twice as effective as placebo to similar to placebo or vitamin B6 | Primary recommendation | • 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 placebo 1,8,9 Adverse effects • May cause nausea, acne, allergic reactions, headaches, and dyspepsia 5 Interactions • None clinically signifi cant noted in the literature 10 • Interactions have NOT been noted with the low-dose oral contraceptive pill 6 Dosage • Typically found in table/capsule form or as a liquid extract • Dosage range: equivalent to dried fruit 1.5-3 g/d 10 • Dosage of the fruit extract is 20 to 40 mg/d although higher doses (up to 1,800 mg/d) have been used 4 • Manufacturers have recommended that vitex preparations be taken daily as a single dose upon rising, before breakfast, throughout the menstrual cycle 10 neurotransmitter biosynthesis (serotonin, dopamine) 11 • Role in synthesis of prostaglandins and fatty acids 11