1

PCOS, Metabolism & Lifestyle:

Putting it into Practice

Dr Jim Parker

No conflicts of interest

practice point

1

Learning Objectives

1. Define revised criteria for the diagnosis PCOS

2. Explain the emerging role of nutritional and

environmental factors in the pathogenesis PCOS

3. Summarise the principles of management of PCOS

using lifestyle-based approaches

2

practice point

1

2

https://www.trybooking.com/book/sessions?eid=424944&ses=1254243

2

Polycystic Ovary Syndrome

• Affects 8-13% of women worldwide

• most common endocrine disorder and cause of infertility

• first degree relative → 25% risk (polygenic inheritance)

• Widespread health consequences

• Significant proportion gynaecological consultations

• Challenging Mx problems - lifestyle/nutritional

• Significant economic burden ($4.36 billion/yr US)

• Significant contribution to chronic diseases epidemic

Diagnosis of PCOS

• Rotterdam criteria (2 of 3 features)

• oligomenorrhoea

• biochem/clinical elevated androgen

• ↑Testosterone, ↑FAI, ↓SHBG

• ultrasound features of PCOS (>10 cysts 2-8mm)

practice point

3

4

3

Health Consequences of PCOS

• Reproductive dysfunction

• menstrual disturbance, acne, hirsuitism, alopecia, infertility

• Weight disorders

• management of obesity and prevention of weight gain

• Metabolic disturbance

• insulin resistance (70%), Gestational Diabetes & Type 2 Diabetes (↑3-5 fold)

• ↑ lipids, metabolic syndrome, CV disease, endometrial cancer (x2-6)

• Psychological disability

• anxiety, depression, quality of life (infertility concern most common)

• Not just a cosmetic & fertility problem but major health problem

PCOS and Insulin Resistance(Marshall JC. All women with PCOS should be treated for insulin resistance. Fertil Steril. 2012 January ; 97(1): 18–22)

• IR & compensatory hyperinsulinaemia affects

• 65-70% PCOS overall

• 70-80% obese (BMI >30) PCOS

• 25-30% lean (BMI

4

MJA InSight: Prof Robert Norman

# “the impetus to develop the guideline came from patients”

# “we consistently had complaints that doctors knew less about PCOS than patients did”

# “the metabolic aspects of PCOS have been emphasised in the guidelines”

# “the guideline sought to reassure patients with PCOS that they could have a normal fertility potential”

National Health and Medical Research Council Polycystic Ovary Syndrome Centre for Research Excellence

71 countries201 pages166 recommendations

practice point

7

1. Lifestyle2. OCP3. Letrozole

Integrative Medicine Resources

• PCOS mindset

• control

• mindfulness

• nurturing

• Nutrition

• food intolerances

• personalised plan

• Exercise

• Stress reduction

• Circadian rhythms

practice point

7

8

5

metabolic hormonal

maternal

paternalfamilial polygenic condition associated

with a varietyof symptoms

depending on genetic background and superimposed

lifestyle factors

Pathogenesis of PCOS

9

Developmental Origins of Health and DiseaseNEM epigenetic effects start in-utero

9

10

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwiagYb5sMzgAhULT30KHeX0DkgQjRx6BAgBEAU&url=https://www.sciencenewsforstudents.org/article/silencing-genes-understand-them&psig=AOvVaw2XmnLU40a7yRWhffMDn0my&ust=1550823088079633http://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwjCy5KlsszgAhUGVH0KHR_ZAZoQjRx6BAgBEAU&url=http://thyroidnosurgery.com/thyroid-cancer/environmental-chemicals-causing-thyroid-cancer-a-wake-up-call-to-action/&psig=AOvVaw37Om5brloRWRXSxzm21fvZ&ust=1550823525097126https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&ved=2ahUKEwiu6ZDMt8zgAhVUfisKHRSLBtAQjRx6BAgBEAU&url=https://www.everydayhealth.com/pcos/symptoms-diagnosis/&psig=AOvVaw0iyRuizrKNJ0auNdQTPJpy&ust=1550825034051490

6

Developmental Origins of PCOSFetal Androgen Excess

• Maternal

• PCOS , obesity, IR, GDM, DM

• Endocrine disrupting chemicals

• CAH & adrenal tumor

• Fetal

• ↑glucose → ↑insulin → ↑androgen

• congenital adrenal hyperplasia

• Placental

• ↓ aromatase

• Rat, ewe & primate studies

11

Androgenic Endocrine Disruptors

• Triclocarban – enhanced testosterone action

• Glyphosate (Roundup) aromatase inhibitor, leaky gut

• BPA (bisphenol A) – effects E2 & androgen metabolism

• Tributyltin - boat paint → seafood. Direct toxicity to HPG axis

• Perfluorinated compounds (PFOA, PFOS)(teflon)

