PMS and PCOS - Genova Diagnostics
Transcription
PMS and PCOS - Genova Diagnostics
Balancing Younger Women’s Hormones PMS, PCOS and Infertility Pamela W. Smith, M.D., MPH, MS 1 Christine Stubbe, ND Medical Education Specialist - Asheville 3 Pamela W. Smith, M.D., MPH, MS Technical Issues & Clinical Questions Please type any technical issue or clinical question into either the “Chat” or “Questions” boxes, making sure to send them to “Organizer” at any time during the webinar. We will be compiling your clinical questions and answering as many as we can the final 15 minutes of the webinar. DISCLAIMER: Please note that any and all emails provided may be used for follow up correspondence and/or for further communication. Need more resources? Ensure you have an account! Balancing Younger Women’s Hormones PMS, PCOS and Infertility Pamela W. Smith, M.D., MPH, MS 6 7 Additional Information • • • • • • • • • • Join us for the Fellowship/Master's Degree in Metabolic and Nutritional Medicine. Each of the modules/courses are offered in conjunction with The University of South Florida Morsani College of Medicine Open to MDs/DOs, Pharmacists, PAs, NPs, NDs, PhDs, DCs, DDSs, CCNs and anyone else who takes care of patients. Module I: A Metabolic/Functional Medicine Approach to Hormone Replacement Therapy, Adrenals, and Hypothyroidism Module II: A Metabolic/Functional Medicine Approach to Hypercholesterolemia, Hypertension and Insulin Resistance/Diabetes Module III: A Metabolic/Functional Medicine Approach to GI Health, Neurology and Neurotransmitters Module IV: Nutritional Depletions Caused by Medications, Amino Acids, Fatty Acids and Liver Detoxification Module V: Clinical Intensives: Numerous Case Histories of Hundreds of Patients from a Metabolic/Functional Medicine Approach Join us on-line or in person. The modules in person are rotated around the U.S. and module V is also offered in the U.S. and overseas. For more information on these educational experiences and 40 other modules that are offered please contact me at: [email protected] Pamela Smith, M.D., MPH, MS. Co-Director, Master's Program in Medical Sciences with a concentration in Metabolic and Nutritional Medicine, Morsani College of Medicine University of South Florida. 8 Reference – Smith, P., What You Must Know About Women’s Hormones, Garden City Park, NY: Square One Publishing, 2009. 9 PMS 10 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. 11 Common PMS Symptoms • • • • • • • • • Abdominal bloating Acne Angry outbursts Anxiety Appetite changes Asthmatic attacks Avoidance of social activities Backache Bladder irritation 12 Common PMS Symptoms (Cont.) • • • • • • • • • Bleeding gums Breast swelling/tenderness Bruising Clumsiness Confusion Conjunctivitis Constipation Cramps Craving salty foods or sweets 13 Common PMS Symptoms (Cont.) • • • • • • • • • Crying spells Decreased hearing Decreased productivity Decreased sex drive Depression Distractibility Dizziness Drowsiness Eye Pain 14 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 15 Common PMS Symptoms (Cont.) • • • • • • • • • Herpetic outbreak Hives or rashes Hot flashes Alcohol sensitivity Sensitivity to light and noise Inefficiency Indecision Insomnia Irritability 16 Common PMS Symptoms (Cont.) • • • • • • • • • Joint pains Leg cramps Leg swelling Mood swings Nausea Palpitations Panic attacks Poor coordination Poor judgment 17 Common PMS Symptoms (Cont.) • • • • • • • • • Poor memory Poor vision Restlessness Ringing in ears Runny nose Seizures Sinusitis Sore throat Spots in front of eyes 18 Common PMS Symptoms (Cont.) • • • • • • • • Suspiciousness Tearfulness Tension Tingling in hands and feet Tremors Visual changes Vomiting Weight gain 19 PMS is Frequently Misdiagnosed as a Psychological Problem • • • • • • • Anxiety disorder Depression Seizure disorder Panic attacks Agoraphobia Eating disorders Various personality disorders 20 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. 21 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. 22 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 23 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) • Avoid caffeine and alcohol who are antagonist to B vitamins 24 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 25 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? 