The PCOS PUZZLE An Integrative Approach to Putting the Pieces Together

PRESENTED BY: ELIZABETH BOARD, MD FOUNDER OF ATLANTA FUNCTIONAL MEDICINE, INC. Agenda 2

uFunctional Medicine Principles uExamine the Pieces uPut them together uCase Examples

Inspiration and some fun Functional Medicine Principles 3

u Biochemical individuality based on genetic and environmental uniqueness u Patient centered versus disease centered u Dynamic balance of internal and external factors u Web-like interconnections of physiological factors u Health as a positive vitality–not merely the absence of disease u Promotion of organ reserve–health span - www. functionalmedicine.org Your Personalized Treatment Plan 4 “God grant me the serenity to accept the things I cannot change, The courage to change the things I can, and the wisdom to know the difference.” Reinhold Niebuhr What Are the Puzzle Pieces? 5

Diet Intestinal Sleep Health We need a framework

Voice Acupuncture to properly Supplements organize all of this Mind Body Activity information Medicine Detoxification Treatment Plan 6 u What do these ladies have in common? 7 They are all DIVAS ! Treatment Plan 8 D = DIET, DETOXIFICATION I = INTESTINAL HEALTH V = VEG OUT , VOICE A = ACTIVITY, ACUPUNCTURE S = SLEEP, SUPPLEMENTS Treatment Plan - DIVAS 9 u D = DIET u Elimination diet and REAL Food uEliminate: dairy, gluten, sugar, corn, fruit juice, processed foods, soy

uFavor low glycemic load uEat unprocessed foods uIf it didn’t grow on a plant or walk, swim or fly it probably is NOT food.

If a machine made it, feed it to a machine! Treatment Plan - DIVAS 10

u Elimination Diet Treatment Plan - DIVAS 11 u D = DIET u Anti-inflammatory diet and High Fiber u The Clean 15 and the Dirty Dozen www.ewg.org u “If it comes in a bag or a box, it’ll put you in a bag or a box”. u Eat Like a Queen, not a pauper. Nutrient Dense foods. Three different colors at each meal. u Use food as medicine when possible What you put in your body can alter your destiny! The Clean 15 The Dirty Dozen 12 u Avocado u Kiwi • Apple • Cherry u Papaya u Eggplant • Strawberries Tomatoes u Pineapple u Grapefruit • Grapes • Sweet Bell u Cabbage u Cantalope • Spinach Peppers u Sweet u Cauliflower • Cucumber • Celery • Potatoes • Peaches peas u Corn • Snap peas u Onions u Honeydew • Nectarines u Asparagus u Mangoes (imported)

www.ewg.org DIVAS – Diet 13 Types of Hunger Treatment Plan – DIVAS- 14 Detoxification u First Step is to limit exposure v Avoid Bisphenol A v Check your makeup: www.ewg.org/skindeep v Avoid heating plastics v Avoid Propyl Paraben (in tortillas, muffins, diet cakes, trail mix and dyes) v Avoid Butylated Hydroxyanisole or BHA in chips, preserved fats and processed meat v Avoid Pesticides www.ewg.org Treatment Plan - DIVAS 15 u I = INTESTINAL HEALTH u Healthy gut? Suspect if any gi sypmtoms. u “Gut Restoration” & Prebiotics and Probiotics u Hormone reabsorption risk u Higher prevalence of IBS compared to controls u Herbal accelerators: grape skin, Brassica family, garlic, rosemary these flavonoids induce phase II (the rate limiting step) u Increase hydration to support kidneys Take the garbage out everyday! Treatment Plan - DIVAS 16 Liver Detoxification

Reactive Phase 2 inter- Excretion mediates The rate limiting step

Zinc, Vitamins A, B3, B5, B6, B12, C, E, beta-carotene and methylfolate. L-cysteine, L-glutamine, taurine N-Acetylcysteine, sodium sulfate, L-glutathione BILE & URINE EGCG: green tea catechins STOOL *DETOXIFICATION IS ENERGY DEPENDENT: quality carbs and proteins needed *Correct constipation prior to detoxification WATER ……. The original energy drink! Treatment Plan – DIVAS 17 u V – “VEG OUT”

Acne, Hirsutism, Stress Clitoral Enlargement, Male Hair Pattern

Overproduction of CRH & Cortisol

Clinical Converts More Disruption Excess LH Elevated Excess Hyperandrog Depressi Elevated Excessive Androgen of & Normal Androgen enism on Adrenal Blood Insulin Hormone GnRH Insufficient Menstrual To Estrogen Cortisol Glucose Secretion Production FSH Cycles Levels Cease