• Nicotine – ↑ serum testosterone in women with PCOS Marraudino M et al. Metabolism Disrupting Chemicals and Alteration of Neuroendocrine Circuits Controlling Food

Intake and Energy Metabolism. Frontiers in endocrinology 9 January 2019. doi: 10.3389/fendo.2018.00766

11

12

7

Polycystic Ovarian Syndrome & the Thrifty Phenotype Hypothesis

A pregnant woman programs her fetus forthe metabolic world in which she lives, and

in which it is expected her child will live

The “messages” passed to the child may have come down from many generations

13

Polycystic Ovary Syndrome(evolutionary paradox)

• Not a disease

• Syndrome = collection of symptoms and test results

• Systemic whole-body disorder affecting• metabolism, immune, CV, gut, skin, mind, fertility

• Ancient disorder• described by Hippocrates 400BC

• How could a condition that impedes fertility persist in 10% of the female population?

13

14

8

PCOS in Hunter-Gatherers

• Ancient PCOS different to modern PCOS

• Mild inherited condition that bestowed advantages

• Slightly higher Testosterone levels• more muscle mass, denser bones, slightly stronger

• “Thrifty genes” & ↑IR more fat storage for famines

• Anovulation and mild subfertility• fewer and better spaced pregnancies

• maternal survival advantage in times of high MM

• Adaptation to hunter-gatherer nomadic life

Pathophysiology of PCOS in Modern Society

• Metabolic dysregulation• SAD diet, microbiome dysbiosis, systemic inflammation• insulin resistance and hyperandrogenism• metabolic-circadian desynchronisation• metabolic, endocrine and reproductive dysfunction

• Environmental disruption• endocrine disrupting chemicals

• Circadian dysregulation• extended light exposure• extended feeding window• shift-work• disturbed oestrogen function

15

16

https://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwiTpMvayrzgAhUMTo8KHSPbCUUQjRx6BAgBEAU&url=https://www.lookandlearn.com/history-images/B001732/Cavemen-dinosaur-and-volcano-for-an-article-about-special-effects?t%3D4%26n%3D12450&psig=AOvVaw09n_xSRMujUvCe0Nz3H62L&ust=1550280406547695

9

Pathogenesis of PCOSDOGMA (dysbiosis of gut microbiota) Theory

(Tremellen K, Pearce K. dysbiosis of Gut Microbiota. Med Hypotheses 2012)

Insulin Resistance

Hyperandrogenaemia

Chronic Inflammation

DIET

17

Pathogenesis of Polycystic Ovary Syndrome(Parker J. Emerging concepts in the pathogenesis and treatment of PCOS.

2014; 10(2): 107-112. Current Women’s Health Reviews)

Genetic Predispositiongonadotrophin genesdiabetes genes

Environmental factorspoor quality dietenvironmental chemicals

In-utero epigenetic effects androgen excess

Childhood risk factorsintractable obesitymetabolic syndromepremature adrenarche

Adolescent onsetoligomenorrhoea, acne, hirsuitism

Adult sequelaeinfertility, menstrual disturbancediabetes, cardiovascular, cancer

Altered bowel flora↓ lactobacillus & bifidobacteria↑ gram negative, clostridium

Bacterial productsLPS, cytokines, metabolites

Immune system activation

(mucosal damage & ↑ permeability)

Chronic inflammation

Insulin resistance hyperandrogenism

practice point

17

18

10

Management of PCOS

• Medical model fragmented

• menstrual symptoms or fertility problem – gynaecologist

• acne – dermatologist

• hirsuitism – endocrinologist

• anxiety/depression - psychologist/psychiatrist

• gut problems (IBS or reflux) – gastroenterologist

• Integrative practitioner

• integrates treatment of all systems

Optimise LIFESTYLE to Support Metabolic Health

• Wholefood nutrition

• Exercise

• Weight reduction

• Environmental expos

• Stress reduction

• Smoking & Alcohol

• Community

• Circadian rhythms

20

19

20

11

COULD WE PREVENT PCOS IN GIRLS?Interventions in pregnancy, infants and girls

• Healthy nutrition intervention for all pregnant women

• Screening for IR in high risk patients (obese/PH GDM)