26 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 27 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 28 Magnesium • Women with PMS have low magnesium levels – Eat foods high in magnesium – Take magnesium supplements (400-600 mg) 29 Vitamin A • Has been shown to relieve PMS symptoms – Is a diuretic – Combats stress and fatigue – Is an antioxidant 30 Exercise • Exercise helps with PMS symptoms – Helps relieve painful muscles and joints, tension headaches, low back pain, lower body bloating, tiredness, and irritability 31 Herbal Therapies • Black Cohosh (Cimicifuga racemosa/Actaea 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. 32 Progesterone • Very effective in treating PMS – Use days 14-25 of cycle 33 PCOS 34 PCOS • Affects nearly 10% of the women in the U.S. • Accounts for 75% of the women with amenorrhea • Accounts for 85% of women with androgen excess and hirsutism. – Marchese, M., “Environmental medicine update,” Townsend Letter Feb/March 2012; p. 66-8. – Guzick, D., “Polycystic ovarian syndrome,” Obstet Gynecol 2004; 103(1):181-93. 35 PCOS (Cont.) • Consensus workshop sponsored by the European Society of Human Reproduction and Embryology (ESHRE) and the American Society of Reproductive Medicine (ASRM) in 2003 agreed upon a new definition of PCOS. 36 PCOS (Cont.) • Two out of three criteria must be present – Oligoovulation and/or anovulation – Clinical or biochemical signs of excess androgen activity – Polycystic ovaries on ultrasound (> or equal 12 follicles 2-9 mm or vol > 10 ml) • Alexander, C., “Polycystic ovary syndrome: a major unrecognized cardiovascular risk factor in women,” Rev Obstet Gynecol 2009; 2(4):23239. • Ibid., Marchese. 37 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. 38 Signs and Symptoms of PCOS (Cont.) • 40% of hirsute women who have normal cycles are anovulatory. – Ibid., Marchese. – Carmina, E., “Diagnosing PCOS in women who menstruate regularly,” Contemp Obstet Gynecol 2003; 53-64. 39 Signs and Symptoms of PCOS (Cont.) • Hirsutism and acne are present in 70% of women with PCOS and 10% of women without PCOS. – Ibid., Marchese. – Hill, K., “Update: the pathogenesis and treatment of PCOS,” Nurse Pract 2003; 28:8-25. 40 Signs and Symptoms of PCOS (Cont.) • Infertility affects 75% of women that are obese with PCOS. • Weight gain is usually around the waist as opposed to overall weight gain. – Ibid., Marchese. – Pritts, E., “Treatment of the infertile woman with polycystic ovarian syndrome,” Obstet Gynecol Surv 2002; 57:587-97. 41 Signs/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 42 Causes of PCOS • Many scientist believe that PCOS has a hereditary component. – Atimo, W., et al., “Familial ssociations 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. 43 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. 44 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. 45 Causes of PCOS (Cont.) • Women that are overweight and women that are not that have PCOS, both have a higher rate of insulin resistance and hyperinsulinemia than controls. – King, J., “Polycystic ovarian syndrome,” Jour Midwifery Women’s Health 2006; 51(6):415-22. 46 Causes of PCOS (Cont.) • Insulin decreases SHBG levels which increases the level of circulating testosterone. – Ibid., King. – Ibid., Tsilchorozidou. • Insulin works with LH to increase androgen production in the ovarian theca cells. – Ibid., Marchese. 47 Causes of PCOS (Cont.) • Women with PCOS have an increase in LH amplitude and frequency which results in an elevated 24-hour secretion of LH. – Ibid., Marchese. • Increased LH levels leads to an increase in androgen production by the theca cells in the ovary. – Ibid., Marchese. 48 Causes of PCOS (Cont.) • Defect in androgen production resulting in increased ovarian androgen production. • Due to an increase in ovarian enzymatic activity involved in the making of testosterone precursors which leads to elevated testosterone levels. – Ibid., Marchese. – Ibid., King. – Ibid., Tsilchorozidou. 49 Causes of PCOS (Cont.) • Phthalates, bisphenol-A, cadmium, and mercury toxicities have all be related to PCOS. – Altering hormones to cause anovulation – Development of insulin resistance – Hyperandrogenemia • Ibid., Marchese. 50 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. 51 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 adrenal steroid production rates,” Jour Clin Endocrino Metab 2003; 88(12):5907-13. 52 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. – Ibid., King. – Tsilchorozidou, T., et al., “The pathophysiology of polycystic ovarian syndrome,” Clin Endocrinol (Oxf) 2004; 60:1-17. 