Elevated Androgen Production Increased Insulin Pancreatic Metabolic Centripetal Resistance Insulin Syndrome Production Amenorrhea, Anovulation, Infertility MIND-BODY Medicine - DIVAS 18 uYoga uMindfulness Meditation uQi Gong uTai Chi uCognitive Behavioral Therapy uImagery, Visualization MIND-BODY Medicine - DIVAS 19 u Yoga was found to decrease anti-mullerian hormone, LH and testosterone in adolescents u Yoga was found to decrease anxiety symptoms in PCOS adolescents u Mindfulness decreases psychological stress, BP, glucose and inflammation and offers positive effects on the central and autonomic nervous system u RCT 2015: decreases saliv.cortisol, anxiety and depression. Improved QOL u Cognitive Behavioral Therapy beneficial for eating disorders. u More studies need to be done utilizing mind-body techniques to lower cortisol and address the dysfunctional HPA axis. Treatment Plan –DIVAS V- “Veg out” 20 u Mind Body Medicine Classes u Breathing Techniques u Go on a Media Fast u Flex Your Fun Muscle u Heart Math u Mobile Apps Treatment Plan - DIVAS 21 u V – VOICE u Throat Chakra: connects the heart to the head u Difficulty: speaking up, expressing truth, asking for help u PCOS challenge u Trouble connecting inside to outside. Spiritual Bridge u FOCUS: Alignment with Divine Will through responsibility for actions; creativity Treatment Plan - DIV S A 22 u A = ACTIVITY : “MOVEMENT MEDICINE” uIncreases insulin sensitivity uImproves Digestion uIncreases sensitivity of cells to thyroid hormone uIncreases Dopamine uReleases Muscular Tension uRaises HDL uDecreases Blood Pressure uIncreases vagal tone & decreases sympathetic modulation in PCOS patients Treatment Plan - DIVAS 23 u Have you ever seen an obese wild animal? They do not eat dessert or They don’t eat bread or sugar. Those that do packaged food. begin to develop human diseases. They move, a lot. The Learn about amount of stress that occurs movement when you confine an medicine animal is deadly. from your healthy dog Treatment Plan - DIVAS 24 Treatment Plan - DIV S A 25 u Acupuncture u Infertility and Amenorrhea u Pelvic Pain u Hormone Balancing and PMS u Stress Reduction u Constipation u Withdrawal from substance abuse u Acne u Weight Loss u Insomnia u Depression and Fatigue Sugar is a substance many abuse or are addicted to DIV S Treatment Plan - A 26 Treatment Plan - DIVAS 27 Treatment Plan - DIVAS 28 uAcupuncture u Very difficult to study in RCT u Decreases in anxiety, LH/FSH ratio, and testosterone. Improved menstrual frequency in PCOS u No difference between Sham and Acupuncture u Highly safe …. HOWEVER: avoid specific points during pregnancy which can stimulate labor Treatment Plan – DIVAS S- SLEEP 29 u Shortened sleep increases Ghrelin levels. u Ghrelin can inhibit GnRH and decrease fertility. u High Ghrelin increases appetite. u Liver function ( detoxification) has a circadian rhythm u Circadian Rhythm essential to stable hormone regulation u Increased risk of Obstructive Sleep Apnea in PCOS patients: STOP BANG u Home sleep study u Sleep apnea: fatigue, inability to lose weight, u Take the Epworth Sleepiness Scale Treatment Plan – DIVA - SLEEP S S 30 This a revision of the popular STOP BANG sleep apnea screening questionnaire.

u Do you SNORE loudly? Yes or No

u Do you often feel tired, fatigued, or sleepy during the daytime? Yes or No

u Has anyone observed you stop breathing during your sleep? Yes or No

u Do you have or are you being treated for high blood pressure? Yes or No

u Are you obese/ very overweight – BMI more than 35 kg/m2? Yes or No

u Age over 50 years old? Yes or No

u Neck Circumference >16 inches? Yes or No

u Are you male? Yes or No ______

u SCORE:

u If YES to 0 – 2, then low risk of sleep apnea

u If YES to 3 – 4 of the above, then you are at intermediate risk of having sleep apnea

