PMS and PCOS Dr Craige Golding MBCHB, FCP(SA), ABAARM, FAAFM Board certified antiaging physician PMS • PMS is a hormonal disorder characterized by the monthly recurrence of certain physical or psychological symptoms during the two weeks before menstruation and the subsiding of those symptoms when flow begins or slightly afterwards. Common PMS Symptoms • • • • • • • • • Abdominal bloating Acne Angry outbursts Anxiety Appetite changes Asthmatic attacks Avoidance of social activities Backache Bladder irritation Common PMS Symptoms (Cont.) • • • • • • • • • Bleeding gums Breast swelling/tenderness Bruising Clumsiness Confusion Conjunctivitis Constipation Cramps Craving salty foods or sweets Common PMS Symptoms (Cont.) • • • • • • • • • Crying spells Decreased hearing Decreased productivity Decreased sex drive Depression Distractibility Dizziness Drowsiness Eye Pain Common PMS Symptoms (Cont.) • • • • • • • • • Facial swelling Fatigue Fear of going out alone Fear of losing control Finger swelling Food sensitivity Forgetfulness Aches and pains Headaches Common PMS Symptoms (Cont.) • • • • • • • • • Herpetic outbreak Hives or rashes Hot flashes Alcohol sensitivity Sensitivity to light and noise Inefficiency Indecision Insomnia Irritability Common PMS Symptoms (Cont.) • • • • • • • • • Joint pains Leg cramps Leg swelling Mood swings Nausea Palpitations Panic attacks Poor coordination Poor judgment Common PMS Symptoms (Cont.) • • • • • • • • • Poor memory Poor vision Restlessness Ringing in ears Runny nose Seizures Sinusitis Sore throat Spots in front of eyes Common PMS Symptoms (Cont.) • • • • • • • • Suspiciousness Tearfulness Tension Tingling in hands and feet Tremors Visual changes Vomiting Weight gain PMS is Frequently Misdiagnosed as a Psychological Problem • Anxiety disorder • Depression • Seizure disorder • Panic attacks • Agoraphobia • Eating disorders • Various personality disorders PMS • Can be treated with a better than 90% success • rate. There is no definitive diagnostic test that confirms a diagnosis of PMS. There is no clear course of development. However, something in the patients lives interferes with the pituitary-ovarian feedback loop, and it decreases the supply of progesterone. • Precipitating Factors For PMS • • • • Oral contraceptives due to progestin Pregnancies Miscarriages and abortions Tubal ligations – 37% of women who have a tubal ligation develop PMS and other complications such as pelvic pain and irregular cycles. – Studies have shown that after tubal ligation women have higher estrogen and lower progesterone levels in the second half of their cycles. Precipitating Factors For PMS (Cont.) • Partial hysterectomy – Even in patients who never had PMS before due to the decreased supply of blood to the ovaries post hysterectomy • Age Key Factor • Low blood sugar – Due to hormonal changes a woman’s body becomes more sensitized to drops in blood sugar the last two weeks of the cycle – Symptoms of hypoglycemia are very much like PMS symptoms – Treatment • 6 small meals a day • No refined sugars • B6 which is needed for the production of dopamine and serotonin (Use B complex) • VOID caffeine and alcohol who are antagonist to B vitamins Caffeine • Caffeine makes things worse – Increases the body’s production of prostaglandins which increase during the premenstrual period and can cause breast tenderness, arthritis, abdominal cramping, headaches and backaches – Acts as a diuretic which depletes the body of potassium, magnesium, B and C vitamins – Causes the release of adrenalin which can lower blood sugar Migraine Headaches • Hormonally related migraines—Test: – Did the headaches have their onset at puberty, or after first taking contraceptive pills, or after a pregnancy? – Did the attacks occur at the same time of each cycle? – Free from headaches during the later states of pregnancy? – Increases in severity of headaches after each pregnancy, abortion or miscarriage? Four Main Mechanisms of Hormonally Related Headaches • Estrogen and progesterone increase at the time of ovulation. This can precipitate a headache. Estrogen binds salt in the body which may cause edema including swelling of the tissues in the brain. • Hypoglycemia • Changing estrogen levels • Estrogen dominance Edema • Avoid foods with high sodium content • Incorporate