53 Differential Diagnosis for PCOS • Differential diagnosis of other disease states with polycysticappearing ovaries – – – – – Hypothyroidism Hypothalamic amenorrhea Cushing’s syndrome Congenital adrenal hyperplasia Ovarian/adrenal tumors 54 References – Ibid., Marchese. – Chang, R., et al., Normal ovulatory women with polycystic ovaries have hypoandrogenic pituitary-ovarian responses to gonadotropin-releasing hormone-agonist testing,” Jour Clin Endocrinol Metab 2000; 85(3):9951000. 55 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. • Heart Disease – Talbott, E., et al., “Cardiovascular risk in women with polycystic ovary syndrome,” Obstet Gynedol Clin North Amer 2001; 28(1):111-33. • Hypertension – Rajkhowa, M., et al., “Polycystic ovary syndrome: a risk for cardiovascular disease,” BJOG: Int Jour Obstet Bynecol 2000; 107(1):11-8. 56 PCOS: Risk Factor For Other Major Diseases (Cont.) • Infertility – 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. • Hormonally related cancers – Radulovic, A., et al., “Obesity and hormone function changes in female patients with polycystic ovaries,” Med Pregl 2003; 56(9-10):476-80. • Obesity – Gonzalez, C., et al., “Polycystic ovarian disease: clinical and biochemical expression,” Ginecol Obstet Mex 2003; 71:253-58. 57 Diabetes and PCOS • PCOS is a risk factor for 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 to get diabetes. – 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. 58 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 irregular cycle increases even more if the patient is obese. • Ibid., Solomon. 59 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. 60 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 longterm 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. 61 Heart Disease and PCOS (Cont.) • Up to 70% of women in the U.S. with PCOS have dyslipidemia. • Ibid., Marchese. • 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):3696-701. • Ibid., Marchese. • Chang, R., “A practical approach to the diagnosis of polycystic ovary syndrome,” Amer Jour Obstet Gynecol 2004; 101:713-17. 62 References (Cont.) – Wild, R., et al., “Assessment of cardiovascular risk and prevention of cardiovascular disease in women with the polycystic syndrome: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) society,” Fertil Steril 20011; 95(3):1073-79. – Ehrmann, D., “Polycystic ovarian syndrome,” NEJM 2005; 353:1223-36. – Phelan, N., et al., “Lipoprotein subclass patterns in women with polycystic ovary syndrome (PCOS) compared with equally insulinresistant women without PCOS; Jour Clin Endocrinol Metab 2010; 95(8):3933-39. 63 Heart Disease and PCOS • 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. 64 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. 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. 66 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. 67 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. 68 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. 69 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. 70 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. 71 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 reporductive 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. 72 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. 73 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. 74 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 31-year study,” Hum Fertil (Camb) 2000; 3(2):101-05. 75 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):883-96. 76 Treatment of PCOS • • • • • • • • • Medications Fiber Low GI program Reduce stress Essential fatty acids Drink enough water Antioxidants Herbal remedies Detoxification 77 Medications • Anti-androgen medications – Aldactone (spironolactone) – Tagament (cimetidine) • Testosterone metabolism blockers – Propecia (finsteride) • Medications to lower blood sugar – Glucophage (metformin) is the most successful • Gonadotropin-Releasing Hormone Antagonists – Lupron (leuprolide) 78 Medications (Cont.) • Hair growth stimulators – Rogaine solution (minoxidil) • Hair metabolism inhibitors – Vaniqa cream (eflornithine) • Menstrual Regulators – Progestins – BCP • Choose ones that are the least androgenic (desogestrel or norgestimate) – Progesterone 79 Medications (Cont.) and Surgical Treatment of PCOS • Ovulation Inducers – – – – Clomid/Serophene (clomiphene) Pergonal/Humegon/Repronex (hMG) Follistim/Gonal (FSH) Profasi/Pregnyl (HCG) • Surgery – Ovarian wedge resection – Laparoscopic ovarian drilling 80 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. 