u If YES to 5 – 8 of the above, then you are at high risk of having sleep apnea Treatment Plan –DIVAS S- Sleep 31 u Adequate Sleep (9 hours?) If not: uSerotonin made in the gut and requires B6 uMagnesium glycinate or aspartate uChamomile tea, Lavendar, Valerian uMelatonin, Vitamin D uTaurine, Theanine, GABA, 5-HTP uMeditation u “The Relaxation Response” Herbert Benson, MD u Use amber glasses to decrease blue light exposure known to decrease melatonin. Treatment Plan – DIVAS 32 u S- SUPPLEMENTS u Ideally: “Food as medicine.” u Undergo a nutritional and/or genetic evaluation and/ or be tested. MTHFR, VDR, COMT u IF YOU USE SUPPLEMENTS: 3rd party tested and certified get the recommendation from a licensed experienced professional. Retest levels and watch Liver enzymes u Vitamin D: 67-85% of women with PCOS <20ng/ml. Vit D is a hormone activating 950 genes. u Magnesium 60% of us are deficient u B vitamins, water soluble, methylated forms of B9 and B12 often preferred Treatment Plan - DIVAS 33 u N-acetyl cysteine: benefit when used with Clomiphene citrate u Licorice: reduces testosterone by blocking 17-hydroxysteroid DH and 17,20 lyase. Watch BP, watch drug interactions. u Flaxseed reduces androgen levels u Saw Palmetto: anti-androgen effects, reduce hirsutism & hair loss u Cinnamon: potentiates insulin, facilitates weight loss u Fenugreek & Gymnema: improve hyperglycemia and lower cholesterol u Chromium and vanadium: improve hyperglycemia, watch quantities. u Milk Thistle used with Metformin -> improved effects. Improves ovulation u Dandelion root: vitamins &minerals great for skin and improves acne u Chasteberry: immediately effects the pituitary, symptomatic relief (caution) u Myo- and Chiro- Inositol: supports insulin signaling in the cell, relieves stress Treatment Plan - DIVAS 34 u S = SUPPLEMENTS u Why Treat insulin Resistance? uDecreases inflammation uDecreases estrogen production in fat uImproves estrogen metabolism uDecreases oxidative stress Support Insulin Signaling: Mixed Vit E: alpha, beta, gamma, delta CLA: conjugated linolenic acid Lipoic acid, Inositol, Magnesium, Biotin Treatment Plan - DIVAS 35 u S = SUPPLEMENTS u Progestin with androgenic properties (NETA) increased insulin resistance, progesterone does not u Vitamin D improves insulin resistance and decreases inflammation u Get your DETOX ON with these foods: • Artichoke: 6 oz whole artichoke or 150-600 mg of leaf extract •Pomegranate: 6 oz of juice, 1 fruit, 30-100 mg of ellagic acid •Watercress: 6 oz or 125 -500 mg of whole plant extract •Green tea: 2-4 cups or 50-150 mg catechins •Asparagus helps with liver drainage. •Broccoli and Cauliflower activate detoxification enzymes Treatment Plan – DIVAS 36 u Metformin use during pregnancy in women w/ PCOS decreased the rate of gestational DM by ~27%, whereas lifestyle modification reduced the risk of gestational DM by ~58%. u MITOCHONDRIAL HEALTH u CoQ10: ubiquinone or ubiquinol u L- Carnitine: transports free fatty acids into the mitochondria -> energy. u B-2 and B-3, Magnesium, alpha-lipoic acid u DECREASE INFLAMMATION u Turmeric (mix with ghee, black pepper or phosphatidylcholine u Boswellia u EPA-DHA u GLA, but always take with twice as much EPA u Pineapple ( especially the stem), Tart Cherries, Almonds Which Puzzle pieces will you use? 37

Diet Intestinal Sleep “If your PCOS Health could be helped by something Voice Acupuncture besides fertility Supplements drugs or BCPs, would that interest Mind you?” 99% Body Activity responded yes Medicine Detoxification Case Studies: #1 Mrs. K 38

u 30 years old, dx’d with PCOS, NASH, married and wants children u Treated at Atlanta Functional Medicine for 8 months,