foods into the diet that are natural • • • • • diuretics like strawberries and parsley Use evening primrose oil (500-3,000 mg qd) Increase water intake Exercise Use progesterone which is a natural diuretic Try not to use prescription diuretics – Use spironolactone using a prescription diuretic Magnesium • Women with PMS have low magnesium levels – Eat foods high in magnesium – Take magnesium supplements (400-600 mg) Vitamin A • Has been shown to relieve PMS symptoms – Is a diuretic – Combats stress and fatigue – Is an antioxidant Exercise • Exercise helps with PMS symptoms – Helps relieve painful muscles and joints, tension headaches, low back pain, lower body bloating, tiredness, and irritability Herbal Therapies • Black Cohash (Cimcifuga racemosa) – – – – Has a balancing affect on estrogen Relaxant Sedative Anti-spasmotic • Chasteberry (Vitex agnus castus) – Decreases LH and prolactin – Raises progesterone and facilitates progesterone function – Acts as a diuretic • Murray, M., The healing Power of Herbs. California: Prima Publications, 1995, p. 375. Progesterone • Very effective in treating PMS – Use days 10-24 of cycle PCOS • Three criteria set up by the National Institutes of Health – Irregular or absence of menstruation – Excess androgen production – Lack of other reasons for irregular or absence of cycles and excess androgens PCOS (Cont.) • Having ovarian cysts is not one of the three criteria for the diagnosis of PCOS • Therefore, ovaries with many cysts does not necessarily mean that the patient has PCOS. Signs and Symptoms of PCOS • • • • • • • • Obesity Irregular or absent menstrual cycles Infertility/recurrent miscarriage Hirsutism Oily skin/acne Alopecia Acrochordons (skin tags) Depression – Ahene, S., et al., ―Polycystic ovary syndrome,‖ Nurs Stand 2004; 18(26):40-4. Symptoms That Are Revealed Through Lab Results or Other Tests • Cysts on the ovaries • High testosterone level • Elevated insulin level/insulin resistance • Elevated LH • Decreased SHBG • Abnormal lipid profile • Hypertension Causes of PCOS • Many scientist believe that PCOS has a hereditary component. – Atimo, W., et al., ―Familial associations in women with polycystic ovary syndrome,‖ Fert Steril 2003; 80(1):143-45. – Gonzalez, C., et al., ―Polycystic ovaries in childhood: a common finding in daughters of PCOS patients of PCOS patients. A pilot study,‖ Hum Repro 2002; 17(3):771-76. Causes of PCOS (Cont.) • There is some suggestion in the medical literature that women with PCOS are born with a gene that triggers higher than normal levels of androgen or insulin. – Strauss, J., et al., ―Some new thoughts on the pathophysiology and genetics of polycystic ovary syndrome,‖ Ann NY Acd Sci 2003; 997:42-8. – Carey, A., et al., ―Evidence for a single gene effect causing polycystic ovaries and male pattern baldness,‖ Clin Endocrinol 38(6):653-8. Causes of PCOS (Cont.) • Studies have shown that the high levels of • • testosterone and insulin in patients with PCOS are linked. This link is a gene called follistatin. Functions of follistatin – Plays a role in the development of the ovaries – Is needed to make insulin • Urbanek, M., et al., Thirty seven candidate genes for PCOS: Strongest evidence of linkage is follistatin,‖ Proc Nat Acd Sci 1999; 38(6):653-58. Causes of PCOS (Cont.) • Stress may be a contributing factor to PCOS. – Marantides, D., et al., ―Management of polycystic ovary syndrome,‖ Nurse Pract 1997; 22(12):34-8, 40-1. Stress and PCOS • Studies have shown that many women with PCOS cannot process cortisol effectively, leading to elevated cortisol levels in the body. – Tsilchorozidou, T., et al., ―Altered cortisol metabolism in polycystic ovary syndrome: insulin enhances 5 alpha-reduction but not the elevated adreanl steroid production rates,‖ Jour Clin Eneocrino Metab 2003; 88(12):5907-13. Stress and PCOS (Cont.) • When women are under stress, too much prolactin may be released. This may affect the ability of the ovaries to produce the right balance of hormones. – Barnea, E., et al., ―Stress-related reproductive failure,‖ Jour IVF Embryo Transfer 1991; 8:15-23. PCOS: Risk Factor For Other Major Diseases • Diabetes – Pelusi, B., et al., ―Type 2 diabetes and the polycystic ovary syndrome,‖ Minerva Ginecol 2004; 56(1):41-51. – Talbott, E., et al., ―Cardiovascular risk in women