• Optimise blood sugar control in diabetics & GDM

• Vaginal birth to optimise microbiome

• Breastfeeding & minimise antibiotics

• Avoid Endocrine Disrupting Chemicals

PCOS and the DoHAD Cycle of Life

poor quality diet & environmental effects

activate thrifty phenotype

in-utero epigenetic

effects

obesity, diabetes, GDM, metabolic syndrome, PCOS

obesity, diabetes, GDMmetabolic syndrome, PCOS

(adult)

(offspring)

22

21

22

12

1. Wholefoods Nutrition2. Dysbiosis3. Trace Elements4. Micronutients5. Supplements6. Insulin Resistance7. Acne8. Weight Loss

Clinical Management of PCOS

• Acute emergencies

• Acute symptom management

• Chronic symptom management

• Prevention

23

24

13

Case Presentation

• 14 yo girl with 7 yr history of recurrent LAP

• Prepubertal US showed enlarged ovaries & normal hormone

• Pubertal development 11 yrs, menarche 13yrs, normal wt

• Mother had PCOS and GDM

• Presented with acute LAP not relieved by narcotics

• ↑HR, ↑temp, normal BP, RIF tender, guarding & rebound

• ↑WBC, US enlarged ovaries and ? right ovarian torsion

shown with patients permission26

25

26

https://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwiYj6X77dbPAhXogVQKHWTgAT0QjRwIBw&url=https://www.studyblue.com/notes/note/n/lecture-22-female-reproductive-system/deck/8882865&psig=AFQjCNFLTk8P_IwWNy_ILCYWJ-EOI4ZgLg&ust=1476416429973437

14

Postoperative History

• 14yo 18mth oligomenorhoea (42-56d)

• Diet history shows SAD diet

• Normal weight (BMI =23) and regular exercise

• No acne or hirsuitism

• No PH of medical problems

• ? investigations

Assessment and Evaluation of PCOSEstablish your baseline

• Menstrual cycle

• Track with calendar or app

• Anthropomorphic

• Weight and BMI, BP

• waste & hip circumference, waist to hip ratio

• Medical tests

practice point

27

28

15

Investigation of PCOS

• Elevated LH:FSH ratio

• Normal prolactin, TSH, T3, T4, DHEAS, tumour marker

• Elevated FAI & testosterone and low normal SHBG

• Normal FBC, LFT, UEC, homocysteine, Vit D, Mg, Zn

• Elevated fasting insulin and normal BSL and HbA1C

• Elevated hsCPR and cholesterol

practice point

Diagnosis & Treatment

• Oligomenorrhoea, ↑T, ↑LH:FSH ratio = PCOS

• ↑hsCRP and diet history = ? dysbiosis

• ? insulin resistance

• insulin 11 (

16

Pathogenesis of Polycystic Ovary Syndrome(Parker J. Emerging concepts in the pathogenesis and treatment of PCOS.

2014; 10(2): 107-112. Current Women’s Health Reviews)

Genetic Predispositiongonadotrophin genesdiabetes genes

Environmental factorspoor quality dietenvironmental chemicals

In-utero epigenetic effects androgen excess

Childhood risk factorsintractable obesitymetabolic syndromepremature adrenarche

Adolescent onsetoligomenorrhoea, acne, hirsuitism

Adult sequelaeinfertility, menstrual disturbancediabetes, cardiovascular, cancer

Altered bowel flora↓ lactobacillus & bifidobacteria↑ gram negative, clostridium

Bacterial productsLPS, cytokines, metabolites

Immune system activation

(mucosal damage & ↑ permeability)

Chronic inflammation

Insulin resistance hyperandrogenism

practice point

Nutritional Management of PCOS

• Evidenced Based

• Clinical Guidelines

• 3,000 health professionals &

consumers worldwide

• 201 pages

• 608 references

To achieve weight lossin those with excess weight,

an energy deficit of30% or 500 - 750 kcal/dayas per general population

recommendation

32

31

32

https://www.monash.edu/__data/assets/pdf_file/0004/1412644/PCOS-Evidence-Based-Guideline.pdf