PCOS SYMPTOMS BEFORE TREATMENT AFTER TREATMENT Amenorrhea(no menstruation) 3 months into treatment, normal 28 day cycle Was told couldn’t have children November 2015 due date Fatigue Began walking, then jogging Morbidly Obese Lost 89 pounds On liver transplant list No longer necessary On Metformin in past, no benefit Off Metformin throughout her tx Case Studies 39

u Vitals and Lab Results LABS BEFORE AFTER 2-17-15 VITALS BEFORE DURING AFTER 2-17-15 ALT 172 24 19 17 Weight 298 254 238 209 AST 230 25 21 20 Blood 145/105 132/89 122/78 Cholesterol 203 153 165 132 Pressure 227 155 128 77 BMI 42.3 36 34.2 Triglycerides Multi- 177 128 117 HDL 32 37 38 38 Symptom Questionnaire Estrogen 36.5 152 113 129 Score Fasting Insulin nc 22 18 15 Hgb A1C 5.9 5.3 5.1 4.9 Progesterone < 0.1 1.64 2.4 14.3 Vitamin D 30 109 51 50 Case Studies Mrs. K 40

METRIC 1-7-14 2-21-14 6-23-14 2-17-15

waist 44.0 41.5 39.75 nc hips 49.5 47.75 45 nc WHR 0.88 0.87 0.85 nc Testosterone nc 29 28 21 FSH/LH 4.4/15.7 4.8/11.7 weight 298 254 238 209 Pregnant but didn’t know it yet Case #2 Miss S. 18 yo presents with 41 anxiety, lack of focus, unable to lose weight, irregular cycles, PCOS Metric 2013 11-4- 3-6-15 6-26-15 7-17-15 2014 dx Gut restoration Zinc weight 144 143 140 137 carnosine & Total Chol 220 275 181 elimination diet. LDL-P 1545 2062 1120 Ovaben (Inositol) HDL-P 46.4 46 40 CoQ10,Vit D, FSH/LH 3/22.7 3.9/21.1 3.1/5.8 Berberine, Testosterone 56.1 35 53 13 Mag/K, Fasting nc 16 24 13 Fish Oil, Phosphatidyl Insulin choline Anxiety high Very high confident confident Armour periods irreg irreg reg reg 15 yo female oligomenorrhea, acne, 42 moodiness, back pain, weight gain. . Treated w acupuncture, back pain resolved. Placed on Elimination Diet, gut restoration program, Vit D

October 2013 December 2014 February 2014 Testosterone 69.6 54.4 31 Estradiol 90 102.5 217 FSH/LH 8.4/16.9 2.3/9 weight 136.2 132 135.2 cycles -0- regular skipped skin acne improved MSQ 58 27 15 attitude moody improved Missed S.A.D. Case Studies 43

u Major factor that impacts outcome –COMPLIANCE! References 44 1. Borissova AM, et al. The effect of vitamin D3 on insulin secretion and peripheral sensitivity in type 2 diabetic patients. Int J Clin Pract. 2003;57:258-261.

2. 2.Chiu KA, et al. Hypovitaminosis D is associated with insulin resistance and beta-cell dysfunction. Am J Clin Nutr 2004;79:820-108.

3. 3.Pittas AG, Lau J Hu FB et al The role of vitamin D and calcium in type 2 . A systematic review and meta- analysis. J Clin Endocrinol Metab. 2007;92:2027-2029

4. Thomson, RL: Vitamin D in the Aetiology and Management of Polycystic Ovary Syndrome. Clin Endocrinology. 2012;77 (3):343-350.

5. Nagarathna, PKM, et al. A Detailed Study on Poly Cystic Ovarian Syndrome and Its Treatment with Natural Products. Intl J of Tox and Pharm Research. 2013-14;5(4): 109-120.

6. "Risk of venous thromboembolism in women with polycystic ovary syndrome: A population-based matched cohort analysis," by Steven T. Bird, Pharm.D., M.S., Abraham G. Hartzema, Ph.D., Pharm.D., James M. Brophy, Ph.D., M.D., and others in the February 5, 2013, Canadian Medical Association Journal 185(2), pp. E115-E120

7. Textbook of Functional Medicine , 2013 The Institute for Functional Medicine

8. Lim CE, et al. Acupuncture for polycystic ovarian syndrome. Cochrane Database Syst Rev. 2016 May 3; (5).

9. Raja-Khan N, Stener-Victorin E, et al. The physiological basis of complementary and alternative medicines for polycystic ovary syndrome. Am J Physiol Endocrinol Metab. 2011 Jul;301(1):E1-E10.

