Module 6. PCOS and Fertility. Phenotype A. Classic PCOS Hyperandrogenism Chronic Anovulation PCOS Morphology. Phenotype A.

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1 1 PCOS and Fertility Module 6 Part 4 (ep 1) Phenotype A 2 Classic PCOS Hyperandrogenism Chronic Anovulation PCOS Morphology Phenotype A 3 Classic PCOS - Highest AMH levels - More pronounced menstrual dysfunction - Higher rates of insulin resistance - Higher risk for metabolic syndrome - Higher BMI and increased prevalence for obesity

2 Phenotype B 4 Hyperandrogenism Chronic Anovulation Phenotype B 5 - High AMH levels - Pronounced menstrual dysfunction - Higher rates of insulin resistance - Higher risk for metabolic syndrome - Higher BMI and increased prevalence for obesity Phenotype C 6 Ovulatory PCOS Hyperandrogenism Some or no ovulation dysfunction No PCOS morphology

3 Phenotype C 7 Intermediate levels of Serum androgens Insulin resistance Hirsutism scores Metabolic syndrome Lean or overweight Phenotype D Ovulation Dysfunction PCO Morphology Nonhyperandrogenic PCOS 8 Phenotype D Mildest degree of endocrine and metabolic dysfunction Lowest level of metabolic syndrome Lower LH to FSH ratios Lower total and free T levels Higher SHBG Highest number of women with alternating regular cycles with irregular cycles 9 Daria Lizneva M.D., Ph.D et al Fertility and Sterility, , Volume 106, Issue 1, Pages 6-15

4 BMN added: Phenotype E 10 Ovulation Dysfunction (Amenorrhea or Significant irregular cycles) PCO Morphology Mild to moderate hyperandrogenism Phenoptype E 11 Lean One of two features of hyperandrogegism usually mild No clear evidence of insulin resistance High AMH Amenorrhea or very irregular cycles Phenotype Weight Androgens PCOS morphology Menstrual cycle disturbance 12 Phenotype A Overweight Higher BMI Highest excess androgen sx excessive Yes Yes amenorrhea oligomenorrhea Phenotype B Overweight Higher BMI Mod to high sx moderate to excessive no Yes oligo or amenorrhea Phenotype C Phenotype D Moderate BMI could be overweight or normal normal weight, overweight or normal Mild to moderate levels sx: Mod to mild no Somewhat irregular mild to none yes regular/ irregular cycles alternating Phenotype E BMN added lean, lower end of BMI or mid range mild to none yes amenorrhea or irregular cycles

5 Underlying Thyroid and/or Adrenal Issues 13 PCOS patients irregardless of phenotype present with thyroid and or adrenal issues Phenotype should not be ignored we will likely find more correlation with nutrients necessary within each phenotype Phenotypes are a great adjunct to assist with diagnosis Address the underlying cause of the issue with glucose metabolism and you will assist more patients with PCOS ANY phenotype Eating plan primary: Eating plan effecting ALWAYS thyroid/adrenals: Thyroid &or Pituitary primary Eating plan some or no progress Adrenal primary Thyroid secondary Eating plan some or no progress 14 Exercise Must balance good carbs, good fats, good protein, remove processed foods/drinks, sugar/ sweetener Sugar/unbalanced carbs are kryptonite Great progress cycles regulate, energy increases, weight reduces if necessary -Low T4 levels -Elevated TSH - Poor nutrient status - Adrenals: cortisol normal or slight high or low if tested Some progress or none with eating plan and exercise but plateau -Opt FT4 -Opt FT4/Low FT3 -Opt FT4/FT3 but Elevated TSH, - Optimal FT4,FT3, ELevated RT3/ FT3 Adrenal: Cortisol low or high DHEA: low Min to no progress with eating plan and exercise. And often get sick/flu cold after starting to exercise Any phenotype Primary Thyroid Primary Adrenal 15 Eating plan Minimize toxins Optimal Supplementation: Standard prenatal, probiotics, fish oil Exercise 2-5x per week Stress Management DAILY Always assessed and continually monitored Most important emphasis Is occupation or environment causing thyroid to be an issue? Highish TSH Inositol sel, zn, chromium Low FT4: iodine, Bladderwrack, Withania, Bacopa Interval training at appropriate level, resistance training, pilates Yoga, meditation, visualization 5-30mins Always assessed and continually monitored Most important emphasis Has there been long term exposure that may be contributing to physiological adrenal stress? Highish TSH, optimal FT4 and FT3: Inositol High FT4, less opt FT3: sel, zn, Cr Low or high cortisol: Adaptogens Start very slow and ramp up slowly. Back off if cont to exp colds, flu fatigue Yoga, meditation, visualization, 15-30mins

