• If no improvement after 2 months, perform the following:
   - ICIM Blood Analysis : this provides comprehensive information about the quality of the patient’s red blood cell’s, white blood cells, liver & kidney function, anaemia (iron, B12, haemolytic anaemia), indications of hormonal imbalance. (See Blood Analysis.)
   - complete blood count (CBC)
   - chemistry panel
   - thyroid panel
   - T3 uptake
   - Thyroxin
   - Free thyroxin index
   - Ferritin
   - Progesterone
   - Oestrogen
   - Prolactin

• If no apparent abnormalities in CBC, chemistry panel, or hormone levels, consider these tests in order of importance: liver detoxification, adrenal stress index, food allergy panel.   

Therapeutic Considerations
At the Irish Centre of Integrated Medicine (ICIM) we find that the primary causes of PMS are:
• Oestrogen excess
• Progesterone deficiency
• Elevated prolactin levels
• Hypothyroidism
• Stress, endogenous opioid deficiency, and adrenal dysfunction
• Depression
• Nutritional abnormalities
- macronutrient disturbances/excesses
- micronutrient deficiency

Oestrogen and Progesterone
Common finding is elevated/progesterone ratio caused by mild oestrogen elevation and mild progesterone deficiency; increased ratio contributes to PMS by inducing impaired liver function, reducing manufacture of serotonin, decreasing action of vitamin B6, increasing aldosterone secretion, and increasing prolactin secretion.
 

• Oestrogen excess and liver function: oestrogen detox is a liver function requiring adequate B-vitamins; detox impaired by cholestasis arising from oestrogen excess or birth control pills, pregnancy, gallstones, alcohol, endotoxins, hereditary disorders (e.g. Gilbert’s syndrome), anabolic steroids, chemicals or drugs; cholestasis may be predisposing factor to PMS.

• Effects of oestrogen on neurotransmitters: elevated oestrogen/progesterone ratio impairs neurotransmitter synthesis; elevated ratio during luteal phase is also linked to decline in endorphins, adversely impacting mood; low endorphins are common in women with PMS.

• Oestrogen impairs vitamin B6: negative effects of oestrogen excess on neurotransmitters may be a consequence of its effect on action of B6; B6 levels are low in depressed patients, especially those taking oestrogens (birth control pills, Premarin); B6 supplements have positive effects on all PMS symptoms, particularly depression.

• Oestrogen effects on aldosterone: oestrogen excess can increase aldosterone secretion 2-8 days prior to menses.

• Oestrogen and prolactin secretion: endogenous and exogenous oestrogens can increase prolactin secretion by pituitary; elevated prolactin linked to breast pain and fibrocystic breast disease; Vitex agnes-castus (chaste berry) may help elevated prolactin due to corpus luteum deficiency; B6 and zinc supplements can lower prolactin; prolactin elevation can also be linked to low thyroid function.

Reducing oestrogen/progesterone ratio
• Dietary recommendations: dietary factors can reduce circulating oestrogens or block their attachment to receptors; increase plant foods (vegetables, fruits, legumes, whole grains, nuts, seeds); low to moderate meat and dairy; reduce fat and sugar intake; increase soy foods; reduce exposure to environmental oestrogens – pesticides, herbicides, etc.

• Establish proper gastrointestinal flora: liver detoxes hormones and carcinogenic compounds by binding them to glucuronic acid and excreting them in bile; undesirable colon bacteria produce enzyme beta-glucuronidase, which uncouples toxins from glucuronic acids, allowing toxins to be reabsorbed into circulation; establishing proper bacterial flora can reduce activity of this enzyme; probiotic supplements (Lactobacillus acidophilus and Bifidobacterium bifidum) can restore healthy flora.

• Enhance liver detoxification: protect liver by following dietary guidelines; use ‘lipotropic factors’ (choline, methionine, betaine, folic acid, vitamin B12, herbal cholagogues and choleretics) to reduce fat deposition in liver by improving fat metabolism; daily dosage of lipotropics; 1,000 mg choline and 500mg methionine and/or cysteine.

• Consider progesterone therapy: clinical trials have failed to demonstrate consistent superiority of progesterone over placebo in PMS, which has a significant placebo response; positive studies used dosages (200-400 mg b.i.d. as vaginal or rectal suppository from 14 days before menses until onset) that far exceed normal progesterone levels and oestrogen/progesterone ratio; mild side-effects are common; menstrual irregularity, vaginal itching, HA; philosophically preferable to address underlying causes (reduced oestrogen detox and reduced corpus luteum function) rather than drastic artificial altering or oestrogen/progesterone ratio.

Low thyroid function in PMS
Hypothyroidism affects large percentage of women with PMS; many women with PMS and confirmed hypothyroidism experience complete relief of symptoms when given thyroid hormone.

Stress, endorphins, and exercise in PMS
Extreme, unusual, or long-lasting stress can trigger brain changes arising from altered adrenal function and endorphin secretion; women in regular exercise programs do not suffer PMS nearly as often as sedentary women; exercise alleviates PMS by elevating endorphins and decreasing cortisol.

• Coping style and PMS: most women with PMS employ ‘negative’ coping style, exemplified by feelings of helplessness, overeating, devoting too much time to television viewing, emotional outbursts, overspending, excessive behaviour, dependence on chemicals (legal and illicit drugs, tobacco, alcohol); patients need to be counselled on more positive ways to cope.

• Psychotherapy: biofeedback and short-term individual counselling (especially cognitive therapy) have documented clinical efficacy; cognitive therapy has advantage over antidepressant drugs of producing excellent results that can be maintained over time.