10. Ram Nidhi, Venkatram Padmalatha,1 Raghuram Nagarathna, and Ram Amritanshu. Effect of holistic yoga program on anxiety symptoms in adolescent girls with polycystic ovarian syndrome: A randomized control trial. Int J Yoga. 2012 Jul- Dec; 5(2): 112–117. References (cont) 45 11. Nidhi R, Padmalatha V, Nagarathna R, Amritanshu R. Effects of a holistic yoga program on endocrine parameters in adolescents with polycystic ovarian syndrome: a randomized controlled trial. J Altern Complement Med. 2013 Feb;19(2):153-60.

12. Correa JB1, Sperry SL, Darkes J. A case report demonstrating the efficacy of a comprehensive cognitive-behavioral therapy approach for treating anxiety, depression, and problematic eating in polycystic ovarian syndrome. Arch Womens Ment Health. 2015 Aug;18(4):649-54.

13. Stefanaki C1, Bacopoulou F, Livadas S, Kandaraki A, Karachalios A, Chrousos GP, Diamanti-Kandarakis E. Impact of a mindfulness stress management program on stress, anxiety, depression and quality of life in women with polycystic ovary syndrome: a randomized controlled trial. Stress. 2015 Jan;18(1):57-66

14. JC1, Costa EC2, da Silva E3, Tamburús NY3, Porta A4, Medeiros LF5, Lemos TM6, Soares EM7, Azevedo GD8. Aerobic exercise improves cardiac autonomic modulation in women with polycystic ovary syndrome. Int J Cardiol. 2016 Jan 1;202:356-61.

15. Lindheim L, Bashir M, Münzker J, Trummer C, Zachhuber V, Pieber TR, Gorkiewicz G, Obermayer-Pietsch B. The Salivary Microbiome in Polycystic Ovary Syndrome (PCOS) and Its Association with Disease- Related Parameters: A Pilot Study. Front Microbiol. 2016 Aug 25;7:1270.

16. Mathur R1, Ko A, Hwang LJ, Low K, Azziz R, Pimentel M. Polycystic ovary syndrome is associated with an increased prevalence of irritable bowel syndrome. Dig Dis Sci. 2010 Apr;55(4):1085-9.

17. Zangeneh FZ, et al. Synchrony between ovarian function & sleep in polycystic ovary syndrome patients. Open Journal of Obst and Gyn, 4, 725-731 Thank you 46 u For additional questions or comments, please contact Elizabeth Board, MD at: Atlanta Functional Medicine, Inc. 5755 North Point Parkway Suite #74 Alpharetta, GA 30022 770-667-3006 [email protected] www.atlantafunctionalmedicine.com 47 Appendix – MSQ 48

AREA SYMPTOM AREA SYMPTOM

HEAD Headaches DIGESTIVE Nausea, vomiting Faintness TRACT Diarrhea Dizziness Constipation Insomnia Bloated feeling EYES Watery or itchy eyes Belching, passing gas Swollen, reddened or sticky eyelids Heartburn Bags or dark circles under eyes Intestinal/stomach pain Blurred or tunnel vision (does not include near or JOINTS/ Pain or aches in joints far-sightedness) MUSCLE EARS Itchy ears Arthritis Earaches, ear infections Stiffness or limitation of movement Drainage from ear Pain or aches in muscles Ringing in ears, hearing loss Feeling of weakness or tiredness NOSE Stuffy nose WEIGHT Binge eating/drinking Sinus problems Craving certain foods Hay fever Excessive weight Sneezing attacks Compulsive eating Excessive mucus formation Water retention MOUTH/ Chronic coughing Underweight THROAT Gagging, frequent need to clear throat ENERGY/ Fatigue, sluggishness Sore throat, hoarseness, loss of voice ACTIVITY Apathy, lethargy Swollen or discolored tongue, gums, lips Hyperactivity Canker sores Restlessness Appendix – MSQ 49

AREA SYMPTOM AREA SYMPTOM

SKIN Acne MIND Poor memory Hives, rashes, dry skin Confusion, poor comprehension Hair loss Poor concentration Flushing, hot flashes Poor physical coordination Excessive sweating Difficulty in making decisions HEART Irregular or skipped heartbeat Stuttering or stammering Rapid or pounding heartbeat Slurred speech Chest pain Learning disabilities LUNGS Chest congestion EMOTIONS Mood swings Asthma, bronchitis Anxiety, fear, nervousness Shortness of breath Anger, irritability, aggressiveness Difficulty breathing Depression OTHER Frequent illness Frequent or urgent urination Genital itch or discharge