6 Case Study year old obese female BMI 38 Phenotype A Classic PCOS Androgens: DHEA, T and F testosterone, Elevated LH/FSH ratio < 2 cycles per year Onset of weight gain at puberty Put on pill at 20 to help with acne Case Study 1 17 Didn t like taking the pill Made her feel weird Reports discharge white, sticky, creamy all the time Tries to lose weight but gets discouraged Doctor says she has to lose 20kilos before they will consider IVF Clomid resistance (6 cycles of Clomid, one ovulatory cycle (first one)) Case Study 1 18 Taking folate 5mg from doctor Metformin 3 times a day (nausea decreased but still there) Never exercises Poor eating plan I know what to eat but am too lazy to fix it Saw a dietician but she didn t feel comfortable with her

7 Case Study 1 19 Objective TSH 3.63 FT4 9.8 nmol/l.76 ng/dl FT3 3.9 pmol/l 253 pg/dl Free test 47 pmol/l 4.7 pg/dl Total test 5nmol/L 144 ng/dl SHBG 43 Case Study 1 20 LH 25 E2 223 pmol/l 60 pg/ml P4.3 nmol/l.09 ng/ml Fasting glucose 5.6 mmol/l mg/dl Triglycerides 3.3 mmol/l 292 mg/dl Vitamin D 55 nmol/l 22 ng/ml Case Study 1 21 A) 32 yo obese female presents with dx of PCOS. Partner not tested but has two children from previous marriage 2 and 4 yo. Thyroid likely contributing to oligomenorrhea and amenorrhea; primary potentially due to eating plan or underlying thyroid issue. Self esteem issues potentially, doesn t appear to have good support system.

8 Case Study 1 22 Plan: Food diary continuous and sx diary including discharge Temperature charting Discuss high dose folate with physician and if agrees switch to Bioceuticals Innatal Ask if can ween off Metformin since hasn t helped with weight loss or ovulation and still experiencing nausea Add probiotic, fish oil Case Study 1 23 Plan continued: Add myoinositol 4g Add Thyroplex Bioceuticals (Thyroid Support USA) twice a day Reviewed how to avoid endocrine disruptors Exercise: start walking on treadmill or outside 10 mins a day Stress management: Record what you are feeling when you want to eat but aren't hungry Visualization before bed Thyroid FT4, FT3, Thyroid antibodies, fasting homocysteine Case Study 1 24 Visit 3 Eating plan changes: Removed all processed foods Still working on getting rid of added sugar in one coffee a day but overall much better No more cooking in microwave

9 Case Study 1 25 Visit 3 Supplementation update Innatal, Thyroplex (Support), Probiotic, Fish Oil, added Inositol 4 g powder Completely off Metformin Added apple cider vinegar before meals Lost 13 kilos in 3 months Fasting homocysteine 6.2 TSH 2.5 from 3.63 First Temperature Chart 26 27

10 Case Study 1 Herbal Formula Withania Thyroid and T4 support 100ml 28 Vitex Agnus Castus Progesterone support 100ml Bacopa T4 Support 100ml Gymnema Glucose Metabolism 50ml Cinnamon Glucose Metabolism 50ml Scullcap Anti-anxiety 50ml Passionflower Ant-anxiety, sleep 50ml Case Study 1 29 Visit 5 Pregnant Last 5 of 7 months had a period (never happened before in her life) Mucus decreased to only around ovulation Total weight loss 22 kilos 44+ pounds 7 months Joined a gym after initial 10 kilo weight loss Before she was pregnant physician noted improvement in her ovaries. Less follicles noted than previous. Case Study 1 30 Final test results FT from 9.8 pmol/l 1.10 from.75ng/dl FT3 4.9 from 3.9 pmol/ 318 from 288pg/dL TSH 1.8 from 3.63 Fasting glucose 5.1 mmol/l mg/dl Progesterone 7DPO 33.7 nmol/l 11.2 ng/ml E2 7DPO 443 pmol/l 118 pg/ml LH 11 FSH 8.9 Free and total testosterone high normal range (was elevated)