with polycystic ovary syndrome,‖ Obstet Gynedol Clin North Amer 2001; 28(1):111-33. – Rajkhowa, M., et al., ―Polycystic ovary syndrome: a risk for cardiovascular disease,‖ BJOG: Int Jour Obstet Gynecol 2000; 107(1):11-8. • Heart Disease • Hypertension PCOS: Risk Factor For Other Major Diseases (Cont.) • Infertility • Hormonally related cancers • Obesity – Trent, M., et al. ―Fertility concerns and sexual behavior in adolescent girls with polycystic ovary syndrome: implications for quality of life,‖ Jour Pedatr Sdolesc Gynecol 2003; 16(1):33-7. – Radulovic, A., et al., ―Obesity and hormone function changes in female patients with polycystic ovaries,‖ Med Pregl 2003; 56(910):476-80. – Gonzalez, C., et al., ―Polycystic ovarian disease: clinical and biochemical expression,‖ Ginecol Obstet Mex 2003; 71:253-58. Diabetes and PCOS • PCOS is a risk factor for diabetes. to get diabetes. – Pelusi, B., et al., ―Type 2 diabetes and the polycystic ovary syndrome,‖ Minerva Ginecol 2004; 56(1):41-51. • If the patient has PCOS they are seven times more likely – Legro, R., et al., ―Prevalence and predictors of risk for Type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women,‖ Jour Clin Endocrinol Metabol 1999; 84(1):165-69. • About half of all women with PCOS have insulin resistance. – De Leo, V., et al., ―Polycystic ovary syndrome and type 2 diabetes mellitus,‖ Minera Ginecol 2004; 56(1):53-62. Diabetes and PCOS (Cont.) • Some studies suggest that women with PCOS who have irregular cycles or no cycles may have double the risk for diabetes. – Solomon, C., et al., ―Long or irregular menstrual cycle as a marker for the risk of type 2 diabetes mellitus,‖ JAMA 2001; 286(19):2421-26. • Risk factor for diabetes in patients with an – Ibid., Solomon. irregular cycle increases even more if the patient is obese. Diabetes and PCOS (Cont.) • The risk of getting diabetes is also increased in patients with PCOS that are not overweight or insulin resistant. – Danaif, A., et al., ―Beta cell dysfunction independent of obesity and glucose intolerance in the polycystic ovary syndrome,‖ Jour Clin Endocrinol Metab 1996; 81:942-47. Heart Disease and PCOS • Women with PCOS have an increased risk of heart disease compared to women without PCOS. – Christian, R., et al., ―Prevalence and predictors of coronary artery calcification in women with polycystic ovary syndrome,‖ Jour Clin Endocrinol Metab 2003; 88(6):2562-68. – Wild, S., et al., ―Cardiovascular disease in women with PCOS: A long-term follow up: A retrospective cohort study,‖ Clin Endocrinol (Oxf) 2000; 52(5):595-600. – Talbot, E., et al., ―Cardiovascular risk in women with polycystic ovary syndrome,‖ Obstet Gynecol Clin North Amer 2001; 28(1):111-33. Heart Disease and PCOS (Cont.) • Women with PCOS frequently have elevated LDL. – Orio, F., et al., ―The cardiovascular risk of young women wit polycystic ovary syndrome: an observational, analytical, prospective case-control study,‖ Jour Clin Endocrinol Metab 2004; 89(8):3696701. • Homocysteine levels are increased in patients with PCOS. – Loverro, G., et al., ―The plasma homocysteine levels are increased in polycystic ovary syndrome,‖ Gynecol Obstet Invest 2002; 53(3):157-62. Heart Disease and PCOS (Cont.) • Women with PCOS have a higher than usual rate of elevated CRP. – Boulman, N., et al., ―Increased C-reactive protein levels in the polycystic ovary syndrome: a marker of cardiovascular disease,‖ Jour Clin Endocrinol Metabol 2004; 89(5):2160-65. Heart Disease and PCOS (Cont.) • Women with PCOS frequently have decreased • total antioxidant status and increased oxidative stress. This pattern may be one of the contributing causes of heart disease in women with PCOS. – Fenkev, I., et al., ―Decreased total antioxidant status and increased oxidative stress in women with polycystic ovary syndrome may contribute to the risk of cardiovascular disease,‖ Fertil Steril 2003; 8091):123-27. Hypertension and PCOS • Women with PCOS have four times the rate of hypertension than women who do not have PCOS. – Lefebvre, P., et al., ―Long-term risks of polycystic ovaries syndrome,‖ Gynecol Obstet Fertil 2004; 32(3):193-98. Hypertension and PCOS (Cont.) • Insulin resistance and hyperinsulinemia raise blood pressure. – Landsberg, M., ―Insulin sensitivity in the pathogenesis of hypertension and