17

What is the Optimal Diet to Prevent PCOS?Wholefoods Diet

practice point

Prevention and Treatment of PCOSWholefoods Diet

practice point

34

33

34

http://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwjn46Ck4LnLAhUnGaYKHTmtDbEQjRwIBw&url=http://www.thefitdecision.com/&bvm=bv.116573086,d.dGY&psig=AFQjCNE2kJXNaUI-NCGDBTd60SUNBQ3fDA&ust=1457824058957165https://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwiNxvCwwZvhAhUZeysKHVW5ATwQjRx6BAgBEAU&url=https://www.123rf.com/photo_68877666_steamed-fish-in-lemon-sauce-on-white-plate.html&psig=AOvVaw13wgdF9-rIAIXL3YanDRK9&ust=1553542071787544http://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwjawf7lwZvhAhVVSX0KHTb9AHgQjRx6BAgBEAU&url=/url?sa%3Di%26rct%3Dj%26q%3D%26esrc%3Ds%26source%3Dimages%26cd%3D%26ved%3D%26url%3Dhttps://www.foodandwine.com/recipes/green-lentil-curry%26psig%3DAOvVaw3Hvusj-JSfu73fqNaAMabd%26ust%3D1553542176679460&psig=AOvVaw3Hvusj-JSfu73fqNaAMabd&ust=1553542176679460https://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwje-a-rwr7bAhVKO7wKHUkVCt4QjRx6BAgBEAU&url=https://en.wikipedia.org/wiki/Olive_oil&psig=AOvVaw3k-sFZmfKxAM2OkcG71_96&ust=1528356592915477https://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwiu5-nbwb7bAhXFWbwKHdQvAEsQjRx6BAgBEAU&url=https://www.tesco.com/groceries/en-GB/products/254918067&psig=AOvVaw0-rjoNxluOCvEfUg9xMzEU&ust=1528356476561329https://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwicnIvywb7bAhUEW7wKHfrADCgQjRx6BAgBEAU&url=https://www.shutterstock.com/search/margarine&psig=AOvVaw09izat7mQVJc32PCSns8IM&ust=1528356529124743https://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwje-a-rwr7bAhVKO7wKHUkVCt4QjRx6BAgBEAU&url=https://en.wikipedia.org/wiki/Olive_oil&psig=AOvVaw3k-sFZmfKxAM2OkcG71_96&ust=1528356592915477https://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwiz14rCwr7bAhVKy7wKHYFACekQjRx6BAgBEAU&url=https://www.shutterstock.com/search/coconut%2Boil&psig=AOvVaw1Xyc3EyRByo37Pnj4O4R1y&ust=1528356696996324https://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwii-sLnwr7bAhXKwbwKHYXbD_sQjRx6BAgBEAU&url=https://www.istockphoto.com/photos/glass-of-water&psig=AOvVaw14KJ-lvGG5zGhFkAWL84dU&ust=1528356764444787https://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwiR-Z2Nw77bAhVFNrwKHb0CDGEQjRx6BAgBEAU&url=https://www.echo.net.au/2018/02/drinking-soft-drink-linked-cancer-risk/&psig=AOvVaw26emwHOFmu2ULynEJCY163&ust=1528356831636428https://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwiVzf3GxL7bAhUFU7wKHSXdAG4QjRx6BAgBEAU&url=https://www.dreamstime.com/photos-images/bread.html&psig=AOvVaw3HKzcF_KYS-hzgOs0n0bh8&ust=1528357243980124http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwi7zdHRv5vhAhUBSX0KHf78D4gQjRx6BAgBEAU&url=/url?sa%3Di%26rct%3Dj%26q%3D%26esrc%3Ds%26source%3Dimages%26cd%3D%26ved%3D%26url%3Dhttps://www.123rf.com/photo_8297195_orange-juice-and-slices-of-orange-isolated-on-white.html%26psig%3DAOvVaw11Aa4UWYDl1Gf2Pui44EhB%26ust%3D1553541605081400&psig=AOvVaw11Aa4UWYDl1Gf2Pui44EhB&ust=1553541605081400

18

Prebiotics: PCRMpractice point

35

practice point

36

35

36

http://www.google.com.au/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwiThqSWnpvaAhWEvbwKHfDJA34QjRx6BAgAEAU&url=http://www.closertothecure.com/dietary-fiber-facts/&psig=AOvVaw3a0Ocz21QoKZ4GV_msUiRN&ust=1522745624186043

19

shown with permission from patient and dietitian

practice point

HEALTHCOACHES

DIETITIAN

37

Minimise Environmental Chemical Exposure

1. Eat organic foods (glyphosate and pesticides)2. Natural personal careproducts for lotion, shampoo, conditioner, sunscreen (carcinogens, reproductive toxicants, substances that cause allergies/immune problems, EDC=triclocarban, phthalate)3. Avoid BPA in food packaging and receipts4. Non-toxic cleaning products5. Create a healthy home

practice point

38

37

38

https://secure.ewg.org/p/salsa/web/common/public/signup?signup_page_KEY=5977&_ga=2.243402949.1749597768.1550632581-524426321.1550632581http://www.corvallisadvocate.com/wp-content/uploads/2013/01/Spraying-Pesticides.jpg