11 Withania Thyroid T4 supprt/ Adaptogen Case Study 1 Herbal Formula Withania Agnus Castus Bladderwrack Gymnema Scullcap Passionflower Bacopa Cinnamon St. Mary s thistle 100ml Vitex Agnus Castus Progesterone 100ml Bladderwrack Thyroid support/iodine 50ml Gymnema Glucose Metabolism 50ml Scullcap Anti-anxiety 50ml Passionflower Anti-depressive 50ml Bacopa T4 support 50ml Cinnamon Glucose Metabolism 25ml 100ml 100ml 50ml 50ml 50ml 50ml 50ml 25 ml 25ml 31 St. Mary s Thistle Hepatoprotective 25ml Case Study 2 32 Phenotype D 29 yo female BMI 21 Last cycle 5 months ago Trying 2 years Had Clomid and Metformin previously no pregnancy Reports hirsutism Supplements: chinese herbs and Elevit Mostly gluten free Case Study 2 33 Temp chart

12 Case Study 2 34 A) 29 yo female lean, normal BMI, dx of PCOS, mild hirsutism so suspect elevated testosterone potentially due to thyroid secondary to low temperatures. Amenorrhea last 5 months prior to that had come off the pill and with Chinese herbs began menstruating but then stopped again the last five months despite the herbs and acupuncture. Case Study 2 35 P) Food diary 10 days Blood tests: TSH, FT4, FT3, thyroid antibodies TPO and TgAb Fasting glucose DHEA Free and total testosterone AM Cortisol Case Study 2 36 Plan continued Discussed endocrine disrupters Supplements: Innatal, probiotic, fish oil Discussed beginning exercise program Discussed meditation, consider circleandbloom.org for visualization.

13 Dong Quai Uterine tonic 100ml 37 Vitex Agnus Castus Progesterone support 100ml Withania Thyroid T4 and Adaptogen 100ml St. Mary s Thistle Hepatoprotective 100ml Peony Excess androgens 50ml Cinnamon Glucose metabolism 50ml Case Study 2 38 Visit 2 Food diary: Significant amount of gluten free processed foods in diet Lacking good fats in eating plan Case Study 2 39 Blood test results SHBG 52 TSH 2.0 FT4 15 pmol/l 1.16 ng/dl FT3 4.6 pmol/l 298 pg/dl DHEA S 6.8 umol/l 252 ug/dl FTest 53 pmol/l 5.3 pg/dl TTest 6.7 nmol/l 193 ng/dl AM Cortisol 625 nmol/l 22.7 ug/dl Vitamin D 62 nmol/l 25 ng/ml Homocys 9.0

14 Case Study 2 40 Dong Quai Uterine tonic 100ml 41 Vitex Agnus Castus Progesterone support 100ml Withania Thyroid T4 and Adaptogen 100ml St. Mary s Thistle Hepatoprotective 100ml Peony Excess androgens 50ml Cinnamon Glucose metabolism 25ml Rhodiola Adaptogen 25ml Case Study 2 42 Supplementation Innatal Probiotic (Ultrabiotic 45 Bioceuticals) Fish oil (EPA/DHA Bioceuticals) Added Thyroplex

15 Case Study 2 43 Exercise: Discussed adding resistance training either with Yoga, or weights (Body Pump) or both Continue working on stress management (listening to relaxing music before bed) Case Study Visit 3 44 Patient reports feeling more energy since starting Body Pump and cutting out the gluten free processed foods Sleeping better overall Improved libido Had her second period on the program Case Study 3 45

16 Case Study 2 46 Kept herbs and supplements the same except adding 4 grams of myo-inositol Patient stayed on track with her eating plan Said her doctor wouldn t do anymore tests until next year when she goes to IVF Visit 4 Case Study 2 47 Case Study 2 48

17 Case Study Case Study 3 51 Phenotype A/B - Moderate sx, overweight/obese BMI 29 Classic PCOS re symptoms Hirsutism and acne PCOS morphology Been trying to become pregnant for 11 years Hadn t had a period for 4 months

18 Case Study 3 52 Subjective Headaches 2-3 times a week Insomnia Periods about every 2-3 months Low libido Vaginal odor Acne worse leading up to period Case Study 3 53 Visit 2 Less headaches Had a period for 11 days Losing weight started low GI eating plan Sex drive returned (hadn t had one in 8 years) Losing weight (won t get on scale) I can see it in my face Sleeping better 54

19 Case Study 3 55 Visit 3 Started the multi vitamin but still no probiotics or fish oil Had another period, spotted for 11 days Some cramping with period Some PMS Less acne Nearly all the symptoms I was experiencing with PCOS is gone. I have way more energy, i never get depressed now 56 Case Study 3 57 Visit 4 Lost 7 kilos 5 day period I have had a cold for the last 3 weeks which has left me exhausted at the end of the day but thats about it Energy: Really high i have started exercising again 40 mins a day i walk on my treadmill. I have not had the time to get the blood tests done that you wanted me to get but i have asked a lady to fill in for me next month so i can get them done for you.