81 Low Glycemic Index Diet, Weight Loss, and Exercise • Place the PCOS patient on a low glycemic index eating program along with moderate exercise. • Study done with 18 women with PCOS involved a 6 month weight loss program and exercise. 82 Low Glycemic Index Diet, Weight Loss, and Exercise • Study revealed the following results – – – – – 11% reduction in central fat 71% improvement in insulin sensitivity index 33% decrease in fasting insulin levels 39% decrease in LH levels 50% of the women started ovulating • Huber-Buchholz, M., et al., “Restoration of reproductive potential by lifestyle modification in obese polycystic ovary syndrome: role of insulin sensitivity and luteinizing hormone,” Jour Clin Endocrinol Metab 1999; 84(4):1470-74. 83 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. 84 Reduce Stress (Cont.) • Consequently, if cortisol levels are elevated, the symptoms of PCOS can be exacerbated. 85 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):615-20. 86 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. 87 Nutritional Treatment of Insulin Resistance • Chromium picolinate (400-600 micrograms) – Decreases sugar cravings and improves insulin sensitivity • Lipoic acid (200-600 mg) – Improves insulin sensitivity and helps prevent neuropathy • CLA (1,000-3,000 mg) – Improves insulin sensitivity • Zinc 25-50 mg) – Helps balance blood sugar levels • Vitamin E (600-800 IU natural) – Helps balance hormonal function 88 Nutritional Treatment of Insulin Resistance • Taurine (1,000-3,000 mg) – Increases activity of insulin receptor and improves sensitivity to insulin • Magnesium (400-800 mg) – Improves glucose uptake • Biotin (4-8 mg) – Increases insulin sensitivity • Vanadium (20-50 mg) – Improves insulin sensitivity • Vitamin D (400-2,000 IU) – Helps pancreas release insulin 89 Nutritional Treatment of Insulin Resistance • Co-enzyme Q-10 (30-300 mg) – Provides energy for metabolic pathways • B complex (50-100 mg) – Aids in glucose metabolism and decreases sugar cravings • Vitamin C (1,000-3,000 mg) – Cofactor in glucose metabolism • Manganese (5-10 mg) – Aids carbohydrate metabolism • Inositol (d-chiroinositol) – Decreases insulin resistance • Lentils, chickpeas, and broccoli all decrease insulin levels. – Smith, P., What You Must Know About Vitamins, Minerals, Herbs, and More. Garden City Park, NY: Square One Publishing, 2008. 90 Herbal Therapies • Trigonella foerum-graecum (fenugreek) – Interferes with absorption and digestion of sugars • Uemura, T., “Diosgenin present in fenugreek improves glucose metabolism by promoting adipocyte differentiation and inhibiting inflammation in adipose tissue,” Mol Nutr Food Res m2010; 54(11):1596-1608. 91 Herbal Therapies (Cont.) • Gymnema sylvestre – Improves insulin sensitivity and interferes with the absorption of glucose – Also reduces total cholesterol, triglycerides, and LDL. May increase HDL. • Luo, H., et al., “Decreased bodyweight without rebound and regulated lipoprotein metabolism by gymnemate in genetic multifactor syndrome animal,” Mol Cell Biochem 2007; 299(1-2):93-8. 92 Herbal Therapies (Cont.) • Cinnamon – Improves glucose utilization and increases insulin receptor sensitivity • FOS • Cimicifuga racemosa (black cohosh) – Binds to estrogen receptors and lowers LH • Vitex agnus castus (chasteberries) – Reduces prolactin secretion and lowers the estrogenprogesterone ratio 93 Herbal Remedies (Cont.) • Serenoa repens (saw palmetto) – Inhibits 5-alpha reductase so inhibits conversion of testosterone to DHT – Reduces androgen effects at the hair follicle and pilosebaceous unit which decreases hirsutism and acne. – 200 mg BID • Ibid., Marchese. • Pais, P., Potency of a novel saw palmetto ethanol extract, SPET-O85, for inhibition of 5alpha-reductase II,” Adv Ther 2010; 27(8):555-63. 94 Herbal Therapies (Cont.) • Urtica dioica (nettle) – Nettle root binds to and increases SHBG decreasing the amount of testosterone available for the body to use. – 300 mg BID • Nettle leaf does not work – Chrubasik, J., et al., “A comprehensive review on the stinging nettle effect and efficacy profiles. Part II: urticae radix,” Phytomedicine 2007; 14(7-8):568-79. – Anon. “Urtica dioica; Urtica urens (nettle),” Monograph Altern Med Rev 2007; 12(3):280. – Ibid., Marchese. 