20

2 years later

• Presentation• acute onset of widespread acne (back & chest)

• oligomenorrhoea

• not adherent to diet

• still exercising and normal weight

• Management• GP referral dermatologist

• minocycline and skin wash

• Dietary advice

PCOS Related Acne

Most common skin condition on earth

Affects 85% of teenagers in western societies

Affects 50% of adults into their 30’s

40

39

40

21

Incidence of Acne inDeveloped vs Developing Nations

(Lynn D et al. The epidemiology of acne in late adolescence. Adolescent health, medicine and therapeutics 2016;7: 13-25)

41

Kitivan Adolescents & AcneAcne Vulgaris: A Disease of Western Civilisation

(Cordain L. Arch Dematol 2002; 138: 1584-1590)

• NE New Guinea - No acne

• 1990 phones,cars,electricity

• 1200/300 adolescent 15-26

• Rich in fresh, natural foods such as tubers, fruit, coconut & fish (wholefoods)

• Low GI→↓insulin→↓T

• Hi fish=hi omega 3 (↓IGF1)

• No dairy →↓mTOR Inuit Eskimos 1971

Ache hunter-gathers Paraguay 1997-2001

42

41

42

https://www.google.com.au/url?sa=i&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwj10tXIpafbAhWGUrwKHXJaAcEQjRx6BAgBEAU&url=https://sporteluxe.com/us/kitava-skin-diet/&psig=AOvVaw23wGj1l74_bZk35cx7xKN-&ust=1527558594285717https://www.google.com.au/url?sa=i&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwip9IGfpqfbAhVPhrwKHTGqACYQjRx6BAgBEAU&url=http://coachmikeblogs.com/you-are-not-a-kitavan-islander/&psig=AOvVaw23wGj1l74_bZk35cx7xKN-&ust=1527558594285717

22

DHT

Acne Vulgaris: A Disease of Western Civilisation(Cordain L. Arch Dematol 2002; 138: 1584-1590)

DHT

Nutritional Management of AcneWhole-foods diet (Kitivan)

• Low GI diet

• ↓ IR → ↓ IGF-1 → ↓ hyperkeratinisation of sebaceous gland & unblocks follicle

• ↓ IR reduces androgens by 20% via ? ↓ ovarian androgen production

• High fibre diet

• testosterone secreted in bile and removed rather than enterohepatic circulation

• Minimise or avoid dairy

• inflammatory and leads to higher androgens

• Eat more omega-3 fa which are anti-inflammatory

• wild-caught fish, oysters, nuts and seeds

• Avoid Endocrine Disrupting Chemicals

• Vitamin D, Zinc, Probiotics, Berberine

practice point

43

44

23

Diagnosis & Treatment of PCOS

• Dysbiosis and “proof of concept studies”

• Hyperandrogenism

• Obesity

• Menstrual symptoms

• Infertility

• Insulin resistance

• Supplementation

Fasting Insulin

1. Physiological IR

2. Fasting hyperglycaemia

practice point

45

46

24

Testing for Insulin ResistanceReference ranges for HOMA-IR in normal weight & obese young caucasians. Shashaj B et al. Acta diabet 2015

euglycaemic hyperinsulinaemic clamp, IV GTT, OGTT, QUICKI, FGIROGTT derived adipocytokine surrogate markers

(physiological insulin resistance, fasting hyperglycaemia)

HOMA-IR = insulin(11) x glucose(5.2) = 2.5 22.5

practice point

Supplements and PCOSPundir J et al. Overview of systematic reviews of non-pharmacological interventions in women with pcos. Hum Reprod Update.. March-April 2019. 25;2:243–256.

• Trace elements: Mg, Cu, Fe, selenium, Zn

• N-acetyl cysteine: medication vs supplement

• Inositol: insulin signalling pathway, neurotransmitter pathways

• Antioxidants: vitamins A, C, E, selenium, resveretrol

• Vitamins D and B group vitamins

• Probiotics

• Fish oil: omega-3 fatty acids

practice point

47

48

25

Conclusions: Polycystic Ovary Syndrome

• Common inherited metabolic disorder

• Significant contribution to chronic disease epidemic

• Diagnosis by revised Rotterdam criteria

• Pathogenesis: nutritional and environment factors

• Mx by lifestyle interventions +/- supplementation

• Ideal opportunity for prevention of chronic disease

Wholefoods DietEndocrine Disrupting Chemicals

foodrelaxation

sleep movement

Thank-you50

49

50