• Depression and low serotonin: depression is a common feature of PMS; PMS symptoms are more severe in depressed women, seemingly because of decreased brain neutrotransmitters; serotonin, gamma-amino-butyric acid; 80% of women on Prozac are women aged between 25-50.

Diet considerations
PMS women tend to eat poorly diets; recommendations; predominantly vegetarian diet, reduce intake of fat, eliminate sugar, avoid environmental oestrogens, increase soy foods, eliminate caffeine, keep salt intake low.

• Vegetarian diet and oestrogen metabolism: vegetarian women excrete two to three times more oestrogen in faeces and have 50% lower free oestrogen in blood compared with omnivores; these differences are consequences of lower fat, higher fiber in vegetarian diets and can explain lower incidence of breast cancer, heart disease, and menopausal symptoms among vegetarian women; minimal changes – reduce saturated fat and cholesterol by eating less animal products; increase fiber-rich plant food (fruits, vegetables, grains, legumes); limit animal protein to no more than 4-6 oz q.d., choosing fish, skinless poultry, lean meats; fiber promotes excretion of oestrogens directly and indirectly by promoting favourable bacteria with lower levels of beta-glucuronidase.

• Fat intake and oestrogen metabolism: reducing percentage of calories as fat (saturated) can dramatically reduce circulating oestrogens; low-fat diet improves PMS symptoms; eliminate margarine and foods containing trans fatty acids and partially hydrogenated oils.

• Eliminate sugar: sugar is detrimental to organs involved in blood sugar control, especially in hypoglycaemic and diabetic patients; sugar plus caffeine combination is detrimental to mood; most significant symptom producing food in PMS is chocolate; high sugar intake may impair oestrogen metabolism; women with high sugar intake have higher frequency of PMS; read food labels carefully to identify all forms of sugar.

• Reducing exposure to environmental oestrogens: halogenated hydrocarbons group includes toxic pesticides (DDT, DDE, PCB, PCP, dieldrin, chlordane), which are not easily biodegraded, are stored in fat cells, and mimic oestrogen in the body; may be a major factor in epidemic of oestrogen related health problems (PMS, breast cancer, oligospermia); concentration of these compounds in fruits and vegetables is much lower than in animal fats, meat, cheese, whole milk, and eggs.

• Increase soy foods: soy contains ‘phytoestrogens’ that bind to oestrogen receptors; phytoestrogens are ‘anti-oestrogens’ with only 2% of potency of endogenous oestrogens; balancing effect of phytoestrogens; low endogenous oestrogen (menopause) augmented by mild oestrogenic effect of phytoestrogens, while high endogenous oestrogen effects (PMS) reduced by binding of less-potent phytoestrogens to oestrogen receptors.

• Caffeine and PMS: avoid caffeine, especially if anxiety, depression, breast tenderness, or fibrocystic breast disease are major symptoms; caffeine is strongly linked to presence and severity of PMS; caffeine is particularly significant in psychological symptoms of PMS.

• Salt and PMS: excess NaCl intake, plus reduced intake of K+, causes kidney stress which, in ‘salt-sensitive’ people, leads to hypertension or water retention; patients with water retention during mid-luteal phase must reduce salt; increase K+ rich foods; avoid processed foods high in Na; keep Na intake < 1,800 mg q.d.

Micronutrients in PMS
• Vitamin B6: B6 supplements alone benefit most patients; some women have impaired ability to convert B6 to active form (pyridoxal-5-phosphate) due to deficiency in other nutrients (vitamin B2); use broader-spectrum nutritional supplements or injectable pyridoxal-5-phosphate.
   - dosage; to be discussed with your practitioner
   - safety of vitamin B6; one-time dose > 2,000mg q.d. can produce neurotoxicity in some patients – tingling sensations in feet, loss of muscle coordination, degeneration of nerve tissue; chronic dosing > 500mg q.d. is toxic if taken for many months or years; toxicity has occurred in some people taking long-term doses as low as 150mg q.d., toxicity may arise from overwhelming liver conversion of B6 to P5P – pyridoxine may itself be toxic to nerve cells or it may block receptors for P5P, leading to intracellular B6 deficiency.
   - B6 and magnesium: work together in many enzyme systems; B6 may improve PMS symptoms by increasing intracellular Mg-B6 is essential to transport of Mg into cell.

• Magnesium and PMS: RBC Mg in PMS patients is much lower than in normal subjects; Mg deficiency may account for wide range of PMS symptoms due to integral role in cell function; Mg supplements are effective treatment for PMS.
   - plasma Mg in PMS patients and controls similar; no menstrual cycle effect on plasma Mg in either group; PMS patients have much lower RBC and MBC (mononuclear blood cell) Mg compared with controls; lower RBC/MBC Mg in PMS is consistent across menstrual cycle; Mg measures do not correlate with severity of PMS symptoms.
   - Women with PMS are vulnerable to luteal phase mood destabilization – chronic intracellular Mg depletion is a major predisposing factor; PMS Mg deficiency is also characterised by nervous sensitivity, generalised aches and pains, and a lowered premenstrual pain threshold.
   - Mg is effective in itself but better combined with B6 and other nutrients
   - Dosage; health maintenance = 6mg/kg (2.2lb) body weight; therapeutic for PMS; 12mg/kg body weight.
   - Prefer Mg bound to Krebs cycle intermediates (malate, succinate, fumarate, citrate) due to better absorption and fewer side-effects (laxative effects).