95 Herbal Therapies (Cont.) • Camellia sinensis (green tea) – Increases SHBG which decreases testosterone – Promotes weight loss • Nagata, C., et al., “Association of coffee, green tea, and caffeine intakes with serum concentrations of estradiol and sex hormone-binding globulin in premenopausal Japanese women,” Nutr Cancer 1998; 30(1):21-4. 96 Herbal Therapies (Cont.) • Camellia sinensis (green tea) (cont.) – Placebo-controlled trial of women with PCOS showed that the body weight of the group that used green-tea decreased by 2.4%. – The weight and BMI of the control group was higher at the end of the study. – 270 mg of EGCG was used • Chan, C., et al., “Polycystic ovary syndrome—a randomized placebocontrolled trial. Effects of Chinese green tea on weight and hormonal and biochemical profiles in obese patients with PCOS,” Jour Soc Gynecol Investig 2006; 13(1):63-8. 97 Herbal Therapies (Cont.) • Glycyrrhiza glabra (licorice root) – Can decrease testosterone synthesis – Study using 3.5 grams of licorice containing 7.6% glycyrrhizic acid (0.25 grams total glycyrrhizic acid qd) for 2 months showed a reduction in testosterone levels. • Ibid., Marchese. • Amanini, D., et al., “History of the endocrine effects of licorice,” Exp Clin Endo Diabetes 2002; 110(6):257-61. • Amanini, D., et al., “Licorice reduces serum testosterone in healthy women,” Steroids 2005; 69:763-66. 98 Herbal Therapies (Cont.) • Spearmint tea – Lowers testosterone levels – May raise FSH and LH – May improve hirsutism • Grant, P., t al., “Spearmint herbal tea has significant anti-androgen effects in polycystic ovarian syndrome. A randomized controlled trial,” Phytother Res 2010; 24:186-88. 99 Herbal Therapies (Cont.) • D-chiro-inositol – Placebo-controlled trial with 44 women. Half received D-chiro-inositol 1200 mg qd for 6-8 weeks. – Insulin and testosterone levels were lowered in all of the women and 18 of them ovulated. • Nestler, J., et al., “Ovulatory and metabolic effects of d-chiro-inositol in the polycystic ovary syndrome,” NEJM 1999; 340:1314-20. • Ibid., Marchese. 100 Herbal Therapies (Cont.) • Maitake mushroom extract (Grifola frondosa) – Study compared patients with PCOS that were given maitake mushroom extract versus clomiphene. – After 3 cycles • Rate of ovulation in maitake group was 76.9% • Rate of ovulation in clomiphene group was 93.5% – Proposed mechanism of action is that maitake mushroom enhanced insulin sensitivity » Chen, J., et al., “Maitake mushroom (Grifola frondosa) extract induces ovulation in patients with polycystic ovary syndrome: a possible monotherapy and a combination therapy after failure with first-line clomiphene citrate,” Jour Altern Complement Med 2010; 16(12):1295-99. » Ibid., Marchese. 101 Detoxification • Test patient for toxic metals and chelate if needed. • Detoxify patient from any other toxin. 102 Supplements to Avoid With PCOS • High doses of niacin – Can worsen insulin sensitivity 103 Reference Book For Patients – The PCOS Protection Plan by Colette Harris and Theresa Cheung. Hay House Inc. 2006. Available worldwide. 104 Case #1 • 20-year-old patient with the chief complaint that she does not cycle on a regular basis. • PH: unremarkable • FH: unremarkable • SH: is a college student • Medications: none • ROS: negative • P/E: normal 108 What Do You Want To Do With This Patient? 109 Conclusion • Doing a 28-day salivary test is very important to help evaluate patients that may have PMS or PCOS. 110 Tests Referenced • • • • • • Rhythm/ Rhythm Plus Adrenocortex Stress Profile Hormonal Health PreD/ MetSyn CV Health Comprehensive Urine Elements Profile/ Toxic Element Clearance Q & A Session © Genova Diagnostics Additional Education Materials: www.gdx.net Sample Reports, Interpretive Guides, Kit Instructions, FAQs, Payment Options, and much more! Additional Education Materials: www.gdx.net © Genova Diagnostics LiveGDX Additional Questions? • US Client Services: 800-522-4762 • UK Client Services: 020.8336.7750 Genova Diagnostics offers Medical Education phone appointments for more specific inquiries or questions we did not have time to answer during the webinar We look forward to hearing from you! Upcoming LiveGDX Webinars Join us next month for another LiveGDX! Register for upcoming LiveGDX Webinars online at www.gdx.net Balancing Younger Women’s Hormones PMS, PCOS and Infertility Pamela W. Smith, M.D., MPH, MS 11 9