20 Case Study 3 58 Visit 5 I have lost 10 kilos (went from 90 to 80K) Missed a period this last month Started to see clear discharge 59 Case Study 3 60 Visit 6 Gained 2 kilos No period for 2 months now Low sex drive Feeling depressed again I have been really stressed lately and have gone back to eating bad. Finding it harder to stick to a low GI eating.

21 61 Case Study 3 62 Pt stopped coming and returned 3 years later: She had gained another 40 kilos Discussed the importance of being compliant with the whole program I suggested we put a team together to help her. I referred her to back to her GP for a dietician consult I referred her to a personal trainer I suggested she see a cognitive behavioral therapist for CBT Noncompliant Patients 63 Encourage them find the underlying cause of why they aren t sticking to the program Looking for a quick fix? Poor support system? Low self image/self esteem Depression (nutrient depletion) Stress management issue; emotional eating? Build rapport and help them identify behavioral pattern that isn t working or them.

22 Case Study 4 64 BMN Phenotype E 37 yo female nurse Normal weight BMI 22 Had a normal cycle then was on roacutane for skin and period stopped and didn t return Tried clomid x 6 Ovulated with drugs, but never fell pregnant. Felt horrible on the drugs Case Study 4 65 Case Study 4 66 No supplements Tubes clear Polyps removed Lining thin Family history of Thyroid issues Multiple small follicles on ovaries Occasional acne Min to no hirsutism

23 Case Study 4 67 A) pt is a 37 yo female with persistent amenorrhea for as long as she can remember. Was on the pill for a brief period (4-5 years) but came off and period never came back.?thyroid? adrenal Case Study 4 68 Plan: Food diary 10 days Discussed exposure to endocrine disruptors Prenatal, Probiotic, Fish oil Patient active with aerobic exercise, suggested decreasing to 2 days per week and yoga 2 days Stress management (shift work) Case Study 4 St. Mary s Thistle Hepatoprotective 125ml 69 Black Cohosh Anti-inflammatory 100ml Shatavari Adaptogen/ Aphrodisiac Estrogen support 100ml Vitex Agnus Castus Progesterone Support 100ml Dong Quai Reproductive tonic 75ml

24 Case Study 4 70 Blood tests: FSH, LH, Thyroid antibodies, TSH, FT4, FT3 Iron Studies Vitamin D DHEA E2 SHBG Free and Total Testosterone Case Study 4 71 Improved libido Noted more clear discharge More lubrication with intercourse Pimple break out mild Better bowel movement and don t feel bloated Added more protein and decreased fruit Likes new eating plan, makes her feel stronger, more energy Case Study 4 TSH 1.9 FT4 12 pmol/l FT3.93 ng/dl 3.5 pmol/l 227 pg/dl Thyroid antb Negative SHBG 33 FSH 9 LH 24 72

25 Case Study 4 73 Vitamin D 68 nmol/l 27 ng/ml Fast gluc 4.6 mmol/l 82.9 mg/dl E2 30 pmol/l 8.17 pg/ml Iron 18 Ferritin 54 High side of normal total testosterone Free testosterone not tested 74 Case 4 75 A) Thyroid conversion an issue. Thyroid/ Adrenal (shift work exacerbating), excess sugar via fruit, too little protein, bowel and elimination improving, low estrogen, high LH, normal total testosterone, free testosterone not tested

26 Case Study 4 76 P) Added Iodine 200mcg, Selenium 100mcg, Zn 20mg and Vit D 4000IU and in addition to the prenatal, added adaptogen to the formulation Have intercourse on the dips in temperature (ask to see if they recorded all of the times they had intercourse) Case Study 4 77 St. Mary s Thistle Hepatoprotective 100ml Black Cohosh Anti-inflammatory 100ml Shatavari Vitex Agnus Castus Adaptogen/ 100ml Aphrodisiac Estrogen support Progesterone Support 100ml Dong Quai Reproductive tonic 50ml Withania Adaptogen 50ml Case Study 4 78 Visit 3 (5months from beginning) Patient was sure she was going to get a period No period came because patient was pregnant

27 79 Case Study 4 80 No period FT4 increased to 15 from 12 pmol/l 1.16 from.93 ng/dl FT3 increased to 4.2 from 3.5 pmol/l 272 from 227 pg/dl Progesterone 35 nmol/l (11.7 ng/ml) was not tested due to amenorrhea Vitamin D 73 from 68 nmol/l 29.3 from 27.4 ng/ml SHBG 65 was 33 Thank YOU!! 81 That concludes your module on PCOS Thanks for your attention! I hope you found this helpful!