hypertensive complications,‖ Clin and Experimental Hyper 1996; 18(3-4):337-46. Hypertension and PCOS (Cont.) How Hyperinsulinemia Causes HTN • High levels of insulin correlate with low sodium • • • in the urine. This leads to an increase in water retention which makes it harder for blood to flow through the circulatory system. Consequently leading to an increase in blood pressure. Insulin also elevates blood pressure by affecting the elasticity of arterial walls. Hypertension and PCOS (Cont.) How Hyperinsulinemia Causes HTN • Insulin alters the mechanical action of the blood • vessel walls by acting on smooth muscle cells stimulating them and making them larger. As smooth muscle cells grow, they make the arterial walls thicker, stiffer, and less supple. This forces the heart to work harder and exert more pressure to force the blood through the narrowed vessels. Infertility and PCOS • In women with PCOS, the ovarian follicles start • • to mature but fail to ripen or to be released. They stay in the ovaries and continue to produce estrogen, but no progesterone. Elevated levels of LH and estrogen have been found in some women with PCOS. This may block ovulation. – Milsom, S., et al., ―LH levels in women with polycystic ovarian syndrome: have modern assays made them irrelevant? British Journ of Obstec and Gynecol 2003; 110(8):760-4. Infertility and PCOS (Cont.) • Higher than normal levels of testosterone are also found in PCOS patients. High levels of testosterone inhibits ovulation. – Franks, S., ―The ubiquituous polycystic ovary,‖ Jour Endocrinol 1991; 129:317-19. • Women with PCOS may miscarry at a higher rate than women without PCOS. – Diejomaoh, M., et al., ―The relationship of recurrent spontaneous miscarriage with reproductive failure, ― Med Princ Pract 2003; 12(2):107-11. – Rai, R., et al., ―Polycystic ovaries and recurrent miscarriage—a reappraisal,‖ Hum Repro 2000; 15:612-15. Infertility and PCOS (Cont.) • Insulin also plays a role in ovulation • The ovaries have insulin receptors • Insulin stimulates an increase in LH and androgen levels decreasing SHBG • In the presence of elevated androgens, LH levels increase and lead to poor follicle development and failure to ovulate. PCOS and Hormonally Related Cancers • Women who had a history of PCOS and irregular periods have a five-fold increase in endometrial cancer. – Hardiman, P., et al., ―Polycystic ovary syndrome and endometrial carcinoma, Lancet 2003; 361(9371):1810-12. • Women who have a history of PCOS may have an increased risk of ovarian cancer. – Spremovi, R., et al., ―The polycystic ovary syndrome associated with ovarian tumor,‖ Srp Arh Celok Lek 1997; 125 (11-12):375-77. PCOS and Hormonally Related Cancers (Cont.) • Women with a history of PCOS may be at risk for breast cancer since they tend to be over weight and have hormonal changes that can lead to unopposed estrogen in the body. – Wild, S., et al., ―Long-term consequences of polycystic ovary syndrome: results of a 31year study,‖ Hum Fertil (Camb) 2000; 3(2):101-05. Obesity • Studies have shown that women with PCOS store fat better and burn calories at a slower rate than women who do not have PCOS. – Robinson, S., et al., ―Postprandial thermogenesis is reduced in polycystic ovary syndrome and is associated with increased insulin resistance,‖ Clin Endocrinol (Oxf) 1992; 36(6):537-43. – Faloia, E., et al., ―Body composition, fat distribution and metabolic characteristics in lean and obese women with polycystic ovary syndrome,‖ Jour Endocrinol Invest 2004; 27(5):424-29. – Gambineri, A., et al., ―Obesity and the polycystic ovary syndrome,‖ Int Jour Obes Relat Metab Disord 2002; 26(7):88396. Treatment of PCOS • • • • • • • • Medications Fiber Low GI program Reduce stress Essential fatty acids Drink enough water Antioxidants Herbal remedies Medications • Anti-androgen medications • Testosterone metabolism blockers • Medications to lower blood sugar • Gonadotropin-Releasing Hormone Antagonists – Lupron (leuprolide) – Glucophage (metformin) is the most successful – Aldactone (spironolactone) – Tagament (cimetidine) – Propecia (finsteride) Medications (Cont.) • Hair growth stimulators • Hair metabolism inhibitors – Rogaine solution (minoxidil) – Vaniqa cream (eflornithine) – Progestins – BCP • Choose ones that are the least androgenic (desogestrel or norgestimate) • Menstrual Regulators – Progesterone Medications (Cont.) and Surgical Treatment of PCOS • Ovulation Inducers – Clomid/Serp[jeme (clomiphene) – Pergonal/Humegon/Repronex (hMG) – Follistim/Gonal (FSH) – Profasi/Pregnyl (HCG) – Ovarian wedge resection – Laparoscopic ovarian drilling • Surgery Fiber • Fiber lowers blood sugar, blood pressure and cholesterol. – Anderson, J., et al., ―Dietary fiber: diabetes and obesity,‖ Amer Jour Gasteroenterol 1986; 81:898-906. – Burke, V., ―Dietary protein and soluble fiber reduce ambulatory blood pressure in treatment of hypertensives,‖ Hypertension 2001; 38(4):821-26. – Anderson, J., et al., ―High-fiber diets for diabetic and hypertriglyceridemic patients,‖ Can Med Assoc Jour 1980; 123:975. – Sprecher, d., et al., ―Efficacy of psyllium in reducing serum cholesterol levels in hypercholesterolemic patietns on high-or low-fat diets,‖ Ann Inter Med 1993; 119:545-54. Low Glyemic Index Diet • Place the PCOS patient on a low glycemic index eating program. Reduce Stress • Cortisol stimulates the release of glucose, fats, and amino acids for the production of energy in the body. • During times of stress, cortisol and insulin levels rise in the body. Cholesterol levels may rise as well. • If cortisol is increased it decreases the making of progesterone and its activity. Cortisol competes with progesterone for common receptors. – Bland, J., ―Introduction to neuroendocrine disorders,‖ Functional Medicine Approaches to Endocrine Disturbances of Aging. Gig Harbor, Washington: The Functional medicine Institute, 2001; p. 121. Reduce Stress (Cont.) • Consequently, if cortisol levels are elevated, the symptoms of PCOS can be exacerbated. Essential Fatty Acids • Essential fatty acids slow down the absorption of carbohydrates into the blood stream. – Kasim Karakas, M., et al., ―Metabolic and endocrine effects of a polyunsaturated fatty acid-rich diet in polycystic ovary syndrome,‖ Jour Clin Endocrinol Metabol 2004; 89(2):61520. Drink Enough Water • The amount of water the body needs in one day is: 1/2 the body weight in oz. every day. • People who drink 5 to 8 glasses of water a day have fewer heart attacks. Dehydration increases the tendency for the blood. – Chan, J., et al., ―Water, other fluids, and fatal coronary heart disease,‖ Amer Jour Epidemiol 2002; 155(9):827-33. Nutritional Treatment of Insulin Resistance • Chromium picolinate (400-600 micrograms) • Lipoic acid (200-600 mg) • CLA (1,000-3,000 mg) • Zinc 25-50 mg) – Decreases sugar cravings and improves insulin sensitivity – Improves insulin sensitivity and helps prevent neuropathy – Improves insulin sensitivity – Helps balance blood sugar levels • Vitamin E (600-800 IU natural) – Helps balance hormonal function Nutritional Treatment of Insulin Resistance • Taurine (1,000-3,000 mg) • Magnesium (400-800 mg) – Increases activity of insulin receptor and improves sensitivity to insulin – Improves glucose uptake – Increases insulin sensitivity – Improves insulin sensitivity – Helps pancreas release insulin • Biotin (4-8 mg) • Vanadium (20-50 mg) • Vitamin D (400-2,000 IU) Nutritional Treatment of Insulin Resistance • Co-enzyme Q-10 (30-300 mg) • B complex (50-100 mg) • Manganese (5-10 mg) • Vitamin C (1,000-3,000 mg) • Inositol (d-chiroinositol) levels. – Provides energy for metabolic pathways – Aids in glucose metabolism and decreases sugar cravings – Cofactor in glucose metabolism – Aids carbohydrate metabolism – Decreases insulin resistance • Lentils, chickpeas, and broccoli all decrease insulin Reference • Smith, P., Vitamins Hype or Hope. Traverse City, Michigan: Healthy Living Books, 2004, p. 210-11. Herbal Remedies • Fenugreek • Gymnema sylvestre • Cinnamon – Interferes with absorption and digestion of sugars – Improves insulin sensitivity and interferes with the absorption of glucose – Improves glucose utilization and increases insulin receptor sensitivity • FOS • Black Cohosh (Cimcifuga racemosa) • Chasteberries (Vitex agnus castus) – Binds to estrogen receptors and lowers LH – Reduces prolactin secretion and lowers the estrogen-progesterone ratio Supplements to Avoid With PCOS • High doses of niacin – Can worsen insulin sensitivity Reference Book For Patients • The PCOS Protection Plan by Colette Harris and Theresa Cheung. Hay House Inc. 2006.